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1.
BMC Infect Dis ; 24(1): 444, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38671365

RESUMO

INTRODUCTION: Carbapenemase-producing Enterobacterales (CPE) are an important public health threat, with costly operational and economic consequences for NHS Integrated Care Systems and NHS Trusts. UK Health Security Agency guidelines recommend that Trusts use locally developed risk assessments to accurately identify high-risk individuals for screening, and implement the most appropriate method of testing, but this presents many challenges. METHODS: A convenience sample of cross-specialty experts from across England met to discuss the barriers and practical solutions to implementing UK Health Security Agency framework into operational and clinical workflows. The group derived responses to six key questions that are frequently asked about screening for CPE. KEY FINDINGS: Four patient groups were identified for CPE screening: high-risk unplanned admissions, high-risk elective admissions, patients in high-risk units, and known positive contacts. Rapid molecular testing is a preferred screening method for some of these settings, offering faster turnaround times and more accurate results than culture-based testing. It is important to stimulate action now, as several lessons can be learnt from screening during the COVID-19 pandemic, as well as from CPE outbreaks. CONCLUSION: Further decisive and instructive information is needed to establish CPE screening protocols based on local epidemiology and risk factors. Local management should continually evaluate local epidemiology, analysing data and undertaking frequent prevalence studies to understand risks, and prepare resources- such as upscaled screening- to prevent increasing prevalence, clusters or outbreaks. Rapid molecular-based methods will be a crucial part of these considerations, as they can reduce unnecessary isolation and opportunity costs.


Assuntos
Proteínas de Bactérias , Infecções por Enterobacteriaceae , Programas de Rastreamento , beta-Lactamases , Humanos , Infecções por Enterobacteriaceae/diagnóstico , Infecções por Enterobacteriaceae/microbiologia , Inglaterra , beta-Lactamases/metabolismo , beta-Lactamases/genética , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Programas de Rastreamento/métodos , Enterobacteriáceas Resistentes a Carbapenêmicos/isolamento & purificação , Hospitais , COVID-19/diagnóstico , SARS-CoV-2 , Enterobacteriaceae/enzimologia , Enterobacteriaceae/isolamento & purificação , Enterobacteriaceae/genética
3.
J Hosp Infect ; 140: 110-116, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37562595

RESUMO

OBJECTIVES: Outbreaks of infection related to flexible endoscopes are well described. However, flexible endoscopy also requires the use of ancillary equipment such as irrigation plugs. These are potential vectors of infection but are infrequently highlighted in the literature. This paper reports a cystoscopy-associated outbreak of Pseudomonas aeruginosa from contaminated irrigation plugs in a UK tertiary care centre. METHODS: Laboratory, clinical and decontamination unit records were reviewed, and audits of the decontamination unit were performed. Flexible cystoscopes and irrigation plugs were assessed for contamination. Retrospective and prospective case finding was performed utilizing the microbiology laboratory information management system. Available P. aeruginosa isolates underwent variable nucleotide tandem repeat (VNTR) typing. Confirmed cases were defined as P. aeruginosa infection with an identical VNTR profile to an outbreak strain. RESULTS: Three strains of P. aeruginosa were isolated from five irrigation plugs but none of the flexible cystoscopes. No acquired resistance mechanisms were detected. Fifteen confirmed infections occurred, including bacteraemia, septic arthritis and urinary tract infection. While failure of decontamination likely occurred because the plugs were not dismantled prior to reprocessing, the manufacturer's reprocessing instructions were also incompatible with standard UK practice. The Medicines and Healthcare Products Regulatory Agency was informed. A field safety notice was issued, and the manufacturer issued updated reprocessing instructions. CONCLUSIONS: Ancillary equipment can represent an important vector for infection, and should be considered during outbreak investigations. Users should review the manufacturer's instructions for reprocessing ancillary equipment to ensure that they are compatible with available procedures.


Assuntos
Infecção Hospitalar , Infecções por Pseudomonas , Humanos , Pseudomonas , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/prevenção & controle , Infecção Hospitalar/complicações , Estudos Retrospectivos , Surtos de Doenças , Pseudomonas aeruginosa , Infecções por Pseudomonas/epidemiologia , Infecções por Pseudomonas/prevenção & controle , Contaminação de Equipamentos
4.
Vet J ; 292: 105953, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36775186

RESUMO

Although the equine sarcoid is the most common skin neoplasm in domesticated horses, histopathological characteristics have not previously been evaluated for association with recurrence. The aim of this retrospective cohort study was to investigate clinical and histopathological features of excised equine sarcoids and to evaluate their association with recurrence at the original surgical site and at new sites. Clinical records and excisional biopsies from 106 equine sarcoids from 64 horses referred to Leahurst Equine Hospital, University of Liverpool, between March 2010 and February 2015 were retrieved. Biopsies were re-evaluated histologically. Clinical data were obtained from hospital records, and owner-reported follow-up data were obtained by telephone questionnaire. Associations between clinical and histopathological features of sarcoids and their recurrence at the surgical site were determined using uni- and multivariable mixed effects logistic regression. Recurrence of sarcoids at the surgical site occurred in 30 horses (46.9%). Sarcoids developed at a distant site in 21 horses (32.8%). In the final mixed effects logistic regression model, only superficial inflammation was associated with reduced odds of recurrence at the surgical site (adjusted odds ratio, 0.32; 95% confidence intervals, 0.10-0.96; P = 0.04). This suggests that the inflammatory process may play a role in protecting horses against the recurrence of sarcoids.

5.
BMJ Mil Health ; 169(3): 271-276, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33547188

RESUMO

Coronavirus disease 2019 (COVID-19) causes significant mortality and morbidity, with an unknown impact in the medium to long term. Evidence from previous coronavirus epidemics indicates that there is likely to be a substantial burden of disease, potentially even in those with a mild acute illness. The clinical and occupational effects of COVID-19 are likely to impact on the operational effectiveness of the Armed Forces. Collaboration between Defence Primary Healthcare, Defence Secondary Healthcare, Defence Rehabilitation and Defence Occupational Medicine resulted in the Defence Medical Rehabilitation Centre COVID-19 Recovery Service (DCRS). This integrated clinical and occupational pathway uses cardiopulmonary assessment as a cornerstone to identify, diagnose and manage post-COVID-19 pathology.


Assuntos
COVID-19 , Epidemias , Medicina , Humanos , Atenção à Saúde , Centros de Reabilitação
6.
Phys Rev Lett ; 129(10): 102701, 2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-36112434

RESUMO

Carbon burning is a key step in the evolution of massive stars, Type 1a supernovae and superbursts in x-ray binary systems. Determining the ^{12}C+^{12}C fusion cross section at relevant energies by extrapolation of direct measurements is challenging due to resonances at and below the Coulomb barrier. A study of the ^{24}Mg(α,α^{'})^{24}Mg reaction has identified several 0^{+} states in ^{24}Mg, close to the ^{12}C+^{12}C threshold, which predominantly decay to ^{20}Ne(ground state)+α. These states were not observed in ^{20}Ne(α,α_{0})^{20}Ne resonance scattering suggesting that they may have a dominant ^{12}C+^{12}C cluster structure. Given the very low angular momentum associated with sub-barrier fusion, these states may play a decisive role in ^{12}C+^{12}C fusion in analogy to the Hoyle state in helium burning. We present estimates of updated ^{12}C+^{12}C fusion reaction rates.

7.
AJNR Am J Neuroradiol ; 43(1): 139-145, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34949592

RESUMO

BACKGROUND AND PURPOSE: Preterm infants are at risk for overt and silent CNS injury, with developmental consequences that are difficult to predict. The novel Specific Test of Early Infant Motor Performance, administered in preterm infants at term age, is indicative of later developmental gross motor and cognitive scores at 12 months. Here, we assessed whether functional performance on this early assessment correlates with CNS integrity via MR spectroscopy or diffusional kurtosis imaging and whether these quantitative neuroimaging methods improve predictions for future 12-month developmental scores. MATERIALS AND METHODS: MR spectroscopy and quantitative diffusion MR imaging data were acquired in preterm infants (n = 16) at term. Testing was performed at term and 3 months using the Specific Test of Early Infant Motor Performance and the Bayley Scales of Infant and Toddler Development, Third Edition, at 12 months. We modeled the relationship of MR spectroscopy and diffusion MR imaging data with both test scores via multiple linear regression. RESULTS: MR spectroscopy NAA ratios at a TE of 270 ms in the frontal WM and basal ganglia and kurtosis metrics in major WM tracts correlated strongly with total Specific Test of Early Infant Motor Performance scores. The addition of MR spectroscopy and diffusion separately improved the functional predictions of 12-month outcomes. CONCLUSIONS: Microstructural integrity of the major WM tracts and metabolism in the basal ganglia and frontal WM strongly correlate with early developmental performance, suggesting that the Specific Test of Early Infant Motor Performance reflects CNS integrity after preterm birth. This study demonstrates that combining quantitative neuroimaging and early functional movement improves the prediction of 12-month outcomes in premature infants.


Assuntos
Recém-Nascido Prematuro , Nascimento Prematuro , Imagem de Tensor de Difusão , Humanos , Lactente , Recém-Nascido , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética
8.
Phys Rev Lett ; 127(20): 202501, 2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34860042

RESUMO

Two long-standing puzzles in the decay of ^{185}Bi, the heaviest known proton-emitting nucleus are revisited. These are the nonobservation of the 9/2^{-} state, which is the ground state of all heavier odd-A Bi isotopes, and the hindered nature of proton and α decays of its presumed 60-µs 1/2^{+} ground state. The ^{185}Bi nucleus has now been studied with the ^{95}Mo(^{93}Nb,3n) reaction in complementary experiments using the Fragment Mass Analyzer and Argonne Gas-Filled Analyzer at Argonne National Laboratory's ATLAS facility. The experiments have established the existence of two states in ^{185}Bi; the short-lived T_{1/2}=2.8_{-1.0}^{+2.3} µs, proton- and α-decaying ground state, and a 58(2)-µs γ-decaying isomer, the half-life of which was previously attributed to the ground state. The reassignment of the ground-state lifetime results in a proton-decay spectroscopic factor close to unity and represents the only known example of a ground-state proton decay to a daughter nucleus (^{184}Pb) with a major shell closure. The data also demonstrate that the ordering of low- and high-spin states in ^{185}Bi is reversed relative to the heavier odd-A Bi isotopes, with the intruder-based 1/2^{+} configuration becoming the ground, similar to the lightest At nuclides.

9.
J Hosp Infect ; 116: 37-46, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34245806

RESUMO

BACKGROUND: The risk of transmission of SARS-CoV-2 from aerosols generated by medical procedures is a cause for concern. AIM: To evaluate the evidence for aerosol production and transmission of respiratory infection associated with procedures that involve airway suctioning or induce coughing/sneezing. METHODS: The review was informed by PRISMA guidelines. Searches were conducted in PubMed for studies published between January 1st, 2003 and October 6th, 2020. Included studies examined whether nasogastric tube insertion, lung function tests, nasendoscopy, dysphagia assessment, or suctioning for airway clearance result in aerosol generation or transmission of SARS-CoV-2, SARS-CoV, MERS, or influenza. Risk of bias assessment focused on robustness of measurement, control for confounding, and applicability to clinical practice. FINDINGS: Eighteen primary studies and two systematic reviews were included. Three epidemiological studies found no association between nasogastric tube insertion and acquisition of respiratory infections. One simulation study found low/very low production of aerosols associated with pulmonary lung function tests. Seven simulation studies of endoscopic sinus surgery suggested significant increases in aerosols but findings were inconsistent; two clinical studies found airborne particles associated with the use of microdebriders/drills. Some simulation studies did not use robust measures to detect particles and are difficult to equate to clinical conditions. CONCLUSION: There was an absence of evidence to suggest that the procedures included in the review were associated with an increased risk of transmission of respiratory infection. In order to better target precautions to mitigate risk, more research is required to determine the characteristics of medical procedures and patients that increase the risk of transmission of SARS-CoV-2.


Assuntos
Aerossóis , COVID-19 , Aerossóis/efeitos adversos , Microbiologia do Ar , COVID-19/transmissão , Humanos , Fenômenos Fisiológicos Respiratórios , SARS-CoV-2
10.
Phys Rev Lett ; 126(7): 072501, 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33666458

RESUMO

We studied the proton-rich T_{z}=-1 nucleus ^{70}Kr through inelastic scattering at intermediate energies in order to extract the reduced transition probability, B(E2;0^{+}→2^{+}). Comparison with the other members of the A=70 isospin triplet, ^{70}Br and ^{70}Se, studied in the same experiment, shows a 3σ deviation from the expected linearity of the electromagnetic matrix elements as a function of T_{z}. At present, no established nuclear structure theory can describe this observed deviation quantitatively. This is the first violation of isospin symmetry at this level observed in the transition matrix elements. A heuristic approach may explain the anomaly by a shape change between the mirror nuclei ^{70}Kr and ^{70}Se contrary to the model predictions.

11.
QJM ; 114(6): 381-389, 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-32589722

RESUMO

BACKGROUND: Perhaps, as never before, we need innovators. With our growing population numbers, and with increasing pressures on our education systems, are we in danger of becoming more rigid and formulaic and increasingly inhibiting innovation? When young can we predict who will become the great innovators? For example, in medicine, who will change clinical practice? AIMS: We therefore determined to assess whether the current academic excellence approach to medical school entrance would have captured previous great innovators in medicine, assuming that they should all have well fulfilled current entrance requirements. METHODS: The authors assembled a list of 100 great medical innovators which was then approved, rejected or added to by a jury of 12 MD fellows of the Royal Society of Canada. Two reviewers, who had taken both the past and present Medical College Admission Test as part of North American medical school entrance requirements, independently assessed each innovator's early life educational history in order to predict the innovator's likely success at medical school entry, assuming excellence in all entrance requirements. RESULTS: Thirty-one percent of the great medical innovators possessed no medical degree and 24% would likely be denied entry to medical school by today's standards (e.g. had a history of poor performance, failure, dropout or expulsion) with only 24% being guaranteed entry. Even if excellence in only one topic was required, the figure would only rise to 41% certain of medical school entry. CONCLUSION: These data show that today's medical school entry standards would have barred many great innovators and raise questions about whether we are losing medical innovators as a consequence. Our findings have important implications for promoting flexibility and innovation for medical education, and for promoting an environment for innovation in general.


Assuntos
Educação Médica , Humanos , Organizações
12.
Ecotoxicol Environ Saf ; 208: 111422, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33091776

RESUMO

Potable water in developing countries often contains levels of toxic metals that exceed the recommended international limits, with impacts on human health. The aim of the present study was to develop a low cost aerogel synthesised from graphene oxide (GO) cross-linked with alginate to remove Pb2+ from potable water. Aerogels were made by a sol-gel of the composite materials followed by a freeze drying method. The shape of the aerogels were 50 mm diameter disks, 5 mm deep and characterised by an open porous network of 50 to 150 micrometres which are mechanically robust upon hydration. Firstly, the study was conducted using a batch adsorption method from a starting concentration 0.48 mM (100 mg/l) of Pb2+ in ultrapure water over 240 min, n = 4 with controls. A second series of experiments compared the adsorption of different competing ions at different valencies (Na+, Ca2+, Cu2+, La3+) in an equivalent media. A third series of experiments explored Pb2+ desorption from the aerogel at low pH and in highly acidic conditions. This simple filter system, based on a batch adsorption methodology expresses a high affinity for Pb2+ resulting in an ultra-high mean maximum adsorption capacity of 504 mg/g of Pb2+ within 240 mins at pH 5. The aerogel can also adsorb other toxic metal salts such as La3+ and Cu2+ with a capacity of 146 and 193 mg/g respectively. Furthermore, the aerogel structure can be acid washed removing 98% of the Pb2+ from the structure within three minutes. Overall, the data shows that GO alginate aerogels are highly effective at removing Pb2+ from water and the primary mechanism involved is ion exchange, although other phenomenon such as proton tunnelling may be a contributing factor to the ultra-high efficiency of the aerogel for Pb2+ remediation.


Assuntos
Água Potável/química , Grafite/química , Chumbo/química , Poluentes Químicos da Água/química , Purificação da Água/métodos , Adsorção , Alginatos/química , Biopolímeros , Humanos , Troca Iônica
13.
Aust Vet J ; 98(11): 546-549, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32743841

RESUMO

To determine the extent to which wild deer are contributing in the transmission of Fasciola hepatica (liver fluke) livers from deer shot by hunters, farmers undertaking population control on their farms and vertebrate pest controllers were collected and frozen. The livers were later thawed, sliced and examined for the presence of adult flukes or evidence of past infection. Livers from 19 deer were examined (18 fallow [Dama dama] and one sambar [Rusa unicolor]). Seventeen of the fallow deer were animals collected on farms near Jindabyne, New South Wales. The remaining fallow deer was collected in the Australian Capital Territory and one sambar deer was collected in north-eastern Victoria. Nine of the 17 deer (53%) from the Jindabyne area were either infected with Fasciola hepatica (liver fluke) or had thickened bile ducts indicating past infection. Infection levels in the infected animals varied widely from 3 liver fluke to over 50 per liver. No sign of infection was present in the deer from the Australian Capital Territory or Victoria. Fallow deer are wide-spread in the Jindabyne area and their population is increasing. It is likely their contribution to the maintenance and distribution of F. hepatica to livestock in the Jindabyne area, and in other livestock rearing areas of south-eastern Australia, is important and increasing.


Assuntos
Cervos , Fasciola hepatica , Animais , New South Wales/epidemiologia , Austrália do Sul , Vitória
14.
Environ Entomol ; 49(4): 956-962, 2020 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-32430509

RESUMO

Habitat disturbance has been found to facilitate the introduction of a wide range of species, including the red imported fire ant Solenopsis invicta Buren (Hymenoptera: Formicidae: Myrmicinae). Despite the link between S. invicta colonization and disturbance, little is known about how different intensities or types of disturbance might impact S. invicta populations. In this study, we used S. invicta populations in cattle pastures to understand how variation in disturbance type and frequency correlates with the density of S. invicta mounds. In total, 56 plots were surveyed for mound abundance during both the wet and dry seasons on a subtropical south Florida ranch. Explanatory variables were grouped into five categories based on disturbance type: 1) historic pasture conversion; 2) modern pasture management (mowing, dragging, chopping, or aerating); 3) grazing intensity (a measure vegetation height and dung pat abundance); 4) distance to human-made and natural localized disturbance (roads, ditches, and wetlands); and 5) abiotic conditions (soil temperature, soil moisture). Overall, the average number of mounds per plot was not significantly different between seasons, but was significantly higher in intensive pastures, which are converted to nonnative forage grasses than in seminative pastures during the dry season. Time since soil disturbance (aeration and chopping of pasture) was a significant predictor of S. invicta densities in both dry and wet seasons, with an increase in time since disturbance being associated with higher mound densities. Other forms of pasture management that did not disturb the soil, such as dragging and mowing, as well as distance to localized disturbances (wetlands, roads, and ditches) were not found to have a significant correlation in either season.


Assuntos
Formigas , Animais , Bovinos , Ecossistema , Florida , Humanos , Estações do Ano , Solo
15.
Phys Rev Lett ; 124(19): 192701, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32469543

RESUMO

The ^{12}C+^{12}C fusion reaction plays a critical role in the evolution of massive stars and also strongly impacts various explosive astrophysical scenarios. The presence of resonances in this reaction at energies around and below the Coulomb barrier makes it impossible to carry out a simple extrapolation down to the Gamow window-the energy regime relevant to carbon burning in massive stars. The ^{12}C+^{12}C system forms a unique laboratory for challenging the contemporary picture of deep sub-barrier fusion (possible sub-barrier hindrance) and its interplay with nuclear structure (sub-barrier resonances). Here, we show that direct measurements of the ^{12}C+^{12}C fusion cross section may be made into the Gamow window using an advanced particle-gamma coincidence technique. The sensitivity of this technique effectively removes ambiguities in existing measurements made with gamma ray or charged-particle detection alone. The present cross-section data span over 8 orders of magnitude and support the fusion-hindrance model at deep sub-barrier energies.

16.
Phys Rev Lett ; 124(15): 152501, 2020 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-32357059

RESUMO

The lifetimes of the first excited 2^{+} states in the N=Z nuclei ^{80}Zr, ^{78}Y, and ^{76}Sr have been measured using the γ-ray line shape method following population via nucleon-knockout reactions from intermediate-energy rare-isotope beams. The extracted reduced electromagnetic transition strengths yield new information on where the collectivity is maximized and provide evidence for a significant, and as yet unexplained, odd-odd vs even-even staggering in the observed values. The experimental results are analyzed in the context of state-of-the-art nuclear density-functional model calculations.

17.
Aust Vet J ; 98(3): 100-102, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32115680

RESUMO

Hydatid disease in beef cattle has been reported to be widespread throughout Australia, but cattle bred and raised in the Northern Territory were previously believed to be free of the disease. Between 2010 and 2016, 1061 cattle from the Northern Territory were slaughtered at a New South Wales abattoir and inspected for hydatid disease. The proportion of cattle reported infected with hydatid disease was 3.5%. Individual cattle identification numbers indicated that the cattle included in the study had most likely remained within the Northern Territory from birth until immediately prior to slaughter, so were assumed to have become infected within the region. We suspect that the sylvatic cycle of Echinococcus granulosus transmission could be responsible for infection of cattle in this region.


Assuntos
Doenças dos Bovinos , Equinococose/veterinária , Echinococcus granulosus , Carne Vermelha , Animais , Bovinos , New South Wales , Northern Territory
18.
Infect Prev Pract ; 2(3): 100033, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34368708

RESUMO

OXA-48 producers can be difficult to detect in clinical specimens due to phenotypic low-level resistance to carbapenems. Additionally, low infection rates make clinical specimens poor sentinels for the presence of OXA-48 producers within a healthcare institution. We report an outbreak of OXA-48-producing Klebsiella pneumoniae (OXAKp) that was discovered following culture of OXAKp in a urine specimen from a patient with no known risk factors for acquisition. Widespread screening across medical wards in the trust revealed evidence of transmission across several wards. Samples from 60 patients were positive for OXAKp. Five patients had OXAKp clinical infection, four of whom were treated with ceftazidime/avibactam. Variable number tandem repeat analysis of the OXAKp isolates revealed two predominant strain types clustered around two groups of wards. Infection prevention measures included isolation and cohort nursing of infected and colonized patients, restriction of affected ward areas to new admissions, stringent hand hygiene and use of personal protective equipment. Environmental cleaning of patient areas was carried out using chlorine-releasing disinfectants and hydrogen peroxide vapour. Entire wards were decanted to enable effective cleaning of empty ward areas. The outbreak lasted almost five months and is estimated to have cost around £400 000. During the course of the outbreak, there were five reported prescription and administration incidents related to confusion between ceftazidime and ceftazidime/avibactam. No patient harm resulted from these incidents and the implementation of brand name prescribing for ceftazidime/avibactam prevented further incidents.

19.
Br J Dermatol ; 182(4): 1026-1033, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31302935

RESUMO

OBJECTIVES: Because current guidelines recognise high-grade anal squamous intraepithelial lesions (HSILs) and low-grade SILs (LSILs), and recommend treatment of all HSILs although not all progress to cancer, this study aims to distinguish transforming and productive HSILs by grading immunohistochemical (IHC) biomarkers p16INK 4a (p16) and E4 in low-risk human papillomavirus (lrHPV) and high-risk (hr)HPV-associated SILs as a potential basis for more selective treatment. METHODS: Immunostaining for p16 and HPV E4 was performed and graded in 183 biopsies from 108 HIV-positive men who have sex with men. The causative HPV genotype of the worst lesion was identified using the HPV SPF10-PCR-DEIA-LiPA25 version 1 system, with laser capture microdissection for multiple infections. The worst lesions were scored for p16 (0-4) to identify activity of the hrHPV E7 gene, and panHPV E4 (0-2) to mark HPV production and life cycle completion. RESULTS: There were 37 normal biopsies, 60 LSILs and 86 HSILs, with 85% of LSILs caused by lrHPV and 93% of HSILs by hrHPV. No normal biopsy showed E4, but 43% of LSILs and 37% of HSILs were E4 positive. No differences in E4 positivity rates were found between lrHPV and hrHPV lesions. Most of the lesions caused by lrHPV (90%) showed very extensive patchy p16 staining; p16 grade in HSILs was variable, with frequency of productive HPV infection dropping with increasing p16 grade. CONCLUSIONS: Combined p16/E4 IHC identifies productive and nonproductive HSILs associated with hrHPV within the group of HSILs defined by the Lower Anogenital Squamous Terminology recommendations. This opens the possibility of investigating selective treatment of advanced transforming HSILs caused by hrHPV, and a 'wait and see' policy for productive HSILs. What's already known about this topic? For preventing anal cancer in high-risk populations, all patients with high-grade squamous intraepithelial lesions (HSILs) are treated, even though this group of lesions is heterogeneous, the histology is variable and regression is frequent. What does this study add? By adding human papillomavirus (HPV) E4 immunohistochemistry to p16 INK4a (p16), and grading expression of both markers, different biomarker expression patterns that reflect the heterogeneity of HSILs can be identified. Moreover, p16/E4 staining can separate high-risk HPV-associated HSILs into productive and more advanced transforming lesions, providing a potential basis for selective treatment.


Assuntos
Alphapapillomavirus , Infecções por Papillomavirus , Minorias Sexuais e de Gênero , Lesões Intraepiteliais Escamosas , Biomarcadores Tumorais , Inibidor p16 de Quinase Dependente de Ciclina , Homossexualidade Masculina , Humanos , Masculino , Papillomaviridae/genética , Infecções por Papillomavirus/complicações
20.
Phys Rev Lett ; 123(3): 032502, 2019 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-31386486

RESUMO

In the past two decades, deeply virtual Compton scattering of electrons has been successfully used to advance our knowledge of the partonic structure of the free proton and investigate correlations between the transverse position and the longitudinal momentum of quarks inside the nucleon. Meanwhile, the structure of bound nucleons in nuclei has been studied in inclusive deep-inelastic lepton scattering experiments off nuclear targets, showing a significant difference in longitudinal momentum distribution of quarks inside the bound nucleon, known as the EMC effect. In this Letter, we report the first beam spin asymmetry (BSA) measurement of exclusive deeply virtual Compton scattering off a proton bound in ^{4}He. The data used here were accumulated using a 6 GeV longitudinally polarized electron beam incident on a pressurized ^{4}He gaseous target placed within the CLAS spectrometer in Hall-B at the Thomas Jefferson National Accelerator Facility. The azimuthal angle (ϕ) dependence of the BSA was studied in a wide range of virtual photon and scattered proton kinematics. The Q^{2}, x_{B}, and t dependencies of the BSA on the bound proton are compared with those on the free proton. In the whole kinematical region of our measurements, the BSA on the bound proton is smaller by 20% to 40%, indicating possible medium modification of its partonic structure.

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