Dry anaerobic co-digestion of roadside grass and cattle manure at a 60 L batch pilot scale.

Roadside grass cuttings and solid cattle manure are resources that are available as input for dry anaerobic co-digestion. Two series of measurements were carried out, one in June 2016 and one in October 2016. The methane potentials were determined on a laboratory scale and revealed a high degree of seasonality, 202.9 and 167.9 Nm3CH4.tVS-1, respectively. Moreover, these substrates were co-digested in reactors by the dry process on a pilot scale (60 L). Two strategies for filling and optimization, as layers or as a mixture, were compared. The seasonality also determined the physicochemical parameters and the hydrodynamic properties involved in percolation of the liquid phase recirculated in the dry digestion process. The production of methane depended on the filling method, the seasonality, and the nature of the input, which in some cases resulted in inhibition of 34.8-44.4 Nm3CH4.tVS-1.

Endocannabinoids participate in placental apoptosis induced by hypoxia inducible factor-1.

During pregnancy, apoptosis is a physiological event critical in the remodeling and aging of the placenta. Increasing evidence has pointed towards the relevance of endocannabinoids (ECs) and hypoxia as modulators of trophoblast cell death. However, the relation between these factors is still unknown. In this report, we evaluated the participation of ECs in placental apoptosis induced by cobalt chloride (CoCl2), a hypoxia mimicking agent that stabilizes the expression of hypoxia inducible factor-1 alpha (HIF-1α). We found that HIF-1α stabilization decreased FAAH mRNA and protein levels, suggesting an increase in ECs tone. Additionally, CoCl2 incubation and Met-AEA treatment reduced cell viability and increased TUNEL-positive staining in syncytiotrophoblast layer. Immunohistochemical analysis demonstrated Bax and Bcl-2 protein expression in the cytoplasm of syncytiotrophoblast. Finally, HIF-1α stabilization produced an increase in Bax/Bcl-2 ratio, activation of caspase 3 and PARP cleavage. All these changes in apoptotic parameters were reversed with AM251, a CB1 antagonist. These results demonstrate that HIF-1α may induce apoptosis in human placenta via intrinsic pathway by a mechanism that involves activation of CB1 receptor suggesting a role of the ECs in this process.

Increased Expression of Aquaporin 9 in Trophoblast From Gestational Diabetic Patients.

Gestational diabetes mellitus is the most frequent pathophysiological alteration in pregnancy, increasing the incidence of complications in both mother and fetus. The macrosomia that occurs in these fetuses may be related with some changes in nutrient transport mechanism in placenta. The presence of aquaporin 9, an aquaglyceroporin, has previously been demonstrated in placenta. We raised the question whether aquaporin 9 expression may be upregulated in placenta from gestational diabetes, thus providing a faster transport of glycerol and water through placenta. We studied 21 placentas (13 controls and 8 gestational diabetes) from cesarean delivery at term. The expression of aquaporin 9 was analyzed by quantitative PCR, immunoblot, and immunohistochemistry. The median values from quantitative PCR were compared by nonparametric tests for independent samples (Mann-Whitney U-test). We have found that trophoblast from gestational diabetes express higher amount of aquaporin 9, which was found statistically significant (p<0.05). The increase in aquaporin 9 expression was confirmed by immunoblot, and localization in the syncytiotrophoblast was checked by immunohistochemistry. The increase in aquaporin 9 expression in placenta from gestational diabetes may contribute to the higher transport rate in this pathology of pregnancy.

Placental programmed cell death: insights into the role of aquaporins.

STUDY HYPOTHESIS: Are the placental aquaporins (AQPs) involved in the apoptosis of human trophoblast? STUDY FINDING: The general blocking of placental AQPs with HgCl2 and, in particular, the blocking of AQP3 activity with CuSO4 abrogated the apoptotic events of human trophoblast cells. WHAT IS KNOWN ALREADY: Although apoptosis of trophoblast cells is a natural event involved in the normal development of the placenta, it is exacerbated in pathological processes, such as pre-eclampsia, where an abnormal expression and functionality of placental AQPs occur without alterations in the feto-maternal water flux. Furthermore, fluctuations in O2 tension are proposed to be a potent inducer of placental apoptotic changes and, in explants exposed to hypoxia/reoxygenation (H/R), transcellular water transport mediated by AQPs was undetectable. This suggests that AQPs might be involved in processes other than water transport, such as apoptosis. STUDY DESIGN, SAMPLES/MATERIALS, METHODS: Explants from normal term placentas were maintained in culture under conditions of normoxia, hypoxia and H/R. Cell viability was determined by assessing 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide incorporation. For the general or specific inhibition of AQPs, 0.3 mM HgCl2, 5 mM CuSO4, 0.3 mM tetraethylammonium chloride (TEA) or 0.5 mM phloretin were added to the culture medium before explants were exposed to each treatment. Oxidative stress parameters and apoptotic indexes were evaluated in the presence or absence of AQPs blockers. AQP3 expression was confirmed by western blot and immunohistochemistry. MAIN RESULTS AND THE ROLE OF CHANCE: First, we observed that in H/R treatments cell viability decreased by 20.16 ± 5.73% compared with those explants cultured in normoxia (P = 0.009; n = 7). Hypoxia did not modify cell viability significantly. Both hypoxia and H/R conditions induced oxidative stress. Spontaneous chemiluminescence and thiobarbituric acid reactive substance levels were significantly increased in explants exposed to hypoxia (n = 6 per group, P = 0.0316 and P = 0.0009, respectively) and H/R conditions (n = 6 per group, P = 0.0281 and P = 0.0001, respectively) compared with those cultured in normoxia. Regarding apoptosis, H/R was a more potent inducer of trophoblast apoptosis than hypoxia alone. Bax expression and the number of apoptotic nuclei were significantly higher in explants cultured in H/R compared with normoxia and hypoxia conditions (n = 12, P = 0.0135 and P = 0.001, respectively). DNA fragmentation was only observed in H/R and, compared with normoxia and hypoxia, the activity of caspase-3 was highest in explants cultured in H/R (n = 12, P = 0.0001). In explants exposed to H/R, steric blocking of AQP activity with HgCl2 showed that DNA degradation was undetectable (n = 12, P = 0.001). Bax expression and caspase-3 activity were drastically reduced (n = 12, P = 0.0146 and P = 0.0001, respectively) compared with explants cultured in H/R but not treated with HgCl2. Similar results were observed in explants exposed to H/R when we blocked AQP3 activity with CuSO4. DNA degradation was undetectable and the number of apoptotic nuclei and caspase-3 activity were significantly decreased compared with explants cultured in H/R but not treated with CuSO4 (n = 12, P = 0.001 and P = 0.0001, respectively). However, TEA and phloretin treatments, to block AQP1/4 or AQP9, respectively, failed in abrogate apoptosis. In addition, we confirmed the expression and localization of AQP3 in explants exposed to H/R. LIMITATIONS, REASONS FOR CAUTION: Our studies are limited by the number of experimental conditions tested, which do not fully capture the variability in oxygen levels, duration of exposure and alternating patterns of oxygen seen in vivo. WIDER IMPLICATIONS OF THE FINDINGS: Our results suggest that any alteration in placental AQP expression might disturb the equilibrium of the normal apoptotic events and may be an underlying cause in the pathophysiology of placental gestational disorders such as pre-eclampsia. Furthermore, the dysregulation of placental AQPs may be one of the crucial factors in triggering the clinical manifestations of pre-eclampsia. LARGE SCALE DATA: n/a. STUDY FUNDING AND COMPETING INTERESTS: This study was supported by UBACyT 20020090200025 and 20020110200207 grants and PIP-CONICET 11220110100561 grant, and the authors have no conflict of interest to declare.

Melanoma detection in Italian pigmented lesion clinics.

AIM: Accuracy in melanoma detection is important to recognize early curable melanomas and to minimize the unnecessary excision of benign lesions. The aim of this paper was to evaluate melanoma screening accuracy of Italian pigmented lesion clinics in terms of number needed to excise (NNE), melanoma thickness, and number of melanomas diagnosed during patient follow-up. METHODS: Information on all skin tumors excised in 2011 were extracted from the databases of the participating centers. Information whether the lesion was excised at the baseline examination or during patient follow-up was recorded, as well as the overall number of patients examined in each center in 2011. RESULTS: After e-mail solicitation, 22 of 40 centers agreed to participate. A total of 8229 excised lesions were collected. The overall number of examined patients was 86.564, thus 9.5% of screened patients had a lesion removed. Of the excised lesions, 866 were diagnosed as melanoma (1% of examined patients) and 5311 (88.9%) were melanocytic nevi. Three NNE were calculated giving values of 7.9 excised lesions to find 1 melanoma, 7.1 melanocytic lesions to find 1 melanoma, and 3.7 lesions to find 1 skin malignancy. The median melanoma thickness was 0.6 mm, with only 15.1% of melanomas ≥ 1 mm of thickness. Melanomas detected over time were 96 (11.1%; mean thickness, 0.3 mm), with 15.6% of lesions excised after short-term follow-up and 84.4% after long-term follow-up. CONCLUSION: The NNE values comparable to those achieved in specialized clinical settings and the high number of early melanomas diagnosed at the baseline examination or during patient follow-up indicate a high level of accuracy in melanoma screening achieved by Italian pigmented lesion clinics.

Reduced expression of Na⁺/H⁺ exchanger isoform 3 (NHE-3) in preeclamptic placentas.

Although the etiology of preeclampsia is unknown, accumulated evidence suggests that the expression of a variety of syncytiotrophoblast transporters is reduced or abnormal. Here, we have examined the expression of NHE-3 in preeclamptic placentas. We found that NHE-3 expression significantly decreased and its labeling was almost undetectable in the cytosol of syncytiotrophoblast cells. Even though the inductor mechanisms of NHE-3 decrease are not clear yet, we speculated that alterations in TNF-α and aldosterone levels observed in preeclampsia might be downregulating NHE-3 expression. Further studies are needed to define whether these alterations play a direct role either in the pathogenesis or in the adaptative response of preeclampsia.

Oxygen tension modulates AQP9 expression in human placenta.

UNLABELLED: Placental hypoxia has been implicated in pregnancy pathologies such as preeclampsia. We have previously reported that AQP9 is highly expressed in syncytiotrophoblast from normal placentas and shows an overexpression in preeclamptic placentas, with a lack of functionality for water transport. Up to now, the response of AQP9 to changes in the oxygen tension in trophoblast cells is still unknown. OBJECTIVE: Our aim was to establish whether alterations in oxygen levels may modulate AQP9 expression in human placenta. METHODS: A theoretical analysis of the human AQP9 gene to find conserved DNA regions that could serve as putative HIF-1 binding sites. Then, explants from normal placentas were cultured at different concentrations of oxygen or with 250 µM CoCl2. AQP9 molecular expression and water uptake was determined. RESULTS: Fourteen consensus HIF-1 binding sites were found in the human AQP9 gene, but none of them in the promoter region. However, placental AQP9 decreased abruptly when HIF-1α is expressed by deprivation of oxygen or CoCl2 stabilization. In contrast, after reoxygenation, HIF-1α was undetectable while AQP9 increased significantly and changed its cellular distribution, showing the same pattern as that previously described in preeclamptic placentas. Accordingly with the decrease in AQP9 expression, water uptake decreased in explants exposed to hypoxia or treated with CoCl2. Conversely as we expected, after reoxygenation, water uptake decreased dramatically compared to the control and was not sensitive to HgCl2. CONCLUSION: Our findings suggest that oxygen tension may modulate AQP9 expression in human placenta. However, the role of AQP9 still remains uncertain.

Differential expression of endocannabinoid system in normal and preeclamptic placentas: effects on nitric oxide synthesis.

Anandamide (AEA) is a lipid mediator that participates in the regulation of several reproductive functions. This study investigated the endocannabinoid system in normal (NP) and preeclamptic (PE) placentas, and analyzed the potential functional role of AEA in the regulation of nitric oxide synthesis. The protein expression and localization of NAPE-PLD, FAAH and CB1 receptor were analyzed in normal and preeclamptic pregnancies using immunoblotting and immunohistochemistry. NAPE-PLD expression was shown to be significantly higher (p < 0.05) in PE tissues than in NP. In contrast, a decrease in FAAH protein (p < 0.001) was detected in placentas collected from women with preeclampsia. Both enzymes were mainly located in the syncytiotrophoblasts from normal and preeclamptic tissues. No differences were seen in CB1 receptor from both groups of placental villous. Exogenous and endogenous AEA significantly increased NOS activity. Although pre-incubation with AM251 (CB1 antagonist) had no effect, co-incubation with both AEA and AM251 diminished NOS activity from normal term placentas. We observed increased NOS activity in placental villous from women with preeclampsia compared with normotensive pregnant women. Furthermore, NOS activity from preeclamptic tissues was diminished by co-treatment with AM251, illustrating that the NO levels could be modulated by AEA. These data suggest that AEA may be one of the factors involved in the regulation of NOS activity in normal and preeclamptic placental villous. Interestingly, the differential expression of NAPE-PLD and FAAH suggests that AEA could play an important role in the pathophysiology of PE.

Evidence for insulin-mediated control of AQP9 expression in human placenta.

UNLABELLED: The AQP9 gene contains a negative insulin response element, suggesting that it may be modulated by insulin. Previously, we reported AQP9 overexpression in preeclamptic placentas but a lack of functionality of AQP9 in water and mannitol transport. We also observed high serum levels of insulin and TNF-α in preeclamptic women. OBJECTIVE: To evaluate whether AQP9 expression is regulated by insulin in the human placenta, and whether the dysregulation of AQP9 observed in preeclamptic placentas may be related to the inability to respond to insulin stimuli. METHODS: Explants from normal and preeclamptic placentas were cultured at different concentrations of insulin. Treatment with TNF-α was used to induce phosphorylation of insulin receptor substrate (IRS), which may desensitize insulin action. AQP9 molecular expression and water uptake was determined. RESULTS: Insulin decreased the molecular expression of AQP9 exclusively in explants from normal placentas in a concentration-dependent manner. Treatment with TNF-α previous to insulin addition prevented these changes. Moreover, insulin treatment did not modify water uptake neither its sensitivity to HgCl(2.) CONCLUSION: AQP9 water permeability seems to be independent of its molecular expression, strongly suggesting that AQP9 might not have a key role in water transport in human placenta. We also propose another mechanism of down-regulation of AQP9 molecular expression mediated by insulin in a concentration-dependent manner in human placenta and provide new evidence that in preeclamptic placentas the mechanisms of insulin signaling may be altered, producing an overexpression of AQP9 that does not correlate with an increase in its functionality.

IFPA Meeting 2010 Workshop Report I: Immunology; ion transport; epigenetics; vascular reactivity; epitheliochorial placentation; proteomics.

Workshops are an important part of the IFPA annual meeting. At IFPA Meeting 2010 there were twelve themed workshops, six of which are summarized in this report. 1. The immunology workshop focused on normal and pathological functions of the maternal immune system in pregnancy. 2. The transport workshop dealt with regulation of ion and water transport across the syncytiotrophoblast of human placenta. 3. The epigenetics workshop covered DNA methylation and its potential role in regulating gene expression in placental development and disease. 4. The vascular reactivity workshop concentrated on methodological approaches used to study placental vascular function. 5. The workshop on epitheliochorial placentation covered current advances from in vivo and in vitro studies of different domestic species. 6. The proteomics workshop focused on a variety of techniques and procedures necessary for proteomic analysis and how they may be implemented for placental research.

Review: Water channel proteins in the human placenta and fetal membranes.

It has been established that the permeability of the human placenta increases with advancing gestation. Indirect evidence has also proposed that aquaporins (AQPs) may be involved in the regulation of placental water flow but the mechanisms are poorly understood. Five AQPs have been found in the human placenta and fetal membranes [AQP1, 3, 4, 8 and 9]. However, the physiological function(s) and the regulation of these proteins remain unknown. Emerging evidence has shown that human fetal membrane AQPs may have a role in intramembranous amniotic fluid water regulation and that alterations in their expression are related to polyhydramnios and oligohydramnios. In addition, we have observed a high expression of AQP3 and AQP9 in the apical membrane of the syncytiotrophoblast. Moreover, AQP9 was found to be increased in preeclamptic placentas, but it could not be related to its functionality for the transport of water and mannitol. However, a significant urea flux was seen. Since preeclampsia is not known to be associated with an altered water flux to the fetus we propose that AQP9 might not have a key role in water transport in human placenta, but a function in the energy metabolism or the urea uptake and elimination across the placenta. However, the role of AQP9 in human placenta is still speculative and needs further studies. Insulin, hCG, cAMP and CFTR have been found to be involved in the regulation of the molecular and functional expression of AQPs. Further insights into these mechanisms may clarify how water moves between the mother and the fetus.

CFTR may modulate AQP9 functionality in preeclamptic placentas.

UNLABELLED: Preeclampsia (PE) is a hypertensive disorder unique to human pregnancy. Although its causes remain unclear, it is known that altered placental villous angiogenesis and a poorly developed fetoplacental vasculature can affect the transport functions of the syncytiotrophoblast (hST). We have previously observed that in preeclamptic placentas there is an increase in AQP9 protein expression, with a lack of functionality. Up to now, the mechanisms for AQP9 regulation and the role of AQP9 in the human placenta remain unknown. However, there is strong evidence that the cystic fibrosis transmembrane conductance regulator (CFTR) regulates AQP9 functionality. OBJECTIVE: Here, we studied CFTR expression and localization in hST from preeclamptic placentas in order to investigate if alterations in CFTR may be associated with the lack of activity of AQP9 observed in PE. METHODS: The expression of CFTR in normal and preeclamptic placentas was determined by Western Blot and immunohistochemistry, and CFTR-AQP9 co-localization was determined by immunoflurescence. Water uptake experiments were performed using explants from human normal term and preeclamptic placentas treated with CFTR inhibitors. RESULTS: We found that CFTR expression significantly decreased in preeclamptic placentas, and that the hST apical labeling almost disappeared, losing its co-localization with AQP9. Functional experiments demonstrated that water uptake diminished in normal term explants incubated with CFTR inhibitors. CONCLUSIONS: These results suggest that CFTR expression decreases in preeclampsia and may thus be implicated in the regulation of AQP9 activity.

Functional and molecular expression of AQP9 channel and UT-A transporter in normal and preeclamptic human placentas.

Transcellular flux of urea across human placenta may be facilitated by aquaglyceroporins and/or by urea transporters (UT). Previously we have reported the presence of AQP3 and AQP9 in the syncytiotrophoblast of human term placenta (hST). In the present study, we detected a significant uptake of water, urea and mannitol sensitive to mercury and phloretin in explants from normal term placenta, which indicates a functional AQP9. In addition, we observed an increase of AQP9 expression in preeclamptic placenta with a lack of functionality of AQP9 for water and mannitol. Our data showed a molecular and functional expression of UT-A in hST from normal and preeclamptic placentas. In the last case, urea uptake sensitive to phloretin and mercury increased and the UT-A protein seems to be augmented. These results suggest that the increase of urea uptake in preeclamptic pregnancies could be attributed to an increase of expression of UT-A more than AQP9 proteins. In conclusion, our results provide new evidences that suggest the involvement of AQP9 and UT-A in the urea excretion mechanism across hST from mother to fetus in physiological conditions. Much further work is needed to define whether the overexpression of AQP9 plays a direct role either in the pathogenesis or in the adaptative response of preeclampsia.

Water channel proteins AQP3 and AQP9 are present in syncytiotrophoblast of human term placenta.

The syncytiotrophoblast of human term placenta (HST) is a continuous, multinucleated structure with minimal tight junctions, which results from the fusion of the underlying cytotrophoblast cells. Consequently, the transport of metabolites, ions and water from mother to fetus could take place primarily via transcellular routes. Transcellular water flux may be facilitated by aquaporins, membrane proteins functioning as water channels that are widely expressed in cells and tissues. Here, we report the presence of AQP3 and AQP9 in the apical membranes of HST using RT-PCR, immunoblotting and immunohistochemistry. Since AQP3 is not only a water channels, but also permits the rapid passage of both urea and glycerol, while AQP9 also mediates the passage of carbamides, polyols, purines, and pyrimidines, we have speculated that these proteins could be involved in the transport of water and solutes from mother to fetus.

Polycystin-2, the protein mutated in autosomal dominant polycystic kidney disease (ADPKD), is a Ca2+-permeable nonselective cation channel.

Defects in polycystin-2, a ubiquitous transmembrane glycoprotein of unknown function, is a major cause of autosomal dominant polycystic kidney disease (ADPKD), whose manifestation entails the development of fluid-filled cysts in target organs. Here, we demonstrate that polycystin-2 is present in term human syncytiotrophoblast, where it behaves as a nonselective cation channel. Lipid bilayer reconstitution of polycystin-2-positive human syncytiotrophoblast apical membranes displayed a nonselective cation channel with multiple subconductance states, and a high perm-selectivity to Ca2+. This channel was inhibited by anti-polycystin-2 antibody, Ca2+, La3+, Gd3+, and the diuretic amiloride. Channel function by polycystin-2 was confirmed by patch-clamping experiments of polycystin-2 heterologously infected Sf9 insect cells. Further, purified insect cell-derived recombinant polycystin-2 and in vitro translated human polycystin-2 had similar ion channel activity. The polycystin-2 channel may be associated with fluid accumulation and/or ion transport regulation in target epithelia, including placenta. Dysregulation of this channel provides a mechanism for the onset and progression of ADPKD.

Evaluation of a measurement strategy for Parkinson's disease: assessing patient health-related quality of life.

This study evaluated the feasibility and psychometric properties of self-completed and telephone interview versions of a patient health-related quality-of-life (HQL) questionnaire for Parkinson's disease that included the SF-36 Health Survey (SF-36), the Parkinson's Disease Questionnaire (PDQ-39), and the Medical Outcomes Study Sexual Function Survey. Parkinson's disease patients (n = 150) completed the questionnaire twice: once at the study site and once over the telephone in a randomized order. Ninety-four percent of enrolled patients completed the first HQL assessment and 88% completed both assessments. Cronbach's alpha exceeded 0.70 for all scales except for the self-completed PDQ-39 Social Support subscale (0.57) and the telephone interview PDQ-39 Social Support (0.60) and Cognitions (0.67) subscales and the SF-36 General Health (0.60) and Social Function (0.61) subscales. There were no statistically significant differences in mean HQL scale scores across the two modes of administration. Mean scores for 3 of the PDQ-39 subscales and the Summary Index were significantly poorer (p < 0.05) for patients at later clinical stages. Similarly, patients with dyskinesias reported significantly poorer scores for 4 of the PDQ-39 subscales and the Summary Index and patients with self-reported comorbidities reported poorer SF-36 Physical Function and General Health subscale scores than patients without dyskinesias and comorbidities, respectively. This study suggests that the self-completed and telephone interview versions of the patient HQL questionnaire are feasible and valid for future clinical trial applications.

Family satisfaction with end-of-life care in seriously ill hospitalized adults.

OBJECTIVE: To examine factors associated with family satisfaction with end-of-life care in the Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments (SUPPORT). DESIGN: A prospective cohort study with patients randomized to either usual care or an intervention that included clinical nurse specialists to assist in symptom control and facilitation of communication and decision-making. SETTING: Five teaching hospitals in the United States. PARTICIPANTS: Family members and other surrogate respondents for 767 seriously ill hospitalized adults who died. MEASUREMENTS: Eight questionnaire items regarding satisfaction with the patient's medical care expressed as two scores, one measuring satisfaction with patient comfort and the other measuring satisfaction with communication and decision-making. RESULTS: Sixteen percent of respondents reported dissatisfaction with patient comfort and 30% reported dissatisfaction with communication and decision-making. Factors found to be significantly associated with satisfaction with communication and decision-making were hospital site, whether death occurred during the index hospitalization (adjusted odds ratio (AOR) 2.2, 95% CI, 1.3-3.9), and for patients who died following discharge, whether the patient received the SUPPORT intervention (AOR 2.0, 1.2-3.2). For satisfaction with comfort, male surrogates reported less satisfaction (0.6, 0.4-1.0), surrogates who reported patients' preferences were followed moderately to not at all had less satisfaction (0.2, 0.1-0.4), and surrogates who reported the patient's illness had greater effect on family finances had less satisfaction (0.4, 0.2-0.8). CONCLUSIONS: Satisfaction scores suggest the need for improvement in end-of-life care, especially in communication and decision making. Further research is needed to understand how factors affect satisfaction with end-of-life care. An intervention like that used in SUPPORT may help family members.

A review of health-related quality-of-life concepts and measures for Parkinson's disease.

Parkinson's disease affects individuals health-related quality of life (HQL). Including standardized HQL assessments in therapeutic clinical trials will broaden our understanding of treatment efficacy. Selecting appropriate HQL measures for clinical studies requires consideration of their comprehensiveness, psychometric properties and feasibility. To facilitate selection, this manuscript reviews the HQL areas affected by Parkinson's disease and available Parkinson's disease-specific HQL measures: the Parkinson's Disease Questionnaire--39 (PDQ-39) and the Parkinson's Disease Quality-of-Life Questionnaire (PDQL). Based on a literature review and consultation with HQL experts, five clinicians and three patients, 12 areas of HQL were identified as particularly relevant to Parkinson's disease: physical function, mental health/emotional well being, self-image, social function, health-related distress, cognitive function, communication, sleep and rest, eating, role function, energy/fatigue, and sexual function. The PDQ-39 measures all areas except for self-image and sexual function. The PDQL measures all areas except for eating and role function. Both measures are brief and are designed and validated to be self-completed by patients. Both measures demonstrate adequate internal consistency (PDQ-39: 0.72-0.95; PDQL: 0.80-0.87) and evidence of cross-sectional validity with patient-reported measures of similar concepts. The PDQ-39 also demonstrates reproducibility (0.68-0.94), significant associations with clinical measures and preliminary evidence of responsiveness. Applications of the PDQ-39 and PDQL to clinical trials will contribute greatly towards their continued validation and interpretation.