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1.
Proc Natl Acad Sci U S A ; 119(33): e2203287119, 2022 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-35939711

RESUMO

Electrical neuron stimulation holds promise for treating chronic neurological disorders, including spinal cord injury, epilepsy, and Parkinson's disease. The implementation of ultrathin, flexible electrodes that can offer noninvasive attachment to soft neural tissues is a breakthrough for timely, continuous, programable, and spatial stimulations. With strict flexibility requirements in neural implanted stimulations, the use of conventional thick and bulky packages is no longer applicable, posing major technical issues such as short device lifetime and long-term stability. We introduce herein a concept of long-lived flexible neural electrodes using silicon carbide (SiC) nanomembranes as a faradic interface and thermal oxide thin films as an electrical barrier layer. The SiC nanomembranes were developed using a chemical vapor deposition (CVD) process at the wafer level, and thermal oxide was grown using a high-quality wet oxidation technique. The proposed material developments are highly scalable and compatible with MEMS technologies, facilitating the mass production of long-lived implanted bioelectrodes. Our experimental results showed excellent stability of the SiC/silicon dioxide (SiO2) bioelectronic system that can potentially last for several decades with well-maintained electronic properties in biofluid environments. We demonstrated the capability of the proposed material system for peripheral nerve stimulation in an animal model, showing muscle contraction responses comparable to those of a standard non-implanted nerve stimulation device. The design concept, scalable fabrication approach, and multimodal functionalities of SiC/SiO2 flexible electronics offer an exciting possibility for fundamental neuroscience studies, as well as for neural stimulation-based therapies.


Assuntos
Terapia por Estimulação Elétrica , Neuroestimuladores Implantáveis , Nanoestruturas , Semicondutores , Compostos Inorgânicos de Carbono/química , Terapia por Estimulação Elétrica/instrumentação , Membranas Artificiais , Compostos de Silício/química , Dióxido de Silício/química
2.
J Comput Chem ; 45(26): 2251-2264, 2024 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-38838302

RESUMO

This study investigates the formation of partial sigma (σ) covalent bonds in experimentally synthesizable biradicals formed from hydrogenated and fluorinated C8, C20, and C60 cage structures, by assessing their stability, geometry, and bonding character in singlet and triplet states using restricted B3LYP-D3/6-31+G(d,p) theory, natural bond orbital (NBO) analysis, and complete active space self-consistent field (CASSCF) method. The results show that these partial σCC bonds have Wiberg bond orders of 0.38 to 0.48 and bond lengths ranging from 2.62 Å to 5.93 Å. Cage size influences the characteristics of the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO), with electrons favoring more antibonding orbitals in smaller cages where electrons reside more on the exterior of the cage and favoring bonding orbitals in larger ones where electrons are more in the interior. Fluorination enhances electron density on bonding orbitals. The analysis further clarified that the differentiation between antibonding and bonding features of HOMOs and LUMOs extends beyond merely electron transfer from s- to p-atomic orbitals, also noting possible interactions of the same symmetry repel. The study also introduces hyperconjugation from α-position CH bonds as a factor in stabilizing partial σ-bond formation. The results also caution against the use of broken symmetry methodology in unrestricted SCF wavefunctions for biradicals, such as those in this study as it may cause large spin contamination and thus errors in the calculated electronic properties results.

3.
J Formos Med Assoc ; 123(3): 357-365, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37714767

RESUMO

BACKGROUND: Acute invasive fungal rhinosinusitis (AIFR) is a potentially lethal infection commonly found in immunocompromised patients. It is considered the most aggressive subtype of fungal sinusitis and can lead to severe morbidity and mortality. There was a significant increase in the incidence of AIFR in post-COVID-19 patients compared to AIFR cases before the COVID-19 pandemic. This study aimed to describe the clinical presentation of AIFR associated with COVID-19 illness. METHODS: A retrospective study included 22 patients diagnosed with AIFR with a recent COVID-19 infection. RESULTS: The most frequent disease associated with AIFR was diabetes mellitus (95.5%). The mycological analysis identified infection caused by Aspergillus species in 72.7% of patients. Along with stabilizing hemodynamic parameters and controlling any comorbidities, all patients in the present study underwent combined surgical debridement followed by antifungal medications. The overall survival rate was 72.7%. The chance of developing a fatal outcome was significantly higher if meningitis presented initially (odds ratio 35.63, p < 0.05). CONCLUSION: The presence of meningitis upon initial diagnosis is related to a significantly higher chance of developing a fatal outcome and should be considered, especially in AIFR patients previously treated for COVID-19 infections. Early diagnosis, early use of antifungal agents, aggressive surgical debridement, and control of comorbid conditions remain crucial in managing AIFR.


Assuntos
COVID-19 , Meningite , Rinite , Rinossinusite , Sinusite , Humanos , Estudos Retrospectivos , Vietnã , Pandemias , Rinite/epidemiologia , Rinite/terapia , COVID-19/complicações , Sinusite/epidemiologia , Sinusite/microbiologia , Doença Aguda , Antifúngicos/uso terapêutico , Meningite/tratamento farmacológico
4.
Clin Infect Dis ; 77(10): 1372-1380, 2023 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-37467019

RESUMO

BACKGROUND: High-dose daptomycin is increasingly used in patients with bone and joint infection (BJI). This raises concerns about a higher risk of adverse events (AEs), including daptomycin-induced eosinophilic pneumonia (DIEP) and myotoxicity. We aimed to examine pharmacokinetic and other potential determinants of DIEP and myotoxicity in patients with BJI receiving daptomycin. METHODS: All patients receiving daptomycin for BJI were identified in a prospective cohort study. Cases were matched at a 1:3 ratio, with controls randomly selected from the same cohort. Bayesian estimation of the daptomycin daily area under the concentration-time curve over 24 hours (AUC24h) was performed with the Monolix software based on therapeutic drug monitoring (TDM) data. Demographic and biological data were also collected. Risk factors of AEs were analyzed using Cox proportional hazards model. RESULTS: From 1130 patients followed over 7 years, 9 with DIEP, 26 with myotoxicity, and 106 controls were included in the final analysis. Daptomycin AUC24h, C-reactive protein, and serum protein levels were associated with the risk of AEs. The adjusted hazard ratio of DIEP or myotoxicity was 3.1 (95% confidence interval [CI], 1.48-6.5; P < .001) for daptomycin AUC24h > 939 mg/h/L, 9.8 (95% CI, 3.94-24.5; P < .001) for C-reactive protein > 21.6 mg/L, and 2.4 (95% CI, 1.02-5.65; P = .04) for serum protein <72 g/L. CONCLUSIONS: We identified common determinants of DIEP and myotoxicity in patients with BJI. Because the risk of AEs was associated with daptomycin exposure, daptomycin TDM and model-informed precision dosing may help optimize the efficacy and safety of daptomycin treatment in this setting. A target AUC24h range of 666 to 939 mg/h/L is suggested.


Assuntos
Daptomicina , Eosinofilia Pulmonar , Humanos , Daptomicina/uso terapêutico , Antibacterianos/uso terapêutico , Eosinofilia Pulmonar/induzido quimicamente , Eosinofilia Pulmonar/tratamento farmacológico , Miotoxicidade/tratamento farmacológico , Estudos Prospectivos , Teorema de Bayes , Proteína C-Reativa , Fatores de Risco
5.
Small ; 19(9): e2204946, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36538749

RESUMO

Flexible and implantable electronics hold tremendous promises for advanced healthcare applications, especially for physiological neural recording and modulations. Key requirements in neural interfaces include miniature dimensions for spatial physiological mapping and low impedance for recognizing small biopotential signals. Herein, a bottom-up mesoporous formation technique and a top-down microlithography process are integrated to create flexible and low-impedance mesoporous gold (Au) electrodes for biosensing and bioimplant applications. The mesoporous architectures developed on a thin and soft polymeric substrate provide excellent mechanical flexibility and stable electrical characteristics capable of sustaining multiple bending cycles. The large surface areas formed within the mesoporous network allow for high current density transfer in standard electrolytes, highly suitable for biological sensing applications as demonstrated in glucose sensors with an excellent detection limit of 1.95 µm and high sensitivity of 6.1 mA cm-2  µM-1 , which is approximately six times higher than that of benchmarking flat/non-porous films. The low impedance of less than 1 kΩ at 1 kHz in the as-synthesized mesoporous electrodes, along with their mechanical flexibility and durability, offer peripheral nerve recording functionalities that are successfully demonstrated in vivo. These features highlight the new possibilities of our novel flexible nanoarchitectonics for neuronal recording and modulation applications.


Assuntos
Técnicas Biossensoriais , Eletrônica , Eletrodos , Monitorização Fisiológica , Porosidade
6.
Sensors (Basel) ; 23(1)2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36617144

RESUMO

In this study, we propose a specimen tube prototype and smart specimen transport box using radio frequency identification (RFID) and narrow band-Internet of Things (NB-IoT) technology to use in the Department of Laboratory Medicine, King Chulalongkorn Memorial Hospital. Our proposed method replaces the existing system, based on barcode technology, with shortage usage and low reliability. In addition, tube-tagged barcode has not eliminated the lost or incorrect delivery issues in many laboratories. In this solution, the passive RFID tag is attached to the surface of the specimen tube and stores information such as patient records, required tests, and receiver laboratory location. This information can be written and read multiple times using an RFID device. While delivering the specimen tubes via our proposed smart specimen transport box from one clinical laboratory to another, the NB-IoT attached to the box monitors the temperature and humidity values inside the box and tracks the box's GPS location to check whether the box arrives at the destination. The environmental condition inside the specimen transport box is sent to the cloud and can be monitored by doctors. The experimental results have proven the innovation of our solution and opened a new dimension for integrating RFID and IoT technologies into the specimen logistic system in the hospital.


Assuntos
Internet das Coisas , Laboratórios Hospitalares , Dispositivo de Identificação por Radiofrequência , Humanos , Dispositivo de Identificação por Radiofrequência/métodos , Reprodutibilidade dos Testes , Tecnologia
7.
Rev Med Suisse ; 19(822): 714-718, 2023 Apr 12.
Artigo em Francês | MEDLINE | ID: mdl-37057852

RESUMO

This article highlights four recent updates in infectious disease in the management of bone and joint infections (BJI). During the first six weeks of treatment of a BJI, with or without orthopedic implant, oral antimicrobial therapy is as effective as intravenous therapy. For periprosthetic joint infections, a randomized control study failed to demonstrate non-inferiority of 6 versus 12 weeks of antibiotic therapy. In diabetic foot osteomyelitis, a 3-week course of antibiotics appears to be non-inferior to a 6-week course. Phage therapy seems promising in adjunctive therapy of complex BJI.


Cet article expose quatre nouveautés thérapeutiques significatives en orthopédie septique. Durant les six premières semaines de traitement d'une infection ostéoarticulaire, avec ou sans matériel, une antibiothérapie per os est aussi efficace qu'une antibiothérapie intraveineuse. Concernant les arthroplasties infectées, il n'y a pas de preuve suffisante à raccourcir le traitement antibiotique à moins de douze semaines. Dans les ostéomyélites de pied diabétique, une antibiothérapie de trois semaines semble non inférieure à une thérapie de six semaines. Finalement, la phagothérapie est prometteuse dans les infections ostéoarticulaires, particulièrement dans les situations d'échec des traitements conventionnels.


Assuntos
Artrite Infecciosa , Doenças Transmissíveis , Pé Diabético , Osteomielite , Humanos , Doenças Transmissíveis/tratamento farmacológico , Artrite Infecciosa/tratamento farmacológico , Osteomielite/terapia , Antibacterianos/uso terapêutico , Pé Diabético/tratamento farmacológico
8.
Am J Transplant ; 22(12): 3031-3046, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36031963

RESUMO

Bone and joint infection (BJI) epidemiology and outcomes in solid organ transplant recipients (SOTr) remain largely unknown. We aim to describe BJI in a multi-center cohort of SOTr (Swiss Transplant Cohort Study). All consecutive SOTr with BJI (01.05.2008-31.12.2019) were included. A nested case-control study to identify risk factors for BJI was performed. Among 4482 patients, 61 SOTr with 82 BJI were included, at an incidence of 1.4% (95% CI 1.1-1.7), higher in heart and kidney-pancreas SOTr (Gray's test p < .01). Although BJI were predominately late events (median of 18.5 months post-SOT), most infections occurred during the first year post-transplant in thoracic SOTr. Diabetic foot osteomyelitis was the most frequent infection (38/82, 46.3%), followed by non-vertebral osteomyelitis (26/82, 31.7%). Pathogens included Gram-positive cocci (70/131, 53.4%), Gram-negative bacilli (34/131, 26.0%), and fungi (9/131, 6.9%). BJI predictors included male gender (OR 2.94, 95% CI 1.26-6.89) and diabetes (OR 2.97, 95% CI 1.34-6.56). Treatment failure was observed in 25.9% (21/81) patients and 1-year mortality post-BJI diagnosis was 14.8% (9/61). BJI remain a rare event in SOTr, associated with subtle clinical presentations, high morbidity and relapses, requiring additional studies in the future.


Assuntos
Transplante de Órgãos , Osteomielite , Humanos , Masculino , Transplante de Órgãos/efeitos adversos , Estudos de Casos e Controles , Estudos de Coortes , Transplantados , Osteomielite/epidemiologia , Osteomielite/etiologia
9.
Ann Surg ; 276(2): 233-238, 2022 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-35623048

RESUMO

BACKGROUND: The optimal duration of antibiotic therapy for soft-tissue infections of the diabetic foot remains unknown. OBJECTIVE: We determine if antibiotic therapy after debridement for a short (10 days), compared with a long (20 days), duration for soft-tissue infections of the diabetic foot results in similar rates of clinical remission and adverse events (AE). SUMMARY OF BACKGROUND DATA: The optimal duration of systemic antibiotic therapy, after successful debridement, for soft tissue infections of diabetic patients is unknown. Because of the high recurrence risk, overuse is commonplace. METHODS: This was a randomized, controlled, non-inferiority pilot trial of cases of diabetic foot infection (excluding osteomyelitis) with the primary outcome of "clinical remission at 2-months follow-up". RESULTS: Among 66 enrolled episodes (17% females; median age 71 years), we randomized 35 to the 10-day arm and 31 to the 20-day arm. The median duration of the parenteral antibiotic therapy was 1 day, with the remainder given orally. In the intention-to-treat population, we achieved clinical remission in 27 (77%) patients in the 10-day arm compared to 22 (71%) in the 20-days arm ( P = 0.57). There were a similar proportion in each arm of AE (14/35 versus 11/31; P = 0.71), and remission in the per-protocol population (25/32 vs 18/27; P = 0.32). Overall, 8 soft tissue DFIs in the 10-day arm and 5 cases in the 20-day arm recurred as a new osteomyelitis [8/35 (23%) versus 5/31 (16%); P = 0.53]. Overall, the number of recurrences limited to the soft tissues was 4 (6%). By multivariate analysis, rates of remission (intention-to-treat population, hazard ratio 0.6, 95%CI 0.3-1.1; per-protocol population 0.8, 95%CI 0.4-1.5) and AE were not significantly different with a 10-day compared to 20-day course. CONCLUSIONS: In this randomized, controlled pilot trial, post-debridement antibiotic therapy for soft tissue DFI for 10 days gave similar (and non-inferior) rates of remission and AEs to 20 days. A larger confirmatory trial is under way. TRIAL REGISTRATION: ClinicalTrials NCT03615807.


Assuntos
Diabetes Mellitus , Pé Diabético , Osteomielite , Infecções dos Tecidos Moles , Idoso , Antibacterianos , Desbridamento , Diabetes Mellitus/tratamento farmacológico , Pé Diabético/complicações , Pé Diabético/tratamento farmacológico , Feminino , Humanos , Masculino , Osteomielite/induzido quimicamente , Osteomielite/etiologia , Projetos Piloto , Infecções dos Tecidos Moles/tratamento farmacológico
10.
Small ; 18(4): e2105748, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34874620

RESUMO

Transformation of conventional 2D platforms into unusual 3D configurations provides exciting opportunities for sensors, electronics, optical devices, and biological systems. Engineering material properties or controlling and modulating stresses in thin films to pop-up 3D structures out of standard planar surfaces has been a highly active research topic over the last decade. Implementation of 3D micro and nanoarchitectures enables unprecedented functionalities including multiplexed, monolithic mechanical sensors, vertical integration of electronics components, and recording of neuron activities in 3D organoids. This paper provides an overview on stress engineering approaches to developing 3D functional microsystems. The paper systematically presents the origin of stresses generated in thin films and methods to transform a 2D design into an out-of-plane configuration. Different types of 3D micro and nanostructures, along with their applications in several areas are discussed. The paper concludes with current technical challenges and potential approaches and applications of this fast-growing research direction.


Assuntos
Eletrônica , Nanoestruturas , Nanoestruturas/química , Organoides
11.
Am J Addict ; 31(1): 85-88, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34713943

RESUMO

BACKGROUND AND OBJECTIVES: Methamphetamine use is a major source of morbidity and mortality but has no reliably effective interventions. We identified cariprazine as an option for treatment of methamphetamine use disorder (MUD) and present two cases. METHODS: Two patients with MUD and psychotic disorders were treated with cariprazine. Abstinence and cravings were assessed using urine drug screens and the Brief Substance Craving Scale, respectively. RESULTS: Both patients reported global functional improvement, reduction in methamphetamine cravings and use with cariprazine, confirmed with negative urine drug screens. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: Cariprazine's unique pharmacodynamic profile conveys potential efficacy for MUD. It would be a novel treatment that targets multiple psychiatric symptoms seen in MUD.


Assuntos
Metanfetamina , Fissura , Humanos , Metanfetamina/efeitos adversos , Piperazinas/farmacologia
12.
Sensors (Basel) ; 22(23)2022 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-36501837

RESUMO

For magnetic levitation systems subject to dynamical uncertainty and exterior perturbations, we implement a real-time Prescribed Performance Control (PPC). A modified function of Global Fast Terminal Sliding Mode Manifold (GFTSMM) based on the transformed error of the novel PPC is introduced; hence, the error variable quickly converges to the equilibrium point with the prescribed performance, which means that maximum overshoot and steady-state of the controlled errors will be in a knowledge-defined boundary. To enhance the performance of Global Fast Terminal Sliding Mode Control (GFTSMC) and to reduce chattering in the control input, a modified third-order sliding mode observer (MTOSMO) is proposed to estimate the whole uncertainty and external disturbance. The combination of the GFTSMC, PPC, and MTOSMO generates a novel solution ensuring a finite-time stable position of the controlled ball and the possibility of performing different orbit tracking missions with an impressive performance in terms of tracking accuracy, fast convergence, stabilization, and chattering reduction. It also possesses a simple design that is suitable for real-time applications. By using the Lyapunov-based method, the stable evidence of the developed method is fully verified. We implement a simulation and an experiment on the laboratory magnetic levitation model to demonstrate the improved performance of the developed control system.


Assuntos
Conhecimento , Laboratórios , Fenômenos Físicos , Simulação por Computador , Fenômenos Magnéticos
13.
Sensors (Basel) ; 22(7)2022 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-35408229

RESUMO

Through this article, we present an advanced prescribed performance-tracking control system with finite-time convergence stability for uncertain robotic manipulators. It is therefore necessary to define a suitable performance function and error transformation to guarantee a prescribed performance within a finite time. Following the definitions mentioned, a modified integral nonlinear sliding-mode hyperplane is constructed from the transformed errors. By using the designed nonlinear sliding-mode surface and the super-twisting reaching control law, an advanced approach to the prescribed performance control was formed for the trajectory tracking control of uncertain robotic manipulators. The proposed controller exhibits improved properties, including estimated convergence speed and a predefined upper and lower limit for maximum overshoot during transient responses. Furthermore, the maximum allowable size of the control errors at the steady-state can be predefined and these errors will inevitably converge to zero within a finite time, while the proposed controller can provide a smooth control torque without the loss of its robustness. It is shown that the proposed control system is globally stable and convergent over a finite time. A comprehensive analysis of the effectiveness of the proposed control algorithm was already conducted via the simulation of an industrial robot manipulator.


Assuntos
Procedimentos Cirúrgicos Robóticos , Robótica , Algoritmos , Simulação por Computador , Incerteza
14.
Sensors (Basel) ; 22(20)2022 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-36298184

RESUMO

In this paper, the problem of an APPTMC for manipulators is investigated. During the robot's operation, the error states should be kept within an outlined range to ensure a steady-state and dynamic attitude. Firstly, we propose the modified PPFs. Afterward, a series of transformed errors is used to convert "constrained" systems into equivalent "unconstrained" ones, to facilitate control design. The modified PPFs ensure position tracking errors are managed in a pre-designed performance domain. Especially, the SSE boundaries will be symmetrical to zero, so when the transformed error is zero, the tracking error will be as well. Secondly, a modified NISMS based on the transformed errors allows for determining the highest acceptable range of the tracking errors in the steady-state, finite-time convergence index, and singularity elimination. Thirdly, a fixed-time USOSMO is proposed to directly estimate the lumped uncertainty. Fourthly, an ASTwCL is applied to deal with observer output errors and chattering. Finally, an observer-based-control solution is synthesized from the above techniques to achieve PCP in the sense of finite-time Lyapunov stability. In addition, the precision, robustness, as well as harmful chattering reduction of the proposed APPTMC are improved significantly. The Lyapunov theory is used to analyze the stability of closed-loop systems. Throughout simulations, the proposed PPTMC has been shown to perform well and be effective.


Assuntos
Procedimentos Cirúrgicos Robóticos , Robótica , Robótica/métodos , Movimento (Física) , Incerteza
15.
Rev Med Suisse ; 18(808): 2358-2362, 2022 Dec 14.
Artigo em Francês | MEDLINE | ID: mdl-36515472

RESUMO

Wound healing issues are not rare after total knee arthroplasty. While most patients heal with local wound care, a minority is susceptible to develop serious complications such as peri-prosthetic joint infection. If direct closure is not feasible, we recommend a multidisciplinary approach based on the ortho-plastic model to determine the optimal wound closure strategy. Negative pressure wound therapy can be used while waiting for definitive coverage to optimise wound environment. Medial gastrocnemius flap is considered as the gold standard procedure for peri-prosthetic substance loss around the knee.


Les problèmes de cicatrisation ne sont pas rares après l'implantation d'une prothèse totale de genou. La plupart des patients guérissent avec des soins locaux mais une minorité d'entre eux peut développer des complications redoutables allant jusqu'à l'infection périprothétique. Hormis les situations pour lesquelles une fermeture directe de la cicatrice chirurgicale peut être réalisée, nous recommandons une approche multidisciplinaire basée sur le modèle de l'ortho-plastique afin de déterminer la stratégie de reconstruction la plus adaptée. La thérapie par pression négative peut être utilisée pour conditionner la plaie en vue d'un geste de couverture définitive. Le lambeau gastrocnémien médial est considéré comme la procédure de référence pour les pertes de substance périprothétique du genou.


Assuntos
Artroplastia do Joelho , Procedimentos de Cirurgia Plástica , Humanos , Artroplastia do Joelho/métodos , Retalhos Cirúrgicos/cirurgia , Articulação do Joelho/cirurgia , Cicatrização , Resultado do Tratamento
16.
Clin Infect Dis ; 73(7): e1539-e1545, 2021 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-33242083

RESUMO

BACKGROUND: In patients with diabetic foot osteomyelitis (DFO) who underwent surgical debridement, we investigated whether a short (3 weeks) duration compared with a long (6 weeks) duration of systemic antibiotic treatment is associated with noninferior results for clinical remission and adverse events (AEs). METHODS: In this prospective, randomized, noninferiority pilot trial, we randomized (allocation 1:1) patients with DFO after surgical debridement to either a 3-week or a 6-week course of antibiotic therapy. The minimal duration of follow-up after the end of therapy was 2 months. We compared outcomes using Cox regression and noninferiority analyses (25% margin, power 80%). RESULTS: Among 93 enrolled patients (18% females; median age 65 years), 44 were randomized to the 3-week arm and 49 to the 6-week arm. The median number of surgical debridements was 1 (range, 0-2 interventions). In the intention-to-treat (ITT) population, remission occurred in 37 (84%) of the patients in the 3-week arm compared with 36 (73%) in the 6-week arm (P = .21). The number of AEs was similar in the 2 study arms (17/44 vs 16/49; P = .51), as were the remission incidences in the per-protocol (PP) population (33/39 vs 32/43; P = .26). In multivariate analysis, treatment with the shorter antibiotic course was not significantly associated with remission (ITT population: hazard ratio [HR], 1.1 [95% confidence interval {CI}, .6-1.7]; PP population: HR, 0.8 [95% CI: .5-1.4]). CONCLUSIONS: In this randomized controlled pilot trial, a postdebridement systemic antibiotic therapy course for DFO of 3 weeks gave similar (and statistically noninferior) incidences of remission and AE to a course of 6 weeks. CLINICAL TRIALS REGISTRATION: NCT03615807; BASEC 2016-01008 (Switzerland).


Assuntos
Diabetes Mellitus , Pé Diabético , Osteomielite , Idoso , Antibacterianos/uso terapêutico , Diabetes Mellitus/tratamento farmacológico , Pé Diabético/tratamento farmacológico , Pé Diabético/cirurgia , Feminino , Humanos , Masculino , Osteomielite/tratamento farmacológico , Projetos Piloto , Estudos Prospectivos
17.
Diabetes Obes Metab ; 23(2): 637-641, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33026129

RESUMO

Clinicians frequently monitor serum C-reactive protein (CRP) levels during therapy for diabetic foot infections (DFIs), but evidence supporting this is unclear. Using a database from prospective controlled DFI trials, with fixed duration of antibiotic therapy, we correlated the CRP levels at study enrolment and at end of therapy (EOT). Among 159 DFI episodes, 93 involved the bone and 66 the soft tissues. Overall, treatment cured 122 infections (77%), while 37 episodes (23%) recurred after a median of 53 days. The median CRP in the groups with cure versus failure differed minimally at enrolment (median 67 vs. 81 mg/L) or EOT (7 vs. 10 mg/L). Similarly, there was negligible difference in the percentage of CRP levels that normalized at EOT (39% vs. 35%). In our prospective cohorts, a blunt iterative monitoring of CRP during DFI treatment, without correlation with clinical findings, failed to predict treatment failures.


Assuntos
Diabetes Mellitus , Pé Diabético , Antibacterianos/uso terapêutico , Proteína C-Reativa/análise , Diabetes Mellitus/tratamento farmacológico , Pé Diabético/tratamento farmacológico , Humanos , Estudos Prospectivos , Recidiva
18.
Bioorg Med Chem Lett ; 46: 128170, 2021 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-34091042

RESUMO

To date, a very limited number of peptides reported as quorum sensing inhibitors. Herein, we report the synthesis and evaluation of a series of ß-turn mimetic-based peptides as potent quorum sensing inhibitors and antibiofilm formation. In this series, peptides P1, P4, and P5 showed very promising anti-quorum sensing activity on lasB-gfp reporter strain of Pseudomonas aeruginosa without affecting bacterial growth. Under our condition, these compounds also showed good anti-violacein production of Chromobacterium violaceum. In terms of antibiofilm formation, except P5, two ß-turn mimetic-based peptides P1 and P4 showed maximum inhibition of 80% total biomass of Pseudomonas aeruginosa. This report provides the first ß-turn mimetic-based scaffold for future drug development.


Assuntos
Antibacterianos/farmacologia , Chromobacterium/efeitos dos fármacos , Descoberta de Drogas , Indóis/antagonistas & inibidores , Peptídeos/farmacologia , Pseudomonas aeruginosa/efeitos dos fármacos , Antibacterianos/síntese química , Antibacterianos/química , Chromobacterium/metabolismo , Relação Dose-Resposta a Droga , Indóis/metabolismo , Testes de Sensibilidade Microbiana , Estrutura Molecular , Peptídeos/síntese química , Peptídeos/química , Percepção de Quorum/efeitos dos fármacos , Relação Estrutura-Atividade
19.
Org Biomol Chem ; 19(46): 10073-10080, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34779471

RESUMO

Herein, we report a green, expeditious, and practically simple protocol for direct coupling of carboxylate salts and ammonium salts under ACN/H2O conditions at room temperature without the addition of tertiary amine bases. The water-soluble coupling reagent EDC·HCl is a key component in the reaction. The reaction runs smoothly with unsubstituted/substituted ammonium salts and provides a clean product without column chromatography. Our reaction tolerates both carboxylate (which are unstable in other forms) and amine salts (which are unstable/volatile when present in free form). We believe that the reported method could be used as an alternative and suitable method at the laboratory and industrial scales.

20.
BMC Cardiovasc Disord ; 21(1): 229, 2021 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-33947343

RESUMO

BACKGROUND: Little is known about the quality of life (QOL) and health status of adults with congenital heart disease (CHD) in developing countries. Therefore, this study aimed to describe the QOL and health status of hospitalized adults with CHD in Vietnam and investigate the association between QOL and their biological-social characteristics. METHODS: A cross-sectional study was conducted with 109 adults with CHD, hospitalized in the Vietnam National Heart Institute, between June and December 2019. Validated instruments to assess QOL and health status describing patient-reported outcomes were used, including the EuroQOL-5 Dimensions-5 Level, Satisfaction with Life Scale, and Hospital Anxiety and Depression Scale. RESULTS: The mean scores on the EuroQOL-descriptive system (EQ-DS) and EuroQOL visual analogue scale (EQ-VAS) were 0.792 (SD = 0.122, 95% confidence interval [CI] 0.769-0.815) and 66.3 (SD = 12.5, 95% CI 63.9-68.7), respectively. A total of 9.2% (n = 9) patients experienced life dissatisfaction. The prevalence of anxiety and depression were 18.7% (n = 20) and 11% (n = 12), respectively. Scores of QOL in patients aged > 30 years were lower than in those aged ≤ 30 years. Stratified multivariate logistic regression revealed that poor QOL related to being unemployed/unstable employment (OR 4.43, 95% CI 1.71-11.47, p = 0.002), life dissatisfaction associated with unmarried status (OR 4.63, 95% CI 1.2-17.86, p = 0.026), anxiety regarding unemployment/unstable employment (OR 3.88, 95% CI 1.27-11.84, p = 0.017) and complex CHD/PAH (OR 4.84, 95% CI 1.33-17.54, p = 0.016), and depression regarding unemployment/unstable employment (OR 4.63, 95% CI 1.22-17.59, p = 0.003). CONCLUSIONS: Reduced QOL and elevated psychological problems were common experiences among hospitalized adults with CHD in Vietnam. Biological-social characteristics such as unmarried status, unemployment/unstable employment, and complex CHD/PAH related to poor QOL, life dissatisfaction, anxiety, and depression.


Assuntos
Indicadores Básicos de Saúde , Cardiopatias Congênitas/diagnóstico , Hospitalização , Qualidade de Vida , Sobreviventes , Adolescente , Adulto , Fatores Etários , Ansiedade/diagnóstico , Ansiedade/psicologia , Estudos Transversais , Depressão/diagnóstico , Depressão/psicologia , Feminino , Nível de Saúde , Cardiopatias Congênitas/fisiopatologia , Cardiopatias Congênitas/psicologia , Humanos , Masculino , Saúde Mental , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Medição de Risco , Fatores de Risco , Determinantes Sociais da Saúde , Fatores Socioeconômicos , Sobreviventes/psicologia , Vietnã , Adulto Jovem
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