Heterogeneous Determinants of Quality of Life in Different Phenotypes of Parkinson’s Disease

Objectives

Health-related quality of life (HRQoL) is considered a very important outcome indicator in patients with Parkinson’s disease (PD). A broad list of motor and non-motor features have been shown to affect HRQoL in PD, however, there is a dearth of information about the complexity of interrelationships between determinants of HRQoL in different PD phenotypes. We aimed to find independent determinates and the best structural model for HRQoL, also to investigate the heterogeneity in HRQoL between PD patients with different phenotypes regarding onset-age, progression rate and dominant symptom.

Methods

A broad spectrum of demographic, motor and non-motor characteristics were collected in 157 idiopathic PD patients, namely comorbidity profile, nutritional status, UPDRS (total items), psychiatric symptoms (depression, anxiety), fatigue and psychosocial functioning through physical examination, validated questionnaires and scales. Structural equation model (SEM) and multivariate regressions were applied to find determinants of Parkinson’s disease summary index (PDSI) and different domains of HRQoL (PDQ-39).

Results

Female sex, anxiety, depression and UPDRS-part II scores were the significant independent determinants of PDSI. A structural model consisting of global motor, global non-motor and co-morbidity indicator as three main components was able to predict 89% of the variance in HRQoL. In older-onset and slow-progression phenotypes, the motor domain showed smaller contribution on HRQoL and the majority of its effects were mediated through non-motor features. Comorbidity component was a significant determinant of HRQoL only among older-onset and non-tremor-dominant PD patients. Fatigue was not a significant indicator of non-motor component to affect HRQoL in rapid-progression PD.

Conclusions

Our findings showed outstanding heterogeneities in the pattern and determinants of HRQoL among PD phenotypes. These factors should be considered during the assessments and developing personalized interventions to improve HRQOL in PD patients with different phenotypes or prominent feature.     

Bayesian analysis of multivariate mixed models for a prospective cohort study using skew‐elliptical distributions

Classical multivariate mixed models that acknowledge the correlation of patients through the incorporation of normal error terms are widely used in cohort studies. Violation of the normality assumption can make the statistical inference vague. In this paper, we propose a Bayesian parametric approach by relaxing this assumption and substituting some flexible distributions in fitting multivariate mixed models. This strategy allows for the skewness and the heavy tails of error‐term distributions and thus makes inferences robust to the violation. This approach uses flexible skew‐elliptical distributions, including skewed, fat, or thin‐tailed distributions, and imposes the normal model as a special case. We use real data obtained from a prospective cohort study on the low back pain to illustrate the usefulness of our proposed approach.     

Impact of IFN-β and LIF overexpression on human adipose-derived stem cells properties

Adipose-derived stem cells (ADSCs) are a subset of mesenchymal stem cells that their therapeutic effects in various diseases make them an interesting tool in cell therapy. In the current study, we aimed to overexpress interferon-β (IFN-β) and leukemia inhibitory factor (LIF) cytokines in human ADSCs to evaluate the impact of this overexpression on human ADSCs properties. Here, we designed a construct containing IFN-β and LIF and then, transduced human adipose-derived stem cells (hADSCs) by this construct via a lentiviral vector (PCDH-513B). We assessed the ability of long-term expression of the transgene in transduced cells by western blot analysis and enzyme-linked immunosorbent assay techniques on Days 15, 45, and 75 after transduction. For the evaluation of stem cell properties, flow cytometry and differentiation assays were performed. Finally, the MTT assay was done to assess the proliferation of transduced cells compares to controls. Our results showed high-efficiency transduction with highest expression rates on Day 75 after transduction which were 70 pg/ml for IFN-β and 77.9 pg/ml for LIF in comparison with 25.60 pg/ml and 27.63 pg/ml, respectively, in untransduced cells (p = .0001). Also, transduced cells expressed a high level of ADSCs surface markers and successfully differentiated into adipocytes, chondrocytes, neural cells, and osteocytes besides the preservation rate of proliferation near untreated cells (p = .88). All in all, we successfully constructed an hADSC population stably overexpressed IFN-β and LIF cytokines. Considering the IFN-β and LIF anti-inflammatory and neuroprotective effects as well as immune-regulatory properties of hADSCs, the obtained cells of this study could be subjected for further evaluations in experimental autoimmune encephalomyelitis mice model.     

Water-retention additives’ effects on plant water status and some physiological parameters of two olive cultivars under reduced irrigation regimes

In arid and semi-arid zones of world, the majority of annual rainfall or irrigation water is lost due to high evaporation from the soil. The amount of available water in soil can be increased by surface mulching. However, the effect varies with soils, climate and kind of mulch material used. Some physiological and biochemical parameters of two olive cultivars (‘Konservolea’ and ‘Manzanilla’) as affected by different water-retention additives (organic, chemical and mineral mulches and hydrogel) and two amounts of irrigation water were studied in pot experiments during 2013. Water stress affects plant water relations and photosynthesis and caused oxidative stress in olive. Our results confirmed that water-retention additives partly mitigated the adverse effects of water stress on olive restoring most of the measured parameters similar to those of control unstressed plants. Mulching treatment enhanced antioxidative defenses and reduced water deficit-induced oxidative damage in olive compared to zero mulching treatment. The results indicated that de-oiled olive pomace mulch and pistachio shell mulch—as new mulch materials—proved to be very effective for soil water conservation under arid conditions. It can be concluded that water management through mulch application can strongly influence the cultivar response to water deficit.     

Nickel oxide hollow microsphere for the chemiluminescence determination of tuberculostatic drug isoniazid

In this article, nickel(II) oxide (NiO) hollow microspheres (HMSs) were fabricated and used to catalyze chemiluminescence (CL) reaction. The studied CL reaction is the luminol-oxygen reaction that was used as a sensitive analytical tool for measuring tuberculostatic drug isoniazid (IND) in pharmaceutical formulations and water samples. The CL method was established based on the suppression impact of IND on the CL reaction. The NiO HMSs were produced by a simple hydrothermal method and characterized by several spectroscopic techniques. The result of essential parameters on the analytical performance of the CL method, including concentrations of sodium hydroxide (NaOH), luminol, and NiO HMSs were investigated. At the optimum conditions, the calibration curve for IND was linear in the range of 8.00 × 10⁻⁷ to 1.00 × 10⁻⁴ mol L⁻¹ (R² = 0.99). A detection limit (3S) of 2.00 × 10⁻⁷ mol L⁻¹ was obtained for this method. The acceptable relative standard deviation (RSD) was obtained for the proposed CL method (2.63%, n = 10) for a 5.00 × 10⁻⁶ mol L⁻¹ IND solution. The mechanism of the CL reaction was also discussed.     

FeS2 nanosheets–luminol–O2 chemiluminescence method for determination of venlafaxine hydrochloride,imipramine hydrochloride,and cefazolin sodium

This study introduces a novel chemiluminescence (CL) approach utilizing FeS₂ nanosheets (NSs) catalyzed luminol–O₂ CL reaction for the measurement of three pharmaceuticals, namely venlafaxine hydrochloride (VFX), imipramine hydrochloride (IPM), and cefazolin sodium (CEF). The CL method involved the phenomenon of quenching induced by the pharmaceuticals in the CL reaction. To achieve the most quenching efficacy of the pharmaceuticals in the CL reaction, the concentrations of reactants comprising luminol, NaOH, and FeS₂ NSs were optimized accordingly. The calibration curves demonstrated exceptional linearity within the concentration range spanning from 4.00 × 10⁻⁷ to 1.00 × 10⁻³ mol L⁻¹, 1.00 × 10⁻⁷ to 1.00 × 10⁻⁴ mol L⁻¹, and 4.00 × 10⁻⁶ to 2.00 × 10⁻⁴ mol L⁻¹ with detection limits (3σ) of 3.54 × 10⁻⁷, 1.08 × 10⁻⁸, and 2.63 × 10⁻⁶ mol L⁻¹ for VFX, IPM, and CEF, respectively. This study synthesized FeS₂ NSs using a facile hydrothermal approach, and then the synthesized FeS₂ NSs were subjected to a comprehensive characterization using a range of spectroscopic methods. The proposed CL method was effective in measuring the aforementioned pharmaceuticals in pharmaceutical formulations as well as different water samples. The mechanism of the CL system has been elucidated.     

The relationship between tomato fruit growth,incidence of blossom-end rot and phytohormone content as affected by sink/source ratio

Blossom-end rot is generally considered a calcium-related physiological disorder. The results of the previous studies show that several factors such as plant conditions can be effective on the blossom-end rot incidence. Therefore, the present study was undertaken to investigate the effect of the sink/source ratio on the incidence of the blossom-end rot of two greenhouse tomato (Solanum lycopersicum L.) cultivars: ‘Grandella’ and ‘Isabella’. To this end, four treatments were applied: saving one fruit per truss (1F), two fruits per truss (2F), three fruits per truss (3F), and no fruit pruning (control). The results showed that the tomato cultivar ‘Isabella’ was more susceptible to the blossom-end rot than ‘Grandella’. Decreasing the sink/source ratio increased the incidence of the blossom-end rot and the relative fruit growth rate. The correlation between the blossom-end rot incidence and the relative fruit growth rate showed that the fruit growth rate could be regarded as an important factor in the incidence of this disorder. Endogenous auxin and cytokinin concentrations acted as the regulators of the fruit growth rate and influenced it. Slowing down the relative growth rate by keeping proper sink/source ratio based on tomato cultivar is, therefore, an effective, cheap and healthy way to control the incidence of the blossom-end rot, especially in organic farming.