Nevin Manimala

Parkinsonism Relat Disord. 2021 Sep 21;91:115-120. doi: 10.1016/j.parkreldis.2021.09.015. Online ahead of print.

ABSTRACT

INTRODUCTION: The non-motor symptoms (NMSs) of Parkinson’s disease (PD) significantly impact the patient’s health-related quality of life. This subanalysis of the J-FIRST study evaluated the effect of istradefylline, a selective adenosine A_2A receptor antagonist, on NMSs in istradefylline-naïve Japanese patients with PD.

METHODS: Patients with PD and ≥1 NMS and ‘wearing-off’ with their current antiparkinsonian treatment were observed for up to 52 weeks. The effect of istradefylline on NMSs was measured in terms of changes in the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part 1 total, individual sub-items scores and the 8 item PD questionnaire (PDQ-8) estimated by the marginal structural model.

RESULTS: Overall, 732 patients were istradefylline-naïve prior to the study, of whom 171 were treated with istradefylline for ≥8 weeks during the observation period (istradefylline-treated patients). At baseline, istradefylline-treated patients were more likely to have a dyskinesia (49.7% vs 40.8%) and received a significantly higher daily dose of levodopa (462.8 mg vs 413.0 mg) than those who did not receive istradefylline (n = 561). MDS-UPDRS Part 1 total score at the end of the 52-week observational period slightly increased in patients who received istradefylline and those who did not (0.49 ± 0.41 vs 0.07 ± 0.20; P = 0.36). There were no statistically significant differences between the two groups of patients in terms of changes in the MDS-UPDRS Part 1 total score or any sub-items, or in the PDQ-8 total score.

CONCLUSION: NMSs remained generally controlled in istradefylline-treated Japanese patients with PD who exhibited wearing-off with their current antiparkinsonian treatment. Istradefylline could be a feasible treatment option for patients with advanced PD, without worsening existing NMSs.

PMID:34583302 | DOI:10.1016/j.parkreldis.2021.09.015

Parkinsonism Relat Disord. 2021 Sep 8;91:109-114. doi: 10.1016/j.parkreldis.2021.09.004. Online ahead of print.

ABSTRACT

BACKGROUND: There are no widely accepted criteria to aid the physician in diagnosing BSP.

OBJECTIVE: To validate recently proposed diagnostic criteria for blepharospasm in a larger and geographically diverse population and to develop a screening system for blepharospasm.

METHODS: Video-recordings from 211 blepharospasm patients and 166 healthy/disease controls were examined by 8 raters. Agreement for presence of orbicularis oculi spasms, sensory trick, and increased blinking was measured by k statistics. Inability to voluntarily suppress the spasms was asked by the examiner but not captured in the video. Patients/controls were also requested to fill a self-administered questionnaire addressing relevant blepharospasm clinical aspects. The diagnosis at each site was the gold standard for sensitivity/specificity.

RESULTS: All the study items yielded satisfactory inter/intra-observer agreement. Combination of items rather than each item alone reached satisfactory sensitivity/specificity. The combined algorithm started with recognition of spasms followed by sensory trick. In the absence of a sensory trick, including “increased blinking” or “inability to voluntarily suppress the spasms” or both items yielded 88-92% sensitivity and 79-83% specificity. No single question of the questionnaire yielded high sensitivity/specificity. Serial application of the questionnaire to our blepharospasm and control subjects and subsequent clinical examination of subjects screening positive by the validated diagnostic algorithms yielded 78-81% sensitivity and 83-91% specificity.

CONCLUSION: These results support the use of proposed diagnostic criteria in multi-ethnic, multi-center cohorts. We also propose a case-finding procedure to screen blepharospasm in a given population with less effort than would be required by examination of all subjects.

PMID:34583301 | DOI:10.1016/j.parkreldis.2021.09.004

Am J Otolaryngol. 2021 Sep 16;43(1):103243. doi: 10.1016/j.amjoto.2021.103243. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the role of social and geographic factors on the likelihood of receiving transoral robotic surgery (TORS) or non-robotic transoral endoscopic surgery treatment in early stage oropharyngeal squamous cell carcinoma (OPSCC).

MATERIALS AND METHODS: The National Cancer Database was queried to form a cohort of patients with T1-T2 N0-N1 M0 OPSCC (AJCC v.7) who underwent treatment from 2010 to 2016. Demographics, tumor characteristics, treatment type, social, and geographic factors were all collected. Univariate analysis and multivariate logistic regression were then performed.

RESULTS: Among 9267 identified patients, 1774 (19.1%) received transoral robotic surgery (TORS), 1191 (12.9%) received transoral endoscopic surgery, and 6302 (68%) received radiation therapy. We found that lower cancer stage, lower comorbidity burden and HPV- positive status predicted a statistically significant increased likelihood of receiving surgery. Patients who reside in suburban or small urban areas (>1 million population), were low-to- middle income, or rely on Medicaid were less likely to receive surgery. Patients that reside in Medicaid-expansion states were more likely to receive TORS (p > .0001). Patients that reside in states that expanded Medicaid January 2014 and after were more likely to receive non-robotic transoral endoscopic surgery (p > .0001).

CONCLUSIONS: Poorer baseline health, lower socioeconomic status and residence in small urban areas may act as barriers to accessing minimally invasive transoral surgery while residence in a Medicaid-expansion state may improve access. Barriers to accessing robotic surgery may be greater than accessing non-robotic surgery.

PMID:34583290 | DOI:10.1016/j.amjoto.2021.103243

J Environ Manage. 2021 Sep 25;301:113820. doi: 10.1016/j.jenvman.2021.113820. Online ahead of print.

ABSTRACT

Soil salinization is a widespread problem affecting global food production. Phytoremediation is emerging as a viable and cost-effective technology to reclaim salt-affected soil. However, its efficiency is not clear due to the uncertainty of plant responses in saline soils. The main objective of this paper is to propose a phytoremediation dynamic model (PDM) for salt-affected soil within the process-based biogeochemical denitrification-decomposition (DNDC) model. The PDM represents two salinity processes of phytoremediation: plant salt uptake and salt-affected biomass growth. The salt-soil-plant interaction is simulated as a coupled mass balance equation of water and salt plant uptake. The salt extraction ability by plant is a combination of salt uptake efficiency (F) and transpiration rate. For water filled pore space (WFPS), the statistical measures RMSE, MAE, and R² during the calibration period are 2.57, 2.14, and 0.49, and they are 2.67, 2.34, and 0.56 during the validation period, respectively. For soil salinity, RMSE, MAE, and R² during the calibration period are 0.02, 0.02, and 0.92, and 0.06, 0.04, and 0.68 during the validation period, respectively, which are reasonably good for further scenario analysis. Over the four years, cumulative salt uptake varied based on weather conditions. At the optimal salt uptake efficiency (F = 20), cumulative salt uptake from soil was 16-90% for alfalfa, 11-70% for barley, and 10-80% for spring wheat. While at the lowest salt uptake efficiency (F = 40), cumulative salt uptake was nearly zero for all crops. Although barley has the highest peak transpiration flux, alfalfa and spring wheat have greater cumulative salt uptake because their peak transpiration fluxes occurred more frequently than in barley. For salt-tolerant crops biomass growth depends on their threshold soil salinity which determines their ability to take up salt without affecting biomass growth. In order to phytoremediate salt-affected soil, salt-tolerant crops having longer duration of crop physiological stages should be used, but their phytoremediation effectiveness will depend on weather conditions and the soil environment.

PMID:34583281 | DOI:10.1016/j.jenvman.2021.113820

Placenta. 2021 Sep 20;115:87-96. doi: 10.1016/j.placenta.2021.09.013. Online ahead of print.

ABSTRACT

INTRODUCTION: Oxidative stress as observed in fetal growth restriction (FGR) and preeclampsia (PE) can be identified by decreased levels of systemic free thiols (FT) and increased levels of plasma ischemia-modified albumin (IMA), which may serve as biomarkers in maternal blood for pregnancy complications. We evaluate the performance of oxidative stress-associated potential biomarkers for FGR and PE, and their relationship with clinical characteristics.

METHODS: A prospective clinical pilot study was performed in healthy controls and women with pregnancies complicated by severe FGR with or without PE. Blood samples were taken directly after inclusion and analyzed for FT; IMA; soluble FMS-like tyrosine kinase-1 (sFlt-1); placenta growth factor (PlGF); and biomarkers like leptin and soluble receptors for advanced glycation end products (sRAGE). Placentas were examined microscopically. Descriptive statistics and receiver operating characteristics statistics were performed.

RESULTS: Mothers with both severe FGR and PE had significantly reduced FT levels (p < 0.001) and PlGF levels (p < 0.001), and increased levels of plasma IMA (p < 0.05), sFlt (p < 0.001), leptin (p < 0.05) and sRAGE (p < 0.01) compared to women with FGR only. Systemic FT levels were significantly inversely associated with blood pressure (p < 0.01) and plasma IMA (p < 0.001), leptin (p = 0.01) and sRAGE (p < 0.001). Systemic FT and leptin showed significant discriminative ability to differentiate mothers with both FGR and PE from mothers with uncomplicated pregnancies or pregnancies complicated by FGR only.

DISCUSSION: There is a significant discriminative capacity of FT, IMA, leptin and sRAGE that harbor potential as biomarkers of pregnancies complicated by combined FGR and PE.

PMID:34583270 | DOI:10.1016/j.placenta.2021.09.013

Environ Pollut. 2021 Sep 21;291:118217. doi: 10.1016/j.envpol.2021.118217. Online ahead of print.

ABSTRACT

Chlorpyrifos, an organophosphate (OP) insecticide, is prevalent in aquatic systems globally and is often implicated in aquatic toxicity during storm events. Chlorpyrifos induces toxicity by inhibition of acetylcholinesterase (AChE) activity, which has been related to alterations to fish swimming performance. Resistance to organophosphate insecticides, including chlorpyrifos, is prevalent in populations of the epibenthic amphipod Hyalella azteca in areas with known OP exposure. Previous studies have demonstrated an elevated bioaccumulation potential of insecticide-resistant prey items, however the potential for trophic transfer of chlorpyrifos from OP-resistant prey items and associated neurotoxic effects in fish predators has not been studied. Consequently, the present study aimed to determine the potential for trophic transfer of chlorpyrifos from OP-resistant H. azteca to a known predator, the inland silverside, Menidia beryllina at two temperatures (18 and 23 °C) to simulate temperature changes associated with global climate change (GCC). Fish were fed either ¹⁴C-chlorpyrifos-dosed H. azteca or control animals for 7 d, after which total bioaccumulation, percent parent chlorpyrifos, brain AChE activity and swimming performance (ramp-U_crit) were determined. Fish fed chlorpyrifos-dosed H. azteca bioaccumulated chlorpyrifos ranging from 29.9 to 1250 ng/g lipid, demonstrating the potential for trophic transfer. Lower bioaccumulation and greater biotransformation were observed in M. beryllina at 23 °C as compared to 18 °C, though this was not statistically significant. A significant 36.5% reduction in brain AChE activity was observed in fish fed chlorpyrifos-dosed H. azteca at 23 °C only, which may be attributed to increased biotransformation of parent chlorpyrifos to more potent AChE-inhibiting metabolites. Dietary chlorpyrifos exposure had no significant effect on swimming performance in M. beryllina, though ramp-U_crit was significantly increased by 25% at 23 as compared to 18 °C. These findings confirm the potential for trophic transfer of chlorpyrifos from OP-resistant prey to fish predators and the potential for elevated temperatures to exacerbate the neurotoxic effects of chlorpyrifos.

PMID:34583267 | DOI:10.1016/j.envpol.2021.118217

Nurse Educ Today. 2021 Sep 11;107:105143. doi: 10.1016/j.nedt.2021.105143. Online ahead of print.

ABSTRACT

BACKGROUND: Research has confirmed a lack of knowledge regarding the risks of unused medications including diversion, misuse, or accidental overdose among health care professionals (Abdulmajeed, 2020). Nurses and pharmacists are often who patients interact with the most regarding medications; therefore, early education on proper storage and disposal is vital (Bowen, Rotz, Patterson, & Sen, 2017; Celio, Ninane, Bugnon, & Schneider, 2018).

OBJECTIVES: The study’s objective is to explore safe drug storage and disposal knowledge, attitudes, and practices of professional pharmacy (Pharm.D.) and nursing students.

DESIGN: This research is an exploratory cross-sectional study from May to September 2019.

METHODS: An anonymous online survey was administered to a purposive sample of Pharm.D. and nursing students who were 18 years and older and enrolled in the site’s accredited Pharm.D. and nursing programs (N = 210). Responses were analyzed using descriptive statistics.

RESULTS: Common disposal methods reported by students of their personal medications such as pills and liquids included discarding medications with the household trash (range 30% to 55%) and medication disposal products/bag (range 19% to 28%). More than half of the participants (50.4%) had unused prescription medication at home, 35% kept the medication for later use, and almost 20% of the participants reported sharing personal medications with others.

CONCLUSION: Although the majority of student participants had adequate knowledge of the appropriate methods for safe drug disposal, few reported using them for their own personal medications. The findings suggest there is a disconnect between the participants’ knowledge of the appropriate methods of safe drug storage and disposal in a professional setting and their own practices. Further research is needed to explore and address the reasons for this disconnect. Additionally, findings from this research will assist in the development of and/or the improvement of interdisciplinary educational materials among pharmacy and nursing students.

PMID:34583239 | DOI:10.1016/j.nedt.2021.105143

Mult Scler Relat Disord. 2021 Sep 21;56:103274. doi: 10.1016/j.msard.2021.103274. Online ahead of print.

ABSTRACT

BACKGROUND: multiple sclerosis (MS) is a complex disease sustained by several pathogenic mechanisms. As such, combination therapy strategies, targeting a range of disease mechanisms, might represent the ideal therapeutic approach. Here we investigated the efficacy of curcumin, a naturally occurring poly-phenolic phytochemical with potent anti-inflammatory and antioxidant properties, in subjects under treatment with IFN β-1a, to test the effects of this combination therapy on clinical and MRI parameters of inflammation and neurodegeneration in relapsing MS (RMS).

METHODS: eighty active RMS were prospectively enrolled, randomized (1:1) to either the IFN-curcumin or the IFN-placebo group and followed up longitudinally with clinical and MRI assessments for 24 months. Primary endpoint was the efficacy of curcumin versus placebo as add-on therapy on new/enlarging T2 lesions in RMS subjects under treatment with subcutaneous IFN β-1a 44 mcg TIW. Efficacy on clinical parameters (relapses and disability progression), other MRI parameters of inflammation (T1 Gd-enhancing lesions, combined unique active-CUA lesions) and neurodegeneration (T1-hypointense lesions, grey matter loss and white matter microstructural damage) as well as safety and tolerability of curcumin were explored as secondary endpoints.

RESULTS: ten subjects dropped out from the study by month 12 (6 in the IFN-curcumin group and 4 in the IFN-placebo group), and 27 by month 24 (11 in the IFN-curcumin group and 16 in the IFN-placebo group). Although no between-group difference was present in terms of proportion of subjects free from new/enlarging T2 lesions, a lower proportion of patients with CUA lesions was noted at month 12 in the IFN-curcumin group in comparison with the IFN-placebo group (7.5% vs 17.5%, χ² test p= 0.0167). This result was not confirmed at month 24. The statistical analysis failed to reveal any difference between the two treatment groups – IFN-curcumin and IFN-placebo – in terms of relapses, disability progression, other MRI metrics of inflammation and MRI changes suggestive of ongoing neurodegeneration. No difference in the rate and nature of adverse events was observed between the two treatment groups.

CONCLUSION: Although the study drop-out rate was too high to allow definite conclusions, our findings suggest that curcumin might add to IFN β-1a efficacy on radiological signs of inflammation in MS, while it did not seem to exert any neuroprotective effect as assessed by clinical and MRI parameters. (NCT01514370).

PMID:34583214 | DOI:10.1016/j.msard.2021.103274

Nutr Res. 2021 Aug 23;94:25-33. doi: 10.1016/j.nutres.2021.08.003. Online ahead of print.

ABSTRACT

The impact of myosteatosis on the outcomes of digestive malignancies has gained great attention recently. However, studies on the impact of myosteatosis show inconsistent results. We conducted a meta-analysis to clarify the relationship between myosteatosis and the overall survival of digestive cancer patients. The systematic literature search was conducted on PubMed/MEDLINE, Web of Science, and Embase from inception through March 27, 2021. Meta-analysis was performed using the random-effects model. Out of 3451 studies screened, 47 studies including 21,194 patients passed the screening criteria. The average prevalence of myosteatosis was 46.4%. Patients with myosteatosis had 44% increased mortality risk compared with non-myosteatosis patients (HR: 1.44, 95% CI: 1.33-1.55, P < .05). The predictive value of myosteatosis held regardless of country zone, study design, statistical model, Newcastle-Ottawa Scale (NOS) scores, treatment, sample size, and tumor stage. Nevertheless, the predictive value of myosteatosis was only evident for patients with esophagogastric cancers, cholangiocarcinoma/pancreatic cancers, or colorectal cancers. Overall, the results of this meta-analysis were robust based on sensitivity, subgroup, meta-regression, and trial sequential analyses and suggested that myosteatosis predicted worse overall survival (OS) in digestive malignancies patients.

PMID:34583210 | DOI:10.1016/j.nutres.2021.08.003

Atherosclerosis. 2021 Sep 23;335:62-67. doi: 10.1016/j.atherosclerosis.2021.09.026. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: The association of plasma trimethylamine N-oxide (TMAO) with atherosclerotic cardiovascular disease (ASCVD), diabetes mellitus (DM) and its determinants, as well as the role of TMAO as a predictor for short and long-term mortality, is still under discussion. We investigated associations between four plasma metabolites of the TMAO pathway and different clinical manifestations of atherosclerosis, diabetes determinants, and risk of short and long-term mortality in patients with stable ASCVD, acute myocardial infarction (AMI), cardiogenic shock (CS), and DM in three independent cohorts.

METHODS: TMAO and its dietary precursors were simultaneously quantified by liquid chromatography-tandem mass spectrometry in a total of 2655 participants of the German Leipzig Research Center for Civilization Diseases (LIFE)-Heart study, LIFE-Adult study, and the European Culprit Lesion Only PCI versus Multivessel PCI in Cardiogenic Shock (CULPRIT-SHOCK) multicenter trial. Associations with ASCVD manifestations, metabolic syndrome, 30-day mortality of patients with AMI and CS, and long-term mortality of subjects with suspected coronary artery disease (CAD) were analyzed.

RESULTS: TMAO plasma levels were not independently associated with stable ASCVD. Elevated TMAO plasma concentrations were independently associated with obesity (odds ratio, 1.23; p < 0.01) and DM (odds ratio, 1.37; p < 0.001) in LIFE-Heart. The latter association was confirmed in LIFE-Adult. We found no association of TMAO plasma levels with short-term mortality in patients with AMI and CS. However, TMAO plasma levels were independent predictors of long-term mortality in patients with suspected CAD (hazard ratio, 1.24; p < 0.05).

CONCLUSIONS: Potential proatherogenic mechanisms of TMAO seem to have no short-term effect in AMI. Presented associations with diabetes mellitus and obesity suggest that TMAO might have a functional role in metabolic syndrome.

PMID:34583200 | DOI:10.1016/j.atherosclerosis.2021.09.026