Tuning the reorganization energy of electron transfer in supramolecular ensembles – metalloporphyrin, oligophenylenevinylenes, and fullerene – and the impact on electron transfer kinetics

Oligo(p-phenylenevinylene) (oPPV) wires of various lengths featuring pyridyls at one terminal and C60 moieties at the other, have been used as molecular building blocks in combination with porphyrins to construct a novel class of electron donor–acceptor architectures. These architectures, which are based on non-covalent, directional interactions between the zinc centers of the porphyrins and the pyridyls, have been characterized by nuclear magnetic resonance spectroscopy and mass spectrometry. Complementary physico-chemical assays focused on the interactions between electron donors and acceptors in the ground and excited states. No appreciable electron interactions were noted in the ground state, which was being probed by electrochemistry, absorption spectroscopy, etc.; the electron acceptors are sufficiently decoupled from the electron donors. In the excited state, a different picture evolved. In particular, steady-state and time-resolved fluorescence and transient absorption measurements revealed substantial electron donor–acceptor interactions. These led, upon photoexcitation of the porphyrins, to tunable intramolecular electron-transfer processes, that is, the oxidation of porphyrin and the reduction of C60. In this regard, the largest impact stems from a rather strong distance dependence of the total reorganization energy in stark contrast to the distance independence seen for covalently linked conjugates

Desigualdades sociais em saúde e o câncer de colo do útero no Brasil: uma análise da realidade brasileira

A detecção precoce do câncer de colo do útero, além de outros fatores, está intimamente relacionada com a prevenção e tratamento da infecção pelo papiloma vírus humano (HPV). Todavia, vários elementos contribuem para a detecção tardia e dificuldade de acesso aos tratamentos adequados. Por isso, objetivamos realizar um debate sobre os principais fatores condicionantes para a detecção tardia do câncer de colo do útero na Política Pública de Saúde do Brasil. Como método de construção deste trabalho realizamos uma abordagem qualitativa através de pesquisa de bibliografias relacionadas à temática. Percebemos com base nas bibliografias que, na população brasileira, os fatores de risco para o desenvolvimento de câncer de colo do útero estão intrinsecamente relacionados com o baixo nível socioeconômico e as grandes dificuldades de acesso à rede de atenção básica.Facultad de Trabajo Socia

Desigualdades sociais em saúde e o câncer de colo do útero no Brasil: uma análise da realidade brasileira

A detecção precoce do câncer de colo do útero, além de outros fatores, está intimamente relacionada com a prevenção e tratamento da infecção pelo papiloma vírus humano (HPV). Todavia, vários elementos contribuem para a detecção tardia e dificuldade de acesso aos tratamentos adequados. Por isso, objetivamos realizar um debate sobre os principais fatores condicionantes para a detecção tardia do câncer de colo do útero na Política Pública de Saúde do Brasil. Como método de construção deste trabalho realizamos uma abordagem qualitativa através de pesquisa de bibliografias relacionadas à temática. Percebemos com base nas bibliografias que, na população brasileira, os fatores de risco para o desenvolvimento de câncer de colo do útero estão intrinsecamente relacionados com o baixo nível socioeconômico e as grandes dificuldades de acesso à rede de atenção básica.Facultad de Trabajo Socia

Maltreatment and parenting in youth with primary and secondary callous‐unemotional traits:Anxiety matters

Background: Youth with conduct disorder (CD) and high callous‐unemotional (CU) traits are not a homogenous group and can be disaggregated into primary and secondary subgroups. However, there are inconsistencies in defining primary and secondary subgroups, with some studies using anxiety, others using maltreatment and still others using both features to identify subgroups. There is a paucity of work comparing primary and secondary subgroups with typically developing (TD) youth on experiences of maltreatment and parenting as well as a lack of studies investigating sex differences. Methods: In a large sample of TD youth (n = 946, 66% female) and youth with CD (n = 885, 60% female), we used latent profile analysis in youth with CD aged between 9 and 18 years to address four aims: (i) to demonstrate how primary and secondary subgroup membership differs when anxiety, maltreatment, or both are used as continuous indicators, (ii) to compare primary and secondary subgroups with TD youth on abuse and neglect measures, and (iii) to compare primary and secondary subgroups with TD youth on parenting experiences, and (iv) to examine whether the results were consistent across sexes. Results: Anxiety without maltreatment yielded the best fitting and most theoretically interpretable classification of primary and secondary subgroups across both sexes (Bayesian information criterion = 17832.33, Entropy = 0.75, Lo‐Mendell‐Rubin: p < 0.01). Compared with TD youth, youth with primary and secondary CU traits experienced greater levels of abuse and neglect (p < 0.001, η2p = 0.04−0.16) and maladaptive parenting practices (p < 0.001, η2p = 0.04−0.13). Youth with primary and secondary CU traits were equally high on levels of abuse, neglect, and maladaptive parenting (all p values >0.05). Conclusions: We provide evidence that anxiety and maltreatment cannot be used interchangeably to identify youth with primary versus secondary CU traits. Anxiey yielded the best fitting and most theoretically interpretable classifications across both sexes. Our results signify the need for researchers and clinicians to adopt a unified approach to defining primary and secondary subgroups of CU traits using anxiety in both sexes

Phosphatidylinositol 3-Kinase -Selective Inhibition With Alpelisib (BYL719) in PIK3CA-Altered Solid Tumors: Results From the First-in-Human Study

PurposeWe report the first-in-human phase Ia study to our knowledge (ClinicalTrials.gov identifier: NCT01219699) identifying the maximum tolerated dose and assessing safety and preliminary efficacy of single-agent alpelisib (BYL719), an oral phosphatidylinositol 3-kinase (PI3K)-selective inhibitor.Patients and MethodsIn the dose-escalation phase, patients with PIK3CA-altered advanced solid tumors received once-daily or twice-daily oral alpelisib on a continuous schedule. In the dose-expansion phase, patients with PIK3CA-altered solid tumors and PIK3CA-wild-type, estrogen receptor-positive/human epidermal growth factor receptor 2-negative breast cancer received alpelisib 400 mg once daily.ResultsOne hundred thirty-four patients received treatment. Alpelisib maximum tolerated doses were established as 400 mg once daily and 150 mg twice daily. Nine patients (13.2%) in the dose-escalation phase had dose-limiting toxicities of hyperglycemia (n = 6), nausea (n = 2), and both hyperglycemia and hypophosphatemia (n = 1). Frequent all-grade, treatment-related adverse events included hyperglycemia (51.5%), nausea (50.0%), decreased appetite (41.8%), diarrhea (40.3%), and vomiting (31.3%). Alpelisib was rapidly absorbed; half-life was 7.6 hours at 400 mg once daily with minimal accumulation. Objective tumor responses were observed at doses 270 mg once daily; overall response rate was 6.0% (n = 8; one patient with endometrial cancer had a complete response, and seven patients with cervical, breast, endometrial, colon, and rectal cancers had partial responses). Stable disease was achieved in 70 (52.2%) patients and was maintained > 24 weeks in 13 (9.7%) patients; disease control rate (complete and partial responses and stable disease) was 58.2%. In patients with estrogen receptor-positive/human epidermal growth factor receptor 2-negative breast cancer, median progression-free survival was 5.5 months. Frequently mutated genes ( 10% tumors) included TP53 (51.3%), APC (23.7%), KRAS (22.4%), ARID1A (13.2%), and FBXW7 (10.5%).ConclusionAlpelisib demonstrated a tolerable safety profile and encouraging preliminary activity in patients with PIK3CA-altered solid tumors, supporting the rationale for selective PI3K inhibition in combination with other agents for the treatment of PIK3CA-mutant tumors

The genomes of two key bumblebee species with primitive eusocial organization

Background: The shift from solitary to social behavior is one of the major evolutionary transitions. Primitively eusocial bumblebees are uniquely placed to illuminate the evolution of highly eusocial insect societies. Bumblebees are also invaluable natural and agricultural pollinators, and there is widespread concern over recent population declines in some species. High-quality genomic data will inform key aspects of bumblebee biology, including susceptibility to implicated population viability threats. Results: We report the high quality draft genome sequences of Bombus terrestris and Bombus impatiens, two ecologically dominant bumblebees and widely utilized study species. Comparing these new genomes to those of the highly eusocial honeybee Apis mellifera and other Hymenoptera, we identify deeply conserved similarities, as well as novelties key to the biology of these organisms. Some honeybee genome features thought to underpin advanced eusociality are also present in bumblebees, indicating an earlier evolution in the bee lineage. Xenobiotic detoxification and immune genes are similarly depauperate in bumblebees and honeybees, and multiple categories of genes linked to social organization, including development and behavior, show high conservation. Key differences identified include a bias in bumblebee chemoreception towards gustation from olfaction, and striking differences in microRNAs, potentially responsible for gene regulation underlying social and other traits. Conclusions: These two bumblebee genomes provide a foundation for post-genomic research on these key pollinators and insect societies. Overall, gene repertoires suggest that the route to advanced eusociality in bees was mediated by many small changes in many genes and processes, and not by notable expansion or depauperation

Adherence to secondary prophylaxis and disease recurrence in 536 Brazilian children with rheumatic fever

<p>Abstract</p> <p>Background</p> <p>More than 15 million people worldwide have rheumatic fever (RF) and rheumatic heart disease due to RF. Secondary prophylaxis is a critical cost-effective intervention for preventing morbidity and mortality related to RF. Ensuring adequate adherence to secondary prophylaxis for RF is a challenging task. This study aimed to describe the rates of recurrent episodes of RF, quantify adherence to secondary prophylaxis, and examine the effects of medication adherence to the rates of RF in a cohort of Brazilian children and adolescents with RF.</p> <p>Methods</p> <p>This retrospective study took place in the Pediatric Rheumatology outpatient clinic at a tertiary care hospital (Instituto de Puericultura e Pediatria Martagão Gesteira) in Rio de Janeiro, Brazil, and included patients with a diagnosis of RF from 1985 to 2005.</p> <p>Results</p> <p>536 patients with RF comprised the study sample. Recurrent episodes of RF occurred in 88 of 536 patients (16.5%). Patients with a recurrent episode of RF were younger (p < 0.0001), more frequently males (p = 0.003), and less adherent (p < 0.0001) to secondary prophylaxis than patients without RF recurrence. Non-adherence to medication at any time during follow-up was detected in 35% of patients. Rates of non-adherence were higher in the group of patients that were lost to follow-up (42%) than in the group of patients still in follow-up (32%) (p = 0.027). Appointment frequency was inadequate in 10% of patients. Higher rates of inadequate appointment frequency were observed among patients who were eventually lost to follow-up (14.5%) than in patients who were successfully followed-up (8%) (p = 0.022). 180 patients (33.5%) were lost to follow up at some point in time.</p> <p>Conclusions</p> <p>We recommend implementation of a registry, and a system of active search of missing patients in every service responsible for the follow-up of RF patients. Measures to increase adherence to secondary prophylaxis need to be implemented formally, once non-adherence to secondary prophylaxis is the main cause of RF recurrence. Detection of irregularity in secondary prophylaxis or in appointments should be an alert about the possibility of loss of follow-up and closer observation should be instituted.</p

Tissue-specific genetic variation suggests distinct molecular pathways between body shape phenotypes and colorectal cancer

It remains unknown whether adiposity subtypes are differentially associated with colorectal cancer (CRC). To move beyond single-trait anthropometric indicators, we derived four multi-trait body shape phenotypes reflecting adiposity subtypes from principal components analysis on body mass index, height, weight, waist-to-hip ratio, and waist and hip circumference. A generally obese (PC1) and a tall, centrally obese (PC3) body shape were both positively associated with CRC risk in observational analyses in 329,828 UK Biobank participants (3728 cases). In genome-wide association studies in 460,198 UK Biobank participants, we identified 3414 genetic variants across four body shapes and Mendelian randomization analyses confirmed positive associations of PC1 and PC3 with CRC risk (52,775 cases/45,940 controls from GECCO/CORECT/CCFR). Brain tissue-specific genetic instruments, mapped to PC1 through enrichment analysis, were responsible for the relationship between PC1 and CRC, while the relationship between PC3 and CRC was predominantly driven by adipose tissue-specific genetic instruments. This study suggests distinct putative causal pathways between adiposity subtypes and CRC