Aneurysmal subarachnoid haemorrhage: effect of CRHR1 genotype on fatigue and depression.

BACKGROUND: Emotional health disturbances are common after aneurysmal subarachnoid hemorrhage (aSAH) and their causes are largely unexplored. Corticotropin-releasing hormone receptor 1 (CRHR1) is a key factor in stress reactivity and development of mental health disturbances after adverse life-events. METHODS: We explore the effect of CRHR1 genotype on mental health after aSAH in a retrospective cohort study. One hundred twenty-five patients have been assessed using EST-Q mental health questionnaire. Genotyping of CRHR1 single nucleotide polymorphisms (SNP-s) was performed (Rs7209436, Rs110402, Rs242924). RESULTS: Fatigue was present in almost half of aSAH patients, depression and anxiety in one-third. There was a high prevalence of insomnia and panic complaints. Rs110402 minor allele decreased the risk of depression (OR = 0.25, p = 0.027 for homozygotes). Depression was present in 14% vs 41% in minor and major allele homozygotes, respectively. Rs110402, Rs242924 and Rs7209436 minor alleles and TAT-haplotype, formed by them, were protective against fatigue. After Bonferroni correction only the association of Rs110402 with fatigue remained statistically significant (OR = 0.21, p = 0.006 for minor allele homozygotes). Results remained statistically significant when adjusted for gender, admission state, age and time from aSAH. In multiple regression analysis occurrence of fatigue was dependent on anxiety, modified Rankin score and Rs110402 genotype (R2 = 0.34, p <  0.001). CONCLUSIONS: CRHR1 minor genotype was associated with a lower risk of fatigue and depression after aSAH. Genetic predisposition to mental health disturbances associated with negative life-events could be a risk factor for fatigue and depression after aSAH and selected patients might benefit from advanced counselling in the recovery phase.

Single session exercises and concurrent functional electrical stimulation are more effective on muscles' force generation than only exercises in spinal cord injured persons: a feasibility study.

OBJECTIVES: To evaluate impact of first therapy session, containing functional electrical stimulation (FES) and therapeutic exercises (TE) on erector spinae (ES) and rectus abdominis (RA) force generation in persons with spinal cord injury (SCI). METHODS: Five men with SCI were divided in two groups - FES+TE received concurrent FES on ES and RA and TE, TE only TE. Participants performed exercises for improving sitting balance and posture. Muscles' electrical activity was evaluated by electromyography; amplitude (AEMG) and median frequency (MF) were used for analysis. RESULTS: AEMG of ES left (L) increased 292.9% (g=-0.92), right (R) 175% (g=-1.01), RA L 314.3% (g=-0,81, P<0.05), R 266.7% (g=-0.08) in FES+TE. AEMG of ES L increased 47.6% (g=-0.46), R 96.4% (g=-0.95); RA L 7.1% (g=-0.97), but R decreased 6.7% (g=0.12) in TE. MF of ES L increased 108.5% (g=-0.74), R 184% (g=-1.25); RA L 886.7% (g=3-05, P<0.05), R 817.6% (g=-2.55, P<0.05) in FES+TE. MF of ES L increased 95.2% (g=-1.02), R 161.4% (g=-1.64); RA L 3,2% (g=-0.06), R 30.8% (g=-0.46) in TE. CONCLUSIONS: In SCI persons, single session exercises and concurrent functional electrical stimulation may be more effective on muscles` force generation than only exercises. However, replication of the results is needed before clinical implementation.

Incidence and Mortality of Parkinson's Disease in Estonia.

BACKGROUND: There is lack of data on the incidence of Parkinson's disease (PD) based on repeat studies. Mortality rates of PD in Estonia have never been studied before. OBJECTIVES: To estimate the incidence and mortality rates of PD in -Estonia, to compare current incidence rates with those of the prior epidemiological study in Estonia, and to examine the reported causes of death of the study population. METHODS: Eligible subjects were identified from multiple case-finding sources. Subjects were subsequently tracked on the Electronic-Health Record until either the end of the study, or their death. Incidence rates and standardized mortality ratios (SMR) were calculated. Causes of death were identified, based on the data from death certificates. RESULTS: In the current study, the overall age-adjusted incidence rate was 28.0/100,000 person-years (95% CI 25.2-30.8). Compared with the previous study, the age-adjusted incidence rate inEstonia has not significantly changed (rate ratio 1.11; p = 0.19). Overall SMR for the inception cohort of PD cases with a median follow-up time of 5 years was 1.12 (95% CI 0.88-1.36; p = 0.3). For those deceased subjects known to have had clinically diagnosed PD, this was mentioned on 46.8% of death certificates. CONCLUSIONS: Over the last 20 years, the overall incidence of PD in Estonia has remained comparatively stable. The data did not show an excess mortality in PD patients (vs. general population) in the first 5 years of the disease.

The Effect of Functional Electrical Stimulation and Therapeutic Exercises on Trunk Muscle Tone and Dynamic Sitting Balance in Persons with Chronic Spinal Cord Injury: A Crossover Trial.

Background and objectives: Functional electrical stimulation (FES) has shown good results in improving static and dynamic sitting balance in persons with spinal cord injuries. There is limited information about how regular surface FES combined with therapeutic exercise (TE) affect dynamic sitting balance and muscle tone. The objective of this study was to evaluate the effectiveness of a six-week physical therapy program consisting of FES and TE on muscle tone and sitting balance in persons with spinal cord injury (SCI). It was also important to explore the relationship between muscle tone and dynamic sitting balance. The third objective was to assess the change of characteristics over a six month period, when no intervention was carried out. Material and methods: Five men with SCI were alternately allocated to two study groups: SCI_FES+TE and SCI_TE. Eight healthy control group participants were recruited to collect reference data. SCI participants' intervention lasted for six weeks in their homes. SCI_FES+TE conducted exercises with FES applied on erector spinae (ES) and rectus abdominis (RA) muscles. SCI_TE conducted exercises only. Muscle oscillation frequency (MOF; characterizing muscle tone) and limits of stability (LOS; characterizing sitting balance) were measured. A crossover study design was used. The time between the initial intervention and the crossover was seven months (ClinicalTrials registration ID NCT03517787). Results: MOF in SCI_FES+TE increased by 6.0% for ES and 6.1% for RA muscles. LOS of flexion increased 30.1% in SCI_FES+TE. Increase in lateral directions was similar for both study groups. Moderate to high negative correlation was found between MOF and LOS. After seven months, MOF of ES decreased 0.8%, MOF or RA decreased 1.4%, LOS of flexion decreased 31.9%, and LOS of lateral flexion to the left decreased 46.4%. Conclusions: The six-week therapy program combining FES and TE increased trunk muscle tone and dynamic sitting balance in flexion more than TE alone. Higher antagonist muscle tone negatively affects dynamic sitting balance and center of pressure (COP) trajectory distance in various directions. After seven months, a slight decline in trunk muscles tone values and an extensive decrease in sitting balance values were noticed.

Headaches after traumatic spinal cord injury in Estonia.

BACKGROUND: Patients with traumatic spinal cord injury (TSCI) often suffer from different types of pain. However, headaches after TSCI have not been studied. AIM: The aim of this article is to examine the occurrence of headache among patients with TSCI. METHODS: This cross-sectional study included individuals with TSCI from 1997 to 2012 in Estonia. Patients with TSCI were interviewed via telephone. The interview was based on a questionnaire specifically designed to identify headache type using the International Classification of Headache Disorders, third edition (beta version). RESULTS: There were 73 patients with a mean age 37.1 ± 10.6 years. The mean time since TSCI was 7.5 ± 4.0 years. The most frequently mentioned pain was headache (71%), followed by back pain (60%) and pain in neck (44%).Headaches were more frequent after the trauma compared with the headaches before TSCI (71% vs 51%, ITALIC! p = 0.02). Headaches that arose after TSCI were not related to the concomitant brain injury ( ITALIC! p = 0.15). The occurrence of headache did not depend on the severity or the level of the TSCI.Eighty-five percent of patients had not contacted any physician and headache was not diagnosed. CONCLUSIONS: This is the first study that evidentially shows that headache is the most prevalent pain condition after TSCI. Despite this, the majority of patients never consult a physician, nor is their headache diagnosed or appropriately managed. This indicates that further studies are needed to provide evidence regarding the prevalence and causes of headache and its impact on quality of life.

Substantia Nigra Hyperechogenicity: Validation of Transcranial Sonography for Parkinson Disease Diagnosis in a Large Estonian Cohort.

OBJECTIVES: Substantia nigra hyperechogenicity is a promising biomarker for Parkinson disease (PD). Substantia nigra hyperechogenicity has previously been established as a useful diagnostic criterion in several European and Asian patient cohorts. However, diagnostic cutoff values for substantia nigra hyperechogenicity remain unknown for most patient populations. This study validated the diagnostic accuracy of substantia nigra hyperechogenicity in a large cohort of patients with PD in Estonia. METHODS: The study included 300 patients with PD from Estonia, representing 10% of the national PD patient population, and 200 healthy control participants. To define the optimal cutoff value in the PD cohort, data from a single assessment versus repetitive assessments by transcranial sonography were compared. With the use of 3 repetitive assessments, the diagnostic accuracy of the data was measured. In addition, calculations for percentile values were used to define substantia nigra hyperechogenicity among controls. RESULTS: Our data showed that the multiassessment approach yielded higher diagnostic accuracy than a single assessment (P = .021). The highest diagnostic accuracy was achieved by using the measurement mean to define substantia nigra hyperechogenicity, which was 0.23 cm(2) (sensitivity, 88.7%; specificity, 92.2%), whereas single measurements detected PD with higher sensitivity (sensitivity, 93.2%; specificity, 85.1%). No significant difference was found between mean and median measurements (P= .18). CONCLUSIONS: This study indicates the diagnostic merit of transcranial sonography in PD diagnosis in an additional population and demonstrates that transcranial sonography of the substantia nigra is a relevant and useful diagnostic tool for patients with PD.

Relationship between neovascularization and degenerative changes in herniated lumbar intervertebral discs.

PURPOSE: Lumbar disc degeneration may be associated with intensity of neovascularization in disc herniations. Our study was designed to evaluate how much the severity of histodegeneration is related to the development of neovascularization and to the level of pleiotrophin in the herniated lumbar discs. METHODS: Surgically excised lumbar disc specimens were obtained from 29 patients with noncontained (i.e., extruding through the posterior longitudinal ligament) and 21 patients with contained disc herniations. The histodegeneration scores and levels of neovascularization were estimated according to semiquantitative analysis in lumbar disc and endplate samples. Immunohistochemical staining were performed to identify the newly formed blood vessels and to detect the presence of pleiotrophin in the specimens. RESULTS: Higher levels of disc and endplate neovascularity were registered in noncontained herniations. The level of neovascularization was significantly related to the score of histodegeneration in the herniated disc tissues but not in the endplate specimens. Both contained and noncontained herniations had the highest values of histodegeneration in conjunction with the highest level of neovascularization but the relations between neovascularity and degenerative changes remained to be significant only in the group of noncontained herniations. Registration or frequency of pleiotrophin positive cells did not correlate significantly with histodegeneration or level of neovascularization in the disc samples. CONCLUSION: Severe histodegeneration of the lumbar disc herniations is associated with enhanced neovascularization and potentially also spontaneous regression of the herniated tissue.

Emotional health and quality of life after aneurysmal subarachnoid hemorrhage.

BACKGROUND: Emotional disorders and decrease in health-related quality of life (HRQoL) are well-documented sequelae of aneurysmal subarachnoid hemorrhage (SAH). The aim of this study was to analyze the impact of emotional disorders on HRQoL in survivors of SAH. METHODS: This was a retrospective study enrolling 114 SAH-survivors at 1-10 years (mean 4,5 years) after the disease. Emotional State Questionnaire (EST-Q) was used to measure emotional health and the Short Form Health Survey (SF-36) was used to assess HRQoL of the patients. RESULTS: Most of the patients reported good recovery, but EST-Q results revealed high prevalence of emotional disorders after SAH. Almost half of the patients had higher than cut-off values indicating fatigue (47 %) and insomnia (46 %). About one third of SAH-patients had higher than cut-off scores demonstrating depression (30 %) and anxiety (31 %). The patients scored significantly lower in all scales of SF-36 as compared to age-matched general population. All EST-Q subscale results were significantly and negatively correlated with SF-36 scores. Fatigue was independently related to all SF-36 subscales and depression to most of the mental health component scores. Emotional symptoms alone were demonstrated to explain 23-47 % of the SF-36 subscale values, and more than half of the variance of mental health component score values were found to be explained by emotional disorders (53 %). CONCLUSIONS: Emotional disorders are frequent after SAH and significantly associated with impairment of HRQOL. Proper and timely screening tests are important to reveal development of emotional problems and improve QoL for the SAH-patients.

Mortality and causes of death after traumatic spinal cord injury in Estonia.

STUDY DESIGN: Retrospective population-based study with mortality follow-up. OBJECTIVE: To study mortality, causes and risk factors for death in Estonian patients with traumatic spinal cord injury (TSCI). SETTING: All Estonian hospitals. METHODS: Medical records of patients with TSCI from all regional, central, general, and rehabilitation hospitals in Estonia from 1997 to 2007, were retrospectively reviewed. Mortality status was ascertained as of 31 December 2011. Causes of death were collected from the Estonian Causes of Death Registry. Standardized mortality ratios (SMRs) were calculated for the entire sample and for causes of death. A Cox proportional hazards modeling was used to identify the risk indicators for death. RESULTS: During the observation period (1997-2011) 162 patients of 595 died. Nearly half of the patients (n = 76) died during the first year after TSCI. The main causes of death were external causes (30%), cardiovascular disease (29%). and suicide (8%). The overall SMR was 2.81 (95% confidence interval 2.40-3.28) and SMR was higher for women than for men (3.80 vs. 2.70). Cause-specific SMRs were markedly elevated for sepsis and suicide. Mortality was significantly affected by the age at the time of injury, neurological level, and extent of the injury as well as the year of TSCI and complications. CONCLUSION: Life expectancy is significantly decreased in patients with TSCI in Estonia compared with the general population. Deaths during the first year after the injury have an important impact on statistics. Treatment of cardiovascular diseases, infections, and prevention of suicide are useful for reducing mortality in patients with TSCI.

Impact of CD133 positive stem cell proportion on survival in patients with glioblastoma multiforme.

BACKGROUND: The aim of the study was to assess the impact of CD133-positive (CD133+) cancer stem cell proportions on treatment results of glioblastoma multiforme (GBM) patients. PATIENTS AND METHODS: Patients with GBM (n = 42) received postoperative radiotherapy (± chemotherapy). Surgically excised GBM tissue sections were immunohistochemically examined for CD133 expression. The proportions of CD133+ GBM cells were determined (%). The proportion of CD133+ GBM stem cells was established by 2 independent researchers whose results were in good accordance (R = 0.8, p < 0.01). Additionally, CD133 expression levels were correlated with patients overall survival. RESULTS: The proportion of CD133+ cells varied between patients, being from 0.5% to 82%. Mean and median proportions of CD133+ cells of the entire study group were 33% ± 24% (mean ± SD) and 28%, respectively. Clinical data do not support the association between higher proportion of stem cells and the aggressiveness of GBM. Median survival time of the study group was 10.0 months (95% CI 9.0-11.0). The survival time clearly depended on the proportion of CD133+ cells (log rank test, p = 0.02). Median survival times for patients with low (< median) and high (≥ median) proportion of CD133+ cells were 9.0 months (95% CI 7.6-10.5) and 12.0 months (95% CI 9.3-14.7), respectively. In multivariate analysis, the proportion of CD133+ cells emerged as a significant independent predictor for longer overall survival (HR 2.0, 95% CI 1.0-3.8, p = 0.04). CONCLUSIONS: In patients with higher stem cell proportion, significantly longer survival times after postoperative radiotherapy were achieved. Underlying reasons and possible higher sensitivity of GBM stem cells to fractionated radio-therapy should be clarified in further studies.

Trends in traumatic spinal cord injuries in Estonia from 1997 to 2018.

OBJECTIVE: To analyze time trends in incidence, causes and risk factors for traumatic spinal cord injuries (TSCI) in Estonia between 1997-2007 and 2008-2018. DESIGN: Retrospective, population-based cohort study. SETTING: Specialized trauma centres in Estonia. PARTICIPANTS: Medical records of patients with TSCI from 1997 to 2018. INTERVENTION: None. OUTCOME MEASURES: Demographical data, crude and age- and sex-adjusted incidence rates, causes of TSCI, level and extent of injury, associated injuries. RESULTS: A total of 940 new patients with TSCI were identified for the period of 1997-2018. The average annual incidence rate (standardized to the Estonian population by age and sex in 2011) decreased significantly from 37.8 (95% confidence interval (CI) 34.6-41.1) in the first period (1997-2008) to 28.2 per million population (95% CI 25.3-31.0) during the second period (2008-2018) (incidence rate ratio 0.74 (95% CI 0.65-0.85), P < 0.0001). The decrease in incidence was most significant among young men. The mean age at injury increased from 38.7 (±16.7) years to 46.6 (±19.9) years, P < 0.0001. Falls were the leading cause of injury during both periods followed by traffic accidents and sports injuries. Still, traffic accidents as a cause of TSCI decreased significantly (from 30.5% to 20.6%, P = 0.001) and falls increased (from 39.9% to 59.5%, P < 0.0001) during the second period. Alcohol consumption prior to injury also decreased significantly from 66.0% to 55.1% (P = 0.006). CONCLUSION: Estonia has become closer to other European countries regarding TSCI during the last decade; TSCI incidence has significantly decreased, the mean age at injury and the percentage of falls have increased.

Subthalamic stimulation improves the cerebral hemodynamic response to the cold pressure test in patients with Parkinson's disease.

PURPOSE: Disturbances of the autonomic nervous system are common in patients with Parkinson's disease (PD) but the effect of deep brain stimulation of the subthalamic nucleus on cerebrovascular reactivity is not entirely known. METHODS: Seven patients in an advanced stage of the disease and seven healthy age-matched controls participated in the study, which took place after one night of drug withdrawal. Cerebral blood flow velocity was continuously monitored on both sides with transcranial Doppler ultrasound, and cerebrovascular reactivity (CR) was evaluated with the cold pressure test. The measurements were repeated and compared during the stimulation-on and -off phases. RESULTS: The PD patients had significantly higher CR values in the stimulation-on than -off conditions (15.1% ± 6.9 versus 9.4% ± 6.2; p = 0.03). CR values were higher in controls than in patients in the stimulation-off condition (20.4% ± 12.5 versus 9.4% ± 6.2; p = 0.007) without a significant difference with the stimulation-on phase. CONCLUSIONS: CR, evaluated by the response to the cold pressure test, is impaired in patients with advanced PD and improved by subthalamic nucleus.

Aneurysmal subarachnoid haemorrhage: Effect of CRHR1 genotype on mental health-related quality of life.

Quality of life (QoL) disturbances are common after aneurysmal subarachnoid hemorrhage (aSAH) both in physical and mental health domains and their causes are not clearly understood. Corticotropin-releasing hormone receptor 1 (CRHR1) is involved in stress reactivity and development of mental health disturbances after negative life-events. We performed a retrospective cohort study of long-term QoL outcomes among 125 surgically treated aSAH patients (2001-2013). QoL was assessed with Short Form Health Survey (SF-36) and compared to an age and gender matched general population. Genotyping of CRHR1 single nucleotide polymorphisms was performed (Rs7209436, Rs110402, Rs242924) and their effect on QoL scores was explored. aSAH patients experienced a reduced quality of life in all domains. CRHR1 minor genotype was associated with higher SF-36 mental health (OR = 1.31-1.6, p < 0.05), role-emotional (OR = 1.57, p = 0.04) and vitality scores (OR = 1.31-1.38, p < 0.05). Association of all studied SNP's with vitality and Rs242924 with mental health scores remained statistically significant after Bonferroni correction. Mental quality of life scores were associated with physical state of patients, antidepressant history and CRHR1 genotype. Predisposition to mental health disturbances after stressful life-events might be associated with reduced mental QoL after aSAH and selected patients could be provided advanced counselling in the recovery phase.

Tumor-penetrating peptide for systemic targeting of Tenascin-C.

Extracellular matrix in solid tumors has emerged as a specific, stable, and abundant target for affinity-guided delivery of anticancer drugs. Here we describe the homing peptide that interacts with the C-isoform of Tenascin-C (TNC-C) upregulated in malignant tissues. TNC-C binding PL3 peptide (amino acid sequence: AGRGRLVR) was identified by in vitro biopanning on recombinant TNC-C. Besides TNC-C, PL3 interacts via its C-end Rule (CendR) motif with cell-and tissue penetration receptor neuropilin-1 (NRP-1). Functionalization of iron oxide nanoworms (NWs) and metallic silver nanoparticles (AgNPs) with PL3 peptide increased tropism of systemic nanoparticles towards glioblastoma (GBM) and prostate carcinoma xenograft lesions in nude mice (eight and five-fold respectively). Treatment of glioma-bearing mice with proapoptotic PL3-guided NWs improved the survival of the mice, whereas treatment with untargeted particles had no effect. PL3-coated nanoparticles were found to accumulate in TNC-C and NRP-1-positive areas in clinical tumor samples, suggesting a translational relevance. The systemic tumor-targeting properties and binding of PL3-NPs to the clinical tumor sections, suggest that the PL3 peptide may have applications as a targeting moiety for the selective delivery of imaging and therapeutic agents to solid tumors.

Influence of alarming auditory cues on viscoelastic stiffness of skeletal muscles in patients with Parkinson's disease.

BACKGROUND: Patients with Parkinson's disease can show brief normalization of motor activity in response to intense external stimuli - a phenomenon known as paradoxical kinesis. The purpose of the present study was to examine the effect of alarming auditory signals on the level of viscoelastic stiffness of skeletal muscles as an indicator of parkinsonian rigidity. METHODS: Myotonometry was used to determine the changes of viscoelastic stiffness of skeletal muscles in ten patients in an advanced stage of Parkinson's disease, treated with deep brain stimulation, and ten healthy controls. The measurements were repeated and compared during the stimulation-on and stimulation-off periods, with and without auditory alarming signals. FINDINGS: The mean values of stiffness measured in the stimulation-off phase (370.4 N/m) were significantly higher than the values obtained in the stimulation-on phase (339.2 N/m) (q = 6.05; P < 0.01) but also in the stimulation-off with alarming signals phase (349.6 N/m) (q = 4.04; P < 0.05). In the normal controls, exposure to the auditory alarming signals did not change the values of viscoelastic stiffness. INTERPRETATION: These findings demonstrate that the phenomenon of paradoxical kinesis is associated with the changes of muscular rigidity in parkinsonian patients. Results from the study may help to establish new strategies for addressing motor disabilities in patients with Parkinson's disease.

Bi-specific tenascin-C and fibronectin targeted peptide for solid tumor delivery.

Oncofetal fibronectin (FN-EDB) and tenascin-C C domain (TNC-C) are nearly absent in extracellular matrix of normal adult tissues but upregulated in malignant tissues. Both FN-EDB and TNC-C are developed as targets of antibody-based therapies. Here we used peptide phage biopanning to identify a novel targeting peptide (PL1, sequence: PPRRGLIKLKTS) that interacts with both FN-EDB and TNC-C. Systemic PL1-functionalized model nanoscale payloads [iron oxide nanoworms (NWs) and metallic silver nanoparticles] homed to glioblastoma (GBM) and prostate carcinoma xenografts, and to non-malignant angiogenic neovessels induced by VEGF-overexpression. Antibody blockage experiments demonstrated that PL1 tumor homing involved interactions with both receptor proteins. Treatment of GBM mice with PL1-targeted model therapeutic nanocarrier (NWs loaded with a proapoptotic peptide) resulted in reduced tumor growth and increased survival, whereas treatment with untargeted particles had no effect. PL1 peptide may have applications as an affinity ligand for delivery of diagnostic and therapeutic compounds to microenvironment of solid tumors.

Effect of Age on Substantia Nigra Hyper-echogenicity in Parkinson's Disease Patients and Healthy Controls.

Substantia nigra (SN) hyper-echogenicity (SN+) describes an enlargement (>90th percentile) of the area of echogenicity at the anatomic site of the SN in the midbrain detected by transcranial sonography. This ultrasound sign has proven to be a valuable marker supporting the clinical diagnosis of Parkinson's disease (PD). Although there is considerable variation in the extent of echogenic signals at the anatomic site of the SN among PD patients, previous work suggests that SN+ is a stable marker throughout the course of the disease. The present study focused on two aspects: (i) determining whether SN+ values differ between the sides, mirroring the asymmetric character of the disease; and (ii) determining whether age has an influence on SN echogenicity. This cross-sectional study included 300 PD patients and 200 healthy controls. SN+ was measured planimetrically by transcranial sonography. Echogenicity was analyzed separately for onset and non-onset sides, with onset side defined as the SN contralateral to the side of the body that first manifested PD-related motor impairment. Age of the patients and healthy controls at study time was used for correlation. We found that the onset SN+ contralateral to the side of initial motor symptoms was on average 17.6% larger than its counterpart. However, we also found that contrary to the control group, where an increase in age was associated with an increase in size of SN+, age of PD patients was associated with a decline in size of the onset SN+. Furthermore, SN measured at the onset side of PD patients correlated significantly with patient age and Hoehn and Yahr stage, a scale that grades PD severity, although this was not the case for the non-onset side. The present study indicates that changes in SN echogenicity have a different dynamic depending on the onset side of the disease. The age at study time had a significantly negative effect on the size of onset SN+, the effect on the non-onset side was non-significant. We conclude that for appropriate PD analysis, onset SN+ is a more important marker than the average of both sides of SN. Furthermore, we found that among healthy controls, the size of SN+ increases with age.

Peptide-guided nanoparticles for glioblastoma targeting.

Tumor-selective drug conjugates can potentially improve the prognosis for patients affected by glioblastoma (GBM) - the most common and malignant type of brain cancer with no effective cure. Here we evaluated a novel tumor penetrating peptide that targets cell surface p32, LinTT1 (AKRGARSTA), as a GBM targeting ligand for systemically-administered nanoparticles. LinTT1-functionalization increased tumor homing of iron oxide nanoworms (NWs) across a panel of five GBM models ranging from infiltratively-disseminating to angiogenic phenotypes. LinTT1-NWs homed to CD31-positive tumor blood vessels, including to transdifferentiated endothelial cells, and showed co-localization with tumor macrophages and lymphatic vessels. LinTT1 functionalization also resulted in increased GBM delivery of other types of systemically-administered nanoparticles: silver nanoparticles and albumin-paclitaxel nanoparticles. Finally, LinTT1-guided proapoptotic NWs exerted strong anti-glioma activity in two models of GBM, including doubling the lifespan of the mice in an aggressive orthotopic stem cell-like GBM that recapitulates the histological hallmarks of human GBM. Our study suggests that LinTT1 targeting strategy can be used to increase GBM uptake of systemic nanoparticles for improved imaging and therapy.

Validation of an Estonian version of the Parkinson's Disease Questionnaire (PDQ-39).

INTRODUCTION: Diagnosis and management of Parkinson's disease (PD) rely heavily on evaluation of clinical symptoms and patients' subjective perception of their condition. The purpose of this study was to evaluate the validity, acceptability, and reliability of the Estonian version of the 39-question Parkinson 's disease Questionnaire (PDQ-39). METHODS: Study subjects were approached during their regular clinic follow-up visits. 104 patients consented to the study and 81 completed questionnaires were used for subsequent testing of psychometric characteristics, validity and reliability. RESULTS: The content validity was assessed through qualitative content analysis during the pilot study. The patients indicated that the questions were relevant to measure the quality of life of people with PD. The analysis of means showed that the ceiling and floor effects of domain results were within the limits of 15% of Summary Index and of all domains except Stigma, Social Support and Communication where the ceiling effect was 16% to 24% of the responses. Convergent validity was interpreted through correlation between disease severity and PDQ-39 domains. There was a statistically significant difference between the domain scores in patients with mild versus moderate PD in domains of Mobility, ADL, and Communication but not for Stigma, Social Support and Cognition. The reliability was good, Cronbach alpha for all domains and summary index was over 0.8 and item-test correlations between domains and summary index ranged from 0.56 to 0.83. CONCLUSION: The psychometric characteristics of an Estonian version of the PDQ-39 were satisfactory. The results of this study were comparable to the results of previous validation studies in other cultural settings in UK, USA, Canada, Spain and Italy. The Estonian version of the PDQ-39 is an acceptable, valid and reliable instrument for quality of life measurement in PD patients.