Treatment Recommendation for Dyspnea in Patients with Advanced Disease: Revised Clinical Guidelines from the Japanese Society for Palliative Medicine.

Dyspnea is one of the most common and distressing symptoms in patients with cancer and noncancer advanced diseases. The Japanese Society for Palliative Medicine revised previous guidelines for the management of respiratory symptoms in patients with cancer and newly developed clinical guidelines for managing dyspnea in patients with advanced disease, based on the result of systematic reviews for each clinical question and consensus among experts. We describe the recommendations of the guidelines as well as provide insights into the reasoning behind the recommendations and their development process. There has been a paucity of evidence regarding the interventions for dyspnea in patients with advanced disease. Thus, more clinical research that includes not only randomized controlled trials but also real-world observational studies is warranted.

Azo dye anaerobic treatment in anaerobic reactors coupled with PVA/Fe/Starch gel bead.

A novel bio-carrier, PVA/Fe/starch gel bead, was fabricated and developed to enhance the anaerobic treatment performance of synthetic azo dye-containing wastewater. PVA-gel beads with 5 % magnetite and 0.5 % starch were optimal for physical strength and treatment performance. A pair of 2 L-up-flow anaerobic sludge blankets (UASB), one with the bead (UB) and another without (U) as a controller, operated continuously at 30 °C and an HRT of 11-24 h for 302 days. UB showed better performance than U in most phases, especially with influent dye of 200 mg·L-1, suggesting a greater tolerance to dye toxicity of UB than U. Microbial analysis revealed that the PVA/Fe/starch gel beads successfully captured the dye degrader Clostridium. Diversity indices indicated that PVA/Fe/Starch gel beads effectively support microbial diversity and resilience under varying dye concentrations. Overall, these findings demonstrate the potential of PVA/Fe/Starch gel beads to improve the stability and efficiency of the dye treatment system.

Factors related to accurate clinicians' prediction of survival: an international multicenter study in East Asia.

PURPOSE: Recent guidelines for prognostic evaluation recommend clinicians' prediction of survival (CPS) for survival prediction in patients with advanced cancer. However, CPS is often inaccurate and optimistic. Studies on factors associated with overestimation or underestimation of CPS are limited. We aimed to investigate the factors associated with the overestimation and underestimation of CPS in patients with far-advanced cancer. METHODS: The current study was a secondary analysis of an international multicenter prospective cohort study, which enrolled newly admitted patients with advanced cancer in palliative care units (PCUs) in Japan, Korea, and Taiwan from 2017 to 2018. We obtained the temporal CPS at enrollment and performed multivariate logistic regression analysis to identify the factors associated with "underestimation (less than 33% of actual survival)" and "overestimation (more than 33% of actual survival)." RESULTS: A total of 2571 patients were assessed and admitted in 37 PCUs between January 2017 and September 2018. Older age (adjusted odds ratio [aOR] 1.01; 95% confidence interval [CI] 1.01-1.02; P < 0.01) and reduced oral intake (aOR 0.68; 95% CI 0.51-0.89; P < 0.01) were identified as significant factors associated with underestimation. Dyspnea (aOR 1.28; 95% CI 1.06-1.54; P = 0.01) and hyperactive delirium (aOR 1.34; 95% CI 1.05-1.72; P = 0.02) were identified as significant factors associated with overestimation. CONCLUSION: Older age was related to underestimation, while dyspnea and hyperactive delirium were related to overestimation of CPS for patients with weeks of survival. However, reduced oral intake was less likely to lead to underestimation.

Efficacy of lenvatinib and transarterial chemoembolization combination therapy in patients with hepatocellular carcinoma administered an insufficient dose of early lenvatinib.

Recently, the relationship between the relative dose intensity (RDI) and efficacy was demonstrated for lenvatinib therapy in patients with advanced hepatocellular carcinoma (HCC), with a higher RDI of lenvatinib monotherapy indicating a higher efficacy. However, not every patient can tolerate a high RDI during the course of treatment; therefore, add-on combination therapy may be necessary for patients requiring a low RDI. The addition of transarterial chemoembolization (TACE) to lenvatinib therapy improves clinical outcomes. Therefore, the aim of the present study was to compare the clinical outcomes of lenvatinib plus TACE (the LEN-TACE group) with those of lenvatinib alone (the LEN group) in patients with unresectable HCC with a high- or low-RDI. A total of 66 patients with advanced HCC were enrolled in the present retrospective study. Eligible patients were those who initiated lenvatinib monotherapy between April 2018 and September 2020. Of these patients, 29 had an 8-week RDI of ≥60%, 6 of which received LEN-TACE. A further 37 patients had an 8-week RDI of <60%, 7 of which received LEN-TACE. In the high-RDI group, both the radiological evaluations and the overall survival (OS) time were improved in those in the low-RDI group. In addition, the median OS of patients treated with LEN-TACE was longer compared with that of patients treated with lenvatinib alone in the low-RDI group (P=0.0467). Therefore, the results of the present study revealed that early TACE should be considered instead of continuing lenvatinib only treatment in patients receiving an insufficient dose of lenvatinib, such as those with an 8-week RDI of <60%.

Distinct comammox Nitrospira in high-rate down-flow hanging sponge reactor treating municipal wastewater.

A down-flow hanging sponge (DHS) reactor is a trickling filter system used for wastewater treatment, which employs sponges to retain biomass. This study assessed the process performance of a compact DHS combined with a sedimentation tank with seven phases at varying hydraulic retention times (HRT) over 500 days. The BOD of the DHS effluent was maintained at 4.0 ±â€¯0.5 mg·L-1 for the shortest HRT 0.3 ±â€¯0.1 h. The nitrification efficiency was considerably impacted by the reduced HRT, with NH4+-N and NO3--N concentrations of 9.0 ±â€¯1.2 mgN·L-1 and 2.2 ±â€¯0.5 mgN·L-1, respectively. Nevertheless, the effluent complied with effluent discharge standards throughout the trial period. The number of comammox 16S rRNA gene copies ranged from 5.58 to 13.2 × 107 copies·mL-1, indicating that sponges biomass retained carrier can provide favorable conditions for comammox growth and could contribute to nitrification in the high-rate DHS reactor.

Alternative magnetic field exposure suppresses tumor growth via metabolic reprogramming.

Application of physical forces, ranging from ultrasound to electric fields, is recommended in various clinical practice guidelines, including those for treating cancers and bone fractures. However, the mechanistic details of such treatments are often inadequately understood, primarily due to the absence of comprehensive study models. In this study, we demonstrate that an alternating magnetic field (AMF) inherently possesses a direct anti-cancer effect by enhancing oxidative phosphorylation (OXPHOS) and thereby inducing metabolic reprogramming. We observed that the proliferation of human glioblastoma multiforme (GBM) cells (U87 and LN229) was inhibited upon exposure to AMF within a specific narrow frequency range, including around 227 kHz. In contrast, this exposure did not affect normal human astrocytes (NHA). Additionally, in mouse models implanted with human GBM cells in the brain, daily exposure to AMF for 30 min over 21 days significantly suppressed tumor growth and prolonged overall survival. This effect was associated with heightened reactive oxygen species (ROS) production and increased manganese superoxide dismutase (MnSOD) expression. The anti-cancer efficacy of AMF was diminished by either a mitochondrial complex IV inhibitor or a ROS scavenger. Along with these observations, there was a decrease in the extracellular acidification rate (ECAR) and an increase in the oxygen consumption rate (OCR). This suggests that AMF-induced metabolic reprogramming occurs in GBM cells but not in normal cells. Our results suggest that AMF exposure may offer a straightforward strategy to inhibit cancer cell growth by leveraging oxidative stress through metabolic reprogramming.

Corallococcus caeni sp. nov., a novel myxobacterium isolated from activated sludge.

Two myxobacterial strains (KH5-1T and NO1) were isolated from the activated sludge tanks treating municipal sewage wastewater in Japan. These strains were recognised as myxobacteria based on their phenotypic characteristics of swarming colonies and fruiting bodies. Phylogenetic analyses using the 16S rRNA gene revealed that strains KH5-1T and NO1 were affiliated with the genus Corallococcus, with the closest neighbours being Corallococcus exercitus AB043AT (99.77% and 99.84%, respectively). Genome comparisons using orthologous average nucleotide identity (orthoANI) and digital DNA-DNA hybridisation similarity (dDDH) with strains KH5-1T and NO1 and their phylogenetically close relatives in Corallococcus spp. were below the thresholds. The major cellular fatty acids of strains KH5-1T and NO1 were iso-C15:0 (31.9%, 30.0%), summed feature 3 (comprising C16:1ω7c and/or C16:1ω6c) (20.2%, 17.7%), and iso-C17:0 (12.1%, 14.8%), and the major respiratory quinone was found to be menaquinone (MK)-8. Based on the phenotypic, chemotaxonomic, and phylogenetic evidence, strains KH5-1T and NO1 represent a new species in the genus Corallococcus, for which the proposed name is Corallococcus caeni sp. nov. The type strain is KH5-1T (= NCIMB 15510T = JCM 36609T).

Harnessing iron materials for enhanced decolorization of azo dye wastewater: A comprehensive review.

Highly colored azo dye-contaminated wastewater poses significant environmental threats and requires effective treatment before discharge. The anaerobic azo dye treatment method is a cost-effective and environmentally friendly solution, while its time-consuming and inefficient processes present substantial challenges for industrial scaling. Thus, the use of iron materials presents a promising alternative. Laboratory studies have demonstrated that systems coupled with iron materials enhance the decolorization efficiency and reduce the processing time. To fully realize the potential of iron materials for anaerobic azo dye treatment, a comprehensive synthesis and evaluation based on individual-related research studies, which have not been conducted to date, are necessary. This review provides, for the first time, an extensive and detailed overview of the utilization of iron materials for azo dye treatment, with a focus on decolorization. It assesses the treatment potential, analyzes the influencing factors and their impacts, and proposes metabolic pathways to enhance anaerobic dye treatment using iron materials. The physicochemical characteristics of iron materials are also discussed to elucidate the mechanisms behind the enhanced bioreduction of azo dyes. This study further addresses the current obstacles and outlines future prospects for industrial-scale application of iron-coupled treatment systems.

Development of an internal two-stage upflow anaerobic reactor integrating biostimulation strategies to enhance the degradation of aromatic compounds in wastewater from purified terephthalic acid and dimethyl terephthalate manufacturing processes.

In this study, we aimed to establish high-rate biological treatment of purified terephthalic acid (PTA) and dimethyl terephthalate (DMT) wastewater that minimizes the inhibitory effects of high concentration benzoate and acetate. To achieve this, we developed a novel bioreactor system and biostimulation strategy. An internal two-stage upflow anaerobic (ITUA) reactor was operated with (i) a packed bed containing green tuff medium underlying (ii) a compartment seeded with anaerobic granular sludge. Ethylene glycol was amended to stimulate syntrophic interactions. Continuous operation of the system for 1,026 days achieve an organic removal rate of 11.0 ± 0.6 kg COD/m3/d. The abundance of aromatic degraders significantly increased during operation. Thus, we successfully developed a high-rate treatment system to treat wastewater from the PTA/DMT manufacturing processes by activating syntrophs in an ITUA reactor.

Relationship between Lipoprotein Lipase Derived from Subcutaneous Adipose Tissue and Cardio-Ankle Vascular Index in Japanese Patients with Severe Obesity.

INTRODUCTION: Cardio-ankle vascular index (CAVI) is an arterial stiffness index that correlates inversely with body mass index (BMI) and subcutaneous fat area. Lipoprotein lipase (LPL) that catalyzes the hydrolysis of serum triglycerides is produced mainly in adipocytes. Serum LPL mass reflects LPL expression in adipose tissue, and its changes correlate inversely with changes in CAVI. We hypothesized that LPL derived from subcutaneous adipose tissue (SAT) suppresses the progression of arteriosclerosis and examined the relationship of LPL gene expression in different adipose tissues and serum LPL mass with CAVI in Japanese patients with severe obesity undergoing laparoscopic sleeve gastrectomy (LSG). METHODS: This study was a single-center retrospective database analysis. Fifty Japanese patients who underwent LSG and had 1-year postoperative follow-up data were enrolled (mean age 47.5 years, baseline BMI 46.6 kg/m2, baseline HbA1c 6.7%). SAT and visceral adipose tissue (VAT) samples were obtained during LSG surgery. LPL gene expression was analyzed by real-time PCR. Serum LPL mass was measured by ELISA using a specific monoclonal antibody against LPL. RESULTS: At baseline, LPL mRNA expression in SAT correlated positively with serum LPL mass, but LPL mRNA expression in VAT did not. LPL mRNA expression in SAT was correlated, and serum LPL mass tended to correlate inversely with the number of metabolic syndrome symptoms, but LPL mRNA expression in VAT did not. LPL mRNA expression in SAT and CAVI tended to correlate inversely in the group with visceral-to-subcutaneous fat ratio of 0.4 or higher, which is considered metabolically severe. Serum LPL mass increased 1 year after LSG. Change in serum LPL mass at 1 year after LSG tended to be an independent factor inversely associated with change in CAVI. CONCLUSIONS: Serum LPL mass reflected LPL mRNA expression in SAT in Japanese patients with severe obesity, and LPL mRNA expression in SAT was associated with CAVI in patients with visceral obesity. The change in serum LPL mass after LSG tended to independently contribute inversely to the change in CAVI. This study suggests that LPL derived from SAT may suppress the progression of arteriosclerosis.

Draft genome sequences of Corallococcus strains KH5-1 and NO1, isolated from activated sludge.

Myxobacteria are known as prolific producers of secondary metabolites with a unique and wide spectrum of bioactivities. Here, we report draft genome sequences of KH5-1 and NO1, myxobacteria isolated from activated sludge, which consist of 9.89 and 9.86 Mb, both of which have G + C contents of 70.7%.

Improved Symptom Change Enhances Quality of Dying in Patients With Advanced Cancer: An East Asian Cross-Cultural Study.

BACKGROUND: Symptom burdens tend to increase for patients with cancer and their families over the disease trajectory. There is still a lack of evidence on the associations between symptom changes and the quality of dying and death. In this context, this research investigated how symptom changes influence the quality of dying and death. METHODS: This international prospective cohort study (the East Asian Collaborative Cross-Cultural Study to Elucidate the Dying Process (EASED), 2017-2019) included 22, 11, and 4 palliative care units across Japan, South Korea, and Taiwan. Eligible participants were adults (Japan and Korea, ≥18 years; Taiwan, ≥20 years) with locally advanced or metastatic cancer. Physical and psychological symptoms were assessed by physicians upon admission and within 3 days before death. Death quality was assessed using the Good Death Scale (GDS), developed in Taiwan. Univariate and multivariate regression analyses were used to identify correlations between symptom severity changes and GDS scores. RESULTS: Among 998 patients (542 [54.3%] men and 456 [45.7%] women; mean [SD] age = 70.1 [± 12.5] years), persistent dyspnea was associated with lower GDS scores when compared to stable dyspnea (ß = -0.427, 95% CI = -0.783 to -0.071). Worsened (-1.381, -1.932 to -0.831) and persistent (-1.680, -2.701 to -0.659) delirium were also significantly associated with lower GDS scores. CONCLUSIONS: Better quality of dying and death was associated with improved symptom control, especially for dyspnea and delirium. Integrating an outcome measurement for the quality of dying and death is important in the management of symptoms across the disease trajectory in a goal-concordant manner.

Malodour from oral malignant fungating wound: sprayed metronidazole - case report.

Metronidazole gel or ointment is recommended for the treatment of malodour from malignant fungating wounds. However, this medication may not settle adequately in oral lesions because its texture causes discomfort and it tends to be washed out by saliva. We report a case of malodour due to an oral lesion that was well controlled with sprayed metronidazole.

Malignancy-related ascites in palliative care units: prognostic factor analysis.

OBJECTIVES: The prognostic factors in patients with malignancy-related ascites (MA) have been poorly investigated. This study aimed to evaluate both the prognostic impact of MA on terminally ill patients with cancer and the prognostic factors in those with MA. METHODS: This was a post hoc analysis of a multicentre, prospective cohort study. Patients with advanced cancer admitted to palliative care units at 23 institutions and aged≥18 years were enrolled between January and December 2017. Overall survival (OS) was compared according to MA. A multivariate analysis was conducted to explore prognostic factors in patients with MA. RESULTS: Of 1896 eligible patients, gastrointestinal and hepatobiliary pancreatic cancers accounted for 42.5%. 568 (30.0%) of the total had MA. Patients with MA had significantly shorter OS than those without MA (median, 14 vs 22 days, respectively; HR, 1.55; 95% CI, 1.39 to 1.72; p<0.01). A multivariate analysis showed that MA was a poor prognostic factor (HR, 1.30; 95% CI, 1.13 to 1.50; p<0.01) and that among patients with MA, significant poor prognostic factors were liver metastasis, moderately to severely reduced oral intake, delirium, oedema, gastric cancer, high serum creatinine, high serum C reactive protein, high serum total bilirubin, dyspnoea and fatigue, while significant good prognostic factors were female sex, good performance status, high serum albumin and colorectal cancer. CONCLUSIONS: MA had a negative impact on survival in terminally ill patients with cancer. A multivariate analysis revealed several prognostic factors in patients with terminal cancer and MA.

How different are accuracies of clinicians' prediction of survival by assessment methods?

BACKGROUND: No standardized method has been established for evaluating the accuracy of a clinicians' prediction of survival (CPS). Till now, no study has compared the accuracy of CPS according to the evaluation methods using the same dataset. We aimed to examine the accuracy of CPS by different statistical approaches in patients with far-advanced cancer. METHODS: The current study was a secondary analysis of an international multicenter prospective cohort study. Newly admitted patients with advanced cancer were enrolled in palliative care units (PCUs) in Japan, Korea, and Taiwan. We obtained the temporal CPS at enrollment. The patients were classified into groups of days (≤7 days) and weeks (≤30 days) based on CPS and actual survival (AS). We evaluated the accuracy of CPS by the distribution, area under the receiver operating characteristics curve (AUROCs), and an estimate ±33% of AS. RESULTS: A total of 2,571 patients were assessed and admitted in 37 PCUs between January 2017 and September 2018. As for the "days" category, the distribution of AS is larger than that of CPS, however, the results are reversed in the "weeks" category. The AUROCs showed over 80% discrimination for both the "days" and "weeks" categories. Accurate CPS within ±33% of AS was approximately 30% in both "days" and "weeks" categories. CONCLUSIONS: We showed a discrepancy of approximately 30-80% in the accuracy of CPS among three different analysis methods: distribution, AUROC, and AS comparison. Considering the low accuracy of AS comparisons, clinicians should provide a wide range of survival time. CPS was able to effectively discriminate and may be useful for risk stratification.

Symptoms and Prognoses of Patients With Breast Cancer and Malignant Wounds in Palliative Care Units: The Multicenter, Prospective, Observational EASED Study.

BACKGROUND: This study sought to investigate the symptoms and prognoses of patients with breast cancer and malignant wounds in the palliative care unit setting. METHODS: This study was a sub-group analysis of a multicenter, prospective, observational study. Patients admitted to 23 palliative care units in Japan between January and December 2017 were enrolled. Data of patients with breast cancer were extracted. We compared demographic characteristics, symptoms, and prognoses by breast cancer malignant wound status. The primary outcome was overall survival. Secondary outcomes included Palliative Prognostic Index (PPI) score, malignant wound characteristics, and symptom burden. RESULTS: Of 1896 patients, 131 (6.9%) had breast cancer. In this cohort, 44 (33.6%) patients had malignant wounds. Most malignant wounds (88%) were on the back and chest. Malignant wounds were associated with skin redness, erosion, necrosis, or fistula. Symptoms included bleeding, exudate, odor, and pain. Twenty-eight patients (63.6%) needed dressing changes and 14 (31.8%) patients experienced bleeding. None died due to bleeding. In the malignant wounds group, 32 (72.8%) patients had used an opioid dose equivalent to 38 mg of oral morphine daily, compared to 25 mg by 57 (65.5%) patients in the non-malignant wounds group (P = .26). Median PPI scores at hospital admission were 4.5 vs 6.5 (P = .08). Median survival was 23 vs 21 days (P = .48). CONCLUSIONS: Patients with malignant wounds had a distinct symptom burden profile and tended to use a higher dose of opioids. The effect of malignant wounds on survival was unclear.

Estrogenic control of reward prediction errors and reinforcement learning.

Gonadal hormones act throughout the brain 1 , and nearly all neuropsychiatric disorders vary in symptom severity with hormonal fluctuations over the reproductive cycle, gestation, and perimenopause 2-4 . Yet the mechanisms by which hormones influence mental and cognitive processes are unclear. Exogenous estrogenic hormones modulate dopamine signaling in the nucleus accumbens core (NAcc) 5,6 , which instantiates reward prediction errors (RPEs) for reinforcement learning 7-16 . Here we show that endogenous estrogenic hormones enhance RPEs and sensitivity to previous rewards by regulating expression of dopamine reuptake proteins in the NAcc. We trained rats to perform a temporal wagering task with different reward states; rats adjusted how quickly they initiated trials across states, balancing effort against expected rewards. Dopamine release in the NAcc reflected RPEs that predicted and causally in-fluenced subsequent initiation times. When fertile, females more quickly adjusted their initiation times to match reward states due to enhanced dopaminergic RPEs in the NAcc. Proteomics revealed reduced expression of dopamine transporters in fertile stages of the reproductive cycle. Finally, genetic suppression of midbrain estrogen receptors eliminated hormonal modulation of behavior. Estrogenic hormones therefore control the rate of reinforcement learning by regulating RPEs via dopamine reuptake, providing a mechanism by which hormones influence neural dynamics for motivation and learning.

Relationship of serum lipid parameters with kidney function decline accompanied by systemic arterial stiffness: a retrospective cohort study.

Background: Dyslipidemia is associated with kidney function decline (KFD), although the non-linear relationship of lipid parameters to KFD has not been fully elucidated. We aimed to determine the detailed relationship of baseline lipid parameters with KFD, considering the mediation of arterial stiffness. Methods: A total of 27 864 urban residents with estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 at baseline, who participated in a median of three (range two to eight) consecutive annual health examinations were studied. Arterial stiffness was assessed by cardio-ankle vascular index (CAVI). KFD was defined as development of eGFR <60 mL/min/1.73 m2. Results: During the study period, 1837 participants (6.6%) developed KFD. Receiver operating characteristic analysis determined that the cutoff values independently associated with KFD are 123 mg/dL for low-density lipoprotein cholesterol (LDL-C) [area under the curve (95% confidence interval) 0.570 (0.557-0.583)], 65 mg/dL for high-density lipoprotein cholesterol (HDL-C) [0.552 (0.539-0.566)], 82 mg/dL for triglycerides (TG) [0.606 (0.593-0.618)] and 1.28 for TG/HDL-C ratio [0.600 (0.587-0.612)]. These cut-offs were independently associated with KFD in Cox analysis. Regarding the contribution of each lipid parameter to KFD, a linear relationship was observed for both TG and TG/HDL-C, and a U-shaped relationship for HDL-C. A adjusted mediating effect of CAVI on the relationship of TG or TG/HDL-C ratio with KFD was observed (mediating rate: 2.9% in TG, 2.5% in TG/HDL-C ratio). Regarding the association to KFD, a linear relationship was observed for both TG and TG/HDL-C, and a U-shaped relationship for HDL-C. A mediating effect of CAVI on the relationship of TG or TG/HDL-C ratio with KFD was observed after adjustment for confounders. Conclusions: TG and TG/HDL-C ratio related linearly to KFD and this was partially mediated by CAVI. A U-shaped relationship was observed between HDL-C and KFD risk. LDL-C showed no significant association. Further study should investigate whether intensive TG-lowering treatment prevents KFD via decreasing CAVI.

Vagus Nerve Ultrasonography Helps Distinguish Multiple System Atrophy from Other Parkinsonian Syndromes.

Background: Distinguishing multiple system atrophy from other parkinsonian syndromes is challenging. Objectives: To evaluate vagus nerve ultrasonography for differentiating parkinsonian syndromes. Methods: A single-center, cross-sectional, observational study assessed 85 consecutive adult patients with de novo parkinsonism between June 2020 and December 2022, using 12 MHz ultrasonography of the vagus nerve cross-sectional area. Results: Bilateral vagus nerves were smaller in multiple system atrophy than in other parkinsonian syndromes. The area under the receiver operating characteristic curve for differentiating multiple system atrophy was 0.79 on the right side and 0.74 on the left. The cut-off values to diagnose multiple system atrophy were 0.71 and 0.86 mm2 on the right and left sides, respectively, with sensitivities of 82.6% and 87.0%, specificities of 74.2% and 64.5%, positive predictive values of 54% and 47.6%, and negative predictive values of 92.0% and 93.0%. Conclusions: Vagus nerve ultrasonography may differentiate multiple system atrophy from other parkinsonian syndromes.