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1.
Med J Aust ; 2024 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-39300747

RESUMEN

OBJECTIVE: To describe the preparedness for, epidemiological characteristics of and public health responses to the first and second waves of coronavirus disease 2019 (COVID-19) in six remote Aboriginal and Torres Strait Islander communities in Queensland from late 2021. DESIGN: This was a descriptive epidemiological study. Data were collated by each participating public health unit. Case and outbreak characteristics were obtained from the statewide Notifiable Conditions System. SETTING, PARTICIPANTS: Six discrete remote First Nations communities across Queensland were selected to represent a broad geographic spread across the state: Badu Island, Cherbourg, Lockhart River, Palm Island, Woorabinda and Yarrabah. People with a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test result recorded between 13 December 2021 and 12 June 2022 who acquired the infection and isolated in one of the six communities. MAIN OUTCOME MEASURES: COVID-19 vaccination coverage among First Nations people; number of COVID-19 cases reported; and attack rates for each community. RESULTS: All six First Nations communities led the COVID-19 preparedness and planning. COVID-19 vaccination coverage rates before the first outbreak ranged from 59% to 84% for the first dose and from 39% to 76% for the second dose across the six communities. During the study period, 2624 cases of COVID-19 in these communities were notified to Queensland Health. Attack rates for each community were: Badu Island, 23%; Cherbourg, 34%; Lockhart River, 18%; and Palm Island, Woorabinda and Yarrabah, 35% each. The 2624 cases included 52 cases (2%) involving hospital admission and two cases (< 1%) in which the person died from COVID-19. CONCLUSIONS: It is likely that the co-designed, collaborative partnerships between local councils, community-controlled health services, state health services and public health units positively impacted the management and outcomes of COVID-19 in each of the six communities.

2.
Proc Natl Acad Sci U S A ; 121(36): e2321874121, 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39207736

RESUMEN

Medium chain fatty acids are commonly consumed as part of diets for endurance sports and as medical treatment in ketogenic diets where these diets regulate energy metabolism and increase adenosine levels. However, the role of the equilibrative nucleoside transporter 1 (ENT1), which is responsible for adenosine transport across membranes in this process, is not well understood. Here, we investigate ENT1 activity in controlling the effects of two dietary medium chain fatty acids (decanoic and octanoic acid), employing the tractable model system Dictyostelium. We show that genetic ablation of three ENT1 orthologues unexpectedly improves cell proliferation specifically following decanoic acid treatment. This effect is not caused by increased adenosine levels triggered by both fatty acids in the presence of ENT1 activity. Instead, we show that decanoic acid increases expression of energy-related genes relevant for fatty acid ß-oxidation, and that pharmacological inhibition of ENT1 activity leads to an enhanced effect of decanoic acid to increase expression of tricarboxylicacid cycle and oxidative phosphorylation components. Importantly, similar transcriptional changes have been shown in the rat hippocampus during ketogenic diet treatment. We validated these changes by showing enhanced mitochondria load and reduced lipid droplets. Thus, our data show that ENT1 regulates the medium chain fatty acid-induced increase in cellular adenosine levels and the decanoic acid-induced expression of important metabolic enzymes in energy provision, identifying a key role for ENT1 proteins in metabolic effects of medium chain fatty acids.


Asunto(s)
Metabolismo Energético , Tranportador Equilibrativo 1 de Nucleósido , Adenosina/metabolismo , Adenosina/farmacología , Caprilatos/farmacología , Proliferación Celular/efectos de los fármacos , Dictyostelium/metabolismo , Dictyostelium/genética , Dictyostelium/efectos de los fármacos , Dieta Cetogénica , Grasas de la Dieta/farmacología , Grasas de la Dieta/metabolismo , Metabolismo Energético/efectos de los fármacos , Tranportador Equilibrativo 1 de Nucleósido/metabolismo , Tranportador Equilibrativo 1 de Nucleósido/genética , Regulación de la Expresión Génica/efectos de los fármacos , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos
3.
Biochem Soc Trans ; 52(4): 1785-1794, 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-38934501

RESUMEN

Macropinocytosis is a broadly conserved endocytic process discovered nearly 100 years ago, yet still poorly understood. It is prominent in cancer cell feeding, immune surveillance, uptake of RNA vaccines and as an invasion route for pathogens. Macropinocytic cells extend large cups or flaps from their plasma membrane to engulf droplets of medium and trap them in micron-sized vesicles. Here they are digested and the products absorbed. A major problem - discussed here - is to understand how cups are shaped and closed. Recently, lattice light-sheet microscopy has given a detailed description of this process in Dictyostelium amoebae, leading to the 'stalled-wave' model for cup formation and closure. This is based on membrane domains of PIP3 and active Ras and Rac that occupy the inner face of macropinocytic cups and are readily visible with suitable reporters. These domains attract activators of dendritic actin polymerization to their periphery, creating a ring of protrusive F-actin around themselves, thus shaping the walls of the cup. As domains grow, they drive a wave of actin polymerization across the plasma membrane that expands the cup. When domains stall, continued actin polymerization under the membrane, combined with increasing membrane tension in the cup, drives closure at lip or base. Modelling supports the feasibility of this scheme. No specialist coat proteins or contractile activities are required to shape and close cups: rings of actin polymerization formed around PIP3 domains that expand and stall seem sufficient. This scheme may be widely applicable and begs many biochemical questions.


Asunto(s)
Membrana Celular , Dictyostelium , Pinocitosis , Pinocitosis/fisiología , Membrana Celular/metabolismo , Humanos , Actinas/metabolismo , Animales , Modelos Biológicos
4.
Science ; 382(6667): 223-230, 2023 10 13.
Artículo en Inglés | MEDLINE | ID: mdl-37824668

RESUMEN

Neurons relay information via specialized presynaptic compartments for neurotransmission. Unlike conventional organelles, the specialized apparatus characterizing the neuronal presynapse must form de novo. How the components for presynaptic neurotransmission are transported and assembled is poorly understood. Our results show that the rare late endosomal signaling lipid phosphatidylinositol 3,5-bisphosphate [PI(3,5)P2] directs the axonal cotransport of synaptic vesicle and active zone proteins in precursor vesicles in human neurons. Precursor vesicles are distinct from conventional secretory organelles, endosomes, and degradative lysosomes and are transported by coincident detection of PI(3,5)P2 and active ARL8 via kinesin KIF1A to the presynaptic compartment. Our findings identify a crucial mechanism that mediates the delivery of synaptic vesicle and active zone proteins to developing synapses.


Asunto(s)
Transporte Axonal , Neuronas , Fosfatos de Fosfatidilinositol , Vesículas Sinápticas , Humanos , Transporte Axonal/fisiología , Cinesinas/metabolismo , Neuronas/metabolismo , Vesículas Sinápticas/metabolismo , Fosfatos de Fosfatidilinositol/metabolismo
5.
Fungal Genet Biol ; 169: 103838, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37716699

RESUMEN

Intimate associations between fungi and intracellular bacterial endosymbionts are becoming increasingly well understood. Phylogenetic analyses demonstrate that bacterial endosymbionts of Mucoromycota fungi are related either to free-living Burkholderia or Mollicutes species. The so-called Burkholderia-related endosymbionts or BRE comprise Mycoavidus, Mycetohabitans and Candidatus Glomeribacter gigasporarum. These endosymbionts are marked by genome contraction thought to be associated with intracellular selection. However, the conclusions drawn thus far are based on a very small subset of endosymbiont genomes, and the mechanisms leading to genome streamlining are not well understood. The purpose of this study was to better understand how intracellular existence shapes Mycoavidus and BRE functionally at the genome level. To this end we generated and analyzed 14 novel draft genomes for Mycoavidus living within the hyphae of Mortierellomycotina fungi. We found that our novel Mycoavidus genomes were significantly reduced compared to free-living Burkholderiales relatives. Using a genome-scale phylogenetic approach including the novel and available existing genomes of Mycoavidus, we show that the genus is an assemblage composed of two independently derived lineages including three well supported clades of Mycoavidus. Using a comparative genomic approach, we shed light on the functional implications of genome reduction, documenting shared and unique gene loss patterns between the three Mycoavidus clades. We found that many endosymbiont isolates demonstrate patterns of vertical transmission and host-specificity, but others are present in phylogenetically disparate hosts. We discuss how reductive evolution and host specificity reflect convergent adaptation to the intrahyphal selective landscape, and commonalities of eukaryotic endosymbiont genome evolution.


Asunto(s)
Burkholderiaceae , Adaptación al Huésped , Filogenia , Burkholderiaceae/genética , Hongos/genética , Bacterias , Simbiosis/genética
6.
JMIR Res Protoc ; 12: e48014, 2023 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-37581914

RESUMEN

BACKGROUND: Fungal-bacterial cocolonization and coinfections pose an emerging challenge among patients suspected of having pulmonary tuberculosis (PTB); however, the underlying pathogenic mechanisms and microbiome interactions are poorly understood. Understanding how environmental microbes, such as fungi and bacteria, coevolve and develop traits to evade host immune responses and resist treatment is critical to controlling opportunistic pulmonary fungal coinfections. In this project, we propose to study the coexistence of fungal and bacterial microbial communities during chronic pulmonary diseases, with a keen interest in underpinning fungal etiological evolution and the predominating interactions that may exist between fungi and bacteria. OBJECTIVE: This is a protocol for a study aimed at investigating the metabolic and molecular ecological evolution of opportunistic pulmonary fungal coinfections through determining and characterizing the burden, etiological profiles, microbial communities, and interactions established between fungi and bacteria as implicated among patients with presumptive PTB. METHODS: This will be a laboratory-based cross-sectional study, with a sample size of 406 participants. From each participant, 2 sputa samples (one on-spot and one early morning) will be collected. These samples will then be analyzed for both fungal and bacterial etiology using conventional metabolic and molecular (intergenic transcribed spacer and 16S ribosomal DNA-based polymerase chain reaction) approaches. We will also attempt to design a genome-scale metabolic model for pulmonary microbial communities to analyze the composition of the entire microbiome (ie, fungi and bacteria) and investigate host-microbial interactions under different patient conditions. This analysis will be based on the interplays of genes (identified by metagenomics) and inferred from amplicon data and metabolites (identified by metabolomics) by analyzing the full data set and using specific computational tools. We will also collect baseline data, including demographic and clinical history, using a patient-reported questionnaire. Altogether, this approach will contribute to a diagnostic-based observational study. The primary outcome will be the overall fungal and bacterial diagnostic profile of the study participants. Other diagnostic factors associated with the etiological profile, such as incidence and prevalence, will also be analyzed using univariate and multivariate schemes. Odds ratios with 95% CIs will be presented with a statistical significance set at P<.05. RESULTS: The study has been approved by the Mbarara University Research Ethic Committee (MUREC1/7-07/09/20) and the Uganda National Council of Science and Technology (HS1233ES). Following careful scrutiny, the protocol was designed to enable patient enrollment, which began in March 2022 at Mbarara University Teaching Hospital. Data collection is ongoing and is expected to be completed by August 2023, and manuscripts will be submitted for publication thereafter. CONCLUSIONS: Through this protocol, we will explore the metabolic and molecular ecological evolution of opportunistic pulmonary fungal coinfections among patients with presumptive PTB. Establishing key fungal-bacterial cross-kingdom synergistic relationships is crucial for instituting fungal bacterial coinfecting etiology. TRIAL REGISTRATION: ISRCTN Registry ISRCTN33572982; https://tinyurl.com/caa2nw69. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/48014.

7.
J Cell Biol ; 222(9)2023 09 04.
Artículo en Inglés | MEDLINE | ID: mdl-37382666

RESUMEN

Phosphoinositide signaling lipids (PIPs) are key regulators of membrane identity and trafficking. Of these, PI(3,5)P2 is one of the least well-understood, despite key roles in many endocytic pathways including phagocytosis and macropinocytosis. PI(3,5)P2 is generated by the phosphoinositide 5-kinase PIKfyve, which is critical for phagosomal digestion and antimicrobial activity. However PI(3,5)P2 dynamics and regulation remain unclear due to lack of reliable reporters. Using the amoeba Dictyostelium discoideum, we identify SnxA as a highly selective PI(3,5)P2-binding protein and characterize its use as a reporter for PI(3,5)P2 in both Dictyostelium and mammalian cells. Using GFP-SnxA, we demonstrate that Dictyostelium phagosomes and macropinosomes accumulate PI(3,5)P2 3 min after engulfment but are then retained differently, indicating pathway-specific regulation. We further find that PIKfyve recruitment and activity are separable and that PIKfyve activation stimulates its own dissociation. SnxA is therefore a new tool for reporting PI(3,5)P2 in live cells that reveals key mechanistic details of the role and regulation of PIKfyve/PI(3,5)P2.


Asunto(s)
Dictyostelium , Fagosomas , Fosfatidilinositol 3-Quinasas , Animales , Dictyostelium/genética , Endosomas , Mamíferos , Fosfatidilinositoles , Fosfatidilinositol 3-Quinasas/metabolismo
8.
Curr Biol ; 33(15): 3083-3096.e6, 2023 08 07.
Artículo en Inglés | MEDLINE | ID: mdl-37379843

RESUMEN

Macropinocytosis is a conserved endocytic process by which cells engulf droplets of medium into micron-sized vesicles. We use light-sheet microscopy to define an underlying set of principles by which macropinocytic cups are shaped and closed in Dictyostelium amoebae. Cups form around domains of PIP3 stretching almost to their lip and are supported by a specialized F-actin scaffold from lip to base. They are shaped by a ring of actin polymerization created by recruiting Scar/WAVE and Arp2/3 around PIP3 domains, but how cups evolve over time to close and form a vesicle is unknown. Custom 3D analysis shows that PIP3 domains expand from small origins, capturing new membrane into the cup, and crucially, that cups close when domain expansion stalls. We show that cups can close in two ways: either at the lip, by inwardly directed actin polymerization, or the base, by stretching and delamination of the membrane. This provides the basis for a conceptual mechanism whereby closure is brought about by a combination of stalled cup expansion, continued actin polymerization at the lip, and membrane tension. We test this through the use of a biophysical model, which can recapitulate both forms of cup closure and explain how 3D cup structures evolve over time to mediate engulfment.


Asunto(s)
Actinas , Dictyostelium , Estructuras de la Membrana Celular , Citoesqueleto de Actina , Endocitosis
9.
J Biomed Opt ; 28(2): 029801, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36864902

RESUMEN

[This corrects the article DOI: 10.1117/1.JBO.27.12.125001.].

10.
BMJ Glob Health ; 8(3)2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36963786

RESUMEN

BACKGROUND: Between 1964 and 1996, the 10-year survival of patients having valve replacement surgery for rheumatic heart disease (RHD) in the Northern Territory, Australia, was 68%. As medical care has evolved since then, this study aimed to determine whether there has been a corresponding improvement in survival. METHODS: A retrospective study of Aboriginal patients with RHD in the Northern Territory, Australia, having their first valve surgery between 1997 and 2016. Survival was examined using Kaplan-Meier and Cox regression analysis. FINDINGS: The cohort included 281 adults and 61 children. The median (IQR) age at first surgery was 31 (18-42) years; 173/342 (51%) had a valve replacement, 113/342 (33%) had a valve repair and 56/342 (16%) had a commissurotomy. There were 93/342 (27%) deaths during a median (IQR) follow-up of 8 (4-12) years. The overall 10-year survival was 70% (95% CI: 64% to 76%). It was 62% (95% CI: 53% to 70%) in those having valve replacement. There were 204/281 (73%) adults with at least 1 preoperative comorbidity. Preoperative comorbidity was associated with earlier death, the risk of death increasing with each comorbidity (HR: 1.3 (95% CI: 1.2 to 1.5), p<0.001). Preoperative chronic kidney disease (HR 6.5 (95% CI: 3.0 to 14.0) p≤0.001)), coronary artery disease (HR 3.3 (95% CI: 1.3 to 8.4) p=0.012) and pulmonary artery systolic pressure>50 mm Hg before surgery (HR 1.9 (95% CI: 1.2 to 3.1) p=0.007) were independently associated with death. INTERPRETATION: Survival after valve replacement for RHD in this region of Australia has not improved. Although the patients were young, many had multiple comorbidities, which influenced long-term outcomes. The increasing prevalence of complex comorbidity in the region is a barrier to achieving optimal health outcomes.


Asunto(s)
Cardiopatía Reumática , Adulto , Niño , Humanos , Cardiopatía Reumática/epidemiología , Cardiopatía Reumática/cirugía , Cardiopatía Reumática/complicaciones , Northern Territory/epidemiología , Estudios Retrospectivos , Comorbilidad , Factores de Edad
11.
Mol Biol Cell ; 34(3): ar12, 2023 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-36598819

RESUMEN

The efficient delivery of lysosomes is essential for many cell functions, such as the degradation of unwanted intracellular components by autophagy and the killing and digestion of extracellular microbes within phagosomes. Using the amoeba Dictyostelium discoideum, we find that cells lacking Katnip (Katanin interacting protein) have a general defect in lysosomal delivery and although they make autophagosomes and phagosomes correctly, cells are then unable to digest them. Katnip is largely unstudied yet highly conserved across evolution. Previously studies found that Katnip mutations in animals cause defects in cilia structure. Here we show that Katnip plays a more general role in maintaining microtubule function. We find that loss of Katnip has no overall effect on microtubule dynamics or organization, but is important for the transport and degradation of endocytic cargos. Strikingly, Katnip mutants become highly sensitive to GFP-tubulin expression, which leads to microtubule tangles, defective anaphase extension, and slow cell growth. Our findings establish a general role for Katnip in regulating microtubule function, beyond the roles previously described in cilia. We speculate this is via a key function in microtubule repair, needed to maintain endosomal trafficking and lysosomal degradation.


Asunto(s)
Autofagosomas , Dictyostelium , Animales , Dictyostelium/metabolismo , Fagosomas/metabolismo , Lisosomas/metabolismo , Autofagia/genética , Microtúbulos
12.
Pediatr Blood Cancer ; 70(1): e30070, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36326111

RESUMEN

BACKGROUND: The Children's Oncology Group Long-Term Follow-Up Guidelines provide exposure-based risks and recommendations for late effects screening of survivors of childhood cancer. Passport for Care (PFC) is a web-based clinical decision support tool for generating a personalized survivorship care plan (SCP) derived from the Guidelines and user-entered exposures. We assessed PFC clinician user practices and perceptions of PFC impact on clinic workflow, guidelines application, and survivor shared decision-making. PROCEDURE: A 35-item REDCap survey was emailed to all PFC users (n = 936) in 146 current and former PFC user clinics. Anonymous responses were permitted. Results were summarized and compared with a 2012 survey. RESULTS: Data were available from 148 respondents representing 64 out of 146 PFC user clinics (minimum clinic response rate 44%, excluding 49 anonymous responses). Generation of a personalized SCP was the most common application of PFC, followed by determination of surveillance recommendations and use as a survivor database. Twenty-five respondents (17%) felt data entry was a significant or insurmountable barrier to PFC application. Sixty-nine percent of respondents attributed PFC with a very high/high impact on guidelines adherence in their clinical practice, compared with 40% who attributed PFC with having a significant impact on adherence in 2012 (p < .001). CONCLUSION: The survey results provide valuable insights on patterns of SCP delivery and Survivor Clinic workflow. User-perceived benefits to PFC included facilitating clinician ability to follow guidelines recommendations in clinical practice. Importantly, some barriers to resource utilization were also identified, suggesting a need for user-informed adaptations to further improve uptake.


Asunto(s)
Sistemas de Apoyo a Decisiones Clínicas , Neoplasias , Niño , Humanos , Supervivencia , Sobrevivientes , Neoplasias/terapia , Internet
13.
J Biomed Opt ; 27(12): 125001, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36530344

RESUMEN

Significance: Traditional pathology workflow suffers from limitations including biopsy invasiveness, small fraction of large tissue samples being analyzed, and complex and time-consuming processing. Aim: We address limitations of conventional pathology workflow through development of a laser microbiopsy device for minimally invasive harvest of sub-microliter tissue volumes. Laser microbiopsy combined with rapid diagnostic methods, such as virtual hematoxylin and eosin (H&E) imaging has potential to provide rapid minimally invasive tissue diagnosis. Approach: Laser microbiopsies were harvested using an annular shaped Ho:YAG laser beam focused onto the tissue surface. As the annulus was ablated, the tissue section in the center of the annulus was ejected and collected directly onto a glass slide for analysis. Cryogen spray cooling was used before and after laser harvest to limit thermal damage. Microbiopsies were collected from porcine skin and kidney. Harvested microbiopsies were imaged with confocal microscopy and digitally false colored to provide virtual H&E images. Results: Microbiopsies were successfully harvested from porcine skin and kidney. Computational and experimental results show the benefit of cryogen pre- and post-cooling to limit thermal damage. Virtual H&E images of microbiopsies retained observable cellular features including cell nuclei. Conclusions: Laser microbiopsy with virtual H&E imaging shows promise as a potential rapid and minimally invasive tool for biopsy and diagnosis.


Asunto(s)
Biopsia , Láseres de Estado Sólido , Animales , Biopsia/métodos , Microscopía Confocal , Porcinos
14.
Subcell Biochem ; 98: 41-59, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35378702

RESUMEN

Macropinocytosis is a relatively unexplored form of large-scale endocytosis driven by the actin cytoskeleton. Dictyostelium amoebae form macropinosomes from cups extended from the plasma membrane, then digest their contents and absorb the nutrients in the endo-lysosomal system. They use macropinocytosis for feeding, maintaining a high rate of fluid uptake that makes assay and experimentation easy. Mutants collected over the years identify cytoskeletal and signalling proteins required for macropinocytosis. Cups are organized around plasma membrane domains of intense PIP3, Ras and Rac signalling, proper formation of which also depends on the RasGAPs NF1 and RGBARG, PTEN, the PIP3-regulated protein kinases Akt and SGK and their activators PDK1 and TORC2, Rho proteins, plus other components yet to be identified. This PIP3 domain directs dendritic actin polymerization to the extending lip of macropinocytic cups by recruiting a ring of the SCAR/WAVE complex around itself and thus activating the Arp2/3 complex. The dynamics of PIP3 domains are proposed to shape macropinocytic cups from start to finish. The role of the Ras-PI3-kinase module in organizing feeding structures in unicellular organisms most likely predates its adoption into growth factor signalling, suggesting an evolutionary origin for growth factor signalling.


Asunto(s)
Amoeba , Dictyostelium , Citoesqueleto de Actina/metabolismo , Amoeba/metabolismo , Dictyostelium/genética , Dictyostelium/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Pinocitosis
15.
Curr Biol ; 32(5): 1115-1130.e6, 2022 03 14.
Artículo en Inglés | MEDLINE | ID: mdl-35134329

RESUMEN

Opportunistic infections by environmental fungi are a growing clinical problem, driven by an increasing population of people with immunocompromising conditions. Spores of the Mucorales order are ubiquitous in the environment but can also cause acute invasive infections in humans through germination and evasion of the mammalian host immune system. How they achieve this and the evolutionary drivers underlying the acquisition of virulence mechanisms are poorly understood. Here, we show that a clinical isolate of Rhizopus microsporus contains a Ralstonia pickettii bacterial endosymbiont required for virulence in both zebrafish and mice and that this endosymbiosis enables the secretion of factors that potently suppress growth of the soil amoeba Dictyostelium discoideum, as well as their ability to engulf and kill other microbes. As amoebas are natural environmental predators of both bacteria and fungi, we propose that this tri-kingdom interaction contributes to establishing endosymbiosis and the acquisition of anti-phagocyte activity. Importantly, we show that this activity also protects fungal spores from phagocytosis and clearance by human macrophages, and endosymbiont removal renders the fungal spores avirulent in vivo. Together, these findings describe a new role for a bacterial endosymbiont in Rhizopus microsporus pathogenesis in animals and suggest a mechanism of virulence acquisition through environmental interactions with amoebas.


Asunto(s)
Amoeba , Dictyostelium , Animales , Bacterias , Hongos , Humanos , Mamíferos , Ratones , Fagocitos , Rhizopus , Virulencia , Pez Cebra
16.
Pediatr Emerg Care ; 38(1): e47-e51, 2022 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-34986586

RESUMEN

OBJECTIVES: Emergency department (ED) visits by children with solid organ transplants have increased significantly. Our objectives were to describe the common complaints, diagnosis, types, and rates of serious bacterial infection (SBI) in children with renal transplant (RT) who present to the hospital. METHODS: We conducted a retrospective study from 2012 to 2016 of RT children up to 18 years who presented to the ED or were directly admitted. We excluded patients who presented for a procedure. We collected demographics, transplant type, immunosuppressive data, chief complaints, diagnostic testing with results, interventions performed, and final diagnosis. RESULTS: We analyzed 131 visits in 29 patients during the study period. Most common chief complaints were infectious (34.4%) and gastrointestinal (26%). Infection was proven in 42.0% of visits with only 3.1% being organ rejection. Serious bacterial infection was diagnosed in 34 visits (26.0%) with urinary tract infection (UTI) being the most common (20.6%). Of the 33 visits for fever, SBI occurred in 16 (48.5%) patients with the most common SBI being UTI 10 (30.3%). Bacteremia occurred in 1 patient and hypotension in 4 patients. Antibiotic administration was the most common intervention performed (78; 59.5%). Significant interventions were uncommon (2 patients). Logistic regression revealed no factors to be associated with SBI. CONCLUSIONS: Our cohort of children with RT presented most commonly with infections to the hospital with UTI being the most common SBI. Bacteremia and significant interventions were rare. Future studies are needed to identify subgroups of low-risk pediatric RT patients who can possibly be safely discharged home from the ED.


Asunto(s)
Infecciones Bacterianas , Trasplante de Riñón , Infecciones Urinarias , Infecciones Bacterianas/epidemiología , Niño , Servicio de Urgencia en Hospital , Humanos , Lactante , Trasplante de Riñón/efectos adversos , Estudios Retrospectivos , Infecciones Urinarias/epidemiología
17.
Child Maltreat ; 27(4): 572-582, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-34311560

RESUMEN

Child welfare workers aim to promote the well-being and safety of children and are the link between the child welfare system and families. Families served by the child welfare system should expect similar service based on clinical factors, not based on their caseworker's characteristics. Using secondary data analyses of the most recent Canadian Incidence Study of Reported Child Abuse and Neglect (CIS-2008) and multilevel modeling, this study examines whether child welfare worker characteristics, such as education level and field, age, and experience predict their perception of the risk of future maltreatment. A total of 1729 case-level investigations and 419 child welfare workers were included in this study. Several one-level logistic regression and two-level logistic regression analyses were run. The best-fit model suggests that caseworkers with a Master's degree, more than 2 years of experience, and more than 18 cases were significantly more likely to perceive risk of future maltreatment. Further, the interaction between degree level and age also significantly predicted the perception of risk of future maltreatment. Results suggest that the perception of risk of future maltreatment may be influenced by caseworker factors, thus service to families may differ based on caseworker characteristics.


Asunto(s)
Maltrato a los Niños , Protección a la Infancia , Canadá/epidemiología , Niño , Estudios de Cohortes , Humanos , Percepción
18.
J Endourol ; 35(S3): S29-S36, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34910606

RESUMEN

Introduction: This study aimed at answering three research questions: (1) Under the experimental conditions studied, what is the dominant mechanism of Holmium:YAG lithotripsy with or without pulse modulation? (2) Under what circumstances can laser pulse modulation increase crater volume of stone ablation per joule of emitted radiant energy? (3) Are BegoStone phantoms a suitable model for laser lithotripsy studies? Materials and Methods: The research questions were addressed by ablation experiments with BegoStone phantoms and native stones. Experiments were performed under three stone conditions: dry stones in air, hydrated stones in air, and hydrated stones in water. Single pulses with and without pulse modulation were applied. For each pulse mode, temporal profile, transmission through 1 mm water, and cavitation bubble collapse pressures were measured and compared. For each stone condition and pulse mode, stones were ablated with a fiber separation distance of 1 mm and crater volumes were measured using optical coherence tomography. Results: Pulses with and without pulse modulation had high (>80%) transmission through 1 mm of water. Pulses without pulse modulation generated much higher peak pressures than those with pulse modulation (62.3 vs 11.4 bar). Pulse modulation resulted in similar or larger craters than without pulse modulation. Trends in BegoStone crater volumes differed from trends in native stones. Conclusions: This results of this study suggest that the dominant mechanism is photothermal with possible photoacoustic contributions for some stone compositions. Pulse modulation can increase ablation volume per joule of emitted radiant energy, but the effect may be composition specific. BegoStones showed unique infrared ablation characteristics compared with native stones and are not a suitable model for laser lithotripsy studies.


Asunto(s)
Cálculos , Láseres de Estado Sólido , Litotripsia por Láser , Litotricia , Holmio , Humanos , Fantasmas de Imagen
19.
Cells ; 10(11)2021 11 05.
Artículo en Inglés | MEDLINE | ID: mdl-34831258

RESUMEN

The social amoeba Dictyostelium discoideum provides an excellent model for research across a broad range of disciplines within biology. The organism diverged from the plant, yeast, fungi and animal kingdoms around 1 billion years ago but retains common aspects found in these kingdoms. Dictyostelium has a low level of genetic complexity and provides a range of molecular, cellular, biochemical and developmental biology experimental techniques, enabling multidisciplinary studies to be carried out in a wide range of areas, leading to research breakthroughs. Numerous laboratories within the United Kingdom employ Dictyostelium as their core research model. This review introduces Dictyostelium and then highlights research from several leading British research laboratories, covering their distinct areas of research, the benefits of using the model, and the breakthroughs that have arisen due to the use of Dictyostelium as a tractable model system.


Asunto(s)
Biología , Dictyostelium/fisiología , Modelos Biológicos , Investigación , Animales , Dictyostelium/citología , Descubrimiento de Drogas , Procesamiento Proteico-Postraduccional , Reino Unido
20.
J Cell Biol ; 220(9)2021 09 06.
Artículo en Inglés | MEDLINE | ID: mdl-34402856

RESUMEN

In this issue, Le et al. (2021. J. Cell Biol.https://doi.org/10.1083/jcb.202012114) describe a new role for the recently discovered protein CYRI in controlling the protrusions that allow cells to engulf extracellular fluid by macropinocytosis. This study helps explain how these structures are disassembled, but also uncovers a new mechanism linking the ability of cells to drink and their capacity for invasive migration.


Asunto(s)
Pinocitosis
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