ABSTRACT
The facile ring contraction of [CoCpâ´(η4-P4)] and [Ta(CO)2Cpâ³(η4-P4)] to [CoCpâ´(η3-P3)][(MeNHC)2P] and [Ta(CO)2Cpâ³(η3-P3)] [(MeNHC)2P] induced by MeNHC and the absence of the ring contraction of [FeCp*(η5-P5)] under the same conditions are studied by density functional theory (DFT) computations. The latter is estimated to be thermodynamically the least favorable reaction and also has a very high energy barrier. The similar strain energies of P3 and P4 rings and the lower strain energy of the P5 ring play a decisive role in the ring contraction capability of these [TM-cyclo-Pn] complexes. Theoretical approaches involving NBO and IBO analysis have been employed to provide a qualitative picture of the overall reactions. The role of substituents and the nature of transition metals in determining the energetics of these reactions has also been studied and an isolobal perspective on these systems affords a simplified picture.
ABSTRACT
The first example of a diphosphaborolediide, the benzo-fused [C6 H4 P2 BPh]2- (12- ), is prepared from ortho-bis(phosphino)benzene (C6 H4 {PH2 }) and dichlorophenylborane, via a sequential lithiation approach. The dilithio-salt can be obtained as an oligomeric THF solvate or discrete TMEDA adduct, both of which are fully characterized, including by X-ray diffraction. Alongside NICS calculations, data strongly suggest some aromaticity within 12- , which is further supported by preliminary coordination studies that demonstrate η5 -coordination to a zerovalent molybdenum center, as observed crystallographically for the oligomeric [{Mo(CO)3 (η5 -1)}{µ-η1 -Mo(CO)3 (TMEDA)}2 ] â [µ-Li(THF)][µ-Li(TMEDA)].
ABSTRACT
BACKGROUND: A qualified consensus suggests that a combination of levodopa with a peripherally acting dopa decarboxylase inhibitor continues to present the gold standard treatment of Parkinson's disease (PD). However, as the disease progresses the therapeutic window of levodopa becomes narrowed. Pharmacological strategies for motor fluctuations are focused on providing less pulsatile and more continuous dopaminergic stimulation. Peripheral catechol-O-methyltransferase (COMT) inhibition improves the bioavailability of levodopa and results in a prolonged response. OBJECTIVE: The primary aim of this study was to investigate the efficacy and safety of the two available COMT inhibitors; entacapone and tolcapone and the recently introduced opicapone. METHODS: Electronic databases were systematically searched for original studies published within the last 37 years. In addition, lists of identified studies, reviews and their references were examined. RESULTS: Twelve studies fulfilled the inclusion criteria. 3701 patients with PD were included in this systematic review. CONCLUSIONS: Adjuvant treatment of PD patients experiencing motor fluctuations with entacapone resulted in improvement of motor function and was well tolerated. Therefore, entacapone presented an acceptable benefit to risk ratio. Tolcapone appeared to result in a greater therapeutic effect. However, this was not consistent across all motor variables and studies, and thus would not support its use, given the current onerous monitoring that is required. Opicapone was not associated with adverse reactions in a phase III trial but did not present a greater efficacy than entacapone, and thus further studies are required in order to illustrate its cost effectiveness.
Subject(s)
Antiparkinson Agents/therapeutic use , Catechol O-Methyltransferase Inhibitors/therapeutic use , Catechols/therapeutic use , Levodopa/therapeutic use , Nitriles/therapeutic use , Parkinson Disease/drug therapy , Tolcapone/therapeutic use , Antiparkinson Agents/adverse effects , Catechol O-Methyltransferase Inhibitors/adverse effects , Catechols/adverse effects , Drug Therapy, Combination , Humans , Nitriles/adverse effects , Tolcapone/adverse effects , Treatment OutcomeABSTRACT
Doxorubicin is an important cause of chemotherapy-induced cardiomyopathy. Prior studies have found conflicting results of whether nonstrain diastolic parameters can predict doxorubicin-induced cardiotoxicity. We performed a systematic review of English written publications using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The following inclusion criteria were applied: cancer subjects, echo-derived nonstrain diastolic profile, and patients compared before and after treatment to predict systolic dysfunction. The following exclusion criteria were applied: other cardiotoxic agents, non-echo studies, or used protective medications. Meta-analysis was performed using comprehensive meta-analysis software V3 to calculate cumulative means, SD, and odds ratios (ORs). Only 4 studies were designed to predict doxorubicin-induced cardiotoxicity. Of the 7 common parameters identified among studies, only 4 were significant: mitral E [OR: 3.4; 95% confidence interval (CI): 1.5-7.8; P = 0.003]; lateral E' (OR: 3.7; 95% CI: 1.5-9.4; P < 0.005); mitral E/A (OR: 4.3; 95% CI: 2.1-8.9; P < 0.0001); and lateral S' (OR: 2.7; 95% CI: 1.2-5.8; P = 0.01). We found that conventional nonstrain diastolic parameters predicted doxorubicin-induced systolic dysfunction. Whether nonstrain diastolic parameters can be used to supplement strain imaging for predicting doxorubicin-induced systolic function warrants further investigation in larger studies.
Subject(s)
Cardiomyopathies , Doxorubicin/adverse effects , Heart Ventricles/diagnostic imaging , Stroke Volume/physiology , Antibiotics, Antineoplastic/adverse effects , Cardiomyopathies/chemically induced , Cardiomyopathies/diagnosis , Cardiomyopathies/physiopathology , Diastole , Echocardiography , Heart Ventricles/drug effects , Heart Ventricles/physiopathology , Humans , Neoplasms/drug therapy , Prognosis , Stroke Volume/drug effectsABSTRACT
Calcium (Ca2+ ) is a physiological key factor, and the precise modulation of free cytosolic Ca2+ levels regulates multiple cellular functions. Store-operated Ca2+ entry (SOCE) is a major mechanism controlling Ca2+ homeostasis, and is mediated by the concerted activity of the Ca2+ sensor STIM1 and the Ca2+ channel ORAI1. Dominant gain-of-function mutations in STIM1 or ORAI1 cause tubular aggregate myopathy (TAM) or Stormorken syndrome, whereas recessive loss-of-function mutations are associated with immunodeficiency. Here, we report the identification and functional characterization of novel ORAI1 mutations in TAM patients. We assess basal activity and SOCE of the mutant ORAI1 channels, and we demonstrate that the G98S and V107M mutations generate constitutively permeable ORAI1 channels, whereas T184M alters the channel permeability only in the presence of STIM1. These data indicate a mutation-dependent pathomechanism and a genotype/phenotype correlation, as the ORAI1 mutations associated with the most severe symptoms induce the strongest functional cellular effect. Examination of the non-muscle features of our patients strongly suggests that TAM and Stormorken syndrome are spectra of the same disease. Overall, our results emphasize the importance of SOCE in skeletal muscle physiology, and provide new insights in the pathomechanisms involving aberrant Ca2+ homeostasis and leading to muscle dysfunction.
Subject(s)
Ion Channel Gating/genetics , Mutation, Missense , Myopathies, Structural, Congenital/genetics , ORAI1 Protein/genetics , Amino Acid Sequence , Animals , Base Sequence , Blood Platelet Disorders/genetics , Blood Platelet Disorders/metabolism , Calcium/metabolism , Cells, Cultured , Dyslexia/genetics , Dyslexia/metabolism , Erythrocytes, Abnormal/metabolism , Female , HEK293 Cells , Humans , Ichthyosis/genetics , Ichthyosis/metabolism , Male , Mice, Knockout , Microscopy, Fluorescence/methods , Migraine Disorders/genetics , Migraine Disorders/metabolism , Miosis/genetics , Miosis/metabolism , Muscle Fatigue/genetics , Myopathies, Structural, Congenital/metabolism , Neoplasm Proteins/genetics , Neoplasm Proteins/metabolism , ORAI1 Protein/metabolism , Pedigree , Sequence Homology, Amino Acid , Spleen/abnormalities , Spleen/metabolism , Stromal Interaction Molecule 1/genetics , Stromal Interaction Molecule 1/metabolismABSTRACT
Eosinophils have been linked with asthma for more than a century, but their role has been unclear. This review discusses the roles of eosinophils in asthma and chronic obstructive pulmonary disease (COPD) and describes therapeutic antibodies that affect eosinophilia. The aims of pharmacologic treatments for pulmonary conditions are to reduce symptoms, slow decline or improve lung function, and reduce the frequency and severity of exacerbations. Inhaled corticosteroids (ICS) are important in managing symptoms and exacerbations in asthma and COPD. However, control with these agents is often suboptimal, especially for patients with severe disease. Recently, new biologics that target eosinophilic inflammation, used as adjunctive therapy to corticosteroids, have proven beneficial and support a pivotal role for eosinophils in the pathology of asthma. Nucala® (mepolizumab; anti-interleukin [IL]-5) and Cinquair® (reslizumab; anti-IL-5), the second and third biologics approved, respectively, for the treatment of asthma, exemplifies these new treatment options. Emerging evidence suggests that eosinophils may contribute to exacerbations and possibly to lung function decline for a subset of patients with COPD. Here we describe the pharmacology of therapeutic antibodies inhibiting IL-5 or targeting the IL-5 receptor, as well as other cytokines contributing to eosinophilic inflammation. We discuss their roles as adjuncts to conventional therapeutic approaches, especially ICS therapy, when disease is suboptimally controlled. These agents have achieved a place in the therapeutic armamentarium for asthma and COPD and will deepen our understanding of the pathogenic role of eosinophils.
Subject(s)
Antibodies, Monoclonal/therapeutic use , Asthma/drug therapy , Pulmonary Disease, Chronic Obstructive/drug therapy , Animals , Anti-Asthmatic Agents/pharmacology , Anti-Asthmatic Agents/therapeutic use , Antibodies, Monoclonal/pharmacology , Asthma/immunology , Asthma/physiopathology , Eosinophils/metabolism , Humans , Inflammation/drug therapy , Inflammation/immunology , Inflammation/physiopathology , Interleukin-5/immunology , Pulmonary Disease, Chronic Obstructive/immunology , Pulmonary Disease, Chronic Obstructive/physiopathology , Receptors, Interleukin-5/immunology , Respiratory Function TestsABSTRACT
Camelina sativa is currently being embraced as a viable industrial bio-platform crop due to a number of desirable agronomic attributes and the unique fatty acid profile of the seed oil that has applications for food, feed and biofuel. The recent completion of the reference genome sequence of C. sativa identified a young hexaploid genome. To complement this work, we have generated a genome-wide developmental transcriptome map by RNA sequencing of 12 different tissues covering major developmental stages during the life cycle of C. sativa. We have generated a digital atlas of this comprehensive transcriptome resource that enables interactive visualization of expression data through a searchable database of electronic fluorescent pictographs (eFP browser). An analysis of this dataset supported expression of 88% of the annotated genes in C. sativa and provided a global overview of the complex architecture of temporal and spatial gene expression patterns active during development. Conventional differential gene expression analysis combined with weighted gene expression network analysis uncovered similarities as well as differences in gene expression patterns between different tissues and identified tissue-specific genes and network modules. A high-quality census of transcription factors, analysis of alternative splicing and tissue-specific genome dominance provided insight into the transcriptional dynamics and sub-genome interplay among the well-preserved triplicated repertoire of homeologous loci. The comprehensive transcriptome atlas in combination with the reference genome sequence provides a powerful resource for genomics research which can be leveraged to identify functional associations between genes and understand the regulatory networks underlying developmental processes.
Subject(s)
Biofuels , Brassicaceae/metabolism , Plant Proteins/metabolism , Transcriptome/genetics , Brassicaceae/genetics , Gene Expression Regulation, Plant/genetics , Gene Expression Regulation, Plant/physiology , Plant Proteins/genetics , Polyploidy , Transcription Factors/genetics , Transcription Factors/metabolismABSTRACT
OBJECTIVE: To expand the clinical phenotype of autosomal dominant congenital spinal muscular atrophy with lower extremity predominance (SMA-LED) due to mutations in the dynein, cytoplasmic 1, heavy chain 1 (DYNC1H1) gene. METHODS: Patients with a phenotype suggestive of a motor, non-length-dependent neuronopathy predominantly affecting the lower limbs were identified at participating neuromuscular centers and referred for targeted sequencing of DYNC1H1. RESULTS: We report a cohort of 30 cases of SMA-LED from 16 families, carrying mutations in the tail and motor domains of DYNC1H1, including 10 novel mutations. These patients are characterized by congenital or childhood-onset lower limb wasting and weakness frequently associated with cognitive impairment. The clinical severity is variable, ranging from generalized arthrogryposis and inability to ambulate to exclusive and mild lower limb weakness. In many individuals with cognitive impairment (9/30 had cognitive impairment) who underwent brain MRI, there was an underlying structural malformation resulting in polymicrogyric appearance. The lower limb muscle MRI shows a distinctive pattern suggestive of denervation characterized by sparing and relative hypertrophy of the adductor longus and semitendinosus muscles at the thigh level, and diffuse involvement with relative sparing of the anterior-medial muscles at the calf level. Proximal muscle histopathology did not always show classic neurogenic features. CONCLUSION: Our report expands the clinical spectrum of DYNC1H1-related SMA-LED to include generalized arthrogryposis. In addition, we report that the neurogenic peripheral pathology and the CNS neuronal migration defects are often associated, reinforcing the importance of DYNC1H1 in both central and peripheral neuronal functions.
Subject(s)
Cytoplasmic Dyneins/genetics , Muscular Atrophy, Spinal/genetics , Mutation , Adolescent , Adult , Aged, 80 and over , Brain/pathology , Child , Child, Preschool , Cohort Studies , Family , Humans , Infant , Leg/pathology , Leg/physiopathology , Middle Aged , Muscular Atrophy, Spinal/pathology , Muscular Atrophy, Spinal/physiopathology , Phenotype , Young AdultABSTRACT
Community-based participatory research (CBPR) is an approach that engages community residents with a goal of influencing change in community health systems, programs, or policies. As such, CBPR is particularly relevant to historically marginalized communities that often have not directly benefited from the knowledge research produces. This article analyzes a youth empowerment program, Chicago's Youth Health Service Corps, from a CBPR perspective. The purpose of this work was (1) to discuss Youth Health Service Corps as a health promotion program, (2) examine the use of CBPR within the immigrant community, and (3) discuss preliminary findings using a model on critical youth empowerment.
Subject(s)
Adolescent Health Services , Community-Based Participatory Research , Emigrants and Immigrants , Health Promotion/methods , Adolescent , Adolescent Health Services/organization & administration , Attitude to Health , Chicago , Female , Health Promotion/organization & administration , Humans , Male , Power, Psychological , Program EvaluationABSTRACT
A patient with a history of rheumatic mitral valve disease and valve replacement in childhood presented with severe, persistent dyspnea. During an electrophyisiologic procedure, she was discovered to have a fistula from the left ventricle to the coronary sinus. She had severe pulmonary hypertension and elevated filling pressures, with a significant left-to-right shunt. Percutaneous closure of the fistula was performed using two vascular plugs. Subsequently the patient's hemodynamics improved and her symptoms subsided. Here, we describe the case and review the literature.
Subject(s)
Cardiac Catheterization , Coronary Sinus/injuries , Fistula/therapy , Heart Diseases/therapy , Heart Injuries/therapy , Heart Ventricles/injuries , Iatrogenic Disease , Prosthesis Implantation/adverse effects , Cardiac Catheterization/instrumentation , Cineangiography , Coronary Sinus/diagnostic imaging , Coronary Sinus/physiopathology , Female , Fistula/diagnosis , Fistula/etiology , Fistula/physiopathology , Heart Diseases/diagnosis , Heart Diseases/etiology , Heart Diseases/physiopathology , Heart Injuries/diagnosis , Heart Injuries/etiology , Heart Injuries/physiopathology , Heart Ventricles/diagnostic imaging , Heart Ventricles/physiopathology , Hemodynamics , Humans , Middle Aged , Pacemaker, Artificial , Prosthesis Implantation/instrumentation , Recovery of Function , Tomography, X-Ray Computed , Treatment Outcome , Ventricular Function, LeftABSTRACT
The Brassicaceae (Cruciferae) family, owing to its remarkable species, genetic, and physiological diversity as well as its significant economic potential, has become a model for polyploidy and evolutionary studies. Utilizing extensive transcriptome pyrosequencing of diverse taxa, we established a resolved phylogeny of a subset of crucifer species. We elucidated the frequency, age, and phylogenetic position of polyploidy and lineage separation events that have marked the evolutionary history of the Brassicaceae. Besides the well-known ancient α (47 million years ago [Mya]) and ß (124 Mya) paleopolyploidy events, several species were shown to have undergone a further more recent (â¼7 to 12 Mya) round of genome multiplication. We identified eight whole-genome duplications corresponding to at least five independent neo/mesopolyploidy events. Although the Brassicaceae family evolved from other eudicots at the beginning of the Cenozoic era of the Earth (60 Mya), major diversification occurred only during the Neogene period (0 to 23 Mya). Remarkably, the widespread species divergence, major polyploidy, and lineage separation events during Brassicaceae evolution are clustered in time around epoch transitions characterized by prolonged unstable climatic conditions. The synchronized diversification of Brassicaceae species suggests that polyploid events may have conferred higher adaptability and increased tolerance toward the drastically changing global environment, thus facilitating species radiation.
Subject(s)
Brassicaceae/genetics , Cleome/genetics , Evolution, Molecular , Genome, Plant/genetics , Base Sequence , Brassicaceae/classification , Cleome/classification , Gene Library , High-Throughput Nucleotide Sequencing , Molecular Sequence Annotation , Molecular Sequence Data , Phylogeny , Plant Leaves/classification , Plant Leaves/genetics , Polyploidy , RNA, Messenger/genetics , RNA, Plant/chemistry , RNA, Plant/genetics , Sequence Analysis, DNA , Time Factors , TranscriptomeABSTRACT
BACKGROUND: Brassica oleracea is a valuable vegetable species that has contributed to human health and nutrition for hundreds of years and comprises multiple distinct cultivar groups with diverse morphological and phytochemical attributes. In addition to this phenotypic wealth, B. oleracea offers unique insights into polyploid evolution, as it results from multiple ancestral polyploidy events and a final Brassiceae-specific triplication event. Further, B. oleracea represents one of the diploid genomes that formed the economically important allopolyploid oilseed, Brassica napus. A deeper understanding of B. oleracea genome architecture provides a foundation for crop improvement strategies throughout the Brassica genus. RESULTS: We generate an assembly representing 75% of the predicted B. oleracea genome using a hybrid Illumina/Roche 454 approach. Two dense genetic maps are generated to anchor almost 92% of the assembled scaffolds to nine pseudo-chromosomes. Over 50,000 genes are annotated and 40% of the genome predicted to be repetitive, thus contributing to the increased genome size of B. oleracea compared to its close relative B. rapa. A snapshot of both the leaf transcriptome and methylome allows comparisons to be made across the triplicated sub-genomes, which resulted from the most recent Brassiceae-specific polyploidy event. CONCLUSIONS: Differential expression of the triplicated syntelogs and cytosine methylation levels across the sub-genomes suggest residual marks of the genome dominance that led to the current genome architecture. Although cytosine methylation does not correlate with individual gene dominance, the independent methylation patterns of triplicated copies suggest epigenetic mechanisms play a role in the functional diversification of duplicate genes.
Subject(s)
Brassica/genetics , Genome, Plant , Transcriptome , Aneuploidy , Brassica/metabolism , Chromosome Mapping , DNA Methylation , Epigenesis, Genetic , Evolution, Molecular , Gene Expression Regulation, Plant , Molecular Sequence Annotation , Molecular Sequence Data , Sequence Analysis, DNAABSTRACT
Camelina sativa is an oilseed with desirable agronomic and oil-quality attributes for a viable industrial oil platform crop. Here we generate the first chromosome-scale high-quality reference genome sequence for C. sativa and annotated 89,418 protein-coding genes, representing a whole-genome triplication event relative to the crucifer model Arabidopsis thaliana. C. sativa represents the first crop species to be sequenced from lineage I of the Brassicaceae. The well-preserved hexaploid genome structure of C. sativa surprisingly mirrors those of economically important amphidiploid Brassica crop species from lineage II as well as wheat and cotton. The three genomes of C. sativa show no evidence of fractionation bias and limited expression-level bias, both characteristics commonly associated with polyploid evolution. The highly undifferentiated polyploid genome of C. sativa presents significant consequences for breeding and genetic manipulation of this industrial oil crop.
Subject(s)
Biofuels , Brassicaceae/genetics , Genome, Plant , Polyploidy , KaryotypingABSTRACT
Mutations in nuclear genes involved in the maintenance of mitochondrial DNA (mtDNA) are associated with an extensive spectrum of clinical phenotypes, manifesting as either mtDNA depletion syndromes or multiple mtDNA deletion disorders.(1.)
Subject(s)
DNA, Mitochondrial/genetics , Gene Deletion , Mutation/genetics , Respiratory Insufficiency/diagnosis , Respiratory Insufficiency/genetics , Thymidine Kinase/genetics , Age Factors , Aged , Female , HumansABSTRACT
Although cancer in children is rare, it is the second most common cause of childhood mortality in developed countries. It often presents with nonspecific symptoms similar to those of benign conditions, leading to delays in the diagnosis and initiation of appropriate treatment. Primary care physicians should have a raised index of suspicion and explore the possibility of cancer in children who have worrisome or persisting signs and symptoms. Red flag signs for leukemia or lymphoma include unexplained and protracted pallor, malaise, fever, anorexia, weight loss, lymphadenopathy, hemorrhagic diathesis, and hepatosplenomegaly. New onset or persistent morning headaches associated with vomiting, neurologic symptoms, or back pain should raise concern for tumors of the central nervous system. Palpable masses in the abdomen or soft tissues, and persistent bone pain that awakens the child are red flags for abdominal, soft tissue, and bone tumors. Leukokoria is a red flag for retinoblastoma. Endocrine symptoms such as growth arrest, diabetes insipidus, and precocious or delayed puberty may be signs of endocranial or germ cell tumors. Paraneoplastic manifestations such as opsoclonus-myoclonus syndrome, rheumatic symptoms, or hypertension are rare and may be related to neuroblastoma, leukemia, or Wilms tumor, respectively. Increased suspicion is also warranted for conditions associated with a higher risk of childhood cancer, including immunodeficiency syndromes and previous malignancies, as well as with certain genetic conditions and familial cancer syndromes such as Down syndrome, Li-Fraumeni syndrome, hemihypertrophy, neurofibromatosis, and retinoblastoma.
Subject(s)
Early Detection of Cancer/methods , Neoplasms/diagnosis , Abdominal Neoplasms/diagnosis , Bone Neoplasms/diagnosis , Central Nervous System Neoplasms/diagnosis , Child , Humans , Leukemia/diagnosis , Lymphoma/diagnosisABSTRACT
Neuromuscular disease is one of the most common indications for the use of intravenous immuno-globulin (IVIG). We describe practical aspects of IVIG administration and dosing in long-term treatment, as well as the setting up of a day-case service in a regional neurology unit to provide a streamlined patient experience. An audit of the safety of IVIG administration and patient satisfaction during implementation supported the fact that this is a relatively safe treatment. Standardised assessment methods have been used both to monitor treatment effect and to provide the necessary outcome measures for Department of Health (DOH) monitoring of IVIG use.
Subject(s)
Day Care, Medical/methods , Immunoglobulins, Intravenous/administration & dosage , Long-Term Care/methods , Neuromuscular Diseases/drug therapy , Adolescent , Adult , Aged , Aged, 80 and over , Female , Follow-Up Studies , Humans , Immunologic Factors/administration & dosage , Male , Middle Aged , Patient Satisfaction , Retrospective Studies , Time Factors , Treatment Outcome , United Kingdom , Young AdultABSTRACT
Limb girdle muscular dystrophy type 2L or anoctaminopathy is a condition mainly characterized by adult onset proximal lower limb muscular weakness and raised CK values, due to recessive ANO5 gene mutations. An exon 5 founder mutation (c.191dupA) has been identified in most of the British and German LGMD2L patients so far reported. We aimed to further investigate the prevalence and spectrum of ANO5 gene mutations and related clinical phenotypes, by screening 205 undiagnosed patients referred to our molecular service with a clinical suspicion of anoctaminopathy. A total of 42 unrelated patients had two ANO5 mutations (21%), whereas 14 carried a single change. We identified 34 pathogenic changes, 15 of which are novel. The c.191dupA mutation represents 61% of mutated alleles and appears to be less prevalent in non-Northern European populations. Retrospective clinical analysis corroborates the prevalently proximal lower limb phenotype, the male predominance and absence of major cardiac or respiratory involvement. Identification of cases with isolated hyperCKaemia and very late symptomatic male and female subjects confirms the extension of the phenotypic spectrum of the disease. Anoctaminopathy appears to be one of the most common adult muscular dystrophies in Northern Europe, with a prevalence of about 20%-25% in unselected undiagnosed cases.
Subject(s)
Chloride Channels/genetics , Muscular Dystrophies, Limb-Girdle/genetics , Mutation , Adult , Aged , Anoctamins , Chloride Channels/metabolism , Europe/epidemiology , Female , Genetic Variation , Humans , Male , Middle Aged , Muscular Dystrophies, Limb-Girdle/epidemiology , Muscular Dystrophies, Limb-Girdle/metabolism , Phenotype , Prevalence , Retrospective Studies , Sex FactorsABSTRACT
BACKGROUND: Social and national health insurance schemes are being introduced in many developing countries in moving towards universal health care. However, gaps in coverage are common and can only be met by out-of-pocket payments, general taxation, or private health insurance (PHI). This study provides an overview of PHI in different health care systems and discusses factors that affect its uptake and equity. METHODS: A representative sample of countries was identified (United States, United Kingdom, The Netherlands, France, Australia, and Latvia) that illustrates the principal forms and roles of PHI. Literature describing each country's health care system was used to summarize how PHI is utilized and the factors that affect its uptake and equity. RESULTS: In the United States, PHI is a primary source of funding in conjunction with tax-based programs to support vulnerable groups; in the UK and Latvia, PHI is used in a supplementary role to universal tax-based systems; in France and Latvia, complementary PHI is utilized to cover gaps in public funding; in The Netherlands, PHI is supplementary to statutory private and social health insurance; in Australia, the government incentivizes the uptake of complementary PHI through tax rebates and penalties. The uptake of PHI is influenced by age, income, education, health care system typology, and the incentives or disincentives applied by governments. The effect on equity can either be positive or negative depending on the type of PHI adopted and its role within the wider health care system. CONCLUSION: PHI has many manifestations depending on the type of health care system used and its role within that system. This study has illustrated its common applications and the factors that affect its uptake and equity in different health care systems. The results are anticipated to be helpful in informing how developing countries may utilize PHI to meet the aim of achieving universal health care.
ABSTRACT
BACKGROUND: Nigeria and Ghana have recently introduced a National Health Insurance Scheme (NHIS) with the aim of moving towards universal health care using more equitable financing mechanisms. This study compares health and economic indicators, describes the structure of each country's NHIS within the wider healthcare system, and analyses impacts on equity in financing and access to health care. METHODS: The World Bank and other sources were used to provide comparative health and economic data. Pubmed, Embase and EconLit were searched to locate studies providing descriptions of each NHIS and empirical evidence regarding equity in financing and access to health care. A diagrammatical representation of revenue-raising, pooling, purchasing and provision was produced in order to analyse the two countries' systems. RESULTS: Over the period 2000-2010, Ghana maintained a marked advantage in life expectancy, infant mortality, under-5 year mortality, and has a lower burden of major diseases. Health care expenditure is about 5% of GDP in both countries but public expenditure in 2010 was 38% of total expenditure in Nigeria and 60% in Ghana. Financing and access are less equitable in Nigeria as, inter alia, private out-of-pocket expenditure has fallen from 80% to 66% of total spending in Ghana since the introduction of its NHIS but has remained at over 90% in Nigeria; NHIS membership in Nigeria and Ghana is approximately 3.5% and 65%, respectively; Nigeria offers a variable benefits package depending on membership category while Ghana has uniform benefits across all beneficiaries. Both countries exhibit improvements in equity but there is a pro-rich and pro-urban bias in membership. CONCLUSIONS: Major health indicators are more favourable in Ghana and overall equity in financing and access are weaker in Nigeria. Nigeria is taking steps to expand NHIS membership and has potential to expand its public spending to achieve greater equity. However, heavy burdens of poverty, disease and remote settings make this a substantial challenge. Ghana's relative success has to be tempered by the high number of exemptions through taxation and the threat of moral hazard. The results and methods are anticipated to be informative for policy makers and researchers in both countries and other developing countries more widely.
Subject(s)
Health Services Accessibility/standards , Healthcare Disparities , Insurance, Health/organization & administration , National Health Programs/organization & administration , Ghana , Health Expenditures , Health Services Accessibility/economics , Health Services Accessibility/organization & administration , Humans , Life Expectancy , National Health Programs/economics , NigeriaABSTRACT
The potential energy surfaces of both neutral and dianionic SnC(2)P(2)R(2) (R=H, tBu) ring systems have been explored at the B3PW91/LANL2DZ (Sn) and 6-311+G* (other atoms) level. In the neutral isomers the global minimum is a nido structure in which a 1,2-diphosphocyclobutadiene ring (1,2-DPCB) is capped by the Sn. Interestingly, the structure established by X-ray diffraction analysis, for R=tBu, is a 1,3-DPCB ring capped by Sn and it is 2.4 kcal mol(-1) higher in energy than the 1,2-DPCB ring isomer. This is possibly related to the kinetic stability of the 1,3-DPCB ring, which might originate from the synthetic precursor ZrCp(2)tBu(2)C(2)P(2). In the case of the dianionic isomers we observe only a 6π-electron aromatic structure as the global minimum, similarly to the cases of our previously reported results with other types of heterodiphospholes. The existence of large numbers of cluster-type isomers in neutral and 6π-planar structures in the dianions SnC(2)P(2)R(2)(2-) (R=H, tBu) is due to 3D aromaticity in neutral clusters and to 2D π aromaticity of the dianionic rings. Relative energies of positional isomers mainly depend on: 1) the valency and coordination number of the Sn centre, 2) individual bond strengths, and 3) the steric effect of tBu groups. A comparison of neutral stannadiphospholes with other structurally related C(5)H(5)(+) analogues indicates that Sn might be a better isolobal analogue to P(+) than to BH or CH(+). The variation in global minima in these C(5)H(5)(+) analogues is due to characteristic features such as 1) the different valencies of C, B, P and Sn, 2) the electron deficiency of B, 3) weaker pπ-pπ bonding by P and Sn atoms, and 4) the tendency of electropositive elements to donate electrons to nido clusters. Unlike the C(5)H(5)(+) systems, all C(5)H(5)(-) analogues have 6π-planar aromatic structures as global minima. The differences in the relative ordering of the positional isomers and ligating properties are significant and depend on 1) the nature of the π orbitals involved, and 2) effective overlap of orbitals.