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1.
PLoS One ; 16(11): e0259525, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34727134

RESUMO

INTRODUCTION: Alcohol and substance misuse are a public health priority. The World Health Organisation (WHO) estimates that harmful alcohol use accounts for 5.1% of the global burden of disease and that 35.6 million people worldwide are affected by substance misuse. The Coronavirus Disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has disrupted delivery of face-to-face alcohol and substance misuse interventions and has forced the development of alternative remote interventions or adaptation to existing ones. Although existing research on remote interventions suggests they might be as effective as face-to-face delivery, there has been a lack of systematic exploration of their content, the experience of service users, and their effectiveness for behavioural outcomes. This review will provide a narrative synthesis of the behaviour change techniques (BCT) contained in interventions for alcohol and/or substance misuse and their association with effectiveness. METHODS AND ANALYSIS: Systematic searches will be conducted in MEDLINE, Scopus, PsycINFO (ProQuest), and the Cochrane Library. Included studies will be those reporting remote interventions focusing on alcohol and/or substance misuse among adults living in the community and which have a primary behaviour change outcome (i.e., alcohol levels consumed). Data extraction will be conducted by one author and moderated by a second, and risk of bias and behaviour change technique (BCT) coding will be conducted by two authors independently. A narrative synthesis will be undertaken focussing upon the association of BCTs with intervention effectiveness using promise ratios. PATIENT AND PUBLIC INVOLVEMENT (PPI): The Public Involvement in Research Group (PIRG), part of the NIHR-funded PHIRST, will be involved in refining the review questions, eligibility criteria, data synthesis and dissemination. DISSEMINATION: Dissemination will be through an academic peer reviewed publication, alongside other outputs to be shared with non-academic policy, professional, and public audiences, including local authorities, service users and community organisations.


Assuntos
Alcoolismo/terapia , Terapia Comportamental , Intervenção Baseada em Internet , Transtornos Relacionados ao Uso de Substâncias/terapia , Etanol , Humanos , Intervenção Baseada em Internet/tendências
2.
Emerg Microbes Infect ; : 1-27, 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34821529

RESUMO

Melioidosis is a serious infectious disease endemic in Southeast Asia, Northern Australia and has been increasingly reported in other tropical and subtropical regions in the world. Percutaneous inoculation through cuts and wounds on the skin is one of the major modes of natural transmission. Despite cuts in skin being a major route of entry, very little is known about how the causative bacterium Burkholderia pseudomallei initiates an infection at the skin and the disease manifestation at the skin known as cutaneous melioidosis. One key issue is the lack of suitable and relevant infection models. Employing an in vitro 2D keratinocyte cell culture, a 3D skin equivalent fibroblast-keratinocyte co-culture and ex vivo organ culture from human skin, we developed infection models utilizing surrogate model organism Burkholderia thailandensis to investigate Burkholderia-skin interactions. Collectively, these models show that the bacterial infection was largely limited at the wound's edge. Infection impedes wound closure, triggers inflammasome activation and cellular extrusion in the keratinocytes as a potential way to control bacterial infectious load at the skin. However, extensive infection over time could result in the epidermal layer being sloughed off, potentially contributing to formation of skin lesions.

3.
Nucleic Acids Res ; 49(20): 11938-11958, 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34751406

RESUMO

The 2A protein of Theiler's murine encephalomyelitis virus (TMEV) acts as a switch to stimulate programmed -1 ribosomal frameshifting (PRF) during infection. Here, we present the X-ray crystal structure of TMEV 2A and define how it recognises the stimulatory RNA element. We demonstrate a critical role for bases upstream of the originally predicted stem-loop, providing evidence for a pseudoknot-like conformation and suggesting that the recognition of this pseudoknot by beta-shell proteins is a conserved feature in cardioviruses. Through examination of PRF in TMEV-infected cells by ribosome profiling, we identify a series of ribosomal pauses around the site of PRF induced by the 2A-pseudoknot complex. Careful normalisation of ribosomal profiling data with a 2A knockout virus facilitated the identification, through disome analysis, of ribosome stacking at the TMEV frameshifting signal. These experiments provide unparalleled detail of the molecular mechanisms underpinning Theilovirus protein-stimulated frameshifting.

4.
J Vasc Access ; : 11297298211053447, 2021 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-34763555

RESUMO

BACKGROUND: The adoption rate of point of care ultrasound (POCUS) for the confirmation of central venous catheter (CVC) positioning and exclusion of post procedure pneumothorax is low despite advantages in workflow compared to traditional chest X-ray (CXR). To explore why, we convened focus groups to address barriers and facilitators of implementation for POCUS guided CVC confirmation and de-implementation of post-procedure CXR. METHODS: We conducted focus groups with emergency medicine and critical care providers to discuss current practices in POCUS for CVC confirmation. The semi-structured focus group interview guide was informed by the Consolidated Framework for Implementation Research (CFIR). We performed qualitative content analysis of the resulting transcripts using a consensual qualitative research approach (NVivo software), aiming to identify priority categories that describe the barriers and facilitators of POCUS guided CVC confirmation. RESULTS: The coding dictionary of barriers and facilitators consisted of 21 codes from the focus group discussions. Our qualitative analysis revealed that 12 codes emerged spontaneously (inductively) within the focus group discussions and aligned directly to CFIR constructs. Common barriers included provider influences (e.g. knowledge and beliefs about POCUS for CVC confirmation), external network (e.g. societal guidelines, ancillary staff, and consultants), and inertia (habit or reflexive processes). Common facilitators included ultrasound protocol advantage and champions. Time and provider outcomes (cognitive offload, ownership, and independence) emerged as early barriers but late facilitators. CONCLUSION: Our qualitative analysis demonstrates real and perceived barriers against implementation of POCUS for CVC position confirmation and pneumothorax exclusion. Our findings discovered organizational and personal constructs that will inform development of multifaceted strategies toward implementation of POCUS after CVC insertion.

5.
Gynecol Oncol ; 163(3): 578-582, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34674889

RESUMO

OBJECTIVE: To identify genetic variants associated with chemotherapy-induced peripheral neuropathy (CIPN) symptoms among gynecologic cancer survivors and determine the variants' predictive power in addition to age and clinical factors at time of diagnosis. METHODS: Participants of a prospective cohort study on gynecologic cancers provided a DNA saliva sample and reported CIPN symptoms (FACT/GOG-Ntx). Genotyping of 23 single nucleotide polymorphisms (SNPs) previously identified as related to platinum- or taxane-induced neuropathy was performed using iPLEX Gold method. Risk allele carrier frequencies of 19 SNPs that passed quality checks were compared between those with/without high CIPN symptoms using logistic regression, adjusting for age. Receiver operating characteristic (ROC) curves using clinical risk factors (age, diabetes, BMI, Charlson Comorbidity Index, previous cancer diagnosis) with and without the identified SNPs were compared. RESULTS: 107 individuals received platinum or taxane-based chemotherapy and provided sufficient DNA for analysis. Median age was 65.1 years; 39.6% had obesity and 8.4% diabetes; most had ovarian (58.9%) or uterine cancer (29.0%). Two SNPs were significantly associated with high CIPN symptomatology: rs3753753 in GPX7, OR = 2.55 (1.13, 5.72) and rs139887 in SOX10, 2.66 (1.18, 6.00). Including these two SNPs in a model with clinical characteristics led to an improved AUC for CIPN symptomatology (0.65 vs. 0.74, p = 0.04). CONCLUSIONS: Genetic and clinical characteristics were predictive of higher CIPN symptomatology in gynecologic cancer survivors, and combining these factors resulted in superior predictive power compared with a model with clinical factors only. Prospective validation and assessment of clinical utility are warranted.

6.
Artigo em Inglês | MEDLINE | ID: mdl-34716662

RESUMO

AIM: Early intervention for people experiencing first episode psychosis is a priority, and keyworkers are vital to such services. However, keyworkers' roles in addressing first episode psychosis patients' physical health are under researched. This study addresses this knowledge gap by evaluating a keyworker-mediated intervention promoting physical health among first episode psychosis patients. METHODS: The study was informed by the Medical Research Council's Framework for Complex Interventions to Improve Health. First episode psychosis participants were recruited from three Irish mental health services. The intervention was evaluated in terms of its feasibility/acceptability. RESULTS: Feasibility outcomes were mixed (recruitment rate = 24/68 [35.3%]; retention rate = 18/24 [75%]). The baseline sample was predominantly male (M:F ratio = 13:6; Med age = 25 y; IQR = 23-42 y). Common health issues among participants included overweightness/obesity (n = 11) and substance use (smoking/alcohol consumption [n = 19]). Participants' initial health priorities included exercising more (n = 10), improving diet (n = 6), weight loss (n = 7) and using various health/healthcare services. The intervention's acceptability was evidenced by the appreciation participants had for physical health keyworkers' support, as well as the healthy lifestyle, which the intervention promoted. Acceptability was somewhat compromised by a low-recruitment rate, variable linkages between keyworkers and general practitioners (GPs) and COVID-19 restrictions. CONCLUSIONS: Physical health-oriented keyworker interventions for first episode psychosis patients show promise and further evaluation of such initiatives is warranted. Future interventions should be mindful of participant recruitment challenges, strategies to enhance relationships between keyworkers and GPs, and if necessary, they should mitigate COVID-19 restrictions' impacts on care.

7.
Biomed Phys Eng Express ; 7(6)2021 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-34644679

RESUMO

Super-resolution ultrasound (SR-US) imaging allows visualization of microvascular structures as small as tens of micrometers in diameter. However, use in the clinical setting has been impeded in part by ultrasound (US) acquisition times exceeding a breath-hold and by the need for extensive offline computation. Deep learning techniques have been shown to be effective in modeling the two more computationally intensive steps of microbubble (MB) contrast agent detection and localization. Performance gains by deep networks over conventional methods are more than two orders of magnitude and in addition the networks can localize overlapping MBs. The ability to separate overlapping MBs allows use of higher contrast agent concentrations and reduces US image acquisition time. Herein we propose a fully convolutional neural network (CNN) architecture to perform the operations of MB detection as well as localization in a single model. Termed SRUSnet, the network is based on the MobileNetV3 architecture modified for 3-D input data, minimal convergence time, and high-resolution data output using a flexible regression head. Also, we propose to combine linear B-mode US imaging and nonlinear contrast pulse sequencing (CPS) which has been shown to increase MB detection and further reduce the US image acquisition time. The network was trained within silicodata and tested onin vitrodata from a tissue-mimicking flow phantom, and onin vivodata from the rat hind limb (N = 3). Images were collected with a programmable US system (Vantage 256, Verasonics Inc., Kirkland, WA) using an L11-4v linear array transducer. The network exceeded 99.9% detection accuracy onin silicodata. The average localization accuracy was smaller than the resolution of a pixel (i.e.λ/8). The average processing time on a Nvidia GeForce 2080Ti GPU was 64.5 ms for a 128 × 128-pixel image.

9.
PLoS Pathog ; 17(8): e1009824, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34398933

RESUMO

The herpes simplex virus (HSV)-1 protein pUL21 is essential for efficient virus replication and dissemination. While pUL21 has been shown to promote multiple steps of virus assembly and spread, the molecular basis of its function remained unclear. Here we identify that pUL21 is a virus-encoded adaptor of protein phosphatase 1 (PP1). pUL21 directs the dephosphorylation of cellular and virus proteins, including components of the viral nuclear egress complex, and we define a conserved non-canonical linear motif in pUL21 that is essential for PP1 recruitment. In vitro evolution experiments reveal that pUL21 antagonises the activity of the virus-encoded kinase pUS3, with growth and spread of pUL21 PP1-binding mutant viruses being restored in adapted strains where pUS3 activity is disrupted. This study shows that virus-directed phosphatase activity is essential for efficient herpesvirus assembly and spread, highlighting the fine balance between kinase and phosphatase activity required for optimal virus replication.

10.
Arch Dis Child ; 2021 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-34312164

RESUMO

OBJECTIVE: To explore perspectives of paediatric cardiac and palliative care professionals on providing palliative care to children with complex cardiac conditions. DESIGN: A national survey including closed-ended and open-ended questions as well as clinical scenarios designed to capture referral practices, attitudes towards palliative care, confidence delivering key components of palliative care and perspectives on for whom to provide palliative care. Responses to closed-ended questions and scenarios were analysed using descriptive statistics. Open-ended responses were analysed thematically. PARTICIPANTS: Paediatric cardiac and palliative care professionals caring for children with complex cardiac conditions in the UK. RESULTS: 177 professionals (91 cardiac care and 86 palliative care) responded. Aspects of advance care planning were the most common reasons for referral to palliative care. Palliative care professionals reported greater confidence than cardiac colleagues with such discussions. Clinicians agreed that children with no further surgical management options, comorbid genetic disorders, antenatal diagnosis of a single ventricle, ventricular device in situ, symptomatic heart failure and those awaiting heart transplantation would benefit from palliative care involvement. CONCLUSIONS: Components of palliative care, such as advance care planning, can be provided by cardiac care professionals alongside the disease-directed care of children with complex cardiac conditions. Further research and training are needed to address confidence levels in cardiac care professionals in delivering components of palliative care as well as clarification of professional roles and parent preferences in delivery of family-centred care for children with complex cardiac conditions.

11.
Lancet HIV ; 8(8): e486-e494, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34217426

RESUMO

BACKGROUND: Daily pre-exposure prophylaxis (PrEP) is effective in preventing HIV, but few long-term data are available on effectiveness and adherence in real-world settings. Here, we report trends in HIV incidence over 3 years in individuals at high risk who were prescribed PrEP in New South Wales (NSW), as well as adherence before the transition to subsidised PrEP. METHODS: Expanded PrEP Implementation in Communities-New South Wales (EPIC-NSW) was a pragmatic, prospective, single-arm, implementation study of daily, oral PrEP in 31 sites (sexual health clinics, general practices, and a hospital) in NSW, Australia. Eligible participants were HIV-negative adults (aged ≥18 years) who were at high risk of HIV infection as defined in local PrEP guidelines. Participants were prescribed coformulated (once-daily, oral tablet) tenofovir disoproxil fumarate (300 mg) and emtricitabine (200 mg) as HIV PrEP and were followed up with HIV testing, sexually transmitted infection testing, and PrEP dispensing. Originally planned for 3700 participants followed for 1 year, the study was expanded so that all eligible participants in the state could obtain PrEP and extended until publicly subsidised PrEP became available in Australia. The primary outcome was new HIV infection among all participants who were dispensed PrEP at least once and had at least one follow-up HIV test result. Adherence was estimated by medication possession ratio (MPR), defined as the proportion of PrEP pills dispensed in 90 days, assuming daily dosing. This study is registered with ClinicalTrials.gov, NCT02870790. FINDINGS: Between March 1, 2016, and April 30, 2018, we enrolled 9709 participants. 9596 participants were dispensed PrEP, of whom 9448 (98·3%) were gay or bisexual men. Participants were followed up until March 31, 2019, with at least one follow-up HIV test available in 9520 (99·2%) participants. Mean MPR declined from 0·93 to 0·64 from the first to the ninth quarter. There were 30 HIV seroconversions over 18 628 person-years, an incidence of 1·61 per 1000 person-years (95% CI 1·13-2·30). Being younger, living in a postcode with fewer gay men, reporting more risk behaviours at baseline, and having an MPR of less than 0·6 were each univariately associated with increased HIV incidence. In the final year of follow-up, when PrEP was mostly purchased rather than provided free by the study, HIV incidence remained low at 2·24 per 1000 person-years (1·46-3·44). INTERPRETATION: HIV incidence remained low over up to 3 years of follow-up, including during a transition from study-provided to publicly subsidised PrEP. In a setting of affordable PrEP and associated health-care services, very low HIV incidence of 1 to 2 per 1000 person-years can be maintained in gay and bisexual men who were previously at high risk. FUNDING: New South Wales Ministry of Health, Australian Capital Territory Health Directorate, Gilead Sciences.


Assuntos
Bissexualidade , Infecções por HIV/prevenção & controle , Homossexualidade Masculina , Profilaxia Pré-Exposição , Administração Oral , Adolescente , Adulto , Idoso , Feminino , Infecções por HIV/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , New South Wales/epidemiologia , Gravidez , Estudos Prospectivos , Adulto Jovem
12.
J Prim Care Community Health ; 12: 21501327211028713, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34219508

RESUMO

Pre-Exposure Prophylaxis (PrEP) has been shown to be an effective method of HIV prevention for men who have sex with-men (MSM) and -transgender women (MSTGWs), serodiscordant couples, and injection drug users; however fewer than 50 000 individuals currently take this regimen. Knowledge of PrEP is low among healthcare providers and much of this lack of knowledge stems from the lack or exposure to PrEP in medical school. We conducted a cross sectional survey of medical schools in the United States to assess the degree to which PrEP for HIV prevention is taught. The survey consisted Likert scale questions assessing how well the students were prepared to perform each skill associated with PrEP delivery, as well as how PrEP education was delivered to students. We contacted 141 medical schools and 71 responded to the survey (50.4%). PrEP education was only reported to be offered at 38% of schools, and only 15.4% reported specific training for Lesbian, Gay, Bisexual, and Transgender (LGBT) patients. The most common delivery methods of PrEP content were didactic sessions with 11 schools reporting this method followed by problem-based learning, direct patient contact, workshops, and small group discussions. Students were more prepared to provide PrEP to MSM compared to other high-risk patients. Few medical schools are preparing their students to prescribe PrEP upon graduation. Further, there is a need to increase the number of direct patient contacts or simulations for students to be better prepared.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Profilaxia Pré-Exposição , Minorias Sexuais e de Gênero , Fármacos Anti-HIV/uso terapêutico , Estudos Transversais , Feminino , Infecções por HIV/prevenção & controle , Homossexualidade Masculina , Humanos , Masculino , Faculdades de Medicina , Estados Unidos
13.
Pilot Feasibility Stud ; 7(1): 145, 2021 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-34311784

RESUMO

BACKGROUND: Male condoms are effective in preventing common sexually transmitted infections (STIs) and unintended pregnancy, if used correctly and consistently. However, condom use errors and problems are common and young people report negative experiences, such as reduced pleasure. The Kinsey Institute Home-Based Exercises for Responsible Sex (KIHERS) is a novel condom promotion intervention for young women, which aims to reduce condom errors and problems, increase self-efficacy and improve attitudes towards condoms, using a pleasure-focussed approach. The study objective was to test the operability, viability and acceptability of an adapted version of the KIHERS intervention with young women aged 16-25 years in the United Kingdom (UK) (Home-Based Exercises for Responsible Sex-UK (HERS-UK). METHODS: A repeated-measures single-arm design was used, with a baseline (T1) and two follow-up assessments (T2 and T3), conducted 4 weeks and 8 weeks post intervention over a 3-month period. Participants were provided a condom kit containing different condoms and lubricants and were asked to experiment with condoms alone using a dildo and/or with a sexual partner. Ten process evaluation interviews were conducted post intervention. RESULTS: Fifty-five young women received the intervention; 36 (65%) completed T2 and 33 (60%) completed T3. Condom use errors and problems decreased, self-efficacy increased and attitudes towards condoms improved significantly. The proportion of participants who reported using a condom for intercourse in the past 4 weeks increased from T1 (20; 47%) to T2 (27; 87%) and T3 (23; 77%) and using lubricant with a condom for intercourse increased from T1 (6; 30%) to T2 (13; 48%)) and T3 (16; 70%). However, motivation to use condoms did not change. Cronbach's alpha scores indicated good internal consistency of measures used. Qualitative data provided strong evidence for the acceptability of the intervention. CONCLUSIONS: HERS-UK was implemented as intended and the recruitment strategy was successful within a college/university setting. This feasibility study provided an early indication of the potential effectiveness and acceptability of the intervention, and the benefits of using a pleasure-focussed approach with young women. Measures used captured change in outcome variables and were deemed fit for purpose. Future research should explore cost-effectiveness of this intervention, in a large-scale controlled trial using a diverse sample and targeting young women most at risk of STIs.

14.
PLoS Pathog ; 17(6): e1009644, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34138976

RESUMO

Coronavirus infection induces the unfolded protein response (UPR), a cellular signalling pathway composed of three branches, triggered by unfolded proteins in the endoplasmic reticulum (ER) due to high ER load. We have used RNA sequencing and ribosome profiling to investigate holistically the transcriptional and translational response to cellular infection by murine hepatitis virus (MHV), often used as a model for the Betacoronavirus genus to which the recently emerged SARS-CoV-2 also belongs. We found the UPR to be amongst the most significantly up-regulated pathways in response to MHV infection. To confirm and extend these observations, we show experimentally the induction of all three branches of the UPR in both MHV- and SARS-CoV-2-infected cells. Over-expression of the SARS-CoV-2 ORF8 or S proteins alone is itself sufficient to induce the UPR. Remarkably, pharmacological inhibition of the UPR greatly reduced the replication of both MHV and SARS-CoV-2, revealing the importance of this pathway for successful coronavirus replication. This was particularly striking when both IRE1α and ATF6 branches of the UPR were inhibited, reducing SARS-CoV-2 virion release (~1,000-fold). Together, these data highlight the UPR as a promising antiviral target to combat coronavirus infection.


Assuntos
Antivirais/farmacologia , COVID-19/tratamento farmacológico , Vírus da Hepatite Murina/efeitos dos fármacos , Resposta a Proteínas não Dobradas/efeitos dos fármacos , Fator 6 Ativador da Transcrição/metabolismo , Animais , Antivirais/uso terapêutico , Linhagem Celular , Chlorocebus aethiops , Sistemas de Liberação de Medicamentos , Endorribonucleases/metabolismo , Células HEK293 , Humanos , Camundongos , Proteínas Serina-Treonina Quinases/metabolismo , RNA-Seq , Células Vero , Proteínas Virais/metabolismo , Replicação Viral/efeitos dos fármacos
15.
Artigo em Inglês | MEDLINE | ID: mdl-34181537

RESUMO

The use of super-resolution ultrasound (SR-US) imaging greatly improves visualization of microvascular structures, but clinical adoption is limited by long imaging times. This method depends on detecting and localizing isolated microbubbles (MBs), forcing the use of a dilute contrast agent concentration. Contrast-enhanced ultrasound (CEUS) image acquisition times as long as minutes arise as the localization of thousands of MBs are acquired to form a complete SR-US image. In this article, we explore the use of nonlinear CEUS strategies using nonlinear fundamental contrast pulse sequencing (CPS) to increase the contrast-to-tissue ratio (CTR) and compare MB detection effectiveness to linear B-mode CEUS imaging. The CPS compositions of amplitude modulation (AM), pulse inversion (PI), and a combination of the two (AMPI) were studied. A simulation study combined the Rayleigh-Plesset-Marmottant (RPM) model of MB characteristics and a nonlinear tissue model using the k-Wave toolbox for MATLAB (MathWorks Inc., Natick, MA, USA). Validation was conducted using an in vitro flow phantom and in vivo in the rat hind-limb. Imaging was performed with a programmable US scanner (Vantage 256, Verasonics Inc., Kirkland, WA, USA) and customized to transmit a set of basis US pulses from which both B-mode US (frame rate (FR) of 800 Hz) and multiple nonlinear CPS compositions (FR of 200 Hz) could be assessed from identical in vitro and in vivo datasets using a near simultaneous method. The simulations suggest that MB characteristics, such as diameter and motion, help to predict which US imaging strategy will enhance MB detection. The in vitro and in vivo US imaging studies revealed that different subpopulations of polydisperse MB contrast agents were detected by linear imaging and by each different nonlinear CPS composition. The most effective single imaging strategy at a 200-Hz FR was found to be B-mode US imaging. However, a combination of B-mode US imaging with a nonlinear CPS imaging strategy was more effective in detecting MBs in vivo at all depths and was shown to shorten image acquisition time by an average of 33.3%-76.7% when combining one or more CPS sequences.


Assuntos
Meios de Contraste , Microbolhas , Animais , Imagens de Fantasmas , Ratos , Ultrassom , Ultrassonografia
16.
Inquiry ; 58: 469580211017666, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34027712

RESUMO

There is growing evidence that pre-exposure prophylaxis (PrEP) prevents HIV acquisition. However, in the United States, approximately only 4% of people who could benefit from PrEP are currently receiving it, and it is estimated only 1 in 5 physicians has ever prescribed PrEP. We conducted a scoping review to gain an understanding of physician-identified barriers to PrEP provision. Four overarching barriers presented in the literature: Purview Paradox, Patient Financial Constraints, Risk Compensation, and Concern for ART Resistance. Considering the physician-identified barriers, we make recommendations for how physicians and students may work to increase PrEP knowledge and competence along each stage of the PrEP cascade. We recommend adopting HIV risk assessment as a standard of care, improving physician ability to identify PrEP candidates, improving physician interest and ability in encouraging PrEP uptake, and increasing utilization of continuous care management to ensure retention and adherence to PrEP.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Médicos , Profilaxia Pré-Exposição , Estudantes de Medicina , Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/prevenção & controle , Humanos , Estados Unidos
17.
Cancer Rep (Hoboken) ; : e1461, 2021 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-34057316

RESUMO

BACKGROUND: Delays in care and increased risk for mental health diagnoses put individuals identifying as a sexual minority with cancer at risk for decreased quality of life. AIM: To assess psychosocial health among sexual minority gynecologic cancer survivors, we compared self-reported quality of life and psychosocial measures between individuals diagnosed with gynecologic cancers identifying as lesbian/gay/bisexual (LGB) and heterosexual. METHODS AND RESULTS: English-speaking adults with gynecologic cancers were invited to participate in an ongoing cohort survey study. Quality of life and psychosocial measures included the Functional Assessment of Cancer Therapy-General, Distress Thermometer (distress), Patient Health Questionnaire-8 (depression), General Anxiety Disorder-7 (anxiety), and Post-traumatic Stress Disorder Checklist for DSM-5 (post-traumatic stress disorder; PTSD). Measures were compared by self-reported sexual orientation (heterosexual vs. LGB) using descriptive statistics (frequencies and means) and linear and logistic regression models, adjusting for college education. Of 814 patients invited, 457 enrolled (56.1%) and 401 (92.6%) completed the survey and provided information on their sexuality. All but one self-identified as cisgender women and 22 (5.5%) as LGB. LGB participants were more likely to have completed college (68.2% vs. 40.1%, p = .009) but were otherwise similar across demographic and clinical characteristics. Quality of life and distress scores were similar between groups. LGB participants, compared to heterosexual, reported higher rates of depression (31.8% vs. 10.6%, adjusted odds ratio [OR] = 4.1 [95% confidence interval [CI]: 1.6-11.0], p = .004), anxiety (25.0% vs. 7.1%, adjusted OR = 5.4 [95% CI: 1.7-16.7], p= .004), and PTSD (13.6% vs. 3.5%, adjusted OR = 4.2 [95% CI: 1.1-16.3], p = .04). CONCLUSION: LGB participants reported poorer emotional health following a gynecologic cancer diagnosis than heterosexual participants. Our data suggest this population may need additional resources and support during and after their cancer diagnosis. Future work is needed to identify additional risk factors and the underlying sources of these disparities in order to improve patient care and wellness in this population.

18.
Int J Mol Sci ; 22(6)2021 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-33807069

RESUMO

Studies implicating an important role for apyrase (NTPDase) enzymes in plant growth and development began appearing in the literature more than three decades ago. After early studies primarily in potato, Arabidopsis and legumes, especially important discoveries that advanced an understanding of the biochemistry, structure and function of these enzymes have been published in the last half-dozen years, revealing that they carry out key functions in diverse other plants. These recent discoveries about plant apyrases include, among others, novel findings on its crystal structures, its biochemistry, its roles in plant stress responses and its induction of major changes in gene expression when its expression is suppressed or enhanced. This review will describe and discuss these recent advances and the major questions about plant apyrases that remain unanswered.


Assuntos
Apirase/química , Apirase/metabolismo , Proteínas de Plantas/química , Proteínas de Plantas/metabolismo , Apirase/antagonistas & inibidores , Apirase/genética , Domínio Catalítico , Fenômenos Químicos , Descoberta de Drogas , Inibidores Enzimáticos/farmacologia , Regulação da Expressão Gênica de Plantas , Modelos Moleculares , Proteínas de Plantas/antagonistas & inibidores , Proteínas de Plantas/genética , Conformação Proteica , Relação Estrutura-Atividade
19.
BMC Public Health ; 21(1): 602, 2021 03 27.
Artigo em Inglês | MEDLINE | ID: mdl-33773593

RESUMO

BACKGROUND: There is growing evidence that a range of pre-injury, injury related and post-injury factors influence social and health outcomes across the injury severity spectrum. This paper documents health related outcomes for people with mild, moderate and severe injury after motor vehicle crash (MVC) injuries in New South Wales, Australia. METHODS: This inception cohort study followed 2019 people injured in MVCs, for 6 and 12 months post-injury. We categorised moderate injury as hospital length-of-stay (LOS) of 2-6 days and Injury Severity Score (ISS) of 4-11, while severe injury as LOS ≥7 days or ISS ≥ 12. We examined differences in paid work status, 12-Item Short Form Survey (SF12), EQ-5D and World Health Organisation Disability Assessment Schedule II (WHODAS) outcomes longitudinally from baseline to 12 months between levels of injury severity using linear mixed models for repeated measures. We first considered minimally sufficient adjustment factors (age, sex, crash role, perceived danger in crash, pre-injury health, pre-injury EQ-5D, recruitment source), and then more extensive adjustments including post-injury factors. The presence of mediating pathways for SF-12 Physical Component Summary (PCS) and Mental Component Summary (MCS) via post-injury factors was evaluated. RESULTS: Based on hospital length of stay (LOS), 25 and 10% of participants sustained moderate and severe injuries, respectively, while 43 and 4% had these injuries based on ISS. Twelve months post-injury LOS ≥7 days versus ≤1 day was associated with an estimated 9 units lower mean SF12 PCS using a minimally sufficient adjustment model, and LOS ≥ 7 days was associated with a 3 units lower mean SF12 MCS score. Mediation analyses (LOS ≥ 7 days vs ≤1 day) found for SF12 MCS outcomes, effects of injury severity were small and mostly indirect (direct effect - 0.03, indirect effect - 0.22). Whereas for SF12 PCS outcomes the effect of having a more severe injury rather than mild were both direct and indirect (direct effect - 0.50, indirect effect - 0.38). CONCLUSIONS: Individuals with severe injuries (those with LOS ≥ 7 days and ISS 12+) had poorer recovery 12 months after the injury. In addition, post-injury mediators have an important role in influencing long-term health outcomes. TRIAL REGISTRATION: Australia New Zealand Clinical trial registry identification number - ACTRN12613000889752 .


Assuntos
Acidentes de Trânsito , Ferimentos e Lesões , Austrália/epidemiologia , Estudos de Coortes , Humanos , Escala de Gravidade do Ferimento , Veículos Automotores , New South Wales/epidemiologia , Qualidade de Vida , Ferimentos e Lesões/epidemiologia
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