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1.
Res Q Exerc Sport ; : 1-10, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38771866

RESUMO

Purpose: Technical approaches (TAs) such as Direct Instruction are commonly utilized when teaching games in Physical Education (PE) classes, but game-based approaches (GBAs) such as Game Sense (GS) have gained greater interest over the past 30 years. However, little is known about which approach promotes more physical activity (PA). The aim of this study was to compare the PA of girls during single-gender PE classes in an invasion games unit utilizing either a GS approach or a TA. Methods: Two upper primary school PE classes were taught invasion games using a GS approach and two classes were taught using a TA. During each of the 7 lessons students wore a wearable GPS sensor (SPT2, Sport Performance Tracking, Australia) which measured total distance, distance in each speed zone, top speed and 3D load. Results: The GS group traveled a greater distance than the TA group (+203 m, p < .001). This result was explained mostly by a greater distance covered in zone 2 speeds (0.6-1.7 m/s). The 3D load was also significantly higher in the GS group, but there were no group differences in top speed. Conclusions: Findings suggested that a GS thematic invasion unit was more effective in promoting PA levels in all-girl primary PE classes than a traditional sport-based invasion unit.

2.
Front Toxicol ; 6: 1287863, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38706568

RESUMO

There is increased emphasis on understanding cumulative risk from the combined effects of chemical and non-chemical stressors as it relates to public health. Recent animal studies have identified pulmonary inflammation as a possible modifier and risk factor for chemical toxicity in the lung after exposure to inhaled pollutants; however, little is known about specific interactions and potential mechanisms of action. In this study, primary human bronchial epithelial cells (HBEC) cultured in 3D at the air-liquid interface (ALI) are utilized as a physiologically relevant model to evaluate the effects of inflammation on toxicity of polycyclic aromatic hydrocarbons (PAHs), a class of contaminants generated from incomplete combustion of fossil fuels. Normal HBEC were differentiated in the presence of IL-13 for 14 days to induce a profibrotic phenotype similar to asthma. Fully differentiated normal and IL-13 phenotype HBEC were treated with benzo[a]pyrene (BAP; 1-40 µg/mL) or 1% DMSO/PBS vehicle at the ALI for 48 h. Cells were evaluated for cytotoxicity, barrier integrity, and transcriptional biomarkers of chemical metabolism and inflammation by quantitative PCR. Cells with the IL-13 phenotype treated with BAP result in significantly (p < 0.05) decreased barrier integrity, less than 50% compared to normal cells. The effect of BAP in the IL-13 phenotype was more apparent when evaluating transcriptional biomarkers of barrier integrity in addition to markers of mucus production, goblet cell hyperplasia, type 2 asthmatic inflammation and chemical metabolism, which all resulted in dose-dependent changes (p < 0.05) in the presence of BAP. Additionally, RNA sequencing data showed that the HBEC with the IL-13 phenotype may have increased potential for uncontrolled proliferation and decreased capacity for immune response after BAP exposure compared to normal phenotype HBEC. These data are the first to evaluate the role of combined environmental factors associated with inflammation from pre-existing disease and PAH exposure on pulmonary toxicity in a physiologically relevant human in vitro model.

3.
Polymers (Basel) ; 16(7)2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38611234

RESUMO

The objective of this paper is to investigate the debonding behavior of the interface between continuously and discontinuously fiber reinforced thermoplastics using the climbing drum peel test. The study emphasizes on the importance of considering different climatic boundary conditions on the properties of thermoplastics. Specimens with varying moisture contents, from 0m.% up to above 6m.% are prepared and tested. It is observed that an increase in moisture content from 0m.% to 2m.% results in an increase of the fracture surface energy from 1.07·103J/m2 to 2.40·103J/m2 required to separate the two materials, but a further increase in moisture to 6.35m.% conversely results in a subsequent decrease of the required energy to 1.91·103J/m2. The study presents an explanatory model of increasing plasticization of the polymer due to increased polymer chain mobility, which results in more deformation energy being required to propagate the crack, which is corroborated in SEM investigations of the fracture surface. A further increase in humidity leads to polymer degradation due to hydrolysis, which explains the subsequent reduction of the fracture energy. The experimental set up is modeled numerically for the first time with cohesive surfaces, which could successfully reproduce the effective force-displacement curve in the experiment by varying the interface parameters in the model over an influence length, allowing the conclusion of a process induced variation in the interface properties over a specific consolidation length.

4.
J Res Adolesc ; 2024 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-38616300

RESUMO

The LGBT People of Color Microaggressions Scale (LGBT-PCMS) is a widely used measure of intersectional microaggression experiences among sexual and gender minority people of color. Although it is widely used-and increasingly used in adolescent and young adult samples-it is unknown whether the LGBT-PCMS demonstrates similar measurement properties across subgroups of sexual and gender minority youth of color (SGMYOC). Among 4142 SGMYOC (ages 13-17) we found evidence for either partial or full scalar invariance (item loadings and intercepts were generally equal) across sexual orientation, race-ethnicity, and gender identity groups for all three subscales. Specific patterns of invariance and noninvariance across groups, as well as implications for the use of the LGBT-PCMS and its subscales among SGMYOC are discussed.

5.
Sci Rep ; 14(1): 9641, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38671198

RESUMO

Computed tomography images are of utmost importance when characterizing the heterogeneous and complex microstructure of discontinuously fiber reinforced polymers. However, the devices are expensive and the scans are time- and energy-intensive. Through recent advances in generative adversarial networks, the instantaneous generation of endless numbers of images that are representative of the input images and hold physical significance becomes possible. Hence, this work presents a deep convolutional generative adversarial network trained on approximately 30,000 input images from carbon fiber reinforced polyamide 6 computed tomography scans. The challenge lies in the low contrast between the two constituents caused by the close proximity of the density of polyamide 6 and carbon fibers as well as the small fiber diameter compared to the necessary resolution of the images. In addition, the stochastic, heterogeneous microstructure does not follow any logical or predictable rules exacerbating their generation. The quality of the images generated by the trained network of 256 pixel × 256 pixel was investigated through the Fréchet inception distance and nearest neighbor considerations based on Euclidean distance and structural similarity index measure. Additional visual qualitative assessment ensured the realistic depiction of the complex mixed single fiber and fiber bundle structure alongside flow-related physically feasible positioning of the fibers in the polymer. The authors foresee additionally huge potential in creating three-dimensional representative volume elements typically used in composites homogenization.

6.
J Res Adolesc ; 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38339824

RESUMO

Family-based microaggressions and discrimination experienced by youth with LGBTQ+ parents are important to understand from their perspectives. Using mixed methods, we examined such experiences among 12- to 25-year-old youth (N = 51) with at least one LGBTQ+ parent in the United States. Youth were diverse in race/ethnicity, family structure, gender and sexual identities, socioeconomic status, and geographic region. Using interviews, we explored LGBTQ+ family-based microaggressions (reported through scale items with feedback) and discrimination (assessed via thematic analysis). Microaggressions and discrimination based on having LGBTQ+ parents were common, yet there were distinctions in direct and indirect stigma across the quantitative items and qualitative themes. These results underscore the value of mixed methods research with youth and implications for future research, practice, and policy.

7.
J Fam Psychol ; 38(4): 643-653, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38358720

RESUMO

In the United States, cultural forces have led to the stigmatization of lesbian, gay, bisexual, transgender, and queer (and additional identities) (LGBTQ+) parenthood. However, pushing back against this stigmatization, developing a positive LGBTQ+ identity, and investing in one's LGBTQ+ community may inform empowering narratives of future parenthood and related constructs, such as LGBTQ+ parent socialization. Perceived self-efficacy related to preparation for bias (i.e., discussions of discrimination, prejudice, or bias-based bullying) socialization is likely associated with an individual's own perceptions or experiences of stigmatization given the conceptual overlap of bias and stigma. However, other constructs related to stigmatization and socialization self-efficacy, such as positive LGBTQ+ identity or community connectedness, have yet to be simultaneously considered (to our knowledge). Further, previous research has rarely included different assessments of stigma (i.e., perceived and enacted) and/or dimensions of positive LGBTQ+ identity (i.e., authenticity and self-awareness). Thus, this study aimed to rectify these gaps and provide a greater understanding of sexual stigma and LGBTQ+ parent socialization self-efficacy. Using data from a survey-based, online, cross-sectional study of LGBTQ+ childfree adults (N = 433; Mage = 29.85 years old) in the United States, we found that experiences of enacted or perceived sexual stigma were differentially associated with LGBTQ+ parent socialization preparation for bias self-efficacy. Further, positive LGBTQ+ identity authenticity and self-awareness, as well as LGBTQ+ community connectedness played distinct roles as mediators of the relationships between sexual stigma and LGBTQ+ parent socialization self-efficacy. These findings have implications for how we might understand the role of stigma, identity, community, and socialization among future LGBTQ+ parents. (PsycInfo Database Record (c) 2024 APA, all rights reserved).


Assuntos
Pais , Autoeficácia , Minorias Sexuais e de Gênero , Estigma Social , Socialização , Humanos , Feminino , Minorias Sexuais e de Gênero/psicologia , Adulto , Masculino , Pais/psicologia , Adulto Jovem , Pessoa de Meia-Idade , Identificação Social , Estados Unidos
8.
J Breath Res ; 18(2)2024 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-38290132

RESUMO

Exhaustive exercise can induce unique physiological responses in the lungs and other parts of the human body. The volatile organic compounds (VOCs) in exhaled breath are ideal for studying the effects of exhaustive exercise on the lungs due to the proximity of the breath matrix to the respiratory tract. As breath VOCs can originate from the bloodstream, changes in abundance should also indicate broader physiological effects of exhaustive exercise on the body. Currently, there is limited published data on the effects of exhaustive exercise on breath VOCs. Breath has great potential for biomarker analysis as it can be collected non-invasively, and capture real-time metabolic changes to better understand the effects of exhaustive exercise. In this study, we collected breath samples from a small group of elite runners participating in the 2019 Ultra-Trail du Mont Blanc ultra-marathon. The final analysis included matched paired samples collected before and after the race from 24 subjects. All 48 samples were analyzed using the Breath Biopsy Platform with GC-Orbitrap™ via thermal desorption gas chromatography-mass spectrometry. The Wilcoxon signed-rank test was used to determine whether VOC abundances differed between pre- and post-race breath samples (adjustedP-value < .05). We identified a total of 793 VOCs in the breath samples of elite runners. Of these, 63 showed significant differences between pre- and post-race samples after correction for multiple testing (12 decreased, 51 increased). The specific VOCs identified suggest the involvement of fatty acid oxidation, inflammation, and possible altered gut microbiome activity in response to exhaustive exercise. This study demonstrates significant changes in VOC abundance resulting from exhaustive exercise. Further investigation of VOC changes along with other physiological measurements can help improve our understanding of the effect of exhaustive exercise on the body and subsequent differences in VOCs in exhaled breath.


Assuntos
Líquidos Corporais , Compostos Orgânicos Voláteis , Humanos , Testes Respiratórios/métodos , Compostos Orgânicos Voláteis/análise , Expiração , Cromatografia Gasosa-Espectrometria de Massas/métodos , Líquidos Corporais/química
9.
Behav Med ; 50(2): 170-180, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37036276

RESUMO

Sexual and gender minority youth (SGMY) report greater alcohol use in comparison to their heterosexual counterparts. Prior research has found that elevated alcohol use among SGMY can be explained by minority stress experiences. Sexual identity outness may be another factor that drives alcohol use among SGMY, given that outness is associated with alcohol use among older sexual and gender minority samples. We examined how patterns of sexual identity outness were associated with lifetime alcohol use, past-30-day alcohol use, and past-30-day heavy episodic drinking. Data were drawn from the LGBTQ National Teen Survey (N = 8884). Participants were SGMY aged 13 to 17 (mean age = 15.59) years living in the US. Latent class analysis was used to identify sexual identity outness patterns. Multinomial regressions were used to examine the probability of class membership by alcohol use. Six outness classes were identified: out to all but teachers (n = 1033), out to siblings and peers (n = 1808), out to siblings and LGBTQ+ peers (n = 1707), out to LGBTQ+ peers (n = 1376), mostly not out (n = 1653), and very much not out (n = 1307). SGMY in classes characterized by greater outness to peers, friends, and family had greater odds of lifetime alcohol use compared with SGMY in classes characterized by lower outness. These findings suggest that SGMY with greater sexual identity outness may be a target for alcohol use prevention programming. Differences in sexual identity outness may be explained by minority stress factors.


Assuntos
Revelação , Minorias Sexuais e de Gênero , Adolescente , Humanos , Identidade de Gênero , Comportamento Sexual , Consumo de Bebidas Alcoólicas
10.
AIDS Behav ; 28(1): 12-18, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37955807

RESUMO

Uptake of HIV testing is a critical step in the HIV prevention and treatment care cascade. Barriers to HIV testing, however, remain and innovative research in this area is warranted to improve uptake of testing. As such, we investigated the role of HIV information avoidance - a novel construct potentially related to HIV testing. We analyzed this construct in relation to other factors known to impact HIV testing, namely HIV stigma and medical mistrust. Multiple linear regression analyses indicated that HIV information avoidance was negatively associated with HIV testing, while medical mistrust was positively associated with HIV testing. HIV testing stigma was not associated with HIV testing. This work contributes to the developing literature on HIV information avoidance and its relationships with HIV stigma and HIV testing uptake. Further, these findings can inform HIV testing interventions which often do not focus on HIV information avoidance. Future research on the mechanisms of information avoidance that are amenable to intervention, and the temporal ordering of the relationship between information avoidance and HIV testing is warranted.


Assuntos
Infecções por HIV , Minorias Sexuais e de Gênero , Masculino , Humanos , Estados Unidos/epidemiologia , Confiança , Evitação da Informação , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Estigma Social , Teste de HIV , Homossexualidade Masculina
12.
Front Bioeng Biotechnol ; 11: 1229388, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37849982

RESUMO

Introduction: Nucleus replacement has been proposed as a treatment to restore biomechanics and relieve pain in degenerate intervertebral discs (IVDs). Multiple nucleus replacement devices (NRDs) have been developed, however, none are currently used routinely in clinic. A better understanding of the interactions between NRDs and surrounding tissues may provide insight into the causes of implant failure and provide target properties for future NRD designs. The aim of this study was to non-invasively quantify 3D strains within the IVD through three stages of nucleus replacement surgery: intact, post-nuclectomy, and post-treatment. Methods: Digital volume correlation (DVC) combined with 9.4T MRI was used to measure strains in seven human cadaveric specimens (42 ± 18 years) when axially compressed to 1 kN. Nucleus material was removed from each specimen creating a cavity that was filled with a hydrogel-based NRD. Results: Nucleus removal led to loss of disc height (12.6 ± 4.4%, p = 0.004) which was restored post-treatment (within 5.3 ± 3.1% of the intact state, p > 0.05). Nuclectomy led to increased circumferential strains in the lateral annulus region compared to the intact state (-4.0 ± 3.4% vs. 1.7 ± 6.0%, p = 0.013), and increased maximum shear strains in the posterior annulus region (14.6 ± 1.7% vs. 19.4 ± 2.6%, p = 0.021). In both cases, the NRD was able to restore these strain values to their intact levels (p ≥ 0.192). Discussion: The ability of the NRD to restore IVD biomechanics and some strain types to intact state levels supports nucleus replacement surgery as a viable treatment option. The DVC-MRI method used in the present study could serve as a useful tool to assess future NRD designs to help improve performance in future clinical trials.

13.
Polymers (Basel) ; 15(17)2023 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-37688170

RESUMO

Plastic-based additive manufacturing processes are becoming increasingly popular in the production of structural parts. Based on the idea of lightweight design and the aim of extending the functionality of additive structures, the production of additively manufactured foam structures has emerged as a new field of application. The optical characterisation of these structures is of particular importance for process adjustments and the identification of (unwanted) changes in the foam structure. The degree of foaming and the fineness of a foam structure are of interest at this point. In this context, only the part of a structure dominated by foam pores is considered a foam structure. So far, there are no sophisticated methods for such an optical characterisation. Therefore, in this work, microscope images of manufactured as well as artificially created additively manufactured foam structures were evaluated. On these images, the features porosity, pore size, pore amount and a measure for the textural change were determined in order to obtain information about changes within an additively manufactured foam structure. It is shown that additive structures show changing pore shapes depending on the orientation of the cutting plane, although there are no changes in the foaming behaviour. Therefore, caution is required when identifying changes within the foam structure. It was also found that, owing to the additive process, the total porosity is already set in the slicing process and remains constant even if the degree of foaming of individual tracks is changed. Therefore, the degree of foaming cannot be determined on the basis of the total porosity, but it can be assessed on the basis of the formation of large networks of process-related pores.

14.
LGBT Health ; 10(S1): S10-S19, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37754921

RESUMO

Purpose: This study examines adolescents' self-reported school-based developmental assets and four intersecting social positions as they relate to prevalence of bullying involvement. Methods: Participants were 80,456 ninth and 11th grade students who participated in the 2019 Minnesota Student Survey (30.2% youth of color; 11% lesbian/gay/bisexual/pansexual/queer/questioning; 2.9% transgender/gender diverse [TGD] or gender questioning). Exhaustive Chi-square Automatic Interaction Detection analysis was used to identify school-based developmental assets (i.e., school safety, school adult support) and intersecting social positions (i.e., sexual identity; gender identity/modality; racial/ethnic identity; physical disabilities/chronic illness; and/or mental health/behavioral/emotional problems) associated with the highest prevalence of involvement as physical and relational bullies, victims, and bully-victims. Results: Adolescents with 2+ marginalized social positions who often lacked school-based developmental assets were part of nearly all the highest prevalence bullying involvement groups. TGD and gender questioning adolescents, Native American youth, and youth living with both physical disabilities/chronic illness and mental health/emotional/behavioral problems-most of whom had additional marginalized social positions and lacked school-based assets-were particularly overrepresented in high prevalence groups. For example, 31.1% of TGD or gender questioning youth of color living with both types of disabilities/health problems who did not feel strongly that school was safe reported involvement as physical bully-victims-nearly six times the sample average rate. Conclusion: Adolescents with multiple marginalized social positions and those lacking certain school-based assets-often overlapping categories-were involved in bullying at higher-than-average rates. Findings underscore the need for schools to address intersecting experiences of stigma and structural oppression that may perpetuate bullying involvement disparities.


Assuntos
Bullying , Pessoas Transgênero , Adolescente , Adulto , Feminino , Humanos , Masculino , Identidade de Gênero , Etnicidade , Prevalência
15.
Contemp Clin Trials ; 132: 107293, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37454727

RESUMO

BACKGROUND: Identifying hypertension (HTN) early is crucial in preventing and lowering the long-term risk of heart disease, yet HTN in children often goes undiagnosed. An electronic health record linked, web-based clinical decision support (CDS) called PedsBP can help address this care gap and has been previously shown to increase recognition of HTN by primary care clinicians. OBJECTIVES: To adapt the PedsBP tool for use in a mostly rural health system and then to evaluate the effectiveness of PedsBP for repeat of hypertensive level blood pressure (BP) measurements and HTN recognition among youth 6-17 years of age in primary care settings, comparing low-intensity and high-intensity implementation approaches. METHODS AND DESIGN: PedsBP was evaluated through a pragmatic, clinic-randomized trial. The tool was piloted in 2 primary care clinics and modified prior to the full trial. Forty community-based, primary care clinics (or clusters of clinics) were randomly allocated in a 1:1:1 ratio to usual care, low-intensity implementation (CDS only), or high-intensity implementation (CDS plus in-person training, monthly use reports, and ongoing communication between study staff and clinics). Accrual of eligible patients started on August 1, 2022 and will continue for 18 months. Primary outcomes include repeating hypertensive level BP measurements at office visits and clinical recognition of HTN. Secondary outcomes include lifestyle counseling, dietician referral, and BP at follow-up. CONCLUSION: This report focuses on the design and feasibility of adapting and implementing PedsBP in a rural primary care setting. The trial and analysis are ongoing with main results expected in mid-2024.


Assuntos
Sistemas de Apoio a Decisões Clínicas , Cardiopatias , Hipertensão , Adolescente , Criança , Humanos , Hipertensão/diagnóstico , Hipertensão/terapia , Saúde da População Rural , Ensaios Clínicos Pragmáticos como Assunto
16.
Int J Tuberc Lung Dis ; 27(8): 584-598, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37491754

RESUMO

BACKGROUND: These clinical standards aim to provide guidance for diagnosis, treatment, and management of drug-susceptible TB in children and adolescents.METHODS: Fifty-two global experts in paediatric TB participated in a Delphi consensus process. After eight rounds of revisions, 51/52 (98%) participants endorsed the final document.RESULTS: Eight standards were identified: Standard 1, Age and developmental stage are critical considerations in the assessment and management of TB; Standard 2, Children and adolescents with symptoms and signs of TB disease should undergo prompt evaluation, and diagnosis and treatment initiation should not depend on microbiological confirmation; Standard 3, Treatment initiation is particularly urgent in children and adolescents with presumptive TB meningitis and disseminated (miliary) TB; Standard 4, Children and adolescents should be treated with an appropriate weight-based regimen; Standard 5, Treating TB infection (TBI) is important to prevent disease; Standard 6, Children and adolescents should receive home-based/community-based treatment support whenever possible; Standard 7, Children, adolescents, and their families should be provided age-appropriate support to optimise engagement in care and clinical outcomes; and Standard 8, Case reporting and contact tracing should be conducted for each child and adolescent.CONCLUSION: These consensus-based clinical standards, which should be adapted to local contexts, will improve the care of children and adolescents affected by TB.


Assuntos
Tuberculose Meníngea , Adolescente , Criança , Humanos , Tuberculose Meníngea/tratamento farmacológico , Padrão de Cuidado , Técnica Delphi , Guias de Prática Clínica como Assunto
17.
Sci Rep ; 13(1): 8831, 2023 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-37258601

RESUMO

Laser wakefield accelerators (LWFAs) can produce high-energy electron bunches in short distances. Successfully coupling these sources with undulators has the potential to form an LWFA-driven free-electron laser (FEL), providing high-intensity short-wavelength radiation. Electron bunches produced from LWFAs have a correlated distribution in longitudinal phase space: a chirp. However, both LWFAs and FELs have strict parameter requirements. The bunch chirp created using ideal LWFA parameters may not suit the FEL; for example, a chirp can reduce the high peak current required for free-electron lasing. We, therefore, design a flexible beamline that can accept either positively or negatively chirped LWFA bunches and adjust the chirp during transport to an undulator. We have used the accelerator design program MAD8 to design a beamline in stages, and to track particle bunches. The final beamline design can produce ambidirectional values of longitudinal dispersion ([Formula: see text]): we demonstrate values of + 0.20 mm, 0.00  mm and - 0.22 mm. Positive or negative values of [Formula: see text] apply a shear forward or backward in the longitudinal phase space of the electron bunch, which provides control of the bunch chirp. This chirp control during the bunch transport gives an additional free parameter and marks a new approach to matching future LWFA-driven FELs.

18.
PLoS One ; 18(5): e0285856, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37192202

RESUMO

Pseudomonas aeruginosa causes a wide range of severe infections. Ceftazidime, a cephalosporin, is a key antibiotic for treating infections but a significant proportion of isolates are ceftazidime-resistant. The aim of this research was to identify mutations that contribute to resistance, and to quantify the impacts of individual mutations and mutation combinations. Thirty-five mutants with reduced susceptibility to ceftazidime were evolved from two antibiotic-sensitive P. aeruginosa reference strains PAO1 and PA14. Mutations were identified by whole genome sequencing. The evolved mutants tolerated ceftazidime at concentrations between 4 and 1000 times that of the parental bacteria, with most mutants being ceftazidime resistant (minimum inhibitory concentration [MIC] ≥ 32 mg/L). Many mutants were also resistant to meropenem, a carbapenem antibiotic. Twenty-eight genes were mutated in multiple mutants, with dacB and mpl being the most frequently mutated. Mutations in six key genes were engineered into the genome of strain PAO1 individually and in combinations. A dacB mutation by itself increased the ceftazidime MIC by 16-fold although the mutant bacteria remained ceftazidime sensitive (MIC < 32 mg/L). Mutations in ampC, mexR, nalC or nalD increased the MIC by 2- to 4-fold. The MIC of a dacB mutant was increased when combined with a mutation in ampC, rendering the bacteria resistant, whereas other mutation combinations did not increase the MIC above those of single mutants. To determine the clinical relevance of mutations identified through experimental evolution, 173 ceftazidime-resistant and 166 sensitive clinical isolates were analysed for the presence of sequence variants that likely alter function of resistance-associated genes. dacB and ampC sequence variants occur most frequently in both resistant and sensitive clinical isolates. Our findings quantify the individual and combinatorial effects of mutations in different genes on ceftazidime susceptibility and demonstrate that the genetic basis of ceftazidime resistance is complex and multifactorial.


Assuntos
Ceftazidima , Infecções por Pseudomonas , Humanos , Ceftazidima/farmacologia , Pseudomonas aeruginosa , Proteínas de Bactérias/genética , Proteínas de Bactérias/farmacologia , Antibacterianos/farmacologia , Cefalosporinas/farmacologia , Testes de Sensibilidade Microbiana , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/microbiologia , Combinação de Medicamentos , Compostos Azabicíclicos/farmacologia
19.
Polymers (Basel) ; 15(6)2023 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-36987296

RESUMO

Technological advances have led to the increased use of plastic-based additive manufacturing processes for the production of consumer goods and spare parts. For this reason, the need for the best possible mechanical properties while maintaining geometric accuracy is becoming increasingly important. One of these additive manufacturing processes is the Arburg Plastic Freeforming process, which differs from the widely used Fused Filament Fabrication process in the way that droplets are discharged along a track instead of continuous extruded tracks. As with all other plastic-based additive manufacturing processes, due to the round shape of the tracks, voids occur between the individual tracks during manufacturing, which effects mechanical properties. In contrast to previous work, which mainly focused on how the mechanical properties change with a change in a single printing parameter, this work focused more closely on the interaction of three relevant printing parameters considered as a parameter set. Their influence on the mechanical properties was investigated by tensile tests, the influence on the residual porosity by density measurements and the influence on the geometric accuracy by surface roughness measurements. It was shown that by considering the parameters as a parameter set, states of high density and therefore high mechanical properties while reaching minimal surface roughness can be achieved for significantly more combinations than previously assumed. However, for these states the residual porosity was slightly different. This difference was explained by a parameter-dependent deformation factor of the droplets, which influences the maximal possible degree of filling during manufacturing. For the optimization of arbitrary parameter sets, an analytical model was derived.

20.
J Zoo Wildl Med ; 53(4): 670-678, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36640068

RESUMO

Appropriate and effective antibiotic use is a critical component of veterinary medicine, but there are variations across species regarding dosage and administration of these drugs. Oral or rectal routes of administration are typically used in elephants, but not all medications can achieve adequate concentrations rectally. The fluoroquinolone antimicrobials are used in elephants because of their favorable antimicrobial spectrum and pharmacokinetics compared with other oral agents. They are commonly used as part of multiple antibiotic regimens for the treatment of tuberculosis (Mycobacterium tuberculosis). The objective of this study was to determine the pharmacokinetic profile of levofloxacin after oral and rectal administration in Asian elephants (Elephas maximus). Dosages of 5 mg/kg orally and 15 mg/kg rectally were evaluated in 13 Asian elephants. Blood was collected at various time points from 0 to 72 h for pharmacokinetic analysis. Pharmacokinetic parameters were determined and reached concentrations above minimum inhibitory concentrations of various bacterial organisms via both routes. A pharmacokinetic-pharmacodynamic assessment was used to estimate appropriate minimal inhibitory concentrations for bacteria that could be potentially treated with this antimicrobial. Based on these findings, levofloxacin may be a consideration for administration orally (5 mg/kg) and rectally (15 mg/kg) in Asian elephants. Antimicrobial stewardship principles, culture and susceptibility of suspected pathogens, and blood level monitoring should be used to tailor administration of levofloxacin in this species.


Assuntos
Anti-Infecciosos , Elefantes , Animais , Levofloxacino , Área Sob a Curva , Antibacterianos
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