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1.
J Nurs Manag ; 30(2): 359-366, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34837274

RESUMO

AIM: The main aim of this study was to understand what health and wellbeing initiatives are helpful for health care workers' stress and psychological distress during the Covid-19 pandemic. BACKGROUND: Health care workers are at increased risk of poor mental health during health emergencies; understanding support required for health care workers is of paramount importance. METHODS: Participants were health care workers at a health and social care organization (N = 159). The study included an online questionnaire including an evaluation of health and wellbeing initiatives and measures of perceived stress and psychological distress. RESULTS: The highest rated resources were counselling, personal protective equipment (PPE) and Covid-19 testing. Those who accessed yoga reported significantly less stress and psychological distress than those who did not access yoga. CONCLUSIONS: Health care workers with higher stress and psychological distress felt less supported by their organization, less listened to and less involved in organizational decisions. IMPLICATIONS FOR NURSING MANAGEMENT: Practical implications are discussed such as forward planning for health emergencies (e.g., PPE supply), accessible Covid-19 testing as well as budgeting for counselling services and exercise classes. In addition, targeted support for those diagnosed with Covid-19 is recommended, alongside involvement of staff members in organizational decisions.


Assuntos
COVID-19 , Angústia Psicológica , COVID-19/epidemiologia , Teste para COVID-19 , Estudos Transversais , Atenção à Saúde , Pessoal de Saúde/psicologia , Humanos , Pandemias , SARS-CoV-2 , Estresse Psicológico/complicações
2.
J Appl Res Intellect Disabil ; 35(1): 252-260, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34676652

RESUMO

BACKGROUND: A recovery approach within mental health services has gained momentum. Its meaning for adults with intellectual disabilities recovering from mental health disorders is less understood. Peoples' experiences of recovery were explored to help inform recovery-focused recommendations for clinical practise. METHOD: A qualitative design using interpretative phenomenological analysis was applied. Nine interviews with people with intellectual disabilities who had experienced mental health disorders were conducted. RESULTS: Two themes that emerged focusing on entry to service and the recovery experience. Subthemes for entry to service included unfair treatment, valuing information and managing expectations. The recovery experience subthemes were therapeutic alliance, self-management, emotional development, autonomy, connectedness, positive identity and a belief in recovery. CONCLUSIONS: Hearing peoples' experiences directly allowed the current themes to emerge in the context of living with lifelong disabilities. This article adds to the sparse literature and highlights considerations for recovery-based interventions for people with intellectual disabilities.


Assuntos
Pessoas com Deficiência , Deficiência Intelectual , Adulto , Emoções , Humanos
3.
J Cardiothorac Vasc Anesth ; 33(9): 2376-2384, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31097337

RESUMO

OBJECTIVE: The authors hypothesized that grading valvular aortic stenosis (AS) with dimensionless index (DI) during intraoperative pre-cardiopulmonary bypass (pre-CPB) transesophageal echocardiography (TEE) would match the grade of AS during preoperative transthoracic echocardiography (TTE) for the same patients more often than when using peak velocity (Vp), mean pressure gradient (PGm), or aortic valve area (AVA). DESIGN: Retrospective, observational. SETTING: Single university hospital. PARTICIPANTS: The participants in this study included 123 cardiac surgical patients with any degree of AS, who underwent open cardiac surgery between 2010 and 2016 at the Medical University of South Carolina and had Vp, PGm, AVA, and DI values available from reporting databases or archived imaging. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: When using DI, pre-CPB TEE grading of AS severity was 1 grade higher 21.1% of the time and 1 grade lower 13.0% of the time compared with TTE, for an overall disagreement rate of 34.1%. The overall disagreement rates between pre-CPB TEE and TTE for Vp, PGm, and AVA were 39.8%, 33.3%, and 33.3%, respectively. CONCLUSIONS: The authors could not demonstrate that DI was better than Vp, PGm, or AVA at matching AS grades between intraoperative pre-CPB TEE and preoperative TTE. When DI was used, pre-CPB TEE was more likely to overestimate than underestimate the severity of AS compared with TTE. However, when Vp or PGm was used, pre-CPB TEE was more likely to underestimate the severity of AS compared with TTE. A comprehensive approach without overemphasis on 1 parameter should be used for AS assessment by intraoperative TEE.


Assuntos
Estenose da Valva Aórtica/diagnóstico por imagem , Ponte Cardiopulmonar/normas , Ecocardiografia Transesofagiana/normas , Ecocardiografia/normas , Cuidados Pré-Operatórios/normas , Índice de Gravidade de Doença , Idoso , Idoso de 80 Anos ou mais , Estenose da Valva Aórtica/cirurgia , Ponte Cardiopulmonar/métodos , Ecocardiografia/métodos , Ecocardiografia Transesofagiana/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cuidados Pré-Operatórios/métodos , Estudos Retrospectivos
4.
J Sci Food Agric ; 98(8): 3190-3197, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29230819

RESUMO

BACKGROUND: The early generation selection of cassava quantitative and qualitative traits saves breeding resources as it can shorten breeding schemes. Inheritance analysis provides important breeding information for developing new improved varieties. This study aimed at developing an F1 segregating cassava population and determining mode of gene action of pulp colour and selected traits at early generation selection (F1 seedling and clones). RESULTS: The 15 families exhibited significant (P < 0.05) phenotypic variation between offspring. The general combining ability (GCA) was significant for all traits except cassava brown streak disease on leaves, whereas specific combining ability (SCA) was significant for all evaluated traits. The Garukansubire and Gitamisi genotypes were the best general combiners for improving fresh storage root yield, while G1 and G2 were the best general combiners for improved carotenoid (yellow/orange pulp colour) and delayed physiological postharvest deterioration. The pulp colour had the highest GCA/SCA ratio and percent sum of squares due to GCA. CONCLUSION: The 15 F1 families exhibited essential genetic diversity for cassava improvement. The expression of most cassava traits was controlled by both additive and non-additive gene action. The study elucidated the role of dominance effects over the additive effects for the evaluated traits. However, the pulp colour was predominantly controlled by additive gene action. This implies the possibility of improving cassava through conventional breeding using recurrent selection for most traits. © 2017 Society of Chemical Industry.


Assuntos
Carotenoides/análise , Manihot/genética , Cruzamento , Carotenoides/metabolismo , Cor , Variação Genética , Genótipo , Manihot/química , Manihot/metabolismo , Raízes de Plantas/química , Raízes de Plantas/genética , Raízes de Plantas/metabolismo
5.
Cephalalgia ; 35(12): 1115-24, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25667300

RESUMO

BACKGROUND: The management of short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) and with short-lasting unilateral neuralgiform headache attacks with autonomic symptoms (SUNA) remains challenging in view of the limited understanding of their pathophysiological mechanisms. METHODS: An initial observation that patients with both chronic migraine (CM) or cluster headache (CH) and SUNCT/SUNA receiving intravenous dihydroergotamine (IV DHE) had complained of dramatic worsening of the latter led to review of the case notes of patients with CM or CH and co-existent SUNCT/SUNA seen between 2008 and 2013 and who had a trial of IV DHE. RESULTS: Twenty-four patients were identified. IV DHE was ineffective for SUNCT/SUNA in 16 patients, while one patient reported a marginal improvement. Five patients reported dramatic worsening of the SUNCT/SUNA. Moreover, two patients developed new-onset SUNA during their first IV DHE infusion. Out of these seven patients, those requiring repeated courses of IV DHE consistently experienced exacerbations of SUNCT/SUNA which were suppressed with IV lidocaine. CONCLUSIONS: DHE is an ineffective treatment option for SUNCT and SUNA. Physicians who intend to offer IV DHE to CH or CM patients should warn them that IV DHE could exacerbate and possibly even lead to a de novo onset of SUNCT/SUNA. In view of the reported worsening or new onset of SUNCT/SUNA in patients using dopamine agonists for the treatment of pituitary prolactinomas, we speculate that DHE might worsen or induce SUNCT and SUNA, at least in a sub-group of patients, through a perturbation in the dopaminergic system.


Assuntos
Doenças do Sistema Nervoso Autônomo/induzido quimicamente , Doenças do Sistema Nervoso Autônomo/tratamento farmacológico , Di-Hidroergotamina/administração & dosagem , Di-Hidroergotamina/efeitos adversos , Síndrome SUNCT/induzido quimicamente , Síndrome SUNCT/tratamento farmacológico , Adulto , Analgésicos não Narcóticos/administração & dosagem , Analgésicos não Narcóticos/efeitos adversos , Feminino , Humanos , Injeções Intravenosas , Masculino , Pessoa de Meia-Idade , Medição da Dor/efeitos dos fármacos , Síndrome SUNCT/diagnóstico , Falha de Tratamento , Vasoconstritores/administração & dosagem , Vasoconstritores/efeitos adversos
6.
Bioorg Med Chem Lett ; 24(24): 5824-5828, 2014 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-25455498

RESUMO

A series of 34 amphiphilic compounds varying in both number of quaternary ammonium groups and length of alkyl chains has been assembled. The synthetic preparations for these structures are simple and generally high-yielding, proceeding in 1-2 steps without the need for chromatography. Antibacterial MIC data for these compounds were determined, and over half boast single digit MIC values against a series of gram-positive and gram-negative bacteria. MIC variation mostly hinged on the length of the alkyl chain, where a dodecyl group led to optimal activity; surprisingly, the number of cations and/or basic nitrogens was less important in dictating bioactivity. Additional structural variation was prepared in a trisamine series dubbed 12,3,X,3,12, providing a series of potent amphiphiles functionalized with varied allyl, alkyl, and benzyl groups. Tetraamines were also investigated, culminating in a two-step preparation of a tetracationic structure that showed only modestly improved bioactivity versus amphiphiles with two or three cations.


Assuntos
Anti-Infecciosos/química , Poliaminas/química , Anti-Infecciosos/síntese química , Anti-Infecciosos/farmacologia , Cátions/química , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Compostos de Amônio Quaternário/química , Relação Estrutura-Atividade
7.
Gerontologist ; 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-39041347

RESUMO

BACKGROUND AND OBJECTIVES: Existing literature highlights notable health and social inequalities for people ageing with a lifelong disability and the need for research to better understand how we can support this group to age well. This scoping review mapped existing literature related to 'ageing well' in people with lifelong disabilities. RESEARCH DESIGN AND METHODS: Five scientific databases and grey literature sources were searched for studies related to 'ageing well' and 'lifelong disability' (defined as a disability that a person had lived with since birth or early childhood). RESULTS: We identified 81 studies that discussed ageing well with a lifelong disability, with most (70%) focusing on intellectual disabilities. Two themes captured existing research on ageing well with a lifelong disability: 1.) Framing ageing well with a lifelong disability, which included the ways that people with lifelong disability, their supporters and existing research frame ageing well for this group and 2.) Supporting people to age well with a lifelong disability, which involves the micro, meso and macro-level factors where research suggests interventions to facilitate ageing well could be situated. DISCUSSION AND IMPLICATIONS: This synthesis highlights how ageing well is currently framed in the literature and where interventions to improve ageing well in this group could be situated. Literature highlights the importance of considering multi-level interventions to improve ageing well. Evidence gaps include the lack of research conducted with groups other than those with intellectual disabilities and the need for more research examining ageing well interventions.

8.
Cephalalgia ; 32(3): 258-62, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22238357

RESUMO

BACKGROUND: Hemiplegic migraine (HM) is a rare subtype of migraine with aura that includes transient hemiparesis of different degrees. The dominantly inherited type, called familial hemiplegic migraine, along with the sporadic type, in which no family history of similar attacks exists, have been recently recognized by the revised International Classification of Headache Disorders (ICHD-2). Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) and short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms (SUNA) are also very rare conditions that are classified as trigeminal autonomic cephalalgias. This report provides the first description of an association between HM and SUNCT/SUNA. CASES: Eight females and two males with both these disorders were identified between 2007 and 2010. CONCLUSION: The coexistence of such rare primary headache disorders is probably due to a common underlining mechanism, with a sodium channelopathy being an attractive potential candidate.


Assuntos
Transtornos de Enxaqueca/complicações , Síndrome SUNCT/complicações , Cefalalgias Autonômicas do Trigêmeo/complicações , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
9.
Health Soc Care Community ; 29(5): 1429-1438, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33064360

RESUMO

Previous research has highlighted a lack of continuity of care when young people with a neurodevelopmental condition make the transition from children's to adult specialist healthcare services. A lack of planning, consistency, and availability of adult services has been found to lead to; increased anxiety, poor health outcomes, reduced support and some young people not receiving healthcare. The majority of transition research has focused on what health professionals consider important in the transition process, rather than focusing on the experiences of the young people and those closest to them. Our objective was to gather evidence from young people (and their families) who had experienced transition from children's to adult specialist healthcare services through semi-structured interviews. Volunteers were recruited from two London boroughs. All young people were aged between 18 and 25 years with a neurodevelopmental condition (Attention Deficit Hyperactivity Disorder, Autism Spectrum Disorder and/or an Intellectual Disability). Overall, we interviewed six young people with support from a family member. Five further family members were interviewed on behalf of the young person. In total, ten semi-structured interviews were transcribed verbatim and analysed using Interpretative Phenomenological Analysis. Four themes emerged from the analysis: (a) Parents as advocates, (b) Availability of adult's specialist health and social care services, (c) Lack of information sharing and (d) Transition as a binary, abrupt change. Our findings suggest the transition experience could be improved by changing service specifications to incorporate assessment and handover across the age range of 16-20 years. Additionally, statutory services should understand and provide the coordination role now offered by parents in transition. We suggest future research could evaluate the feasibility of a patient-owned online information sharing tool with information about relevant services for young people and their families.


Assuntos
Transtorno do Espectro Autista , Serviços de Saúde Mental , Transição para Assistência do Adulto , Adolescente , Adulto , Criança , Atenção à Saúde , Humanos , Pais , Adulto Jovem
10.
Curr Biol ; 12(7): 599-605, 2002 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-11937031

RESUMO

Cyclin-dependent kinases (CDKs) are absolutely required for DNA replication in eukaryotic cells. CDKs are thought to activate one or more replication factors, but the identities of these proteins are unknown. Here we describe fission yeast Drc1, a protein required for DNA replication that is phosphorylated by Cdc2. Drc1 depletion leads to catastrophic mitotic divisions with incompletely replicated DNA, indicating that Drc1 is required for DNA synthesis and S-M replication checkpoint control. Drc1 associates with Cdc2 and is phosphorylated at the onset of S phase when Cdc2 is activated. Mutant Drc1 that lacks CDK phosphorylation sites is nonfunctional and fails to interact with Cut5 replication factor. These data suggest that Cdc2 promotes DNA replication by phosphorylating Drc1 and regulating its association with Cut5.


Assuntos
Proteína Quinase CDC2/metabolismo , Proteínas de Ciclo Celular/metabolismo , Replicação do DNA , DNA Fúngico/biossíntese , Proteínas Fúngicas/metabolismo , Proteínas de Saccharomyces cerevisiae , Proteínas de Schizosaccharomyces pombe , Proteína Quinase CDC2/genética , Proteínas de Ciclo Celular/genética , Ciclina B/genética , Ciclina B/metabolismo , Ciclinas/genética , Ciclinas/metabolismo , Proteínas Fúngicas/genética , Fosforilação , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Schizosaccharomyces/genética
11.
Curr Biol ; 13(14): 1201-5, 2003 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-12867030

RESUMO

What promotes motor recovery from stroke? To date, studies of recovery from stroke have shown alterations in function in various cortical areas, including the contralesional (unaffected) motor cortex (M1). However, whether these changes contribute to recovery or are mere epiphenomena remains unclear. We therefore sought evidence that the ipsilateral M1 can compensate for dysfunction of the contralateral M1. We recorded the change in force production during a finger-tapping task in response to acute disruption of M1 function by repetitive transcranial magnetic stimulation (rTMS). Neither control (occipital) nor ipsilateral M1 rTMS lead to a change in tapping force. RTMS over contralateral M1 had a short-lived effect and induced changes in ipsilateral M1 excitability around the time that these behavioral effects abated, consistent with delayed compensation by the ipsilateral M1. Simultaneous bilateral M1 stimulation, designed to prevent compensation by the ipsilateral M1, had a large and prolonged effect on tapping force. This is the first demonstration that the ipsilateral primary motor cortex is capable of functionally significant compensation for focal contralateral cortical dysfunction in the adult human and provides a rational basis for interventional treatments aimed at promoting functional compensation in unaffected cortical areas after stroke.


Assuntos
Campos Eletromagnéticos , Lateralidade Funcional/fisiologia , Atividade Motora/fisiologia , Córtex Motor/fisiologia , Plasticidade Neuronal/fisiologia , Fenômenos Biomecânicos , Dedos/fisiologia , Humanos , Córtex Motor/efeitos da radiação
12.
Mol Cell Biol ; 23(16): 5939-46, 2003 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-12897162

RESUMO

Genome integrity is protected by Cds1 (Chk2), a checkpoint kinase that stabilizes arrested replication forks. How Cds1 accomplishes this task is unknown. We report that Cds1 interacts with Rad60, a protein required for recombinational repair in fission yeast. Cds1 activation triggers Rad60 phosphorylation and nuclear delocalization. A Rad60 mutant that inhibits regulation by Cds1 renders cells specifically sensitive to replication fork arrest. Genetic and biochemical studies indicate that Rad60 functions codependently with Smc5 and Smc6, subunits of an SMC (structural maintenance of chromosomes) complex required for recombinational repair. These studies indicate that regulation of Rad60 is an important part of the replication checkpoint response controlled by Cds1. We propose that control of Rad60 regulates recombination events at stalled forks.


Assuntos
Proteínas Cromossômicas não Histona/metabolismo , Proteínas Quinases/metabolismo , Proteínas Serina-Treonina Quinases , Recombinação Genética , Proteínas de Schizosaccharomyces pombe/metabolismo , Sequência de Aminoácidos , Núcleo Celular/metabolismo , Sobrevivência Celular , Quinase do Ponto de Checagem 2 , Relação Dose-Resposta a Droga , Relação Dose-Resposta à Radiação , Immunoblotting , Modelos Biológicos , Dados de Sequência Molecular , Mutação , Fosforilação , Ligação Proteica , Saccharomycetales
13.
Postgrad Med J ; 82(974): e29, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17148696

RESUMO

Tako-tsubo cardiomyopathy is a cardiac syndrome precipitated by profound emotional stress and anxiety, particularly in middle-aged women. It presents as a mimic of acute myocardial infarction, but coronary angiography shows normal coronary arteries and a characteristic left ventriculogram resembling an "octopus pot". The condition seems to have a favourable prognosis. Initially described in Japan, and with many names in the literature, it is being increasingly recognised in the West owing to early coronary angiography and primary coronary intervention, accounting for up to 1 in 30 primary cases of angioplasty in some institutions. A typical case is described, and the clinical features, pathophysiology and management reviewed.


Assuntos
Cardiomiopatias/psicologia , Movimento (Física) , Infarto do Miocárdio/psicologia , Estresse Psicológico/complicações , Idoso , Eletrocardiografia , Feminino , Transtornos da Cefaleia/psicologia , Humanos , Síndrome
14.
Genetics ; 165(4): 2289-93, 2003 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-14704204

RESUMO

Most models of homologous recombination invoke cleavage of Holliday junctions to explain crossing over. The Mus81.Eme1 endonuclease from fission yeast and humans cleaves Holliday junctions and other branched DNA structures, leaving its physiological substrate uncertain. We report here that Schizosaccharomyces pombe mus81 mutants have normal or elevated frequencies of gene conversion but 20- to 100-fold reduced frequencies of crossing over. Thus, gene conversion and crossing over can be genetically separated, and Mus81 is required for crossing over, supporting the hypothesis that the fission yeast Mus81.Eme1 protein complex resolves Holliday junctions in meiotic cells.


Assuntos
Troca Genética , Proteínas de Ligação a DNA/fisiologia , Endonucleases/fisiologia , Conversão Gênica , Meiose/fisiologia , Proteínas de Schizosaccharomyces pombe/fisiologia , Schizosaccharomyces/genética , Dano ao DNA , Proteínas de Saccharomyces cerevisiae , Schizosaccharomyces/enzimologia , Schizosaccharomyces/efeitos da radiação
15.
Pain Physician ; 17(1): 29-41, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24452643

RESUMO

BACKGROUND: Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) or with cranial autonomic symptoms (SUNA) are primary headaches characterized by frequent attacks of severe headaches in association with cranial autonomic features. Patients with chronic SUNCT or SUNA have unremitting symptoms that necessitate prolonged use of medical preventive treatments, many of which are prone to causing side effects. They can be medically intractable, in which case neurally destructive or cranially invasive surgical treatments can be offered, though these have hitherto yielded conflicting results. Occipital nerve stimulation (ONS) offers a nondestructive and relatively low risk surgical alternative. OBJECTIVE: To assess the efficacy and safety of ONS in chronic, medically intractable SUNCT and SUNA patients. STUDY DESIGN: Prospective open-label study. METHODS: Nine medically intractable, chronic SUNCT and SUNA patients were implanted with electrodes for bilateral occipital nerve stimulation. Data were collected prospectively for pre- and postimplantation headache characteristics, including frequency, intensity and duration of attacks. Diaries were used to assess headache improvement. RESULTS: At a median follow-up of 38 months (range 24-55 months), all but one patient reported substantial improvement. Four patients became pain-free, 3 were almost pain-free (96 - 98% improvement), and one had a marked reduction in attack frequency and severity (81% improvement). After an initial rapid improvement, the maximum benefit of ONS was attained after a lag of a few months. Device malfunction was followed by recurrence or worsening of the attacks within a few days in most patients. Adverse events included lead migration, exposure of the electrode, and pain due to muscle recruitment over the leads. One patient developed hemicrania continua one month after implantation and was successfully treated with indomethacin. CONCLUSION: ONS appears to offer an effective and safe treatment option, without significant morbidity, for medically intractable SUNCT and SUNA. Given the variable results with cranially invasive or neurally destructive surgery, ONS might be considered the surgical treatment of choice for medically intractable SUNCT and SUNA.


Assuntos
Doenças do Sistema Nervoso Autônomo/terapia , Terapia por Estimulação Elétrica/métodos , Síndrome SUNCT/terapia , Nervos Espinhais/fisiologia , Adulto , Idoso , Doenças do Sistema Nervoso Autônomo/diagnóstico por imagem , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Radiografia , Síndrome SUNCT/diagnóstico por imagem
16.
Nat Struct Mol Biol ; 20(5): 598-603, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23584455

RESUMO

Structure-specific DNA endonucleases have critical roles during DNA replication, repair and recombination, yet they also have the potential for causing genome instability. Controlling these enzymes may be essential to ensure efficient processing of ad hoc substrates and to prevent random, unscheduled processing of other DNA structures, but it is unknown whether structure-specific endonucleases are regulated in response to DNA damage. Here, we uncover DNA damage-induced activation of Mus81-Eme1 Holliday junction resolvase in fission yeast. This new regulation requires both Cdc2(CDK1)- and Rad3(ATR)-dependent phosphorylation of Eme1. Mus81-Eme1 activation prevents gross chromosomal rearrangements in cells lacking the BLM-related DNA helicase Rqh1. We propose that linking Mus81-Eme1 DNA damage-induced activation to cell-cycle progression ensures efficient resolution of Holliday junctions that escape dissolution by Rqh1-TopIII while preventing unnecessary DNA cleavages.


Assuntos
Dano ao DNA , Proteínas de Ligação a DNA/metabolismo , Endonucleases/metabolismo , Regulação Fúngica da Expressão Gênica , Resolvases de Junção Holliday/metabolismo , Proteínas de Schizosaccharomyces pombe/metabolismo , Schizosaccharomyces/enzimologia , Proteína Quinase CDC2/metabolismo , Proteínas de Ciclo Celular/metabolismo , Quinase do Ponto de Checagem 2 , Modelos Biológicos , Fosforilação , Proteínas Quinases/metabolismo , Processamento de Proteína Pós-Traducional , Transdução de Sinais
17.
J Neurophysiol ; 96(4): 1711-7, 2006 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16790603

RESUMO

Short-interval intracortical inhibition (SICI) decreases during voluntary contraction of the target muscle. It is unknown whether this effect also occurs with postural contractions. We have compared the effects of voluntary and postural contractions on SICI in the soleus (SOL) muscle. We applied transcranial magnetic stimuli (TMS) in subjects under three tasks: sitting at rest (Rest), sitting while activating the SOL muscle (Voluntary), or standing quietly (Postural). In control trials, we applied suprathreshold TMS to obtain unconditioned motor-evoked potentials (MEPs). In test trials, the same TMS was preceded by a subthreshold TMS at different interstimulus intervals (ISIs), to obtain a conditioned MEP. SICI and intracortical facilitation (ICF) were expressed as the decrease or increase in MEP size relative to unconditioned MEPs. There was significant effect of task in mean SICI or mean ICF in SOL. Mean SICI in SOL was 52% in Rest and decreased to 21% in Voluntary and 15% in Postural. Mean ICF in SOL was 132% and decreased to 113% in Voluntary and to 108% in Postural. Mean SICI in SOL was not different in Voluntary and Postural tasks. There was no effect of task in mean SICI or mean ICF in TA. Our results indicate that decrease of SICI with muscle contraction occurs to a similar extent with tonic voluntary and postural activation, suggesting that those contractions require a similar type of cortical involvement. However, it cannot be excluded that some part of the SICI reduction with muscle contraction depends on changes in segmental excitability.


Assuntos
Córtex Motor/fisiologia , Músculo Esquelético/fisiologia , Inibição Neural/fisiologia , Postura/fisiologia , Adulto , Potencial Evocado Motor/fisiologia , Humanos , Pessoa de Meia-Idade , Contração Muscular/fisiologia , Músculo Esquelético/inervação , Descanso/fisiologia , Estimulação Magnética Transcraniana
18.
J Behav Med ; 29(5): 411-8, 2006 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16865552

RESUMO

The purpose of this study was to assess the prevalence and correlates of comorbid diabetes and Post-Traumatic Stress disorder(PTSD)and potential relationships between PTSD and diabetes outcomes. Male patients enrolled in a VA primary care database (N = 73,270) were classified as having diabetes from pharmacy records (N = 14,438) and grouped into those with diagnoses of PTSD with depression (N = 649), PTSD-only (N = 480), Depression-only (N = 1696), Other psychiatric diagnosis (N = 736), or No psychiatric diagnosis (N = 10,877) based on the Purpose of Visit diagnoses in the medical record. Outcomes included glycemic control (HbA1c), cholesterol and triglycerides. Correlates were age, substance use disorder, other psychiatric diagnosis, number of primary care encounters, and medications. The prevalence of comorbid diabetes and PTSD was 8% (n = 1129). Of these, 57% (n = 649) had comorbid depression. Patients with PTSD and depression had higher rates of substance use disorder and higher cholesterol and LDL. Patients with depression had poorer glycemic control. Patients with PTSD and depression weighed more and had higher BMI than patients with neither diagnosis. Thus, male diabetes patients with PTSD and depression may be vulnerable to substance use disorders and to weight/lipid problems that can affect health. Depression is a likely contributor to poor glycemic control. Careful screening for mental health comorbidities is needed for diabetes patients.


Assuntos
Distúrbios de Guerra/epidemiologia , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Veteranos/psicologia , Idoso , Glicemia/metabolismo , Índice de Massa Corporal , Colesterol/sangue , Distúrbios de Guerra/sangue , Distúrbios de Guerra/psicologia , Comorbidade , Estudos Transversais , Transtorno Depressivo/sangue , Transtorno Depressivo/epidemiologia , Transtorno Depressivo/psicologia , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/psicologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/psicologia , Hemoglobinas Glicadas/metabolismo , Comportamentos Relacionados com a Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Estatística como Assunto , Transtornos Relacionados ao Uso de Substâncias/sangue , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/psicologia , Resultado do Tratamento , Recusa do Paciente ao Tratamento/psicologia , Recusa do Paciente ao Tratamento/estatística & dados numéricos , Triglicerídeos/sangue
20.
Mol Cell ; 12(3): 747-59, 2003 09.
Artigo em Inglês | MEDLINE | ID: mdl-14527419

RESUMO

Functional studies strongly suggest that the Mus81-Eme1 complex resolves Holliday junctions (HJs) in fission yeast, but in vitro it preferentially cleaves flexible three-way branched structures that model replication forks or 3' flaps. Here we report that a nicked HJ is the preferred substrate of endogenous and recombinant Mus81-Eme1. Cleavage occurs specifically on the strand that opposes the nick, resulting in resolution of the structure into linear duplex products. Resolving cuts made by the endogenous Mus81-Eme1 complex on an intact HJ are quasi-simultaneous, indicating that Mus81-Eme1 resolves HJs by a nick and counternick mechanism, with a large rate enhancement of the second cut arising from the flexible nature of the nicked HJ intermediate. Recombinant Mus81-Eme1 is ineffective at making the first cut. We also report that HJs accumulate in a DNA polymerase alpha mutant that lacks Mus81, providing further evidence that the Mus81-Eme1 complex targets HJs in vivo.


Assuntos
Replicação do DNA/genética , Proteínas de Ligação a DNA/metabolismo , DNA/metabolismo , Endonucleases/metabolismo , Proteínas de Schizosaccharomyces pombe/metabolismo , Schizosaccharomyces/enzimologia , Células Cultivadas , DNA/genética , DNA Polimerase I/genética , DNA Polimerase I/metabolismo , Proteínas de Ligação a DNA/genética , Endonucleases/genética , Regulação Enzimológica da Expressão Gênica/genética , Regulação Fúngica da Expressão Gênica/genética , Substâncias Macromoleculares , Mutação/genética , Conformação de Ácido Nucleico , Proteínas/metabolismo , Proteínas de Saccharomyces cerevisiae , Schizosaccharomyces/genética , Proteínas de Schizosaccharomyces pombe/genética , Especificidade por Substrato
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