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1.
JMIR Aging ; 3(2): e15600, 2020 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-32706650

RESUMO

BACKGROUND: Dementia is a neurodegenerative chronic condition characterized by a progressive decline in a person's memory, thinking, learning skills, and the ability to perform activities of daily living. Previous research has indicated that there are many types of technology interventions available in the literature that have shown promising results in improving disease progression, disease management, and the well-being of people with dementia (PwD) and their informal caregiver, thus facilitating dementia care and living. Technology-driven home care interventions, such as Connected Health (CH), could offer a convenient and low-cost alternative to traditional home care, providing an informal caregiver with the support they may need at home while caring for a PwD, improving their physical and mental well-being. OBJECTIVE: This study aimed (1) to create a multidimensional profile for evaluating the well-being progression of the PwD-informal caregiver dyad for a year during their use of a CH platform, designed for monitoring PwD and supporting their informal caregivers at home, and (2) to conduct a long-term follow-up using the proposed well-being profile at different time-interval evaluations. METHODS: The PwD-informal caregiver well-being profile was created based on the World Health Organization International Classification of Functioning considering the following outcomes: functional status, cognitive status, and quality of life for the PwD and mental well-being, sleeping quality, and burden for the informal caregiver. Over a year, comprehensive assessments of these outcomes were conducted every 3 months to evaluate the well-being of PwD-informal caregivers, using international and standardized validated questionnaires. Participants' demographic information was analyzed using descriptive statistics and presented as means and SDs. A nonparametric Friedman test was used to analyze the outcome changes and the progression in the PwD-caregiver dyads and to determine if those changes were statistically significant. RESULTS: There were no significant changes in the well-being of PwD or their caregivers over the year of follow-up, with the majority of the PwD-caregiver dyads remaining stable. The only instances in which significant changes were observed were the functional status in the PwD and sleep quality in their caregivers. In each of these measures, post hoc pairwise comparisons did not indicate that the changes observed were related to the deployment of the CH platform. CONCLUSIONS: The follow-up of this population of PwD and their informal caregivers has shown that disease progression and physical and mental well-being do not change significantly during the time, being a slow and gradual process. The well-being profile created to analyze the potential impact of the CH platform on the PwD-informal caregiver dyad well-being, once validated, could be used as a future tool to conduct the same analyses with other CH technologies for this population. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/13280.

2.
PLoS One ; 15(5): e0233473, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32469923

RESUMO

African Swine Fever (ASF) is one of the most complex and significant diseases from a sanitary-economic perspective currently affecting the world's swine-farming industry. ASF has been endemic in Sardinia (Italy) since 1978, and several control and eradication programmes have met with limited success. In this traditional ASF endemic area, there are three susceptible host populations for this virus sharing the same habitat: wild boar, farmed domestic pigs and non-registered free-ranging pigs (known as "brado" animals). The main goal of this study was to determine and predict fine-scale spatial interactions of this multi-host system in relation to the epidemiology of ASF in the main endemic area of Sardinia, Montes-Orgosolo. To this end, simultaneous monitoring of GPS-GSM collared wild boar and free-ranging pigs sightings were performed to predict interaction indexes through latent selection difference functions with environmental, human and farming factors. Regarding epidemiological assessment, the spatial inter-specific interaction indexes obtained here were used to correlate ASF notifications in wild boar and domestic pig farms. Daily movement patterns, home ranges (between 120.7 and 2,622.8 ha) and resource selection of wild boar were obtained for the first time on the island. Overall, our prediction model showed the highest spatial interactions between wild boar and free-ranging pigs in areas close to pig farms. A spatially explicit model was obtained to map inter-specific interaction over the complete ASF-endemic area of the island. Our approach to monitoring interaction indexes may help explain the occurrence of ASF notifications in wild boar and domestic pigs on a fine-spatial scale. These results support the recent and effective eradication measures taken in Sardinia. In addition, this methodology could be extrapolated to apply in the current epidemiological scenarios of ASF in Eurasia, where exist multi-host systems involving free-ranging pigs and wild boar.


Assuntos
Febre Suína Africana/epidemiologia , Febre Suína Africana/transmissão , Febre Suína Africana/virologia , Vírus da Febre Suína Africana/isolamento & purificação , Vírus da Febre Suína Africana/patogenicidade , Criação de Animais Domésticos , Migração Animal , Animais , Surtos de Doenças/prevenção & controle , Surtos de Doenças/veterinária , Reservatórios de Doenças/veterinária , Reservatórios de Doenças/virologia , Suscetibilidade a Doenças/veterinária , Doenças Endêmicas/prevenção & controle , Doenças Endêmicas/veterinária , Fazendas , Feminino , Sistemas de Informação Geográfica , Itália/epidemiologia , Masculino , Estudos Retrospectivos , Análise Espacial , Sus scrofa , Suínos , Telemetria/veterinária
4.
Sci Total Environ ; 715: 136861, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32040996

RESUMO

Betulaceae family is a dominant tree pollen type in the atmosphere at Northwest Spain, being a major cause of allergenic rhinitis or asthma symptoms. Alnus pollen cause symptoms in the 9-20% of the total hay fever sufferers mean while the 41.89% of patients present a positive skin-prick-test for Betula allergens. Aln g1 and Bet v1 aeroallergens belong to PR-10 protein family and are associated to cross-reactivity processes. Airborne pollen and aeroallergens from Alnus and Betula were sampled during their Main Pollen Season from 2016 to 2019. Pollen sampling was conducted by means of a Hirst volumetric trap and aeroallergens were sampled using a Multi Vial Cyclone Sampler. Alnus flowering took place from January to February, with an average duration of 44 days. Betula bloom occurred from April to May with an average pollen season of 33 days. The major innovation of our study was the first detection of Aln g1 allergens in the atmosphere by using Bet v1 antibodies. This fact verified the cross-reactivity between the main allergens of Betula and Alnus pollen. Along the study period, an average of 18 days/year and 14 days/year with high potential risk of allergy due to Alnus pollen and allergen respectively, was registered. For Betula an average of 16 days/year with high potential risk of allergy due to pollen and 22 days for allergen was registered. The main consequence of the successive bloom of both trees would be the so-called "priming effect". Urban population sensitized to Betula pollen could suffer allergic symptoms during winter (as a consequence of Alnus), and in spring with the manifestation of higher symptoms under low birch pollen grain levels in the atmosphere. The traditional information to prevent allergies, such as the airborne pollen concentrations, should be combined with the data of aeroallergen to identify the real allergenic load in the atmosphere.


Assuntos
Betulaceae , Alérgenos , Betula , Pólen , Espanha
5.
ACS Catal ; 9(12): 11530-11541, 2019 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-31840009

RESUMO

The catalytic subnanometric metal clusters with a few atoms can be regarded as an intermediate state between single atoms and metal nanoparticles (>1 nm). Their molecule-like electronic structures and flexible geometric structures bring rich chemistry and also a different catalytic behavior, in comparison with the single-atom or nanoparticulate counterparts. In this work, by combination of operando IR spectroscopy techniques and electronic structure calculations, we will show a comparative study on Pt catalysts for CO + NO reaction at a very low temperature range (140-200 K). It has been found that single Pt atoms immobilized on MCM-22 zeolite are not stable under reaction conditions and agglomerate into Pt nanoclusters and particles, which are the working active sites for CO + NO reaction. In the case of the catalyst containing Pt nanoparticles (∼2 nm), the oxidation of CO to CO2 occurs in a much lower extension, and Pt nanoparticles become poisoned under reaction conditions because of a strong interaction with CO and NO. Therefore, only subnanometric Pt clusters allow NO dissociation at a low temperature and CO oxidation to occur well on the surface, while CO interaction is weak enough to avoid catalyst poisoning, resulting in a good balance to achieve enhanced catalytic performance.

6.
Oncotarget ; 10(60): 6444-6455, 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31741709

RESUMO

Background: Contradictory results are reported for the role of angiopoietin-like 4 (ANGPTL-4) in the development of cancer-cachexia and inflammation, given its importance in angiogenesis and inflammatory signaling. Our aim was to analyze the levels of ANGPTL-4 in colorectal cancer patients with a stable weight and those with cachexia in order to establish a relationship between ANGPTL-4 and the inflammatory process. Results: Plasma and tumor levels of ANGPTL-4 were higher in CC in comparison to other groups. A positive association was verified between plasmatic ANGPTL-4 and NFκB levels in tumor from CC. In WSC, we identified an association between the plasmatic ANGPTL-4, IL-15, and IL-10 in tumor and IL-15 in MES. Increased levels of NFκB and TNF-R1 in MES were detected in CC in comparison to WSC. Specifically in CC-group, a positive correlation was found between ANGPTL-4 levels and those of IL-1ß, TNF-α, and NFκB in tumor, along with an association between ANGPTL-4 levels with IL-1ß and MCP-1 levels in tumor; and ANGPTL-4 and IL-1ß levels in MES. Methods: We studied 102 patients, who were divided into three groups: control patients (C, n=37), cancer patients with a stable weight (WSC, n=23), and cancer-cachexia patients (CC, n=42). Samples of plasma, tumor, mesenteric (MES) and subcutaneous adipose tissue were removed for the determination of ANGPTL-4 levels and other proinflammatory factors. Conclusions: ANGPTL-4 levels were higher in plasma and tumor of CC-group, and positively associated with pro-inflammatory and pro-tumorigenic factors. Our results suggest an opposite effect of ANGPTL-4 depending on the concentration and presence of cachexia.

7.
Front Vet Sci ; 6: 376, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31737649

RESUMO

African swine fever virus (ASFV) is spreading throughout Eurasia and there is no vaccine nor treatment available, so the control is based on the implementation of strict sanitary measures. These measures include depopulation of infected and in-contact animals and export restrictions, which can lead to important economic losses, making currently African swine fever (ASF) the greatest threat to the global swine industry. ASF has been endemic on the island of Sardinia since 1978, the longest persistence of anywhere in Eurasia. In Sardinia, eradication programs have failed, in large part due to the lack of farm professionalism, the high density of wild boar and the presence of non-registered domestic pigs (free-ranging pigs). In order to clarify how the virus is transmitted from domestic to wild swine, we examined the interaction between free-ranging pigs and wild boar in an ASF-endemic area of Sardinia. To this end, a field study was carried out on direct and indirect interactions, using monitoring by camera trapping in different areas and risk points. Critical time windows (CTWs) for the virus to survive in the environment (long window) and remain infectious (short window) were estimated, and based on these, the number of indirect interactions were determined. Free-ranging pigs indirectly interacted often with wild boar (long window = 6.47 interactions/day, short window = 1.31 interactions/day) and these interactions (long window) were mainly at water sources. They also directly interacted 0.37 times per day, especially between 14:00 and 21:00 h, which is much higher than for other interspecific interactions observed in Mediterranean scenarios. The highly frequent interactions at this interspecific interface may help explain the more than four-decade-long endemicity of ASF on the island. Supporting that free-ranging pigs can act as a bridge to transmit ASFV between wild boar and registered domestic pigs. This study contributes broadly to improving the knowledge on the estimation of frequencies of direct and indirect interactions between wild and free-ranging domestic swine. As well as supporting the importance of the analysis of interspecific interactions in shared infectious diseases, especially for guiding disease management. Finally, this work illustrates the power of the camera-trapping method for analyzing interspecific interfaces.

8.
Sci Rep ; 9(1): 14423, 2019 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-31594957

RESUMO

African swine fever causes substantial economic losses in the swine industry in affected countries. Traditionally confined to Africa with only occasional incursions into other regions, ASF began spreading into Caucasian countries and Eastern Europe in 2007, followed by Western Europe and Asia in 2018. Such a dramatic change in the global epidemiology of ASF has resulted in concerns that the disease may continue to spread into disease-free regions such as the US. In this study, we estimated the risk of introduction of ASF virus into the US through smuggling of pork in air passenger luggage. Results suggest that the mean risk of ASFV introduction into the US via this route has increased by 183.33% from the risk estimated before the disease had spread into Western Europe or Asia. Most of the risk (67.68%) was associated with flights originating from China and Hong Kong, followed by the Russian Federation (26.92%). Five US airports accounted for >90% of the risk. Results here will help to inform decisions related to the design of ASF virus surveillance strategies in the US.

9.
JMIR Aging ; 2(1): e12192, 2019 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-31518262

RESUMO

BACKGROUND: Smart Health technologies (s-Health technologies) are being developed to support people with dementia (PwD) and their informal caregivers at home, to improve care and reduce the levels of burden and stress they experience. However, although s-Health technologies have the potential to facilitate this, the factors influencing a successful implementation in this population are still unknown. OBJECTIVE: The aim of this study was to review existing literature to explore the factors influencing PwD and their informal caregivers' adoption of s-Health technologies for home care. METHODS: Following the Arksey and O'Malley methodology, this study is a scoping review providing a narrative description of the scientific literature on factors influencing s-Health technology adoption for PwD and their informal caregivers. A search was conducted using PubMed, the Cochrane library, the IEEE library, and Scopus. Publications screening was conducted by 2 researchers based on inclusion criteria, and full-text analysis was then conducted by 1 researcher. The included articles were thematically analyzed by 2 researchers to gain an insight into factors influencing adoption that PwD and their informal caregivers have to encounter when using s-Health technologies. Relevant information was identified and coded. Codes were later discussed between the researchers for developing and modifying them and for achieving a consensus, and the researchers organized the codes into broader themes. RESULTS: Emerging themes were built in a way that said something specific and meaningful about the research question, creating a list of factors influencing the adoption of s-Health technologies for PwD and their informal caregivers, including attitudinal aspects, ethical issues, technology-related challenges, condition-related challenges, and identified gaps. A design framework was created as a guide for future research and innovation in the area of s-Health technologies for PwD and their informal caregivers: DemDesCon for s-Health Technologies. DemDesCon for s-Health Technologies addresses 4 domains to consider for the design and development of s-Health technologies for this population: cognitive decline domain, physical decline domain, social domain, and development domain. CONCLUSIONS: Although s-Health technologies have been used in health care scenarios, more work is needed for them to fully achieve their potential for use in dementia care. Researchers, businesses, and public governments need to collaborate to design and implement effective technology solutions for PwD and their informal caregivers, but the lack of clear design guidelines seems to be slowing the process. We believe that the DemDesCon framework will provide them with the guidance and assistance needed for creating meaningful devices for PwD home care and informal caregivers, filling a much-needed space in the present knowledge gap.

10.
JMIR Res Protoc ; 8(8): 13280, 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31464187

RESUMO

BACKGROUND: Dementia disease is a chronic condition that leads a person with dementia (PwD) into a state of progressive deterioration and a greater dependence in performing their activities of daily living (ADL). It is believed nowadays that PwDs and their informal caregivers can have a better life when provided with the appropriate services and support. Connected Health (CH) is a new technology-enabled model of chronic care delivery where the stakeholders are connected through a health portal, ensuring continuity and efficient flow of information. CH has demonstrated promising results regarding supporting informal home care and Aging in Place, and it has been increasingly considered by researchers and health care providers as a method for dementia home care management. OBJECTIVE: This study aims to describe the development and implementation protocol of a CH platform system to support informal caregivers of PwDs at home. METHODS: This is a longitudinal observational mixed methods study where quantitative and qualitative data will be combined for determining the utility of the CH platform for dementia home care. Dyads, consisting of a PwD and their informal caregiver living in the community, will be divided into 2 groups: the intervention group, which will receive the CH technology package at home, and the usual care group, which will not have any CH technology at all. Dyads will be followed up for 12 months during which they will continue with their traditional care plan, but in addition, the intervention group will receive the CH package for their use at home during 6 months (months 3 to 9 of the yearly follow-up). Further comprehensive assessments related to the caregiver's and PwD's emotional and physical well-being will be performed at the initial assessment and at 3, 6, 9, and 12 months using international and standardized validated questionnaires and semistructured individual interviews. RESULTS: This 3-year funded study (2016-2019) is currently in its implementation phase and is expected to finish by December 2019. We believe that CH can potentially change the PwD current care model, facilitating a proactive and preventive model, utilizing self-management-based strategies, and enhancing caregivers' involvement in the management of health care at home for PwDs. CONCLUSIONS: We foresee that our CH platform will provide knowledge and promote autonomy for the caregivers, which may empower them into greater control of the care for PwDs, and with it, improve the quality of life and well-being for the person they are caring for and for themselves through a physical and cognitive decline predictive model. We also believe that facilitating information sharing between all the PwDs' care stakeholders may enable a stronger relationship between them, facilitate a more coordinated care plan, and increase the feelings of empowerment in the informal caregivers. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/13280.

11.
J Med Internet Res ; 21(8): e14086, 2019 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-31407668

RESUMO

BACKGROUND: Health information technologies (HITs) such as electronic health records (EHR) and telemedicine services are currently used to assist clinicians provide care to patients. There are many barriers to HIT adoption, including mismatches between investments and benefits, disruptions in the workflow, and concerns about privacy and confidentiality. The lack of HIT training of health professionals as a workforce is an increasingly recognized and understudied barrier. OBJECTIVE: The purpose of this study is to describe what courses on HIT topics are available at the graduate level for future health professionals in the European Union (EU) and to explore possible determining factors for their exposure to these courses. METHODS: A cross-sectional descriptive study of EU medical schools was performed to explore the prevalence of HIT courses. The curricula of all identified higher learning institutions that offer a medical degree were manually explored to identify graduate-level courses that offer specific training on HIT topics. HIT topics were defined as courses or subjects that provided knowledge on the design, development, use, and implementation of HIT. Associations among potential factors such as population, yearly medical graduates, total number of physicians, EHR presence, and gross domestic product (GDP) were explored. RESULTS: A total of 302 medical schools from the 28 member states of the EU were explored. Only about one-third (90/302, 29.80%) of all medical degree curricula offered any kind of HIT course at the graduate level; in the medical schools that offered HIT courses, the courses were often mandatory (58/90, 64.44%). In most EU countries, HIT courses are offered in less than half of the medical schools, regardless of the country's GDP per capita. Countries with the highest percentages of HIT course presence have the lowest GDP per capita. There seems to be a weak inverse correlation (-0.49) between the two variables (GDP per capita and HIT course presence). There is a trend between the availability of medical human resources and an increase in the presence of HIT courses, with Romania, Croatia, and Greece as outliers in this respect. CONCLUSIONS: The current state of medical training in the EU leaves much room for improvement. Further studies are required for in-depth analysis of the content and manner of instruction that would fit present and future needs of HIT.


Assuntos
Informática Médica/métodos , Médicos/normas , Estudos Transversais , União Europeia , Humanos
12.
Front Genet ; 10: 568, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31249599

RESUMO

Tyrosinase, encoded by TYR gene, is an enzyme that plays a major role in mammalian pigmentation. It catalyzes the oxidation of L-dihydroxy-phenylalanine (DOPA) to DOPA quinone, a precursor of both types of melanin: eumelanin and pheomelanin. TYR is commonly known as the albino locus since mutations in this gene result in albinism in several species. However, many other TYR mutations have been found to cause diluted phenotypes, like the Himalayan or chinchilla phenotypes in mice. The llama (Lama glama) presents a wide variety of coat colors ranging from non-diluted phenotypes (eumelanic and pheomelanic), through different degrees of dilution, to white. To investigate the possible contribution of TYR gene to coat color variation in llamas, we sequenced TYR exons and their flanking regions and genotyped animals with diluted, non-diluted, and white coat, including three blue-eyed white individuals. Moreover, we analyzed mRNA expression levels in skin biopsies by qPCR. TYR coding region presented nine SNPs, of which three were non-synonymous, c.428A > G, c.859G > T, and c.1490G > T. We also identified seven polymorphisms in non-coding regions, including two microsatellites, an homopolymeric repeat, and five SNPs: one in the promoter region (c.1-26C > T), two in the 3'-UTR, and two flanking the exons. Although no complete association was found between coat color and SNPs, c.1-26C > T was partially associated to diluted phenotypes. Additionally, the frequency of the G allele from c.428A > G was significantly higher in white compared to non-diluted. Results from qPCR showed that expression levels of TYR in white llamas were significantly lower (p < 0.05) than those in diluted and non-diluted phenotypes. Screening for variation in regulatory regions of TYR did not reveal polymorphisms that explain such differences. However, data from this study showed that TYR expression levels play a role in llama pigmentation.

13.
J Exp Bot ; 70(15): 4011-4026, 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31173098

RESUMO

Aphids, including the bird cherry-oat aphid (Rhopalosiphum padi), are significant agricultural pests. The wild relative of barley, Hordeum spontaneum 5 (Hsp5), has been described to be partially resistant to R. padi, with this resistance proposed to involve higher thionin and lipoxygenase gene expression. However, the specificity of this resistance to aphids and its underlying mechanistic processes are unknown. In this study, we assessed the specificity of Hsp5 resistance to aphids and analysed differences in aphid probing and feeding behaviour on Hsp5 and a susceptible barley cultivar (Concerto). We found that partial resistance in Hsp5 to R. padi extends to two other aphid pests of grasses. Using the electrical penetration graph technique, we show that partial resistance is mediated by phloem- and mesophyll-based resistance factors that limit aphid phloem ingestion. To gain insight into plant traits responsible for partial resistance, we compared non-glandular trichome density, defence gene expression, and phloem composition of Hsp5 with those of the susceptible barley cultivar Concerto. We show that Hsp5 partial resistance involves elevated basal expression of thionin and phytohormone signalling genes, and a reduction in phloem quality. This study highlights plant traits that may contribute to broad-spectrum partial resistance to aphids in barley.

14.
Front Vet Sci ; 6: 137, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31106218

RESUMO

African swine fever (ASF), the most significant threat to the pig industry worldwide, has spread to more than 55 countries on three continents, and it affects more than 77% of the world swine population. In the European Union, wild boar (Sus scrofa) is the most severely affected host. The main reasons for the unprecedented and constant spread of ASF in Europe are the trade activities, the continuous movement of infected-wild boar populations among regions and the lack of vaccine to prevent ASF infection. In this study, we demonstrate that oral immunization of wild boar with a non-hemadsorbing, attenuated ASF virus of genotype II isolated in Latvia in 2017 (Lv17/WB/Rie1) conferred 92% protection against challenge with a virulent ASF virus isolate (Arm07). This is, to our knowledge, the first report of a promising vaccine against ASF virus in wild boar by oral administration. Further studies should assess the safety of repeated administration and overdose, characterize long-term shedding and verify the genetic stability of the vaccine virus to confirm if Lv17/WB/Rie1 could be used for free-ranging wild boar in ASF control programs.

15.
Cell Rep ; 26(6): 1585-1597.e4, 2019 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-30726740

RESUMO

Spondweni virus (SPOV) is the flavivirus that is most closely related to Zika virus (ZIKV). Although SPOV causes sporadic human infections in Africa, recently it was found in Culex mosquitoes in Haiti. To investigate the pathogenic spectrum of SPOV, we developed infection models in mice. Although two SPOV strains failed to cause disease in immunocompetent mice, each accumulated in the brain, spleen, eye, testis, and kidney when type I interferon signaling was blocked and unexpectedly caused infection, immune cell infiltration, and swelling in the ankle. In pregnant mice, SPOV replicated in the placenta and fetus but did not cause placental insufficiency or microcephaly. We identified human antibodies from ZIKV or DENV immune subjects that neutralized SPOV infection and protected against lethal challenge. Our experiments describe similarities and differences in clinical syndromes between SPOV and ZIKV and suggest that their serological relatedness has implications for antibody therapeutics and flavivirus vaccine development.


Assuntos
Anticorpos Monoclonais/imunologia , Anticorpos Antivirais/imunologia , Reações Cruzadas , Vírus da Dengue/imunologia , Infecções por Flavivirus/imunologia , Zika virus/imunologia , Animais , Anticorpos Neutralizantes/imunologia , Células Cultivadas , Feminino , Infecções por Flavivirus/prevenção & controle , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL
16.
J Am Chem Soc ; 141(5): 1928-1940, 2019 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-30640461

RESUMO

The assumption that oxidative addition is the key step during the cross-coupling reaction of aryl halides has led to the development of a plethora of increasingly complex metal catalysts, thereby obviating in many cases the exact influence of the base, which is a simple, inexpensive, and necessary reagent for this paramount transformation. Here, a combined experimental and computational study shows that the oxidative addition is not the single kinetically relevant step in different cross-coupling reactions catalyzed by sub-nanometer Pt or Pd species, since the reactivity control is shifted toward subtle changes in the base. The exposed metal atoms in the cluster cooperate to enable an extremely easy oxidative addition of the aryl halide, even chlorides, and allow the base to bifurcate the coupling. With sub-nanometer Pd species, amines drive to the Heck reaction, carbonate drives to the Sonogahira reaction, and phosphate drives to the Suzuki reaction, while for Pt clusters and single atoms, good conversion is only achieved using acetate as a base. This base-controlled orthogonal reactivity with ligand-free catalysts opens new avenues in the design of cross-coupling reactions in organic synthesis.

17.
Proc Natl Acad Sci U S A ; 116(5): 1591-1596, 2019 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-30642974

RESUMO

Zika virus (ZIKV) is a major human pathogen and member of the Flavivirus genus in the Flaviviridae family. In contrast to most other insect-transmitted flaviviruses, ZIKV also can be transmitted sexually and from mother to fetus in humans. During recent outbreaks, ZIKV infections have been linked to microcephaly, congenital disease, and Guillain-Barré syndrome. Neutralizing antibodies have potential as therapeutic agents. We report here a 4-Å-resolution cryo-electron microscopy structure of the ZIKV virion in complex with Fab fragments of the potently neutralizing human monoclonal antibody ZIKV-195. The footprint of the ZIKV-195 Fab fragment expands across two adjacent envelope (E) protein protomers. ZIKV neutralization by this antibody is presumably accomplished by cross-linking the E proteins, which likely prevents formation of E protein trimers required for fusion of the viral and cellular membranes. A single dose of ZIKV-195 administered 5 days after virus inoculation showed marked protection against lethality in a stringent mouse model of infection.


Assuntos
Anticorpos Monoclonais/imunologia , Epitopos/imunologia , Infecção por Zika virus/imunologia , Zika virus/imunologia , Animais , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Microscopia Crioeletrônica/métodos , Modelos Animais de Doenças , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Vacinação/métodos , Proteínas do Envelope Viral/imunologia
18.
J Phys Condens Matter ; 31(1): 013002, 2019 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-30499451

RESUMO

Sub nanometer transition metal clusters composed of a small number of atoms exhibit unexpected electronic, optical, magnetic and catalytic properties that often change substantially as a function of cluster atomicity. Several factors influence their unique catalytic behavior, including their discrete electronic structure of molecular-like orbitals and the accessibility of their low-coordinated atoms. In addition, these factors are strongly correlated so that changes in their morphology may provoke large modifications to their electronic structure and vice versa. The thermodynamic instability of clusters makes it necessary to stabilize them with protective ligands in solution or to support them on solid matrices for practical applications, which introduces non-negligible modifications into their properties. Understanding their cause and extent is the key point to potentially achieve a fine tuning of their catalytic behavior. Selected examples are discussed illustrating important points on this matter, such as the influence of cluster morphology on reactivity, the need of anchoring clusters to avoid sintering and deactivation, and the possible formation of clusters in solution or under reaction conditions, with the associated difficulty to identify them as the true active species.

19.
New Phytol ; 221(4): 2250-2260, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30347456

RESUMO

Insect herbivore damage and abundance are often reduced in diverse plant stands. However, few studies have explored whether this phenomenon is a result of plant diversity effects on host plant traits. We explored indirect effects of tree species diversity on herbivory via changes in leaf traits in a long-term forest diversity experiment in Finland. We measured 16 leaf traits and leaf damage by four insect guilds (chewers, gall formers, leaf miners and rollers) on silver birch (Betula pendula) trees growing in one-, two-, three- and five-species mixtures. A decline in the frequency of birch in mixed stands resulted in reduced leaf area. This, in turn, mediated the reduction in chewing damage in mixed stands. In contrast, associational resistance of birch to leaf miners was not trait-mediated but driven directly by concurrent declines in birch frequency as tree species richness increased. Our results show that leaf trait variation across the diversity gradient might promote associational resistance, but these patterns are driven by an increase in the relative abundance of heterospecifics rather than by tree species richness per se. Therefore, accounting for concurrent changes in stand structure and key foliar traits is important for the interpretation of plant diversity effects and predictions of associational patterns.


Assuntos
Biodiversidade , Florestas , Herbivoria/fisiologia , Insetos/fisiologia , Folhas de Planta/fisiologia , Característica Quantitativa Herdável , Animais , Modelos Biológicos , Especificidade da Espécie , Árvores/fisiologia
20.
JMIR Mhealth Uhealth ; 6(5): e10512, 2018 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-29792295

RESUMO

BACKGROUND: Multiple sclerosis (MS) is a non-curable chronic inflammatory disease of the central nervous system that affects more than 2 million people worldwide. MS-related symptoms impact negatively on the quality of life of persons with MS, who need to be active in the management of their health. mHealth apps could support these patient groups by offering useful tools, providing reliable information, and monitoring symptoms. A previous study from this group identified needs, barriers, and facilitators for the use of mHealth solutions among persons with MS. It is unknown how commercially available health apps meet these needs. OBJECTIVE: The main objective of this review was to assess how the features present in MS apps meet the reported needs of persons with MS. METHODS: We followed a combination of scoping review methodology and systematic assessment of features and content of mHealth apps. A search strategy was defined for the two most popular app stores (Google Play and Apple App Store) to identify relevant apps. Reviewers independently conducted a screening process to filter apps according to the selection criteria. Interrater reliability was assessed through the Fleiss-Cohen coefficient (k=.885). Data from the included MS apps were extracted and explored according to classification criteria. RESULTS: An initial total of 581 potentially relevant apps was found. After removing duplicates and applying inclusion and exclusion criteria, 30 unique apps were included in the study. A similar number of apps was found in both stores. The majority of the apps dealt with disease management and disease and treatment information. Most apps were developed by small and medium-sized enterprises, followed by pharmaceutical companies. Patient education and personal data management were among the most frequently included features in these apps. Energy management and remote monitoring were often not present in MS apps. Very few contained gamification elements. CONCLUSIONS: Currently available MS apps fail to meet the needs and demands of persons with MS. There is a need for health professionals, researchers, and industry partners to collaborate in the design of mHealth solutions for persons with MS to increase adoption and engagement.

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