Uncoordinated Loss of Chromatid Cohesion Is a Common Outcome of Extended Metaphase Arrest

Chromosome segregation requires coordinated separation of sister chromatids following biorientation of all chromosomes on the mitotic spindle. Chromatid separation at the metaphase-to-anaphase transition is accomplished by cleavage of the cohesin complex that holds chromatids together. Here we show using live-cell imaging that extending the metaphase bioriented state using five independent perturbations (expression of non-degradable Cyclin B, expression of a Spindly point mutant that prevents spindle checkpoint silencing, depletion of the anaphase inducer Cdc20, treatment with a proteasome inhibitor, or treatment with an inhibitor of the mitotic kinesin CENP-E) leads to eventual scattering of chromosomes on the spindle. This scattering phenotype is characterized by uncoordinated loss of cohesion between some, but not all sister chromatids and subsequent spindle defects that include centriole separation. Cells with scattered chromosomes persist long-term in a mitotic state and eventually die or exit. Partial cohesion loss-associated scattering is observed in both transformed cells and in karyotypically normal human cells, albeit at lower penetrance. Suppressing microtubule dynamics reduces scattering, suggesting that cohesion at centromeres is unable to resist dynamic microtubule-dependent pulling forces on the kinetochores. Consistent with this view, strengthening cohesion by inhibiting the two pathways responsible for its removal significantly inhibits scattering. These results establish that chromosome scattering due to uncoordinated partial loss of chromatid cohesion is a common outcome following extended arrest with bioriented chromosomes in human cells. These findings have important implications for analysis of mitotic phenotypes in human cells and for development of anti-mitotic chemotherapeutic approaches in the treatment of cancer

Predictors of dizziness in older persons: a 10-year prospective cohort study in the community

BACKGROUND: The current diagnosis-oriented approach of dizziness does not suit older patients. Often, it is difficult to identify a single underlying cause, and when a diagnosis is made, therapeutic options may be limited. Identification of predictors of dizziness may provide new leads for the management of dizziness in older patients. The aim of the present study was to investigate long-term predictors of regular dizziness in older persons. METHODS: Population-based cohort study of 1,379 community-dwelling participants, aged ≥60 years, from the Longitudinal Aging Study Amsterdam (LASA). Regular dizziness was ascertained during face-to-face medical interviews during 7- and 10-year follow-up. We investigated 26 predictors at baseline from six domains: socio-demographic, medical history, medication, psychological, sensory, and balance/gait. We performed multivariate logistic regression analyses with presence of regular dizziness at 7- and 10-year follow-up as dependent variables. We assessed the performance of the models by calculating calibration and discrimination. RESULTS: Predictors of regular dizziness at 7-year follow-up were living alone, history of dizziness, history of osteo/rheumatoid arthritis, use of nitrates, presence of anxiety or depression, impaired vision, and impaired function of lower extremities. Predictors of regular dizziness at 10-year follow-up were history of dizziness and impaired function of lower extremities. Both models showed good calibration (Hosmer-Lemeshow P value of 0.36 and 0.31, respectively) and acceptable discrimination (adjusted AUC after bootstrapping of 0.77 and 0.71). CONCLUSIONS: Dizziness in older age was predicted by multiple factors. A multifactorial approach, targeting potentially modifiable predictors (e.g., physical exercise for impaired function of lower extremities), may add to the current diagnosis-oriented approach. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2318-14-133) contains supplementary material, which is available to authorized users

Newly diagnosed incident dizziness of older patients: a follow-up study in primary care

<p>Abstract</p> <p>Background</p> <p>Dizziness is a common complaint of older patients in primary care, yet not much is known about the course of incident dizziness. The aim of the study was to follow-up symptoms, subjective impairments and needs of older patients (≥65) with incident dizziness and to determine predictors of chronic dizziness. Furthermore, we analysed general practitioners' (GPs') initial diagnoses, referrals and revised diagnoses after six months.</p> <p>Methods</p> <p>An observational study was performed in 21 primary care practices in Germany, including a four-week and six-month follow-up. A questionnaire comprising characteristic matters of dizziness and a series of validated instruments was completed by 66 participants during enrolment and follow-up (after 1 month and 6 months). After six months, chart reviews and face-to-face interviews were also performed with the GPs.</p> <p>Results</p> <p>Mean scores of dizziness handicap, depression and quality of life were not or only slightly affected, and did not deteriorate during follow-up; however, 24 patients (34.8%) showed a moderate or severe dizziness handicap, and 43 (62.3%) showed a certain disability in terms of quality of life at the time of enrolment. In multivariate analysis, n = 44 patients suffering from chronic dizziness (dependent variable, i.e. relapsing or persistent at six months) initially had a greater dizziness handicap (OR 1.42, 95%CI 1.05-1.47) than patients with transient dizziness. GPs referred 47.8% of the patients to specialists who detected two additional cases of benign paroxysmal positional vertigo (BPPV).</p> <p>Conclusions</p> <p>New-onset dizziness relapsed or persisted in a considerable number of patients within six months. This was difficult to predict due to the patients' heterogeneous complaints and characteristics. Symptom persistence does not seem to be associated with deterioration of the psychological status in older primary care patients. Management strategies should routinely consider BPPV as differential diagnosis.</p

Quedas intra-hospitalares na Santa Casa de Belo Horizonte MG são adequadamente relatadas?

O envelhecimento populacional é uma realidade que chega imbuída de complicações as quais muitas vezes tornam-se problema de saúde pública, como é o caso das quedas hospitalares. Estas acarretam uma série de conseqüências negativas ao paciente e sua família, bem como ao sistema de saúde. O objetivo deste estudo foi avaliar e quantificar, por meio de entrevistas com os profissionais responsáveis pelos cuidados dos pacientes da Santa Casa de Belo Horizonte, a ocorrência de quedas durante a hospitalização. Foram entrevistados 37 profissionais (médicos, residentes, enfermeiros e prestadores de serviços) através de questionário semi-estruturado com 11 questões referentes ao histórico de quedas no setor, englobando informações sobre número de episódios, local, horário, idade do paciente, atividade que realizava no momento, conseqüências, bem como questões referentes à adaptação ambiental. A análise dos dados feita por meio de estatísticas descritivas. Os resultados mostraram que 65% dos funcionários relataram a ocorrência de quedas. A maioria dos caidores (73%) eram homens, com média de idade de 78,62 anos (DP +- 7,63) e caíram mais nos períodos da manhã (31%) e noite (31%), principalmente no quarto (48%) e no banheiro (42%) sendo que 50% dos episódios não foram injuriosos. Conclui-se que os episódios de quedas ocorrem no ambiente hospitalar, mas não são reportados de maneira adequada, tornando necessário adoção de medidas educativas aos profissionais que lidam com esta população.The Population ageing is a reality that comes gripped by complications related to aging, being in-hospital falls one of the most important, considering that they bring on a lot of negative consequences to the patient and his family as well as to the health system. The objective of this study was to assess and quantify, through the analyses of interviews with professionals responsible for the care of the patients at Santa Casa of Belo Horizonte, the occurrence of in-hospital falls. The interview was accomplished with 37 professionals(doctors, interns and nurses) through a semi-structured questionnaire which comprehended 11 questions related to the historical of falls in the sector, comprising information on the number of episodes, setting, time, patient age, activity performed at the moment, consequences, as well as questions regarding to environment adaptation. Data analysis conducted by means of descriptive statistics of the interviews showed that 65% of the employee reported the occurrence of falls. The majority (73%) of fallers was men, with mean age of 78, 62 years (SD +- 7, 63) and fell more in the morning (31%) and in the evening (31%), mainly in the room (48%) and in the bathroom (42%), being 50% of the episodes non-injurious. We conclude that falls episodes occur in the hospital setting, but are not reported adequately, showing the need of adoption of educational measures to the professional who deal with this population