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1.
Proc Natl Acad Sci U S A ; 120(46): e2219547120, 2023 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-37903246

RESUMO

The Hunga Tonga-Hunga Ha'apai (HT-HH) volcanic eruptions on January 13 and 15, 2022, produced a plume with the highest signal in stratospheric aerosol optical depth observed since the eruption of Mt. Pinatubo in 1991. Suites of balloon-borne instruments on a series of launches from Réunion Island intercepted the HT-HH plume between 7 and 10 d of the eruptions, yielding observations of the aerosol number and size distribution and sulfur dioxide (SO2) and water vapor (H2O) concentrations. The measurements reveal an unexpected abundance of large particles in the plume, constrain the total sulfur injected to approximately 0.2 Tg, provide information on the altitude of the injection, and indicate that the formation of sulfuric acid aerosol was complete within 3 wk. Large H2O enhancements contributed as much as ~30% to ambient aerosol surface area and likely accelerated SO2 oxidation and aerosol formation rates in the plume to approximately three times faster than under normal stratospheric conditions.

2.
Bioorg Chem ; 144: 107112, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38237390

RESUMO

We report here the virtual screening design, synthesis and activity of eight new inhibitors of SphK1. For this study we used a pre-trained Graph Convolutional Network (GCN) combined with docking calculations. This exploratory analysis proposed nine compounds from which eight displayed significant inhibitory effect against sphingosine kinase 1 (SphK1) demonstrating a high level of efficacy for this approach. Four of these compounds also displayed anticancer activity against different tumor cell lines, and three of them (5), (6) and (7) have shown a wide inhibitory action against many of the cancer cell line tested, with GI50 below 5 µM, being (5) the most promising with TGI below 10 µM for the half of cell lines. Our results suggest that the three most promising compounds reported here are the pyrimidine-quinolone hybrids (1) and (6) linked by p-aminophenylsulfanyl and o-aminophenol fragments respectively, and (8) without such aryl linker. We also performed an exhaustive study about the molecular interactions that stabilize the different ligands at the binding site of SphK1. This molecular modeling analysis was carried out by using combined techniques: docking calculations, MD simulations and QTAIM analysis. In this study we also included PF543, as reference compound, in order to better understand the molecular behavior of these ligands at the binding site of SphK1.These results provide useful information for the design of new inhibitors of SphK1 possessing these structural scaffolds.


Assuntos
Antineoplásicos , Fosfotransferases (Aceptor do Grupo Álcool) , Quinolonas , Quinolonas/farmacologia , Inibidores de Proteínas Quinases , Antineoplásicos/química , Modelos Moleculares , Linhagem Celular Tumoral , Simulação de Acoplamento Molecular , Ensaios de Seleção de Medicamentos Antitumorais , Proliferação de Células , Relação Estrutura-Atividade , Estrutura Molecular
3.
J Environ Manage ; 357: 120799, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38581895

RESUMO

Policies and management decisions in the marine environment are driven in part by public sentiment which can grow more intense during hazard events like Harmful Algae Blooms (HABs). The public conversations on social media sites like Twitter (before X) reveal the polarized nature of HABs through nuanced language and sentiment. This article uses mixed methods of machine learned topic modeling and inductive qualitative coding to describe the ways the long-term 2017-2019 Karenia brevis "red tide" bloom were politicized across Florida's South West coast. It finds that there are topical differences in keywords related to place (e.g. beach, Florida, coast), agent (individual or organization), and epistemic values (reliance on scientific and/or media reports). These topical differences demonstrate different levels of politicization and partisanship in qualitative analysis. Conceptually, this research demonstrates the ways different dimensions of a long-duration marine hazard can be polarized. Regarding management, this research provides insights to political and organizational stakeholders and the gaps in the discourse shaping marine hazards which can be used to strategically guide future social media engagement to manage politicization. What if all the careful work that resource and environmental managers do can be undone by simple, seemingly uncontroversial words? In an era of increased environmental and marine distress-coupled with short format communication-the ways environmental managers choose their words is crucial, even between ostensibly inconsequential nouns like "red tide" or "algae bloom." Policies and management decisions in the marine environment are driven in part by public sentiment which can grow more intense during hazard events like Harmful Algae Blooms (HABs). The public conversations on social media sites like Twitter (before X) reveal the polarized nature of HABs through nuanced language and sentiment. This article relies on mining social media posts, and uses mixed methods of machine-learned topic modeling and human-driven inductive qualitative coding to describe the ways the long-term 2017-2019 Karenia brevis "red tide" blooms were politicized across Florida's South West coast. It finds that there are topical differences in keywords related to place (e.g. beach, Florida, coast), agent (individual or organization), and epistemic values (reliance on scientific and/or media reports). These topical differences demonstrate different levels of politicization and partisanship in qualitative analysis. Conceptually, this research demonstrates the ways different dimensions of a long-duration marine hazard can be polarized. Regarding management, this research provides insights to political and organizational stakeholders and the gaps in the discourse shaping marine hazards which can be used to strategically guide future social media engagement to manage politicization.


Assuntos
Dinoflagellida , Mídias Sociais , Humanos , Proliferação Nociva de Algas , Toxinas Marinhas/análise , Florida
4.
J Environ Manage ; 351: 119811, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38157578

RESUMO

Harmful algae blooms (HABs) occur in water bodies throughout the globe and can have multi-faceted impacts on tourism. However, little is known of the magnitude of economic losses to the tourism sector as a result of HABs. There is limited understanding of the empirical relationships between HAB intensity and duration, and the effects of this phenomenon on the tourism sector. This study is based in the state of Florida, USA, a notable sun, sand, and sea destination in the western hemisphere, where blooms of a marine harmful algae are a recurrent threat to coastal tourism. The empirical framework is based on a month and county-level panel database that combines sales by tourism-related businesses with observations from the official HAB surveillance system of the state of Florida. We use time and space fixed-effects regressions to estimate the loss in tourism revenue associated with one additional day of red tide. Results indicate that impacts of HABs on tourism do not follow a linear pattern with increasing HAB concentrations, but rather appear to follow an inverted-U pattern. In other words, higher concentrations of the HAB organism do not necessarily imply higher economic losses, suggesting that the impacts of HABs on tourism are not driven solely by the biophysical element of cell density. Rather, these impacts appear to be mediated and amplified by human dimensions. The loss to tourism-related businesses due to the 2018 Florida red tide bloom was estimated to be $2.7 billion USD, which implies that HABs and their impact on tourism can be considered as a potential 'billion-dollar' disaster.


Assuntos
Proliferação Nociva de Algas , Turismo , Humanos
5.
Artigo em Inglês | MEDLINE | ID: mdl-38594456

RESUMO

OBJECTIVE: To determine the necessity of reduction in the treatment of overriding metaphyseal distal radius fractures (DRF) in children under 11 years. METHODS: In this systematic review and meta-analysis, PubMed, Embase, and Cochrane databases were searched to retrieve studies published from inception to 2023. Two reviewers independently screened for studies with observational or randomized control design comparing two treatments for overriding metaphyseal DRF in patients under 11 years: simple casting without reduction (SC group) versus closed reduction plus casting or pin fixation (CRC/F group); with varying outcomes reported (CRD471761). The risk of bias was assessed using the ROBINS-I tool. RESULTS: Out of 3,024 screened studies, three met the inclusion criteria, 180 children (mean age 7.1 ± 0.9 years) with overriding metaphyseal DRF: SC-group (n = 79) versus CRC/F-group (n = 101). Both treatment groups achieved 100% fracture consolidation without requiring further manipulation. The SC-group showed significantly fewer complications (mean difference [MD] 0.08; 95% CI [0.01, 0.53]; I2 = 22%; P < 0.009) and trends towards better sagittal alignment (MD 5.11; 95% CI [11.92, 1.71]; I2 = 94%; P < 0.14), less reinterventions (MD 0.31; 95% CI [0.01, 8.31]; P < 0.48), and fewer patients with motion limitation at the end of follow-up (MD 0.23; 95% CI [0.03,  1.98]; P < 0.18), although these findings were not statistically significant. CONCLUSIONS: Despite a limited number of studies comparing SC versus CRC/F in overriding DRF in children under 11 years, this study suggests that anatomical reduction is not necessary. Treating these fractures with SC, even when presenting with an overriding position, leads to reduced complications, shows a trend towards fewer reinterventions, improved sagittal alignment, and less limitation in patient motion. LEVEL OF EVIDENCE: Level III, Systematic review of Level-III studies.

6.
J Vasc Interv Radiol ; 34(6): 1070-1074, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36764445

RESUMO

Transjugular intrahepatic portosystemic shunt (TIPS) creation is a standard therapeutic procedure for the management of complications of portal hypertension. However, in small children, this procedure is infrequently performed because of technical difficulties owing to their small size and scarce information on outcomes. This article presents the results of treatment of variceal bleeding with TIPS creation in 8 children weighing <10 kg, along with the description of the unconventional techniques and materials required. Technical and clinical success rates were 100%. Although this was a small cohort of patients, the results obtained suggest that this is a safe and technically and clinically effective treatment option for complications of portal hypertension in this age group.


Assuntos
Varizes Esofágicas e Gástricas , Hipertensão Portal , Derivação Portossistêmica Transjugular Intra-Hepática , Humanos , Criança , Derivação Portossistêmica Transjugular Intra-Hepática/efeitos adversos , Derivação Portossistêmica Transjugular Intra-Hepática/métodos , Varizes Esofágicas e Gástricas/diagnóstico por imagem , Varizes Esofágicas e Gástricas/etiologia , Varizes Esofágicas e Gástricas/cirurgia , Hemorragia Gastrointestinal/diagnóstico por imagem , Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/cirurgia , Hipertensão Portal/diagnóstico por imagem , Hipertensão Portal/cirurgia , Hipertensão Portal/complicações , Resultado do Tratamento
7.
J Cardiovasc Pharmacol ; 81(1): 70-75, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36219195

RESUMO

ABSTRACT: Low-density lipoprotein cholesterol (LDLc) is the lead effector of atherosclerosis and main treatment target. Bempedoic acid is a novel oral drug in the therapeutic armamentarium which is able to reduce LDLc. The objectives of this study were (1) to select the potential patients for administering bempedoic acid such as those with a very high cardiovascular risk in which objectives of LDLc were not achieved despite conventional treatment with PCSK9 inhibitors (PCSK9i) and/or statins and ezetimibe and (2) to estimate the cost-effectiveness of bempedoic acid in different scenarios. The methods used were a multicenter and retrospective study of 652 patients initiating treatment with any PCSK9 inhibitor in 17 different hospitals. Before and on-treatment LDLc cholesterol levels, medical treatments, clinical indication, and baseline characteristics were recorded. The results obtained from 443 subjects in secondary prevention were analyzed. The mean (±) LDLc level at baseline was 142.5 ± 46.4 mg/dL and 61.5 ± 40.5 mg/dL in the follow-up, with a reduction of 55.9% ( P < 0.0001); 71.6% of the patients reached the target of LDL < 55 mg/dL or >50% reduction. Of those patients treated with medium-intensity and low-intensity statins plus PCSK9 inhibitors (with or without ezetimibe), only 5.7% of them were able to reduce LDL below 55 mg/dL and the main LDLc reduction in this group was the lowest (42.9% on average). Patients with TG values >135 mg/dL represented 41.6% of the sample, of which approximately 10% of them were using fibrates. Assuming only LDLc reduction and the UK price, the incremental cost-effectiveness ratio was 88,359€; 83,117€; 82,378€; and 79,015€ for different discount rates. In conclusion, one-third of the patients could achieve the target LDL proposed in the 2019 ESC/EAS guidelines. Approximately 10% of them could also benefit from treating hypertriglyceridemia as indicated in the 2021 ESC guidelines on cardiovascular disease prevention. Patients with medium-intensity and low-intensity statins plus PCSK9i and ezetimibe would be the most benefited. Bempedoic acid could be a not cost-efficacy therapy in all the scenarios, but we need to wait for the CLEAR OUTCOMES Trial results.


Assuntos
Anticolesterolemiantes , Doenças Cardiovasculares , Inibidores de Hidroximetilglutaril-CoA Redutases , Humanos , Anticolesterolemiantes/efeitos adversos , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/epidemiologia , LDL-Colesterol , Análise de Custo-Efetividade , Ezetimiba/efeitos adversos , Fatores de Risco de Doenças Cardíacas , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Inibidores de PCSK9 , Pró-Proteína Convertase 9 , Estudos Retrospectivos , Fatores de Risco
8.
Environ Sci Technol ; 57(13): 5149-5159, 2023 04 04.
Artigo em Inglês | MEDLINE | ID: mdl-36939598

RESUMO

We measured submicron aerosols (PM1) at a beachfront site in Texas in Spring 2021 to characterize the "background" aerosol chemical composition advecting into Texas and the factors controlling this composition. Observations show that marine "background" aerosols from the Gulf of Mexico were highly processed and acidic; sulfate was the most abundant component (on average 57% of total PM1 mass), followed by organic material (26%). These chemical characteristics are similar to those observed at other marine locations globally. However, Gulf "background" aerosols were much more polluted; the average non-refractory (NR-) PM1 mass concentration was 3-70 times higher than that observed in other clean marine atmospheres. Anthropogenic shipping emissions over the Gulf of Mexico explain 78.3% of the total measured "background" sulfate in the Gulf air. We frequently observed haze pollution in the air mass from the Gulf, with significantly elevated concentrations of sulfate, organosulfates, and secondary organic aerosol associated with sulfuric acid. Analysis suggests that aqueous oxidation of shipping emissions over the Gulf of Mexico by peroxides in the particles might potentially be an important pathway for the rapid production of acidic sulfate and organosulfates during the haze episodes under acidic conditions.


Assuntos
Poluentes Atmosféricos , Sulfatos , Sulfatos/análise , Poluentes Atmosféricos/análise , Golfo do México , Oxirredução , Óxidos de Enxofre/análise , Aerossóis/análise , Material Particulado/análise , Monitoramento Ambiental , China
9.
Alzheimers Dement ; 19(5): 1938-1946, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36373344

RESUMO

INTRODUCTION: The Alzheimer's Prevention Initiative Autosomal-Dominant Alzheimer's Disease (API ADAD) Trial evaluated the anti-oligomeric amyloid beta (Aß) antibody therapy crenezumab in cognitively unimpaired members of the Colombian presenilin 1 (PSEN1) E280A kindred. We report availability, methods employed to protect confidentiality and anonymity of participants, and process for requesting and accessing baseline data. METHODS: We developed mechanisms to share baseline data from the API ADAD Trial in consultation with experts and other groups sharing data from Alzheimer's disease (AD) prevention trials, balancing the need to protect anonymity and trial integrity with making data broadly available to accelerate progress in the field. We pressure-tested deliberate and inadvertent potential threats under specific assumptions, employed a system to suppress or mask both direct and indirect identifying variables, limited and firewalled data managers, and put forth specific principles requisite to receive data. RESULTS: Baseline demographic, PSEN1 E280A and apolipoprotein E genotypes, florbetapir and fluorodeoxyglucose positron emission tomography, magnetic resonance imaging, clinical, and cognitive data can now be requested by interested researchers. DISCUSSION: Baseline data are publicly available; treatment data and biological samples, including baseline and treatment-related blood-based biomarker data will become available in accordance with our original trial agreement and subsequently developed Collaboration for Alzheimer's Prevention principles. Sharing of these data will allow exploration of important questions including the differential effects of initiating an investigational AD prevention therapy both before as well as after measurable Aß plaque deposition.


Assuntos
Doença de Alzheimer , Humanos , Doença de Alzheimer/genética , Doença de Alzheimer/prevenção & controle , Peptídeos beta-Amiloides , Tomografia por Emissão de Pósitrons
10.
Eur J Clin Invest ; 52(12): e13863, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36039486

RESUMO

BACKGROUND: Monoclonal antibodies that inhibit the proprotein convertase subtilisin/kexin type 9 (PCSK9) reduce low-density lipoprotein cholesterol (LDLc) by 55%, regardless of baseline treatments. Nonetheless, the effect of other lipid parameters, such as cholesterol remnants or, the so-called lipid residual risk, is unknown. METHODS: Multicenter and retrospective registry of patients treated with PCSK9 inhibitors from 14 different hospitals in Spain. Before and on-treatment lipid parameters were recorded. Residual lipid risk was estimated by (1) cholesterol remnants, (2) triglycerides/HDLc ratio (TG/HDL), (3) total cholesterol/HDLc (TC/HDL) and (4) the triglycerides-to-glucose index (TGGi). RESULTS: Six hundred fifty-two patients were analysed, mean age of 60.2 (9.63) years, 24.69% women and mean LDLc before treatment 149.24 (49.86) mg/dl. Median time to second blood determination was 187.5 days. On-treatment LDLc was 67.46 (45.78) mg/dl, which represented a 55% reduction. Significant reductions were observed for TG/HDL ratio, cholesterol remnants, TC/HDL ratio and TGGi. As consequence, 34.61% patients had LDLc <55 mg/dl and cholesterol remnants <30 mg/dl; additionally, 31.95% had cholesterol remnants <30 mg/dl but LDLc >55 mg/dl. Patients who had levels of cholesterol remnants >30 mg/dl before initiating the treatment with PCSK9 had higher reductions in cholesterol remnants, TG/HDL ratio, TC/HDL and TGGi. By contrast, no reduction differences were observed according to baseline LDLc (< or > the mean), age, gender or obesity. CONCLUSIONS: This multicenter and retrospective registry of real-world patients treated with PCSK9 inhibitors demonstrates a positive effect on cholesterol remnants and lipid residual risk beyond LDLc reductions.


Assuntos
Inibidores de PCSK9 , Pró-Proteína Convertase 9 , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Estudos Retrospectivos , Colesterol , Triglicerídeos , Sistema de Registros , HDL-Colesterol
11.
J Cardiovasc Pharmacol ; 79(4): 523-529, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-34983910

RESUMO

BACKGROUND: Previous evidence supports that monoclonal antibodies that inhibit the proprotein convertase subtilisin/kexin type 9 (PCSK9) reduce low-density lipoprotein cholesterol (LDLc) by 50%-65%, regardless of baseline treatments. We tested possible sex differences in a multicentre registry of real-world patients treated with PCSK9 inhibitors. METHODS: This is a multicentre and retrospective study of 652 patients initiating treatment with any PCSK9 inhibitor in 18 different hospitals. Before-treatment and on-treatment LDLc and medical treatments, clinical indication, and clinical features were recorded. RESULTS: Women represented 24.69% of the cohort. The use of statins was similar in both sexes, but women were receiving most frequently ezetimibe. Before-treatment median LDLc was 135 (interquartile range 115-166) mg, and it was higher in women. The median on-treatment LDLc was 57 (interquartile range 38-84) mg/dL, which represented a mean 54.5% reduction. On-treatment LDLc was higher in women, and the mean LDLc reduction was lower in women (47.4% vs. 56.9%; P = 0.0002) receiving evolocumab or alirocumab. The percentage of patients who achieved ≥50% LDLc reduction was higher in men (71.36% vs. 57.62%; P = 0.002). According to LDLc before-treatment quartiles, LDLc reduction was statistically lower in women in the 2 highest and a significant interaction of women and baseline LDLc >135 mg/dL was observed. Women were negatively associated with lower rates of LDLc treatment target achievement (odds ratio: 0.31). Differences were also observed in women with body mas index >25 kg/m2. Only 14 patients (2.14%) presented side effects. CONCLUSIONS: This multicentre and retrospective registry of real-world patients treated with PCSK9 inhibitors highlights significant gender differences in LDLc reduction.


Assuntos
Anticolesterolemiantes , Inibidores de Hidroximetilglutaril-CoA Redutases , Anticolesterolemiantes/efeitos adversos , LDL-Colesterol , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Masculino , Inibidores de PCSK9 , Pró-Proteína Convertase 9 , Sistema de Registros , Estudos Retrospectivos , Caracteres Sexuais , Fatores Sexuais
12.
J Pediatr Orthop ; 42(7): e756-e761, 2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35671235

RESUMO

BACKGROUND: Many operative methods have been reported for the treatment of congenital radioulnar synostosis (CRUS) and their indications remain controversial. The aim of this study is to evaluate the clinical, radiologic, and functional results of the 2-stage derotational osteotomy with periosteal preservation for CRUS in children. METHODS: From a total of 102 children with CRUS, a retrospective evaluation of 14 consecutive patients (18 forearms) who underwent 2-stage derotational osteotomy of the distal third radius and proximal third ulna with periosteal preservation, bone segment removal, morselization and grafting and cast immobilization was performed. Children with bilateral involvement and/or pronation (>60 degrees), and substantial functional limitations in daily activities were considered candidates for surgery to obtain the desired position of 0 to 20 degrees of pronation. Electronic medical records, preoperative and postoperative clinical and radiologic examinations were reviewed. Also, functional results and parental satisfaction were assessed and statistically analyzed. RESULTS: The median age at the time of surgery was 6.87 (5.02 to 11.22) years. The median follow-up was 38.62 (24.79 to 81.20) months. The median preoperative pronation deformity was 80 (70 to 90) degrees, while the final position was 0 (0 to 10) degrees of pronation ( P <0.01). Elbow flexion and extension showed no changes after surgery. All patients successfully achieved union at 8 (6 to 10) weeks. No complications were observed, and no patient required revision surgeries. The ability to perform daily activities improved markedly, and all patients were satisfied with the results of the surgery. CONCLUSIONS: Two-stage double-level intraperiosteal derotational osteotomy is a safe, simple, and effective procedure in children with CRUS with severe deformity and limitation in performing basic daily living activities. Functional improvement and patient satisfaction are total, and so far no complications have been reported. LEVEL OF EVIDENCE: Level III-treatment study, retrospective comparative study.


Assuntos
Sinostose , Criança , Humanos , Osteotomia/métodos , Rádio (Anatomia)/anormalidades , Estudos Retrospectivos , Sinostose/cirurgia , Ulna/anormalidades , Ulna/cirurgia
13.
Alzheimers Dement ; 18(11): 2272-2282, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35103388

RESUMO

INTRODUCTION: Females may have greater susceptibility to Alzheimer's disease (AD)-pathology. We examined the effect of sex on pathology, neurodegeneration, and memory in cognitively-unimpaired Presenilin-1 (PSEN1) E280A mutation carriers and non-carriers. METHODS: We analyzed baseline data from 167 mutation carriers and 75 non-carriers (ages 30 to 53) from the Alzheimer's Prevention Initiative Autosomal Dominant AD Trial, including florbetapir- and fludeoxyglucose-PET, MRI based hippocampal volume and cognitive testing. RESULTS: Females exhibited better delayed recall than males, controlling for age, precuneus glucose metabolism, and mutation status, although the effect was not significant among PSEN1 mutation carriers only. APOE ε4 did not modify the effect of sex on AD biomarkers and memory. DISCUSSION: Our findings suggest that, among cognitively-unimpaired individuals at genetic risk for autosomal-dominant AD, females may have greater cognitive resilience to AD pathology and neurodegeneration than males. Further investigation of sex-specific differences in autosomal-dominant AD is key to elucidating mechanisms of AD risk and resilience.


Assuntos
Doença de Alzheimer , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Alzheimer/metabolismo , Cognição , Colômbia , Testes Neuropsicológicos , Presenilina-1/genética , Caracteres Sexuais
14.
J Environ Manage ; 314: 115061, 2022 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-35436709

RESUMO

A quantitative assessment of the embodied environmental impacts of infrastructures can provide initial guidance to industry practitioners and engineers at the outset of the construction projects. This study presents the applicability of the Environmentally Extended Input-Output Analysis as a pre-construction evaluation tool for quantifying the embodied environmental impacts of a small diversion dam in Spain. Seven impact categories are assessed from a production-based and consumption-based perspective identifying the main sectors and regions contributing to the environmental impacts. From the consumption-based perspective, Spain is the only contributor to the environmental impacts, and from the production-based perspective, Spain is the main polluting country in all the impact categories contributing on average 68.9%. The use of high quantities of construction material leads to the sectors of steel and cement to significantly increase the environmental impacts. From the production-based perspective, steel and cement contribute on average 29.5% and 17.2%, respectively. From the consumption-based perspective, both sectors account for 74% of the overall environmental impacts. As observed in this case study, the application of the EEIOA model enables engineers and designers to focus during the early design stages on decisions that achieve high embodied impact reductions, such as prioritizing recycled materials for the construction of this infrastructure and, when possible, use materials from a less polluting origin.


Assuntos
Materiais de Construção , Meio Ambiente , Indústrias , Espanha , Aço
15.
J Hand Surg Am ; 46(4): 344.e1-344.e9, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-32611484

RESUMO

Bizarre parosteal osteochondromatous proliferation, or Nora tumor, is an uncommon lesion affecting the tubular bones of the hands and feet. Normally arising from the cortical surface and periosteum of these bones, these lesions histologically consist of a hypercellular cartilaginous cap covering a bony stalk that is surrounded by ossified areas and spindle cell stroma. The differential diagnosis includes conditions involving the periosteum such as chondrosarcoma, parosteal osteosarcoma, osteochondroma, turret exostosis, and florid reactive periostitis. The only effective treatment is wide surgical excision; nevertheless, local recurrence rates are extremely high and may necessitate revision surgery. In the present study, we report 3 cases of Nora lesion located in the hand in pediatric patients. The diagnosis in these cases was challenging owing to their presenting symptoms and radiographic findings. The diagnosis was made based on characteristic findings noted on the radiographic images and was confirmed by histological examination following excision.


Assuntos
Neoplasias Ósseas , Osteocondroma , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/cirurgia , Proliferação de Células , Criança , Diagnóstico Diferencial , Mãos , Humanos , Recidiva Local de Neoplasia , Osteocondroma/diagnóstico por imagem , Osteocondroma/cirurgia
16.
Bioorg Chem ; 103: 104145, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32801082

RESUMO

The oncogenic mutated kinase BRAFV600E is an attractive molecular target because it is expressed in several human cancers, including melanoma. To present, only three BRAF small inhibitors are approved by the FDA for the treatment of patients with metastatic melanoma: Vemurafenib, Dabrafenib and Encorafenib. Although many protocol treatments have been probed in clinical trials, BRAF inhibition has a limited effectiveness because patients invariably develop resistance and secondary toxic effects associated with the therapy. These limitations highlight the importance of designing new and better inhibitors with different structures that could establish different interactions in the active site of the enzyme and therefore decrease resistance progress. Considering the data from our previous report, here we studied two series of derivatives of structural scaffolds as potential BRAF inhibitors: hydroxynaphthalenecarboxamides and substituted piperazinylpropandiols. Our results indicate that structural analogues of substituted piperazinylpropandiols do not show significantly better activities to that previously reported. In contrast, the hydroxynaphthalenecarboxamides derivatives significantly inhibited cell viability and ERK phosphorylation, a measure of BRAF activity, in Lu1205 BRAFV600E melanoma cells. In order to better understand these experimental results, we carried out a molecular modeling study using different combined techniques: docking, MD simulations and quantum theory of atoms in molecules (QTAIM) calculations. Thus, by using this approach we determined that the molecular interactions that stabilize the different molecular complexes are closely related to Vemurafenib, a well-documented BRAF inhibitor. Furthermore, we found that bi-substituted compounds may interact more strongly respect to the mono-substituted analogues, by establishing additional interactions with the DFG-loop at the BRAF-active site. On the bases of these results we synthesized and tested a new series of hydroxynaphthalenecarboxamides bi-substituted. Remarkably, all these compounds displayed significant inhibitory effects on the bioassays performed. Thus, the structural information reported here is important for the design of new BRAFV600E inhibitors possessing this type of structural scaffold.


Assuntos
Antineoplásicos/uso terapêutico , Melanoma/tratamento farmacológico , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Antineoplásicos/farmacologia , Humanos , Modelos Moleculares , Fosforilação
17.
Fam Pract ; 37(3): 390-394, 2020 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-31848589

RESUMO

BACKGROUND: Potentially preventable hospitalizations (PPH) are defined as unplanned hospital admissions which could potentially have been prevented with the provision of effective, timely outpatient care. To better understand and ultimately reduce rates of PPH, a means of identifying those which are actually preventable is required. The Preventability Assessment Tool (PAT) was designed for use by hospital clinicians to assess the preventability of unplanned admissions for chronic conditions. OBJECTIVE: The present study examined the ability of the PAT to distinguish between those unplanned admissions which are preventable and those which are not, compared to the assessments of an Expert Panel. METHODS: Data were collected between November 2014 and June 2017 at three hospitals in NSW, Australia. Participants were community-dwelling patients with unplanned hospital admissions for congestive heart failure, chronic obstructive pulmonary disease, diabetes complications or angina pectoris. A nurse and a doctor caring for the patient made assessments of the preventability of the admission using the PAT. Expert Panels made assessments of the preventability of each admission based on a comprehensive case report and consensus process. RESULTS: There was little concordance between the hospital doctors and nurses regarding the preventability of admissions, nor between the assessments of the Expert Panel and the hospital nurse or the Expert Panel and the hospital doctor. CONCLUSIONS: The PAT demonstrated poor concurrent validity and is not a valid tool for assessing the preventability of unplanned hospital admissions. The use of Expert Panels provides a more rigorous approach to assessing the preventability of such admissions.


Assuntos
Doença Crônica , Hospitalização/estatística & dados numéricos , Avaliação de Resultados em Cuidados de Saúde , Idoso , Idoso de 80 Anos ou mais , Austrália , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
18.
J Pediatr Orthop ; 40(1): e68-e76, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30925579

RESUMO

BACKGROUND: A variety of treatment methods have so far been described for unicameral bone cysts (UBC). However, to the best of our knowledge, no particular consensus has yet been reached on when to operatively treat a patient with a humeral UBC. Therefore, members of the European Pediatric Orthopedic Society (EPOS) and Pediatric Orthopedic Society of North America (POSNA) were surveyed to characterize current treatment preferences. METHODS: An online electronic questionnaire was sent out to all registered EPOS and POSNA members. The survey comprised 45 questions related to the diagnosis, treatment, and follow-up characteristics of patients with UBCs of the humerus. Particular questions related to the nonoperative or surgical treatment of pathologic proximal humerus and humeral shaft fractures were also included. RESULTS: In total, 444 participants (132 EPOS and 292 POSNA members) responded, of whom 400 were actively involved in UBC treatment. The preferred diagnostic modalities to confirm the diagnosis of a UBC in the humerus were radiographs (88%), MRI in cases of questionable diagnosis (58%) or CT scan (8%). For painless UBCs 67% prefer no treatment at all except when the fracture risk is deemed high (then 53% recommend surgery); 71% of respondents would treat painful UBCs with surgery. Most common surgical techniques comprise curettage (45%), artificial bone substitutes (37%), corticosteroid injection (29%), or intramedullary stabilization (eg, rodding; 24%).Fractured, nondisplaced and mildly displaced proximal humerus UBCs and mildly displaced pathologic humerus shaft fractures are all preferably treated nonoperatively (94%, 91%, 83%, respectively). Severely displaced pathologic proximal humerus fractures are treated less often conservatively (36%) than surgically (40%), and severely displaced humerus shaft fractures are preferably treated surgically (63%) by intramedullary stabilization (60%). CONCLUSIONS: There is great variation among EPOS and POSNA members with regards to the diagnosis and treatment of UBCs in the humerus. Although some consensus on general treatment principles is seen, specific surgical treatment indications vary.Prospective randomized-controlled studies are needed to evaluate the outcomes of the different surgical approaches compared with nonoperative strategies. LEVEL OF EVIDENCE: Level V-expert opinion.


Assuntos
Cistos Ósseos/terapia , Fraturas Espontâneas/terapia , Fraturas do Úmero/terapia , Padrões de Prática Médica/tendências , Fraturas do Ombro/terapia , Cistos Ósseos/complicações , Cistos Ósseos/diagnóstico por imagem , Tratamento Conservador , Europa (Continente) , Fraturas Espontâneas/diagnóstico por imagem , Fraturas Espontâneas/etiologia , Humanos , Fraturas do Úmero/diagnóstico por imagem , Fraturas do Úmero/etiologia , Imageamento por Ressonância Magnética , Dor Musculoesquelética/etiologia , América do Norte , Procedimentos Ortopédicos/métodos , Ortopedia , Pediatria , Estudos Prospectivos , Fraturas do Ombro/diagnóstico por imagem , Fraturas do Ombro/etiologia , Inquéritos e Questionários , Tomografia Computadorizada por Raios X
19.
Rev Esp Enferm Dig ; 112(10): 805-806, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32954786

RESUMO

A 43-year-old male with an uneventful history presented with fever and ingestion-triggered retrosternal chest pain of a three-day duration, which was aggravated by deep breathing and the supine position. When asked regarding the possible ingestion of a foreign body he recalled having accidentally swallowed tiny glass shards from a broken bottle.


Assuntos
Esofagite , Corpos Estranhos , Adulto , Esofagite/induzido quimicamente , Esofagite/diagnóstico por imagem , Corpos Estranhos/complicações , Corpos Estranhos/diagnóstico por imagem , Corpos Estranhos/cirurgia , Humanos , Masculino
20.
Am J Transplant ; 19(2): 475-487, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-29900661

RESUMO

Tolerance induction through simultaneous hematopoietic stem cell and renal transplantation has shown promising results, but it is hampered by the toxicity of preconditioning therapies and graft-versus-host disease (GVHD). Moreover, renal function has never been compared to conventionally transplanted patients, thus, whether donor-specific tolerance results in improved outcomes remains unanswered. We collected follow-up data of published cases of renal transplantations after hematopoietic stem cell transplantation from the same donor and compared patient and transplant kidney survival as well as function with caliper-matched living-donor renal transplantations from the Austrian dialysis and transplant registry. Overall, 22 tolerant and 20 control patients were included (median observation period 10 years [range 11 months to 26 years]). In the tolerant group, no renal allograft loss was reported, whereas 3 were lost in the control group. Median creatinine levels were 85 µmol/l (interquartile range [IQR] 72-99) in the tolerant cohort and 118 µmol/l (IQR 99-143) in the control group. Mixed linear-model showed around 29% lower average creatinine levels throughout follow-up in the tolerant group (P < .01). Our data clearly show stable renal graft function without long-term immunosuppression for many years, suggesting permanent donor-specific tolerance. Thus sequential transplantation might be an alternative approach for future studies targeting tolerance induction in renal allograft recipients.


Assuntos
Sobrevivência de Enxerto , Transplante de Células-Tronco Hematopoéticas/mortalidade , Falência Renal Crônica/mortalidade , Transplante de Rim/mortalidade , Doadores Vivos/provisão & distribuição , Adolescente , Adulto , Aloenxertos , Estudos de Casos e Controles , Terapia Combinada , Feminino , Seguimentos , Humanos , Imunossupressores/uso terapêutico , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , Taxa de Sobrevida , Transplante Homólogo , Adulto Jovem
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