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During a 2023 outbreak of Mycoplasma pneumoniae-associated community-acquired pneumonia among children in northern Vietnam, we analyzed M. pneumoniae isolated from nasopharyngeal samples. In almost half (6 of 13) of samples tested, we found known A2063G mutations (macrolide resistance) and a novel C2353T variant on the 23S rRNA gene.
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Mutação , Mycoplasma pneumoniae , Pneumonia por Mycoplasma , RNA Ribossômico 23S , Mycoplasma pneumoniae/genética , Mycoplasma pneumoniae/classificação , Humanos , Vietnã/epidemiologia , RNA Ribossômico 23S/genética , Pneumonia por Mycoplasma/microbiologia , Pneumonia por Mycoplasma/epidemiologia , Pneumonia por Mycoplasma/história , Criança , Pré-Escolar , Infecções Comunitárias Adquiridas/microbiologia , Infecções Comunitárias Adquiridas/epidemiologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana/genéticaRESUMO
Traumatic brain injury (TBI) is a key contributor to global morbidity that lacks effective treatments. Microbial infections are common in TBI patients, and their presence could modify the physiological response to TBI. It is estimated that one-third of the human population is incurably infected with the feline-borne parasite, Toxoplasma gondii, which can invade the central nervous system and result in chronic low-grade neuroinflammation, oxidative stress, and excitotoxicity-all of which are also important pathophysiological processes in TBI. Considering the large number of TBI patients that have a pre-existing T. gondii infection prior to injury, and the potential mechanistic synergies between the conditions, this study investigated how a pre-existing T. gondii infection modified TBI outcomes across acute, sub-acute and chronic recovery in male and female mice. Gene expression analysis of brain tissue found that neuroinflammation and immune cell markers were amplified in the combined T. gondii + TBI setting in both males and females as early as 2-h post-injury. Glutamatergic, neurotoxic, and oxidative stress markers were altered in a sex-specific manner in T. gondii + TBI mice. Structural MRI found that male, but not female, T. gondii + TBI mice had a significantly larger lesion size compared to their uninfected counterparts at 18-weeks post-injury. Similarly, diffusion MRI revealed that T. gondii + TBI mice had exacerbated white matter tract abnormalities, particularly in male mice. These novel findings indicate that a pre-existing T. gondii infection affects the pathophysiological aftermath of TBI in a sex-dependent manner, and may be an important modifier to consider in the care and prognostication of TBI patients.
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Lesões Encefálicas Traumáticas , Lesões Encefálicas , Toxoplasmose , Humanos , Animais , Gatos , Feminino , Masculino , Camundongos , Doenças Neuroinflamatórias , Lesões Encefálicas/complicações , Lesões Encefálicas Traumáticas/complicações , Toxoplasmose/complicações , EncéfaloRESUMO
PURPOSE OF REVIEW: Kidney stone disease is recognized to negatively impact quality of life. This pertains to acute episodes, surgical interventions and even during asymptomatic periods. Over time there has been increased attention towards assessing this subjective parameter, including as a determinant of treatment success. Our aim was to evaluate the current status and emerging trends in this field. RECENT FINDINGS: Patient groups most affected appear to be recurrent stone formers, cystine stone formers, women, younger populations, non-Caucasians and low-income populations. Several stone specific patient reported outcome measures are now available of which, WISQol has been implemented the most in clinical research studies. More invasive interventions such as percutaneous nephrolithotomy impede quality of life to greater extent than alternatives such as shockwave lithotripsy. SUMMARY: There are certain patient groups who are more vulnerable to the negative impact of kidney stone disease on their quality of life. Urologists can improve patient care by recognizing these particular populations as well as by implemented patient reported outcome measures in their routine clinical practice and when performing research.
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Cálculos Renais , Litotripsia , Nefrolitotomia Percutânea , Humanos , Feminino , Qualidade de Vida , Resultado do TratamentoRESUMO
BACKGROUND: MGMT (O 6 -methylguanine-DNA methyltransferase) promoter methylation is a commonly assessed prognostic marker in glioblastoma (GBM). Epigenetic silencing of the MGMT gene by promoter methylation is associated with greater overall and progression free survival with alkylating agent regimens. To date, there is marked heterogeneity in how MGMT promoter methylation is tested and which CpG sites are interrogated. METHODS: To further elucidate which MGMT promoter CpG sites are of greatest interest, we performed comprehensive searches in PubMed, Web of Science, and Embase and reviewed 2,925 article abstracts. We followed the GRADE scoring system to assess risk of bias and the quality of the studies we included. RESULTS: We included articles on adult glioblastoma that examined significant sites or regions within MGMT promoter for the outcomes: overall survival, progression free survival, and/or MGMT expression. We excluded systemic reviews and articles on lower grade glioma. fifteen articles met inclusion criteria with variable overlap in laboratory and statistical methods employed, as well as CpG sites interrogated. Pyrosequencing or BeadChip arrays were the most popular methods utilized, and CpG sites between CpG's 70-90 were most frequently investigated. Overall, there was moderate concordance between the CpG sites that the studies reported to be highly predictive of prognosis. Combinations or means of sites between CpG's 73-89 were associated with improved OS and PFS. Six studies identified CpG sites associated with prognosis that were closer to the transcription start site: CpG's 8, 19, 22, 25, 27, 32,38, and CpG sites 21-37, as well as low methylation level of the enhancer regions. CONCLUSION: The following systematic review details a comprehensive investigation of the current literature and highlights several potential key CpG sites that demonstrate significant association with OS, PFS, and MGMT expression. However, the relationship between extent of MGMT promoter methylation and survival may be non-linear and could be influenced by potential CpG hotspots, the extent of methylation at each CpG site, and MGMT enhancer methylation status. There were several limitations within the studies such as smaller sample sizes, variance between methylation testing methods, and differences in the various statistical methods to test for association to outcome. Further studies of high impact CpG sites in MGMT methylation is warranted.
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Neoplasias Encefálicas , Glioblastoma , Glioma , Humanos , Neoplasias Encefálicas/genética , Metilação de DNA/genética , Metilases de Modificação do DNA/genética , Enzimas Reparadoras do DNA/genética , Glioblastoma/genética , Glioma/genética , Prognóstico , Proteínas Supressoras de Tumor/genéticaRESUMO
Biological cell membranes are primarily comprised of a diverse lipid bilayer with multiple phospholipid (lipid) types, each of which is comprised of a hydrophilic headgroup and two hydrophobic hydrocarbon tails. The lipid type determines the molecular structure of head and tail groups, which can affect membrane mechanics at nanoscale and subsequently cell viability under mechanical loading. Hence, using molecular dynamics simulations, the current study investigated seven membrane phospholipids and the effect of their structural differences on physical deformation, mechanoporation damage, and mechanical failure of the membranes under tension. The inspected phospholipids showed similar yield stresses and strains, as well as pore evolution and damage, but significantly different failure strains. In general, failure occurred at a lower strain for lipids with a larger equilibrium area per lipid. The obtained results suggest that larger headgroup structure, greater degree of unsaturation, and tail-length asymmetry influenced the phospholipids' ability to pack against each other, increased the fluidity and equilibrium area per lipid of the membrane, and resulted in lower failure strain. Overall, this study provides insights on how different phospholipid structures affect membrane physical responses at the molecular level and serves as a reference for future studies of more complex membrane systems with intricate biophysical properties.
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Membrana Celular , Simulação de Dinâmica Molecular , Fosfolipídeos , Fosfolipídeos/química , Membrana Celular/química , Bicamadas Lipídicas/química , Estrutura MolecularRESUMO
Little is known about how insecure attachment affects aggressive behavior and well-being among Vietnamese youth. Using structural equation modeling, we investigate the mediating role of subjective social status (SSS) on the paths from insecure attachment to overt aggressive behavior (OAB) and psychological well-being (PW) in a sample of 1753 Vietnamese adolescents (Mage = 16.136, SD = 0.784) and test whether the results will be replicated in another sample of 601 Vietnamese young adults (Mage = 19.93, SD = 1.35). Participants complete a survey comprising demographic information, attachment styles, SSS, OAB, and PW questionnaires. Our main findings include: (a) anxious attachment positively related to OAB in both samples, (b) anxious attachment was only negatively associated with adolescents' PW, (c) avoidant attachment was positively correlated to OAB in adolescents but negatively correlated in young adults, and (d) avoidant attachment was negatively related to PW in both samples. In addition, (e) in adolescents, the mediation role of SSS was significant in all paths, but (f) SSS only mediated the link from avoidant attachment to PW of young adults. The present study suggests that aggressive behavior might not be associated with social status or attachment in the same way in adolescents compared to young adult Vietnamese samples.
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DNAM-1 is an activating immunoreceptor on T cells and natural killer (NK) cells. Expression levels of its ligands, CD155 and CD112, are up-regulated on tumor cells. The interaction of DNAM-1 on CD8+ T cells and NK cells with the ligands on tumor cells plays an important role in tumor immunity. We previously reported that mice deficient in DNAM-1 showed accelerated growth of tumors induced by the chemical carcinogen 7,12-dimethylbenz[a]anthracene (DMBA). Contrary to those results, we show here that tumor development induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) together with DMBA was suppressed in DNAM-1-deficient mice. In this model, DNAM-1 enhanced IFN-γ secretion from conventional CD4+ T cells to promote inflammation-related tumor development. These findings suggest that, under inflammatory conditions, DNAM-1 contributes to tumor development via conventional CD4+ T cells.
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Antígenos de Diferenciação de Linfócitos T , Neoplasias , Animais , Antígenos de Diferenciação de Linfócitos T/metabolismo , Inflamação/metabolismo , Interferon gama/metabolismo , Células Matadoras Naturais , Ligantes , CamundongosRESUMO
Myeloproliferative neoplasms are hematological disorders characterized by increased production in one or more myeloid cell lines, associated with driver mutations in JAK2-, MPL- and CALR-genes. The aims of this study were to investigate the prevalence of these driver mutations in a Norwegian patient cohort with myeloproliferative neoplasms, and to assess whether the different mutations were associated with different clinical presentation and natural history.Results from 820 patients in whom analysis for JAK2V617F-, CALR- and MPL had been performed at Haukeland University Hospital in the period 2014-2019 were retrieved and analyzed together with clinical variables related to diagnosis, hematological blood parameters and complications, obtained from patient records.We identified 182 cases of myeloproliferative neoplasms: 78 with JAK2V617F, 28 with CALR-mutations, two with MPL-mutations and 23 cases without a driver mutation. There was a lower prevalence of JAK2V617F mutation than expected in the polycythemia vera group, likely related to overdiagnosis. In patients with essential thrombocytosis, we found significantly higher levels of hemoglobin and erythrocyte volume fraction for JAK2V617F-mutated disease, and significantly higher levels of platelets and lactate dehydrogenase for CALR-mutated disease. Patients with JAK2V617F-mutated primary myelofibrosis had significantly higher levels of hemoglobin, and there was an increased number of smokers or former smokers in this group compared to patients with CALR-mutations.Except for a lower prevalence of JAK2V617F-mutation in polycythemia vera, the mutational distribution in our patient cohort was similar to previous findings in other populations. The novel finding of a higher prevalence of smokers in JAK2V617F-mutated primary myelofibrosis warrants further investigation.
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Calreticulina , Janus Quinase 2 , Transtornos Mieloproliferativos , Receptores de Trombopoetina , Humanos , Hemoglobinas , Janus Quinase 2/genética , Janus Quinase 2/metabolismo , Mutação , Transtornos Mieloproliferativos/diagnóstico , Transtornos Mieloproliferativos/genética , Policitemia Vera/genética , Mielofibrose Primária/genética , Receptores de Trombopoetina/genética , Receptores de Trombopoetina/metabolismo , Calreticulina/metabolismoRESUMO
COVID-19 testing is an important risk mitigation strategy for COVID-19 prevention in school settings, where the virus continues to pose a public health challenge for in-person learning. Socially vulnerable school communities with the highest proportion of low-income, minority, and non-English speaking families have the least testing access despite shouldering a disproportionate burden of COVID-19 morbidity and mortality. Through the Safer at School Early Alert (SASEA) program, we investigated community perceptions of testing in San Diego County schools, with a focus on barriers and facilitators from the perspective of socially vulnerable parents and school staff. Using a mixed-methods approach, we administered a community survey and conducted focus group discussions (FGDs) with staff and parents from SASEA-affiliated schools and childcares. We recruited 299 survey respondents and 42 FGD participants. Protecting one's family (96.6%) and protecting one's community (96.6%) were marked as key motivators to testing uptake. School staff in particular reported that the reassurance of a negative status mitigated concerns about COVID-19 infection in schools. Participants expressed that COVID-19-related stigma, loss of income as a result of isolation/quarantine requirements, and lack of multilingual materials were the most significant barriers to testing. Our findings suggest that the testing barriers faced by school community members are predominantly structural. Testing uptake efforts must provide support and resources to manage the social and financial consequences of testing while continuously communicating its benefits. There is a clear need to continue to incorporate testing as a strategy to maintain school safety and facilitate access for vulnerable community members.
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Teste para COVID-19 , COVID-19 , Humanos , COVID-19/diagnóstico , COVID-19/prevenção & controle , Grupos Focais , Pobreza , PaisRESUMO
Patients with hematological malignancies or undergoing hematopoietic stem cell transplantation are vulnerable to colonization and infection with multidrug-resistant organisms, including vancomycin-resistant Enterococcus faecium (VREfm). Over a 10-y period, we collected and sequenced the genomes of 110 VREfm isolates from gastrointestinal and blood cultures of 24 pediatric patients undergoing chemotherapy or hematopoietic stem cell transplantation for hematological malignancy at St. Jude Children's Research Hospital. We used patient-specific reference genomes to identify variants that arose over time in subsequent gastrointestinal and blood isolates from each patient and analyzed these variants for insight into how VREfm adapted during colonization and bloodstream infection within each patient. Variants were enriched in genes involved in carbohydrate metabolism, and phenotypic analysis identified associated differences in carbohydrate utilization among isolates. In particular, a Y585C mutation in the sorbitol operon transcriptional regulator gutR was associated with increased bacterial growth in the presence of sorbitol. We also found differences in biofilm-formation capability between isolates and observed that increased biofilm formation correlated with mutations in the putative E. faecium capsular polysaccharide (cps) biosynthetic locus, with different mutations arising independently in distinct genetic backgrounds. Isolates with cps mutations showed improved survival following exposure to lysozyme, suggesting a possible reason for the selection of capsule-lacking bacteria. Finally, we observed mutations conferring increased tolerance of linezolid and daptomycin in patients who were treated with these antibiotics. Overall, this study documents known and previously undescribed ways that VREfm evolve during intestinal colonization and subsequent bloodstream infection in immunocompromised pediatric patients.
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Enterococcus faecium , Infecções por Bactérias Gram-Positivas/microbiologia , Enterococos Resistentes à Vancomicina , Antibacterianos/farmacologia , Bacteriemia/microbiologia , Biofilmes , Criança , Enterococcus faecium/efeitos dos fármacos , Enterococcus faecium/genética , Enterococcus faecium/patogenicidade , Evolução Molecular , Feminino , Microbioma Gastrointestinal/genética , Genoma Bacteriano/genética , Humanos , Hospedeiro Imunocomprometido , Masculino , Mutação/genética , Sorbitol/metabolismo , Enterococos Resistentes à Vancomicina/efeitos dos fármacos , Enterococos Resistentes à Vancomicina/genética , Enterococos Resistentes à Vancomicina/patogenicidadeRESUMO
Development of efficient surface passivation methods for semiconductor devices is crucial to counter the degradation in their electrical performance owing to scattering or trapping of carriers in the channels induced by molecular adsorption from the ambient environment. However, conventional dielectric deposition involves the formation of additional interfacial defects associated with broken covalent bonds, resulting in accidental electrostatic doping or enhanced hysteretic behavior. In this study, centimeter-scaled van der Waals passivation of transition metal dichalcogenides (TMDCs) is demonstrated by stacking hydrocarbon (HC) dielectrics onto MoSe2 field-effect transistors (FETs), thereby enhancing the electric performance and stability of the device, accompanied with the suppression of chemical disorder at the HC/TMDCs interface. The stacking of HC onto MoSe2 FETs enhances the carrier mobility of MoSe2 FET by over 50% at the n-branch, and a significant decrease in hysteresis, owing to the screening of molecular adsorption. The electron mobility and hysteresis of the HC/MoSe2 FETs are verified to be nearly intact compared to those of the fabricated HC/MoSe2 FETs after exposure to ambient environment for 3 months. Consequently, the proposed design can act as a model for developing advanced nanoelectronics applications based on layered materials for mass production.
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Patients with cystic fibrosis (CF) have altered fecal microbiomes compared to those of healthy controls. The magnitude of this dysbiosis correlates with measures of CF gastrointestinal (GI) disease, including GI inflammation and nutrient malabsorption. However, whether this dysbiosis is caused by mutations in the CFTR gene, the underlying defect in CF, or whether CF-associated dysbiosis augments GI disease was not clear. To test the relationships between CFTR dysfunction, microbes, and intestinal health, we established a germ-free (GF) CF mouse model and demonstrated that CFTR gene mutations are sufficient to alter the GI microbiome. Furthermore, flow cytometric analysis demonstrated that colonized CF mice have increased mesenteric lymph node and spleen TH17+ cells compared with non-CF mice, suggesting that CFTR defects alter adaptive immune responses. Our findings demonstrate that CFTR mutations modulate both the host adaptive immune response and the intestinal microbiome.
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Regulador de Condutância Transmembrana em Fibrose Cística/genética , Fibrose Cística/microbiologia , Disbiose/microbiologia , Microbioma Gastrointestinal , Animais , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Fibrose Cística/genética , Fibrose Cística/imunologia , Regulador de Condutância Transmembrana em Fibrose Cística/imunologia , Modelos Animais de Doenças , Disbiose/genética , Disbiose/imunologia , Feminino , Humanos , Intestinos/imunologia , Intestinos/microbiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , MutaçãoRESUMO
Modulators of epithelial-to-mesenchymal transition (EMT) have recently emerged as novel players in the field of leukemia biology. The mechanisms by which EMT modulators contribute to leukemia pathogenesis, however, remain to be elucidated. Here we show that overexpression of SNAI1, a key modulator of EMT, is a pathologically relevant event in human acute myeloid leukemia (AML) that contributes to impaired differentiation, enhanced self-renewal, and proliferation of immature myeloid cells. We demonstrate that ectopic expression of Snai1 in hematopoietic cells predisposes mice to AML development. This effect is mediated by interaction with the histone demethylase KDM1A/LSD1. Our data shed new light on the role of SNAI1 in leukemia development and identify a novel mechanism of LSD1 corruption in cancer. This is particularly pertinent given the current interest surrounding the use of LSD1 inhibitors in the treatment of multiple different malignancies, including AML.
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Transformação Celular Neoplásica , Transição Epitelial-Mesenquimal/genética , Histona Desmetilases/metabolismo , Leucemia Mieloide Aguda/patologia , Fatores de Transcrição da Família Snail/fisiologia , Animais , Linhagem Celular Tumoral , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/metabolismo , Células HEK293 , Células HL-60 , Histona Desmetilases/genética , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Camundongos , Camundongos Transgênicos , Ligação Proteica , Fatores de Transcrição da Família Snail/genética , Fatores de Transcrição da Família Snail/metabolismoRESUMO
BACKGROUND AIMS: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective treatment for patients with hematological malignancies; however, allo-HSCT does not come without the cost of treatment-related morbidity and mortality. Early detection of risk factors could be helpful in identifying patients who could benefit from early interventions. Many patients gain weight during the allo-HSCT treatment, although little is known about the impact of weight gain. METHODS: Weight gain in 146 consecutively enrolled adult patients undergoing allo-HSCT was explored. RESULTS: In total, 141 patients (97%) gained weight along the course of allo-HSCT. Median weight increase was 4.8 kg (range 0.0-16.1 kg), with median increase in body weight 6.5% (range 0.0%-30.8%). Maximum weight increase was observed at day +7 (range day -8, +44). Weight gain was associated with increased incidence of acute graft-versus-host disease. Patients with weight gain >10% had a significantly greater 5-year mortality compared with those with lower weight gain (P = 0.031, rank sum test). CONCLUSIONS: Weight gain is a simple variable with the ability to provide prognostic information for patients undergoing allo-HSCT.
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Doença Enxerto-Hospedeiro , Neoplasias Hematológicas , Transplante de Células-Tronco Hematopoéticas , Humanos , Adulto , Transplante Homólogo/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/terapia , Neoplasias Hematológicas/terapia , Neoplasias Hematológicas/complicações , Resultado do Tratamento , Aumento de Peso , Estudos RetrospectivosRESUMO
BACKGROUND: A single-entry model in healthcare consolidates waiting lists through a central intake and allows patients to see the next available health care provider based on the prioritization. This study aimed to examine whether and to what extent the prioritization reduced wait times for hip and knee replacement surgeries. METHOD: The survival regression method was used to estimate the effects of priority levels on wait times for consultation and surgery for hip and knee replacements. The sample data included patients who were referred to the Orthopedic Central Intake clinic at the Eastern Health region of Newfoundland and Labrador and had surgery of hip and knee replacements between 2011 and 2019. RESULT: After adjusting for covariates, the hazard of having consultation booked was greater in patients with priority 1 and 2 than those in priority 3 when and at 90 days after the referral was made for both hip and knee replacements. Regarding wait time for surgery after the decision for surgery was made, while the hazard of having surgery was lower in priority 2 than in priority 3 when and indifferent at 182 days after the decision was made, it was not significantly different between priority 1 and priority 3 among hip replacement patients. Priority levels were not significantly related to the hazard of having surgery for a knee replacement after the decision for surgery was made. Overall, the hazard of having surgery after the referral was made by a primary care physician was greater for patients in high priority than those in low priority. Preferring a specific surgeon indicated at referral was found to delay consultation and it was not significantly related to the total wait time for surgery. Incomplete referral forms prolonged wait time for consultation and patients under age 65 had a longer total wait time than those aged 65 or above. CONCLUSION: Patients with high priority could have a consultation booked earlier than those with low priority and prioritization in a single entrance model shortens the total wait time for surgery. However, the association between priority levels and wait for surgery after the decision for surgery was made has not well-established.
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Artroplastia de Quadril , Artroplastia do Joelho , Idoso , Humanos , Terra Nova e Labrador , Encaminhamento e Consulta , Listas de EsperaRESUMO
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.
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Conhecimento , Laboratórios , Fenômenos Físicos , Simulação por Computador , Fenômenos MagnéticosRESUMO
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.
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Procedimentos Cirúrgicos Robóticos , Robótica , Algoritmos , Simulação por Computador , IncertezaRESUMO
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.
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Procedimentos Cirúrgicos Robóticos , Robótica , Robótica/métodos , Movimento (Física) , IncertezaRESUMO
BACKGROUND: Infants with cystic fibrosis (CF) suffer from gastrointestinal (GI) complications, including pancreatic insufficiency and intestinal inflammation, which have been associated with impaired nutrition and growth. Recent evidence identified altered fecal microbiota taxonomic compositions in infants with CF relative to healthy infants that were characterized by differences in the abundances of taxa associated with GI health and nutrition. Furthermore, these taxonomic differences were more pronounced in low length infants with CF, suggesting a potential link to linear growth failure. We hypothesized that these differences would entail shifts in the microbiome's functional capacities that could contribute to inflammation and nutritional failure in infants with CF. RESULTS: To test this hypothesis, we compared fecal microbial metagenomic content between healthy infants and infants with CF, supplemented with an analysis of fecal metabolomes in infants with CF. We identified notable differences in CF fecal microbial functional capacities, including metabolic and environmental response functions, compared to healthy infants that intensified during the first year of life. A machine learning-based longitudinal metagenomic age analysis of healthy and CF fecal metagenomic functional profiles further demonstrated that these differences are characterized by a CF-associated delay in the development of these functional capacities. Moreover, we found metagenomic differences in functions related to metabolism among infants with CF that were associated with diet and antibiotic exposure, and identified several taxa as potential drivers of these functional differences. An integrated metagenomic and metabolomic analysis further revealed that abundances of several fecal GI metabolites important for nutrient absorption, including three bile acids, correlated with specific microbes in infants with CF. CONCLUSIONS: Our results highlight several metagenomic and metabolomic factors, including bile acids and other microbial metabolites, that may impact nutrition, growth, and GI health in infants with CF. These factors could serve as promising avenues for novel microbiome-based therapeutics to improve health outcomes in these infants.
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Fibrose Cística/complicações , Fibrose Cística/microbiologia , Disbiose/complicações , Fezes/microbiologia , Gastroenteropatias/etiologia , Metaboloma , Metagenoma , Gastroenteropatias/microbiologia , Gastroenteropatias/fisiopatologia , Humanos , Lactente , Estudos Longitudinais , Metabolômica/métodos , Estudos ProspectivosRESUMO
Ungulate protoparvovirus 1, also known as porcine parvovirus 1 (PPV1), is considered to be one of the major causes of reproductive failure in pig breeding herds. Other parvoviruses have also been identified in pigs, including ungulate tetraparvovirus 3, or PPV2, ungulate tetraparvovirus 2, or PPV3, and ungulate copiparvovirus 2, or PPV4, but their significance for pigs is unknown. In the present study, the prevalence of PPV1-4 was investigated using a total of 231 lung and serum samples collected from slaughterhouses in 13 provinces throughout Vietnam. The overall prevalence was 54.5% (126/231) for PPV1, 28.0% (65/231) for PPV2, 17.7% (41/231) for PPV3, and 7.8% (18/231) for PPV4. While PPV1 and PPV2 were found in 11 provinces, PPV4 was detected in only three provinces. Co-circulation of PPV1, PPV2 and PPV3 was frequently observed, with PPV1/PPV2 coinfection predominating, with 20.8% (48/231). All four PPVs were detected together in only one sample from Thua Thien Hue. Three nearly complete PPV4 genome sequences of 5,453 nt were determined and deposited in the GenBank database. Alignment and comparison of the three genome sequences showed 99.5-99.6% nucleotide sequence identity, and the deduced amino acid sequences of open reading frames 1-3 were 99.6-99.9% identical to each other, 98.9-99.3% identical to those of other Vietnamese strains and 99.4-99.7% identical to those of Chinese strains). Phylogenetic analysis further confirmed a close relationship between Vietnamese and Chinese PPV4 strains. These results are the first to report the prevalence of PPV1, PPV2, PPV3, and PPV4 and nearly complete genomic sequences of PPV4 in pigs from slaughterhouses in Vietnam.