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1.
HIV Med ; 22(9): 867-876, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34324783

RESUMO

OBJECTIVES: We compared the characteristics and clinical outcomes of hospitalized individuals with COVID-19 with [people with HIV (PWH)] and without (non-PWH) HIV co-infection in Spain during the first wave of the pandemic. METHODS: This was a retrospective matched cohort study. People with HIV were identified by reviewing clinical records and laboratory registries of 10 922 patients in active-follow-up within the Spanish HIV Research Network (CoRIS) up to 30 June 2020. Each hospitalized PWH was matched with five non-PWH of the same age and sex randomly selected from COVID-19@Spain, a multicentre cohort of 4035 patients hospitalized with confirmed COVID-19. The main outcome was all-cause in-hospital mortality. RESULTS: Forty-five PWH with PCR-confirmed COVID-19 were identified in CoRIS, 21 of whom were hospitalized. A total of 105 age/sex-matched controls were selected from the COVID-19@Spain cohort. The median age in both groups was 53 (Q1-Q3, 46-56) years, and 90.5% were men. In PWH, 19.1% were injecting drug users, 95.2% were on antiretroviral therapy, 94.4% had HIV-RNA < 50 copies/mL, and the median (Q1-Q3) CD4 count was 595 (349-798) cells/µL. No statistically significant differences were found between PWH and non-PWH in number of comorbidities, presenting signs and symptoms, laboratory parameters, radiology findings and severity scores on admission. Corticosteroids were administered to 33.3% and 27.4% of PWH and non-PWH, respectively (P = 0.580). Deaths during admission were documented in two (9.5%) PWH and 12 (11.4%) non-PWH (P = 0.800). CONCLUSIONS: Our findings suggest that well-controlled HIV infection does not modify the clinical presentation or worsen clinical outcomes of COVID-19 hospitalization.


Assuntos
COVID-19/epidemiologia , Usuários de Drogas/estatística & dados numéricos , Infecções por HIV/epidemiologia , Hospitalização/estatística & dados numéricos , Adolescente , Corticosteroides/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Fármacos Anti-HIV/uso terapêutico , Contagem de Linfócito CD4 , COVID-19/mortalidade , Criança , Pré-Escolar , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/mortalidade , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Espanha/epidemiologia , Adulto Jovem , Tratamento Farmacológico da COVID-19
2.
Anesth Analg ; 133(4): 852-859, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-33346986

RESUMO

Focused cardiac ultrasound (FoCUS) has become a valuable tool to assess unexplained hypotension in critically ill patients. Due to increasing availability of transthoracic echocardiography (TTE) equipment in the operating room, there is a widespread interest in its usefulness for intraoperative diagnosis of hypotension as an alternative to transesophageal echocardiography (TEE). The objective of this systematic review is to evaluate the utility of intraoperative FoCUS to assess patients experiencing unexplained hypotension while undergoing noncardiac surgery. We performed a systematic literature search of multiple publication databases for studies that evaluated the utility of intraoperative FoCUS for assessment and management of unexplained hypotension in patients undergoing noncardiac surgery, including retro- and prospective clinical studies. A summary of the study findings, study quality, and assessment of level of evidence is presented. We identified 2227 unique articles from the literature search, of which 27 were potentially relevant, and 9 were included in this review. The number of patients pooled from these studies was 255, of whom 228 had intraoperative diagnoses with the aid of intraoperative FoCUS. The level of evidence of all studies included was very low according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) guidelines. This systematic review has demonstrated that FoCUS may be a useful, noninvasive method to differentiate causes of intraoperative hypotension and guide correcting interventions, although the quality of evidence is very low. Further prospective high-quality studies are needed to investigate whether intraoperative FoCUS has a diagnostic utility that is associated with improved outcomes.


Assuntos
Pressão Sanguínea , Ecocardiografia , Hipotensão/diagnóstico por imagem , Cuidados Intraoperatórios , Procedimentos Cirúrgicos Operatórios/efeitos adversos , Diagnóstico Diferencial , Humanos , Hipotensão/etiologia , Hipotensão/fisiopatologia , Hipotensão/terapia , Valor Preditivo dos Testes , Medição de Risco , Fatores de Risco
3.
BMC Anesthesiol ; 21(1): 258, 2021 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-34706655

RESUMO

BACKGROUND: The World Symposium of Pulmonary Hypertension in 2018, updated the definition of pulmonary hypertension (PH) as mean pulmonary artery pressures (PAP) > 20 mmHg. Pulmonary venous hypertension secondary to left-heart disease, constitutes the most common cause of PH, and the determination of a co-existent pre-capillary (primary) PH becomes paramount, particularly at the moment of evaluating and managing patients with heart failure. Pulmonary artery pressures above the systemic pressures define supra-systemic PH and generally leads to frank right ventricular failure and high mortality. CASE PRESENTATION: We present the perioperative management of a patient with rheumatic mitral valve disease, initially found to have severe PH due to pulmonary venous hypertension, who underwent percutaneous mitral balloon valvuloplasty complicated with mitral chordae rupture, severe mitral regurgitation and supra-systemic PH. Multiple medical therapies and an intra-aortic balloon pump were used as means of non-surgical management of this complication. CONCLUSIONS: This case report illustrates the perioperative implications of combined pre- and post-capillary PH and supra-systemic PH, as this has not been widely discussed in previous literature. A thorough literature review of the clinical characteristics of PH, methods to determine co-existent pre- and post-capillary PH components, as well as concomitant right ventricular failure is presented. Severe PH has known detrimental effects on the hemodynamic status of patients, which can ultimately lead to a decrease in effective cardiac output and poor tissue perfusion.


Assuntos
Valvuloplastia com Balão , Hipertensão Pulmonar/terapia , Estenose da Valva Mitral/terapia , Cordas Tendinosas/lesões , Feminino , Humanos , Balão Intra-Aórtico , Pessoa de Meia-Idade , Insuficiência da Valva Mitral/terapia , Pirimidinas/uso terapêutico , Cardiopatia Reumática/complicações , Cardiopatia Reumática/terapia , Ruptura Espontânea , Sulfonamidas/uso terapêutico , Vasodilatadores/uso terapêutico
4.
BMC Anesthesiol ; 21(1): 77, 2021 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-33711919

RESUMO

BACKGROUND: The complexity of extracorporeal membrane oxygenation (ECMO) techniques continues to evolve. Different cannulation methods and configurations have been proposed as a response to a challenging cardiovascular and pulmonary physiology of the patients. The use of parallel ECMO circuits represents a unique and novel approach for patients with refractory respiratory failure and cardiovascular collapse with very large body surface areas. CASE PRESENTATION: We present the case of a 25-year-old morbidly obese male patient admitted for severe acute respiratory distress syndrome (ARDS) and refractory hypoxemia, requiring institution of double cannulation for veno-venous ECMO. Since his hypoxemia persisted, likely due to insufficient flows given his large body surface area, an additional drainage venous cannula was implemented to provide higher flows, temporarily addressing his oxygenation status. Unfortunately, the patient developed concomitant cardiogenic shock refractory to inotropic support and extracorporeal fluid removal, further worsening his oxygenation status, thus the decision was to institute four-cannulation/parallel-circuits veno-venous and veno-arterial ECMO, successfully controlling both refractory hypoxemia and cardiogenic shock. CONCLUSIONS: Our case illustrates a novel and complex approach for combined severe ARDS and cardiovascular collapse through the use of parallel veno-venous and veno-arterial ECMO circuits, and exemplifies the expansion of ECMO techniques and its life-saving capabilities when conservative approaches are futile.


Assuntos
Oxigenação por Membrana Extracorpórea/instrumentação , Hipóxia/complicações , Obesidade Mórbida/complicações , Síndrome do Desconforto Respiratório/complicações , Insuficiência Respiratória/complicações , Choque Cardiogênico/complicações , Adulto , Oxigenação por Membrana Extracorpórea/métodos , Humanos , Hipóxia/terapia , Masculino , Respiração Artificial/métodos , Síndrome do Desconforto Respiratório/terapia , Insuficiência Respiratória/terapia , Choque Cardiogênico/terapia
5.
J Cardiothorac Vasc Anesth ; 35(8): 2471-2479, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33726942

RESUMO

The use and evolution of oral anticoagulation therapies continue to advance for multiple reasons, including a growing segment of older patients with associated chronic prothrombotic illnesses including cardiovascular, pulmonary, hematologic and oncologic conditions. Correlated to this increased use of oral anticoagulants is bleeding complications associated with their use. Based on these trends, it is expected that perioperative physicians will be facing more and more of these patients requiring scheduled, urgent or emergent surgical procedures During May 2020, the American College of Cardiology updated its Expert Consensus Decision Pathway devoted to the approach of bleeding in patients on oral anticoagulants. This updated version emphasized the expanding role of the direct-acting oral anticoagulants in other conditions beyond nonvalvular atrial fibrillation, such as venous thromboembolism. Several details discussed within this most recent update are pertinent to perioperative physicians, who frequently deal with bleeding in the setting of anticoagulation. The purpose of this narrative review is to highlight and expand on these salient points because they relate to perioperative management.


Assuntos
Fibrilação Atrial , Cardiologia , Médicos , Administração Oral , Anticoagulantes/efeitos adversos , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Consenso , Humanos , Estados Unidos/epidemiologia
6.
BMC Anesthesiol ; 20(1): 177, 2020 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-32689937

RESUMO

The management of Acute Respiratory Distress Syndrome (ARDS) secondary to the novel Coronavirus Disease 2019 (COVID-19) proves to be challenging and controversial. Multiple studies have suggested the likelihood of an atypical pathophysiology to explain the spectrum of pulmonary and systemic manifestations caused by the virus. The principal paradox of COVID-19 pneumonia is the presence of severe hypoxemia with preserved pulmonary mechanics. Data derived from the experience of multiple centers around the world have demonstrated that initial clinical efforts should be focused into avoid intubation and mechanical ventilation in hypoxemic COVID-19 patients. On the other hand, COVID-19 patients progressing or presenting into frank ARDS with typical decreased pulmonary compliance, represents another clinical enigma to many clinicians, since routine therapeutic interventions for ARDS are still a subject of debate.


Assuntos
Betacoronavirus , Infecções por Coronavirus/terapia , Cuidados Críticos/métodos , Pneumonia Viral/terapia , Síndrome do Desconforto Respiratório/terapia , Corticosteroides/uso terapêutico , Biomarcadores/metabolismo , COVID-19 , Teste para COVID-19 , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/transmissão , Infecção Hospitalar/transmissão , Citocinas/metabolismo , Diagnóstico por Imagem , Oxigenação por Membrana Extracorpórea/métodos , Humanos , Hipóxia/virologia , Doenças do Sistema Imunitário/virologia , Intubação Intratraqueal , Bloqueio Neuromuscular/métodos , Pandemias , Posicionamento do Paciente/métodos , Pneumonia Viral/diagnóstico , Pneumonia Viral/transmissão , Pneumonia Viral/virologia , Decúbito Ventral/fisiologia , Respiração Artificial/métodos , Síndrome do Desconforto Respiratório/virologia , SARS-CoV-2 , Trombofilia/virologia , Vasodilatadores/uso terapêutico , Tratamento Farmacológico da COVID-19
7.
J Cardiothorac Vasc Anesth ; 33(12): 3303-3308, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30850225

RESUMO

OBJECTIVE: To compare outcomes among patients with and without preprocedural radial arterial catheters who underwent transfemoral transcatheter aortic valve replacement (TF-TAVR) under deep intravenous (IV) sedation and to assess predictive variables for preprocedural placement. DESIGN: Single-center, retrospective, cohort analysis. SETTING: Department of Anesthesiology, Pain Management and Perioperative Medicine, Henry Ford Hospital, which is a tertiary care, university-affiliated hospital. PARTICIPANTS: The study comprised 157 patients. The primary focus was the 106 patients who underwent TF-TAVR when routine placement of preprocedure radial arterial catheters was abandoned. They were analyzed for hospital length of stay, 30-day mortality, and predictive factors of preprocedure placement. The remaining patients served as historical controls when routine radial artery catheter placement was practiced. INTERVENTIONS: Patient, procedure, and provider factors were analyzed. The transitional period consisted of 169 consecutive days from April 13 to September 28, 2017. A reference group of historical patients served as a control. MEASUREMENTS AND MAIN RESULTS: Seventy-five of 106 patients did not have a preprocedural radial arterial catheter. The primary outcome measures of length of stay and 30-day mortality within the transitional group were not different. Secondary outcome measures included identification of predictive variables for preprocedure placement and outcome comparisons between the transitional and historical groups. Anesthesia provider (p = 0.015) and ejection fraction (p = 0.039) were significant factors. There were no differences in outcome measures. CONCLUSION: There was no difference in primary outcomes in patients with or without radial arterial catheters for TF-TAVR. The findings of this study suggest anesthesia provider and ejection fraction were significant factors for preprocedural placement.


Assuntos
Estenose da Valva Aórtica/cirurgia , Pressão Sanguínea/fisiologia , Cateterismo Periférico/métodos , Sedação Consciente/métodos , Monitorização Fisiológica/métodos , Substituição da Valva Aórtica Transcateter/métodos , Idoso , Valva Aórtica/cirurgia , Estenose da Valva Aórtica/diagnóstico , Ecocardiografia Transesofagiana , Feminino , Artéria Femoral , Seguimentos , Humanos , Tempo de Internação/tendências , Masculino , Artéria Radial , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo
8.
J Cardiothorac Vasc Anesth ; 33(9): 2414-2418, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31076296

RESUMO

OBJECTIVE: The purposes of this study were to establish whether implementing a curriculum of perioperative point-of-care ultrasound (POCUS) of the heart and lungs for current in-training anesthesia residents during their required month of cardiac anesthesia was feasible and whether an evaluation tool would demonstrate improvement in the residents' baseline knowledge of POCUS. DESIGN: Single-center, prospective, cohort, and observational study. SETTING: A tertiary-care, university-affiliated hospital. PARTICIPANTS: The study comprised 16 anesthesia residents on their third postgraduate training year during their required cardiac anesthesia rotation. INTERVENTIONS: The implementation of a curriculum to educate anesthesia residents in perioperative POCUS of the heart and lungs on patients undergoing elective cardiothoracic procedures that included both theoretical and practical approaches. A 21-question, multiple-choice, electronic-generated test was developed to gauge performance improvement from before ("pretest") to after ("posttest") the 4-week period. MEASUREMENTS AND MAIN RESULTS: Of the 16 residents, 13 (81.3%) showed improved scores between the pretest and posttest periods after the 4-week rotation. The difference between pretest and posttest mean score was 5 (p = 0.001). CONCLUSIONS: This study demonstrates that integrating a curriculum dedicated to perioperative POCUS of the heart and lungs as part of the goals and objectives during the rotation of cardiac anesthesia is feasible and that anesthesia residents who received the training proposed by the authors improved their cognitive and technical skills.


Assuntos
Anestesiologia/educação , Anestesiologia/normas , Competência Clínica/normas , Internato e Residência/normas , Sistemas Automatizados de Assistência Junto ao Leito/normas , Ultrassonografia de Intervenção/normas , Anestesia/normas , Estudos de Coortes , Feminino , Hospitais Universitários/normas , Humanos , Masculino , Estudos Prospectivos
9.
Enferm Infecc Microbiol Clin ; 34(6): 346-52, 2016.
Artigo em Espanhol | MEDLINE | ID: mdl-26530224

RESUMO

INTRODUCTION: The objective of the study is to validate the relevant GESIDA quality indicators for HIV infection, assessing the reliability, feasibility and adherence to them. METHODS: The reliability was evaluated using the reproducibility of 6 indicators in peer review, with the second observer being an outsider. The feasibility and measurement of the level of adherence to the 22 indicators was conducted with annual fragmented retrospective collection of information from specific databases or the clinical charts of the nine participating hospitals. RESULTS: Reliability was very high, with interobserver agreement levels higher than 95% in 5 of the 6 indicators. The median time to achieve the indicators ranged between 5 and 600minutes, but could be achieved progressively from specific databases, enabling obtaining them automatically. As regards adherence to the indicators related with the initial evaluation of the patients, instructions and suitability of the guidelines for ART, adherence to ART, follow-up in clinics, and achieve an undetectable HIV by PCR at week 48 of the ART. Indicators of quality related to the prevention of opportunistic infections and control of comorbidities, the standards set were not achieved, and significant heterogeneity was observed between hospitals. CONCLUSION: The GESIDA quality indicators of HIV infection enabled the relevant indicators to be feasibly and reliably measured, and should be collected in all the units that care for patients with HIV infection.


Assuntos
Infecções por HIV/terapia , Indicadores de Qualidade em Assistência à Saúde/normas , Estudos de Viabilidade , Infecções por HIV/epidemiologia , Humanos , Reprodutibilidade dos Testes , Estudos Retrospectivos , Espanha/epidemiologia
10.
Psychol Rep ; 116(2): 422-37, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25730750

RESUMO

This study analyzes, in a sample of Mexican students, the factor structure of the Physical Self-Concept Questionnaire of Goñi, Ruiz de Azúa, and Rodríguez (2006), which assesses physical ability, physical fitness, attractiveness, strength, general physical self-concept, and global self-concept. A representative sample of 1,466 Mexican university physical education students was selected (754 men, 712 women; M age=20.6 yr., SD=2.0). Confirmatory factor analysis showed a two-factor structure (motor competency and physical attractiveness). The two-factor structure, regarding statistical and substantive criteria, had good fit indices. Results of the factor analyses carried out with the sub-samples indicated a strong stability and evidence for the factor structure obtained. The findings support the use of this questionnaire to measure physical self-concept in Mexican university students. Future studies should replicate these findings in other populations.


Assuntos
Imagem Corporal/psicologia , Psicometria/instrumentação , Autoimagem , Estudantes/psicologia , Inquéritos e Questionários/normas , Adulto , Beleza , Feminino , Humanos , Masculino , México , Aptidão Física , Universidades , Adulto Jovem
13.
J Infect Dis ; 207(8): 1235-41, 2013 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-23325914

RESUMO

We estimated the effect of sexual behavior, age, and immunodeficiency on the number of high-risk human papillomavirus (HR-HPV) types in the anal canal among human immunodeficiency virus-positive men who have sex with men (MSM). Anal samples were genotyped with the Linear Array HPV Genotyping Test, and risk factors were investigated with Poisson regression. Of 586 MSM, 69% were Spanish, and 25.6% were Latin American; the median age was 34.9 years (interquartile range [IQR], 30.1-40.8). The median number of recent sex partners was 6 (IQR, 2-24 sex partners), and the median CD4(+) T-cell count was 531.5 cells/mm(3) (IQR, 403-701 cells/mm(3)). The prevalence of any and multiple HR-HPV infections was 83.4% and 60.5%, respectively. The most common types were HPV-16 (42%), HPV-51 (24%), HPV-39 (23.7%), and HPV-59 (23.5%). Age had a statistically significant, nonlinear association with the number of types, with the highest number detected around 35 years of age (P < .001). The number of recent sex partners had a statistically significant, fairly linear association on the log scale (P = .033). The high prevalence of HR-HPV types is associated with recent sexual behavior and age.


Assuntos
Canal Anal/virologia , Infecções por HIV/virologia , Papillomaviridae/classificação , Infecções por Papillomavirus/virologia , Comportamento Sexual , Adulto , Fatores Etários , Contagem de Linfócito CD4 , Coinfecção/epidemiologia , Coinfecção/virologia , DNA Viral/análise , DNA Viral/genética , Genótipo , Técnicas de Genotipagem , HIV/patogenicidade , Infecções por HIV/epidemiologia , Papillomavirus Humano 16/classificação , Papillomavirus Humano 16/genética , Papillomavirus Humano 16/isolamento & purificação , Papillomavirus Humano 16/patogenicidade , Humanos , América Latina/epidemiologia , Masculino , Pessoa de Meia-Idade , Papillomaviridae/genética , Papillomaviridae/isolamento & purificação , Papillomaviridae/patogenicidade , Infecções por Papillomavirus/epidemiologia , Distribuição de Poisson , Prevalência , Fatores de Risco , Parceiros Sexuais , Espanha/epidemiologia , Carga Viral
14.
Saudi J Anaesth ; 18(2): 257-264, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38654884

RESUMO

Enhanced recovery after cardiac surgery (ERACS) represents a constellation of evidence-based peri-operative methods aimed to reduce the physiological and psychological stress patients experience after cardiac surgery, with the primary objective of providing an expedited recovery to pre-operative functional status. The method involves pre-operative, intra-operative, and post-operative interventions as well as direct patient engagement to be successful. Numerous publications in regard to the benefits of enhanced recovery have been presented, including decreased post-operative complications, shortened length of stay, decreased overall healthcare costs, and higher patient satisfaction. Implementing an ERACS program undeniably requires a culture change, a methodical shift in the approach of these patients that ultimately allows the team to achieve the aforementioned goals; therefore, team-building, planning, and anticipation of obstacles should be expected.

15.
EMBO J ; 28(11): 1666-78, 2009 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-19440202

RESUMO

RepB initiates plasmid rolling-circle replication by binding to a triple 11-bp direct repeat (bind locus) and cleaving the DNA at a specific distant site located in a hairpin loop within the nic locus of the origin. The structure of native full-length RepB reveals a hexameric ring molecule, where each protomer has two domains. The origin-binding and catalytic domains show a three-layer alpha-beta-alpha sandwich fold. The active site is positioned at one of the faces of the beta-sheet and coordinates a Mn2+ ion at short distance from the essential nucleophilic Y99. The oligomerization domains (ODs), each consisting of four alpha-helices, together define a compact ring with a central channel, a feature found in ring helicases. The toroidal arrangement of RepB suggests that, similar to ring helicases, it encircles one of the DNA strands during replication to confer processivity to the replisome complex. The catalytic domains appear to be highly mobile with respect to ODs. This mobility may account for the adaptation of the protein to two distinct DNA recognition sites.


Assuntos
DNA Helicases/química , DNA Helicases/metabolismo , Subunidades Proteicas/química , Sequência de Aminoácidos , Sítios de Ligação , Domínio Catalítico , Modelos Moleculares , Dados de Sequência Molecular , Multimerização Proteica , Estrutura Quaternária de Proteína , Estrutura Secundária de Proteína , Estrutura Terciária de Proteína
17.
Biochim Biophys Acta Rev Cancer ; 1878(3): 188900, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37105413

RESUMO

The molecular machinery of the circadian clock regulates the expression of many genes and processes in the organism, allowing the adaptation of cellular activities to the daily light-dark cycles. Disruption of the circadian rhythm can lead to various pathologies, including cancer. Thus, disturbance of the normal circadian clock at both genetic and environmental levels has been described as an independent risk factor for cancer. In addition, researchers have proposed that circadian genes may have a tissue-dependent and/or context-dependent role in tumorigenesis and may function both as tumor suppressors and oncogenes. Finally, circadian clock core genes may trigger or at least be involved in different hallmarks of cancer. Hence, expanding the knowledge of the molecular basis of the circadian clock would be helpful to identify new prognostic markers of tumorigenesis and potential therapeutic targets.


Assuntos
Relógios Circadianos , Neoplasias , Humanos , Relógios Circadianos/genética , Ritmo Circadiano/genética , Neoplasias/genética , Carcinogênese , Transformação Celular Neoplásica
19.
Pathogens ; 11(5)2022 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-35631049

RESUMO

During recent decades, a tick-borne rickettsial syndrome, characterized by eschar and painful lymphadenopathy after Dermacentor marginatus-bite, has been described as an emerging rickettsiosis in Europe. Our group named it DEBONEL (Dermacentor-borne-necrosis-erythema-lymphadenopathy), regarding the vector and the main infection signs. Other groups called it TIBOLA (tick-borne-lymphadenophathy) and, later, SENLAT (scalp-eschar-and-neck-lymphadenopathy-after-tick-bite), expanding, in the latter, the etiological spectrum to other pathogens. Objective: To investigate the etiology of DEBONEL agents in our area, and to compare their epidemiological/clinical/microbiological characteristics. During 2001-2020, 216 patients clinically diagnosed of DEBONEL (the largest series from one center) in La Rioja (northern Spain) were examined. Rickettsia spp. were amplified in 14/104 (13.46%) blood samples, 69/142 (48.59%) eschar swabs, 7/7 (100%) biopsies, and 71/71 (100%) D. marginatus from patients. For samples in which Rickettsia was undetected, no other microorganisms were found. 'Candidatus Rickettsia rioja', Rickettsia slovaca, Rickettsia raoultii, and Rickettsia DmS1 genotype were detected in 91, 66, 4, and 3 patients, respectively. DEBONEL should be considered in patients with clinical manifestations herein described in areas associated to Dermacentor. The most frequently involved agent in our environment is 'Ca. R. rioja'. The finding of Rickettsia sp. DmS1 in ticks attached to DEBONEL patients suggests the implication of other rickettsia genotypes.

20.
Nat Commun ; 13(1): 74, 2022 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-35013193

RESUMO

Tyrosine hydroxylase (TH) catalyzes the rate-limiting step in the biosynthesis of dopamine (DA) and other catecholamines, and its dysfunction leads to DA deficiency and parkinsonisms. Inhibition by catecholamines and reactivation by S40 phosphorylation are key regulatory mechanisms of TH activity and conformational stability. We used Cryo-EM to determine the structures of full-length human TH without and with DA, and the structure of S40 phosphorylated TH, complemented with biophysical and biochemical characterizations and molecular dynamics simulations. TH presents a tetrameric structure with dimerized regulatory domains that are separated 15 Å from the catalytic domains. Upon DA binding, a 20-residue α-helix in the flexible N-terminal tail of the regulatory domain is fixed in the active site, blocking it, while S40-phosphorylation forces its egress. The structures reveal the molecular basis of the inhibitory and stabilizing effects of DA and its counteraction by S40-phosphorylation, key regulatory mechanisms for homeostasis of DA and TH.


Assuntos
Dopamina/farmacologia , Inibidores Enzimáticos/farmacologia , Tirosina 3-Mono-Oxigenase/antagonistas & inibidores , Tirosina 3-Mono-Oxigenase/química , Sequência de Aminoácidos , Domínio Catalítico , Catecolaminas/metabolismo , Microscopia Crioeletrônica , Dopamina/química , Dopamina/metabolismo , Inibidores Enzimáticos/química , Inibidores Enzimáticos/metabolismo , Humanos , Modelos Moleculares , Fosforilação , Ligação Proteica , Domínios Proteicos , Tirosina 3-Mono-Oxigenase/genética , Tirosina 3-Mono-Oxigenase/metabolismo
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