Effectiveness of a Regional Prepregnancy Care Program in Women With Type 1 and Type 2 Diabetes: Benefits beyond glycemic control

OBJECTIVE: To implement and evaluate a regional prepregnancy care program in women with type 1 and type 2 diabetes. RESEARCH DESIGN AND METHODS: Prepregnancy care was promoted among patients and health professionals and delivered across 10 regional maternity units. A prospective cohort study of 680 pregnancies in women with type 1 and type 2 diabetes was performed. Primary outcomes were adverse pregnancy outcome (congenital malformation, stillbirth, or neonatal death), congenital malformation, and indicators of pregnancy preparation (5 mg folic acid, gestational age, and A1C). Comparisons were made with a historical cohort (n = 613 pregnancies) from the same units during 1999-2004. RESULTS: A total of 181 (27%) women attended, and 499 women (73%) did not attend prepregnancy care. Women with prepregnancy care presented earlier (6.7 vs. 7.7 weeks; P < 0.001), were more likely to take 5 mg preconception folic acid (88.2 vs. 26.7%; P < 0.0001) and had lower A1C levels (A1C 6.9 vs. 7.6%; P < 0.0001). They had fewer adverse pregnancy outcomes (1.3 vs. 7.8%; P = 0.009). Multivariate logistic regression confirmed that in addition to glycemic control, lack of prepregnancy care was independently associated with adverse outcome (odds ratio 0.2 [95% CI 0.05-0.89]; P = 0.03). Compared with 1999-2004, folic acid supplementation increased (40.7 vs. 32.5%; P = 0.006) and congenital malformations decreased (4.3 vs. 7.3%; P = 0.04). CONCLUSIONS: Regional prepregnancy care was associated with improved pregnancy preparation and reduced risk of adverse pregnancy outcome in type 1 and type 2 diabetes. Prepregnancy care had benefits beyond improved glycemic control and was a stronger predictor of pregnancy outcome than maternal obesity, ethnicity, or social disadvantage

Retrospective Evaluation of the Role of Gemcitabine-Docetaxel in Well-Differentiated and Dedifferentiated Liposarcoma

OBJECTIVE: Well-differentiated (WDLPS) and dedifferentiated liposarcoma (DDLPS) account for the majority of liposarcomas. Although gemcitabine-docetaxel is used as second-line treatment in soft tissue sarcomas, its efficacy in WDLPS/DDLPS is not established. This study retrospectively analyzed the efficacy of gemcitabine regimens in WDLPS/DDLPS. METHODS: All patients with WDLPS or DDLPS who received gemcitabine-based chemotherapy at our institution between September 2002 and January 2021 were included. Response was evaluated by an independent radiologist using RECIST 1.1. The Kaplan-Meier method was used to estimate distributions of survival outcomes and log-rank tests were used to compare survival outcomes between subgroups. RESULTS: Sixty-five WDLPS/DDLPS patients were included. Seven patients (10.8%) received a gemcitabine-based regimen more than once, totaling 72 treatments. The median age at the start of treatment was 66 years (range 32-80 years). Sixty-five (90.3%) regimens were gemcitabine-docetaxel, and 7 (9.7%) were gemcitabine alone. Majorities of treatments were for disease that was recurrent/metastatic (86.1%), was abdominal/retroperitoneal (83.3%), and had DDLPS components (88.9%), while 25.0% of treatments were for multifocal disease. The overall response rate was 9.7% (7/72). All responses were in patients with documented DDLPS. The median time to progression was 9.2 months (95% CI 5.3-12.3 months). The median overall survival from the start of therapy was 18.8 months (95% CI 13.1-32.4 months). CONCLUSION: Gemcitabine-docetaxel is an efficacious second-line treatment for DDLPS. Though cross study comparisons are not advisable, response to gemcitabine-docetaxel compares favorably to current standard options trabectedin and eribulin. This combination is a valid comparator arm for future second-line trials in DDLPS

Implicit modeling to detail the Temporal Conceptual Model of a Complex Area with remediation of Combined Plumes in the Metropolitan Region of São Paulo

There are contaminated properties and regions that have been named abroad as Complex Areas due to the existence of technical or non-technical challenges that require atypical strategies and timelines for their restoration. One such study area, with more than 20 years of environmental management, was subjected to Implicit Modelling to assist in the detailing and evaluation of its Temporal Conceptual Model. The results reinforced a clear and holistic understanding of its evolution and challenges, including the existence of Combined Plumes generated from distinctly source areas. Interventions in the area were confirmed to have benefited from regional understandings and aspects of Adaptive Management, such as the definition of intermediate objectives, continuous refinement of the conceptual model and remediation. It was concluded that recognizing Complex Areas and applying Adaptive Management has the potential to assist the management of more sites in Brazil. This is recommended to be done while taking into account local adaptations and considerations, such as: including in the definition of Complex Areas that the challenges should demonstrably present high complexity and require atypical times for restoration or rehabilitation (more than 15 years, in São Paulo); considering as a technical challenge the extensive mantle of weathering of humid tropical regions; considering as a technical and non-technical challenge the high number of unregistered catchment wells; considering as a non-technical challenge the existence of socioeconomic conflicts; evaluating, including with isotopic studies, the possible presence of Combined Plumes.Existem propriedades e regiões contaminadas que têm sido denominadas no exterior como Áreas Complexas em virtude de desafios técnicos ou não técnicos que requerem estratégias e prazos atípicos para sua restauração. Uma área de estudo desse tipo, com mais de 20 anos de gerenciamento ambiental, foi objeto de modelagem implícita para auxiliar no detalhamento e avaliação do seu Modelo Conceitual Temporal. Os resultados reforçaram o entendimento claro e holístico sobre sua evolução e seus desafios, incluindo Plumas Combinadas geradas de fontes com localização distinta. Foi confirmado que as intervenções na área se beneficiaram de entendimentos regionais e aspectos de Gerenciamento Adaptativo, tais como a definição de objetivos intermediários e o contínuo aperfeiçoamento do modelo conceitual e da remediação. Concluiu-se que o reconhecimento de Áreas Complexas e a aplicação de Gerenciamento Adaptativo têm o potencial de auxiliar no gerenciamento de mais locais no Brasil. Recomenda-se que isso seja feito contemplando adaptações e considerações locais, tais como: englobar, na definição de Áreas Complexas, que os desafios devem, comprovadamente, apresentar alta complexidade e requerer tempos atípicos para sua restauração ou reabilitação (mais de 15 anos, em São Paulo); considerar como desafio técnico o extenso manto de intemperismo de regiões tropicais úmidas; apreciar como desafio técnico e não técnico o alto número de poços de captação não outorgados; considerar como desafio não técnico a existência de conflitos socioeconômicos; e avaliar, inclusive com estudos isotópicos, a possível presença de Plumas Combinadas

Modelagem implícita para detalhamento do Modelo Conceitual Temporal de Área Complexa com remediação de Plumas Combinadas na Região Metropolitana de São Paulo

Existem propriedades e regiões contaminadas que têm sido denominadas no exterior como Áreas Complexas em virtude de desafios técnicos ou não técnicos que requerem estratégias e prazos atípicos para sua restauração. Uma área de estudo desse tipo, com mais de 20 anos de gerenciamento ambiental, foi objeto de modelagem implícita para auxiliar no detalhamento e avaliação do seu Modelo Conceitual Temporal. Os resultados reforçaram o entendimento claro e holístico sobre sua evolução e seus desafios, incluindo Plumas Combinadas geradas de fontes com localização distinta. Foi confirmado que as intervenções na área se beneficiaram de entendimentos regionais e aspectos de Gerenciamento Adaptativo, tais como a definição de objetivos intermediários e o contínuo aperfeiçoamento do modelo conceitual e da remediação. Concluiu-se que o reconhecimento de Áreas Complexas e a aplicação de Gerenciamento Adaptativo têm o potencial de auxiliar no gerenciamento de mais locais no Brasil. Recomenda-se que isso seja feito contemplando adaptações e considerações locais, tais como: englobar, na definição de Áreas Complexas, que os desafios devem, comprovadamente, apresentar alta complexidade e requerer tempos atípicos para sua restauração ou reabilitação (mais de 15 anos, em São Paulo); considerar como desafio técnico o extenso manto de intemperismo de regiões tropicais úmidas; apreciar como desafio técnico e não técnico o alto número de poços de captação não outorgados; considerar como desafio não técnico a existência de conflitos socioeconômicos; e avaliar, inclusive com estudos isotópicos, a possível presença de Plumas Combinadas

From nucleotides to ribozymes — A comparison of their metal ion binding properties

It is undisputable that the fates of metal ions and nucleic acids are inescapably interwoven. Metal ions are essential for charge compensation of the negatively charged phosphate–sugar backbone, they are instrumental for proper folding, and last but not least they are crucial cofactors for ribozyme catalysis. Considerable progress has been achieved in the past few years on the identification of metal ion binding sites in large DNA and RNA molecules, like in ribozymes including the ribosome. Hereby, most information was gained from crystallography, which fails to explain metal ion binding equilibria in solution as well as the factors that determine the coordination of a metal ion to a specific site. In contrast, such information is readily available for the low-molecular building blocks of large nucleic acids, i.e. for mononucleotides and to some extent also dinucleotides. In this review, we combine and compare for the first time both sets of information. The focus is thereby set on Mg2+, Ca2+, Mn2+, and Cd2+ because these four metal ions are either freely available in cells, have a large impact on the catalytic rate of ribozymes, and/or are often applied in RNA biochemistry. Our comparisons show that results obtained from small molecules can be directly transposed to the findings in large RNA structures like the ribosome. For example, the basic coordination-chemical properties of the different metal ions are reflected in their binding to large nucleic acid structures: macrochelate formation, e.g. the simultaneous intranucleotide coordination of a Mg2+ ion to the phosphate unit and the N7 site of a purine nucleobase (be it inner- or outersphere), is well known for mononucleotides. We show that the frequency of occurrence of this type of coordination is the same for mononucleotides and the ribosome