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1.
Foot Ankle Surg ; 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38653635

RESUMO

BACKGROUND: Total ankle replacement is an established treatment for end-stage arthritis. However, there is little data examining outcomes in sequential bilateral replacements. This study aimed to compare outcomes between first and second ankles in sequential replacement. METHODS: Patients were retrospectively contacted to complete a follow-up questionnaire including the Manchester-Oxford Foot Questionnaire (MOXFQ), EQ-5D-3 L, and a question assessing satisfaction. Electronic records identified demographics, procedural details, and complications. RESULTS: Twenty patients underwent sequential bilateral ankle replacement over the study period. At a mean follow-up of four years, 18 patients completed the follow-up questionnaire. There was no statistically significant difference between first and second ankles in terms of MOXFQ score, EQ-5D-3 L or satisfaction. Eleven complications were noted. CONCLUSIONS: We report excellent outcomes after sequential bilateral ankle replacement with no difference in outcomes between first and second ankles. These results can be used to counsel patients in the future and manage expectations. LEVEL OF EVIDENCE: IV.

3.
Sci Rep ; 12(1): 15623, 2022 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-36114230

RESUMO

Dynein light chain LC8 is a small dimeric hub protein that recognizes its partners through short linear motifs and is commonly assumed to drive their dimerization. It has more than 100 known binding partners involved in a wide range of cellular processes. Recent large-scale interaction studies suggested that LC8 could also play a role in the ciliary/centrosome system. However, the cellular function of LC8 in this system remains elusive. In this work, we characterized the interaction of LC8 with the centrosomal protein lebercilin (LCA5), which is associated with a specific form of ciliopathy. We showed that LCA5 binds LC8 through two linear motifs. In contrast to the commonly accepted model, LCA5 forms dimers through extensive coiled coil formation in a LC8-independent manner. However, LC8 enhances the oligomerization ability of LCA5 that requires a finely balanced interplay of coiled coil segments and both binding motifs. Based on our results, we propose that LC8 acts as an oligomerization engine that is responsible for the higher order oligomer formation of LCA5. As LCA5 shares several common features with other centrosomal proteins, the presented LC8 driven oligomerization could be widespread among centrosomal proteins, highlighting an important novel cellular function of LC8.


Assuntos
Centrossomo , Dineínas , Centrossomo/metabolismo , Dimerização , Dineínas/metabolismo , Ligação Proteica
4.
Cell Mol Life Sci ; 79(9): 471, 2022 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-35932293

RESUMO

In synapses that show signs of local apoptosis and mitochondrial stress and undergo neuro-immunological synapse pruning, an increase in the levels of the presynaptic protein, neuronal-specific septin-3 can be observed. Septin-3 is a member of the septin GTPase family with the ability to form multimers and contribute to the cytoskeleton. However, the function of septin-3 remains elusive. Here, we provide evidence that septin-3 is capable of binding the most-studied autophagy protein Atg8 homolog microtubule-associated protein 1 light chain 3B (LC3B), besides another homolog, GABA receptor-associated protein-like 2 (GABARAPL2). Moreover, we demonstrate that colocalization of septin-3 and LC3B increases upon chemical autophagy induction in primary neuronal cells. Septin-3 is accumulated in primary neurons upon autophagy enhancement or blockade, similar to autophagy proteins. Using electron microscopy, we also show that septin-3 localizes to LC3B positive membranes and can be found at mitochondria. However, colocalization results of septin-3 and the early mitophagy marker PTEN-induced kinase 1 (PINK1) do not support that binding of septin-3 to mitochondria is mitophagy related. We conclude that septin-3 correlates with synaptic/neuronal autophagy, binds Atg8 and localizes to autophagic membranes that can be enhanced with chemical autophagy induction. Based on our results, elevated septin-3 levels might indicate enhanced or impeded autophagy in neurons.


Assuntos
Autofagossomos , Septinas , Autofagossomos/metabolismo , Autofagia , Proteínas Associadas aos Microtúbulos/metabolismo , Mitofagia , Neurônios/metabolismo , Septinas/metabolismo
5.
J Biol Chem ; 298(7): 102113, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35690144

RESUMO

Complement component C1q is a protein complex of the innate immune system with well-characterized binding partners that constitutes part of the classical complement pathway. In addition, C1q was recently described in the central nervous system as having a role in synapse elimination both in the healthy brain and in neurodegenerative diseases. However, the molecular mechanism of C1q-associated synapse phagocytosis is still unclear. Here, we designed monomer and multimer protein constructs, which comprised the globular interaction recognition parts of mouse C1q (globular part of C1q [gC1q]) as single-chain molecules (sc-gC1q proteins) lacking the collagen-like effector region. These molecules, which can competitively inhibit the function of C1q, were expressed in an Escherichia coli expression system, and their structure and capabilities to bind known complement pathway activators were validated by mass spectrometry, analytical size-exclusion chromatography, analytical ultracentrifugation, CD spectroscopy, and ELISA. We further characterized the interactions between these molecules and immunoglobulins and neuronal pentraxins using surface plasmon resonance spectroscopy. We demonstrated that sc-gC1qs potently inhibited the function of C1q. Furthermore, these sc-gC1qs competed with C1q in binding to the embryonal neuronal cell membrane. We conclude that the application of sc-gC1qs can reveal neuronal localization and functions of C1q in assays in vivo and might serve as a basis for engineering inhibitors for therapeutic purposes.


Assuntos
Complemento C1q , Via Clássica do Complemento , Animais , Ensaio de Imunoadsorção Enzimática , Camundongos
6.
Lancet Public Health ; 7(2): e156-e168, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35122759

RESUMO

BACKGROUND: There is strong evidence that suicides increase after media stories about suicides by celebrities, particularly those that highlight the suicide method (the Werther effect). Much less is known about the Papageno effect-the protective effects of media stories of hope and recovery from suicidal crises. A synthesis of the retrievable evidence is lacking. We aim to summarise findings from randomised controlled trials about the effects of stories of hope and recovery on individuals with some degree of vulnerability to suicide. METHODS: For this systematic review and individual participant data meta-analysis, we searched PubMed (including MEDLINE), Scopus, Embase, PsycInfo, Web of Science, and Google Scholar published from inception to Sept 6, 2021, without language restrictions. We included trials that reported suicidal ideation (the primary outcome) or help-seeking attitudes or intentions (the secondary outcome) and tested a media narrative of hope and recovery. Studies were excluded if they did not feature a clearly positive story of hope and recovery, or had a control group exposed to suicide-related stimulus material. We contacted the lead or senior authors of all original studies to obtain participant-level data for this study. The primary analysis was restricted to individuals with some vulnerability to suicide. Risk of bias was assessed using the Cochrane risk-of-bias tool for randomised trials. The study is registered with PROSPERO, number CRD42020221341. FINDINGS: Our search yielded 7347 records. 3920 records were screened by title and abstract, and 25 full-text records assessed for eligibility. There were eight eligible studies with 2350 participants for which individual participant data were sought. For suicidal ideation, six studies met the inclusion criteria for the primary analysis. Follow-up responses were available for 569 (90%) of 633 participants who were randomised with high vulnerability (345 [55%] allocated to the intervention group and 288 [45%] to the control group). The pooled standardised mean difference (SMD) indicated a small reduction in suicidal ideation of -0·22 (95% CI -0·39 to -0·04, p=0·017; six studies) in the intervention group. For help-seeking attitudes and intentions, four studies met the inclusion criteria and follow-up data were available for 362 (86%) of 420 participants (247 [59%] allocated to the intervention group and 173 [41%] to the control group). The pooled SMD showed no evidence of a difference between the groups (SMD=0·14, 95% CI -0·15 to 0·43, p=0·35; four studies). Low levels of cross-study heterogeneity effects were observed for both analyses (I2=5% [suicidal ideation] and I2=36% [help-seeking attitudes and intentions]). We found no evidence of publication bias. INTERPRETATION: Media narratives of hope and recovery from suicidal crises appear to have a beneficial effect on suicidal ideation in individuals with some vulnerability, but there is insufficient evidence regarding help-seeking attitudes and intentions. These findings provide new evidence about narratives for suicide prevention. FUNDING: None.


Assuntos
Meios de Comunicação de Massa/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Ideação Suicida , Atitude , Esperança , Humanos
7.
Clin Genet ; 100(1): 14-28, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33619735

RESUMO

Up to 40% of neurodevelopmental disorders (NDDs) such as intellectual disability, developmental delay, autism spectrum disorder, and developmental motor abnormalities have a documented underlying monogenic defect, primarily due to de novo variants. Still, the overall burden of de novo variants as well as novel disease genes in NDDs await discovery. We performed parent-offspring trio exome sequencing in 231 individuals with NDDs. Phenotypes were compiled using human phenotype ontology terms. The overall diagnostic yield was 49.8% (n = 115/231) with de novo variants contributing to more than 80% (n = 93/115) of all solved cases. De novo variants affected 72 different-mostly constrained-genes. In addition, we identified putative pathogenic variants in 16 genes not linked to NDDs to date. Reanalysis performed in 80 initially unsolved cases revealed a definitive diagnosis in two additional cases. Our study consolidates the contribution and genetic heterogeneity of de novo variants in NDDs highlighting trio exome sequencing as effective diagnostic tool for NDDs. Besides, we illustrate the potential of a trio-approach for candidate gene discovery and the power of systematic reanalysis of unsolved cases.


Assuntos
Variação Genética/genética , Transtornos do Neurodesenvolvimento/genética , Adolescente , Adulto , Criança , Pré-Escolar , Exoma/genética , Feminino , Predisposição Genética para Doença/genética , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Fenótipo , Estudos Retrospectivos , Centros de Atenção Terciária , Sequenciamento do Exoma/métodos , Adulto Jovem
8.
Appl Environ Microbiol ; 87(9)2021 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-33637571

RESUMO

Glutathione (GSH) is an abundant tripeptide that plays a crucial role in shielding cellular macromolecules from various reactive oxygen and nitrogen species in fungi. Understanding GSH metabolism is of vital importance for deciphering redox regulation in these microorganisms. In the present study, to better understand the GSH metabolism in filamentous fungi, we investigated functions of the dugB and dugC genes in the model fungus Aspergillus nidulans These genes are orthologues of dug2 and dug3, which are involved in cytosolic GSH degradation in Saccharomyces cerevisiae The deletion of dugB, dugC, or both resulted in a moderate increase in the GSH content in mycelia grown on glucose, reduced conidium production, and disturbed sexual development. In agreement with these observations, transcriptome data showed that genes encoding mitogen-activated protein (MAP) kinase pathway elements (e.g., steC, sskB, hogA, and mkkA) or regulatory proteins of conidiogenesis and sexual differentiation (e.g., flbA, flbC, flbE, nosA, rosA, nsdC, and nsdD) were downregulated in the ΔdugB ΔdugC mutant. Deletion of dugB and/or dugC slowed the depletion of GSH pools during carbon starvation. It also reduced accumulation of reactive oxygen species and decreased autolytic cell wall degradation and enzyme secretion but increased sterigmatocystin formation. Transcriptome data demonstrated that enzyme secretions-in contrast to mycotoxin production-were controlled at the posttranscriptional level. We suggest that GSH connects starvation and redox regulation to each other: cells utilize GSH as a stored carbon source during starvation. The reduction of GSH content alters the redox state, activating regulatory pathways responsible for carbon starvation stress responses.IMPORTANCE Glutathione (GSH) is a widely distributed tripeptide in both eukaryotes and prokaryotes. Owing to its very low redox potential, antioxidative character, and high intracellular concentration, GSH profoundly shapes the redox status of cells. Our observations suggest that GSH metabolism and/or the redox status of cells plays a determinative role in several important aspects of fungal life, including oxidative stress defense, protein secretion, and secondary metabolite production (including mycotoxin formation), as well as sexual and asexual differentiations. We demonstrated that even a slightly elevated GSH level can substantially disturb the homeostasis of fungi. This information could be important for development of new GSH-producing strains or for any biotechnologically relevant processes where the GSH content, antioxidant capacity, or oxidative stress tolerance of a fungal strain is manipulated.


Assuntos
Aspergillus nidulans/metabolismo , Carbono-Nitrogênio Ligases/metabolismo , Proteínas Fúngicas/metabolismo , Glutationa/metabolismo , Peptídeo Hidrolases/metabolismo , Aspergillus nidulans/genética , Carbono-Nitrogênio Ligases/genética , Proteínas Fúngicas/genética , Regulação Fúngica da Expressão Gênica , Mutação , Peptídeo Hidrolases/genética , Transcriptoma
9.
Rev Sci Instrum ; 92(1): 015120, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33514212

RESUMO

In this work, we report the development of a measurement chamber linked with a quadrupole mass spectrometer (QMS) for in situ investigation of the effect of thin film cracking on the gas permeation of coated flexible polymeric substrates. The chamber enables the establishment of a bulged state of the substrate/coating system, which causes the cracking of the coating layer. The increase in the gas permeation rate due to the presence of cracks can be monitored precisely using the QMS without movement or re-clamping of the samples between each measurement step. This method eliminates the probability of uncontrollable mechanical changes in the sample, and with the mass spectrometer, high sensitivity, reliability, and reproducibility of the experimental data become available.

10.
Anaerobe ; 65: 102241, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32777291

RESUMO

Solobacterium moorei is a strict anaerobic gram-positive rod. It is found in the human microbiota in different parts of the body, but it also appears to be an opportunistic pathogen in some infectious processes. We describe six cases of severe infections identified in 2016 in which S. moorei was isolated alone or in mixed culture involving other anaerobes or both aerobic and anaerobic bacteria. Three cases were associated with the oral cavity, including a middle ear infection, a wound infection after total laryngectomy, and a mandibular abscess as a result of bisphosphonate therapy. In the other three patients, the sites of infection had no connections with the oral cavity and included chronic osteomyelitis of the tibia, a superinfection of cutaneous tuberculosis associated with hidradenitis suppurativa, and the isolation of S. moorei from the blood culture of a cachectic man with several comorbidities. Based on our findings, S. moorei does not appear to be that virulent of a bacterium; except for the case with bacteraemia, S. moorei was recovered as a co-pathogen in patients with several immunosuppressive predisposing factors. We highlight the finding that the routine use of MALDI-TOF MS in microbiology laboratories can in a timely and detailed manner identify members of mixed infections involving different anaerobic bacteria that may be rare and difficult-to-culture and identify species, such as S. moorei.


Assuntos
Firmicutes/isolamento & purificação , Infecções por Bactérias Gram-Positivas/diagnóstico , Infecções por Bactérias Gram-Positivas/microbiologia , Bacteriemia/diagnóstico , Bacteriemia/microbiologia , Bactérias Anaeróbias , Técnicas de Tipagem Bacteriana , Comorbidade , Diagnóstico Diferencial , Firmicutes/classificação , Firmicutes/patogenicidade , Humanos , Otite Média/diagnóstico , Otite Média/microbiologia , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Estomatite/diagnóstico , Estomatite/microbiologia
11.
Cell Mol Life Sci ; 77(24): 5243-5258, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32034429

RESUMO

Synaptic functional disturbances with concomitant synapse loss represent central pathological hallmarks of Alzheimer's disease. Excessive accumulation of cytotoxic amyloid oligomers is widely recognized as a key event that underlies neurodegeneration. Certain complement components are crucial instruments of widespread synapse loss because they can tag synapses with functional impairments leading to their engulfment by microglia. However, an exact understanding of the affected synaptic functions that predispose to complement-mediated synapse elimination is lacking. Therefore, we conducted systematic proteomic examinations on synaptosomes prepared from an amyloidogenic mouse model of Alzheimer's disease (APP/PS1). Synaptic fractions were separated according to the presence of the C1q-tag using fluorescence-activated synaptosome sorting and subjected to proteomic comparisons. The results raised the decline of mitochondrial functions in the C1q-tagged synapses of APP/PS1 mice based on enrichment analyses, which was verified using flow cytometry. Additionally, proteomics results revealed extensive alterations in the level of septin protein family members, which are known to dynamically form highly organized pre- and postsynaptic supramolecular structures, thereby affecting synaptic transmission. High-resolution microscopy investigations demonstrated that synapses with considerable amounts of septin-3 and septin-5 show increased accumulation of C1q in APP/PS1 mice compared to the wild-type ones. Moreover, a strong positive correlation was apparent between synaptic septin-3 levels and C1q deposition as revealed via flow cytometry and confocal microscopy examinations. In sum, our results imply that deterioration of synaptic mitochondrial functions and alterations in the organization of synaptic septins are associated with complement-dependent synapse loss in Alzheimer's disease.


Assuntos
Doença de Alzheimer/genética , Amiloide/metabolismo , Proteoma/genética , Sinapses/genética , Doença de Alzheimer/patologia , Amiloide/toxicidade , Proteínas Amiloidogênicas/genética , Animais , Modelos Animais de Doenças , Regulação da Expressão Gênica/genética , Humanos , Camundongos , Microglia/metabolismo , Microglia/patologia , Mitocôndrias/genética , Mitocôndrias/patologia , Oligopeptídeos/genética , Placa Amiloide/genética , Placa Amiloide/patologia , Septinas/genética , Sinapses/metabolismo , Sinapses/patologia , Sinaptossomos/metabolismo , Sinaptossomos/patologia
12.
Front Immunol ; 11: 599771, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33628204

RESUMO

Elements of the immune system particularly that of innate immunity, play important roles beyond their traditional tasks in host defense, including manifold roles in the nervous system. Complement-mediated synaptic pruning is essential in the developing and healthy functioning brain and becomes aberrant in neurodegenerative disorders. C1q, component of the classical complement pathway, plays a central role in tagging synapses for elimination; however, the underlying molecular mechanisms and interaction partners are mostly unknown. Neuronal pentraxins (NPs) are involved in synapse formation and plasticity, moreover, NP1 contributes to cell death and neurodegeneration under adverse conditions. Here, we investigated the potential interaction between C1q and NPs, and its role in microglial phagocytosis of synapses in adult mice. We verified in vitro that NPs interact with C1q, as well as activate the complement system. Flow cytometry, immunostaining and co-immunoprecipitation showed that synapse-bound C1q colocalizes and interacts with NPs. High-resolution confocal microscopy revealed that microglia-surrounded C1q-tagged synapses are NP1 positive. We have also observed the synaptic occurrence of C4 suggesting that activation of the classical pathway cannot be ruled out in synaptic plasticity in healthy adult animals. In summary, our results indicate that NPs play a regulatory role in the synaptic function of C1q. Whether this role can be intensified upon pathological conditions, such as in Alzheimer's disease, is to be disclosed.


Assuntos
Proteína C-Reativa/imunologia , Complemento C1q/imunologia , Microglia/imunologia , Proteínas do Tecido Nervoso/imunologia , Fagocitose , Sinapses/imunologia , Doença de Alzheimer/imunologia , Animais , Complemento C4/imunologia , Masculino , Camundongos
13.
J Strength Cond Res ; 32(12): 3319-3325, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30335722

RESUMO

Brewer, W, Kovacs, R, Hogan, K, Felder, D, and Mitchell, H. Metabolic responses to a battling rope protocol performed in the seated or stance positions. J Strength Cond Res 32(12): 3319-3325, 2018-The purpose of this study is to compare the levels of oxygen consumption and heart rate responses elicited by a treadmill or cycle V[Combining Dot Above]O2max test with a standing or sitting battling rope protocol (BRP) (treadmill vs. standing BRP) (cycle vs. seated BRP). Forty healthy subjects performed either a ramped V[Combining Dot Above]O2max treadmill or cycle test. At least 3 days later, the subjects who performed the ramped treadmill test did the standing BRP, and the subjects who performed the ramped cycle test did the sitting BRP. Each BRP consisted of 10 sets of 15/45 seconds of work/rest for 10 sets. V[Combining Dot Above]O2peak and HRpeak were recorded. Metabolic responses were significantly lower for the sitting BRP and standing as compared to the HRmax and V[Combining Dot Above]O2max values derived from the bicycle and treadmill tests. The BRP produced a V[Combining Dot Above]O2peak that was 71.87% (sitting) and 68.37% (standing) of the subjects' V[Combining Dot Above]O2max assessed u the bicycle and treadmill protocol. Moderate correlations were found between the V[Combining Dot Above]O2 during the seated (r = 0.61; p = 0.003) and standing (r = 0.43; p = 0.03) BRP and the bicycle and treadmill V[Combining Dot Above]O2max tests, respectively. The HRpeak elicited by the BRP performed in sitting (r = 0.52; p = 0.009) and standing (r = 0.67; p = 0.001) had a moderate correlation with the HRmax derived from the bicycle and treadmill tests. Battling ropes may be a low cost, accessible option to improve cardiovascular endurance for individuals who cannot stand or move their lower extremities in a rhythmic manner to conduct aerobic exercise.


Assuntos
Teste de Esforço/métodos , Frequência Cardíaca , Consumo de Oxigênio , Postura Sentada , Posição Ortostática , Adulto , Exercício Físico , Tolerância ao Exercício , Feminino , Humanos , Masculino , Resistência Física , Adulto Jovem
15.
Children (Basel) ; 5(7)2018 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-29970830

RESUMO

Cystic fibrosis (CF) is the most common fatal genetic diseases in the United States in Caucasians. More than 2000 genetic mutations have been described and CF is now known to affect other races. The incidence of CF in individuals of Hispanic descent is estimated to be 1:9200. An uncommon mutation, 1811+1643G>T, was recently reported. We report four patients with the 1811+1643G>T mutation (homozygous or heterozygous) and describe their clinical features and compare them to the remainder of our Hispanic cohort group. The homozygous patients had a more severe phenotype compared to the Hispanic cohort in the following areas: their pancreatic status, forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC), chronic Pseudomonas aeruginosa (PA) colonization, pulmonary exacerbations requiring oral and intravenous antibiotics, and hospitalization rate. These preliminary findings suggest that future studies investigating the clinical trajectory with a larger cohort of patients homozygous for the 1811+1643G>T mutation are needed.

16.
Sleep Breath ; 22(2): 541-546, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29520669

RESUMO

PURPOSE: In 2005, the American Academy of Sleep Medicine stated, "Oral appliances are indicated for use in patients with mild to moderate obstructive sleep apnea (OSA) who prefer them to CPAP therapy, or who do not respond to, are not appropriate candidates for, or who fail treatment attempts with CPAP." However, this recommendation is based upon variable results from only six studies with more than 100 participants. These studies have assessed the effectiveness of mandibular advancement devices (MADs) in specific groups (military populations, academic institutions, or hospital settings) with no large study conducted in a fee-for-service private practice where the majority of patients receive MADs for OSA. The purpose of this study is to report outcomes of a board-certified dental sleep practitioner managing mild, moderate, and severe OSA using customized titratable MADs. We hypothesize that patients will demonstrate a significant reduction in apnea-hypopnea index (AHI) scores after adjusting their customized titratable MADs. METHODS: This is a 14-year retrospective study design with pre- and post-treatment sleep studies. An AHI score < 10 respiratory events per hour with therapy is defined as treatment success. This study was performed by a single private practitioner. RESULTS: Of 2419 patient records analyzed, 544 (22%) had pre- and post-treatment sleep studies (89% polysomnograms). Of 510 patients with complete data, 459 (90%) revealed a decrease in AHI score < 10 respiratory events per hour indicating treatment success. Only 51 of these patients (10%) had a final AHI ≥ 10 and were considered treatment failures. Among the patients who lacked post overnight polysomnogram, 66/1921 (3%) discontinued the MAD due to adverse effects. Considering these patients as treatment failures as well, and therefore adding their number to the patients with complete sleep study data, the total treatment failures were 117/576 or 20%. Of the treatment successes, OSA was categorized by AHI at baseline as mild in 170 (34%), moderate in 181 (36%), and severe in 138 (28%). CONCLUSIONS: In patients with evaluable data, there was an 80% success rate for treatment of OSA using a custom-fabricated adjustable MAD including substantial numbers of patients with moderate and severe disease.


Assuntos
Avanço Mandibular , Prática Privada , Apneia Obstrutiva do Sono/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polissonografia , Estudos Retrospectivos , Resultado do Tratamento
17.
Hum Resour Health ; 15(1): 78, 2017 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-29121943

RESUMO

BACKGROUND: The WHO Global Code of Practice on the International Recruitment of Health Personnel provides for guidance in health workforce management and cooperation in the international context. This article aims to examine whether the principles of the voluntary WHO Global Code of Practice can be applied to trigger health policy decisions within the EU zone of free movement of persons. METHODS: In the framework of the Joint Action on European Health Workforce Planning and Forecasting project (Grant Agreement: JA EUHWF 20122201 (see healthworkforce.eu)), focus group discussions were organised with over 30 experts representing ministries, universities and professional and international organisations. Ideas were collected about the applicability of the principles and with the aim to find EU law compatible, relevant solutions using a qualitative approach based on a standardised, semi-structured interview guide and pre-defined statements. RESULTS: Based on implementation practices summarised, focus group experts concluded that positive effects of adhering to the Code can be identified and useful ideas-compatible with EU law-exist to manage intra-EU mobility. The most relevant areas for intervention include bilateral cooperations, better use of EU financial resources, improved retention and integration policies and better data flow and monitoring. Improving retention is of key importance; however, ethical considerations should also apply within the EU. Compensation of source countries can be a solution to further elaborate on when developing EU financial mechanisms. Intra-EU circular mobility might be feasible and made more transparent if directed by tailor-made, institutional-level bilateral cooperations adjusted to different groups and profiles of health professionals. Integration policies should be improved as discrimination still exists when offering jobs despite the legal environment facilitating the recognition of professional qualifications. A system of feedback on registration/licencing data should be promoted providing for more evidence on intra-EU mobility and support its management. CONCLUSIONS: Workforce planning in EU Member States can be supported, and more equitable distribution of the workforce can be provided by building policy decisions on the principles of the WHO Code. Political commitment has to be strengthened in EU countries to adopt implementation solutions for intra-EU problems. Long-term benefits of respecting global principles of the Code should be better demonstrated in order to incentivise all parties to follow such long-term objectives.


Assuntos
União Europeia , Pessoal Profissional Estrangeiro , Pessoal de Saúde , Mão de Obra em Saúde/organização & administração , Seleção de Pessoal/ética , Organização Mundial da Saúde , Emigração e Imigração , Política de Saúde , Humanos , Cooperação Internacional
18.
PDA J Pharm Sci Technol ; 71(3): 234-244, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28089966

RESUMO

In this case study, the principles of quality risk management were applied to review sampling points and monitoring frequencies in the hormonal tableting unit of a formulation development pilot plant. In the cleanroom area, premises of different functions are located. Therefore a general method was established for risk evaluation based on the Hazard Analysis and Critical Control Points (HACCP) method to evaluate these premises (i.e., production area itself and ancillary clean areas) from the point of view of microbial load and state in order to observe whether the existing monitoring program met the emerged advanced monitoring practice.LAY ABSTRACT: In pharmaceutical production, cleanrooms are needed for the manufacturing of final dosage forms of drugs-intended for human or veterinary use-in order to protect the patient's weakened body from further infections. Cleanrooms are premises with a controlled level of contamination that is specified by the number of particles per cubic meter at a specified particle size or number of microorganisms (i.e. microbial count) per surface area. To ensure a low microbial count over time, microorganisms are detected and counted by environmental monitoring methods regularly. It is reasonable to find the easily infected places by risk analysis to make sure the obtained results really represent the state of the whole room. This paper presents a risk analysis method for the optimization of environmental monitoring and verification of the suitability of the method.


Assuntos
Contaminação de Medicamentos/prevenção & controle , Ambiente Controlado , Monitoramento Ambiental/métodos , Arquitetura de Instituições de Saúde , Técnicas Microbiológicas , Preparações Farmacêuticas/análise , Controle de Qualidade , Tecnologia Farmacêutica/métodos , Descontaminação , Monitoramento Ambiental/normas , Contaminação de Equipamentos/prevenção & controle , Umidade , Técnicas Microbiológicas/normas , Medição de Risco , Fatores de Risco , Gestão de Riscos , Tecnologia Farmacêutica/normas , Temperatura , Fatores de Tempo
19.
Orv Hetil ; 157(47): 1859-1865, 2016 Nov.
Artigo em Húngaro | MEDLINE | ID: mdl-27868444

RESUMO

Plant-based diet is an old-new trend in nutrition. In this review based on a historical context, we wish to introduce this popular nutritional trend. Our aim is to present plant-based diet as a primary measure for prevention. We intend to critically analyse some past stereotypes related to plant-based diet - whose main components include fruits, vegetables, whole grains, legumes, nuts and seeds - according to the literature (e.g. protein, vitamin B12, folic acid, and iron intake) by doing so we wish to create an adequate conceptual basis for its interpretation. We discuss positive physiological effects of plant-based diet and its possible role in diseases risk reduction. Cardiovascular and metabolic diseases developing due to obesity could be prevented by a properly compiled plant-based diet. For patients with cancer minimizing the intake of foods of animal origin - as opposed to plant-based ones - has proved to have positive effects. Our review suggests this diet can be used in a number of diseases and it also provides long-term sustainable solutions for the health care challenges of the newest era. Orv. Hetil., 2016, 157(47), 1859-1865.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Dieta Vegetariana/normas , Preferências Alimentares , Estado Nutricional , Doença Crônica/prevenção & controle , Frutas , Nível de Saúde , Humanos , Nozes , Fatores de Risco , Verduras
20.
Hum Resour Health ; 14(Suppl 1): 42, 2016 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-27423330

RESUMO

BACKGROUND: Health workforce (HWF) planning and monitoring processes face challenges regarding data and appropriate indicators. One such area fraught with difficulties is labour activity and, more specifically, defining headcount and full-time equivalent (FTE). This study aims to review national practices in FTE calculation formulas for selected EU Member States (MS). METHODS: The research was conducted as a part of the Joint Action on European Health Workforce Planning and Forecasting. Definitions, categories and terms concerning the five sectoral professions were examined in 14 MS by conducting a survey. To gain a deeper understanding of the international data-reporting processes (Joint Questionnaire on Non-Monetary Health Care Statistics-JQ), six international expert interviews were conducted by using a semi-structured interview guide. RESULTS: Of the 14 investigated countries, four MS indicated that they report FTE to the JQ and that they also calculate FTE data for national planning purposes. The other countries do not use FTE data for national purposes, but most of them do use special calculations and/or estimation methods for converting headcount to FTE. The findings revealed significant differences between national calculation methods when reporting FTE data to the JQ. This diversity in terms of calculations and estimations can lead to biases with respect to international comparisons. This finding was reinforced by the expert interviews, since the experts agreed that the activities of healthcare professionals are a fundamental factor in HWF monitoring and planning. Experts underscored that activity should also be measured by FTE, and not only by headcount. CONCLUSIONS: FTE and headcount are significant factors in HWF planning and monitoring; therefore, national data collections should place emphasis on collecting data and calculating the appropriate indicators. National FTE could serve as a call to action for HWF planners due to the lack of matching international FTE data. At the international level, it is beneficial to monitor the trends and numbers regarding human resources and working time. For the moment, the exchange of information and mutual assistance for developing the capacity to apply common methodology could be a first step towards the standardisation of data collections.


Assuntos
Coleta de Dados/métodos , Emprego , Pessoal de Saúde , Planejamento em Saúde , Europa (Continente) , União Europeia , Humanos
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