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1.
Ann Hematol ; 103(3): 725-727, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38279007

RESUMO

It has been proposed that the onset of Acquired Thrombotic Thrombocytopenic Purpura (iTTP) is more severe than subsequent relapses; however, existing studies have limitations. We conducted a retrospective observational study to compare analytical and clinical severity of onset and relapse aTTP cases between 2012 and 2023. A total of 370 episodes of aTTP were analyzed, comprising 272 at initial diagnosis and 98 relapses. At onset, analytical parameters indicative of severity (low hemoglobin, low platelet count, and increased LDH) were significantly worse; patients had severe neurological symptoms (p<0.001) and ≥ 3 points in the TMA mortality score (p<0.001). In conclusion, the onset of aTTP is associated with worse analytical parameters and severe neurological involvement.


Assuntos
Púrpura Trombocitopênica Trombótica , Humanos , Púrpura Trombocitopênica Trombótica/diagnóstico , Púrpura Trombocitopênica Trombótica/terapia , Estudos Retrospectivos , Recidiva , Proteína ADAMTS13
2.
PLoS Comput Biol ; 18(12): e1010094, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36455063

RESUMO

Theta and gamma oscillations in the hippocampus have been hypothesized to play a role in the encoding and retrieval of memories. Recently, it was shown that an intrinsic fast gamma mechanism in medial entorhinal cortex can be recruited by optogenetic stimulation at theta frequencies, which can persist with fast excitatory synaptic transmission blocked, suggesting a contribution of interneuronal network gamma (ING). We calibrated the passive and active properties of a 100-neuron model network to capture the range of passive properties and frequency/current relationships of experimentally recorded PV+ neurons in the medial entorhinal cortex (mEC). The strength and probabilities of chemical and electrical synapses were also calibrated using paired recordings, as were the kinetics and short-term depression (STD) of the chemical synapses. Gap junctions that contribute a noticeable fraction of the input resistance were required for synchrony with hyperpolarizing inhibition; these networks exhibited theta-nested high frequency oscillations similar to the putative ING observed experimentally in the optogenetically-driven PV-ChR2 mice. With STD included in the model, the network desynchronized at frequencies above ~200 Hz, so for sufficiently strong drive, fast oscillations were only observed before the peak of the theta. Because hyperpolarizing synapses provide a synchronizing drive that contributes to robustness in the presence of heterogeneity, synchronization decreases as the hyperpolarizing inhibition becomes weaker. In contrast, networks with shunting inhibition required non-physiological levels of gap junctions to synchronize using conduction delays within the measured range.


Assuntos
Depressão , Infecções Sexualmente Transmissíveis , Camundongos , Animais , Interneurônios/fisiologia , Transmissão Sináptica/fisiologia , Junções Comunicantes/fisiologia , Hipocampo/fisiologia
3.
Ann Hematol ; 101(7): 1465-1471, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35467101

RESUMO

Most ß-thalassemias are caused by mutations involving one or a limited number of nucleotides within the gene or its adjacent regions. They can be substitutions or deletions; in these cases, the loss ranges from a single nucleotide to even the entire HBB gene, so we wonder if the phenotype is due to the size of the deletion or the location of the mutation. To clarify this, we present two new deletions in the ß-globin gene that cause ß0-thalassemia. The hematological parameters were determined with an automated cell counter; the Hb A2 and Hb F levels were measured by performance liquid chromatography. Hemoglobins were analyzed by capillary zone electrophoresis (Sebia Capillarys Flex system) and ion-exchange HPLC (BioRad Variant II ß-thalassemia Short Program). Molecular characterization was performed by automatic Sanger sequencing. The screening of common α-thalassemia point mutations and deletions in the world (21 in total) were carried out using multiplex PCR followed by reverse-hybridization with a commercial Alpha-Globin StripAssay kit. We have characterized two new mutations-(1) 1-bp deletion [CD61/62(-G)] [HBB:c.186_187delG], (2) 105-bp deletion [IVS-2-nt767-CD111] [HBB:c.316-84_333del]-and we have described, for first time in Spain, the 25-bp deletion [ß nts 252 - 276 deleted] [HBB:c.93-22_95del] mutation. These mutations were classified as pathogenic by UniProt Variants confirmed according to the American College of Medical Genetics and Genomics guidelines. These mutations present a phenotype compatible with ß0-thalassemia, supported by hematological parameters that correlate the degree of reduction in the synthesis of the ß-globin chain. Identification of this type of mutation is important for genetic counselling of partners where both are carriers, so that they are aware of the genetic risk of having affected children, allowing them to take an informed decision about their reproductive choices.


Assuntos
Talassemia alfa , Talassemia beta , Genótipo , Hemoglobina A2/genética , Hemoglobinas/genética , Humanos , Mutação , alfa-Globinas/genética , Talassemia alfa/genética , Globinas beta/genética , Talassemia beta/diagnóstico , Talassemia beta/genética
4.
J Oncol Pharm Pract ; 28(3): 736-739, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34878360

RESUMO

INTRODUCTION: Nivolumab is a fully human IgG4 monoclonal antibody (moAb) against programmed cell death protein 1, approved for the treatment of over ten types of cancer. The use of this and other moAbs has augmented considerably in recent years and this in turn has caused an increase of hypersensitivity reactions (HSR). CASE REPORT: We present the case of a patient with metastatic renal cell cancer (RCC) who developed a grade 3 cytokine release reaction (CRR) to nivolumab. The maintenance of the symptoms despite of the administration of symptomatic treatment and slowing down the infusion rate of nivolumab during the 1st and 2nd reaction required an allergy evaluation of our patient. MANAGEMENT AND OUTCOME: Skin testing to Nivolumab with negative results and baseline tryptase within the normal range were observed during the allergy workout. A desensitization protocol with specific premedication was applied to reintroduce the moAb, with no further issues. Moreover, a follow up of the patient in the oncology setting was done showing disease stabilization. DISCUSSION: The CRR should be treated by desensitization, in contrast to infusion reactions. The diagnosis of CRR phenotype is based on the clinical presentation and recently, and elevation of IL-6 levels has been shown to be a useful biomarker along with negative skin testing. We can conclude that after a HSR and an appropriate allergy diagnosis of CRR, nivolumab can be safely reintroduced by desensitization without reducing the target dose or the appropriate dilution concentration.


Assuntos
Hipersensibilidade a Drogas , Nivolumabe , Algoritmos , Anticorpos Monoclonais/efeitos adversos , Citocinas , Hipersensibilidade a Drogas/diagnóstico , Hipersensibilidade a Drogas/etiologia , Hipersensibilidade a Drogas/terapia , Humanos , Nivolumabe/efeitos adversos , Testes Cutâneos/efeitos adversos
5.
Sensors (Basel) ; 22(3)2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-35161852

RESUMO

As an inevitable process, the number of older adults is increasing in many countries worldwide. Two of the main problems that society is being confronted with more and more, in this respect, are the inter-related aspects of feelings of loneliness and social isolation among older adults. In particular, the ongoing COVID-19 crisis and its associated restrictions have exacerbated the loneliness and social-isolation problems. This paper is first and foremost a comprehensive survey of loneliness monitoring and management solutions, from the multidisciplinary perspective of technology, gerontology, socio-psychology, and urban built environment. In addition, our paper also investigates machine learning-based technological solutions with wearable-sensor data, suitable to measure, monitor, manage, and/or diminish the levels of loneliness and social isolation, when one also considers the constraints and characteristics coming from social science, gerontology, and architecture/urban built environments points of view. Compared to the existing state of the art, our work is unique from the cross-disciplinary point of view, because our authors' team combines the expertise from four distinct domains, i.e., gerontology, social psychology, architecture, and wireless technology in addressing the two inter-related problems of loneliness and social isolation in older adults. This work combines a cross-disciplinary survey of the literature in the four aforementioned domains with a proposed wearable-based technological solution, introduced first as a generic framework and, then, exemplified through a simple proof of concept with dummy data. As the main findings, we provide a comprehensive view on challenges and solutions in utilizing various technologies, particularly those carried by users, also known as wearables, to measure, manage, and/or diminish the social isolation and the perceived loneliness among older adults. In addition, we also summarize the identified solutions which can be used for measuring and monitoring various loneliness- and social isolation-related metrics, and we present and validate, through a simple proof-of-concept mechanism, an approach based on machine learning for predicting and estimating loneliness levels. Open research issues in this field are also discussed.


Assuntos
COVID-19 , Dispositivos Eletrônicos Vestíveis , Idoso , Humanos , Solidão , SARS-CoV-2 , Isolamento Social
6.
J Neurosci ; 40(50): 9576-9588, 2020 12 09.
Artigo em Inglês | MEDLINE | ID: mdl-33158963

RESUMO

Single-cell analysis is revealing increasing diversity in gene expression profiles among brain cells. Traditional promotor-based viral gene expression techniques, however, cannot capture the growing variety among single cells. We demonstrate a novel viral gene expression strategy to target cells with specific miRNA expression using miRNA-guided neuron tags (mAGNET). We designed mAGNET viral vectors containing a CaMKIIα promoter and microRNA-128 (miR-128) binding sites, and labeled CaMKIIα+ cells with naturally low expression of miR-128 (Lm128C cells) in male and female mice. Although CaMKIIα has traditionally been considered as an excitatory neuron marker, our single-cell sequencing results reveal that Lm128C cells are CaMKIIα+ inhibitory neurons of parvalbumin or somatostatin subtypes. Further evaluation of the physiological properties of Lm128C cell in brain slices showed that Lm128C cells exhibit elevated membrane excitability, with biophysical properties closely resembling those of fast-spiking interneurons, consistent with previous transcriptomic findings of miR-128 in regulating gene networks that govern membrane excitability. To further demonstrate the utility of this new viral expression strategy, we expressed GCaMP6f in Lm128C cells in the superficial layers of the motor cortex and performed in vivo calcium imaging in mice during locomotion. We found that Lm128C cells exhibit elevated calcium event rates and greater intrapopulation correlation than the overall CaMKIIα+ cells during movement. In summary, the miRNA-based viral gene targeting strategy described here allows us to label a sparse population of CaMKIIα+ interneurons for functional studies, providing new capabilities to investigate the relationship between gene expression and physiological properties in the brain.SIGNIFICANCE STATEMENT We report the discovery of a class of CaMKIIα+ cortical interneurons, labeled via a novel miRNA-based viral gene targeting strategy, combinatorial to traditional promoter-based strategies. The fact that we found a small, yet distinct, population of cortical inhibitory neurons that express CaMKIIα demonstrates that CaMKIIα is not as specific for excitatory neurons as commonly believed. As single-cell sequencing tools are providing increasing insights into the gene expression diversity of neurons, including miRNA profile data, we expect that the miRNA-based gene targeting strategy presented here can help delineate many neuron populations whose physiological properties can be readily related to the miRNA gene regulatory networks.


Assuntos
Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/genética , Marcação de Genes , Interneurônios/metabolismo , MicroRNAs/genética , Córtex Motor/metabolismo , Animais , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Feminino , Vetores Genéticos , Masculino , Camundongos , MicroRNAs/metabolismo
7.
J Med Internet Res ; 23(12): e28022, 2021 12 30.
Artigo em Inglês | MEDLINE | ID: mdl-34967760

RESUMO

BACKGROUND: Loneliness and social isolation can have severe effects on human health and well-being. Partial solutions to combat these circumstances in demographically aging societies have been sought from the field of information and communication technology (ICT). OBJECTIVE: This systematic literature review investigates the research conducted on older adults' loneliness and social isolation, and physical ICTs, namely robots, wearables, and smart homes, in the era of ambient assisted living (AAL). The aim is to gain insight into how technology can help overcome loneliness and social isolation other than by fostering social communication with people and what the main open-ended challenges according to the reviewed studies are. METHODS: The data were collected from 7 bibliographic databases. A preliminary search resulted in 1271 entries that were screened based on predefined inclusion criteria. The characteristics of the selected studies were coded, and the results were summarized to answer our research questions. RESULTS: The final data set consisted of 23 empirical studies. We found out that ICT solutions such as smart homes can help detect and predict loneliness and social isolation, and technologies such as robotic pets and some other social robots can help alleviate loneliness to some extent. The main open-ended challenges across studies relate to the need for more robust study samples and study designs. Further, the reviewed studies report technology- and topic-specific open-ended challenges. CONCLUSIONS: Technology can help assess older adults' loneliness and social isolation, and alleviate loneliness without direct interaction with other people. The results are highly relevant in the COVID-19 era, where various social restrictions have been introduced all over the world, and the amount of research literature in this regard has increased recently.


Assuntos
Inteligência Ambiental , COVID-19 , Idoso , Comunicação , Humanos , Solidão , SARS-CoV-2 , Isolamento Social , Tecnologia
8.
J Neurosci ; 39(12): 2221-2237, 2019 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-30655351

RESUMO

Under awake and idling conditions, spontaneous intracellular membrane voltage is characterized by large, synchronous, low-frequency fluctuations. Although these properties reflect correlations in synaptic inputs, intrinsic membrane properties often indicate voltage-dependent changes in membrane resistance and time constant values that can amplify and help to generate low-frequency voltage fluctuations. The specific contribution of intrinsic and synaptic factors to the generation of spontaneous fluctuations, however, remains poorly understood. Using visually guided intracellular recordings of somatosensory layer 2/3 pyramidal cells and interneurons in awake male and female mice, we measured the spectrum and size of voltage fluctuation and intrinsic cellular properties at different voltages. In both cell types, depolarizing neurons increased the size of voltage fluctuations. Amplitude changes scaled with voltage-dependent changes in membrane input resistance. Because of the small membrane time constants observed in both pyramidal cells and interneuron cell bodies, the low-frequency content of membrane fluctuations reflects correlations in the synaptic current inputs rather than significant filtering associated with membrane capacitance. Further, blocking synaptic inputs minimally altered somatic membrane resistance and time constant values. Overall, these results indicate that spontaneous synaptic inputs generate a low-conductance state in which the amplitude, but not frequency structure, is influenced by intrinsic membrane properties.SIGNIFICANCE STATEMENT In the absence of sensory drive, cortical activity in awake animals is associated with self-generated and seemingly random membrane voltage fluctuations characterized by large amplitude and low frequency. Partially, these properties reflect correlations in synaptic input. Nonetheless, neurons express voltage-dependent intrinsic properties that can potentially influence the amplitude and frequency of spontaneous activity. Using visually guided intracellular recordings of cortical neurons in awake mice, we measured the voltage dependence of spontaneous voltage fluctuations and intrinsic membrane properties. We show that voltage-dependent changes in membrane resistance amplify synaptic activity, whereas the frequency of voltage fluctuations reflects correlations in synaptic inputs. Last, synaptic activity has a small impact on intrinsic membrane properties in both pyramidal cells and interneurons.


Assuntos
Interneurônios/fisiologia , Potenciais da Membrana/fisiologia , Células Piramidais/fisiologia , Córtex Somatossensorial/fisiologia , Animais , Feminino , Masculino , Camundongos Endogâmicos C57BL , Atividade Motora/fisiologia , Vibrissas/fisiologia
9.
Echocardiography ; 37(12): 2018-2028, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33211337

RESUMO

BACKGROUND: Left atrial (LA) deformation during the reservoir phase (LASr) has demonstrated strong prognostic value in different clinical settings. Although determinants of left atrial reservoir strain including left atrial relaxation, left atrial compliance, and left ventricular longitudinal systolic function are fairly well defined, there is incomplete information regarding the effect of left atrial volume on this relationship which is the focus of our study. METHOD: Consecutive patients without prior cardiac disease referred for transthoracic echocardiography were prospectively recruited. All participants underwent clinical assessment, transthoracic echocardiography (TTE), and screening exercise stress test. Only patients with normal left ventricular ejection fraction (LVEF) without left ventricular hypertrophy (LVH) or myocardial ischemia on stress testing were included. RESULTS: A total of 260 patients (57% male, mean age 59 ± 14 years) were included. 70% had hypertension, 33% had diabetes mellitus, and 31% had both HTN and DM. On multivariate analysis, age, e', LAVI, and LV GLS (P < .01 for all) showed an independent association with LASr. Of interest, at lower tertiles of LAVI, a linear decrease in LASr was observed parallel to worsening LV GLS, whilst at higher tertiles of LAVI, the reduction in LASr was non-linear implying that LA enlargement, consequent to LA remodeling, had an incremental effect on LASr. CONCLUSION: Age, e', LV GLS, and LAVI were independently associated with LASr. LA remodeling reflected by larger LAVI had an incremental negative association with LASr independent of LV GLS.


Assuntos
Função do Átrio Esquerdo , Disfunção Ventricular Esquerda , Idoso , Ecocardiografia , Feminino , Átrios do Coração/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Volume Sistólico , Disfunção Ventricular Esquerda/diagnóstico por imagem , Função Ventricular Esquerda
10.
Sensors (Basel) ; 20(22)2020 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-33202674

RESUMO

Using Automated Planning for the high level control of robotic architectures is becoming very popular thanks mainly to its capability to define the tasks to perform in a declarative way. However, classical planning tasks, even in its basic standard Planning Domain Definition Language (PDDL) format, are still very hard to formalize for non expert engineers when the use case to model is complex. Human Robot Interaction (HRI) is one of those complex environments. This manuscript describes the rationale followed to design a planning model able to control social autonomous robots interacting with humans. It is the result of the authors' experience in modeling use cases for Social Assistive Robotics (SAR) in two areas related to healthcare: Comprehensive Geriatric Assessment (CGA) and non-contact rehabilitation therapies for patients with physical impairments. In this work a general definition of these two use cases in a unique planning domain is proposed, which favors the management and integration with the software robotic architecture, as well as the addition of new use cases. Results show that the model is able to capture all the relevant aspects of the Human-Robot interaction in those scenarios, allowing the robot to autonomously perform the tasks by using a standard planning-execution architecture.


Assuntos
Robótica , Tecnologia Assistiva , Idoso , Avaliação Geriátrica , Humanos , Reabilitação , Software
11.
Entropy (Basel) ; 22(6)2020 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-33286447

RESUMO

Nowadays, across the most important problems faced by health centers are those caused by the existence of patients who do not attend their appointments. Among others, these patients cause loss of revenue to the health centers and increase the patients' waiting list. In order to tackle these problems, several scheduling systems have been developed. Many of them require predicting whether a patient will show up for an appointment. However, obtaining these estimates accurately is currently a challenging problem. In this work, a systematic review of the literature on predicting patient no-shows is conducted aiming at establishing the current state-of-the-art. Based on a systematic review following the PRISMA methodology, 50 articles were found and analyzed. Of these articles, 82% were published in the last 10 years and the most used technique was logistic regression. In addition, there is significant growth in the size of the databases used to build the classifiers. An important finding is that only two studies achieved an accuracy higher than the show rate. Moreover, a single study attained an area under the curve greater than the 0.9 value. These facts indicate the difficulty of this problem and the need for further research.

12.
Hippocampus ; 29(12): 1178-1189, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31301195

RESUMO

Numerous synaptic and intrinsic membrane mechanisms have been proposed for generating oscillatory activity in the hippocampus. Few studies, however, have directly measured synaptic conductances and membrane properties during oscillations. The time course and relative contribution of excitatory and inhibitory synaptic conductances, as well as the role of intrinsic membrane properties in amplifying synaptic inputs, remains unclear. To address this issue, we used an isolated whole hippocampal preparation that generates autonomous low-frequency oscillations near the theta range. Using 2-photon microscopy and expression of genetically encoded fluorophores, we obtained on-cell and whole-cell patch recordings of pyramidal cells and fast-firing interneurons in the distal subiculum. Pyramidal cell and interneuron spiking shared similar phase-locking to local field potential oscillations. In pyramidal cells, spiking resulted from a concomitant and balanced increase in excitatory and inhibitory synaptic currents. In contrast, interneuron spiking was driven almost exclusively by excitatory synaptic current. Thus, similar to tightly balanced networks underlying hippocampal gamma oscillations and ripples, balanced synaptic inputs in the whole hippocampal preparation drive highly phase-locked spiking at the peak of slower network oscillations.


Assuntos
Potenciais Pós-Sinápticos Excitadores/fisiologia , Ritmo Gama/fisiologia , Hipocampo/fisiologia , Sinapses/fisiologia , Transmissão Sináptica/fisiologia , Animais , Feminino , Hipocampo/citologia , Interneurônios/fisiologia , Masculino , Camundongos , Camundongos Transgênicos , Técnicas de Cultura de Órgãos , Células Piramidais/fisiologia
13.
Hippocampus ; 29(9): 773-786, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-30417958

RESUMO

Sharp wave-ripples (140-220 Hz) are patterns of brain activity observed in the local field potential of the hippocampus which are present during memory consolidation. As rodents switch from memory consolidation to memory encoding behaviors, cholinergic inputs to the hippocampus from neurons in the medial septum-diagonal band of Broca cause a marked reduction in ripple incidence. The mechanism for this disruption in ripple power is not fully understood. In isolated neurons, the major effect of cholinergic input on hippocampal neurons is depolarization of the membrane potential, which affects both hippocampal pyramidal neurons and inhibitory interneurons. Using an existing model of ripple-frequency oscillations that includes both pyramidal neurons and interneurons, we investigated the mechanism whereby depolarizing inputs to these neurons can affect ripple power and frequency. We observed that ripple power and frequency are maintained, as long as inputs to pyramidal neurons and interneurons are balanced. Preferential drive to pyramidal neurons or interneurons, however, affects ripple power and can disrupt ripple oscillations by pushing ripple frequency higher or lower. Thus, an imbalance in drive to pyramidal neurons and interneurons provides a means whereby cholinergic input can suppress hippocampal ripples.


Assuntos
Hipocampo/fisiologia , Inibição Neural/fisiologia , Sistema Nervoso Parassimpático/fisiologia , Algoritmos , Eletroencefalografia , Fenômenos Eletrofisiológicos/fisiologia , Potenciais Evocados , Humanos , Interneurônios/fisiologia , Potenciais da Membrana/fisiologia , Consolidação da Memória/fisiologia , Modelos Neurológicos , Neurônios/fisiologia , Células Piramidais/fisiologia
14.
Conserv Biol ; 33(1): 88-98, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-29998590

RESUMO

Rewilding has been an increasingly popular tool to restore plant-animal interactions and ecological processes impaired by defaunation. However, the reestablishment of such processes has seldom been assessed. We investigated the restoration of ecological interactions following the reintroduction of the brown howler monkey (Alouatta guariba) to a defaunated Atlantic forest site. We expected the reintroduction to restore plant-animal interactions and interactions between howlers and dung beetles, which promote secondary seed dispersal. We estimated the number of interactions expected to be restored by the reintroduction to provide the baseline interaction richness that could be restored. We followed the reintroduced howler monkeys twice a week for 24 months (337 hours total) to assess their diet. We used howler monkey dung in secondary seed dispersal experiments with 2484 seed mimics to estimate the removal rates by dung beetles and collected the beetles to assess community attributes. We compared the potential future contribution of howler monkeys and other frugivores to seed dispersal based on the seed sizes they disperse in other areas where they occur. In 2 years, howler monkeys consumed 60 animal-dispersed plant species out of the 330 estimated. Twenty-one dung beetle species were attracted to experimentally provided dung; most of them were tunnelers, nocturnal, and large-sized (>10 mm). On average 30% (range 0-100%) of the large seed mimics (14 mm) were moved by dung beetles. About 91% of the species consumed by howlers (size range 0.3-34.3 mm) overlapped in seed size with those removed by dung beetles. In our study area, howler monkeys may consume more large-seeded fruit species than most other frugivores, highlighting their potential to affect forest regeneration. Our results show reintroductions may effectively restore ecological links and enhance ecological processes.


Assuntos
Alouatta , Dispersão de Sementes , Animais , Conservação dos Recursos Naturais , Ecologia , Florestas
15.
BMC Infect Dis ; 19(1): 291, 2019 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-30922322

RESUMO

BACKGROUND: Streptococcus tigurinus was recently described as a new streptococcal species within the viridans group streptococci (VGS). The objectives of the present work were to analyse the clinical and microbiological characteristics of S. tigurinus isolated from patients with bacteraemias, to determine the prevalence of S. tigurinus among VGS endocarditis in Spain, and to compare the clinical characteristics and outcomes of endocarditis caused by S. tigurinus and other VGS. METHODS: Retrospective nationwide study, performed between 2008 and 2016 in 9 Spanish hospitals from 7 different provinces comprising 237 cases of infective endocarditis. Streptococcal isolates were identified by sequencing fragments of their 16S rRNA, sodA and groEL genes. Clinical data of patients with streptococcal endocarditis were prospectively collected according to a pre-established protocol. RESULTS: Patients with endocarditis represented 7/9 (77.8%) and 26/86 (30.2%) of the bacteraemias caused by S. tigurinus and other VGS, respectively (p < 0.001), in two of the hospital participants. Among patients with streptococcal endocarditis, 12 different Streptococcus species were recognized being S. oralis, S. tigurinus and S. mitis the three more common. No relevant statistical differences were observed in the clinical characteristics and outcomes of endocarditis caused by the different VGS species. CONCLUSIONS: In this multicenter study performed in Spain, S. tigurinus showed a higher predilection for the endocardial endothelium as compared to other VGS. However, clinical characteristics and outcomes of endocarditis caused by S. tigurinus did not significantly differ from endocarditis caused by other oral streptococci.


Assuntos
Endocardite Bacteriana/diagnóstico , Endocardite Bacteriana/epidemiologia , Infecções Estreptocócicas/diagnóstico , Infecções Estreptocócicas/epidemiologia , Estreptococos Viridans/isolamento & purificação , Adulto , Idoso , Idoso de 80 Anos ou mais , Bacteriemia/diagnóstico , Bacteriemia/epidemiologia , Bacteriemia/microbiologia , Endocardite Bacteriana/microbiologia , Monitoramento Epidemiológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Espanha/epidemiologia , Infecções Estreptocócicas/complicações , Infecções Estreptocócicas/microbiologia , Estreptococos Viridans/classificação , Estreptococos Viridans/fisiologia , Adulto Jovem
18.
Eur J Haematol ; 101(3): 368-378, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29901818

RESUMO

INTRODUCTION: Congenital dyserythropoietic anemias (CDA) are characterized by hyporegenerative anemia with inadequate reticulocyte values, ineffective erythropoiesis, and hemolysis. Distinctive morphology of bone marrow erythroblasts and identification of causative genes allow classification into 4 types caused by variants in CDAN1, c15orf41, SEC23B, KIF23, and KLF1 genes. OBJECTIVE: Identify pathogenic variants in CDA patients. METHODS: Massive parallel sequencing with a targeted gene panel, Sanger sequencing, Comparative Genome Hybridization (CGH), and in silico predictive analysis of pathogenicity. RESULTS: Pathogenic variants were found in 21 of 53 patients studied from 44 unrelated families. Six variants were found in CDAN1: two reported, p.Arg714Trp and p.Arg725Trp and, four novel, p.Arg623Trp, p.Arg946Trp, p.Phe1125Ser and p.Ser1227Gly. Twelve variants were found in SEC23B: seven reported, p.Arg14Trp, p.Glu109Lys, p.Arg217Ter, c.835-2A>G, p.Arg535Ter, p.Arg550Ter and p.Arg718Ter and, five novel, p.Val164Leu, p.Arg190Gln, p.Gln521Ter, p.Arg546Trp, and p.Arg611Gln. The variant p.Glu325Lys in KLF1 was found in one patient and p.Tyr365Cys in ALAS2 in an other. Moreover, we identified genomic rearrangements by CGH in some SEC23B-monoallelic patients. CONCLUSIONS: New technologies for genetic studies will help to find variants in other genes, in addition to those known, that contribute to or modulate the CDA phenotype or support the correct diagnosis.


Assuntos
Anemia Diseritropoética Congênita/diagnóstico , Anemia Diseritropoética Congênita/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Anemia Diseritropoética Congênita/sangue , Criança , Pré-Escolar , Hibridização Genômica Comparativa , Bases de Dados de Ácidos Nucleicos , Feminino , Estudos de Associação Genética/métodos , Variação Genética , Genótipo , Glicoproteínas/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Nucleares , Adulto Jovem
19.
Stereotact Funct Neurosurg ; 96(4): 215-222, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30064130

RESUMO

BACKGROUND: Deep brain stimulation (DBS) and the proper target for chronic cluster headache (CCH) are still subjects of controversy. OBJECTIVES: We present our long-term results of analysis of the target and its structural connectivity. METHODS: Fifteen patients with drug-resistant CCH underwent DBS in coordinates 4 mm lateral to the III ventricular wall and 2 mm behind and 5 mm below the intercommissural point. The clinical parameters recorded were the number of weekly attacks, pain intensity, and duration of the headache. Structural connectivity was studied using 3-T MR diffusion tensor imaging (DTI). RESULTS: All of our patients improved from a mean of 39 attacks/week to 2; pain intensity decreased from 9 to 3 out of 10, and the mean cephalalgia duration decreased from 53 to 8 min. The mean stereotactic coordinates of the effective contact location were 6.1 mm lateral to the midcommissural point and 1.2 mm behind and 4.0 mm below the intercommissural point. DTI analysis showed that this target was connected to tracts and nuclei of the posterior mesencephalic tegmentum, specifically the dorsal longitudinal and mamillotegmental fasciculi. CONCLUSIONS: Our data showed DBS to be a safe and useful procedure for the treatment of drug-resistant CCH; the rate of improvement was higher than those found in other series. Although these are promising results, larger series targeting those fasciculi with a longer follow-up are needed.


Assuntos
Cefaleia Histamínica/terapia , Estimulação Encefálica Profunda/métodos , Subtálamo/fisiopatologia , Adulto , Cefaleia Histamínica/diagnóstico por imagem , Cefaleia Histamínica/fisiopatologia , Imagem de Tensor de Difusão , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Subtálamo/diagnóstico por imagem , Resultado do Tratamento
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