Validation and cross-cultural adaptation of the Self-Assessment Disability Scale in patients with Parkinson’s disease in Serbia

The symptoms of Parkinson’s disease (PD) worsen over time affecting performance and causing disability. The purpose of this study was to translate the Self-Assessment Disability Scale in patients with Parkinson's disease (SADS-PD) into the Serbian language and assess its validity and reliability. From January to July 2012, 114 consecutive PD patients were recruited at the Neurology Clinic in Belgrade. The inclusion criteria were: ability to walk independently for at least 10 m, ability to stand for at least 90 s. The exclusion criteria were: cognitive impairment, the presence of other major neurologic, psychiatric, visual, audio-vestibular, and orthopedic disturbances. The 25-item SADS-PD was translated according to internationally-accepted methodology. The internal consistency of the scale was evaluated using Cronbach’s alpha coefficient. Test–retest reliability was evaluated using Kendall’s concordance coefficient for total scores. To evaluate construct validity, an exploratory factor analysis (principal component analysis, varimax rotation) was performed. Cronbach’s alpha coefficient was 0.984. Kendall’s concordance coefficient was 0.994. Duration of the disease, Hoehn & Yahr (H&Y) stage, Unified Parkinson’s Disease Rating Scale (UPDRS) motor score, history of falls, Hamilton’s Depression and Anxiety Rating Scales (HDRS and HARS) scores were significantly correlated with the total SADS-PD score. On factor analysis 25 items in the SADS-PD questionnaire were separated in two clusters with total matrix variance of 79.7 %. The psychometric properties of the cross-culturally adapted SADS-PD questionnaire (Serbian version) have outstanding validity and reliability as an instrument for evaluation of the extent of disability in patients with PD.     

Numerical assessment of radiation binary targeted therapy for HER-2 positive breast cancers: advanced calculations and radiation dosimetry

In our previous publication (Mundy et al 2006 Phys. Med. Biol. 51 1377) we have described the theoretical assessment of our novel approach in radiation binary targeted therapy for HER-2 positive breast cancers and summarized the future directions in this area of research. In this paper we advanced the numerical analysis to show the detailed radiation dose distribution for various neutron sources in combination with the required boron concentration and allowed radiation skin doses. We once again proved the feasibility of the concept and will use these data and conclusions to start with the experimental verifications.     

Biological evaluation of selected 3,4‐dihydro‐2(1H)‐quinoxalinones and 3,4‐dihydro‐1,4‐benzoxazin‐2‐ones: Molecular docking study

In order to investigate new potential therapeutically active agents, we investigated the biological properties of two small libraries of quinoxalinones and 1,4‐benzoxazin‐2‐ones. The results obtained showed that compounds 5 , 9–11 have good cytotoxic activity against HeLa cells where the lowest IC₅₀ value (10.46 ± 0.82 μM/mL) was measured for compound 10 . Additionally, the most active compounds ( 5 , 9 – 11 ) showed much better selectivity for MRC‐5 cells (up to 17.4) compared to cisplatin. In vitro evaluation of the inhibition of the enzyme α‐glucosidase showed that compounds 10 and 11 exert significant inhibition of the enzyme at 52.54 ± 0.09 and 40.09 ± 0.49 μM, respectively. Competitive experiments with ethidium bromide (EB) indicated that all tested compounds have affinity to displace EB from the EB‐DNA complex through intercalation, suggesting good competition with EB (K_sv = (3.1 ± 0.2), (5.1 ± 0.1), (5.6 ± 0.2), and (6.3 ± 0.2) × 10³ M^?1). A molecular docking study was also performed to better understand the binding modes and to conclude the structure–activity relationships of the synthesized compounds.

     

Seroepidemiology of hepatitis E in patients on haemodialysis in Croatia

International Urology and Nephrology - Data on the seroprevalence of hepatitis E virus (HEV) in heamodialysis (HD) patients are conflicting, ranging from 0 to 44%. The aim of this study was to...     

Overexpression of oxytocin receptors in the hypothalamic PVN increases baroreceptor reflex sensitivity and buffers BP variability in conscious rats

Background and Purpose

The paraventricular nucleus (PVN) of the hypothalamus is an important integrative site for neuroendocrine control of the circulation. We investigated the role of oxytocin receptors (OT receptors) in PVN in cardiovascular homeostasis.

Experimental Approach

Experiments were performed in conscious male Wistar rats equipped with a radiotelemetric device. The PVN was unilaterally co-transfected with an adenoviral vector (Ad), engineered to overexpress OT receptors, and an enhanced green fluorescent protein (eGFP) tag. Control groups: PVN was transfected with an Ad expressing eGFP alone or untransfected, sham rats (Wt). Recordings were obtained without and with selective blockade of OT receptors (OTX), during both baseline and stressful conditions. Baroreceptor reflex sensitivity (BRS) and cardiovascular short-term variability were evaluated using the sequence method and spectral methodology respectively.

Key Results

Under baseline conditions, rats overexpressing OT receptors (OTR) exhibited enhanced BRS and reduced BP variability compared to control groups. Exposure to stress increased BP, BP variability and HR in all rats. In control groups, but not in OTR rats, BRS decreased during stress. Pretreatment of OTR rats with OTX reduced BRS and enhanced BP and HR variability under baseline and stressful conditions. Pretreatment of Wt rats with OTX, reduced BRS and increased BP variability under baseline and stressful conditions, but only increased HR variability during stress.

Conclusions and Implications

OT receptors in PVN are involved in tonic neural control of BRS and cardiovascular short-term variability. The failure of this mechanism could critically contribute to the loss of autonomic control in cardiovascular disease.     

Unrelated stem cell transplantation in multiple myeloma after a reduced-intensity conditioning with pretransplantation antithymocyte globulin is highly effective with low transplantation-related mortality

We investigated the feasibility of unrelated stem cell transplantation in 21 patients with advanced stage II/III multiple myeloma after a reduced-intensity conditioning regimen consisting of fludarabine (150 mg/m(2)), melphalan (100-140 mg/m(2)), and antithymocyte globulin (ATG; 10 mg/kg on 3 days). The median patient age was 50 years (range, 32-61 years). All patients had received at least one prior autologous transplantation, in 9 cases as part of an autologous-allogeneic tandem protocol. No graft failure was observed. At day 40 complete donor chimerism was detected in all patients. Grade II to IV acute graft-versus-host disease (GVHD) was seen in 8 patients (38%), and severe grade III/IV GVHD was observed in 4 patients (19%). Six patients (37%) developed chronic GVHD, but only 2 patients (12%) experienced extensive chronic GVHD. The estimated probability of nonrelapse mortality at day 100 was 10% and at 1 year was 26%. After allografting, 40% of the patients achieved a complete remission, and 50% achieved a partial remission, resulting in an overall response rate of 90%. After a median follow-up of 13 months, the 2-year estimated overall and progression-free survival rates are 74% (95% CI, 54%-94%) and 53% (95% CI, 29%-87%), respectively. A shorter progression-free survival was seen in patients who already experienced relapse to prior autograft (26% versus 86%, P =.04). Dose-reduced conditioning with pretransplantation ATG followed by unrelated stem cell transplantation provides durable engraftment and donor chimerism, reduces substantially the risk of transplant-related organ toxicity, and induces high remission rates.