Identification and validation of N-acetylputrescine in combination with non-canonical clinical features as a Parkinson's disease biomarker panel.

Parkinson's disease is a progressive neurodegenerative disorder in which loss of dopaminergic neurons in the substantia nigra results in a clinically heterogeneous group with variable motor and non-motor symptoms with a degree of misdiagnosis. Only 3-25% of sporadic Parkinson's patients present with genetic abnormalities that could represent a risk factor, thus environmental, metabolic, and other unknown causes contribute to the pathogenesis of Parkinson's disease, which highlights the critical need for biomarkers. In the present study, we prospectively collected and analyzed plasma samples from 194 Parkinson's disease patients and 197 age-matched non-diseased controls. N-acetyl putrescine (NAP) in combination with sense of smell (B-SIT), depression/anxiety (HADS), and acting out dreams (RBD1Q) clinical measurements demonstrated combined diagnostic utility. NAP was increased by 28% in Parkinsons disease patients and exhibited an AUC of 0.72 as well as an OR of 4.79. The clinical and NAP panel demonstrated an area under the curve, AUC = 0.9 and an OR of 20.4. The assessed diagnostic panel demonstrates combinatorial utility in diagnosing Parkinson's disease, allowing for an integrated interpretation of disease pathophysiology and highlighting the use of multi-tiered panels in neurological disease diagnosis.

Physical Analysis of Heat for Formation and Entropy of Ceria Oxide Using Topological Indices.

BACKGROUND: Cerium oxide nanoparticles (CeO2 NPs) have gained their importance as engineered nanomaterials (ENMs) that have wide applications as catalysts in industry, which direct to their prominent occurrence in natural and engineered water systems. Cerium oxide nanoparticles (CeO2 NPs) have gained their importance as engineered nanomaterials (ENMs) that have wide applications as catalysts in industry, which direct to their prominent occurrence in natural and engineered water systems. In wastewater treatment plants, CeO2 NPs can stay colloidally stable and be unconstrained in the secondary effluents. As they entered into tertiary treatment, such as advanced oxidation processes (AOPs), it is noteworthy that how the generated reactive oxygen species will change the colloidal stability, aggregation, and the surface chemistry of CeO2 NPs. AIM AND OBJECTIVE: The study was aimed to analyze the chemical graph of the crystal structure of Ceria Oxide(cuprite) CeO2. Also, our main objective is to compute the Heat of Formation and Entropy using degree based topological indices. MATERIALS AND METHODS: Chemical graph theory plays an important role in modeling and designing any chemical structure. The topological indices are the numerical invariants of a molecular graph and are very useful for predicting their physical properties. For calculation, we have utilized the combinatorial processing strategy, edge partition technique, vertex partition strategy, analytic procedures, graph hypothetical tools, degree counting technique and entirety of degrees of neighbor technique. Moreover, Matlab programming has been utilized for numerical computations and checks. We likewise utilized the maple for plotting these numerical outcomes. RESULTS: We have computed Heat of Formation and Entropy using degree based topological indices. Our main results are based on some degree based topological indices, namely, the atom bond connectivity index ABC, geometric arithmetic index GA, general Randi index, Forgotten index, Augmented zagreb index and Balban index for the chemical graph of the crystal structure of cuprite CeO2[p, q, t] We also provide a detailed application of the computed results. CONCLUSION: We discuss these indices exhibited difference with the reported heat of formation and entropy of cuprite CeO2[p, q, t] In almost all the cases, an exponential increase of aforementioned indices is observed with the increase in the number of cells or other words size of cuprite CeO2[p, q, t] nanocrystal. On the other hand, a linear relationship of indices with respect to the number of formula units suggests a slight modification of these indices for an appropriate explanation of the physical properties of cuprite CeO2[p, q, t] nanocrystal of varying size and hence its prospective application in nanoceria engineering.

Clustering of motor and nonmotor traits in leucine-rich repeat kinase 2 G2019S Parkinson's disease nonparkinsonian relatives: A multicenter family study.

OBJECTIVES: The objective of this study was to determine phenotypic features that differentiate nonparkinsonian first-degree relatives of PD leucine-rich repeat kinase 2 (LRRK2) G2019S multiplex families, regardless of carrier status, from healthy controls because nonparkinsonian individuals in multiplex families seem to share a propensity to present neurological features. METHODS: We included nonparkinsonian first-degree relatives of LRRK2 G2019S familial PD cases and unrelated healthy controls participating in established multiplex family LRRK2 cohorts. Study participants underwent neurologic assessment including cognitive screening, olfaction testing, and questionnaires for daytime sleepiness, depression, and anxiety. We used a multiple logistic regression model with backward variable selection, validated with bootstrap resampling, to establish the best combination of motor and nonmotor features that differentiates nonparkinsonian first-degree relatives of LRRK2 G2019S familial PD cases from unrelated healthy controls. RESULTS: We included 142 nonparkinsonian family members and 172 unrelated healthy controls. The combination of past or current symptoms of anxiety (adjusted odds ratio, 4.16; 95% confidence interval, 2.01-8.63), less daytime sleepiness (adjusted odds ratio [1 unit], 0.90; 95% confidence interval, 0.83-0.97], and worse motor UPDRS score (adjusted odds ratio [1 unit], 1.4; 95% confidence interval, 1.20-1.67) distinguished nonparkinsonian family members, regardless of LRRK2 G2019S mutation status, from unrelated healthy controls. The model accuracy was good (area under the curve = 79.3%). CONCLUSIONS: A set of motor and nonmotor features distinguishes first-degree relatives of LRRK2 G2019S probands, regardless of mutation status, from unrelated healthy controls. Environmental or non-LRRK2 genetic factors in LRRK2-associated PD may influence penetrance of the LRRK2 G2019S mutation. The relationship of these features to actual PD risk requires longitudinal observation of LRRK2 familial PD cohorts. © 2018 International Parkinson and Movement Disorder Society.

Penetrance estimate of LRRK2 p.G2019S mutation in individuals of non-Ashkenazi Jewish ancestry.

BACKGROUND: Penetrance estimates of the leucine-rich repeat kinase 2 (LRRK2) p.G2019S mutation for PD vary widely (24%-100%). The p.G2019S penetrance in individuals of Ashkenazi Jewish ancestry has been estimated as 25%, adjusted for multiple covariates. It is unknown whether penetrance varies among different ethnic groups. The objective of this study was to estimate the penetrance of p.G2019S in individuals of non-Ashkenazi Jewish ancestry and compare penetrance between Ashkenazi Jews and non-Ashkenazi Jews to age 80. METHODS: The kin-cohort method was used to estimate penetrance in 474 first-degree relatives of 69 non-Ashkenazi Jewish LRRK2 p.G2019S carrier probands at 8 sites from the Michael J. Fox LRRK2 Cohort Consortium. An identical validated family history interview was administered to assess age at onset of PD, current age, or age at death for relatives in different ethnic groups at each site. Neurological examination and LRRK2 genotype of relatives were included when available. RESULTS: Risk of PD in non-Ashkenazi Jewish relatives who carry a LRRK2 p.G2019S mutation was 42.5% (95% confidence interval [CI]: 26.3%-65.8%) to age 80, which is not significantly higher than the previously estimated 25% (95% CI: 16.7%-34.2%) in Ashkenazi Jewish carrier relatives. The penetrance of PD to age 80 in LRRK2 p.G2019S mutation carrier relatives was significantly higher than the noncarrier relatives, as seen in Ashkenazi Jewish relatives. CONCLUSIONS: The similar penetrance of LRRK2 p.G2019S estimated in Ashkenazi Jewish carriers and non-Ashkenazi Jewish carriers confirms that p.G2019S penetrance is 25% to 42.5% at age 80 in all populations analyzed. © 2017 International Parkinson and Movement Disorder Society.

Heart rate variability in leucine-rich repeat kinase 2-associated Parkinson's disease.

BACKGROUND: Heart rate variability is reduced in idiopathic PD, indicating cardiac autonomic dysfunction likely resulting from peripheral autonomic synucleinopathy. Little is known about heart rate variability in leucine-rich repeat kinase 2-associated PD. OBJECTIVES: This study investigated heart rate variability in LRRK2-associated PD. METHODS: Resting electrocardiograms were obtained from 20 individuals with LRRK2-associated PD, 37 nonmanifesting carriers, 48 related noncarriers, 26 idiopathic PD patients, and 32 controls. Linear regression modelling compared time and frequency domain values, adjusting for age, sex, heart rate, and disease duration. RESULTS: Low-frequency power and the ratio of low-high frequency power were reduced in idiopathic PD versus controls (P < .008, P < .029 respectively). In contrast, individuals with LRRK2-associated PD were not statistically different from controls in any parameter measured. Furthermore, all parameters trended toward being higher in LRRK2-associated PD when compared with idiopathic PD. CONCLUSIONS: Heart rate variability may remain intact in LRRK2-associated PD, adding to a growing literature supporting clinical-pathologic differences between LRRK2-associated and idiopathic PD. © 2017 International Parkinson and Movement Disorder Society.

Nurses in low resource settings save mothers' lives with non-pneumatic anti-shock garment.

PURPOSE: To discuss the role of nurses and nurse-midwives in preventing and treating postpartum hemorrhage (PPH) from uterine atony in developing countries and examine the role of a new device, the non-pneumatic anti-shock garment (NASG), in improving the outcomes for these patients. STUDY DESIGN AND METHODS: In this subanalysis of a larger preintervention phase/intervention phase study of 1,442 women with obstetric hemorrhage, postpartum women with hypovolemic shock (N = 578) from uterine atony (≥750 mL blood loss; systolic blood pressure <100 mmHg and/or pulse >100 beats per minute) were enrolled in two referral facilities in Egypt and four referral facilities in Nigeria. The study had two temporal phases: a preintervention phase and an NASG-intervention phase. Women with hemorrhage and shock in both phases were treated with the same evidence-based protocols for management of hypovolemic shock and hemorrhage, but women in the NASG-intervention phase also received the NASG. Relative risks (RRs) with 95% confidence intervals (CIs) were estimated for primary outcomes-measured blood loss, incidence of emergency hysterectomy, and mortality. RESULTS: Women in the NASG-intervention phase had significantly better outcomes, 50% lower blood loss, reduced rates of hysterectomy (8.9% vs. 4%), and mortality decreased from 8.5% to 2.3% (RR = 0.27, 95% CI: 0.12-0.60). CLINICAL IMPLICATIONS: In low-resource settings nurses have few resources with which to stabilize women with severe PPH. With training nurses and nurse-midwives can stabilize hemorrhaging women with the NASG, a low-technology first-aid device that shows promise for reducing blood loss, rates of hysterectomy, and mortality.