Let-7b inhibits the malignant behavior of glioma cells and glioma stem-like cells via downregulation of E2F2

Abstract

Glioblastoma multiforme (GBM), the most common and lethal primary brain tumor in adults characterized by high proliferative ability and mortality rate, contains a small subpopulation of cancer stem-like cells (CSCs), which is responsible for GBM progression and therapeutic resistance. Numerous microRNAs are strongly implicated in the malignancy of glioma. However, their specific functions and roles have yet to be fully demonstrated. In the present study, we revealed that the upregulation of Let-7b, a member of the Let-7 microRNA family, inhibited proliferation, migration, and invasion in glioma cell lines. Using bioinformatics, expression analysis, and luciferase assay, E2F2 was confirmed as a candidate target of Let-7b. Moreover, we also observed that elevated levels of Let-7b resulted in a reduction of tumor sphere growth and stemness of glioma stem-like cells. Furthermore, we found that knockdown of E2F2 expression could reduce the proliferation of glioma and GSCs, while overexpression of E2F2 partially abrogated the inhibitory effect of Let-7b on the proliferation of glioma and GSCs. In conclusion, we suggest that Let-7b could be developed into a promising anticancer target in glioma.

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Depression predicts functional outcome in geriatric inpatient rehabilitation

Publication date: Available online 13 August 2016
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Saba Shahab, Diana-Felicia Nicolici, Alva Tang, Paul Katz, Linda Mah
ObjectiveTo evaluate the effect of depression on functional recovery in geriatric patients who have completed an inpatient rehabilitation program.DesignProspective cohort study.SettingUniversity-affiliated multidisciplinary, high-tolerance, short-duration geriatric rehabilitation.ParticipantsConvenience sample of 65 patients [mean age 81.6, 25 males] admitted to rehabilitation over a 10-month period. Patients over the age of 60 who were proficient in English and capable of providing informed consent were eligible to participate in the study.InterventionsDepression was assessed using both the Geriatric Depression Scale-Short Form (GDS-15) and the Patient Health Questionnaire (PHQ-9). Measures of well-established predictors of rehabilitation outcome, which may interact with depression, were also obtained and multiple regression linear modeling was used to evaluate the relationship between depression and functional outcome over and above the contribution of these other factors.Main Outcome MeasureFunctional Independence Measure at discharge from the rehabilitation programResultsDepression, as assessed by the GDS-15, but not the PHQ-9, was predictive of functional outcome (standardized β=-.165, p=.021) after controlling for other significant predictors, which included baseline disability, pain, cognition, and educational level. Participation in recreational, but not physio- or occupational, therapy additionally contributed to a small amount of variance in the functional outcome.ConclusionsOur findings suggest that self-report of depression is an independent predictor of functional outcome in high-tolerance, short duration geriatric rehabilitation. Routine assessment of depressive symptoms in older adults using an instrument, such as the GDS-15 may help identify those at risk for poorer outcomes in rehabilitation.



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Sarcopenia and Physical Function in Middle-Aged and Older Stroke Survivors

Publication date: Available online 13 August 2016
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Alice S. Ryan, Frederick M. Ivey, Monica C. Serra, Joseph Hartstein, Charlene E. Hafer-Macko
ObjectiveTo determine the prevalence of sarcopenia in stroke survivors using different methodologies and compared a subset of the stroke group to age, sex, and BMI-matched non-stroke control counterparts.DesignCohort StudySettingVeterans Affairs Medical Center and University HospitalParticipantsMild to moderately disabled chronic participants with stroke aged 40-84 yrs (n=190, 61% male, 57% African American, BMI: 29±1 kg/m², X±SEM)InterventionsNot applicableMain Outcome MeasuresDXA scans to assess appendicular lean mass (ALM). Rates of sarcopenia were determined using four established methods: 1) ALM/ht²; 2) European Working Group on Sarcopenia in Older Persons; 3) International Working Group on Sarcopenia; and 4) ALM/BMI.ResultsSarcopenia prevalence in our stroke cohort ranged between 14% and 18%. The stroke survivor subset (n=38) matched one-for-one with control counterparts for race, sex, age±4 years and BMI±2.5 units had higher prevalence rates compared to their non-stroke counterparts (13.2% vs. 5.3%, P<0.0001). ALM/ht² was related to six-minute walking speed (r=0.28, P<0.01) and VO2peak (l/min r=0.58, P<0.0001) for the stroke group.ConclusionsStroke survivors show an elevated prevalence of sarcopenia when considering age, sex, and race to non-stroke individuals.



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A Clinical Prediction Rule for Declines in Activities of Daily Living at 6 Months after Surgery for Hip Fracture Repair

Publication date: Available online 13 August 2016
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Ryo Tanaka, Takuya Umehara, Takafumi Fujimura, Junya Ozawa
ObjectiveTo develop and assess a clinical prediction rule (CPR) to predict declines in activities of daily living (ADL) at 6 months after surgery for hip fracture repair.DesignA prospective, cohort study.SettingFrom hospital to home.ParticipantsOne hundred and four patients with hip fractures after surgery.InterventionsNo special intervention was employed in this study.Main Outcome MeasureADL was assessed using the Barthel Index at 6 months after surgery.ResultsAt 6 months after surgery, 86 patients (82.6%) were known to be alive, one patient died, and 17 (16.3%) were lost to follow-up. Thirty-two patients (37.2%) did not recover their ADL at 6 months after surgery to levels before fracture. The Classification and Regression Trees (CART) methodology was used to develop two models to predict a decline in ADL: model-1, which included age, type of fracture, care-level before fracture (sensitivity = 0.750, specificity = 0.815, positive predictive value = 70.6%, and positive likelihood ratio = 4.050), and model-2, which included the independence of post-surgery 2 weeks ADL chair transfer and ambulation and age (sensitivity = 0.656, specificity = 0.870, positive predictive value = 75.0%, and positive likelihood ratio = 5.063). The areas under receiver-operator characteristic curves of both CPR models were 0.825 [95% confidential interval (CI) = 0.728–0.923) and 0.790 (95% CI = 0.683–0.897), respectively.ConclusionCPRs with moderate accuracy were developed to predict declines in ADL at 6 months after surgery for hip fracture repair.



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Ultrasonographic assessment of superficial fibular nerve branches

Peripheral nerve injury is a possible complication of orthopaedic surgery and the correct diagnosis of patient's condition, after the intervention, is crucial for the specific rehabilitation program (Bade et al., 2010). The use of ultrasound (US) to assess nerves is well known and extensively shown in literature by many studies (Padua et al., 2013). High-frequency US is routinely applied for the evaluation of the main and largest nerve structures in limbs, like fibular nerve (Coraci et al., 2015).

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Added diagnostic value of magnetoencephalography (MEG) in patients suspected for epilepsy, where previous, extensive EEG workup was unrevealing

Although epilepsy can be diagnosed solely on clinical data, additional investigations are often needed after the first seizure to assess the probability of recurring seizures (Fisher et al. 2014). EEG is one of the most important investigations, which besides supporting diagnosis of epilepsy, also contributes to its classification (Berg et al. 2010). It is well established that in about 10-20% of patients with epilepsy, multiple EEG studies including sleep deprived EEG, fail to show abnormalities (Alving and Beniczky.

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Repetitive facial nerve stimulation in myasthenia gravis 1 minute after muscle activation is inferior to testing a second muscle at rest

To explore the increased diagnostic yield of repetitive nerve stimulation (RNS) following activation for myasthenia gravis (MG) diagnosis, and compare with testing an additional muscle at rest only.

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