On Aharonov-Casher bound states

In this work bound states for the Aharonov-Casher problem are considered. According to Hagen's work on the exact equivalence between spin-1/2 Aharonov-Bohm and Aharonov-Casher effects, is known that the $\boldsymbol{\nabla}\cdot\mathbf{E}$ term cannot be neglected in the Hamiltonian if the spin of particle is considered. This term leads to the existence of a singular potential at the origin. By modeling the problem by boundary conditions at the origin which arises by the self-adjoint extension of the Hamiltonian, we derive for the first time an expression for the bound state energy of the Aharonov-Casher problem. As an application, we consider the Aharonov-Casher plus a two-dimensional harmonic oscillator. We derive the expression for the harmonic oscillator energies and compare it with the expression obtained in the case without singularity. At the end, an approach for determination of the self-adjoint extension parameter is given. In our approach, the parameter is obtained essentially in terms of physics of the problem.Comment: 11 pages, matches published versio

HER Family Receptors are Important Theranostic Biomarkers for Cervical Cancer: Blocking Glucose Metabolism Enhances the Therapeutic Effect of HER Inhibitors

Persistent HPV infection alone is not sufficient for cervical cancer development, which requires additional molecular alterations for tumor progression and metastasis ultimately leading to a lethal disease. In this study, we performed a comprehensive analysis of HER family receptor alterations in cervical adenocarcinoma. We detected overexpression of HER protein, mainly HER2, which was an independent prognostic marker for these patients. By using in vitro and in vivo approaches, we provided evidence that HER inhibitors, allitinib and lapatinib, were effective in reducing cervical cancer aggressiveness. Furthermore, combination of these drugs with glucose uptake blockers could overcome the putative HIF1-a-mediated resistance to HER-targeted therapies. Thus, we propose that the use of HER inhibitors in association with glycolysis blockers can be a potentially effective treatment option for HER-positive cervical cancer patients.FINEP (MCTI/FINEP/MS/SCTIE/DECIT-BIOPLAT (1302/13), Brazil and co-funded by the project “ON.2 SR&TD Integrated Program (NORTE-07-0124-FEDER-000017)” co-funded by Programa Operacional Regional do Norte (ON.2- O Novo Norte), Quadro de Referência Estratégico Nacional (QREN), through Fundo Europeu de Desenvolvimento Regional (FEDER). OM is recipient of a post-doc fellowship (SFRH/BPD/108351/2015) from Fundação para a Ciência e Tecnologia (FCT), Portugal. FC is recipient of a master fellowship (2014/03684-0) from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP). VMG is recipient from a PhD fellowship (SFRH/BD/51997/2012) from Fundação para a Ciência e Tecnologia (FCT), Portugalinfo:eu-repo/semantics/publishedVersio

Pyruvate Dehydrogenase Complex Deficiency: Updating the Clinical, Metabolic and Mutational Landscapes in a Cohort of Portuguese Patients

Background: The pyruvate dehydrogenase complex (PDC) catalyzes the irreversible decarboxylation of pyruvate into acetyl-CoA. PDC deficiency can be caused by alterations in any of the genes encoding its several subunits. The resulting phenotype, though very heterogeneous, mainly affects the central nervous system. The aim of this study is to describe and discuss the clinical, biochemical and genotypic information from thirteen PDC deficient patients, thus seeking to establish possible genotype-phenotype correlations. Results: The mutational spectrum showed that seven patients carry mutations in the PDHA1 gene encoding the E1α subunit, five patients carry mutations in the PDHX gene encoding the E3 binding protein, and the remaining patient carries mutations in the DLD gene encoding the E3 subunit. These data corroborate earlier reports describing PDHA1 mutations as the predominant cause of PDC deficiency but also reveal a notable prevalence of PDHX mutations among Portuguese patients, most of them carrying what seems to be a private mutation (p.R284X). The biochemical analyses revealed high lactate and pyruvate plasma levels whereas the lactate/pyruvate ratio was below 16; enzymatic activities, when compared to control values, indicated to be independent from the genotype and ranged from 8.5% to 30%, the latter being considered a cut-off value for primary PDC deficiency. Concerning the clinical features, all patients displayed psychomotor retardation/developmental delay, the severity of which seems to correlate with the type and localization of the mutation carried by the patient. The therapeutic options essentially include the administration of a ketogenic diet and supplementation with thiamine, although arginine aspartate intake revealed to be beneficial in some patients. Moreover, in silico analysis of the missense mutations present in this PDC deficient population allowed to envisage the molecular mechanism underlying these pathogenic variants. Conclusion: The identification of the disease-causing mutations, together with the functional and structural characterization of the mutant protein variants, allow to obtain an insight on the severity of the clinical phenotype and the selection of the most appropriate therapy.info:eu-repo/semantics/publishedVersio

Health workers' perspectives on asthma care coordination between primary and specialised healthcare in the COVID-19 pandemic: a protocol for a qualitative study in Ecuador and Brazil.

INTRODUCTION: Asthma is a common long-term disorder and strategies to improve asthma control are still a challenge. Integrated delivery of health systems is critical for effective asthma care: there is limited information on experiences of care coordination for asthma from Latin America, especially on perspectives of health personnel and in the context of the COVID-19 pandemic. METHODS AND ANALYSIS: This protocol details a qualitative approach to analyse health workers' perspectives of healthcare coordination for asthma control during COVID-19 pandemic in Ecuador and Brazil, at primary and specialised levels, through in-depth semistructured interviews using a video communications platform. The analysis will identify knowledge and perspectives based on coordination of clinical information, clinical management and administrative coordination. Theoretical sampling will be used to obtain approximately equal numbers of women and men within each level of healthcare; data saturation will be used to determine sample size. Transcripts will be analysed using content-coding procedures to mark quotations related to major topics and subthemes included in the interview guide, and narrative analysis will be based on a theoretical framework for healthcare coordination to identify new themes and subthemes. ETHICS AND DISSEMINATION: Ethical approval was obtained from the ethics committees of Hospital General Docente Calderón, Quito, Ecuador; and Universidade Federal da Bahia, Salvador, Brazil. The findings of this study will be disseminated through peer-reviewed articles, conference presentations and condensed summaries for key stakeholders and partners

The Genome of Anopheles darlingi, the main neotropical Malaria vector

Anopheles darlingi is the principal neotropical malaria vector, responsible for more than a million cases of malaria per year on the American continent. Anopheles darlingi diverged from the African and Asian malaria vectors ∼100 million years ago (mya) and successfully adapted to the New World environment. Here we present an annotated reference A. darlingi genome, sequenced from a wild population of males and females collected in the Brazilian Amazon. A total of 10 481 predicted protein-coding genes were annotated, 72% of which have their closest counterpart in Anopheles gambiae and 21% have highest similarity with other mosquito species. In spite of a long period of divergent evolution, conserved gene synteny was observed between A. darlingi and A. gambiae. More than 10 million single nucleotide polymorphisms and short indels with potential use as genetic markers were identified. Transposable elements correspond to 2.3% of the A. darlingi genome. Genes associated with hematophagy, immunity and insecticide resistance, directly involved in vector–human and vector–parasite interactions, were identified and discussed. This study represents the first effort to sequence the genome of a neotropical malaria vector, and opens a new window through which we can contemplate the evolutionary history of anopheline mosquitoes. It also provides valuable information that may lead to novel strategies to reduce malaria transmission on the South American continent. The A. darlingi genome is accessible a