People with Parkinson's Disease: What Symptoms Do They Most Want to Improve and How Does This Change with Disease Duration?

BACKGROUND: Parkinson's disease (PD) is a neurodegenerative condition with a diverse and complex pattern of motor and non-motor symptoms which change over time with disease duration. OBJECTIVE: The aims of the present study were to discover what symptoms matter most to people with the condition and to examine how these priorities change with disease duration. METHODS: A simple free-text online survey (using SmartSurvey) was developed by Parkinson's UK, which asked participants to identify up to three aspects of the condition they would most like to see improvement in. RESULTS: 790 people participated reporting 2,295 issues related to PD which were grouped into 24 broad symptom domains. Of these, 1,358 (59.1%) were categorised as motor symptoms, 859 (37.4%) as non-motor issues and 78 (3.4%) as medication problems. This study reveals how certain features of PD become more or less important to patients as the condition progresses. Non-motor symptoms were highly cited from the very earliest stages of PD. Problems with walking, balance and falls, speech problems, freezing and dyskinesia become increasingly important as the condition progresses whereas tremor, stiffness and psychological health become decreasingly important as the condition progresses. CONCLUSIONS: The data suggest that the priorities of people affected by PD for improving life are personal and change with duration of the condition. These findings have implications for developing person-centred management and care, as well as for directing future research to improve quality of life

Functional consequences of seven novel mutations in the CYP11B1 Gene: four mutations associated with nonclassic and three mutations causing classic 11 -Hydroxylase Deficiency

Context: Steroid 11β-hydroxylase (CYP11B1) deficiency (11OHD) is the second most common form of congenital adrenal hyperplasia (CAH). Cases of nonclassic 11OHD are rare compared with the incidence of nonclassic 21-hydroxylase deficiency. Objective: The aim of the study was to analyze the functional consequences of seven novel CYP11B1 mutations (p.M88I, p.W116G, p.P159L, p.A165D, p.K254_A259del, p.R366C, p.T401A) found in three patients with classic 11OHD, two patients with nonclassic 11OHD, and three heterozygous carriers for CYP11B1 mutations. Methods: We conducted functional studies employing a COS7 cell in vitro expression system comparing wild-type (WT) and mutant CYP11B1 activity. Mutants were examined in a computational three-dimensional model of the CYP11B1 protein. Results: All mutations (p.W116G, p.A165D, p.K254_A259del) found in patients with classic 11OHD have absent or very little 11β-hydroxylase activity relative to WT. The mutations detected in patients with nonclassic 11OHD showed partial functional impairment, with one patient being homozygous (p.P159L; 25% of WT) and the other patient compound heterozygous for a novel mild p.M88I (40% of WT) and the known severe p.R383Q mutation. The two mutations detected in heterozygous carriers (p.R366C, p.T401A) also reduced CYP11B1 activity by 23 to 37%, respectively. Conclusion: Functional analysis results allow for the classification of novel CYP11B1 mutations as causative for classic and nonclassic 11OHD, respectively. Four partially inactivating mutations are predicted to result in nonclassic 11OHD. These findings double the number of mild CYP11B1 mutations previously described as associated with mild 11OHD. Our data are important to predict phenotypic expression and provide important information for clinical and genetic counseling i

Nephrolithiasis related to inborn metabolic diseases

Nephrolithiasis associated with inborn metabolic diseases is a very rare condition with some common characteristics: early onset of symptoms, family history, associated tubular impairment, bilateral, multiple and recurrent stones, and association with nephrocalcinosis. The prognosis of such diseases may lead to life threatening conditions, not only because of unabated kidney damage but also because of progressive extra-renal involvement, either in a systemic form (e.g. primary hyperoxaluria type 1, requiring combined liver and kidney transplantation), or in a neurological form (Lesch–Nyhan syndrome leading to auto-mutilation and disability, phosphoribosyl pyrophosphate synthetase superactivity, which is associated with mental retardation). Patients with other inborn metabolic diseases present only with recurrent stone formation, such as cystinuria, adenine phosphoribosyl-transferase deficiency, xanthine deficiency. Finally, nephrolithiasis may be secondarily part of some other metabolic diseases, such as glycogen storage disease type 1 or inborn errors of metabolism leading to Fanconi syndrome (nephropathic cystinosis, tyrosinaemia type 1, fructose intolerance, Wilson disease, respiratory chain disorders, etc.). The diagnosis is based on highly specific investigations, including crystal identification, biochemical analyses and DNA study. The treatment of nephrolithiasis requires hydration as well as specific measures. Compliance is a major issue regarding the progression of renal damage, but the overall outcome mainly depends on extra-renal involvement in relation to the metabolic defect

An agenda for creative practice in the new mobilities paradigm

Creative practices have made a standing contribution to mobilities research. We write this article as a collective of 25 scholars and practitioners to make a provocation: to further position creative mobilities research as a fundamental contribution and component in this field. The article explores how creative forms of research—whether in the form of artworks, exhibitions, performances, collaborations, and more—has been a foundational part of shaping the new mobilities paradigm, and continues to influence its methodological, epistemological, and ontological concerns. We tour through the interwoven history of art and mobilities research, outlining five central contributions that creativity brings. Through short vignettes of each author’s creative practice, we discuss how creativity has been key to the evolution and emergence of how mobilities research has expanded to global audiences of scholars, practitioners, and communities. The article concludes by highlighting the potency of the arts for lively and transdisciplinary pathways for future mobilities research in the uncertainties that lay ahead

A novel point mutation in P450c17 (CYP17) causing combined 17 alpha-hydroxylase/17,20-lyase deficiency

Context: Combined 17 alpha-hydroxylase/17,20-lyase deficiency is a rare cause of congenital adrenal hyperplasia and hypogonadism. Novel single amino acid changes in P450c17 provide potentially important insights into key structural domains for enzyme function.Objective, Design, and Setting: We report a novel missense mutation in P450c17 in a 17-yr-old female presenting with a malignant mixed germ cell tumor with yolk sac elements who demonstrated clinical and biochemical features of combined 17 alpha-hydroxylase/17,20-lyase deficiency.Methods: Quantitative urinary steroid analysis was performed by high resolution gas chromatography. All eight coding exons of CYP17 were PCR amplified and sequenced. The position of arginine at codon 96 was modeled using the CYP17 structure 2c17 (www.rcsb.org). The CYP17 genes were subcloned into pcDNA3, expressed in HEK-293 cells, and chromatographed.Patient and Results: 17 beta-Hydroxylase deficiency was confirmed by marked reductions in urinary and serum cortisol, androgens, and estradiol. Mutational analysis revealed a novel homozygous R96Q missense mutation in P450c17, affecting an amino acid in a key substrate-binding region of the enzyme, leading to complete inactivity.Conclusion: The description of a second missense mutation at codon 96 (R96W and R96Q) in the substrate-binding region of P450c17 provides strong evidence for the key role of this amino acid in 17 alpha-hydroxylase/17,20-lyase function. An association between a malignant germ cell tumor and 17 alpha-hydroxylase deficiency has not been reported previously, although the presence of gonadoblastoma in the ovary of a patient with this condition has recently been described

Rumours, sects and rallies : the ethnic politics of recent Hmong Millenarian movements in Vietnam’s highlands

Contrary to modernist assumptions, millenarianism has not died out but continues to influence the politics of many marginalised groups in upland Southeast Asia, including the Hmong. This article summarises and analyses post-World War II Hmong millenarian activity in Vietnam, focusing on three case studies from the 1980s onwards, within the political backdrop of ongoing government suspicions of ethnic separatism and foreign interference. Far from being isolated or peripheral, Hmong millenarian rumours and movements interact with overseas diasporas, human rights agencies and international religious networks to influence state responses, sometimes in unexpected ways