Cerebral microbleeds (CMBs), which indicate hemorrhage-prone disease, may associate with hemostatic abnormalities, but the association between CMBs and coagulation function is uncertain. We aimed to examine this possible association. The following coagulation function indicators were evaluated in 85 consecutive ischemic stroke patients diagnosed with atrial fibrillation and/or rheumatic heart disease: prothrombintime (PT), activated partial thromboplastin time (APTT), and levels of D-dimer and fibrinogen. Indicators were assessed within 24 h after admission. CMBs were identified based on published criteria by two experienced stroke neurologists working independently. PT, APPT, and levels of D-dimer and fibrinogen were compared between patients with and without CMBs using univariate and multivariate analysis. CMBs were detected in 48 patients (56.5%), and fibrinogen levels in these patients were independently and significantly higher than in patients without CMBs after adjustment (OR 2.16, 95% CI 1.20-3.90, P=0.01), whereas the two types of patients did not differ significantly in PT, APPT, or D-dimer levels. The presence of CMBs in ischemic stroke patients with atrial fibrillation and/or rheumatic heart disease is associated with elevated levels of fibrinogen. Larger prospective studies are needed to verify this association and explore the mechanisms involved.
Dural venous sinus thrombosis (DVST) is a rare cause of stroke, which typically affects young women. The importance of identifying pre-disposing factors that lead to venous stasis lies in the foundation of understanding the etiology, pathophysiology and clinical presentation. The precise therapeutic role of interventional therapies is not fully understood though the current data do suggest potential applications. The aim of the study was to perform a systematic review and meta-analysis to evaluate the utility of and short-term 30-day survival after endovascular therapy for patients with DVST. Standard PRISMA guidelines were followed. Data sources included PubMed keywords and phrases, which were also incorporated into a MeSH search to yield articles indexed in Medline over a 5-year period. All RCTs, observational cohort studies, and administrative registries comparing or reporting DVST were included. Sixty-six studies met inclusion criteria. 35 articles investigating treatment in a summation of 10,285 patients were eligible for data extraction and included in the review of treatment modalities. A total of 312 patients were included for statistical analysis. All patients included received endovascular intervention with direct thrombolysis, mechanical thrombectomy or both. 133 (42.6%) patients were documented to have a neurologic decline, which prompted endovascular intervention. All patients who had endovascular interventions were those who were started on and failed systemic anticoagulation. 44 patients were reported to have intracranial hemorrhages after intervention. Regardless of systemic anticoagulation, patients were still reported to have complications of VTE and PE. Primary outcome at 3-6 month follow up revealed mRS<1 in 224 patients. DVST presents with many diagnostic and therapeutic challenges. The utility of invasive interventions such as local thrombolysis and mechanical thrombectomy is not fully understood. It is exceedingly difficult to conduct large randomized trials for this low incidence disease process with large pathophysiological heterogeneity.
Cellular senescence can be described as a complex stress response that leads to irreversible cell cycle arrest. This process was originally described as an event that primary cells go through after many passages of cells during cell culture. More recently, cellular senescence is viewed as a programmed process by which the cell displays a senescence phenotype when exposed to a variety of stresses. Cellular senescence has been implicated in tumor suppression and aging such that senescence may contribute to both tumor progression and normal tissue repair. Here, we review different forms of cellular senescence, as well as current biomarkers used to identify senescent cells in vitro and in vivo. Additionally, we highlight the role of senescence-associated long noncoding RNAs (lncRNAs).
Allergy reactions are the most common immunological diseases and represent one of the most widespread and fast growing chronic human health problems among people over 15 years of age in developed countries. As populations get older worldwide, allergy manifestations in aged persons will occur more often in the future. To date, there has been much more studies on allergies in children than in adults. As the population ages, clinicians must be prepared to meet all the elderly's health care needs, including these new and emerging health issue. Allergic diseases represent an old/new emerging health issue. Because many common illnesses masquerade as atopic disease, the differential diagnosis of suspected allergic diseases becomes more expanded in an aging population. Research in the field needs to focus on both human and animal model systems to investigate the impact of the aging process on the immunologic pathways underpinning allergy and its different facets.
This study analyzes the technologies used in dealing with frailty within the following areas: prevention, care, diagnosis and treatment. The aim of this paper is, on the one hand, to analyze the extent to which technology is present in terms of its relationship with frailty and what technological resources are used to treat it. Its other purpose is to define new challenges and contributions made by physiotherapy using technology. Eighty documents related to research, validation and/or the ascertaining of different types of hardware, software or both were reviewed in prominent areas. The authors used the following scales: in the area of diagnosis, Fried’s phenotype model of frailty and a model based on trials for the design of devices. The technologies developed that are based on these models accounted for 55% and 45% of cases respectively. In the area of prevention, the results proved similar regarding the use of wireless sensors with cameras (35.71%), and Kinect™ sensors (28.57%) to analyze movements and postures that indicate a risk of falling. In the area of care, results were found referring to the use of different motion, physiological and environmental wireless sensors (46,15%), i.e. so-called smart homes. In the area of treatment, the results show with a percentage of 37.5% that the Nintendo® Wii™ console is the most used tool for treating frailty in elderly persons. Further work needs to be carried out to reduce the gap existing between technology, frail elderly persons, healthcare professionals and carers to bring together the different views about technology. This need raises the challenge of developing and implementing technology in physiotherapy via serious games that may via play and connectivity help to improve the functional capacity, general health and quality of life of frail individuals.
Ischemic stroke is a major cause of morbidity and mortality, incurring significant cost. Intracranial atherosclerotic disease (ICAD) accounts for 10-15% of ischemic stroke in Western societies, but is an underlying pathology in up to 54% of ischemic strokes in Asian populations. ICAD has largely been treated with medical management, although a few studies have examined outcomes following endovascular treatment. Our objective was to summarize the major trials that have been performed thus far in regard to the endovascular treatment of ICAD and to provide direction for future management of this disease process. Systematic review of the literature from 1966 to 2015, was conducted in regard to intracranial angioplasty and stenting. Studies were analyzed from PubMed, American Heart Association and Society of Neurointerventional Surgery databases. SAMMPRIS and VISSIT are the only randomized controlled trials from which Western guidelines of intracranial stenting have been derived, which have displayed the superiority of medical management. However, pooled reviews of smaller studies and other nonrandomized trials have shown better outcomes with endovascular therapy in select patient subsets, such as intracranial vertebrobasilar stenosis or in the presence of robust collaterals. Suboptimal cases, including longer lesions, bifurcations and significant tortuosity tend to fair better with medical management. Medical management has been shown to be more efficacious with less adverse outcomes than endovascular therapy. However, the majority of studies on endovascular management included a diverse patient population without ideal selection criteria, resulting in higher adverse outcomes. Population analyses and selective utilization of endovascular therapy have shown that the treatment may be superior to other management in select patients.
Stroke survivors are typically left with structural brain damage and associated functional impairment in the chronic phase of injury, for which few therapeutic options exist. We reported previously that transplantation of human embryonic stem cell (hESC)-derived neural stem cells together with Matrigel scaffolding into the brains of rats after focal ischemia reduced infarct volume and improved neurobehavioral performance. Matrigel is a gelatinous protein mixture extracted from mouse sarcoma cells, thus would not be approved for use as a scaffold clinically. In this study, we generated a gel-like scaffold from plasma that was controlled by changing the concentration of CaCl2. In vitro study confirmed that 10-20 mM CaCl2 and 10-40% plasma did not affect the viability and proliferation of human and rat bone marrow mesenchymal stem/stromal cells (BMSCs) and neural stem cells (NSCs). We transplanted plasma scaffold in combination of BMSCs into the cystic cavity after focal cerebral ischemia, and found that the atrophy volume was dramatically reduced and motor function was significantly improved in the group transplanted with scaffold/BMSCs compared with the groups treated with vehicle, scaffold or BMSCs only. Our data suggest that plasma-derived scaffold in combination of BMSCs is feasible for tissue engineering approach for the stroke treatment.
This pilot study examined the status of the master iron regulatory peptide, hepcidin, and peripheral related iron parameters in Alzheimer’s disease (AD) and mild cognitive impairment patients, and evaluated the relationship between iron dyshomeostasis and amyloid-beta (Aβ), cognitive assessment tests, neuroimaging and clinical data. Frozen serum samples from the Oregon Tissue Bank were used to measure serum levels of hepcidin, ferritin, Aβ40, Aβ42 using enzyme-linked immunosorbent assay. Serum transferrin levels were determined indirectly as total iron binding capacity, serum iron was measured and the percent saturation of transferrin calculated. The study variables were correlated with the patients’ existing cognitive assessment tests, neuroimaging, and clinical data. Hepcidin, and iron-related proteins tended to be higher in AD patients than controls, reaching statistical significance for ferritin, whereas Aβ40, Aβ42 serum levels tended to be lower. Patients with pure AD had three times higher serum hepcidin levels than controls; gender differences in hepcidin and iron-related proteins were observed. Patient stratification based on clinical dementia rating-sum of boxes revealed significantly higher levels of iron and iron-related proteins in AD patients in the upper 50% as compared to controls, suggesting that iron dyshomeostasis worsens as cognitive impairment increases. Unlike Aβ peptides, iron and iron-related proteins showed significant association with cognitive assessment tests, neuroimaging, and clinical data. Hepcidin and iron-related proteins comprise a group of serum biomarkers that relate to AD diagnosis and AD disease progression. Future studies should determine whether strategies targeted to diminishing hepcidin synthesis/secretion and improving iron homeostasis could have a beneficial impact on AD progression.
The mitochondrial toxicity of nucleoside reverse transcriptase inhibitors (NRTIs) is due to the inhibition of mitochondrial DNA (mtDNA) polymerase γ (pol γ). Previous studies have shown that wild type p53 (wtp53) can interact with pol γ and mtDNA to enhance mitochondrial DNA base excision repair (mtBER) activity and increase the accuracy of DNA synthesis. The N-terminal transactivation domain and central specific DNA-binding domain of p53 play critical roles in the stimulation of BER. In this study, we identified the possible roles of wtp53, Δ40p53 and Δ133p53 in regulating mtDNA pol γ activity in cells with d4T treatment. The results show that Δ40p53 and Δ133p53 can exist in mitochondrial fragments and form polymers with themselves or wtp53. Unlike wtP53, Δ133p53 alone cannot increase DNA pol γ activity. More importantly, we found that Δ133p53 played a negative role in p53 stimulation of DNA pol γ activity when studied in d4T-treated and d4T-untreated mitochondrial extracts. Gel shift data also indicate that Δ40p53 and Δ133p53 cannot interact with APE. Wtp53 and Δ40p53 can act antagonize the effect of d4T inhibition of DNA pol γ activity. However, when wtp53 interacted with Δ133p53, DNA pol γ activity was significantly decreased. Conclusion: Δ133p53 negatively regulates p53’s stimulation of pol γ in the presence and absence of d4T.
Obesity has been associated with higher risk of frailty in older adults, but the pathophysiological mechanisms are unclear. No previous study has examined the association between leptin, an adipokine, and the risk of frailty in older adults, and whether this association could be explained by insulin resistance or chronic inflammation. Data were taken from 1,573 individuals without diabetes mellitus, aged ≥60 years, from the Seniors-ENRICA cohort. In 2008-2010, leptin, the homeostasis model assessment of insulin resistance (HOMA-IR) and C-reactive protein (CRP) were measured. Study participants were followed-up through 2012 to assess incident frailty, defined as at least two of the following Fried criteria: exhaustion, weakness, low physical activity, and slow walking speed. Analyses were performed with logistic regression and adjusted for the main confounders. Over a median follow-up of 3.5 years, 280 cases of incident frailty were identified. Compared to individuals in the lowest tertile of serum leptin, those in the highest tertile showed an increased risk of frailty (odds ratio [OR]: 2.12; 95% confidence interval [CI]: 1.47-3.06; p-trend <0.001). Further adjustment for the percentage of body fat led to an OR of 1.69 (95% CI: 1.11-2.61; p-trend=0.01). After additional adjustment for HOMA-IR and CRP, the OR for frailty was 1.59 (95% CI: 1.01-2.52; p-trend=0.04). Results did not vary according to sex, abdominal obesity or the percentage of body fat. Being in the highest versus lowest tertile of leptin was associated with increased risk of exhaustion (OR: 2.16; 95% CI: 1.32-3.55; p-trend=0.001) and muscle weakness (OR: 1.77; 95% CI: 1.25-2.51; p-trend=0.001), in the analyses adjusted for potential confounders and body fat. Higher leptin concentration was associated with greater risk of frailty in older adults. This association was only modestly explained by insulin resistance and chronic inflammation, as measured by CRP.