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1.
J Clin Sleep Med ; 2024 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-38217481

RESUMO

STUDY OBJECTIVES: Four well-established predictors of obstructive sleep apnea risk are body mass index, age, gender, and neck circumference. We have previously reported cheeks appearance as an OSA predictor, which may represent a combination of such predictors in a single readily available feature. This study sought to answer the question: Is cheeks appearance an OSA risk predictor? METHODS: A prospective cross-sectional diagnostic accuracy study based on STARD. Patients undergoing polysomnography to investigate sleep complaints at a sleep clinic affiliated to a university hospital were assessed using cheeks appearance scored 0-3 for volume from and 0-3 for flaccidity to create the cheeks appearance for sleep apnea (CASA) score ranging from 0-6. Appearance was judged by three blinded and independent evaluators. RESULTS: Among 265 patients evaluated, 248 were included. Fifty-seven patients had a CASA score of 0, 191 had a CASA score between 1-6. Polysomnography diagnosed 177 of the individuals with OSA; of these 167 had altered CASA score. Sensitivity was 87%, specificity 82%, positive predictive value 94%, negative predictive value 66%, accuracy 86%. CONCLUSIONS: Our results suggest that combining volume and flaccidity of cheeks appearance in a single index may constitute a reliable OSA predictor. CASA score is a novel predictor of obstructive sleep apnea with internal validity in sleep laboratory adult population. Our findings support further studies to confirm external validity of this practical diagnostic tool. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Title: Cheeks Appearance as a Novel Predictor of Obstructive Sleep Apnea: The CASA Score Study (CASA); Identifier: NCT04980586; URL: https://clinicaltrials.gov/study/NCT04980586.

2.
Commun Biol ; 6(1): 1075, 2023 10 21.
Artigo em Inglês | MEDLINE | ID: mdl-37865695

RESUMO

Hfq is a pleitropic actor that serves as stress response and virulence factor in the bacterial cell. To execute its multiple functions, Hfq assembles into symmetric torus-shaped hexamers. Extending outward from the hexameric core, Hfq presents a C-terminal region, described as intrinsically disordered in solution. Many aspects of the role and the structure of this region remain unclear. For instance, in its truncated form it can promote amyloid-like filament assembly. Here, we show that a minimal 11-residue motif at the C-terminal end of Hfq assembles into filaments with amyloid characteristics. Our data suggest that the full-length Hfq in its filamentous state contains a similar molecular fingerprint than that of the short ß-strand peptide, and that the Sm-core structure is not affected by filament formation. Hfq proteins might thus co-exist in two forms in vivo, either as isolated, soluble hexamers or as self-assembled hexamers through amyloid-reminiscent interactions, modulating Hfq cellular functions.


Assuntos
Proteínas de Escherichia coli , Proteínas de Escherichia coli/metabolismo , Escherichia coli/metabolismo , Peptídeos beta-Amiloides/metabolismo , Ligação Proteica , Fator Proteico 1 do Hospedeiro/genética , Fator Proteico 1 do Hospedeiro/metabolismo
3.
Blood Press Monit ; 28(6): 289-294, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37466401

RESUMO

OBJECTIVE: To compare the effects of chlortalidone plus amiloride and amlodipine on blood pressure (BP) variability in patients with hypertension and obstructive sleep apnea syndrome (OSA). METHODS: A randomized, controlled, double-blind trial enrolled men and women aged 40 years or older with a diagnosis of OSA (apnea-hypopnea index 10-40 apneas/h of sleep) confirmed by overnight laboratory polysomnography and systolic BP 140-159 mmHg or diastolic BP 90-99 mmHg. Participants were randomized to receive chlortalidone 25 mg plus amiloride 5 mg daily or amlodipine 10 mg daily for 8 weeks. BP variability was calculated from 24-hour ambulatory BP monitoring at baseline and follow-up using the following indices: SD, coefficient of variation, average real variability (ARV), time-rate index, and variability independent of the mean (VIM). RESULTS: The study included 65 patients, with 33 assigned to the chlortalidone plus amiloride group and 32 to the amlodipine group. Participants in both groups had similar baseline characteristics. Short-term BP variability decreased within groups for SD and ARV indexes for 24-hour systolic BP and daytime systolic BP, but statistically significant time*group interactions were found for sleep systolic SD and VIM, with greater reduction in patients treated with amlodipine. CONCLUSION: In brief, our study has shown that the use of chlorthalidone in combination with amiloride and amlodipine produces comparable effects on short-term BP variability in patients with hypertension and OSA. Therefore, our findings suggest that BP variability may not be a significant factor when choosing between these medications for the treatment of hypertension and OSA.


Assuntos
Hipertensão , Apneia Obstrutiva do Sono , Feminino , Humanos , Masculino , Amilorida/farmacologia , Anlodipino/farmacologia , Anti-Hipertensivos/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Monitorização Ambulatorial da Pressão Arterial , Clortalidona/farmacologia , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Hipertensão/diagnóstico , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/tratamento farmacológico , Adulto , Pessoa de Meia-Idade
4.
J Clin Med ; 12(11)2023 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-37297980

RESUMO

Hypertension is highly prevalent in patients with obstructive sleep apnea (OSA), and fluid retention with its nighttime rostral distribution is one potential mechanism. We tested whether or not diuretics differ from amlodipine in their impact on echocardiographic parameters. Patients with moderate OSA and hypertension were randomized to receive diuretics (chlorthalidone plus amiloride) or amlodipine daily for 8 weeks. We compared their effects on left and right ventricular global longitudinal strain (LV-GLS and RV-GLS, respectively), on LV diastolic parameters, and on LV remodeling. In the 55 participants who had echocardiographic images feasible for strain analysis, all echocardiographic parameters were within normal ranges. After 8 weeks, the 24 h blood pressure (BP) reduction values were similar, while most echocardiographic metrics were kept unchanged, except for LV-GLS and LV mass. In conclusion, the use of diuretics or amlodipine had small and similar effects on echocardiographic parameters in patients with moderate OSA and hypertension, suggesting that they do not have important effects on mediating the interaction between OSA and hypertension.

5.
Int J Mol Sci ; 23(15)2022 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-35955871

RESUMO

Hfq is a pleiotropic regulator that mediates several aspects of bacterial RNA metabolism. The protein notably regulates translation efficiency and RNA decay in Gram-negative bacteria, usually via its interaction with small regulatory RNAs. Previously, we showed that the Hfq C-terminal region forms an amyloid-like structure and that these fibrils interact with membranes. The immediate consequence of this interaction is a disruption of the membrane, but the effect on Hfq structure was unknown. To investigate details of the mechanism of interaction, the present work uses different in vitro biophysical approaches. We show that the Hfq C-terminal region influences membrane integrity and, conversely, that the membrane specifically affects the amyloid assembly. The reported effect of this bacterial master regulator on membrane integrity is discussed in light of the possible consequence on small regulatory RNA-based regulation.


Assuntos
Proteínas de Escherichia coli , RNA Bacteriano , Proteínas Amiloidogênicas/metabolismo , Bactérias/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Proteínas de Escherichia coli/metabolismo , Regulação Bacteriana da Expressão Gênica , Fator Proteico 1 do Hospedeiro/genética , Fator Proteico 1 do Hospedeiro/metabolismo , RNA Bacteriano/metabolismo
6.
Sleep Med ; 95: 37-46, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35561473

RESUMO

OBJECTIVES/BACKGROUND: The prevalence of obstructive sleep apnea (OSA) in people over 70 years can reach up to 95%. Aerobic or combined exercise programs have been shown to impact positively on OSA severity. Resistance training changes leg fluid retention. We hypothesized that through this mechanism it may have an impact on the OSA severity in older adults. PATIENTS/METHODS: We evaluated changes in the respiratory event index (REI) of older adults with moderate-severe obstructive sleep apnea in a randomized, masked, controlled, parallel group trial. Participants between the age of 65 and 80 years with REI between 20 and 50 events/hour were assigned randomly to 12 weeks of resistance training or healthy life-style recommendations. Change in REI was the primary outcome. Muscle thickness, maximum strength, and physical function were secondary outcomes and body mass index (BMI) and body water content were assessed as mediators. RESULTS: Twenty-three subjects were included, 57% men, aged 71 ± 5 years, randomized to training (n = 12) and control intervention (n = 11). The baseline REI in the training and control groups were 30 ± 7/h and 29 ± 9/h; at follow-up, the delta REI were -3.6/hour (95% confidence interval -0.7 to -5.4) and 6.7/hour (5.2-8.6), respectively, with significant time × group interaction that remained significant after adjusting the generalized estimating equations model for delta BMI and delta body water content. CONCLUSIONS: Twelve weeks of resistance training in older adults significantly changed the respiratory event index and was well tolerated. Changes in body water content were slight but cannot be dismissed as contributing to REI reduction.


Assuntos
Treinamento de Força , Apneia Obstrutiva do Sono , Idoso , Água Corporal , Pré-Escolar , Exercício Físico , Feminino , Humanos , Lactente , Masculino , Prevalência , Apneia Obstrutiva do Sono/complicações
7.
J Clin Sleep Med ; 18(5): 1467-1469, 2022 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-35034685

RESUMO

Restless legs syndrome (RLS) is characterized by an urge to move the legs, predominantly at night. About one quarter of the patients with RLS report painful symptoms in the legs. In this case report, the patient presented at the sleep clinic with a chief complaint of insomnia and the classical symptoms of RLS. He also mentioned a chronic testicular pain (CTP). For over a year, the patient had undergone urologic investigation and empiric treatments, with only mild improvement of the testicular pain. After 3 months of therapy with pramipexole, the RLS symptoms and the CTP were no longer present. Finding an etiology for CTP can be challenging and many cases are diagnosed as idiopathic. RLS may be a forgotten and unidentified etiology for CTP in typical urological care. Considering the high prevalence of RLS and CTP, it is relevant to clarify the possible association. CITATION: Tedesco Silva LM, Lenz MCS, Martinez D. Chronic testicular pain cured by low-dose pramipexole: Is there an association with restless legs syndrome? J Clin Sleep Med. 2022;18(5):1467-1469.


Assuntos
Dor Crônica , Síndrome das Pernas Inquietas , Humanos , Masculino , Dor Crônica/tratamento farmacológico , Perna (Membro) , Pramipexol/uso terapêutico , Síndrome das Pernas Inquietas/complicações , Síndrome das Pernas Inquietas/diagnóstico , Síndrome das Pernas Inquietas/tratamento farmacológico
8.
Clinics (Sao Paulo) ; 76: e3056, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34614114

RESUMO

OBJECTIVES: Owing to the fact that obstructive sleep apnea (OSA) is an underreported disease, the strategy used for the diagnosis of OSA has been extensively dissected to devise a simplified process that can be accessed by the public health services. Polysomnography (PSG) type I, the gold standard for the diagnosis of OSA, is expensive and difficult to access by low-income populations. In this study, we aimed to verify the accuracy of the oxyhemoglobin desaturation index (ODI) in comparison to the apnea-hypopnea index (AHI) using a portable monitor. METHODS: We evaluated 94 type III PSG home test results of 65 elderly patients (69.21±6.94 years old), along with information, such as the body mass index (BMI) and sex, using data obtained from a clinical trial database. RESULTS: A significant linear positive correlation (r=0.93, p<0.05) was observed between ODI and AHI, without any interference from sex, BMI, and positional component. The sensitivity of ODI compared to that of AHI increased with an increase in the severity of OSA, while the specificity of ODI in comparison to that of AHI was high for all degrees of severity. The accuracy of ODI was 80.7% for distinguishing between patients with mild and moderate apnea and 84.4% for distinguishing between patients with moderate and severe apnea. CONCLUSION: The ODI values obtained in uncontrolled conditions exhibited high sensitivity for identifying severe apnea compared to the AHI values, and correctly identified the severity of OSA in more than 80% of the cases. Thus, oximetry is promising strategy for diagnosing OSA.


Assuntos
Apneia Obstrutiva do Sono , Idoso , Índice de Massa Corporal , Humanos , Pessoa de Meia-Idade , Oximetria , Polissonografia , Apneia Obstrutiva do Sono/diagnóstico
10.
Clinics (Sao Paulo) ; 76: e2926, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34495079

RESUMO

OBJECTIVES: To describe the MORPHEOS (Morbidity in patients with uncontrolled HTN and OSA) trial, and describe the challenges imposed by the COVID-19 pandemic. METHODS: MORPHEOS is a multicenter (n=6) randomized controlled trial designed to evaluate the blood pressure (BP) lowering effects of treatment with continuous positive airway pressure (CPAP) or placebo (nasal strips) for 6 months in adult patients with uncontrolled hypertension (HTN) and moderate-to-severe obstructive sleep apnea (OSA). Patients using at least one antihypertensive medication were included. Uncontrolled HTN was confirmed by at least one abnormal parameter in the 24-hour ABPM and ≥80% medication adherence evaluated by pill counting after the run-in period. OSA was defined by an apnea-hypopnea index ≥15 events/hours. The co-primary endpoints are brachial BP (office and ambulatory BP monitoring, ABPM) and central BP. Secondary outcomes include hypertension-mediated organ damage (HMOD) to heart, aorta, eye, and kidney. We pre-specified several sub-studies from this investigation. Visits occur once a week in the first month and once a month thereafter. The programmed sample size was 176 patients but the pandemic prevented this final target. A post-hoc power analysis will be calculated from the final sample. ClinicalTrials.gov: NCT02270658. RESULTS: The first 100 patients are predominantly males (n=69), age: 52±10 years, body mass index: 32.7±3.9 kg/m2 with frequent co-morbidities. CONCLUSIONS: The MORPHEOS trial has a unique study design including a run-in period; pill counting, and detailed analysis of hypertension-mediated organ damage in patients with uncontrolled HTN that will allow clarification of the impact of OSA treatment with CPAP.


Assuntos
COVID-19 , Hipertensão , Apneia Obstrutiva do Sono , Adulto , Pressão Sanguínea , Pressão Positiva Contínua nas Vias Aéreas , Humanos , Hipertensão/epidemiologia , Hipertensão/terapia , Masculino , Pessoa de Meia-Idade , Pandemias , SARS-CoV-2 , Apneia Obstrutiva do Sono/terapia
11.
Trials ; 22(1): 638, 2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34535165

RESUMO

BACKGROUND: Sleep apnea and coronary artery disease are prevalent and relevant diseases. The mechanism by which sleep apnea leads to coronary artery disease remains unclear. Intermittent hypoxia, caused by sleep apnea, leads to inflammation and consequent endothelial dysfunction. Endothelial dysfunction precedes the development of atherosclerotic disease and the occurrence of cardiovascular events. Agents that potentially act to improve endothelial function can help prevent cardiovascular events. Patients using immunomodulators due to rheumatic diseases have a lower prevalence of cardiovascular diseases. However, the potential cardioprotective effect of these drugs in patients without autoimmune diseases is not clear. Hydroxychloroquine (HCQ) is an immunomodulator used to treat rheumatoid arthritis and systemic lupus erythematosus. In addition to its anti-inflammatory properties, HCQ reduces cholesterol and blood glucose levels and has antithrombotic effects. The drug is inexpensive and widely available. Adverse effects of HCQ are rare and occur more frequently with high doses. OBJECTIVE: In this randomized clinical trial, the effect of HCQ treatment on endothelial function will be tested in seniors with sleep apnea. METHODS: We will recruit participants over the age of 65 and with moderate-severe sleep apnea from an ongoing cohort. We chose to use this sample already evaluated for sleep apnea for reasons of convenience, but also because the elderly with sleep apnea are vulnerable to heart disease. Endothelial function will be assessed by examining flow-mediated dilation of the brachial artery, the gold standard method, considered an independent predictor of cardiovascular events in the general population and by peripheral arterial tonometry, the most recent and most easily obtained method. Hydroxychloroquine will be used at a dose of 400 mg/daily for 8 weeks. DISCUSSION: Our study aims to obtain evidence, albeit preliminary, of the efficacy of hydroxychloroquine in improving endothelial function and reducing cardiovascular risk markers. If the improvement occurs, we plan to design a randomized multicenter clinical trial to confirm the findings. TRIAL REGISTRATION: ClinicalTrials.gov NCT04161339 . Registered on November 2019.


Assuntos
Artrite Reumatoide , Doenças Cardiovasculares , Lúpus Eritematoso Sistêmico , Síndromes da Apneia do Sono , Idoso , Humanos , Hidroxicloroquina/efeitos adversos , Estudos Multicêntricos como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Síndromes da Apneia do Sono/diagnóstico , Síndromes da Apneia do Sono/tratamento farmacológico , Resultado do Tratamento
12.
Front Mol Neurosci ; 14: 670513, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34276304

RESUMO

Infectious proteins or prions are a remarkable class of pathogens, where pathogenicity and infectious state correspond to conformational transition of a protein fold. The conformational change translates into the formation by the protein of insoluble amyloid aggregates, associated in humans with various neurodegenerative disorders and systemic protein-deposition diseases. The prion principle, however, is not limited to pathogenicity. While pathological amyloids (and prions) emerge from protein misfolding, a class of functional amyloids has been defined, consisting of amyloid-forming domains under natural selection and with diverse biological roles. Although of great importance, prion amyloid structures remain challenging for conventional structural biology techniques. Solid-state nuclear magnetic resonance (SSNMR) has been preferentially used to investigate these insoluble, morphologically heterogeneous aggregates with poor crystallinity. SSNMR methods have yielded a wealth of knowledge regarding the fundamentals of prion biology and have helped to solve the structures of several prion and prion-like fibrils. Here, we will review pathological and functional amyloid structures and will discuss some of the obtained structural models. We will finish the review with a perspective on integrative approaches combining solid-state NMR, electron paramagnetic resonance and cryo-electron microscopy, which can complement and extend our toolkit to structurally explore various facets of prion biology.

13.
J Colloid Interface Sci ; 594: 857-863, 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-33794407

RESUMO

Supramolecular chemistry has garnered important interest in recent years toward improving therapeutic efficacy via drug delivery approaches. Although self-assemblies have been deeply investigated, the design of novel drugs leveraging supramolecular chemistry is less known. In this contribution, we show that a Low Molecular Weight Gel (LMWG) can elicit cancer cell apoptosis. This biological effect results from the unique supramolecular properties of a bolaamphiphile-based gelator, which allow for strong interaction with the lipid membrane. This novel supramolecular-drug paradigm opens up new possibilities for therapeutic applications targeting membrane lipids.


Assuntos
Sistemas de Liberação de Medicamentos , Furanos , Géis , Piridonas
15.
Proc Natl Acad Sci U S A ; 118(1)2021 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-33443172

RESUMO

Neurodegenerative disorders are frequently associated with ß-sheet-rich amyloid deposits. Amyloid-forming proteins can aggregate under different structural conformations known as strains, which can exhibit a prion-like behavior and distinct pathophenotypes. Precise molecular determinants defining strain specificity and cross-strain interactions (cross-seeding) are currently unknown. The HET-s prion protein from the fungus Podospora anserina represents a model system to study the fundamental properties of prion amyloids. Here, we report the amyloid prion structure of HELLF, a distant homolog of the model prion HET-s. We find that these two amyloids, sharing only 17% sequence identity, have nearly identical ß-solenoid folds but lack cross-seeding ability in vivo, indicating that prion specificity can differ in extremely similar amyloid folds. We engineer the HELLF sequence to explore the limits of the sequence-to-fold conservation and to pinpoint determinants of cross-seeding and prion specificity. We find that amyloid fold conservation occurs even at an exceedingly low level of identity to HET-s (5%). Next, we derive a HELLF-based sequence, termed HEC, able to breach the cross-seeding barrier in vivo between HELLF and HET-s, unveiling determinants controlling cross-seeding at residue level. These findings show that virtually identical amyloid backbone structures might not be sufficient for cross-seeding and that critical side-chain positions could determine the seeding specificity of an amyloid fold. Our work redefines the conceptual boundaries of prion strain and sheds light on key molecular features concerning an important class of pathogenic agents.


Assuntos
Amiloide/química , Amiloide/metabolismo , Príons/metabolismo , Sequência de Aminoácidos/genética , Amiloide/ultraestrutura , Proteínas Amiloidogênicas/química , Proteínas Amiloidogênicas/metabolismo , Sequência Conservada/genética , Proteínas Fúngicas/metabolismo , Modelos Biológicos , Podospora/genética , Agregados Proteicos/fisiologia , Dobramento de Proteína , Estrutura Terciária de Proteína , Alinhamento de Sequência
16.
Clinics ; 76: e2926, 2021. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1339699

RESUMO

OBJECTIVES: To describe the MORPHEOS (Morbidity in patients with uncontrolled HTN and OSA) trial, and describe the challenges imposed by the COVID-19 pandemic. METHODS: MORPHEOS is a multicenter (n=6) randomized controlled trial designed to evaluate the blood pressure (BP) lowering effects of treatment with continuous positive airway pressure (CPAP) or placebo (nasal strips) for 6 months in adult patients with uncontrolled hypertension (HTN) and moderate-to-severe obstructive sleep apnea (OSA). Patients using at least one antihypertensive medication were included. Uncontrolled HTN was confirmed by at least one abnormal parameter in the 24-hour ABPM and ≥80% medication adherence evaluated by pill counting after the run-in period. OSA was defined by an apnea-hypopnea index ≥15 events/hours. The co-primary endpoints are brachial BP (office and ambulatory BP monitoring, ABPM) and central BP. Secondary outcomes include hypertension-mediated organ damage (HMOD) to heart, aorta, eye, and kidney. We pre-specified several sub-studies from this investigation. Visits occur once a week in the first month and once a month thereafter. The programmed sample size was 176 patients but the pandemic prevented this final target. A post-hoc power analysis will be calculated from the final sample. ClinicalTrials.gov: NCT02270658. RESULTS: The first 100 patients are predominantly males (n=69), age: 52±10 years, body mass index: 32.7±3.9 kg/m2 with frequent co-morbidities. CONCLUSIONS: The MORPHEOS trial has a unique study design including a run-in period; pill counting, and detailed analysis of hypertension-mediated organ damage in patients with uncontrolled HTN that will allow clarification of the impact of OSA treatment with CPAP.


Assuntos
Humanos , Masculino , Adulto , Pessoa de Meia-Idade , Apneia Obstrutiva do Sono/terapia , COVID-19 , Hipertensão/terapia , Hipertensão/epidemiologia , Pressão Sanguínea , Pressão Positiva Contínua nas Vias Aéreas , Pandemias , SARS-CoV-2
17.
Clinics ; 76: e3056, 2021. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1339714

RESUMO

OBJECTIVES: Owing to the fact that obstructive sleep apnea (OSA) is an underreported disease, the strategy used for the diagnosis of OSA has been extensively dissected to devise a simplified process that can be accessed by the public health services. Polysomnography (PSG) type I, the gold standard for the diagnosis of OSA, is expensive and difficult to access by low-income populations. In this study, we aimed to verify the accuracy of the oxyhemoglobin desaturation index (ODI) in comparison to the apnea-hypopnea index (AHI) using a portable monitor. METHODS: We evaluated 94 type III PSG home test results of 65 elderly patients (69.21±6.94 years old), along with information, such as the body mass index (BMI) and sex, using data obtained from a clinical trial database. RESULTS: A significant linear positive correlation (r=0.93, p<0.05) was observed between ODI and AHI, without any interference from sex, BMI, and positional component. The sensitivity of ODI compared to that of AHI increased with an increase in the severity of OSA, while the specificity of ODI in comparison to that of AHI was high for all degrees of severity. The accuracy of ODI was 80.7% for distinguishing between patients with mild and moderate apnea and 84.4% for distinguishing between patients with moderate and severe apnea. CONCLUSION: The ODI values obtained in uncontrolled conditions exhibited high sensitivity for identifying severe apnea compared to the AHI values, and correctly identified the severity of OSA in more than 80% of the cases. Thus, oximetry is promising strategy for diagnosing OSA.


Assuntos
Humanos , Pessoa de Meia-Idade , Idoso , Apneia Obstrutiva do Sono/diagnóstico , Oximetria , Índice de Massa Corporal , Polissonografia
18.
Elife ; 92020 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-32662773

RESUMO

The bacterial plasma membrane is an important cellular compartment. In recent years it has become obvious that protein complexes and lipids are not uniformly distributed within membranes. Current hypotheses suggest that flotillin proteins are required for the formation of complexes of membrane proteins including cell-wall synthetic proteins. We show here that bacterial flotillins are important factors for membrane fluidity homeostasis. Loss of flotillins leads to a decrease in membrane fluidity that in turn leads to alterations in MreB dynamics and, as a consequence, in peptidoglycan synthesis. These alterations are reverted when membrane fluidity is restored by a chemical fluidizer. In vitro, the addition of a flotillin increases membrane fluidity of liposomes. Our data support a model in which flotillins are required for direct control of membrane fluidity rather than for the formation of protein complexes via direct protein-protein interactions.


Every living cell is enclosed by a flexible membrane made of molecules known as phospholipids, which protects the cell from harmful chemicals and other threats. In bacteria and some other organisms, a rigid structure known as the cell wall sits just outside of the membrane and determines the cell's shape. There are several proteins in the membrane of bacteria that allow the cell to grow by assembling new pieces of the cell wall. To ensure these proteins expand the cell wall at the right locations, another protein known as MreB moves and organizes them to the appropriate place in the membrane and controls their activity. Previous studies have found that another class of proteins called flotillins are involved in arranging proteins and phospholipid molecules within membranes. Bacteria lacking these proteins do not grow properly and are unable to maintain their normal shape. However, the precise role of the flotillins remained unclear. Here, Zielinska, Savietto et al. used microscopy approaches to study flotillins in a bacterium known as Bacillus subtilis. The experiments found that, in the presence of flotillins, MreB moved around the membrane more quickly (suggesting it was more active) than when no flotillins were present. Similar results were observed when bacterial cells lacking flotillins were treated with a chemical that made membranes more 'fluid' ­ that is, made it easier for the molecules within the membrane to travel around. Further experiments found that flotillins allowed the phospholipid molecules within an artificial membrane to move around more freely, which increases the fluidity of the membrane. These findings suggest that flotillins make the membranes of bacterial cells more fluid to help cells expand their walls and perform several other processes. Understanding how bacteria control the components of their membranes will further our understanding of how many currently available antibiotics work and may potentially lead to the design of new antibiotics in the future.


Assuntos
Bacillus subtilis/fisiologia , Proteínas de Bactérias/fisiologia , Fluidez de Membrana/fisiologia , Proteínas de Membrana/metabolismo , Peptidoglicano/biossíntese
19.
Sci Rep ; 10(1): 4051, 2020 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-32132631

RESUMO

MapZ localizes at midcell and acts as a molecular beacon for the positioning of the cell division machinery in the bacterium Streptococcus pneumoniae. MapZ contains a single transmembrane helix that separates the C-terminal extracellular domain from the N-terminal cytoplasmic domain. Only the structure and function of the extracellular domain is known. Here, we demonstrate that large parts of the cytoplasmic domain is intrinsically disordered and that there are two regions (from residues 45 to 68 and 79 to 95) with a tendency to fold into amphipathic helices. We further reveal that these regions interact with the surface of liposomes that mimic the Streptococcus pneumoniae cell membrane. The highly conserved and unfolded N-terminal region (from residues 17 to 43) specifically interacts with FtsZ independently of FtsZ polymerization state. Moreover, we show that MapZ phosphorylation at positions Thr67 and Thr68 does not impact the interaction with FtsZ or liposomes. Altogether, we propose a model in which the MapZ-mediated recruitment of FtsZ to mid-cell is modulated through competition of MapZ binding to the cell membrane. The molecular interplay between the components of this tripartite complex could represent a key step toward the complete assembly of the divisome.


Assuntos
Proteínas de Bactérias/metabolismo , Membrana Celular/metabolismo , Proteínas do Citoesqueleto/metabolismo , Streptococcus pneumoniae/metabolismo , Proteínas de Bactérias/genética , Membrana Celular/genética , Proteínas do Citoesqueleto/genética , Streptococcus pneumoniae/genética
20.
J Clin Sleep Med ; 16(2): 199-206, 2020 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-31992408

RESUMO

STUDY OBJECTIVES: The accuracy of obstructive sleep apnea (OSA) screening instruments in seniors may change as the predictive role of sex, age, and body mass index (BMI) changes with aging. We investigated the diagnostic performance of the STOP-BANG questionnaire in older individuals with aging-adapted scores and thresholds. METHODS: Independent community-dwelling adults aged 65 years or older were screened for OSA. The STOP-BANG questionnaire was tested with different configurations and compared to the apnea-hypopnea index (AHI) obtained from home sleep apnea testing (HSAT). Epworth Sleepiness Scale (ESS) and Athens Insomnia Scale (AIS) were tested as possible supplementary screening criteria. RESULTS: We recruited 458 individuals with a mean age of 71 ± 5 years, 41% men, BMI of 28.5 ± 4.6 kg/m². Mild, moderate, and severe OSA were present in, respectively, 34%, 30%, and 19% of the sample. The STOP questions had an area under the curve (AUC) of the receiver operating characteristic curve significantly lower than the STOP-BANG and the STOP+BMI > 28 kg/m² (STOP-B28). Both STOP-BANG and STOP-B28 had high sensitivity and low specificity in all OSA levels with similar AUC to predict AHI ≥ 5 events/h, 0.64. ESS and AIS were nonsignificant as adjunctive instruments. CONCLUSIONS: Novel modifications of a standard instrument created the STOP-B28, a simpler-to-obtain and similarly performing variation of the STOP-BANG using fewer inputs, and useful to exclude OSA. Screening seniors via questionnaires to detect OSA is problematic. Considering the 83% OSA prevalence in this age group, it may be a sensible option to indicate objective tests, oximetry, HSAT, or even polysomnography, as a first step in OSA investigation.


Assuntos
Apneia Obstrutiva do Sono , Adulto , Idoso , Feminino , Humanos , Masculino , Programas de Rastreamento , Oximetria , Polissonografia , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/epidemiologia , Inquéritos e Questionários
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