Dysfunctional suction dynamics in newborns with ankyloglossia / Dinâmica de sucção disfuncional em recém-nascidos com anquiloglossia

ABSTRACT Purpose Compare infant suction in babies with and without ankyloglossia using a microprocessor-controlled pressure sensor coupled to a pacifier. Methods Fifty-five infants from 0 to 2 months of age underwent clinical examination for ankyloglossia, after which they were offered a silicone pacifier connected to the pressure acquisition device and suction activity was recorded. Thus, we extracted the frequency of sucks within a burst, the average suck duration, the burst duration, the number of sucks per burst, the maximum amplitude of sucks per burst and the inter-burst interval. Results The key difference in newborns with ankyloglossia in relation to control was that they perform longer bursts of suction activity. Conclusion The longer burst durations are likely a compensatory strategy and may underlie the pain reported by mothers during breastfeeding. We therefore propose a method for objectively quantifying some parameters of infant suction capacity and demonstrate its use in assisting the evaluation of ankyloglossia.

RESUMO Objetivo Comparar a sucção infantil em bebês com e sem anquiloglossia usando um sensor de pressão controlado por microprocessador acoplado a uma chupeta. Método Cinquenta e cinco lactentes de 0 a 2 meses de idade foram submetidos ao exame clínico de anquiloglossia, em seguida foi oferecido uma chupeta de silicone conectada ao dispositivo de aquisição de pressão e a atividade de sucção foi registrada. Assim, obtivemos dados sobre a frequência de sucções dentro de um período de sucções, a duração média da sucção, a duração da rajada, o número de sucções por rajada, a amplitude máxima das sucções por rajada e o intervalo entre rajadas. O teste t não pareado foi utilizado para comparações entre os grupos. Resultados A principal diferença dos recém-nascidos com anquiloglossia em relação aos do grupo controle é que eles realizam rajadas mais longas durante a atividade de sucção. Conclusão A duração mais longa das rajadas é provavelmente uma estratégia compensatória e pode estar por trás da dor relatada pelas mães durante a amamentação. Portanto, propomos um método para quantificar objetivamente alguns parâmetros da sucção infantil e demonstramos seu uso para auxiliar na avaliação da anquiloglossia.

Are there synergies in the decarbonization of aviation and shipping? An integrated perspective for the case of Brazil.

Aviation and shipping account for 22% of total transport-related CO2 emissions. Low-carbon fuels (such as biofuels and e-fuels) are the most promising alternatives to deeply decarbonize air and maritime transport. A number of technological routes focused on the production of renewable jet fuel can coproduce marine fuels, emulating the economies of scope of crude oil refineries. This work aims to investigate possible synergies in the decarbonization of aviation and shipping in Brazil, selected as an interesting case study. An Integrated Assessment Model (IAM) of national scope is used to explore different combinations of sectoral and national climate targets. This IAM represents not only the energy supply and transport systems but also the agricultural and land-use systems. In the absence of a deep mitigation policy for Brazil, results indicate synergies related to oilseed- and lignocellulosic-based biofuels production routes. Imposing a strict carbon budget to the Brazilian economy compatible with a world well below 2°C, the portfolio of aviation and shipping fuels changes significantly with the need for carbon dioxide removal strategies based on bioenergy. In such a scenario, synergies between the two sectors still exist, but most renewable marine energy supply is a by-product of synthetic diesel produced for road transport, revealing a synergy different from the one originally investigated by this work.

Global roll-out of comprehensive policy measures may aid in bridging emissions gap.

Closing the emissions gap between Nationally Determined Contributions (NDCs) and the global emissions levels needed to achieve the Paris Agreement's climate goals will require a comprehensive package of policy measures. National and sectoral policies can help fill the gap, but success stories in one country cannot be automatically replicated in other countries. They need to be adapted to the local context. Here, we develop a new Bridge scenario based on nationally relevant, short-term measures informed by interactions with country experts. These good practice policies are rolled out globally between now and 2030 and combined with carbon pricing thereafter. We implement this scenario with an ensemble of global integrated assessment models. We show that the Bridge scenario closes two-thirds of the emissions gap between NDC and 2 °C scenarios by 2030 and enables a pathway in line with the 2 °C goal when combined with the necessary long-term changes, i.e. more comprehensive pricing measures after 2030. The Bridge scenario leads to a scale-up of renewable energy (reaching 52%-88% of global electricity supply by 2050), electrification of end-uses, efficiency improvements in energy demand sectors, and enhanced afforestation and reforestation. Our analysis suggests that early action via good-practice policies is less costly than a delay in global climate cooperation.

New set of microsatellite markers for the Great-billed Seed-finch (Sporophila maximiliani - Passeriformes: Thraupidae): tools for inspection and conservation.

The Thraupidae family is one of the most wanted by bird breeders in Brazil because it is represented by its diverse, colorful and melodious singers. The Great-billed Seed-finch, Sporophila maximiliani, is the only representative of the genus Sporophila considered critically endangered in Brazil. Due to the demands of environmental agencies and of conservation programs, there is a need to increase the number of molecular markers available for the genus and specially for S. maximiliani. Therefore, this work aimed to provide a new set of microsatellite markers for S. maximiliani in order to help bird breeders and environmental agencies on fulfilling its demands as well as contributing with extra genetics tools for conservation programs of the S. maximiliani. Of the 30 markers developed, 25 successfully amplified, and 22 were polymorphic. Annealing temperature varied from 52 to 64 °C, number of alleles from 2 to 13, and the medium allele richness was 7.25 and medium expected, observed heterozygosity and PIC were, respectively, 0.812, 0.661 and 0.752. The probability of identity estimate was 8.54 × 10-27 and all the other probabilities of non-exclusion (sib-identity, parent pair and first-parent) were < 0.001, indicating that this set of microsatellite markers have high genetic variability and high power of individual genetic differentiation for S. maximiliani. Therefore, this work increases the options of molecular markers to be used on inspection for environmental agencies and for conservation programs on analyzing genetic variability and population studies for S. maximiliani.

Computational evaluation of natural compounds as potential inhibitors of human PEPCK-M: an alternative for lung cancer therapy.

BACKGROUND: Lung cancer is the leading cause of cancer-related death worldwide. Among its subtypes, non-small cell lung cancer (NSCLC) is the most common. Recently, the mitochondrial isoform of the enzyme phosphoenolpyruvate carboxykinase (HsPEPCK-M) was identified as responsible for the metabolic adaptation in the NSCLC allowing tumor growth even under conditions of glucose deficiency. This adaptation is possible due to the role of HsPEPCK-M in gluconeogenesis, converting the oxaloacetate to phosphoenolpyruvate in the presence of GTP, which plays an important role in the energetic support of these tumors. In this context, it was shown that the inhibition or knockdown of this enzyme was able to induce apoptosis in NSCLC under low glucose conditions. PURPOSE: In this study, novel putative inhibitors were proposed for the human PEPCK-M (HsPEPCK-M) based on a computer-aided approach. METHODS: Comparative modeling was used to generate 3D models for HsPEPCK-M. Subsequently, the set of natural compounds of the ZINC database was screened against HsPEPCK-M models using structure-based pharmacophore modeling and molecular docking approaches. The selected compounds were evaluated according to its chemical diversity and clustered based on chemical similarity. RESULTS: The pharmacophore hypotheses, generated based on known PEPCK inhibitors, were able to select 7,124 candidate compounds. These compounds were submitted to molecular docking studies using three conformations of HsPEPCK-M generated by comparative modeling. The aim was to select compounds with high predicted binding affinity for at least one of the conformations of HsPEPCK-M. After molecular docking, 612 molecules were selected as potential inhibitors of HsPEPCK-M. These compounds were clustered according to their structural similarity. Chemical profiling and binding mode analyses of these compounds allowed the proposal of four promising compounds: ZINC01656421, ZINC895296, ZINC00895535 and ZINC02571340. CONCLUSION: These compounds may be considered as potential candidates for HsPEPCK-M inhibitors and may also be used as lead compounds for the development of novel HsPEPCK-M inhibitors.

Avaliação computacional de compostos naturais como potenciais inibidores para PEPCK-M humana: uma alternativa para terapia contra o câncer de pulmão / Computational evaluation of natural compounds as potential inhibitors for human PEPCK-M: an alternative for lung cancer therapy

O câncer de pulmão é a principal causa de morte relacionada ao câncer no mundo. Entre os seus subtipos, o câncer de pulmão de células não-pequenas (CPCNP) é o mais frequente. Apesar dos tratamentos disponíveis, a taxa de sobrevida ainda é baixa para este subtipo, enfatizando a necessidade de novas alternativas terapêuticas. Recentemente, a isoforma mitocondrial da enzima fosfoenolpiruvato carboxiquinase (HsPEPCK-M) foi apontada como responsável pela adaptação metabólica no CPCNP capaz de permitir o crescimento tumoral mesmo em condições de deficiência de glicose. Esta adaptação é possível devido a função da HsPEPCK-M na gliconeogênese, convertendo o oxaloacetato em fosfoenolpiruvato na presença de GTP, o que representa um papel importante no suporte energético desses tumores. Neste contexto, foi demonstrado que a inibição ou knockdown desta enzima foi capaz de induzir a apoptose em CPCNP em condições de baixa glicose. Estes dados realçam a importância de identificar inibidores eficazes para HsPEPCK-M que possam, potencialmente, se tornar uma alternativa para o tratamento do CPCNP

Neste estudo, novos inibidores putativos foram propostos para a PEPCK-M humana (HsPEPCK-M) com base em uma abordagem guiada por computador, incluindo a modelagem de farmacóforo baseada em estrutura e triagem por atracamento molecular. As hipóteses de farmacóforo geradas foram utilizadas para a triagem virtual do conjunto de compostos naturais do banco ZINC, produzindo 7.124 compostos candidatos. Estes foram submetidos à estudos de atracamento molecular utilizando três conformações de HsPEPCK-M geradas por modelagem comparativa. O objetivo foi selecionar compostos com alta afinidade de ligação predita em relação a pelo menos uma das conformações de HsPEPCK-M. Após o atracamento molecular, 612 moléculas foram selecionadas como potenciais inibidores de HsPEPCK-M. Estes compostos foram então agrupados de acordo com sua similaridade estrutural. A análise do perfil químico e as análises do modo de ligação destes compostos permitiram a proposta de quatro compostos promissores: ZINC01656421, ZINC895296, ZINC00895535 e ZINC02571340. Estes compostos podem ser considerados potenciais candidatos a inibidores de HsPEPCK-M e também podem ser utilizados como compostos líderes para o desenvolvimento de novos inibidores de HsPEPCK-M. (AU)

Docking simulation between HIV peptidase inhibitors and Trypanosoma cruzi aspartyl peptidase.

OBJECTIVE: The low investment in research, diagnosis and treatment are factors that contribute to the continuity of Chagas' disease as a neglected tropical diseases (NTDs). In this context, the repositioning of drugs represents a useful strategy, in the search for new chemotherapeutic approaches for NTDs. HIV aspartic peptidase inhibitors (HIV IPs) are good candidates for drug repurposing. Here, we modeled the three dimensional structure of an aspartyl peptidase of Trypanosoma cruzi, the causative agent of Chagas' disease, aligned it to the HIV aspartyl peptidase and performed docking binding assays with the HIV PIs. RESULTS: The 3D structure confirmed the presence of acid aspartic residues, which are critical to enzyme activity. The docking experiment revealed that HIV IPs bind to the active site of the enzyme, being ritonavir and lopinavir the ones with greater affinity. Benznidazole presented the worst binding affinity, this drug is currently used in Chagas' disease treatment and was included as negative control. These results together with previous data on the trypanocidal effect of the HIV PIs support the hypothesis that a T. cruzi aspartyl peptidase can be the intracellular target of these inhibitors. However, the direct demonstration of the inhibition of T. cruzi aspartyl peptidase activity by HIV PIs is still a goal to be persuaded.

In silico identification of inhibitors of ribose 5-phosphate isomerase from Trypanosoma cruzi using ligand and structure based approaches.

Chagas disease, caused by the protozoan Trypanosoma cruzi, affects approximately seven million people, mainly in Latin America, and causes about 7000 deaths annually. The available treatments are unsatisfactory and search for more effective drugs against this pathogen is critical. In this context, the ribose 5-phosphate isomerase (Rpi) enzyme is a potential drug target mainly due to its function in the pentose phosphate pathway and its essentiality (previously shown in other trypanosomatids). In this study, we propose novel potential inhibitors for the Rpi of T. cruzi (TcRpi) based on a computer-aided approach, including structure-based and ligand-based pharmacophore modeling. Along with a substructural and similarity search, the selected pharmacophore hypotheses were used to screen the purchasable subset of the ZINC Database, yielding 20,183 candidate compounds. These compounds were submitted to molecular docking studies in the TcRpi and Human Rpi (HsRpi) active sites in order to identify potential selective inhibitors for the T. cruzi enzyme. After the molecular docking and ADME-T (absorption, distribution, metabolism, excretion and toxicity)/PAINS (pan-assay interference compounds) screenings, 211 molecules were selected as potential TcRpi inhibitors. Out of these, three compounds - ZINC36975961, ZINC63480117, and ZINC43763931 - were submitted to molecular dynamics simulations and two of them - ZINC36975961 and ZINC43763931- had good performance and made interactions with important active site residues over all the simulation time. These compounds could be considered potential TcRpi inhibitors candidates and also may be used as leads for developing new TcRpi inhibitors.

Structural modeling and docking studies of ribose 5-phosphate isomerase from Leishmania major and Homo sapiens: a comparative analysis for Leishmaniasis treatment.

Leishmaniases are caused by protozoa of the genus Leishmania and are considered the second-highest cause of death worldwide by parasitic infection. The drugs available for treatment in humans are becoming ineffective mainly due to parasite resistance; therefore, it is extremely important to develop a new chemotherapy against these parasites. A crucial aspect of drug design development is the identification and characterization of novel molecular targets. In this work, through an in silico comparative analysis between the genomes of Leishmania major and Homo sapiens, the enzyme ribose 5-phosphate isomerase (R5PI) was indicated as a promising molecular target. R5PI is an important enzyme that acts in the pentose phosphate pathway and catalyzes the interconversion of d-ribose-5-phosphate (R5P) and d-ribulose-5-phosphate (5RP). R5PI activity is found in two analogous groups of enzymes called RpiA (found in H. sapiens) and RpiB (found in L. major). Here, we present the first report of the three-dimensional (3D) structures and active sites of RpiB from L. major (LmRpiB) and RpiA from H. sapiens (HsRpiA). Three-dimensional models were constructed by applying a hybrid methodology that combines comparative and ab initio modeling techniques, and the active site was characterized based on docking studies of the substrates R5P (furanose and ring-opened forms) and 5RP. Our comparative analyses show that these proteins are structural analogs and that distinct residues participate in the interconversion of R5P and 5RP. We propose two distinct reaction mechanisms for the reversible isomerization of R5P to 5RP, which is catalyzed by LmRpiB and HsRpiA. We expect that the present results will be important in guiding future molecular modeling studies to develop new drugs that are specially designed to inhibit the parasitic form of the enzyme without significant effects on the human analog.

Análise da freqüência cardíaca, pressão arterial e duplo-produto em diferentes posições corporais nos exercícios resistidos / Analysis on the cardiac rate, blood pressure and doubled-product in different body positions in resisted exercises

Atualmente, os exercícios resistidos (ER) vêm sofrendo uma série de investigações, devido à importância que atingiram no desenvolvimento do condicionamento cardiorrespiratório e neuromuscular. Para prescrição dos ER, algumas variáveis devem ser monitoradas, tais como freqüência cardíaca (FC) e a pressão arterial (PA). A associação entre FC e PA fornece dados para se obter o duplo produto (DP). Essas variáveis foram utilizadas para analisar e comparar as respostas hemodinâmicas do supino reto sentado (SRS) e o supino reto deitado (SRD), sendo realizadas 10 repetições a 65 por cento de uma repetição máxima (1RM). A amostra foi constituída de 14 indivíduos (10 mulheres e quatro homens), idade 23 (± 4 anos), peso corporal 61 (± 7kg) e estatura 168cm (± 5cm). Como material de coleta foram utilizados freqüencímetro Polar MZ1 (Finlândia), esfigmomanômetro Vasquez-Lubry (Alemanha) e um estetoscópio Littman (EUA). Foi utilizado o teste t-Student pareado, para efeito de comparação entre os valores encontrados nas variáveis fisiológicas. A análise estatística teve como critério de significância p < 0,05. Todas as variáveis apresentaram valor médio mais alto no SRS em relação ao SRD. Foram consideradas FC, PAS, PAD e DP pré e pós-exercício. Entende-se que o valor absoluto da PA medido pelo método auscultatório tende a ser inferior àquele registrado dentro da artéria, mas, em situações de testes em exercícios com intensidades diferentes, a variação percentual da PAS apresenta a mesma tendência que o método invasivo. Concluímos, então, que os exercícios de SRS e SRD não apresentaram diferenças significativas em nenhum dos parâmetros fisiológicos estudados. Porém, no SRD observaram-se respostas um pouco abaixo destes parâmetros. Sendo assim, faz-se necessária realização de outros estudos analisando diferentes posições corporais, para que através de comparações possamos estabelecer uma conduta quanto à prescrição destes exercícios.

Lepra e acromegalia

O autor relata um caso de lepra nervosa e acromegalia. Julga ser o primeiro caso observado, pois revsndo cuidadosamente a literatura, somente encontrou referencia a 2 casos, ambos de lepra cutanea e acromegalia. Diz que a acromegalia é indiscutivel, não podendo entretando, afirmar si é posterior ou anterior á lepra e evidenciar a sua causa. O autor chama ainda a atenção neste caso e em 11 ginecomestias por ele observados, não ter notado lesões evidentes da hipofise pelos processos semiologicos atuaes, não obstante haver sinais clinicos declarados.

Contribuição ao tratamento das dôres em doentes de lepra

Quem trabalha em serviço de lepra, principlamente em hospitais, sabe perfeitamente que entre os males que mais torturam os pacientes e que mais os cruciam, estão sem duvidas as dôres......