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1.
Proc Natl Acad Sci U S A ; 120(12): e2217254120, 2023 03 21.
Artículo en Inglés | MEDLINE | ID: mdl-36917671

RESUMEN

The potentiation of antibiotics is a promising strategy for combatting antibiotic-resistant/tolerant bacteria. Herein, we report that a 5-min sublethal heat shock enhances the bactericidal actions of aminoglycoside antibiotics by six orders of magnitude against both exponential- and stationary-phase Escherichia coli. This combined treatment also effectively kills various E. coli persisters, E. coli clinical isolates, and numerous gram-negative but not gram-positive bacteria and enables aminoglycosides at 5% of minimum inhibitory concentrations to eradicate multidrug-resistant pathogens Acinetobacter baumannii and Klebsiella pneumoniae. Mechanistically, the potentiation is achieved comprehensively by heat shock-enhanced proton motive force that thus promotes the bacterial uptake of aminoglycosides, as well as by increasing irreversible protein aggregation and reactive oxygen species that further augment the downstream lethality of aminoglycosides. Consistently, protonophores, chemical chaperones, antioxidants, and anaerobic culturing abolish heat shock-enhanced aminoglycoside lethality. We also demonstrate as a proof of concept that infrared irradiation- or photothermal nanosphere-induced thermal treatments potentiate aminoglycoside killing of Pseudomonas aeruginosa in a mouse acute skin wound model. Our study advances the understanding of the mechanism of actions of aminoglycosides and demonstrates a high potential for thermal ablation in curing bacterial infections when combined with aminoglycosides.


Asunto(s)
Aminoglicósidos , Antibacterianos , Ratones , Animales , Antibacterianos/farmacología , Antibacterianos/química , Aminoglicósidos/farmacología , Aminoglicósidos/química , Especies Reactivas de Oxígeno/farmacología , Agregado de Proteínas , Escherichia coli , Bacterias Gramnegativas , Bacterias , Respuesta al Choque Térmico , Pruebas de Sensibilidad Microbiana
2.
J Virol ; : e0151324, 2024 Oct 24.
Artículo en Inglés | MEDLINE | ID: mdl-39445801

RESUMEN

Toxin/antitoxin (TA) systems are present in nearly every prokaryotic genome and play the important physiological roles of phage inhibition by reducing metabolism (this includes persistence for the extreme case of complete cessation of metabolism), genetic element stabilization, and biofilm formation. TA systems have also been incorporated into other cell systems, such as CRISPR-Cas and phage quorum sensing. For the simplest and best-studied case, proteinaceous toxins and antitoxins (i.e., type II), toxin activity is masked by direct binding of the antitoxin. A long-standing, unresolved question in the TA field is how toxins are activated when bound to antitoxins at nanomolar affinity. The current paradigm envisions preferential degradation of the antitoxin by a protease, but this is highly unlikely in that a protease cannot discriminate between bound toxin and bound antitoxin because both are highly structured. Strikingly, recent results from several studies show one likely mechanism for toxin activation is conformational changes in the TA complex that result in the release or activation of the toxin as a result of a protein trigger, such as that from phages, and as a result of thermally-driven refolding dynamics.

3.
Proc Natl Acad Sci U S A ; 119(26): e2122069119, 2022 06 28.
Artículo en Inglés | MEDLINE | ID: mdl-35727983

RESUMEN

Although experiments show that exposure to factual information can increase factual accuracy, the public remains stubbornly misinformed about many issues. Why do misperceptions persist even when factual interventions generally succeed at increasing the accuracy of people's beliefs? We seek to answer this question by testing the role of information exposure and decay effects in a four-wave panel experiment (n = 2,898 at wave 4) in which we randomize the media content that people in the United States see about climate change. Our results indicate that science coverage of climate change increases belief accuracy and support for government action immediately after exposure, including among Republicans and people who reject anthropogenic climate change. However, both effects decay over time and can be attenuated by exposure to skeptical opinion content (but not issue coverage featuring partisan conflict). These findings demonstrate that the increases in belief accuracy generated by science coverage are short lived and can be neutralized by skeptical opinion content.


Asunto(s)
Actitud , Cambio Climático , Confianza , Comunicación , Humanos , Estados Unidos
4.
Biophys J ; 2024 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-39390745

RESUMEN

Multiple-particle tracking (MPT) is a microscopy technique capable of simultaneously tracking hundreds to thousands of nanoparticles in a biological sample and has been used extensively to characterize biological microenvironments, including the brain extracellular space (ECS). Machine learning techniques have been applied to MPT data sets to predict the diffusion mode of nanoparticle trajectories as well as more complex biological variables, such as biological age. In this study, we develop a machine learning pipeline to predict and investigate changes to the brain ECS due to injury using supervised classification and feature importance calculations. We first validate the pipeline on three related but distinct MPT data sets from the living brain ECS-age differences, region differences, and enzymatic degradation of ECS structure. We predict three ages with 86% accuracy, three regions with 90% accuracy, and healthy versus enzyme-treated tissue with 69% accuracy. Since injury across groups is normally compared with traditional statistical approaches, we first used linear mixed effects models to compare features between healthy control conditions and injury induced by two different oxygen glucose deprivation exposure times. We then used machine learning to predict injury state using MPT features. We show that the pipeline predicts between the healthy control, 0.5 h OGD treatment, and 1.5 h OGD treatment with 59% accuracy in the cortex and 66% in the striatum, and identifies nonlinear relationships between trajectory features that were not evident from traditional linear models. Our work demonstrates that machine learning applied to MPT data is effective across multiple experimental conditions and can find unique biologically relevant features of nanoparticle diffusion.

5.
J Pediatr ; 268: 113933, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38309524

RESUMEN

OBJECTIVE: To compare the short- and long-term outcomes of infants with hypoxic-ischemic encephalopathy (HIE) treated with whole-body therapeutic hypothermia (TH), monitored by esophageal vs rectal temperature. STUDY DESIGN: We conducted a secondary analysis of the multicenter High-Dose Erythropoietin for Asphyxia and Encephalopathy (HEAL) trial. All infants had moderate or severe HIE and were treated with whole-body TH. The primary outcome was death or neurodevelopmental impairment (NDI) at 22-36 months of age. Secondary outcomes included seizures, evidence of brain injury on magnetic resonance imaging, and complications of hypothermia. Logistic regression was used with adjustment for disease severity and site as clustering variable because cooling modality differed by site. RESULTS: Of the 500 infants who underwent TH, 294 (59%) and 206 (41%) had esophageal and rectal temperature monitoring, respectively. There were no differences in death or NDI, seizures, or evidence of injury on magnetic resonance imaging between the 2 groups. Infants treated with TH and rectal temperature monitoring had lower odds of overcooling (OR 0.52, 95% CI 0.34-0.80) and lower odds of hypotension (OR 0.57, 95% CI 0.39-0.84) compared with those with esophageal temperature monitoring. CONCLUSIONS: Although infants undergoing TH with esophageal monitoring were more likely to experience overcooling and hypotension, the rate of death or NDI was similar whether esophageal monitoring or rectal temperature monitoring was used. Further studies are needed to investigate whether esophageal temperature monitoring during TH is associated with an increased risk of overcooling and hypotension.


Asunto(s)
Temperatura Corporal , Esófago , Hipotermia Inducida , Hipoxia-Isquemia Encefálica , Recto , Humanos , Hipotermia Inducida/métodos , Hipoxia-Isquemia Encefálica/terapia , Masculino , Femenino , Recién Nacido , Lactante , Esófago/diagnóstico por imagen , Resultado del Tratamiento , Monitoreo Fisiológico/métodos , Imagen por Resonancia Magnética , Preescolar
6.
J Pediatr ; 266: 113853, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38006967

RESUMEN

OBJECTIVE: To determine if time to reaching target temperature (TT) is associated with death or neurodevelopmental impairment (NDI) at 2 years of age in infants with hypoxic-ischemic encephalopathy (HIE). STUDY DESIGN: Newborn infants ≥36 weeks of gestation diagnosed with moderate or severe HIE and treated with therapeutic hypothermia were stratified based on time at which TT was reached, defined as early (ie, ≤4 hours of age) or late (>4 hours of age). Primary outcomes were death or NDI. Secondary outcomes included neurodevelopmental assessment with Bayley Scales of Infant and Toddler Development, third edition (BSID-III) at age 2. RESULTS: Among 500 infants, the median time to reaching TT was 4.3 hours (IWR, 3.2-5.7 hours). Infants in early TT group (n = 211 [42%]) compared with the late TT group (n = 289 [58%]) were more likely to be inborn (23% vs 13%; P < .001) and have severe HIE (28% vs 19%; P = .03). The early and late TT groups did not differ in the primary outcome of death or any NDI (adjusted RR, 1.05; 95% CI, 0.85-0.30; P = .62). Among survivors, neurodevelopmental outcomes did not differ significantly in the 2 groups (adjusted mean difference in Bayley Scales of Infant Development-III scores: cognitive, -2.8 [95% CI, -6.1 to 0.5], language -3.3 [95% CI, -7.4 to 0.8], and motor -3.5 [95% CI, -7.3 to 0.3]). CONCLUSIONS: In infants with HIE, time to reach TT is not independently associated with risk of death or NDI at age 2 years. Among survivors, developmental outcomes are similar between those who reached TT at <4 and ≥4 hours of age. TRIAL REGISTRATION: High-dose Erythropoietin for Asphyxia and Encephalopathy (HEAL); NCT02811263; https://beta. CLINICALTRIALS: gov/study/NCT02811263.


Asunto(s)
Hipotermia Inducida , Hipoxia-Isquemia Encefálica , Humanos , Recién Nacido , Frío , Discapacidades del Desarrollo/complicaciones , Hipoxia-Isquemia Encefálica/terapia , Hipoxia-Isquemia Encefálica/complicaciones , Temperatura
7.
Pediatr Res ; 95(1): 84-92, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37684430

RESUMEN

BACKGROUND: Neonatal encephalopathy (NE) remains a common cause of infant morbidity and mortality. Neuropathological corollaries of NE associated with acute hypoxia-ischemia include a central injury pattern involving the basal ganglia and thalamus, which may interfere with thermoregulatory circuits. Spontaneous hypothermia (SH) occurs in both preclinical models and clinical hypoxic-ischemic NE and may provide an early biomarker of injury severity. To determine whether SH predicts the degree of injury in a ferret model of hypoxic-ischemic NE, we investigated whether rectal temperature (RT) 1 h after insult correlated with long-term outcomes. METHODS: Postnatal day (P)17 ferrets were presensitized with Escherichia coli lipopolysaccharide before undergoing hypoxia-ischemia/hyperoxia (HIH): bilateral carotid artery ligation, hypoxia-hyperoxia-hypoxia, and right ligation reversal. One hour later, nesting RTs were measured. RESULTS: Animals exposed to HIH were separated into normothermic (NT; ≥34.4 °C) or spontaneously hypothermic (SH; <34.4 °C) groups. At P42, cortical development, ex vivo MRI, and neuropathology were quantitated. Whole-brain volume and fractional anisotropy in SH brains were significantly decreased compared to control and NT animals. SH brains also had significantly altered gyrification, greater cortical pathology, and increased corpus callosum GFAP staining relative to NT and control brains. CONCLUSION: In near-term-equivalent ferrets, nesting RT 1 h after HIH may predict long-term neuropathological outcomes. IMPACT: High-throughput methods to determine injury severity prior to treatment in animal studies of neonatal brain injury are lacking. In a gyrified animal model of neonatal inflammation-sensitized hypoxic-ischemic brain injury in the ferret, rectal temperature 1 h after hypoxia predicts animals who will have increased cortical pathology and white matter changes on MRI. These changes parallel similar responses in rodents and humans but have not previously been correlated with long-term neuropathological outcomes in gyrified animal models. Endogenous thermoregulatory responses to injury may provide a translational marker of injury severity to help stratify animals to treatment groups or predict outcome in preclinical studies.


Asunto(s)
Lesiones Encefálicas , Hiperoxia , Hipotermia Inducida , Hipotermia , Hipoxia-Isquemia Encefálica , Sustancia Blanca , Humanos , Recién Nacido , Animales , Hurones , Animales Recién Nacidos , Sustancia Blanca/patología , Hiperoxia/patología , Temperatura , Hipoxia/patología , Isquemia/patología , Hipoxia-Isquemia Encefálica/terapia , Hipotermia Inducida/métodos , Encéfalo/patología , Hipotermia/terapia , Lesiones Encefálicas/terapia
8.
BMC Psychiatry ; 24(1): 530, 2024 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-39049010

RESUMEN

BACKGROUND: Pooling data from different sources will advance mental health research by providing larger sample sizes and allowing cross-study comparisons; however, the heterogeneity in how variables are measured across studies poses a challenge to this process. METHODS: This study explored the potential of using natural language processing (NLP) to harmonise different mental health questionnaires by matching individual questions based on their semantic content. Using the Sentence-BERT model, we calculated the semantic similarity (cosine index) between 741 pairs of questions from five questionnaires. Drawing on data from a representative UK sample of adults (N = 2,058), we calculated a Spearman rank correlation for each of the same pairs of items, and then estimated the correlation between the cosine values and Spearman coefficients. We also used network analysis to explore the model's ability to uncover structures within the data and metadata. RESULTS: We found a moderate overall correlation (r = .48, p < .001) between the two indices. In a holdout sample, the cosine scores predicted the real-world correlations with a small degree of error (MAE = 0.05, MedAE = 0.04, RMSE = 0.064) suggesting the utility of NLP in identifying similar items for cross-study data pooling. Our NLP model could detect more complex patterns in our data, however it required manual rules to decide which edges to include in the network. CONCLUSIONS: This research shows that it is possible to quantify the semantic similarity between pairs of questionnaire items from their meta-data, and these similarity indices correlate with how participants would answer the same two items. This highlights the potential of NLP to facilitate cross-study data pooling in mental health research. Nevertheless, researchers are cautioned to verify the psychometric equivalence of matched items.


Asunto(s)
Salud Mental , Procesamiento de Lenguaje Natural , Humanos , Encuestas y Cuestionarios/normas , Adulto , Femenino , Masculino , Semántica , Persona de Mediana Edad , Reino Unido
9.
Nucleic Acids Res ; 50(1): 227-243, 2022 01 11.
Artículo en Inglés | MEDLINE | ID: mdl-34928327

RESUMEN

Pseudomonas aeruginosa uses three type six secretion systems (H1-, H2- and H3-T6SS) to manipulate its environment, subvert host cells and for microbial competition. These T6SS machines are loaded with a variety of effectors/toxins, many being associated with a specific VgrG. How P. aeruginosa transcriptionally coordinates the main T6SS clusters and the multiple vgrG islands spread through the genome is unknown. Here we show an unprecedented level of control with RsmA repressing most known T6SS-related genes. Moreover, each of the H2- and H3-T6SS clusters encodes a sigma factor activator (SFA) protein called, Sfa2 and Sfa3, respectively. SFA proteins are enhancer binding proteins necessary for the sigma factor RpoN. Using a combination of RNA-seq, ChIP-seq and molecular biology approaches, we demonstrate that RpoN coordinates the T6SSs of P. aeruginosa by activating the H2-T6SS but repressing the H1- and H3-T6SS. Furthermore, RpoN and Sfa2 control the expression of the H2-T6SS-linked VgrGs and their effector arsenal to enable very effective interbacterial killing. Sfa2 is specific as Sfa3 from the H3-T6SS cannot complement loss of Sfa2. Our study further delineates the regulatory mechanisms that modulate the deployment of an arsenal of T6SS effectors likely enabling P. aeruginosa to adapt to a range of environmental conditions.


Asunto(s)
Sistemas de Secreción Bacterianos/genética , Pseudomonas aeruginosa/metabolismo , ARN Polimerasa Sigma 54/metabolismo , Sistemas de Secreción Bacterianos/metabolismo , Toxinas Bacterianas/genética , Toxinas Bacterianas/metabolismo , Regulación Bacteriana de la Expresión Génica , Pseudomonas aeruginosa/genética , ARN Polimerasa Sigma 54/genética
10.
J Ultrasound Med ; 43(6): 1089-1097, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38404126

RESUMEN

OBJECTIVE: Despite strong evidence for its utility in clinical management and diagnosis of intracranial hemorrhage (ICH), the use of neonatal cranial point-of-care ultrasound (POCUS) has not been standardized in neonatal intensive care units (NICUs) in the United States. The primary aim of this study was to evaluate the feasibility of training NICU providers to perform cranial POCUS by tracking the quality of image acquisition following training. METHODS: Observational single-center cohort study of cranial POCUS images obtained by trained neonatal practitioners (attendings, fellows, and advanced practice providers) using a protocol developed by a radiologist and neonatologist. Exams were performed on infants born ≤1250 g and/or ≤30 weeks gestation within the first 3 days after birth. A survey to assess attitudes regarding cranial POCUS was given before each of three training sessions. Demographic and clinical data collection were portrayed with descriptive statistics. Metrics of image quality were assessed by a radiologist and sonographer independently. Analysis of trends in quality of POCUS images over time was performed using a multinomial Cochran-Armitage test. RESULTS: Eighty-two cranial POCUS scans were performed over a 2-year period. Infant median age at exam was 14 hours (IQR 7-22 hours). Metrics of image quality depicted quarterly demonstrated a significant improvement in depth (P = .01), gain (P = .048), and quality of anatomy images captured (P < .001) over time. Providers perceived increased utility and safety of cranial POCUS over time. CONCLUSION: Cranial POCUS image acquisition improved significantly following care team training, which may enable providers to diagnose ICH at the bedside.


Asunto(s)
Estudios de Factibilidad , Sistemas de Atención de Punto , Ultrasonografía , Humanos , Recién Nacido , Femenino , Masculino , Ultrasonografía/métodos , Estudios de Cohortes , Hemorragias Intracraneales/diagnóstico por imagen , Unidades de Cuidado Intensivo Neonatal , Encéfalo/diagnóstico por imagen
11.
Proc Natl Acad Sci U S A ; 118(37)2021 09 14.
Artículo en Inglés | MEDLINE | ID: mdl-34507996

RESUMEN

The spread of misinformation is a global phenomenon, with implications for elections, state-sanctioned violence, and health outcomes. Yet, even though scholars have investigated the capacity of fact-checking to reduce belief in misinformation, little evidence exists on the global effectiveness of this approach. We describe fact-checking experiments conducted simultaneously in Argentina, Nigeria, South Africa, and the United Kingdom, in which we studied whether fact-checking can durably reduce belief in misinformation. In total, we evaluated 22 fact-checks, including two that were tested in all four countries. Fact-checking reduced belief in misinformation, with most effects still apparent more than 2 wk later. A meta-analytic procedure indicates that fact-checks reduced belief in misinformation by at least 0.59 points on a 5-point scale. Exposure to misinformation, however, only increased false beliefs by less than 0.07 points on the same scale. Across continents, fact-checks reduce belief in misinformation, often durably so.


Asunto(s)
COVID-19/epidemiología , Comunicación , Calentamiento Global , Difusión de la Información , Reconocimiento en Psicología/fisiología , Medios de Comunicación Sociales/provisión & distribución , Argentina/epidemiología , COVID-19/transmisión , COVID-19/virología , Humanos , Nigeria/epidemiología , Sudáfrica/epidemiología , Reino Unido/epidemiología
12.
Proc Natl Acad Sci U S A ; 118(23)2021 06 08.
Artículo en Inglés | MEDLINE | ID: mdl-34078668

RESUMEN

Democratic stability depends on citizens on the losing side accepting election outcomes. Can rhetoric by political leaders undermine this norm? Using a panel survey experiment, we evaluate the effects of exposure to multiple statements from former president Donald Trump attacking the legitimacy of the 2020 US presidential election. Although exposure to these statements does not measurably affect general support for political violence or belief in democracy, it erodes trust and confidence in elections and increases belief that the election is rigged among people who approve of Trump's job performance. These results suggest that rhetoric from political elites can undermine respect for critical democratic norms among their supporters.


Asunto(s)
Lenguaje , Liderazgo , Política , Humanos , Sociología , Encuestas y Cuestionarios , Estados Unidos , Violencia
13.
Proc Natl Acad Sci U S A ; 118(4)2021 01 26.
Artículo en Inglés | MEDLINE | ID: mdl-33483419

RESUMEN

Toxin-antitoxin (TA) loci were initially identified on conjugative plasmids, and one function of plasmid-encoded TA systems is to stabilize plasmids or increase plasmid competition via postsegregational killing. Here, we discovered that the type II TA system, Pseudoalteromonas rubra plasmid toxin-antitoxin PrpT/PrpA, on a low-copy-number conjugative plasmid, directly controls plasmid replication. Toxin PrpT resembles ParE of plasmid RK2 while antitoxin PrpA (PF03693) shares no similarity with previously characterized antitoxins. Surprisingly, deleting this prpA-prpT operon from the plasmid does not result in plasmid segregational loss, but greatly increases plasmid copy number. Mechanistically, the antitoxin PrpA functions as a negative regulator of plasmid replication, by binding to the iterons in the plasmid origin that inhibits the binding of the replication initiator to the iterons. We also demonstrated that PrpA is produced at a higher level than PrpT to prevent the plasmid from overreplicating, while partial or complete degradation of labile PrpA derepresses plasmid replication. Importantly, the PrpT/PrpA TA system is conserved and is widespread on many conjugative plasmids. Altogether, we discovered a function of a plasmid-encoded TA system that provides new insights into the physiological significance of TA systems.


Asunto(s)
Replicación del ADN/genética , Plásmidos/genética , Pseudoalteromonas/genética , Sistemas Toxina-Antitoxina/genética , Proteínas Bacterianas/genética , Toxinas Bacterianas/genética , Variaciones en el Número de Copia de ADN/genética , Topoisomerasa de ADN IV/genética , Escherichia coli/genética
14.
Proc Natl Acad Sci U S A ; 118(27)2021 07 06.
Artículo en Inglés | MEDLINE | ID: mdl-34210797

RESUMEN

While modulatory effects of gut microbes on neurological phenotypes have been reported, the mechanisms remain largely unknown. Here, we demonstrate that indole, a tryptophan metabolite produced by tryptophanase-expressing gut microbes, elicits neurogenic effects in the adult mouse hippocampus. Neurogenesis is reduced in germ-free (GF) mice and in GF mice monocolonized with a single-gene tnaA knockout (KO) mutant Escherichia coli unable to produce indole. External administration of systemic indole increases adult neurogenesis in the dentate gyrus in these mouse models and in specific pathogen-free (SPF) control mice. Indole-treated mice display elevated synaptic markers postsynaptic density protein 95 and synaptophysin, suggesting synaptic maturation effects in vivo. By contrast, neurogenesis is not induced by indole in aryl hydrocarbon receptor KO (AhR-/-) mice or in ex vivo neurospheres derived from them. Neural progenitor cells exposed to indole exit the cell cycle, terminally differentiate, and mature into neurons that display longer and more branched neurites. These effects are not observed with kynurenine, another AhR ligand. The indole-AhR-mediated signaling pathway elevated the expression of ß-catenin, Neurog2, and VEGF-α genes, thus identifying a molecular pathway connecting gut microbiota composition and their metabolic function to neurogenesis in the adult hippocampus. Our data have implications for the understanding of mechanisms of brain aging and for potential next-generation therapeutic opportunities.


Asunto(s)
Envejecimiento/metabolismo , Microbioma Gastrointestinal , Neurogénesis , Receptores de Hidrocarburo de Aril/metabolismo , Triptófano/metabolismo , Animales , Indoles/farmacología , Masculino , Ratones Endogámicos C57BL , Ratones Noqueados , Mutación/genética , Células-Madre Neurales/metabolismo
15.
Surg Innov ; 31(3): 324-330, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38446503

RESUMEN

Laparoscopic surgery is extensively utilized to treat a range of gynaecological conditions and pathologies. The advantages of laparoscopic surgery include the minimalization of blood loss and scarring, improved recovery times, and shorter hospital admissions. However, robotic technologies have had an increasing presence within gynaecological laparoscopic surgery in recent decades. This literature review therefore aims to discuss laparoscopy from 3 perspectives. First, the evolution of laparoscopy is reviewed with a focus on its origins, its transition from a diagnostic to an operative tool, and its role in present-day gynaecology. Second, interventions for benign gynaecological conditions (including excision of benign ovarian tumours, total laparoscopic hysterectomy, and laparoscopic myomectomy) are reviewed. The laparoscopic management of malignant gynaecology (including ovarian cancer, endometrial cancer, and cervical cancer) is also discussed. Finally, whilst robot-assisted laparoscopic surgery is experiencing rapid technological advancement, it is pertinent to consider the extent of its benefits when compared to open or conventional laparoscopic approaches in gynaecological surgery.


Asunto(s)
Procedimientos Quirúrgicos Ginecológicos , Laparoscopía , Procedimientos Quirúrgicos Robotizados , Humanos , Procedimientos Quirúrgicos Robotizados/métodos , Laparoscopía/métodos , Femenino , Procedimientos Quirúrgicos Ginecológicos/métodos
16.
Int Orthop ; 48(9): 2283-2291, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39007939

RESUMEN

PURPOSE: With over 100,000 procedures completed per year, hip and knee arthroplasty are two of the most common surgical procedures performed in Canada. There has been literature indicating that patient reported outcome measures (PROM) will start to plateau between six and 12 months. The purpose of this paper was to analyze the trajectory of PROMs following total hip and knee arthroplasty (THA and TKA), as well as assess the impact of any potential confounders on this trajectory. The central research question was: At what point do PROMS plateau among patients that undergo elective THA and TKA? METHODS: This study was a retrospective analysis of data from a prospective database. Patients were eligible if they had undergone an elective, primary THA/TKA with Oxford Scores recorded pre-operatively, and at least at two of the following four time points: six weeks, six months, one year, and two years. RESULTS: Mean pre-operative Oxford scores were 18.0 (7.8) for THA, and 20.1 (7.5) for TKA. For both THA and TKA, there were statistically significant interval improvements in Oxford scores from six weeks [THA: 33.8 (7.9)/TKA: 28.7 (7.8)] to six months [THA: 40.2 (7.3)/TKA: 35.9 (8.3)], and from six months to one year [THA: 41.0 (7.3)/TKA: 37.3 (8.4)], but not from one to two years [THA: 40.0 (8.5)/TKA: 36.4 (9.6)]. CONCLUSIONS: Patients undergoing either primary THA or TKA can expect clinically meaningful improvements in the first six months after surgery. Beyond this time point, there is a plateau in PROMs. These findings are important for both setting patient expectations in pre-operative discussions, and allowing surgeons to have a realistic understanding of their patients' expected post-operative course.


Asunto(s)
Artroplastia de Reemplazo de Cadera , Artroplastia de Reemplazo de Rodilla , Medición de Resultados Informados por el Paciente , Humanos , Artroplastia de Reemplazo de Rodilla/métodos , Artroplastia de Reemplazo de Cadera/métodos , Femenino , Masculino , Anciano , Estudios Retrospectivos , Persona de Mediana Edad , Recuperación de la Función , Resultado del Tratamiento , Factores de Tiempo , Canadá/epidemiología
17.
Artículo en Inglés | MEDLINE | ID: mdl-39259311

RESUMEN

INTRODUCTION: It remains unclear if distal femoral morphology should be a key consideration when selecting the implant or fixation strategy. A novel radiological index has been proposed to classify patients' distal femoral morphology. This study aims to evaluate the validity of this classification system in a cohort of patients undergoing hinged Total Knee Arthroplasty (TKA), and to determine if distal femoral morphology is a risk factor for aseptic loosening or all cause revision following hinged TKA. MATERIALS AND METHODS: This study was a retrospective analysis of our institutional database. Fifty-nine patients having undergone hinged TKA with adequate radiographs for examination were eligible for inclusion. Radiographic measurements were performed using the Citak radiological index criteria. The proportion of aseptic loosening and all-cause revisions were compared between the different classification groups. RESULTS: The analysis included 41 females (69.5%) and 18 males (30.5%). The mean age of the participants was 71.2 years (SD = 12.6). For inner canal diameter patients were classified as: Type A (31/59, 53%), Type B (19/59, 32%), and Type C (9/59, 15%). For the Index Classification Group, patients were classified as: Group A (26/59, 44%), Group B (20/59, 34%), and Group C (13/59, 22%). There was no significant difference in overall revision rate between the three groups (χ2 = 3.25, P = .197 from a Chi-square test). There was a significantly higher rate of aseptic loosening in Group C compared to Groups A and B, with no significant difference between Groups A and B in terms of aseptic loosening rates (χ2 = 8.72, P = .013 from a Chi-square test). CONCLUSIONS: Distal femoral morphology plays an important role in the risk of aseptic loosening following hinged knee replacement, and should be considered when deciding implant type and fixation in these patients.

18.
Semin Cancer Biol ; 86(Pt 2): 1014-1025, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-33989734

RESUMEN

Bacteria are associated with the human body and colonize the gut, skin, and mucous membranes. These associations can be either symbiotic or pathogenic. In either case, bacteria derive more benefit from their host. The ability of bacteria to enter and survive within the human body can be exploited for human benefit. They can be used as a vehicle for delivering or producing bioactive molecules, such as toxins and lytic enzymes, and eventually for killing tumor cells. Clostridium and Salmonella have been shown to infect and survive within the human body, including in tumors. There is a need to develop genetic circuits, which enable bacterial cells to carry out the following activities: (i) escape the human immune system, (ii) invade tumors, (iii) multiply within the tumorous cells, (iv) produce toxins via quorum sensing at low cell densities, and (v) express suicide genes to undergo cell death or cell lysis after the tumor has been lysed. Thus, bacteria have the potential to be exploited as anticancer agents.


Asunto(s)
Antineoplásicos , Neoplasias , Humanos , Percepción de Quorum , Bacterias , Neoplasias/tratamiento farmacológico , Neoplasias/etiología , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico
19.
J Am Chem Soc ; 145(13): 7569-7579, 2023 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-36961918

RESUMEN

While polymers containing chain or ring motifs in their backbone are ubiquitous, those containing well-defined molecular cages are very rare and essentially unknown for the inorganic elements. We report that a rigid and dinucleophilic cage (PNSiMe3)2(NMe)6, which is chemically robust and accessible on a multi-gram scale from commercial precursors, serves as a linear and divalent connector that forms cage-dense inorganic materials. Reaction of the cage with various ditopic P(III) dihalide comonomers proceeded via Me3SiCl elimination to give high molecular weight (30 000-70 000 g mol-1), solution-processable polymers that form free-standing films. The end groups of the polymers could be tuned to engender orthogonal reactivity and form block copolymers. Networked cage-dense materials could be accessed by using PCl3 as a tritopic P(III) linker. Detailed mechanistic studies implicate a stepwise polycondensation that proceeds via phosphino-phosphonium ion intermediates, prior to Me3SiCl loss. Thus, metathesis between the dinucleophilic cage and polyhalides represents a general strategy to making cage-dense polymers, setting the stage for systematically understanding the consequences of the three-dimensional microstructure on macroscopic material properties.

20.
Appl Environ Microbiol ; 89(11): e0123923, 2023 11 29.
Artículo en Inglés | MEDLINE | ID: mdl-37902333

RESUMEN

IMPORTANCE: Microorganisms that live on or inside plants can influence plant growth and health. Among the plant-associated bacteria, streptomycetes play an important role in defense against plant diseases, but the underlying mechanisms are not well understood. Here, we demonstrate that the plant hormones jasmonic acid (JA) and methyl jasmonate directly affect the life cycle of streptomycetes by modulating antibiotic synthesis and promoting faster development. Moreover, the plant hormones specifically stimulate the synthesis of the polyketide antibiotic actinorhodin in Streptomyces coelicolor. JA is then modified in the cell by amino acid conjugation, thereby quenching toxicity. Collectively, these results provide new insight into the impact of a key plant hormone on diverse phenotypic responses of streptomycetes.


Asunto(s)
Aminoácidos , Reguladores del Crecimiento de las Plantas , Antibacterianos , Hormonas
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