Unmet Needs in Dystonia: Genetics and Molecular Biology-How Many Dystonias?
Ontology highlight
ABSTRACT:
SUBMITTER: Verbeek DS
PROVIDER: S-EPMC5237827 | biostudies-literature | 2016
REPOSITORIES: biostudies-literature
Publications
Unmet Needs in Dystonia: Genetics and Molecular Biology-How Many Dystonias?
Verbeek Dineke S DS Gasser Thomas T
Frontiers in neurology 20170116
Genetic findings of the past years have provided ample evidence for a substantial etiologic heterogeneity of dystonic syndromes. While an increasing number of genes are being identified for Mendelian forms of isolated and combined dystonias using classical genetic mapping and whole-exome sequencing techniques, their precise role in the molecular pathogenesis is still largely unknown. Also, the role of genetic risk factors in the etiology of sporadic dystonias is still enigmatic. Only the systema ...[more]
Similar Datasets
Project description:Literary reports on dystonia date back to post-Medieval times. Medical reports are instead more recent. We review here the early descriptions and the historical establishment of a consensus on the clinical phenomenology and the diagnostic features of dystonia syndromes. Lumping and splitting exercises have characterized this area of knowledge, and it remains largely unclear how many dystonia types we are to count. This review describes the history leading to recognize that focal dystonia syndromes are a coherent clinical set encompassing cranial dystonia (including blepharospasm), oromandibular dystonia, spasmodic torticollis, truncal dystonia, writer's cramp, and other occupational dystonias. Papers describing features of dystonia and diagnostic criteria are critically analyzed and put into historical perspective. Issues and inconsistencies in this lumping effort are discussed, and the currently unmet needs are critically reviewed.
| S-EPMC5289979 | biostudies-literature
Project description:Dystonia has been defined as a syndrome of involuntary, sustained muscle contractions affecting one or more sites of the body, frequently causing twisting and repetitive movements or abnormal postures. Dystonia is also a clinical sign that can be the presenting or prominent manifestation of many neurodegenerative and neurometabolic disorders. Etiological categories include primary dystonia, secondary dystonia, heredodegenerative diseases with dystonia, and dystonia plus. Primary dystonia includes syndromes in which dystonia is the sole phenotypic manifestation with the exception that tremor can be present as well. Most primary dystonia begins in adults, and approximately 10% of probands report one or more affected family members. Many cases of childhood- and adolescent-onset dystonia are due to mutations in TOR1A and THAP1. Mutations in THAP1 and CIZ1 have been associated with sporadic and familial adult-onset dystonia. Although significant recent progress had been made in defining the genetic basis for most of the dystonia-plus and heredodegenerative diseases with dystonia, a major gap remains in understanding the genetic etiologies for most cases of adult-onset primary dystonia. Common themes in the cellular biology of dystonia include G1/S cell cycle control, monoaminergic neurotransmission, mitochondrial dysfunction, and the neuronal stress response.
| S-EPMC4879967 | biostudies-literature
Project description:IntroductionPrevalence of chronic kidney disease (CKD) varies around the world. Little is known about the discrepancy between the general population's needs and nephrology care offered. We aimed to contribute to filling this gap and propose a means to infer the number of patients needing follow-up.MethodsAll patients undergoing at least one nephrology consultation in 2019 were enrolled. We used the ratio between CKD Stages 3 and 4 reported in the literature, and considered that only 25-50% of CKD Stage 3 patients have progressive CKD, to hypothesize different scenarios to estimate the number of CKD Stage 3 patients still needing nephrology follow-up.ResultsThe 1992 CKD patients were followed-up in our centre (56.93% males; age 66.71 ± 18.32 years; 16.82% Stage 1; 14.66% Stage 2; 39.46% Stage 3; 19.88% Stage 4; 7.68% Stage 5). The ratio between Stages 3 and 4 in population studies ranged from 7.72 to 51.29, being 1.98 in our centre. Hypothesizing that we followed-up 100, 70 or 50% of CKD Stage 4 patients, 528-2506 CKD Stage 3 patients in our area would need nephrology follow-up [1885-8946 per million population (p.m.p.)]. Three to 17 additional nephrologists p.m.p. would be necessary to fully cover the need for care.ConclusionsThe number of patients with CKD Stage 3 who would benefit from nephrology care is high. Considering that one patient-year of delay of dialysis could cover a nephrologist's annual salary, interventions aimed to improve the care of advanced CKD may be economically sound.
| S-EPMC8598117 | biostudies-literature
Project description:T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy caused by the accumulation of genomic lesions that affect the development of T cells. For many years, it has been established that deregulated expression of transcription factors, impairment of the CDKN2A/2B cell-cycle regulators, and hyperactive NOTCH1 signaling play prominent roles in the pathogenesis of this leukemia. In the past decade, systematic screening of T-ALL genomes by high-resolution copy-number arrays and next-generation sequencing technologies has revealed that T-cell progenitors accumulate additional mutations affecting JAK/STAT signaling, protein translation, and epigenetic control, providing novel attractive targets for therapy. In this review, we provide an update on our knowledge of T-ALL pathogenesis, the opportunities for the introduction of targeted therapy, and the challenges that are still ahead.
| S-EPMC5363819 | biostudies-literature
Project description:Dermatomyositis is a heterogeneous idiopathic inflammatory myopathy associated with various cutaneous manifestations and variable presence of myositis, interstitial lung disease, and other visceral organ involvement. An accurate diagnosis of dermatomyositis requires correlating clinical examination findings with serological and histological findings. Familiarity with pathognomonic and common cutaneous manifestations of dermatomyositis, which are highlighted here, can be especially helpful in making an accurate diagnosis. Additionally, evaluating patients for presence of myositis-specific autoantibodies can further support or refute a dermatomyositis diagnosis. When present, myositis-specific autoantibodies can also help guide workups for various dermatomyositis-associated manifestations, as each is associated with relatively distinct clinical characteristics. Evaluating patients for various systemic manifestations often relies on expert opinion recommendations; however, societal guideline statements concerning the evaluation of some manifestations have recently been described. Although malignancy-associated dermatomyositis is a well-accepted subtype, there is limited evidence to support extensive malignancy screening has a favorable benefit-risk ratio in most dermatomyositis patients. However, recent research has uncovered novel associations between dermatomyositis and malignancy, suggesting the possibility of identifying high-risk subsets of dermatomyositis patients in whom malignancy screening may have a high value. Treatment for dermatomyositis has remained largely unchanged over the past several decades. Although many dermatomyositis patients can be effectively treated with current options, either as monotherapy or with combination regimens, there is a need for more targeted and effective DM therapies, in general, and for MDA5(+) dermatomyositis-associated rapidly progressive interstitial lung disease. Fortunately, significant current and emerging research activities evaluating various novel medications for dermatomyositis provide hope for exciting future advances in patients with this intriguing immune-mediated disease.
| S-EPMC10924937 | biostudies-literature
Project description:Despite the recent developments in the diagnosis and management of inflammatory bowel diseases (IBD), patients still suffer from disabling bowel symptoms and significant disease complications and many questions remain to improve their care. IBD is a chronic disease, whose management could be divided into the five different stages of chronic diseases, ranging from the pre-treatment evaluation phase to the induction therapy, maintenance therapy, monitor and re-establishment of control and the cessation of the disease. Reconciling these phases with the current unmet needs in IBD could help tailor priorities for research. In this review, some of the unanswered questions in the management of both Crohn's Disease and Ulcerative Colitis will be addressed, by following this paradigm of chronic diseases' management.
| S-EPMC8710990 | biostudies-literature
Project description:We present several novel drugs in development for enhancing cognition, treating negative symptoms, and providing improved options for treatment-resistant patients. Drug makers aim to enhance safety profiles and increase patient compliance to therapy.
| S-EPMC5265239 | biostudies-other
Project description:Triple negative breast cancer (TNBC) is an aggressive clinical phenotype characterized by lack of expression (or minimal expression) of estrogen receptor (ER) and progesterone receptor (PR) as well as an absence of human epidermal growth factor receptor-2 (HER2) overexpression. It shows substantial overlap with basal-type and BRCA1-related breast cancers, both of which also have aggressive clinical courses. However, this overlap is not complete, and the expression of ER, PR, and HER2 has been noted in basal-like tumors. TNBC also includes the normal-like subtype, and not all patients with TNBC harbor BRCA1 mutations. Because of its expression profile, TNBC is not amenable to treatment with hormone therapy or the anti-HER2 monoclonal antibody trastuzumab, and systemic treatment options are currently limited to cytotoxic chemotherapy. Overall survival, whether in early-stage or advanced disease, is poor compared with that in patients who have other phenotypes. A number of targeted approaches to TNBC are undergoing clinical evaluation, including the use of agents with poly(ADP-ribose) polymerase inhibitory properties such as iniparib (the United States Adopted Name for the investigational agent BSI-201), olaparib (AZD2281), and veliparib (ABT-888), antiangiogenic agents such as bevacizumab and sunitinib, and epidermal growth factor receptor blockers such as cetuximab and erlotinib. Encouraging results with some of these agents have been reported, thereby offering the promise for improved outcomes in patients with TNBC. The clinical characteristics of TNBC and clinical experience to date with novel targeted agents under development for this aggressive phenotype is reviewed.
| S-EPMC3244802 | biostudies-literature
Project description:BACKGROUND:Non-compliance to, or drop-out from treatment for childhood ADHD, result in suboptimal outcome. Non-compliance and drop-out may be due to mismatches between patients' care needs and treatments provided. This study investigated unmet care needs in ADHD patients. Unmet needs were assessed in two different treatment settings (general outpatient setting versus youth-ACT). Youth-ACT treatment is an intensive outreach-oriented treatment for patients with severe psychiatric and psychosocial problems. Comparison of a general outpatient sample with a youth-ACT sample enabled us to assess the influence of severity of psychiatric and psychosocial problems on perceived care needs. METHODS:Self-reported unmet care needs were assessed among 105 ADHD patients between 6 and 17 years of age in a general outpatient (n = 52) and a youth-ACT setting (n = 53). RESULTS:ADHD patients most frequently reported unmet needs regarding mental health problems, information on diagnosis/treatment, and future prospects. Outpatients differed from youth-ACT patients with respect to 30% of the unmet care needs that were investigated. Outpatients perceived more unmet needs regarding information on diagnosis/treatment (p = 0.014). Youth-ACT patients perceived more unmet needs concerning medication side effects (p = 0.038), quality and/or quantity of food (p = 0.016), self-care abilities (p = 0.016), regular/suitable school or other daytime activities (p = 0.013), making and/or keeping friends (p = 0.049), and future prospects (p = 0.045). CONCLUSIONS:Focusing treatment of ADHD patients on unmet needs may reduce non-compliance and drop-out. In clinical practice, systematic assessment of unmet care needs in all ADHD patients may be warranted, e.g. using the CANSAS questionnaire during the screening/intake phase.
| S-EPMC6968878 | biostudies-literature
Project description:BackgroundIn the past twenty years the heaviest burden of cardiovascular diseases has begun to shift from developed to developing countries. However, little is known about the real needs for cardiovascular care in these countries and how well those needs are being met. This study aims to investigate the prevalence and determinants of unmet needs for cardiovascular care based on objective assessment.Methods and findingsMultilevel analysis is used to analyse the determinants of met needs and multilevel multiple imputation is applied to manage missing data. The 2008 Indonesian Family Life Survey (IFLS4) survey is the source of the household data used in this study, while district data is sourced from the Ministry of Health and Ministry of Finance. The data shows that nearly 70% of respondents with moderate to high cardiovascular risk failed to receive cardiovascular care. Higher income, possession of health insurance and residence in urban areas are significantly associated with met needs for cardiovascular care, while health facility density and physician density show no association with them.ConclusionsThe prevalence of unmet needs for cardiovascular care is considerable in Indonesia. Inequality persists as a factor in meeting needs for cardiovascular care as the needs of people with higher incomes and those living in urban areas are more likely to be met. Alleviation of poverty, provision of health care insurance for the poor, and improvement in the quality of healthcare providers are recommended in order to meet this ever-increasing need.
| S-EPMC4141811 | biostudies-literature