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1.
BMC Sports Sci Med Rehabil ; 16(1): 88, 2024 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-38641624

RESUMEN

INTRODUCTION: Due to a variety of barriers, the majority of cancer survivors do not do enough physical activity to meet current recommendations. This study will assess the feasibility of participation in parkrun walk-run events as a novel mode of community rehabilitation exercise. METHODS: This protocol describes a single-arm intervention study with participants acting as their own controls. The study accepts adults diagnosed with any type of cancer, undergoing treatment or in remission. Participants must be able to walk and have medical clearance to exercise. A sample of 100 participants will be recruited across the Sunshine Coast over two years. Data will be collected over 9-months at 4 time points: Baseline (T1); after 4-weeks of usual daily activities and cancer management prior to parkrun participation(T2); after a 6-month parkrun intervention (T3); at 2-month follow-up (T4). The primary objectives are to assess the acceptability of, and adherence to, parkrun as rehabilitation exercise. Secondary outcomes include wellness, health-related quality of life, anxiety, depression, mood, physical function, parkrun metrics, dietary intake, and diet and exercise behaviour. CONCLUSION: This study will be the first to examine the long-term effects of parkrun as a cancer rehabilitation modality with regard to physical function, psychosocial outcomes and dietary intake. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry ACTRN12623000473662 registered 09/05/2023.Approved by UniSC Human Research Ethics Committee (A221828) and the UK parkrun Research Board. Original protocol. Authors SB, RB, HHW, MM, YK.

2.
bioRxiv ; 2024 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-38352443

RESUMEN

Genetically engineered mouse models (GEMM) have fundamentally changed how ovarian cancer etiology, early detection, and treatment is understood. However, previous GEMMs of high-grade serous ovarian cancer (HGSOC) have had to utilize genetics rarely or never found in human HGSOC to yield ovarian cancer within the lifespan of a mouse. MYC, an oncogene, is amongst the most amplified genes in HGSOC, but it has not previously been utilized to drive HGSOC GEMMs. We coupled Myc and dominant negative mutant p53-R270H with a fallopian tube epithelium-specific promoter Ovgp1 to generate a new GEMM of HGSOC. Female mice developed lethal cancer at an average of 15.1 months. Histopathological examination of mice revealed HGSOC characteristics including nuclear p53 and nuclear MYC in clusters of cells within the fallopian tube epithelium and ovarian surface epithelium. Unexpectedly, nuclear p53 and MYC clustered cell expression was also identified in the uterine luminal epithelium, possibly from intraepithelial metastasis from the fallopian tube epithelium (FTE). Extracted tumor cells exhibited strong loss of heterozygosity at the p53 locus, leaving the mutant allele. Copy number alterations in these cancer cells were prevalent, disrupting a large fraction of genes. Transcriptome profiles most closely matched human HGSOC and serous endometrial cancer. Taken together, these results demonstrate the Myc and Trp53-R270H transgene was able to recapitulate many phenotypic hallmarks of HGSOC through the utilization of strictly human-mimetic genetic hallmarks of HGSOC. This new mouse model enables further exploration of ovarian cancer pathogenesis, particularly in the 50% of HGSOC which lack homology directed repair mutations. Histological and transcriptomic findings are consistent with the hypothesis that uterine serous cancer may originate from the fallopian tube epithelium.

3.
Can Vet J ; 65(2): 138-140, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38304482

RESUMEN

Three dogs were diagnosed with naturally occurring cheyletiellosis based on clinical signs and visualization of parasites and ova. Treatment with fluralaner (orally) resulted in a rapid resolution of clinical signs with no evidence of mites or ova at 1 or 2 mo post-treatment. This is apparently the first published report of an isoxazoline being used to successfully treat cheyletiellosis in veterinary medicine. Therefore, fluralaner may be an effective option for treatment or prevention of canine cheyletiellosis, although research is needed to confirm its effectiveness for treatment of cheyletiellosis in dogs and other species. Key clinical message: This is apparently the first published report of an isoxazoline being used to successfully treat cheyletiellosis in companion animal practice. These parasites are both contagious and zoonotic and there are currently no approved products for treatment or prevention of cheyletiellosis.


Traitement réussi de 3 cas de cheylétiellose canine acquis naturellement avec du fluralaner. Trois chiens ont été diagnostiqués avec une cheylétiellose acquise naturellement sur la base des signes cliniques et la visualisation des parasites et des œufs. Un traitement avec du fluralaner (oralement) a résulté en une résolution rapide des signes cliniques sans aucune évidence de mites ou d'œufs à 1 ou 2-mois post-traitement. Ceci semble être le premier rapport publié d'un isoxazoline utilisé pour traiter avec succès la cheylétiellose en médecine vétérinaire. Ainsi, le fluralaner serait une option efficace pour le traitement ou la prévention de la cheylétiellose canine, bien que de la recherche soit nécessaire pour confirmer son efficacité pour le traitement de la cheylétiellose chez les chiens et les autres espèces.Message clinique clé :Ceci semble être le premier rapport publié de l'utilisation d'un isoxazoline pour traiter avec succès la cheylétiellose en pratique des animaux de compagnie. Ces parasites sont contagieux et zoonotiques et il n'y a à l'heure actuelle aucun produit approuvé pour le traitement ou la prévention de la cheylétiellose.(Traduit par Dr Serge Messier).


Asunto(s)
Enfermedades de los Perros , Insecticidas , Infestaciones por Ácaros , Ácaros , Animales , Perros , Enfermedades de los Perros/tratamiento farmacológico , Enfermedades de los Perros/parasitología , Infestaciones por Ácaros/tratamiento farmacológico , Infestaciones por Ácaros/veterinaria , Isoxazoles/uso terapéutico , Insecticidas/uso terapéutico
5.
J Interpers Violence ; 39(9-10): 1952-1975, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-37961902

RESUMEN

Sexual assault is a global problem, with the risk highest among university students. Bystander intervention preventing sexual assaults has primarily been researched using quantitative methods to understand what factors influence it. However, both sexual assault and bystander intervention are complex with many subtle and overlapping issues that, when analyzed qualitatively, can offer new insights. The current study aimed to explore and develop a nuanced and comprehensive understanding of students' perceptions of sexual assault and bystander intervention across two universities, one in the United Kingdom and one in Australia. Thirty-nine university students (19 in the United Kingdom; 20 in Australia) took part in one-to-one semistructured interviews. Using inductive thematic analysis, two overarching themes were identified: (a) navigating the complex dynamics of sexual assault; and (b) decisions to intervene or not to intervene. Findings suggest that the complexity and ambiguity around sexual assault can forestall bystander intervention. As such, increasing education, awareness, and discussions around sexual assault and bystander intervention is vital to increase awareness of the problem and mobilize action from bystanders to prevent sexual assault.


Asunto(s)
Delitos Sexuales , Humanos , Universidades , Australia , Delitos Sexuales/prevención & control , Estudiantes , Escolaridad
6.
Violence Against Women ; 30(3-4): 890-910, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37872683

RESUMEN

This article examines the experiences of female partners and relatives of child sexual abuse material offenders and the (il)legibility of their experiences within prevailing theoretical frameworks and policy responses to violence against women. Drawing on survey and interview data with clients of a specialist support agency, we situate the lack of understanding and support available to these women within the systematic depoliticization of child sexual abuse. The article traces how women developed their own social critique of child sexual exploitation as a form of gendered violence and called for a feminist reengagement with the politics of child sexual abuse.


Asunto(s)
Abuso Sexual Infantil , Maltrato a los Niños , Niño , Femenino , Humanos , Violencia , Feminismo , Conducta Sexual
7.
BMC Public Health ; 23(1): 1763, 2023 09 11.
Artículo en Inglés | MEDLINE | ID: mdl-37697365

RESUMEN

BACKGROUND: COVID-19 outbreaks have disproportionately affected Residential Aged Care Facilities (RACFs) around the world, with devastating impacts for residents and their families. Many factors such as community prevalence, facility layout, and infection control practices have been linked to resident outcomes. At present, there are no scoring systems designed to quantify these factors and assess their level of association with resident attack rates and mortality rates. METHODS: We constructed a novel Infection Prevention and Control (IPC) scoring system to quantify facility layout, ability to cohort residents, and IPC practices in RACFs. We conducted a retrospective observational cohort study of COVID-19 outbreaks, applying our IPC scoring system to all COVID-19 outbreaks occurring in RACFs in Sydney Local Health District during the Delta and Omicron waves of the COVID-19 pandemic in New South Wales, Australia. RESULTS: Twenty-six COVID-19 outbreaks in 23 facilities in the Delta wave, and 84 outbreaks in 53 facilities in the Omicron wave were included in the study. A linear Generalised Estimating Equation model was fitted to the Omicron data. Higher IPC scores were associated with higher attack rates and mortality rates. Facilities with IPC scores greater than 75.0% had attack rates 19.6% higher [95% CI: 6.4%-32.8%] and mortality rates 1.7% higher [95% CI: 0.6%-2.7%] than facilities with an IPC score of less than 60.0%. CONCLUSIONS: The results of this study suggest the utility of the IPC scoring system for identifying facilities at greater risk of adverse outcomes from COVID-19 outbreaks. While further validation and replication of accuracy is required, the IPC scoring system could be used and adapted to improve planning, policy, and resource allocation for future outbreaks.


Asunto(s)
COVID-19 , Humanos , Anciano , COVID-19/epidemiología , COVID-19/prevención & control , Pandemias/prevención & control , Estudios Retrospectivos , Australia/epidemiología , Brotes de Enfermedades/prevención & control
8.
Am J Dermatopathol ; 45(8): 567-571, 2023 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-37377207

RESUMEN

BACKGROUND: Mycosis fungoides (MF) is a rare primary cutaneous T-cell lymphoma, accounting for 50%-60% of all cutaneous T-cell lymphoma cases. It has a prevalence of approximately 5-6 cases per 1 million people annually and a higher incidence in dark-skinned populations. CASE PRESENTATION: We report a case of hyperpigmented MF in a 72-year-old dark-skinned man with a 5-year history of progressive, widespread poikilodermatous patches and thin plaques on the back and bilateral legs. The patient had been treated for lichen planus pigmentosus for 5 years without significant response to therapy. ASSESSMENT: Multiple biopsies revealed a band-like lymphoid infiltrate in the dermis, accompanied by intraepidermal lymphocytes, some of which had larger hyperchromatic nuclei. CD4 + T lymphocytes were predominant over CD8 + T-positive cells located along the epidermis, dermoepidermal junction, and in the dermis. DIAGNOSIS: A diagnosis of hyperpigmented MF was made based on the clinical, histopathological, and immunohistochemical findings. CONCLUSION: This case report highlights the importance of considering hyperpigmented MF as a differential diagnosis in patients with longstanding lichen planus pigmentosus, particularly when there is a lack of response to therapy.


Asunto(s)
Hiperpigmentación , Liquen Plano , Micosis Fungoide , Neoplasias Cutáneas , Masculino , Humanos , Anciano , Micosis Fungoide/patología , Hiperpigmentación/patología , Linfocitos T CD8-positivos/patología , Liquen Plano/patología , Neoplasias Cutáneas/patología
9.
Can Vet J ; 64(6): 558-564, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-37265812

RESUMEN

Objective: The aim of this study was to investigate the bacterial population and antimicrobial resistance of bacteria isolated from feline urine from 2012 to 2018 in the Canadian provinces of Alberta and British Columbia. Animals and procedure: IDEXX Reference Laboratories provided data from urine samples submitted from Alberta and British Columbia for aerobic culture and susceptibility testing from January 1, 2012 to December 31, 2018. The analysis included 8084 bacterial isolates from 7522 cystocentesis samples, with at least 1000 colony-forming units per mL. Results: Escherichia coli, Enterococcus species, and Staphylococcus species were the most commonly isolated bacteria, at 60.0%, 22.7%, and 11.8%, respectively. The proportions did not vary significantly throughout the study period or between British Columbia and Alberta. Apart from an increase in the resistance of Staphylococcus species to clindamycin, there was minimal change in the antimicrobial susceptibility of the 3 most commonly isolated bacteria over the study period. More than 85% of Gram-positive organisms were susceptible to amoxicillin with or without clavulanic acid, and > 85% of Gram-negative organisms were susceptible to amoxicillin with clavulanic acid and trimethoprim with sulfamethoxazole. Conclusion and clinical relevance: Treatment with amoxicillin, with or without clavulanic acid, may be considered for bacterial feline lower urinary tract disease in Alberta and British Columbia while awaiting culture results.


Agents pathogènes des voies urinaires félines dans l'Ouest canadien: prévalence des espèces bactériennes et résistance aux antimicrobiens de 2012 à 2018. Objectif: Le but de cette étude était d'étudier la population bactérienne et la résistance antimicrobienne des bactéries isolées de l'urine féline de 2012 à 2018 dans les provinces canadiennes de l'Alberta et de la Colombie-Britannique. Animaux et procédure: Les Laboratoires de référence IDEXX ont fourni des données à partir d'échantillons d'urine soumis par l'Alberta et la Colombie-Britannique pour une culture aérobie et des tests de sensibilité du 1er janvier 2012 au 31 décembre 2018. L'analyse comprenait 8084 isolats bactériens provenant de 7522 échantillons d'urine obtenus par cystocentèse, avec au moins 1000 unités formant des colonies/mL. Résultats: Escherichia coli, les espèces appartenant aux genres Enterococcus et Staphylococcus étaient les bactéries les plus couramment isolées, à 60,0 %, 22,7 % et 11,8 %, respectivement. Les proportions n'ont pas varié de manière significative tout au long de la période d'étude ni entre la Colombie-Britannique et l'Alberta. Hormis une augmentation de la résistance des espèces de Staphylococcus à la clindamycine, il y a eu un changement minime de la sensibilité aux antimicrobiens des 3 bactéries les plus couramment isolées au cours de la période d'étude. Plus de 85 % des organismes à Gram positif étaient sensibles à l'amoxicilline avec ou sans acide clavulanique, et > 85 % des organismes à Gram négatif étaient sensibles à l'amoxicilline avec acide clavulanique et à la combinaison triméthoprime-sulfaméthoxazole. Conclusion et pertinence clinique: Un traitement à l'amoxicilline, avec ou sans acide clavulanique, peut être envisagé pour les infections bactérienne urinaires félines en Alberta et en Colombie-Britannique en attendant les résultats de la culture.(Traduit par Dr Serge Messier).


Asunto(s)
Enfermedades de los Gatos , Infecciones Urinarias , Sistema Urinario , Gatos , Animales , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Infecciones Urinarias/tratamiento farmacológico , Infecciones Urinarias/epidemiología , Infecciones Urinarias/veterinaria , Prevalencia , Farmacorresistencia Bacteriana , Pruebas de Sensibilidad Microbiana/veterinaria , Bacterias , Amoxicilina/uso terapéutico , Staphylococcus , Ácido Clavulánico/uso terapéutico , Alberta/epidemiología , Enfermedades de los Gatos/tratamiento farmacológico , Enfermedades de los Gatos/epidemiología
10.
Virtual Real ; : 1-13, 2022 Nov 10.
Artículo en Inglés | MEDLINE | ID: mdl-36405877

RESUMEN

Recent advancement in technology has made virtual reality (VR) more accessible and immersive than ever before, resulting in its increasing utility in various industries. Despite this, VR has remained an underutilised tool within clinical psychology. This study aimed to explore the potential of using VR for therapeutic benefits through examining the level of flow and anxiety-reducing effects of freeform drawing in real life (on paper) versus drawing in VR (using Tilt Brush) via a randomised-controlled trial with 40 participants. State and trait anxiety was measured using the State-Trait Anxiety Inventory, level of flow was measured using the Long Flow State Scale, and level of presence was measured using the iGroup Presence Questionnaire. Overall level of flow was not significantly different between both groups, implying drawing in VR induces as much flow as drawing in real life. Level of flow was positively correlated to level of presence experienced in the VR group (p < .01). Although there was no significant interaction effect, both groups experienced an overall decrease in state anxiety, with the VR group experiencing a significant reduction of state anxiety from pre- to post-test (p < .01).

11.
Aust N Z J Public Health ; 46(6): 884-888, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36190193

RESUMEN

OBJECTIVE: Western Sydney Local Health District (WSLHD) measured the utility and validity of rapid molecular point-of-care testing (POCT) in aged care facilities (ACFs) experiencing influenza-like illness (ILI) outbreaks against routine laboratory testing. METHODS: A descriptive epidemiological study into 82 respiratory outbreaks reported across 63 ACFs within WSLHD supporting approximately 6,500 residents aged ≥65 years and staffed by ∼6,500 employees, from 1 August 2018 to 31 December 2019. RESULTS: WSLHD Public Health Unit performed on-site testing at 27 ACF outbreaks (34%), while 53(66%) ACFs conducted only routine laboratory testing. The Xpert®Xpress Flu/RSV molecular PCR provided a sensitivity and specificity of 100%. Those with on-site testing, antiviral prophylaxis was prescribed at 75% of facilities within 24 hours of testing, as opposed to 32% of those using laboratory testing (p<0.01). There were 24 of 181 ACF residents hospitalised in the POCT group compared to 76 of 357 in the laboratory-only group (OR=0.57; p=0.02). CONCLUSIONS: On-site ACF testing is reliable and practical for early identification of influenza, enabling timely use of antiviral treatment and prophylaxis, and was associated with decreased hospitalisation. PUBLIC HEALTH IMPLICATIONS: Enhanced respiratory surveillance and on-site testing should be strongly considered as part of routine management of respiratory outbreaks in ACFs and may reduce outbreak severity.


Asunto(s)
Gripe Humana , Humanos , Gripe Humana/diagnóstico , Gripe Humana/tratamiento farmacológico , Gripe Humana/epidemiología , Antivirales/uso terapéutico , Brotes de Enfermedades/prevención & control , Pruebas en el Punto de Atención , Hospitalización
12.
Front Bioeng Biotechnol ; 10: 915702, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35928950

RESUMEN

Tissue-engineered skin constructs have been under development since the 1980s as a replacement for human skin tissues and animal models for therapeutics and cosmetic testing. These have evolved from simple single-cell assays to increasingly complex models with integrated dermal equivalents and multiple cell types including a dermis, epidermis, and vasculature. The development of micro-engineered platforms and biomaterials has enabled scientists to better recreate and capture the tissue microenvironment in vitro, including the vascularization of tissue models and their integration into microfluidic chips. However, to date, microvascularized human skin equivalents in a microfluidic context have not been reported. Here, we present the design of a novel skin-on-a-chip model integrating human-derived primary and immortalized cells in a full-thickness skin equivalent. The model is housed in a microfluidic device, in which a microvasculature was previously established. We characterize the impact of our chip design on the quality of the microvascular networks formed and evidence that this enables the formation of more homogenous networks. We developed a methodology to harvest tissues from embedded chips, after 14 days of culture, and characterize the impact of culture conditions and vascularization (including with pericyte co-cultures) on the stratification of the epidermis in the resulting skin equivalents. Our results indicate that vascularization enhances stratification and differentiation (thickness, architecture, and expression of terminal differentiation markers such as involucrin and transglutaminase 1), allowing the formation of more mature skin equivalents in microfluidic chips. The skin-on-a-chip tissue equivalents developed, because of their realistic microvasculature, may find applications for testing efficacy and safety of therapeutics delivered systemically, in a human context.

13.
Artículo en Inglés | MEDLINE | ID: mdl-35981816

RESUMEN

Background: Human metapneumovirus (hMPV), first described in 2001, is a cause of acute respiratory tract infection in the elderly, with symptoms ranging from mild to severe, including pneumonia, but outbreaks are rarely described. Methods: Between 1 July and 31 December 2018, there were three outbreaks of Influenza-like Illness (ILI) where hMPV was the primary pathogen observed, among 64 aged-care facilities (ACFs) in Western Sydney. These outbreaks were investigated by the Western Sydney Local Health District (WSLHD) Public Health Unit (PHU); multiplex polymerase chain reaction (PCR) testing was performed on nasopharyngeal swabs collected by the ACF. Results: hMPV was the main causative pathogen in three outbreaks (27, 28, and 15 symptomatic cases, respectively) in late winter and early spring. Fifty-five residents and 15 staff cases (70 total cases) were identified; hMPV was detected in 12 of 63 specimens submitted. Of the cases in residents, eight were hospitalised (8/63; 15%), including five with confirmed hMPV and a further one epidemiologically linked to a positive case. Six residents died (6/63; 11%) during the hMPV outbreaks; four of these had laboratory-confirmed hMPV, with a further case epidemiologically linked to a hMPV case, with a primary diagnosis of pneumonia/viral pneumonia. The sixth death was not epidemiologically linked, nor did this case exhibit any respiratory symptoms during the outbreak; however, it was reported in line with public health guidelines. Conclusion: A major challenge in 2018 was the incompleteness of testing for, and awareness of, hMPV as a viral cause of ILI by facilities, laboratories, and emergency departments, which generally opted for rapid testing for influenza and RSV only. There is no licensed vaccine or approved treatment for hMPV, so efficient infection control measures are most important.


Asunto(s)
Gripe Humana , Metapneumovirus , Infecciones por Paramyxoviridae , Neumonía Viral , Anciano , Australia/epidemiología , Brotes de Enfermedades , Humanos , Gripe Humana/epidemiología , Infecciones por Paramyxoviridae/diagnóstico , Infecciones por Paramyxoviridae/epidemiología , Neumonía Viral/epidemiología
15.
Sci Rep ; 12(1): 6544, 2022 04 21.
Artículo en Inglés | MEDLINE | ID: mdl-35449381

RESUMEN

In 2018, the giant manta ray was listed as threatened under the U.S. Endangered Species Act. We integrated decades of sightings and survey effort data from multiple sources in a comprehensive species distribution modeling (SDM) framework to evaluate the distribution of giant manta rays off the eastern United States, including the Gulf of Mexico. Manta rays were most commonly detected at productive nearshore and shelf-edge upwelling zones at surface thermal frontal boundaries within a temperature range of approximately 20-30 °C. SDMs predicted highest nearshore occurrence off northeastern Florida during April, with the distribution extending northward along the shelf-edge as temperatures warm, leading to higher occurrences north of Cape Hatteras, North Carolina from June to October, and then south of Savannah, Georgia from November to March as temperatures cool. In the Gulf of Mexico, the highest nearshore occurrence was predicted around the Mississippi River delta from April to June and again from October to November. SDM predictions will allow resource managers to more effectively protect manta rays from fisheries bycatch, boat strikes, oil and gas activities, contaminants and pollutants, and other threats.


Asunto(s)
Elasmobranquios , Rajidae , Animales , Océano Atlántico , Especies en Peligro de Extinción , Explotaciones Pesqueras , Georgia , Estados Unidos
16.
BMC Cancer ; 22(1): 410, 2022 Apr 14.
Artículo en Inglés | MEDLINE | ID: mdl-35421971

RESUMEN

BACKGROUND: Genomic instability and chemoresistance can arise in cancer due to a unique form of plasticity: that of polyploid giant cancer cells (PGCCs). These cells form under the stress of chemotherapy and have higher than diploid chromosome content. PGCCs are able to then repopulate tumors through an asymmetric daughter cell budding process. PGCCs have been observed in ovarian cancer histology, including the deadly and common form high-grade serous ovarian carcinoma (HGSC). We previously discovered that drugs which disrupt the cellular recycling process of autophagy are uniquely efficacious in pre-clinical HGSC models. While autophagy induction has been associated with PGCCs, it has never been previously investigated if autophagy modulation interacts with the PGCC life cycle and this form of tumor cell plasticity. METHODS: CAOV3 and OVCAR3 ovarian cancer cell lines were treated with carboplatin or docetaxel to induce PGCC formation. Microscopy was used to characterize and quantify PGCCs formed by chemotherapy. Two clinically available drugs that inhibit autophagy, hydroxychloroquine and nelfinavir, and a clinically available activator of autophagy, rapamycin, were employed to test the effect of these autophagy modulators on PGCC induction and subsequent colony formation from PGCCs. Crystal violet-stained colony formation assays were used to quantify the tumor-repopulating stage of the PGCC life cycle. RESULTS: Autophagy inhibitors did not prevent PGCC formation in OVCAR3 or CAOV3 cells. Rapamycin did not induce PGCC formation on its own nor did it exacerbate PGCC formation by chemotherapy. However, hydroxychloroquine prevented efficient colony formation in CAOV3 PGCCs induced by carboplatin (27% inhibition) or docetaxel (41% inhibition), as well as in OVCAR3 cells (95% and 77%, respectively). Nelfinavir similarly prevented colony formation in CAOV3 PGCCs induced by carboplatin (64% inhibition) or docetaxel (94% inhibition) as well as in OVCAR3 cells (89% and 80%, respectively). Rapamycin surprisingly also prevented PGCC colony outgrowth (52-84% inhibition). CONCLUSIONS: While the autophagy previously observed to correlate with PGCC formation is unlikely necessary for PGCCs to form, autophagy modulating drugs severely impair the ability of HGSC PGCCs to form colonies. Clinical trials which utilize hydroxychloroquine, nelfinavir, and/or rapamycin after chemotherapy may be of future interest.


Asunto(s)
Apoptosis , Neoplasias Ováricas , Autofagia , Carboplatino/farmacología , Carcinoma Epitelial de Ovario/patología , Línea Celular Tumoral , Docetaxel/farmacología , Femenino , Células Gigantes/patología , Humanos , Hidroxicloroquina/farmacología , Nelfinavir , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética , Neoplasias Ováricas/metabolismo , Poliploidía , Sirolimus/farmacología
17.
Nucleic Acids Res ; 50(7): 3673-3692, 2022 04 22.
Artículo en Inglés | MEDLINE | ID: mdl-35380699

RESUMEN

Haploinsufficiency drives Darwinian evolution. Siblings, while alike in many aspects, differ due to monoallelic differences inherited from each parent. In cancer, solid tumors exhibit aneuploid genetics resulting in hundreds to thousands of monoallelic gene-level copy-number alterations (CNAs) in each tumor. Aneuploidy patterns are heterogeneous, posing a challenge to identify drivers in this high-noise genetic environment. Here, we developed Shifted Weighted Annotation Network (SWAN) analysis to assess biology impacted by cumulative monoallelic changes. SWAN enables an integrated pathway-network analysis of CNAs, RNA expression, and mutations via a simple web platform. SWAN is optimized to best prioritize known and novel tumor suppressors and oncogenes, thereby identifying drivers and potential druggable vulnerabilities within cancer CNAs. Protein homeostasis, phospholipid dephosphorylation, and ion transport pathways are commonly suppressed. An atlas of CNA pathways altered in each cancer type is released. These CNA network shifts highlight new, attractive targets to exploit in solid tumors.


Asunto(s)
Algoritmos , Genes Supresores de Tumor , Neoplasias , Oncogenes , Aneuploidia , Línea Celular Tumoral , Variaciones en el Número de Copia de ADN , Humanos , Neoplasias/genética , Neoplasias/patología , Transducción de Señal
18.
Appl Ergon ; 101: 103698, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35151982

RESUMEN

This study investigated symptoms of cybersickness and postural instability experienced by new users of head-mounted display virtual reality (HMD-VR), playing VR videogames over long and repeated sessions, and moderation of these symptoms by previous videogame experience and intensity of videogame stimulus. Cybersickness (SSQ) and postural stability (anterior-posterior path-velocity) of new users of VR (n = 80) was collected PRE-VR, POST-VR and 10 min after completing (POST-RECOVERY) a VR gaming experience. Users comprised of videogamers (n = 40) and non-videogamers (n = 40), who were randomly assigned to play either action (high-intensity stimuli) or adventure (low-intensity stimuli) games in VR for 30 min and repeated twice, one week apart. All participants, irrespective of gaming status and genre of game, experienced significant cybersickness after 30 min in VR using current-generation HMD-VR technology, and did not adapt (POST-VR) after two sessions. However videogamers were able to recover (POST-RECOVERY) from cybersickness induced in VR significantly better than non-videogamers. All participants experienced significantly better postural stability after 30 min in VR, irrespective of gaming experience or genre of game. Developers should create VR experiences that minimise negative symptoms of cybersickness and postural instability experience by new users of VR.


Asunto(s)
Gafas Inteligentes , Juegos de Video , Realidad Virtual , Adaptación Fisiológica , Humanos , Recreación
19.
Women Birth ; 35(2): e172-e180, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33985916

RESUMEN

BACKGROUND: Childbearing women engage in large public pregnancy and parenting forums, primarily for the purpose of seeking information and advice. There is an absence of research related to women's engagement in closed and private online mothers' groups. AIM: The aim of this study was to explore the experiences of participation and support for members within a closed online mothers' group. METHOD: A qualitative study using in-depth interviews. Reflexive thematic analysis was used to analyse the data. FINDINGS: This study demonstrated that a closed online mothers' group enabled a group of childbearing women to overcome isolation and form sustained, evolving and supportive friendships within a small, private and trusted group. The technology allowed women to engage and share at a level much deeper than what they would in "real life". The depth of sharing was enhanced in a closed online mothers' group due to a smaller, private audience of trusted friends. Virtual support felt safer than face-to-face support as information could not impact one's real world reputation, and communication was able to be controlled. This was particularly helpful to women experiencing social difficulties or isolation. CONCLUSION: This study has provided a unique and rare insight into the private world of closed online mothers' groups. As a virtual village, this closed group enabled childbearing women to form a small community with members sharing responsibility and working for the wellbeing and benefit of all. By encouraging, locating and establishing similar groups, maternity health professionals may assist women to access their own 'virtual village'.


Asunto(s)
Madres , Medios de Comunicación Sociales , Femenino , Humanos , Responsabilidad Parental , Embarazo , Investigación Cualitativa , Grupos de Autoayuda , Apoyo Social
20.
Nanomedicine ; 40: 102506, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34875352

RESUMEN

Oncolytic viruses (OVs) selectively replicate in and destroy cancer cells resulting in anti-tumor immunity. However, clinical use remains a challenge because of virus clearance upon intravenous delivery. OV packaging using a nanomedicine approach could overcome this. Here we encapsulate an oncolytic adenovirus (Ad[I/PPT-E1A]) into CCL2-coated liposomes in order to exploit recruitment of CCR2-expressing circulating monocytes into tumors. We demonstrate successful encapsulation of Ad[I/PPT-E1A] into CCL2-coated liposomes that were preferentially taken up by CCR2-expressing monocytes. No complex-related toxicities were observed following incubation with prostate tumor cells and the encapsulation did not affect virus oncolytic activity in vitro. Furthermore, intravenous administration of our nanomedicine resulted in a significant reduction in tumor size and pulmonary metastasis in prostate cancer-bearing mice whereby a 1000-fold less virus was needed compared to Ad[I/PPT-E1A] alone. Taken together our data provide an opportunity to target OVs via circulation to inaccessible tumors using liposome-assisted drug delivery.


Asunto(s)
Adenoviridae , Viroterapia Oncolítica , Adenoviridae/genética , Animales , Línea Celular Tumoral , Quimiocina CCL2/genética , Vectores Genéticos , Humanos , Liposomas , Masculino , Ratones , Monocitos , Viroterapia Oncolítica/métodos
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