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1.
Malar J ; 23(1): 204, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38982496

RESUMO

BACKGROUND: Attractive Targeted Sugar Baits (ATSBs) offer a complementary vector control strategy to interventions targeting blood feeding or larval control by attacking the sugar feeding behaviour of adult mosquitoes using an attract-and-kill approach. Western Zambia was the first location to receive and deploy ATSB Sarabi version 1.2 stations in a Phase III cluster randomized controlled trial. This paper describes ATSB station installation, monitoring, removal, and disposal, quantifies ATSB station coverage, and reports major reasons for ATSB station replacement. METHODS: ATSB stations were deployed during two annual transmission seasons, through scheduled installation and removal campaigns. During deployment, monitoring was conducted per protocol to maintain high coverage of the ATSB stations in good condition. Routine monitoring visits during the trial captured details on ATSB station damage necessitating replacement following pre-defined replacement criteria. Annual cross-sectional household surveys measured ATSB station coverage during peak malaria transmission. RESULTS: A total of 67,945 ATSB stations were installed in Year 1 (41,695 initially installed+ 26,250 installed during monitoring) and 69,494 ATSB stations were installed in Year 2 (41,982 initially installed+ 27,512 installed during monitoring) across 35 intervention clusters to maintain high coverage of two ATSB stations in good condition per eligible household structure. The primary reasons for ATSB station replacement due to damage were holes/tears and presence of mold. Cross-sectional household surveys documented high coverage of ATSB stations across Year 1 and Year 2 with 93.1% of eligible structures having ≥ 2 ATSB stations in any condition. DISCUSSION: ATSB station deployment and monitoring efforts were conducted in the context of a controlled cRCT to assess potential product efficacy. Damage to ATSB stations during deployment required replacement of a subset of stations. High coverage of eligible structures was maintained over the two-year study despite replacement requirements. Additional research is needed to better understand the impact of damage on ATSB station effectiveness under programmatic conditions, including thresholds of threats to physical integrity and biological deterioration on product efficacy. CONCLUSIONS: Optimizing ATSB stations to address causes of damage and conducting implementation research to inform optimal delivery and cost-effective deployment will be important to facilitate scale-up of ATSB interventions.


Assuntos
Controle de Mosquitos , Zâmbia , Controle de Mosquitos/métodos , Humanos , Animais , Feminino , Malária/prevenção & controle , Açúcares , Estudos Transversais , Mosquitos Vetores/fisiologia , Anopheles/fisiologia , Masculino
2.
Front Aging Neurosci ; 16: 1417938, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38974902

RESUMO

Background: Parkinson's disease (PD) affects more than 6 million people worldwide. Along with motor impairments, patients and animal models exhibiting PD symptoms also experience cognitive impairment, fatigue, anxiety, and depression. Currently, there are no drugs available for PD that alter the progression of the disease. A body of evidence suggests that increased GABA levels contribute to the reduced expression of tyrosine hydroxylase (TH) and accompanying behavioral deficits. TH expression may be restored by blocking GABAA receptors. We hypothesized that golexanolone (GR3027), a well-tolerated GABAA receptor-modulating steroid antagonist (GAMSA), may improve Parkinson's symptoms in a rat model of PD. Objectives: The aims of this study were to assess whether golexanolone can ameliorate motor and non-motor symptoms in a rat model of PD and to identify some underlying mechanisms. Methods: We used the unilateral 6-OHDA rat model of PD. The golexanolone treatment started 4 weeks after surgery. Motor symptoms were assessed using Motorater and CatWalk tests. We also analyzed fatigue (using a treadmill test), anhedonia (via the sucrose preference test), anxiety (with an open field test), and short-term memory (using a Y maze). Glial activation and key proteins involved in PD pathogenesis were analyzed using immunohistochemistry and Western blot. Results: Rats with PD showed motor incoordination and impaired locomotor gait, increased fatigue, anxiety, depression, and impaired short-term memory. Golexanolone treatment led to improvements in motor incoordination, certain aspects of locomotor gait, fatigue, anxiety, depression, and short-term memory. Notably, golexanolone reduced the activation of microglia and astrocytes, mitigated TH loss at 5 weeks after surgery, and prevented the increase of α-synuclein levels at 10 weeks. Conclusions: Golexanolone may be useful in improving both motor and non-motor symptoms that adversely affect the quality of life in PD patients, such as anxiety, depression, fatigue, motor coordination, locomotor gait, and certain cognitive alterations.

3.
J Chem Phys ; 161(1)2024 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-38949594

RESUMO

Electron transfer reactions play an essential role in many chemical and biological processes. Fermi's golden rule (GR), which assumes that the coupling between electronic states is small, has formed the foundation of electron transfer rate theory; however, in short range electron/energy transfer reactions, this coupling can become very large, and, therefore, Fermi's GR fails to make even qualitatively accurate rate predictions. In this paper, I present a simple modified GR theory to describe electron transfer in the Marcus inverted regime at arbitrarily large electronic coupling strengths. This theory is based on an optimal global rotation of the diabatic states, which makes it compatible with existing methods for calculating GR rates that can account for nuclear quantum effects with anharmonic potentials. Furthermore, the optimal GR (OGR) theory can also be combined with analytic theories for non-adiabatic rates, such as Marcus theory and Marcus-Levich-Jortner theory, offering clear physical insights into strong electronic coupling effects in non-adiabatic processes. OGR theory is also tested on a large set of spin-boson models and an anharmonic model against exact quantum dynamics calculations, where it performs well, correctly predicting rate turnover at large coupling strengths. Finally, an example application to a boron-dipyrromethane-anthracene photosensitizer reveals that strong coupling effects inhibit excited state charge recombination in this system, reducing the rate of this process by a factor of 4. Overall, OGR theory offers a new approach to calculating electron transfer rates at strong couplings, offering new physical insights into a range of non-adiabatic processes.

4.
World J Orthop ; 15(6): 554-559, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38947266

RESUMO

BACKGROUND: Hip resurfacing arthroplasty (HRA) is an alternative to total hip arthroplasty (THA) that is typically reserved for young active patients because it preserves bone. However, the benefits of HRA only hold true if conversion THA after failed HRA provides acceptable outcomes. AIM: To compare patient reported outcomes for conversion THA after HRA failure to primary THA. METHODS: A retrospective review of 36 patients (37 hips) that underwent conversion THA for failed HRA between October 2006 and May 2019 by a single surgeon was performed. Patient reported outcomes [modified Harris Hip Score (mHHS), University of California Los Angeles (UCLA) activity score] were obtained via an email-based responder-anonymous survey. Outcomes were compared to normative data of a primary THA cohort with similar demographics. Subgroup analysis was performed comparing outcomes of conversion THA for adverse local tissue reaction (ALTR) vs all other causes for failure. RESULTS: The study group had a lower mHHS than the control group (81.7 ± 13.8 vs 90.2 ± 11.6, P < 0.01); however, both groups had similar UCLA activity levels (7.5 ± 2.3 vs 7.2 ± 1.6, P = 0.51). Patients that underwent conversion for non-ATLR causes had similar mHHS (85.2 ± 11.5 vs 90.2 ± 11.6, P = 0.11) and higher UCLA activity levels (8.5 ± 1.8 vs 7.2 ± 1.6, P < 0.01) compared to the control group. Patients that underwent conversion for ATLR had worse mHHS (77.1 ± 14.5 vs 90.2 ± 11.6, P < 0.01) and UCLA activity levels (6.1 ± 2.3 vs 7.2 ± 1.6, P = 0.05) when compared to the control group. CONCLUSION: Patient outcomes equivalent to primary THA can be achieved following HRA conversion to THA. However, inferior outcomes were demonstrated for ALTR-related HRA failure. Patient selection and perhaps further studies examining alternative HRA bearing surfaces should be considered.

5.
Evol Appl ; 17(7): e13739, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38948538

RESUMO

The Seychelles magpie-robin's (SMR) five island populations exhibit some of the lowest recorded levels of genetic diversity among endangered birds, and high levels of inbreeding. These populations collapsed during the 20th century, and the species was listed as Critically Endangered in the IUCN Red List in 1994. An assisted translocation-for-recovery program initiated in the 1990s increased the number of mature individuals, resulting in its downlisting to Endangered in 2005. Here, we explore the temporal genomic erosion of the SMR based on a dataset of 201 re-sequenced whole genomes that span the past ~150 years. Our sample set includes individuals that predate the bottleneck by up to 100 years, as well as individuals from contemporary populations established during the species recovery program. Despite the SMR's recent demographic recovery, our data reveal a marked increase in both the genetic load and realized load in the extant populations when compared to the historical samples. Conservation management may have reduced the intensity of selection by increasing juvenile survival and relaxing intraspecific competition between individuals, resulting in the accumulation of loss-of-function mutations (i.e. severely deleterious variants) in the rapidly recovering population. In addition, we found a 3-fold decrease in genetic diversity between temporal samples. While the low genetic diversity in modern populations may limit the species' adaptability to future environmental changes, future conservation efforts (including IUCN assessments) may also need to assess the threats posed by their high genetic load. Our computer simulations highlight the value of translocations for genetic rescue and show how this could halt genomic erosion in threatened species such as the SMR.

6.
Artigo em Inglês | MEDLINE | ID: mdl-38960137

RESUMO

OBJECTIVES: To investigate the usefulness of the routinely planned six-week outpatient visit and x-ray in patients treated surgically for the most common upper extremity fractures including clavicle, proximal humerus, humeral shaft, olecranon, radial shaft and distal radius. METHOD: This was a retrospective cohort study of all patients treated surgically for the most common upper extremity fractures between 2019 and 2022 in a level 1 trauma center. The first outcome of interest was the incidence of abnormalities found on the x-ray made at the 6-week outpatient visit. Abnormalities were defined as all differences between the intra-operative (or direct postoperative) and 6-week x-ray. In case an abnormality was detected, the hospital records were screened to determine its clinical consequence. The clinical consequences were categorized into requiring either additional diagnostics, additional interventions, change of standard postoperative immobilization, weightbearing or allowed range of motion (ROM). The second outcome of interest was the incidence of deviations from the local standard post operative treatment and follow-up protocol based on the 6-week outpatient visit as a whole. Deviations were also categorized into either requiring additional diagnostics, additional interventions, change of standard postoperative immobilization, weightbearing or allowed range of motion. RESULTS: A total of 267 patients were included. Abnormalities on x-ray at 6 weeks postoperatively were found in only 10 (3.7%) patients of which only 4 (1.5%) had clinical implications (in three patients extra imaging was required and in one patient it was necessary to deviate from standard weightbearing/ROM limitation regime). The clinical/radiological findings during the 6-week outpatient visit led to a deviation from standard in only 8 (3.0%) patients. Notably, the majority of these patients experienced symptoms suggestive for complications. CONCLUSION: The routine 6-week outpatient visit and x-ray, after surgery for common upper extremity fractures, rarely has clinical consequences. It should be questioned whether these routine visits are necessary and whether a more selective approach should be considered. LEVEL OF EVIDENCE: Level IV; Case Series; Prognosis Study.

8.
BMJ Open ; 14(7): e087950, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38977366

RESUMO

INTRODUCTION: Black emerging adults (18-28 years) have the highest risk of short sleep duration and obesity. This increased risk may be partly explained by greater stress levels, which may result from race-related stress (racial discrimination and heightened race-related vigilance) or living in more disadvantaged home and neighbourhood environments. Insufficient sleep may also impact obesity risk via several weight-related mechanisms including energy balance, appetite and food reward, cortisol profiles and hydration status. This paper describes the rationale, design and methods for the Sleep, Health Outcomes and Body Weight (SHOW) study. This study aims to prospectively assess the effects of sleep, race-related stress and home/neighbourhood environments on weight-related mechanisms and obesity markers (body weight, waist circumference and fat mass) in 150 black emerging adults. METHODS AND ANALYSIS: The SHOW study follows a measurement burst design that includes 3, 7-day data collection bursts (baseline, 6-month and 12-month follow-ups). Sleep is measured with three methods: sleep diary, actigraphy and polysomnography. Energy balance over 7 days is based on resting and postprandial energy expenditure measured via indirect calorimetry, physical activity via accelerometry and self-reported and ad libitum energy intake methods. Self-reported methods and blood biomarkers assess fasting and postprandial appetite profiles and a behavioural-choice task measures food reward. Cortisol awakening response and diurnal cortisol profiles over 3 days are assessed via saliva samples and chronic cortisol exposure via a hair sample. Hydration markers are assessed with 24-hour urine collection over 3 days and fasting blood biomarkers. Race-related stress is self-reported over 7 days. Home and neighbourhood environments (via the Windshield Survey) is observer assessed. ETHICS AND DISSEMINATION: Ethics approval was granted by the University of North Carolina at Greensboro's Institutional Review Board. Study findings will be disseminated through peer-reviewed publications, presentations at scientific meetings and reports, briefs/infographics for lay and community audiences.


Assuntos
Negro ou Afro-Americano , Obesidade , Sono , Humanos , Adulto , Adulto Jovem , Masculino , North Carolina/epidemiologia , Adolescente , Feminino , Fatores de Risco , Sono/fisiologia , Peso Corporal , Estudos Prospectivos , Projetos de Pesquisa , Metabolismo Energético , Estresse Psicológico , Hidrocortisona/análise , Hidrocortisona/sangue , Hidrocortisona/metabolismo , Actigrafia , Circunferência da Cintura
9.
PLoS One ; 19(6): e0305369, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38865434

RESUMO

Determining space use for species is fundamental to understanding their ecology, and tracking animals can reveal insights into their spatial ecology on home ranges and territories. Recent technological advances have led to GPS-tracking devices light enough for birds as small as ~30 g, creating novel opportunities to remotely monitor fine-scale movements and space use for these smaller species. We tested whether miniaturized GPS tags can allow us to understand space use of migratory birds away from their capture sites and sought to understand both pre-breeding space use as well as territory and habitat use on the breeding grounds. We used GPS tags to characterize home ranges on the breeding grounds for a migratory songbird with limited available breeding information, the Golden-crowned Sparrow (Zonotrichia atricapilla). Using GPS points from 23 individuals across 26 tags (three birds tagged twice), we found home ranges in Alaska and British Columbia were on average 44.1 ha (95% kernel density estimate). In addition, estimates of territory sizes based on field observations (mean 2.1 ha, 95% minimum convex polygon [MCP]) were three times smaller than 95% MCPs created using GPS tags (mean 6.5 ha). Home ranges included a variety of land cover classes, with shrubland particularly dominant (64-100% of home range cover for all but one bird). Three birds tracked twice returned to the same breeding area each year, supporting high breeding site fidelity for this species. We found reverse spring migration for five birds that flew up to 154 km past breeding destinations before returning. GPS-tracking technology allowed for critical ecological insights into this migratory species that breeds in very remote locations.


Assuntos
Migração Animal , Sistemas de Informação Geográfica , Comportamento de Retorno ao Território Vital , Estações do Ano , Pardais , Animais , Migração Animal/fisiologia , Pardais/fisiologia , Comportamento de Retorno ao Território Vital/fisiologia , Cruzamento , Ecossistema , Colúmbia Britânica , Alaska , Comportamento de Nidação/fisiologia
10.
Clin Biomech (Bristol, Avon) ; 116: 106286, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38850881

RESUMO

BACKGROUND: The aim of this study was to test the hypothesis that proinflammatory cytokines correlate with knee loading mechanics during gait following a mechanical walking stimulus in subjects 2 years after anterior cruciate ligament reconstruction. Elevated systemic levels of proinflammatory cytokines can be sustained for years after injury. Considering roughly 50% of these patients progress to Osteoarthritis 10-15 years after injury, a better understanding of the role of proinflammatory cytokines such as tumor necrosis factor-α and Interleukin-1ß on Osteoarthritis risk is needed. METHODS: Serum proinflammatory cytokines concentrations were measured in 21 subjects 2 years after unilateral ACLR from blood drawn at rest and 3.5 h after 30 min of walking. An optoelectronic system and a force plate measured subjects' knee kinetics. Correlations were tested between inflammatory marker response and knee extension and knee adduction moments. FINDINGS: Changes in proinflammatory cytokines due to mechanical stimulus were correlated (R = 0.86) and showed substantial variation between subjects in both cytokines at 3.5 h post-walk. Knee loading correlated with 3.5-h changes in tumor necrosis factor-α concentration (Knee extension moment: R = -0.5, Knee adduction moment: R = -0.5) and Interleukin-1ß concentration (Knee extension moment: R = -0.44). However, no significant changes in concentrations were observed in tumor necrosis factor-α and Interleukin-1ß when comparing baseline and post walking stimulus conditions. INTERPRETATION: The significant associations between changes in serum proinflammatory markers following a mechanical stimulus and gait metrics in subjects at risk for developing Osteoarthritis underscore the importance of investigating the interaction between biomarkers and biomechanical factors in Osteoarthritis development.


Assuntos
Reconstrução do Ligamento Cruzado Anterior , Citocinas , Articulação do Joelho , Humanos , Masculino , Feminino , Citocinas/sangue , Adulto , Articulação do Joelho/fisiopatologia , Marcha , Lesões do Ligamento Cruzado Anterior/cirurgia , Lesões do Ligamento Cruzado Anterior/fisiopatologia , Suporte de Carga , Interleucina-1beta/sangue , Caminhada , Fator de Necrose Tumoral alfa/sangue , Adulto Jovem , Osteoartrite do Joelho/fisiopatologia , Osteoartrite do Joelho/sangue , Osteoartrite do Joelho/cirurgia , Fenômenos Biomecânicos , Biomarcadores/sangue , Estresse Mecânico , Ligamento Cruzado Anterior/cirurgia
12.
Crit Rev Eukaryot Gene Expr ; 34(6): 61-69, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38912963

RESUMO

Objective criteria are required for prostate cancer (PCa) risk assessment, treatment decisions, evaluation of therapy, and initial indications of recurrence. Circulating microRNAs were utilized as biomarkers to distinguish PCa patients from cancer-free subjects or those encountering benign prostate hyperplasia. A panel of 60 microRNAs was developed with established roles in PCa initiation, progression, metastasis, and recurrence. Utilizing the FirePlex® platform for microRNA analysis, we demonstrated the efficacy and reproducibility of a rapid, high-throughput, serum-based assay for PCa biomarkers that circumvents the requirement for extraction and fractionation of patient specimens supporting feasibility for expanded clinical research and diagnostic applications.


Assuntos
Biomarcadores Tumorais , MicroRNAs , Neoplasias da Próstata , Humanos , Masculino , Neoplasias da Próstata/genética , Neoplasias da Próstata/diagnóstico , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/sangue , MicroRNAs/genética , MicroRNAs/sangue , Medição de Risco/métodos
14.
J Clin Med ; 13(11)2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38893055

RESUMO

Background: The treatment of complex proximal humerus fractures in elderly patients is not yet fully elucidated. Of all treatment options, reverse shoulder arthroplasty (RSA) and non-operative treatment (NOT) appear to provide the best results. Evidence to guide the choice between the two is sparse. Therefore, this review provides an overview of the available evidence on RSA versus NOT. Methods: Studies comparing complex proximal humerus fractures in patients aged >65 years treated either with RSA or NOT were included for systematic review and direct comparison via pooled analysis of patient-rated outcome and range of motion. Indirect comparison of case series and non-comparative studies on either treatment was performed separately. Results: Three comparative studies including 77 patients treated with RSA and 81 treated non-operatively were analysed. The RSA group scored better for both the Constant-Murley score (mean difference 6 points) and DASH score (mean difference 8 points). No differences were detected in ASES, PENN score, pain scores, or range of motion between treatment groups. The most common complications for RSA were infection (3%), nerve injury (2%), and dislocation (2%). Reoperation was required in 5%. In the NOT group, common complications included malunion (42%), osteonecrosis (25%), and non-union (3%); no reoperation was required. Patient satisfaction was equal in both groups. Conclusions: The functional outcomes and range of motion after RSA seemed satisfactory and potentially superior to NOT in elderly patients. Patient satisfaction was comparable despite a high malunion and osteonecrosis rate in the non-operative treatment group, which did not require re-interventions.

15.
J Arthroplasty ; 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38897261

RESUMO

INTRODUCTION: Modular metaphyseal engaging (MME) femoral components in total hip arthroplasty (THA) allow optimized femoral length, offset, and anteversion and are useful in patients with unusual proximal femoral anatomy. Fretting, corrosion, and stem fractures above the modular sleeve are complications associated with these implants. The purpose of this study was to identify failure mechanisms of retrieved MME femoral components at our institution, identify all broken stem cases, and evaluate how often an extended trochanteric osteotomy (ETO) was required for removal. METHODS: All consecutively retrieved MME femoral components from September 2002 to May 2023 were reviewed. Patient demographics, procedure information, component specifications, indications for removal, and requirements for further revision surgery were reviewed. Descriptive statistics were calculated for the variables of interest. RESULTS: There were 131 retrieved MME components. The mean age at surgery was 59 years (range, 28 to 75), 49% were women, the mean body mass index (BMI) was 29.4 (range, 20.7 to 33.3), and the mean American Society of Anesthesiologists (ASA) score was 2.4 ± 0.5. There were 102 (78%) stems of one design (Stem A), and the remaining 29 (22%) were of a different design (Stem B). Of the 131 components, ten (7.6%) failed secondary to a stem fracture proximal to the modular sleeve. Regarding each MME stem design, 4 of 102 (4%) of Stem A and 6 of 29 (21% of Stem B) fractured. All broken stems required additional intervention for removal during revision THA, using an extended trochanteric osteotomy (N = 9) or cortical window (N = 1) in which an intraoperative proximal femoral fracture occurred. CONCLUSIONS: Broken MME stems present a challenge for orthopaedic surgeons during revision THA. When a stem fracture occurs above the ingrown sleeve, the distal splines may also have osseous interdigitation into the clothespin. Thus, when revising a broken MME stem, an ETO should be performed, and the segment should be long enough to allow distal access.

16.
J Innate Immun ; 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38901409

RESUMO

INTRODUCTION: The hydrophilic, polymeric chain of the lipoteichoic acid (LTA) of the Gram-positive pathobiont Streptococcus pneumoniae is covalently linked to the glycosylglycerolipid -D-glucopyranosyl-(1,3)-diacylglycerol by the lipoteichoic acid ligase TacL, leading to its fixation in the cytoplasmic membrane. Pneumococcal LTA, sharing identical repeating units with the wall teichoic acids, are dispensable for normal growth but required for full-virulence in invasive infections. METHODS: Mutants deficient in TacL and complemented strains constructed were tested for their growth, resistance against oxidative stress and susceptibility against antimicrobial peptides. Further, the membrane fluidity of pneumococci, their capability to adhere to lung epithelial cells and virulence in a Galleria mellonella as well as intranasal mouse infection model were assessed. RESULTS: In the present study, we indicate that LTA is already indispensable for pneumococcal adherence to human nasopharyngeal cells and colonization in an intranasal mouse infection model. Mutants deficient for TacL did not show morphological defects. However, our analysis of pneumococcal membranes in different serotypes showed an altered membrane fluidity and surface protein abundance of lipoproteins in mutants deficient for LTA but not WTA. These mutants had a decreased membrane fluidity, exhibited higher amounts of lipoproteins, and showed an increased susceptibility to antimicrobial peptides. In complemented mutant strains this defect was fully restored. CONCLUSION: Taken together, LTA is crucial for colonization and required to effectively protect pneumococci from innate immune defence mechanisms by maintaining the membrane integrity.

17.
Clin Infect Dis ; 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38902929

RESUMO

The in vitro susceptibility testing interpretive criteria (STIC) for TZP against Enterobacterales were recently updated by the Food and Drug Administration (FDA), Clinical & Laboratory Standards Institute (CLSI), and European Committee on Antimicrobial Susceptibility Testing (EUCAST). The United States Committee on Antimicrobial Susceptibility Testing (USCAST) also recently reviewed TZP STIC for Enterobacterales and arrived at different STIC for Enterobacterales and herein we explain our recommendations and rationale behind them. Based on our review of the available data, USCAST does not recommend TZP STIC for certain Enterobacterales species that have a moderate to high likelihood of clinically significant AmpC production (E. cloacae, C. freundii, and K. aerogenes only) or for third-generation cephalosporin-non-susceptible (3GC-NS) Enterobacterales. USCAST recommends a TZP susceptibility breakpoint of ≤ 16/4 mg/L for third-generation cephalosporin-susceptible (3GC-S) Enterobacterales but only endorses the use of extended infusion TZP regimens for patients with infections due to these pathogens.

19.
Nat Commun ; 15(1): 5360, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38918375

RESUMO

Oxygen homeostasis is maintained in plants and animals by O2-sensing enzymes initiating adaptive responses to low O2 (hypoxia). Recently, the O2-sensitive enzyme ADO was shown to initiate degradation of target proteins RGS4/5 and IL32 via the Cysteine/Arginine N-degron pathway. ADO functions by catalysing oxidation of N-terminal cysteine residues, but despite multiple proteins in the human proteome having an N-terminal cysteine, other endogenous ADO substrates have not yet been identified. This could be because alternative modifications of N-terminal cysteine residues, including acetylation, prevent ADO-catalysed oxidation. Here we investigate the relationship between ADO-catalysed oxidation and NatA-catalysed acetylation of a broad range of protein sequences with N-terminal cysteines. We present evidence that human NatA catalyses N-terminal cysteine acetylation in vitro and in vivo. We then show that sequences downstream of the N-terminal cysteine dictate whether this residue is oxidised or acetylated, with ADO preferring basic and aromatic amino acids and NatA preferring acidic or polar residues. In vitro, the two modifications appear to be mutually exclusive, suggesting that distinct pools of N-terminal cysteine proteins may be acetylated or oxidised. These results reveal the sequence determinants that contribute to N-terminal cysteine protein modifications, with implications for O2-dependent protein stability and the hypoxic response.


Assuntos
Cisteína , Oxirredução , Estabilidade Proteica , Cisteína/metabolismo , Cisteína/química , Acetilação , Humanos , Oxigênio/metabolismo , Oxigênio/química , Processamento de Proteína Pós-Traducional , Sequência de Aminoácidos , Células HEK293
20.
Biosensors (Basel) ; 14(6)2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38920605

RESUMO

Three-dimensional (3D) printing presents a compelling alternative for fabricating microfluidic devices, circumventing certain limitations associated with traditional soft lithography methods. Microfluidics play a crucial role in the biomedical sciences, particularly in the creation of tissue spheroids and pharmaceutical research. Among the various 3D printing techniques, light-driven methods such as stereolithography (SLA), digital light processing (DLP), and photopolymer inkjet printing have gained prominence in microfluidics due to their rapid prototyping capabilities, high-resolution printing, and low processing temperatures. This review offers a comprehensive overview of light-driven 3D printing techniques used in the fabrication of advanced microfluidic devices. It explores biomedical applications for 3D-printed microfluidics and provides insights into their potential impact and functionality within the biomedical field. We further summarize three light-driven 3D printing strategies for producing biomedical microfluidic systems: direct construction of microfluidic devices for cell culture, PDMS-based microfluidic devices for tissue engineering, and a modular SLA-printed microfluidic chip to co-culture and monitor cells.


Assuntos
Dispositivos Lab-On-A-Chip , Impressão Tridimensional , Engenharia Tecidual , Humanos , Luz , Microfluídica , Técnicas de Cultura de Tecidos
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