bluuebunny/crossref_metadata_2025 huggingface dataset:
Correlação entre os scores dos testes de aptidão funcional GDLAM e escala funcional de Katz de idosos fisicamente independentes
Authors: Araujo Gabriel Vargas Malini , Rica Roberta Luksevicius , Leopoldo Ana Paula Lima , Alonso Angelica Castilho , Silva-Grigoletto Marzo Edir da , Cadore Eduardo , Evangelista Alexandre Lopes , Barbosa Welmo A. , Gomes Michelli Christian Soares Santos , Bocalini Danilo Sales
Published: April 2021

Objetivo: O objetivo deste estudo foi avaliar a correlação entre os testes de aptidão funcional desenvolvido pelo Grupo de Desenvolvimento Latino-Americano para a Maturidade (GDLAM) e a escala de aptidão funcional de Katz em idosos fisicamente independentes. Métodos: Cem idosos com idade ≥ 60 anos participaram do estudo. Os seguintes parâmetros foram investigados: composição corporal (estatura, massa corporal, perimetria), funcionalidade objetiva por meio da aplicação do teste objetivo GDLAM (andar 10m, levantar-se a partir de uma posição sentada, subida da posição prona e levantar-se da cadeira e deslocar-se pela casa) e escala funcional subjetiva de Katz (percepção do idoso seis itens para atividades diárias, como, banhar-se, vestir-se, utilizar o banheiro ou ato de ir ao banheiro para excreções, higiene pessoal, arrumar a roupa, transferência, avaliada no desempenho de sair da cama e se sentar em uma cadeira e vice-versa, continência, referente a autocontrole de eliminação de urina e fezes e alimentação, ato de dirigir a comida à boca). Resultados: A comparação dos resultados de concordância entre os testes de aptidão física objetivo (GDLAM) e subjetivo (Katz) apresentaram alto grau de concordância entre os scores, tanto na avaliação geral (r = 0,6636) quanto nos grupos feminino (r = 0,8662) quanto masculino (r = 0,8380). Conclusão: Os dois testes de aptidão física se correlacionaram moderadamente e apresentam boa aplicação prática. Isto sugere a intermutabilidade dos testes.
Relação da apneia obstrutiva do sono com consumo de oxigênio, atividade fí­sica e alimentação
Authors: Brito Einstein Zeus Alves de , Guimarães Manoel Pereira , Fernandes Danilo Sobral da Silva , Neves Victor Ribeiro , Gambassi Bruno Bavaresco , Schwingel Paulo Adriano , Mesquita Fabrí­cio Olinda de Souza
Published: April 2021

Objetivo: Avaliar o consumo máximo de oxigênio (VO2máx), nível de atividade física, consumo alimentar e qualidade de vida em pacientes com apneia obstrutiva do sono (AOS). Métodos: Estudo descritivo quali-quantitativo com análise transversal a partir de aplicação de questionários estruturados, realizado em uma clínica privada de Petrolina, PE. A qualidade de vida foi avaliada pelo WHOQOL-bref, o consumo alimentar pelo formulário de marcadores do consumo alimentar que consta no Protocolo do SISVAN e o nível de atividade física pela versão curta do IPAQ. Resultados: Dos 16 pacientes incluídos, 6 não tinham AOS, 4 apresentaram AOS leve, 2 AOS moderada e 4 AOS grave. Sedentarismo foi prevalente em 20% dos pacientes com AOS leve, em 50% dos com AOS moderada e em 75% dos com AOS grave. Consumo alimentar saudável prevaleceu em todos os grupos, com maior consumo de alimentos não saudáveis por pacientes com AOS grave. Foi identificado predomínio de qualidade de vida regular em todos os grupos, necessitando melhorar especialmente o domínio físico de todos eles. Tanto VO2máx quanto o limiar anaeróbico apresentaram valores reduzidos à medida que a gravidade da doença aumentava, sendo menores os valores nos pacientes com a forma mais grave da doença. Conclusão: Foi constatada relação inversa entre AOS mais grave com o VO2máx e os níveis de atividade física dos pacientes analisados. Há um maior consumo de alimentos não saudáveis com má alimentação e comportamento sedentário que constituem importantes fatores de risco para o desenvolvimento e agravamento da doença.
Фармакодинамічна взаємодія модифікованого аналога кінцевого фрагмента нейропептиду Y з речовинами, що пригнічують або збуджують центральну нервову систему
Authors: Гаврилов І. О. , Штриголь С. Ю.
Published: April 2021

Мета дослідження – вивчити взаємодію пептиду NP9 – оригінального модифікованого аналога кінцевого фрагмента нейропептиду Y – з речовинами, що пригнічують (етанол, тіопентал-натрій) або стимулюють (пентилентетразол, тіосемікарбазид) центральну нервову систему (ЦНС).Експеримент проведено на 90 білих нелінійних мишах-самках. Нонапептид NP9 вводили тваринам інтраназально в дозі 0,2 мг/кг за 30 хв до експерименту. Досліджували взаємодію пептиду NP9 з етанолом (5,5 г/кг у вигляді 12,5 % розчину), тіопентал-натрієм (70 мг/кг), пентилентетразолом (75 мг/кг) і тіосемікарбазидом (25 мг/кг). Як референтний препарат використовували Семакс у дозі 0,1 мг/кг інтраназально.Показано, що пептид NP9 не виявляє суттєвого впливу на депримувальну дію етанолу, але пришвидшує настання та збільшує тривалість тіопенталового наркозу, що може вказувати на його ГАМКпозитивні властивості. Суттєвої взаємодії пептиду NP9 з пентилентетразолом і тіосемікарбазидом не було виявлено. Отримані результати вказують на відсутність небезпечних фармакодинамічних взаємодій пептиду NP9 зі сполуками, що збуджують або пригнічують ЦНС за допомогою різних механізмів. Це експериментально обґрунтовує можливість його безпечного використання в комбінаціях з відповідними лікарськими препаратами.
Анализ ЭКГ при моделировании хронической сердечной недостаточности у крыс и курсовом введении нового потенциального препарата «Гипертрил»
Authors: Беленичев И. Ф. , Бак П. Г. , Абрамов А. В. , Кучеренко Л. И. , Бухтиярова Н. В. , Рыженко В. П.
Published: April 2021

Цель исследования – на основании результатов электрокардиографии (ЭКГ) и их анализа оценить кардиопротекторную активность и особенности действия потенциального препарата «Гипертрил» при экспериментальной хронической сердечной недостаточности (ХСН).Экспериментальная часть работы выполнена на 70 белых беспородных крысах массой 190 – 220 г. ХСН моделировали введением доксорубицина (внутрибрюшинно в кумулятивной дозе 15 мг/кг, разделенной на 6 инъекций в течение 14 дней). Исследуемые препараты – Гипертрил вводили 1 раз в сутки внутрижелудочно в дозе 3,5 мг/кг на протяжении 30 суток; метопролола сукцинат – по такой же схеме в дозе 15 мг/кг. Наличие ХСН подтверждали методом ЭКГ при помощи компьютерного анализатора Cardio Com-2000 plus (ХАИ-медика, Украина).Моделирование ХСН у экспериментальных животных приводило к элевации сегмента ST над изолинией примерно на 0,1 мВ (в 14,3 раза), к увеличению сократительной функции желудочков (увеличение амплитуды зубца R на 36 %) в сочетании с удлинением фазы их деполяризации (комплекс QRS) на 11,5 % и реполяризации (зубец Т) на 9,5 % относительно длительности сердечного цикла, снижением спектральной мощности сердечного ритма TPW и увеличением стресс-индекса SI в 2,7 раза, к сокращению времени электрической диастолы до (4,2 ± 0,2) мс (в 11,6 раза). На фоне введения метопролола длительность реполяризации более чем на 40 % превышала аналогичный показатель у интактных крыс и нелеченных животных с ХСН, и составляла 50 % от длительности сердечного цикла RR. Длительность электрической диастолы ТР хотя и увеличивалась в 2 раза по сравнению с животными с ХСН, но оставалась при этом в 5 раз короче, чем у интактных животных. На фоне введения Гипертрила на ЭКГ отмечалась нормализация амплитуды желудочкового зубца R и нормализация амплитуды зубца реполяризации T, существенное снижение амплитуды сегмента ST над изолинией – в 4 раза по сравнению с контрольной группой и в 2,5 раза по сравнению с животными, получавшими курсом метопролол, нормализация длительности комплекса QRS и зубца Т, а также интервала ТР. Это свидетельствует о том, что курсовое применение Гипертрила предотвращает формирование диастолической дисфункции.Полученные результаты являются экспериментальным обоснованиям перспективности дальнейшего исследования потенциального препарата «Гипертрил» в виде таблеток.
Proposed Regulation of Third-Party Funding in Investor-State Dispute Settlement
Authors: Tamlander Matias
Published: April 2021

Third-party litigation funding is increasingly used to finance legal claims in investor-state dispute settlement, with financiers funding investor claims against sovereign states in exchange for a share of potentially substantial compensation rendered in eventual arbitral awards. A chiefly unregulated phenomenon, third-party funding has been perceived especially controversial in the context of the investment arbitration regime, a system some allege is already ingrained with inequities. Third-party funding raises numerous policy questions, such as conflicts of interests, disclosure, costs of the proceedings, and even the entire permissibility of the practice in investor-state dispute settlement. This review raises various issues and concerns related to third-party funding in investor-state dispute settlement and presents the regulatory efforts and criticism thereof with regards to the reform of rules of both the International Centre for Settlement of Investment Disputes and the United Nations Commission on International Trade Law.
First evidence of underwater sounds emitted by the living fossils Lepidurus lubbocki and Triops cancriformis (Branchiopoda: Notostraca)
Authors: Buscaino G , Ceraulo M , Canale DE , Papale E , Marrone F
Published: April 2021

Sound is the most effective means of communication in marine and freshwater ecosystems. However, no data about acoustic emissions from non-malacostracan crustaceans are currently available, so their ability to produce sounds is unknown. For the first time, this study investigated the sound produced by 2 tadpole shrimp species,Triops cancriformisandLepidurus lubbocki.L. lubbockiindividuals were collected from a natural temporary pond in Sicily (Italy), whereasT. cancriformisindividuals were obtained from eggs contained in sediment from a rock pool in Sardinia (Italy). In the laboratory, experimental tanks with the animals (one species at a time) were acoustically monitored. Both species produced high-frequency, wideband pulses distinguishable by their sound pressure level, which was higher inL. lubbocki(146 dB) than inT. cancriformis(130 dB), and by their first and second peak frequencies, which were higher inL. lubbocki(65 and 86 kHz) than inT. cancriformis(63 and 71 kHz). The energy distributions in the power density spectra showed different shapes, as revealed by the 3 dB bandwidth and centre frequency. The pulse durations were 88 and 97 µs inL. lubbockiandT. cancriformis, respectively.L. lubbockipresented a higher emission rate thanT. cancriformisand a marked circadian pattern, with a higher abundance of sounds during the night. This study reports the first evidence of sound emissions from non-malacostracan crustaceans and reveals the high potential of passive acoustic monitoring to detect the presence, abundance, and life cycle of these elusive keystone species of temporary water bodies.
Shifted dynamics of plankton communities in a restored lake: exploring the effects of climate change on phenology through four decades
Authors: Moe SJ , Hobæk A , Persson J , Skjelbred B , Løvik JE
Published: April 2021

Lake surface temperatures have increased globally in recent decades. Climate change can affect lake biota directly via enhanced water temperatures, shorter ice cover duration and prolonged stratification, and indirectly via changes in species interactions. Changes in the seasonal dynamics of phytoplankton and zooplankton can further affect whole lake ecosystems. However, separating the effects of climate change from the more direct and dominating effects of nutrients is a challenge. Our aim was to explore the ecological effects of climate change while accounting for the effects of re-oligotrophication in Lake Mjøsa, the largest lake in Norway. While restoration measures since the 1970s have resulted in strongly reduced nutrient levels, the surface water temperature has increased by almost 0.4°C decade-1 during the same period. We analysed long-term trends and abrupt changes in environmental and biological time series as well as changes in the seasonal dynamics of individual plankton taxa. The general long-term trends in phenology were diverging for phytoplankton (later peaks) vs. zooplankton (earlier peaks). However, individual taxa of both phytoplankton and zooplankton displayed earlier peaks. Earlier peaks of the phytoplankton group Cryptophyceae can be explained by increased spring temperature or other climate-related changes. Earlier onset of population growth of certain zooplankton species (Limnocalanus macrurus and Holopedium gibberum) can also be explained by climatic change, either directly (earlier temperature increase) or more indirectly (earlier availability of Cryptophyceae as a food source). In the long run, climate-related changes in both phytoplankton and zooplankton phenology may have implications for the fish communities of this lake.
Protected area use by two sympatric marine predators repopulating their historical range
Authors: Salton M , Carr M , Tarjan LM , Clarke J , Kirkwood R , Slip D , Harcourt R
Published: April 2021

As large carnivores recover from over-exploitation, managers often lack evidence-based information on species habitat requirements and the efficacy of management practices, particularly where species repopulate areas from which they have long been extirpated. We investigated the movement and habitat use by 2 semi-aquatic carnivores (Australian fur seals Arctocephalus pusillus doriferus and New Zealand fur seals A. forsteri) at the northern end of their distributions in Australia, where after a long absence both are recolonising their historic range. We also assessed male fur seal habitat use overlap with terrestrial and marine protected areas (PAs). While at the margin of the range during winter and early spring, the males remained inshore close to terrestrial sites and where interactions with humans often occur. From early spring, the males from the range margin showed uniform movement toward colonies in the core of the species’ range prior to their breeding seasons. This contrasts with males tracked from the core of the species’ range that returned periodically to colonies during the year, and highlights the importance of range-wide monitoring of a species to inform conservation planning. Habitat use by some males included over 90% of a marine PA at the margin of the species’ range. Most terrestrial haul-outs used were within terrestrial PAs, while sites not protected were on the margin of the range. Despite wide-ranging habits, their dependence on coastal sites, where human access and activities can be regulated and more readily enforced, suggests that terrestrial and marine PAs will continue to play an important role in managing the recovery of these fur seals.
Zero, one or more broods: reproductive plasticity in response to temperature, food, and body size in the live-bearing rosy rockfish Sebastes rosaceus
Authors: Beyer SG , Alonzo SH , Sogard SM
Published: April 2021

Patterns of reproduction, such as size-fecundity relationships used in models to assess fish populations, are generally treated as static through time and invariant to environmental change. However, growing evidence suggests that changes in ocean conditions, such as warming water temperatures and reduced primary productivity, affect life history traits, including reproduction. Under controlled experimental conditions, we documented reproductive plasticity in the live-bearing rosy rockfish Sebastes rosaceus in response to different temperature and feeding regimes, with maternal size as a covariate. Rosy rockfish occur throughout the California Current, a highly dynamic ecosystem for which increased environmental variability is predicted with climate change. Females produced 0-5 larval broods annually. Larger females had disproportionately higher fecundity than smaller females by producing larger-sized broods and a greater number of annual broods. Warmer water temperature decreased the time interval between brood releases, likely reflecting faster egg and larval development. However, warmer temperature did not increase the total number of broods, potentially reflecting a tradeoff with increased metabolic demand. Well-fed females had better body condition and higher annual fecundity compared to poorly fed females, primarily due to a greater number of broods. Conversely, females with poor body condition at the start of the reproductive season did not reproduce, providing possible evidence of delayed maturation at smaller sizes or skipped spawning at larger sizes. Reproductive plasticity (in terms of whether and how many broods are produced per year) in response to the environment likely contributes to high inter-annual variation in population larval production. Understanding the causes and consequences of reproductive plasticity is critical to developing sustainable management strategies and predicting population response to changing climate conditions.
Correlational Analysis of the Availability and Usage of Geographic Information Systems by Students and Lecturers an Higher Educational Institutions
Authors: Osakwe Jude Odiakaosa , Ankome Teresia , Ujakpa Martin
Published: April 2021

There has been a rapid development of Information and communication Technologies (ICTs) globally, and this includes the Geographic Information Systems (GISs) which has evolved over the years and aimed at solving many geographic problems as fast and efficiently as possible. The importance of GIS to students and lecturers in higher educational institutions is it’s ability to easily analyse locations together with the conventional database systems. This paper assessed the correlation between the availability and use of GIS in Higher Educational Institutions (HEIs). The study is exploratory in nature and employed the use of questionnaires as instrument to collect data. Simple random sampling technique was used to select one hundred and ten (110) lecturers one thousand five hundred and seventy-nine (1579) students from a university. Findings revealed that GIS for analysis is still at its lowest ebb and hence calls for an action to motivate or encourage lecturers and students to use it. Though there are indications that GIS will be of great value in schools, students and lecturers they will be happy to use it for their teaching and learning.   The study also revealed availability of GIS was not tied to its usage.
Strategy of Indonesian Navy Big Data Development Using SWOT Analysis and Analytic Hierarchy Process
Authors: Suharjo Bambang , Wibawa Aria Cakra
Published: April 2021

The Indonesian Navy organization has the duties and responsibilities of state sovereignty. In carrying out its duties, very large and large data and real time data include data on ships in all Indonesian waters from satellite and terrestrial AIS, from radar, data from long range cameras, data from other agencies such as weather data, marine accident data, natural disasters data and fishing areas data. The managed data consists of structured, semi-structured and unstructured data. Thus, big data is needed within the Indonesian Navy. Therefore, this study analyzes the strategies that need to be taken to be able to develop a big data in the Indonesian Navy. The method used is qualitative analytic research using SWOT and AHP. The research subjects were Section Heads at command and control center, Head of Section at Information and Data Processing Services. Data With this combined method, the resulting main strategy is to implement Big Data with existing and adequate system resources, manageable costs, set up network infrastructure and sufficient bandwidth using available big data software by optimizing government regulations regarding single data for communication and data sharing from other agencies and optimizing advanced API technology.
Sistem Informasi Geografis (SIG) Pemetaan Lokasi Pertambangan Batu Bara Berbasis Quantum GIS (Studi Kasus: PT. Hasil Bumi Kalimantan)
Authors: Fenando Fenando
Published: April 2021

During this time, the determination of the mine coordinates location done by the fieldman of PT. Kalimantan Earth Results was using a GPS locator. Found 27 points of coal mines and 18 coal ports spread across the southern Sumatra region. At present the process of recording and mapping locations is still done conventionally, causing frequent data loss, inaccuracies in the location of mining and information about mining results are less up-to-date. Systematic determination of location points is needed to make the companies and customers easier to see the coal mine profiles, coal quality, find out the location of each mine, and up-to-date mining results reports via webgis The prototype model was chosen as a method in system development. As well as UML (Unified Modeling Language), Quantum GIS (Qgis) and php will be used for the designers, builders of the webgis. This research is expected to produce a geographic information system (GIS) mapping of coal mining location points.
A potencialidade dos encontros com a rede de proteção social na justiça juvenil restaurativa
Authors: Orth Glaucia Mayara Niedermeyer , Moreira Dircéia , Bourguignon Jussara Ayres
Published: April 2021

O artigo objetivou investigar a potencialidade dos encontros de profissionais da rede de proteção social com os adolescentes autores de ato infracional e seus familiares na justiça restaurativa para o enfrentamento das condições de vulnerabilidade social e acesso a direitos. Realizamos pesquisa bibliográfica e entrevistas semiestruturadas com adolescentes, familiares, facilitadores e membros da rede de proteção social de quatro cidades do país: Caxias do Sul-RS, Ponta Grossa-PR, Belém-PA e Santarém-PA. Os depoimentos dos participantes foram analisados com base na literatura sobre emoções, segundo Espinosa, Vigotski, Marilena Chauí e Bader Sawaia. Concluímos que a autonomia, o protagonismo das famílias, a ampliação da capacidade de escolha e de controle sobre sua vida é um produto que emerge das relações que se estabelecem entre profissionais e famílias, quando regidos por uma lógica intersetorial, pela horizontalidade das relações entre familiares e profissionais, pelo vínculo e afeto mobilizados nos encontros.
Galleria mellonella Larvae as an Infection Model to Investigate sRNA-Mediated Pathogenesis in Staphylococcus aureus
Authors: Ménard Guillaume , Rouillon Astrid , Ghukasyan Gevorg , Emily Mathieu , Felden Brice , Donnio Pierre-Yves
Published: April 2021

Small regulatory RNAs (sRNAs) are key players in bacterial regulatory networks. Monitoring their expression inside living colonized or infected organisms is essential for identifying sRNA functions, but few studies have looked at sRNA expression during host infection with bacterial pathogens. Insufficient in vivo studies monitoring sRNA expression attest to the difficulties in collecting such data, we therefore developed a non-mammalian infection model using larval Galleria mellonella to analyze the roles of Staphylococcus aureus sRNAs during larval infection and to quickly determine possible sRNA involvement in staphylococcal virulence before proceeding to more complicated animal testing. We began by using the model to test infected larvae for immunohistochemical evidence of infection as well as host inflammatory responses over time. To monitor sRNA expression during infection, total RNAs were extracted from the larvae and invading bacteria at different time points. The expression profiles of the tested sRNAs were distinct and they fluctuated over time, with expression of both sprD and sprC increased during infection and associated with mortality, while rnaIII expression remained barely detectable over time. A strong correlation was observed between sprD expression and the mortality. To confirm these results, we used sRNA-knockout mutants to investigate sRNA involvement in Staphylococcus aureus pathogenesis, finding that the decrease in death rates is delayed when either sprD or sprC was lacking. These results demonstrate the relevance of this G. mellonella model for investigating the role of sRNAs as transcriptional regulators involved in staphylococcal virulence. This insect model provides a fast and easy method for monitoring sRNA (and mRNA) participation in S. aureus pathogenesis, and can also be used for other human bacterial pathogens.
Changes in Ground Temperature and Dynamics in Mountain Permafrost in the Swiss Alps
Authors: Haberkorn Anna , Kenner Robert , Noetzli Jeannette , Phillips Marcia
Published: April 2021

Rising air temperatures and increasingly intense precipitation are being observed in the Swiss Alps. These changes strongly affect the evolution of the temperature regime and the dynamics of mountain permafrost. Changes occur at different rates depending on ground ice content. Long-term monitoring reveals progressive warming and degradation of permafrost and accelerating rock glacier velocities. This study analyses changes occurring in ice-rich (excess-ice) and ice-poor mountain permafrost in Switzerland between 1997 and 2019 on the basis of ground temperature and rock glacier dynamics measurements carried out by the WSL Institute for Snow and Avalanche Research SLF at seven sites. Long-term borehole data indicate an increase of ground temperatures at all depths, in particular at ice-poor and nearly snow-free sites. Active layers are thickening at most sites and prolonged periods of active layer thaw are observed. Long autumn zero curtains are observed in ice-rich permafrost, possibly leading to an overall acceleration of rock glaciers. All these changes point towards ongoing permafrost warming and permafrost degradation in future.
Teriparatide and Abaloparatide Have a Similar Effect on Bone in Mice
Authors: Brent Mikkel Bo , Stoltenborg Frederik Eriksen , Brüel Annemarie , Thomsen Jesper Skovhus
Published: April 2021

Three bone anabolic pharmaceuticals are currently approved for treatment of osteoporosis, teriparatide (PTH (1–34)), the parathyroid hormone-related protein analog abaloparatide (ABL), and romosozumab. The present study compared the effect of intermittent PTH (1–34) and ABL on bone tissue directly mole-to-mole in female mice. Forty-seven C57BL/6 mice were randomly allocated to the following groups: Baseline (n = 11), Control (Ctrl) (n = 12), PTH (n = 12), and ABL (n = 12). The mice were injected s.c. with PTH (100 µg/kg), ABL (96 µg/kg), or saline (Ctrl) five days a week for three weeks. To assess the effect of PTH and ABL, the hindlimb bones were analyzed with DXA, µCT, mechanical testing, dynamic bone histomorphometry, and histological quantification of bone cells. In addition, serum calcium concentration was determined. PTH and ABL significantly increased femoral areal bone mineral density (aBMD) (borderline significant p = 0.06 for PTH), femoral mid-diaphyseal bone strength, femoral metaphyseal and epiphyseal and vertebral bone volume fraction (BV/TV), connectivity density, volumetric bone mineral density (vBMD), and bone formation rate (BFR/BS) compared to Ctrl. In addition, ABL also significantly increased mid-diaphyseal cortical thickness and bone area compared to Ctrl. Neither PTH nor ABL significantly increased bone strength at the femoral neck. In conclusion, abaloparatide and PTH have similar bone anabolic properties when compared directly mole-to-mole in mice.
Early Exposure to High-Sucrose Diet Leads to Deteriorated Ovarian Health
Authors: de Melo Giuliane Barros , Soares Jéssica Furtado , Costa Thamyres Cristhina Lima , Benevides Renata Ohana Alves , Vale Caroline Castro , Paes Antonio Marcus de Andrade , Gaspar Renato Simões
Published: April 2021

Background

The metabolic syndrome (MetS) is correlated with disorders of the reproductive system, such as the polycystic ovary syndrome (PCOS). While consumption of a diet rich in carbohydrates is linked to the development of MetS, it is still unclear if this diet leads to ovarian dysfunction and PCOS.

Objectives

We investigated the influence of a high-sucrose diet (HSD) on the ovarian milieu of Wistar rats and studied the correlation between high consumption of sugary drinks and the prevalence of PCOS in women.

Methods

Wistar rats were given a standard laboratory diet (CTR, 10% sucrose, n = 8) or HSD (HSD, 25% sucrose, n = 8) from postnatal day 21 to 120. Animals were evaluated weekly to calculate food intake, feed efficiency and weight gain. Both onset of puberty and estrous cycle were monitored. Metabolic serum biochemistry, organ morphometry and ovarian histology were performed upon euthanasia. In parallel, a fixed-effects multiple linear regression analysis was performed using data from Brazilian states (459 state-year observations) to test the correlation between the consumption of sugar-sweetened beverages (surrogate for HSD intake) and the prevalence of PCOS (surrogate for ovarian dysfunction).

Results

HSD animals showed increased adipose tissue accumulation, hyperglycaemia and insulin resistance when compared to CTR. Interestingly HSD rats also entered puberty earlier than CTR. Moreover, ovaries from HSD animals had an increased number of atretic antral follicles and cystic follicles, which were correlated with the hypertrophy of periovarian adipocytes. Finally, there was a positive correlation between the intake of sugary drinks and prevalence of PCOS in women of reproductive age.

Conclusions

HSD ingestion leads to ovarian dysfunction in rats and could be correlated with PCOS in women, suggesting these alterations could lead to public health issues. Therefore, we reinforce the deleterious impact of HSD to the ovarian system and suggest that the reduction of added sugars intake could be beneficial to ovarian health.
Metformin Attenuates ROS via FOXO3 Activation in Immune Cells
Authors: Hartwig Jelka , Loebel Madlen , Steiner Sophie , Bauer Sandra , Karadeniz Zehra , Roeger Carsten , Skurk Carsten , Scheibenbogen Carmen , Sotzny Franziska
Published: April 2021

Forkhead box O 3 (FOXO3) is a transcription factor involved in cell metabolism, inflammation and longevity. Here, we investigated if metformin can activate FOXO3 in human immune cells and affects the subsequent level of reactive oxygen/nitrogen species (ROS/RNS) in immune cells. AMP-activated protein kinase (AMPK) and FOXO3 activation were investigated by immunoblot or flow cytometry (FC) analysis, respectively. FOXO3 target gene expression was quantified by real-time PCR. ROS/RNS measurement using dichlorodihydrofluorescein diacetate (DCFH-DA) dye was investigated by FC. The role of the FOXO3 single nucleotide polymorphisms (SNPs) rs12212067, rs2802292 and rs12206094 on ROS/RNS production was studied using allelic discrimination PCR. Metformin induced activation of AMPK (pT172) and FOXO3 (pS413). ROS/RNS level was reduced in immune cells after metformin stimulation accompanied by induction of the FOXO3 targets mitochondrial superoxide dismutase and cytochrome c. Studies in Foxo3 deficient (Foxo3-/-) mouse splenocytes confirmed that metformin mediates its effects via Foxo3 as it attenuates ROS/RNS in myeloid cells of wildtype (WT) but not of Foxo3-/- mice. Our results suggest that FOXO3 can be activated by metformin leading to reduced ROS/RNS level in immune cells. This may add to the beneficial clinical effects of metformin observed in large cohort studies on longevity, cardiovascular and cancer risk.
Lung Marginated and Splenic Murine Resident Neutrophils Constitute Pioneers in Tissue-Defense During Systemic E. coli Challenge
Authors: Juzenaite Goda , Secklehner Judith , Vuononvirta Juho , Helbawi Yoseph , Mackey John B. G. , Dean Charlotte , Harker James A. , Carlin Leo M. , Rankin Sara , De Filippo Katia
Published: April 2021

The rapid response of neutrophils throughout the body to a systemic challenge is a critical first step in resolution of bacterial infection such as Escherichia coli (E. coli). Here we delineated the dynamics of this response, revealing novel insights into the molecular mechanisms using lung and spleen intravital microscopy and 3D ex vivo culture of living precision cut splenic slices in combination with fluorescent labelling of endogenous leukocytes. Within seconds after challenge, intravascular marginated neutrophils and lung endothelial cells (ECs) work cooperatively to capture pathogens. Neutrophils retained on lung ECs slow their velocity and aggregate in clusters that enlarge as circulating neutrophils carrying E. coli stop within the microvasculature. The absolute number of splenic neutrophils does not change following challenge; however, neutrophils increase their velocity, migrate to the marginal zone (MZ) and form clusters. Irrespective of their location all neutrophils capturing heat-inactivated E. coli take on an activated phenotype showing increasing surface CD11b. At a molecular level we show that neutralization of ICAM-1 results in splenic neutrophil redistribution to the MZ under homeostasis. Following challenge, splenic levels of CXCL12 and ICAM-1 are reduced allowing neutrophils to migrate to the MZ in a CD29-integrin dependent manner, where the enlargement of splenic neutrophil clusters is CXCR2-CXCL2 dependent. We show directly molecular mechanisms that allow tissue resident neutrophils to provide the first lines of antimicrobial defense by capturing circulating E. coli and forming clusters both in the microvessels of the lung and in the parenchyma of the spleen.
Therapeutic Approaches Targeting the Natural Killer-Myeloid Cell Axis in the Tumor Microenvironment
Authors: Carnevalli Larissa S. , Ghadially Hormas , Barry Simon T.
Published: April 2021

Immunotherapy has transformed cancer treatment by promoting durable clinical responses in a proportion of patients; however, treatment still fails in many patients. Innate immune cells play a key role in the response to immunotherapy. Crosstalk between innate and adaptive immune systems drives T-cell activation but also limits immunotherapy response, as myeloid cells are commonly associated with resistance. Hence, innate cells have both negative and positive effects within the tumor microenvironment (TME), and despite investment in early clinical trials targeting innate cells, they have seen limited success. Suppressive myeloid cells facilitate metastasis and immunotherapy resistance through TME remodeling and inhibition of adaptive immune cells. Natural killer (NK) cells, in contrast, secrete inflammatory cytokines and directly kill transformed cells, playing a key immunosurveillance role in early tumor development. Myeloid and NK cells show reciprocal crosstalk, influencing myeloid cell functional status or antigen presentation and NK effector function, respectively. Crosstalk between myeloid cells and the NK immune network in the TME is especially important in the context of therapeutic intervention. Here we discuss how myeloid and NK cell interactions shape anti-tumor responses by influencing an immunosuppressive TME and how this may influence outcomes of treatment strategies involving drugs that target myeloid and NK cells.
Molecular Characterization of Complement Component 3 (C3) in the Pearl Oyster Pinctada fucata Improves Our Understanding of the Primitive Complement System in Bivalve
Authors: Wang Zhongliang , Liang Xueru , Li Guiying , Liufu Bai , Lin Kaiqi , Li Jinfeng , Wang Jing , Wang Bei
Published: April 2021

As the central component in the complement system, complement component 3 (C3) plays essential roles in both the innate and adaptive immune responses. Here, a C3 gene (designated aspf-C3) was obtained from the pearl oysterPinctada fucataby RT-PCR and rapid amplification of cDNA ends (RACE). Thepf-C3cDNA consists of 5,634 bp with an open reading frame (ORF) of 5,193 bp encoding a protein of 1,730 amino acids with a 19 residue signal peptide. The deduced pf-C3 protein possessed the characteristic structural features present in its homologs and contained the A2M_N_2, ANATO, A2M, A2M_comp, A2M_recep, and C345C domains, as well as the C3 convertase cleavage site, thioester motif, and conserved Cys, His, and Glu residues. Phylogenetic analysis revealed that pf-C3 is closely related to the C3s from other mollusks.Pf-C3mRNA was expressed in all examined tissues including gill, digestive gland, adductor muscle, mantle and foot, while the highest expression was found in the digestive gland. Following the challenge withVibrio alginolyticus,pf-C3expression was significantly induced in hemocytes. Luciferase reporter assays indicated that pf-C3a could activate the NF-κB signal pathway in HEK293T cells. Further knockdown ofpf-C3by specific siRNA could significantly reduce the phagocytosis ofV. alginolyticusby hemocytesin vitro. These results would help increase understanding of the function of C3 in the invertebrate immune system and therefore provide new insights into the roles of the primitive complement system in invertebrates.
LUBAC Suppresses IL-21-Induced Apoptosis in CD40-Activated Murine B Cells and Promotes Germinal Center B Cell Survival and the T-Dependent Antibody Response
Authors: Wang Jingwei , Li Tianbao , Zan Hong , Rivera Carlos E. , Yan Hui , Xu Zhenming
Published: April 2021

B cell activation by Tfh cells, i.e., through CD154 engagement of CD40 and IL-21, and survival within GCs are crucial for the T-dependent Ab response. LUBAC, composed of HOIP, SHARPIN, and HOIL-1, catalyzes linear ubiquitination (Linear M1-Ub) to mediate NF-κB activation and cell survival induced by TNF receptor superfamily members, which include CD40. As shown in this study, B cells expressing the Sharpin null mutation cpdm (Sharpincpdm) could undergo proliferation, CSR, and SHM in response to immunization by a T-dependent Ag, but were defective in survival within GCs, enrichment of a mutation enhancing the BCR affinity, and production of specific Abs. Sharpincpdm B cells stimulated in vitro with CD154 displayed normal proliferation and differentiation, marginally impaired NF-κB activation and survival, but markedly exacerbated death triggered by IL-21. While activating the mitochondria-dependent apoptosis pathway in both Sharpin+/+ and Sharpincpdm B cells, IL-21 induced Sharpincpdm B cells to undergo sustained activation of caspase 9 and caspase 8 of the mitochondria-dependent and independent pathway, respectively, and ultimately caspase 3 in effecting apoptosis. These were associated with loss of the caspase 8 inhibitor cFLIP and reduction in cFLIP Linear M1-Ub, which interferes with cFLIP poly-ubiquitination at Lys48 and degradation. Finally, the viability of Sharpincpdm B cells was rescued by caspase inhibitors but virtually abrogated – together with Linear M1-Ub and cFLIP levels – by a small molecule HOIP inhibitor. Thus, LUBAC controls the cFLIP expression and inhibits the effects of caspase 8 and IL-21-activated caspase 9, thereby suppressing apoptosis of CD40 and IL-21-activated B cells and promoting GC B cell survival.
Host-Directed Therapies: Modulating Inflammation to Treat Tuberculosis
Authors: Krug Stefanie , Parveen Sadiya , Bishai William R.
Published: April 2021

Following infection with Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), most human hosts are able to contain the infection and avoid progression to active TB disease through expression of a balanced, homeostatic immune response. Proinflammatory mechanisms aiming to kill, slow and sequester the pathogen are key to a successful host response. However, an excessive or inappropriate pro-inflammatory response may lead to granuloma enlargement and tissue damage, which may prolong the TB treatment duration and permanently diminish the lung function of TB survivors. The host also expresses certain anti-inflammatory mediators which may play either beneficial or detrimental roles depending on the timing of their deployment. The balance between the timing and expression levels of pro- and anti-inflammatory responses plays an important role in the fate of infection. Interestingly, M. tuberculosis appears to manipulate both sides of the human immune response to remodel the host environment for its own benefit. Consequently, therapies which modulate either end of this spectrum of immune responses at the appropriate time may have the potential to improve the treatment of TB or to reduce the formation of permanent lung damage after microbiological cure. Here, we highlight host-directed TB therapies targeting pro- or anti-inflammatory processes that have been evaluated in pre-clinical models. The repurposing of already available drugs known to modulate these responses may improve the future of TB therapy.
Immune Reconstitution in the Aging Host: Opportunities for Mechanism-Based Therapy in Allogeneic Hematopoietic Cell Transplantation
Authors: Lin Richard J. , Elias Harold K. , van den Brink Marcel R. M.
Published: April 2021

Older patients with hematologic malignancies are increasingly considered for allogeneic hematopoietic cell transplantation with encouraging outcomes. While aging-related thymic dysfunction remains a major obstacle to optimal and timely immune reconstitution post- transplantation, recent accumulating evidence has suggested that various aging hallmarks such as cellular senescence, inflamm-aging, and hematopoietic stem cell exhaustion, could also impact immune reconstitution post-transplantation in both thymic-dependent and independent manner. Here we review molecular and cellular aspects of immune senescence and immune rejuvenation related to allogeneic hematopoietic cell transplantation among older patients and discuss potential strategies for mechanism-based therapeutic intervention.
Surveillance of Resistance to New Antibiotics in an Era of Limited Treatment Options
Authors: Morel Chantal M. , de Kraker Marlieke E. A. , Harbarth Stephan ,   The Enhanced Surveillance Expert Consensus Group (CANSORT-SCI)
Published: April 2021

As with any health threat, our ability to respond to the emergence and spread of antimicrobial resistance depends on our ability to understand the scale of the problem, magnitude, geographical spread, and trends over time. This is especially true for resistance emergence to newer antibiotics coming to the market as last-resort treatments. Yet current antibiotic surveillance systems are limited to monitoring resistance to commonly prescribed drugs that have been on the market for a long time. This qualitative study determined the essential elements and requirements of antimicrobial resistance surveillance for new antibiotics based on literature review, interviews and expert consensus. After an extensive mapping exercise, 10 experts participated in a modified Delphi consultation to identify consensus on all elements required for surveillance of resistance to novel antibiotics. The main findings indicate that there is a need for a two-phase system; an early alert system transitioning to routine surveillance, led by the public sector to gather and share essential data on resistance to newer antibiotics in a transparent manner. The system should be decentralized, run largely from national level, but be coordinated by an arm of an existing international public health institution. Priority should be given to monitoring emergence of resistance among already multi-drug resistant pathogens causing infections, over a broader selection of pathogens to maximize clinical impact. In conclusion, we cannot rely on current AMR surveillance systems to monitor resistance emergence to new antibiotics. A new, public system should be set-up, starting with a focus on detecting resistance emergence, but expanding to a more comprehensive surveillance as soon as there is regional spread of resistance to the new antibiotic. This article provides a framework based on expert agreement, which could guide future initiatives.
Resurgence of an Inborn Attraction for Animate Objects via Thyroid Hormone T3
Authors: Lorenzi Elena , Lemaire Bastien Samuel , Versace Elisabetta , Matsushima Toshiya , Vallortigara Giorgio
Published: April 2021

For inexperienced brains, some stimuli are more attractive than others. Human neonates and newly hatched chicks preferentially orient towards face-like stimuli, biological motion, and objects changing speed. In chicks, this enhances exposure to social partners, and subsequent attachment trough filial imprinting. Early preferences are not steady. For instance, preference for stimuli changing speed fades away after 2 days in chicks. To understand the physiological mechanisms underlying these transient responses, we tested whether early preferences for objects changing speed can be promoted by thyroid hormone 3,5,3′-triiodothyronine (T3). This hormone determines the start of imprinting’s sensitive period. We found that the preference for objects changing speed can be re-established in female chicks treated with T3. Moreover, day-1 chicks treated with an inhibitor of endogenous T3did not show any preference. These results suggest that the time windows of early predispositions and of sensitive period for imprinting are controlled by the same molecular mechanisms.
Proceedings of the Eighth Annual Deep Brain Stimulation Think Tank: Advances in Optogenetics, Ethical Issues Affecting DBS Research, Neuromodulatory Approaches for Depression, Adaptive Neurostimulation, and Emerging DBS Technologies
Authors: Vedam-Mai Vinata , Deisseroth Karl , Giordano James , Lazaro-Munoz Gabriel , Chiong Winston , Suthana Nanthia , Langevin Jean-Philippe , Gill Jay , Goodman Wayne , Provenza Nicole R. , Halpern Casey H. , Shivacharan Rajat S. , Cunningham Tricia N. , Sheth Sameer A. , Pouratian Nader , Scangos Katherine W. , Mayberg Helen S. , Horn Andreas , Johnson Kara A. , Butson Christopher R. , Gilron Ro’ee , de Hemptinne Coralie , Wilt Robert , Yaroshinsky Maria , Little Simon , Starr Philip , Worrell Greg , Shirvalkar Prasad , Chang Edward , Volkmann Jens , Muthuraman Muthuraman , Groppa Sergiu , Kühn Andrea A. , Li Luming , Johnson Matthew , Otto Kevin J. , Raike Robert , Goetz Steve , Wu Chengyuan , Silburn Peter , Cheeran Binith , Pathak Yagna J. , Malekmohammadi Mahsa , Gunduz Aysegul , Wong Joshua K. , Cernera Stephanie , Hu Wei , Wagle Shukla Aparna , Ramirez-Zamora Adolfo , Deeb Wissam , Patterson Addie , Foote Kelly D. , Okun Michael S.
Published: April 2021

We estimate that 208,000 deep brain stimulation (DBS) devices have been implanted to address neurological and neuropsychiatric disorders worldwide. DBS Think Tank presenters pooled data and determined that DBS expanded in its scope and has been applied to multiple brain disorders in an effort to modulate neural circuitry. The DBS Think Tank was founded in 2012 providing a space where clinicians, engineers, researchers from industry and academia discuss current and emerging DBS technologies and logistical and ethical issues facing the field. The emphasis is on cutting edge research and collaboration aimed to advance the DBS field. The Eighth Annual DBS Think Tank was held virtually on September 1 and 2, 2020 (Zoom Video Communications) due to restrictions related to the COVID-19 pandemic. The meeting focused on advances in: (1) optogenetics as a tool for comprehending neurobiology of diseases and on optogenetically-inspired DBS, (2) cutting edge of emerging DBS technologies, (3) ethical issues affecting DBS research and access to care, (4) neuromodulatory approaches for depression, (5) advancing novel hardware, software and imaging methodologies, (6) use of neurophysiological signals in adaptive neurostimulation, and (7) use of more advanced technologies to improve DBS clinical outcomes. There were 178 attendees who participated in a DBS Think Tank survey, which revealed the expansion of DBS into several indications such as obesity, post-traumatic stress disorder, addiction and Alzheimer’s disease. This proceedings summarizes the advances discussed at the Eighth Annual DBS Think Tank.