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1.
Development ; 150(1)2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36633189

RESUMO

Adult neurogenesis is supported by multipotent neural stem cells (NSCs) with unique properties and growth requirements. Adult NSCs constitute a reversibly quiescent cell population that can be activated by extracellular signals from the microenvironment in which they reside in vivo. Although genomic imprinting plays a role in adult neurogenesis through dose regulation of some relevant signals, the roles of many imprinted genes in the process remain elusive. Insulin-like growth factor 2 (IGF2) is encoded by an imprinted gene that contributes to NSC maintenance in the adult subventricular zone through a biallelic expression in only the vascular compartment. We show here that IGF2 additionally promotes terminal differentiation of NSCs into astrocytes, neurons and oligodendrocytes by inducing the expression of the maternally expressed gene cyclin-dependent kinase inhibitor 1c (Cdkn1c), encoding the cell cycle inhibitor p57. Using intraventricular infusion of recombinant IGF2 in a conditional mutant strain with Cdkn1c-deficient NSCs, we confirm that p57 partially mediates the differentiation effects of IGF2 in NSCs and that this occurs independently of its role in cell-cycle progression, balancing the relationship between astrogliogenesis, neurogenesis and oligodendrogenesis.


Assuntos
Inibidor de Quinase Dependente de Ciclina p57 , Impressão Genômica , Fator de Crescimento Insulin-Like II , Células-Tronco Neurais , Neurogênese , Neurônios , Inibidor de Quinase Dependente de Ciclina p57/genética , Células-Tronco Neurais/citologia , Neurônios/citologia , Neurogênese/genética , Fator de Crescimento Insulin-Like II/genética , Animais , Camundongos , Camundongos Endogâmicos C57BL
2.
Development ; 148(16)2021 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-34351428

RESUMO

Neocortical progenitor cells generate subtypes of excitatory projection neurons in sequential order followed by the generation of astrocytes. The transcription factor zinc finger and BTB domain-containing protein 20 (ZBTB20) has been implicated in regulation of cell specification during neocortical development. Here, we show that ZBTB20 instructs the generation of a subset of callosal projections neurons in cortical layers II/III in mouse. Conditional deletion of Zbtb20 in cortical progenitors, and to a lesser degree in differentiating neurons, leads to an increase in the number of layer IV neurons at the expense of layer II/III neurons. Astrogliogenesis is also affected in the mutants with an increase in the number of a specific subset of astrocytes expressing GFAP. Astrogliogenesis is more severely disrupted by a ZBTB20 protein containing dominant mutations linked to Primrose syndrome, suggesting that ZBTB20 acts in concert with other ZBTB proteins that were also affected by the dominant-negative protein to instruct astrogliogenesis. Overall, our data suggest that ZBTB20 acts both in progenitors and in postmitotic cells to regulate cell fate specification in the mammalian neocortex.


Assuntos
Astrócitos/metabolismo , Neocórtex/crescimento & desenvolvimento , Neurogênese/genética , Neurônios/metabolismo , Fatores de Transcrição/metabolismo , Anormalidades Múltiplas/genética , Animais , Calcinose/genética , Otopatias/genética , Feminino , Técnicas de Inativação de Genes , Deficiência Intelectual/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Atrofia Muscular/genética , Mutação de Sentido Incorreto , Neocórtex/metabolismo , Transdução de Sinais/genética , Células-Tronco/metabolismo , Fatores de Transcrição/genética
3.
Phys Chem Chem Phys ; 25(41): 28052-28062, 2023 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-37843378

RESUMO

A new set of six accurate ab initio potential energy surfaces (PESs) is presented for the first three singlet and triplet states of LiH2+ (1,21A', 11A'', 1,23A', and 13A'' states, where four of them are investigated for the first time), which have allowed new detailed studies gaining a global view on this interesting system. These states are relevant for the study of the most important reactions of lithium chemistry in the early universe. More than 45 000 energy points were calculated using the multi-reference configuration interaction level of theory using explicitly correlated methods (ic-MRCI-F12), and the results obtained for each individual electronic state were fitted to an analytical function. Using quasiclassical trajectories and considering the initial diatomic fragment in the ground rovibrational state, we have determined the integral cross sections for the H + LiH+(X2Σ+, C2Π) and H+ + LiH(X1Σ+, B1Π) reactions. In these calculations all available reaction channels were considered: the chemically most important H or H+ transfer/abstraction as well as atom exchange and collision induced dissociation for up to 1.0 eV of collision energy.

4.
Phys Chem Chem Phys ; 25(44): 30330-30342, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37909202

RESUMO

We report quantum calculations involving the dynamics of rotational energy-transfer processes, by collision with He atoms in interstellar environments, of the title molecular species which share the presence of the CN backbone and are considered of importance in those environments. The latter structural feature is taken to be especially relevant for prebiotic chemistry and for its possible role in the processing of the heterocyclic rings of RNA and DNA nucleobases in the interstellar space. We carry out ab initio calculations of their interaction potentials with He atoms and further obtain the state-to-state rotationally inelastic cross sections and rate coefficients over the relevant range of temperatures. The similarities and differences between such species and other similar partners which have been already detected are analyzed and discussed for their significance on internal state populations in interstellar space for the two title molecular radicals.

5.
J Phys Chem A ; 127(3): 765-774, 2023 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-36598007

RESUMO

We present accurate ab initio calculations on several properties of a gas-phase system of interest in the interstellar medium (ISM), where the title molecular anion has been often surmised but not yet confirmed by observations. The CH-3Σ+ constitutes the smallest term in the series of longer anionic polyynes which have been observed in the ISM (e.g., C4H- and several others). Hence, its dynamical behavior in collision with He atoms, one of the most abundant atoms in that environment, can provide quantitative indicators on the changes which can occur in the rotational state population of the title anion when driven by this collision dynamics. We therefore report an accurate evaluation of the full potential energy surface (PES) which acts between the molecular anion in its ground vibrational state and the He atom. The relevant inelastic scattering cross sections and the corresponding inelastic rate coefficients are then computed within a quantum treatment of the collisions. We find that the fairly small values of the final inelastic rate coefficients indicate state-changing processes by collisions to be inefficient paths for modifying the rotational state populations of this anion and therefore to aid its possible observation from direct radiative emission in the microwave region.

6.
Int J Qual Health Care ; 35(2)2023 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-37043330

RESUMO

Knowing the frequency and characteristics of adverse events (AEs) is key to implementing actions that can prevent their occurrence. However, reporting systems are insufficient for this purpose and epidemiological studies are also required. Currently, the reviewing of clinical records is the gold standard method for knowing the frequency and characteristics of AEs. Research on AEs in a primary care setting has been limited and primarily focuses on specific types of events (medication errors, etc.) or patients. Large studies that search for any kind of AE in all patients are scarce. This study aimed to estimate the prevalence of AEs in the primary care setting and their characteristics. SETTING: all 262 primary health-care centres in the Madrid region (Spain) during the last quarter of 2018. DESIGN: cross-sectional descriptive study. Eligible population: subjects over 18 years of age who attended medical consultation over the last year (N = 2 743 719); a randomized sample stratified by age. MAIN OUTCOMES: age, sex, occurrence of an AE, number of consultations in the study period, avoidability, severity, place of occurrence, type of event, and contributory factors. The clinical records were reviewed by three teams, each composed of one doctor and one nurse trained and with expertise in patient safety. The SPSS software package (version 26) was used for the statistical analyses. The evaluators reviewed 1797 clinical records. The prevalence of AEs over the study period was 5.0% [95% confidence interval (CI): 4.0%‒6.0%], with higher values in women (5.7%; 95% CI: 4.6%‒6.8%;P = 0.10) and patients over 75 years of age (10.3%; 95% CI: 8.9%‒11.7%; P < 0.001). The overall occurrence per hundred consultations was estimated to be 1.58% (95% CI: 1.28%‒1.94%). Of the detected AEs, 71.3% (95% CI: 62.1%‒80.5%) were avoidable. Additionally, 60.6% (95% CI: 50.7%‒70.5%) were categorized as mild, 31.9% (95% CI: 22.4%‒41.4%) as moderate, and 7.4% (95% CI: 2.1%‒12.7%) as severe. Primary care was the occurrence setting in 76.6% (95% CI: 68.0%‒85.2%) of cases. The overall incidence of AEs related to medication was 53.2% (95% CI: 50.9%‒55.5%). The most frequent types of AEs were prescription errors (28.7%; 95% CI: 19.5%‒37.9%), followed by drug administration errors by patients (17.0%; 95% CI: 9.4%‒24.6%), and clinical assessment errors (11.7%; 95% CI: 5.2%‒18.2%). The most common contributory factors were those related to the patient (80.6%; 95% CI: 71.1%‒90.1%) and tasks (59.7%; 95% CI: 48.0%‒71.4%). A high prevalence of AEs (1 in 66 consultations) was observed, which was slightly higher than that reported in similar studies. About 3 out of 4 such events were considered to be avoidable and 1 out of 13 was severe. Prescription errors, drug administration errors by patients, and clinical assessment errors were the most frequent types of AEs. Graphical Abstract.


Assuntos
Erros Médicos , Atenção Primária à Saúde , Humanos , Feminino , Adolescente , Adulto , Erros Médicos/prevenção & controle , Prevalência , Estudos Transversais , Fatores de Risco
7.
Int J Mol Sci ; 24(8)2023 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-37108586

RESUMO

The deprotonation of an organic substrate is a common preactivation step for the enzymatic cofactorless addition of O2 to this substrate, as it promotes charge-transfer between the two partners, inducing intersystem crossing between the triplet and singlet states involved in the process. Nevertheless, the spin-forbidden addition of O2 to uncharged ligands has also been observed in the laboratory, and the detailed mechanism of how the system circumvents the spin-forbiddenness of the reaction is still unknown. One of these examples is the cofactorless peroxidation of 2-methyl-3,4-dihydro-1-naphthol, which will be studied computationally using single and multi-reference electronic structure calculations. Our results show that the preferred mechanism is that in which O2 picks a proton from the substrate in the triplet state, and subsequently hops to the singlet state in which the product is stable. For this reaction, the formation of the radical pair is associated with a higher barrier than that associated with the intersystem crossing, even though the absence of the negative charge leads to relatively small values of the spin-orbit coupling.


Assuntos
Tetralonas , Descarboxilação , Oxigênio/química
8.
J Neurosci ; 41(33): 6969-6986, 2021 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-34266896

RESUMO

Radial glial progenitor cells (RGCs) in the dorsal telencephalon directly or indirectly produce excitatory projection neurons and macroglia of the neocortex. Recent evidence shows that the pool of RGCs is more heterogeneous than originally thought and that progenitor subpopulations can generate particular neuronal cell types. Using single-cell RNA sequencing, we have studied gene expression patterns of RGCs with different neurogenic behavior at early stages of cortical development. At this early age, some RGCs rapidly produce postmitotic neurons, whereas others self-renew and undergo neurogenic divisions at a later age. We have identified candidate genes that are differentially expressed among these early RGC subpopulations, including the transcription factor Sox9. Using in utero electroporation in embryonic mice of either sex, we demonstrate that elevated Sox9 expression in progenitors affects RGC cell cycle duration and leads to the generation of upper layer cortical neurons. Our data thus reveal molecular differences between progenitor cells with different neurogenic behavior at early stages of corticogenesis and indicates that Sox9 is critical for the maintenance of RGCs to regulate the generation of upper layer neurons.SIGNIFICANCE STATEMENT The existence of heterogeneity in the pool of RGCs and its relationship with the generation of cellular diversity in the cerebral cortex has been an interesting topic of debate for many years. Here we describe the existence of RGCs with reduced neurogenic behavior at early embryonic ages presenting a particular molecular signature. This molecular signature consists of differential expression of some genes including the transcription factor Sox9, which has been found to be a specific regulator of this subpopulation of progenitor cells. Functional experiments perturbing expression levels of Sox9 reveal its instructive role in the regulation of the neurogenic behavior of RGCs and its relationship with the generation of upper layer projection neurons at later ages.


Assuntos
Autorrenovação Celular/genética , Células Ependimogliais/citologia , Regulação da Expressão Gênica no Desenvolvimento/genética , Neocórtex/citologia , Proteínas do Tecido Nervoso/fisiologia , Neurogênese/genética , Fatores de Transcrição SOX9/fisiologia , Animais , Ciclo Celular/genética , Eletroporação , Células Ependimogliais/metabolismo , Feminino , Genes Reporter , Vetores Genéticos/administração & dosagem , Injeções Intraventriculares , Camundongos , Camundongos Endogâmicos C57BL , Neocórtex/embriologia , Neocórtex/crescimento & desenvolvimento , Proteínas do Tecido Nervoso/biossíntese , Proteínas do Tecido Nervoso/genética , Neuroglia/citologia , Neurônios/citologia , Gravidez , Regiões Promotoras Genéticas/genética , Fatores de Transcrição SOX9/biossíntese , Fatores de Transcrição SOX9/genética , Análise de Célula Única , Transcrição Gênica
9.
Transfusion ; 62(5): 974-981, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35338710

RESUMO

BACKGROUND: Despite most controlled trials have shown no measurable benefit of COVID-19 convalescent plasma (CCP) in patients with COVID-19, some studies suggest that early administration of CCP with high-titer anti-SARS-CoV-2 can be beneficial in selected patients. We investigated the efficacy of early administration of high-titer CCP to patients with COVID-19 who required hospitalization, STUDY DESIGN AND METHODS: Observational, propensity score (PS) matched case-control study of COVID-19 patients treated with CCP within 72 h of hospital admission and untreated controls from August 2020 to February 2021. All CCP donations had a Euroimmun anti-SARS-CoV-2 sample-to-cutoff ratio ≥3. PS matching was based on prognostic factors and presented features with high-standardized differences between the treated and control groups. The primary endpoint was mortality within 30 days of diagnosis. RESULTS: A total of 1604 patients were analyzed, 261 of whom received CCP, most (82%) within 24 h after admission. Median age was 67 years (interquartile range: 56-79), and 953 (60%) were men. Presenting factors independently associated with higher 30-day mortality were increased age, cardiac disease, hypoxemic respiratory failure, renal failure, and plasma d-dimer >700 ng/ml. After PS matching, transfusion of CCP was associated with a significant reduction in the 30-day mortality rate (odds ratio [OR]; 0.94, 95% confidence interval [CI]: 0.91-0.98; p = .001) that extended to the 60th day after COVID-19 diagnosis (OR: 0.95; 95% CI: 0.92-0.99; p = .01). CONCLUSION: Our results suggest that CCP can still be helpful in selected patients with COVID-19 and call for further studies before withdrawing CCP from the COVID-19 therapeutic armamentarium.


Assuntos
COVID-19 , Idoso , Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19/terapia , Teste para COVID-19 , Estudos de Casos e Controles , Feminino , Humanos , Imunização Passiva , Masculino , SARS-CoV-2 , Soroterapia para COVID-19
10.
Ann Hematol ; 101(10): 2231-2239, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36042023

RESUMO

Hematological control, incidence of complications, and need for cytoreduction were studied in 453 patients with low-risk polycythemia vera (PV) treated with phlebotomies alone. Median hematocrit value decreased from 54% at diagnosis to 45% at 12 months, and adequate hematocrit control over time (< 45%) was observed in 36%, 44%, and 32% of the patients at 6, 12, and 24 months, respectively. More than 5 phlebotomies per year in the maintenance phase were required in 19% of patients. Worsening thrombocytosis, age > 60 years, and microvascular symptoms constituted the main indications for starting cytoreduction. Median duration without initiating cytoreduction was significantly longer in patients younger than 50 years (< 0.0001). The incidence rate of thrombosis under phlebotomies alone was 0.8% per year and the estimated probability of thrombosis at 10 years was 8.5%. The probability of arterial thrombosis was significantly higher in patients with arterial hypertension whereas there was a trend to higher risk of venous thrombosis in cases with high JAK2V617F allele burden. Rates of major bleeding and second primary neoplasm were low. With a median follow-up of 9 years, survival probability at 10 years was 97%, whereas the probability of myelofibrosis at 10 and 20 years was 7% and 20%, respectively. Progression to acute myeloid leukemia was documented in 3 cases (1%). Current management of low-risk PV patients is associated with low rate of thrombosis and long survival. New treatment strategies are needed for improving hematological control and, in the long term, reducing progression to myelofibrosis.


Assuntos
Leucemia Mieloide Aguda , Policitemia Vera , Mielofibrose Primária , Trombose , Humanos , Leucemia Mieloide Aguda/complicações , Pessoa de Meia-Idade , Flebotomia/efeitos adversos , Policitemia Vera/complicações , Policitemia Vera/diagnóstico , Policitemia Vera/cirurgia , Mielofibrose Primária/diagnóstico , Sistema de Registros , Trombose/complicações , Trombose/etiologia
11.
Curr Psychol ; : 1-13, 2022 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-36406840

RESUMO

Healthcare workers' professional quality of life has been increasingly under the spotlight, even more so during the COVID-19 pandemic, which has posed a genuine challenge for them. This study aims to describe the professional quality of life profiles of a sample of Spanish palliative care professionals during the COVID-19 pandemic, encompassing aspects such as work satisfaction, burnout, compassion fatigue, and compassion satisfaction; while studying the relationships between these profiles and sociodemographic variables, clinical situations experienced during the pandemic, protectors of professional quality of life, the quality of care delivered, and the professionals' wellbeing. Data from a survey of Spanish palliative care professionals were used. The variables measured were professional quality of life, sociodemographic characteristics, COVID-19-related experiences, protectors of professional quality of life, wellbeing, and quality of care. Our research included latent profile analyses, along with chi-squared and t-tests. The results suggested two profiles of professional quality of life, namely low (32.78%) and high (67.22%). The following profile displayed a higher likelihood of having a low professional quality of life: younger professionals, registered nurses, with a decrease in their teamwork, without specific training in palliative care, in coping with death and stress or emotional training and with lower levels of self-care and self-compassion, whose patients were unable to die a dignified death. Similarly, a low professional quality of life profile was associated with reduced wellbeing and poorer quality of care offered. In conclusion, providing professionals with education and training to improve their ability to handle end-of-life care and stress, maintaining cohesive teams and promoting self-care and self-compassion are pivotal to maintaining the quality of life and wellbeing of palliative care professionals and the quality of care that they provide.

12.
Chemistry ; 27(5): 1700-1712, 2021 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-32975323

RESUMO

Despite being a very strong oxidizing agent, most organic molecules are not oxidized in the presence of O2 at room temperature because O2 is a diradical whereas most organic molecules are closed-shell. Oxidation then requires a change in the spin state of the system, which is forbidden according to non-relativistic quantum theory. To overcome this limitation, oxygenases usually rely on metal or redox cofactors to catalyze the incorporation of, at least, one oxygen atom into an organic substrate. However, some oxygenases do not require any cofactor, and the detailed mechanism followed by these enzymes remains elusive. To fill this gap, here the mechanism for the enzymatic cofactor-independent oxidation of 3,5-dihydroxyphenylacetyl-CoA (DPA-CoA) is studied by combining multireference calculations on a model system with QM/MM calculations. Our results reveal that intersystem crossing takes place without requiring the previous protonation of molecular oxygen. The characterization of the electronic states reveals that electron transfer is concomitant with the triplet-singlet transition. The enzyme plays a passive role in promoting the intersystem crossing, although spontaneous reorganization of the water wire connecting the active site with the bulk presets the substrate for subsequent chemical transformations. The results show that the stabilization of the singlet radical-pair between dioxygen and enolate is enough to promote spin-forbidden reaction without the need for neither metal cofactors nor basic residues in the active site.


Assuntos
Biocatálise , Coenzima A/química , Coenzima A/metabolismo , Oxigenases/metabolismo , Transporte de Elétrons , Oxigenases/química , Teoria Quântica
13.
Phys Chem Chem Phys ; 23(13): 7735-7747, 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-32930276

RESUMO

Full dimensional analytical fits of the coupled potential energy surfaces for the three lower singlet and triplet adiabatic states of H are developed, providing analytic derivatives and non-adiabatic coupling matrix elements. The fits are highly accurate and include an improved description of the long range interactions, including new terms for the description of the long range in the diatomic fits and the atom-diatom dissociation channels. The fits are based on the DIM formalism including three body terms in Hamiltonian matrix elements, each of them obeying S2 permutational symmetry, where the positive charge is placed in either of the three hydrogen atoms, but the full system obeys S3 permutational symmetry, invariant under all permutations of the nuclei. The ab initio points used in the fitting are obtained from a complete basis set extrapolation, made for all electronic states. Total root mean square errors of the fits are 27 and 12 cm-1, for the singlet and triplet states, respectively. The errors in the channels are lower than 2 cm-1 and 6 cm-1 for the H + H and H+ + H2 channels respectively. The new fits have been used to calculate the rovibrational bound states of the lowest singlet and lowest triplet states showing very good agreement with previous calculations in the literature.

14.
J Chem Phys ; 154(10): 104104, 2021 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-33722048

RESUMO

The non-adiabatic quantum dynamics of the H + H2 + → H2 + H+ charge transfer reactions, and some isotopic variants, is studied with an accurate wave packet method. A recently developed 3 × 3 diabatic potential model is used, which is based on very accurate ab initio calculations and includes the long-range interactions for ground and excited states. It is found that for initial H2 +(v = 0), the quasi-degenerate H2(v' = 4) non-reactive charge transfer product is enhanced, producing an increase in the reaction probability and cross section. It becomes the dominant channel from collision energies above 0.2 eV, producing a ratio between v' = 4 and the rest of v's, which that increase up to 1 eV. The H + H2 + → H2 + + H exchange reaction channel is nearly negligible, while the reactive and non-reactive charge transfer reaction channels are of the same order, except that corresponding to H2(v' = 4), and the two charge transfer processes compete below 0.2 eV. This enhancement is expected to play an important vibrational and isotopic effect that needs to be evaluated. For the three proton case, the problem of the permutation symmetry is discussed when using reactant Jacobi coordinates.

15.
Echocardiography ; 38(6): 1089-1092, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34013545

RESUMO

In this rare case of intrahepatic cholangiocarcinoma (ICC) tumor thrombus with right atrial (RA) invasion, we describe its diagnostic workup based on cardiac magnetic resonance imaging (cMRI). An 85-year-old man underwent transthoracic echocardiography due to dyspnea, revealing a RA mass. Comprehensive cMRI evaluation, including cine bright blood, T1- and T2-weighed, fat-suppressed, and contrast-enhanced imaging, was performed and diagnosis of ICC tumor thrombus with RA invasion was made. This first description of cMRI-guided diagnosis of RA invasion by ICC tumor thrombus points out the usefulness of cMRI for the diagnostic approach of RA masses suggestive of tumor thrombus.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Idoso de 80 Anos ou mais , Neoplasias dos Ductos Biliares/diagnóstico por imagem , Ductos Biliares Intra-Hepáticos , Colangiocarcinoma/diagnóstico por imagem , Átrios do Coração/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Masculino
16.
J Electrocardiol ; 67: 107-109, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34139616

RESUMO

Thyrotoxic periodic paralysis (TPP) is a rare but potentially life-threatening entity, which is characterized by sudden onset of muscle weakness and can in exceptional cases be associated with more severe symptoms, such as severe hypokalemia. We present the rare case of a young patient presenting with monomorphic ventricular tachycardia secondary to hypokalemia due to TPP. This case report highlights the importance of recognition of TPP as a rare cause of VT. A high index of suspicion is needed since signs of hyperthyroidism may be subtle. However, early diagnosis is crucial in order to avoid cardiovascular complications and improve outcomes.


Assuntos
Hipertireoidismo , Hipopotassemia , Taquicardia Ventricular , Eletrocardiografia , Humanos , Hipertireoidismo/complicações , Hipertireoidismo/diagnóstico , Hipopotassemia/complicações , Hipopotassemia/diagnóstico , Paralisia , Potássio , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/etiologia
17.
J Headache Pain ; 21(1): 94, 2020 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-32727345

RESUMO

INTRODUCTION: Headache is one of the most frequent neurologic manifestations in COVID-19. We aimed to analyze which symptoms and laboratory abnormalities were associated with the presence of headache and to evaluate if patients with headache had a higher adjusted in-hospital risk of mortality. METHODS: Retrospective cohort study. We included all consecutive patients admitted to the Hospital with confirmed SARS-CoV-2 infection between March 8th and April 11th, 2020. We collected demographic data, clinical variables and laboratory abnormalities. We used multivariate regression analysis. RESULTS: During the study period, 576 patients were included, aged 67.2 (SD: 14.7), and 250/576 (43.3%) being female. Presence of headache was described by 137 (23.7%) patients. The all-cause in-hospital mortality rate was 127/576 (20.0%). In the multivariate analysis, patients with headache had a lower risk of mortality (OR: 0.39, 95% CI: 0.17-0.88, p = 0.007). After adjusting for multiple comparisons in a multivariate analysis, variables that were independently associated with a higher odds of having headache in COVID-19 patients were anosmia, myalgia, female sex and fever; variables that were associated with a lower odds of having headache were younger age, lower score on modified Rankin scale, and, regarding laboratory variables on admission, increased C-reactive protein, abnormal platelet values, lymphopenia and increased D-dimer. CONCLUSION: Headache is a frequent symptom in COVID-19 patients and its presence is an independent predictor of lower risk of mortality in COVID-19 hospitalized patients.


Assuntos
Betacoronavirus , Infecções por Coronavirus/epidemiologia , Cefaleia/epidemiologia , Mortalidade Hospitalar , Pneumonia Viral/epidemiologia , Idoso , Idoso de 80 Anos ou mais , COVID-19 , Infecções por Coronavirus/complicações , Infecções por Coronavirus/mortalidade , Feminino , Cefaleia/etiologia , Cefaleia/mortalidade , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/mortalidade , Prognóstico , Estudos Retrospectivos , SARS-CoV-2 , Taxa de Sobrevida
18.
Development ; 143(12): 2121-34, 2016 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-27151949

RESUMO

Cadherins are crucial for the radial migration of excitatory projection neurons into the developing neocortical wall. However, the specific cadherins and the signaling pathways that regulate radial migration are not well understood. Here, we show that cadherin 2 (CDH2) and CDH4 cooperate to regulate radial migration in mouse brain via the protein tyrosine phosphatase 1B (PTP1B) and α- and ß-catenins. Surprisingly, perturbation of cadherin-mediated signaling does not affect the formation and extension of leading processes of migrating neocortical neurons. Instead, movement of the cell body and nucleus (nucleokinesis) is disrupted. This defect is partially rescued by overexpression of LIS1, a microtubule-associated protein that has previously been shown to regulate nucleokinesis. Taken together, our findings indicate that cadherin-mediated signaling to the cytoskeleton is crucial for nucleokinesis of neocortical projection neurons during their radial migration.


Assuntos
Caderinas/metabolismo , Cateninas/metabolismo , Movimento Celular , Núcleo Celular/metabolismo , Neocórtex/citologia , Neurônios/citologia , Proteína Tirosina Fosfatase não Receptora Tipo 1/metabolismo , 1-Alquil-2-acetilglicerofosfocolina Esterase/metabolismo , Actinas/metabolismo , Animais , Caderinas/genética , Adesão Celular , Centrossomo/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Camundongos Endogâmicos C57BL , Proteínas Associadas aos Microtúbulos/metabolismo , Neurônios/ultraestrutura , Ligação Proteica , Pseudópodes/metabolismo , Transdução de Sinais
19.
Phys Chem Chem Phys ; 21(26): 14429-14439, 2019 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-30899926

RESUMO

In a seminal work the photodissociation of IBr has been controlled using a strong non-resonant IR pulse [Sussman et al., Science, 2006, 314, 274], changing the branching ratio of products in different final states via the relative timing of pump and control pulses. In this paper, we revisit the control of this molecule. Potential surfaces for the complete spin-orbit manifold of IBr states dissociating into the ground and first excited states of the constituent atoms have been calculated at the multi-reference configuration interaction (MRCI) level of theory as a function of applied field. Both the strength and direction of field have been taken into account and it is seen how the avoided crossing between the states thought to be key in the control mechanism shift as a function of field strength. These surfaces will enable full calculations of the molecule in the pump-control field. Preliminary dynamics calculations with the field placed along the molecular axis show that a Hamiltonian including all 36-states agrees with earlier results and is able to model the basic features of the control. However, just like earlier results, this restricted model is not able to reproduce the timescale of the control.

20.
J Phys Chem A ; 123(41): 8766-8775, 2019 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-31545608

RESUMO

The title reaction and its isotopic variants are studied using quasi-classical trajectory (QCT) (without taking into account corrections to account for the possible zero point energy breakdown) and ring polymer molecular dynamics (RPMD) methods with a full dimensional and accurate potential energy surface which presents an exchange barrier of approximately 0.144 eV. The QCT rate constant increases when the temperature decreases from 1500 to 10 K. On the contrary, the RPMD rate constant decreases with decreasing temperature, in semiquantitative agreement with recent experimental results. The present RPMD results are in between the thermal and translational experimental rate constants, extracted from the measured data to eliminate the initial vibrational excitation of H3+, obtained in an arc discharge. The difference between the present RPMD results and experimental values is attributed to the possible existence of non thermal vibrational excitation of H3+, not completely removed by the semiempirical model used for the analysis of the experimental results. Also, it is found that, below 200 K, the RPMD trajectories are trapped, forming long-lived collision complexes, with lifetimes longer than 1 ns. These collision complexes can fragment by either redissociating back to reactants or react to products, in the two cases tunneling through the centrifugal and reaction barriers, respectively. The contribution of the formation of the complex to the total deuteration rate should be calculated with more accurate quantum methods, as has been found recently for reactions of larger systems, and the present four atoms system is a good candidate to benchmark the adequacy of RPMD method at temperatures below 100 K.

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