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1.
Nicotine Tob Res ; 26(11): 1463-1471, 2024 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-38160709

RESUMO

INTRODUCTION: A method for delivering vaporized nicotine to animals has been developed using e-cigarette devices. The present experiment was designed to measure the effects of e-cigarette nicotine on pubertal onset and development of reproductive behavior in female and male Long-Evans rats. AIM AND METHODS: Rats received daily 10-min sessions of electronic-cigarette vaporized nicotine (5% Virginia Tobacco JUUL Pods) or room air in a whole-body exposure chamber (postnatal day 28-31). Pubertal onset was monitored daily (ie, vaginal opening in females, preputial separation in males). Two weeks later, rats were tested for sexual motivation using the partner-preference paradigm, whereby subjects were given the opportunity to approach either a sexual partner or a same-sex social partner. Four weeks later, partner preference was assessed again, 10 min after rats were re-exposed to their same prepubertal treatment. RESULTS: We found that prepubescent electronic-cigarette vaporized nicotine disrupted puberty and sexual motivation in female but not male rats. In vaped females, vaginal opening was delayed and less time was spent with the male stimulus compared to room-air controls. In contrast, no effect of e-cigarette vapor was observed on pubertal onset or on any measures of sexual behavior in male rats. No effects were observed in either female or male rats on the second partner-preference test. CONCLUSIONS: Prepubescent vaporized nicotine affected the development of reproductive physiology and behavior in female rats but not in male rats, whereas an additional acute exposure to nicotine vapor had no effect in either female or male adult rats. IMPLICATIONS: Given the prevalence of increasingly younger users, more animal research is needed to explore the effects of e-cigarette smoking on multiple developmental systems including reproductive physiology and behavior. This model could be useful in exploring multiple behavioral and physiological endpoints in both sexes. Adjustments to the duration of exposure and control conditions will be necessary for future experiments to best model human use.


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Motivação , Ratos Long-Evans , Comportamento Sexual Animal , Maturidade Sexual , Animais , Masculino , Feminino , Ratos , Comportamento Sexual Animal/efeitos dos fármacos , Motivação/efeitos dos fármacos , Maturidade Sexual/efeitos dos fármacos , Nicotina/farmacologia , Vaping
2.
Reprod Health ; 20(Suppl 1): 193, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38840263

RESUMO

BACKGROUND: Medical abortion with mifepristone and misoprostol can be provided up to 63 days' gestation in India. This accounts for 67.5 percent of all abortions in the country. We conducted an assessment to determine the availability of medical abortion medicines, specifically the combi-pack, in India. METHODS: We applied the World Health Organization landscape assessment protocol at the national level. The assessment protocol included a five-step adaptation of an existing availability framework, including online data collection, desk review, country-level key informant interviews, and an analysis to identify barriers and opportunities to improve medical abortion availability. The assessment was conducted between August and March 2021. RESULTS: Medicines for medical abortion are included in the national essential drug list and available with prescription in India. The assessment identified 42 combi-pack products developed by 35 manufacturers. The quality of medical abortion medicines is regulated by national authorities; but as health is devolved to states, there are significant inter-state variations. This is seen across financing, procurement, manufacturing, and monitoring mechanisms for quality assurance of medical abortion medicines prior to distribution. There is a need to strengthen supply chain systems, ensure consistent availability of trained providers and build community awareness on use of medical abortion medicines for early abortions, at the time of the assessment. CONCLUSION: Opportunities to improve availability and quality of medical abortion medicines exist. For example, uniform implementation of regulatory standards, greater emphasis on quality-assurance during manufacturing, and standardizing of procurement and supply chain systems across states. Regular in-service training of providers on medical abortion is required. Finally, innovations in evidence dissemination and community engagement about the recently amended abortion law are needed.


Medical abortion is popular in India and benefits from a liberal legal context. It is important to understand the availability of quality abortion medicines in the country. Using the World Health Organization country assessment protocol and availability framework for medical abortion medicines we examined the availability of these medicines from supply to demand. We used this information to identify opportunities for increasing availability of quality-assured medical abortion medicines. We found that the context for medical abortion varies across states. Strengthening procurement and supply chain management, with a greater emphasis on quality-assurance and regulation of manufacturing should be instituted at the state-level. Training is also needed to increase provider knowledge of the latest national guidelines and laws to ensure respectful and person-centered services. Finally, the public should be informed about medical abortion as a safe and effective choice, especially for early abortions.


Assuntos
Abortivos , Aborto Induzido , Acessibilidade aos Serviços de Saúde , Misoprostol , Humanos , Índia , Aborto Induzido/estatística & dados numéricos , Aborto Induzido/métodos , Feminino , Gravidez , Abortivos/provisão & distribuição , Misoprostol/provisão & distribuição , Mifepristona/provisão & distribuição , Medicamentos Essenciais/provisão & distribuição
3.
J Adv Nurs ; 80(3): 1188-1200, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37731325

RESUMO

AIM: To evaluate gynaecological patients' preferences and satisfaction regarding information provision, exploring enablers and barriers to information access. DESIGN: A descriptive cross-sectional survey design was used. METHODS: A total of 293 women accessing gynaecological services responded to the survey. Quantitative analysis included descriptive and inferential statistics. Content analysis was conducted on qualitative data. RESULTS: Health professionals were the most common and preferred sources of gynaecological health information. Enablers to information provision included positive communication strategies by health professionals, participants having prior knowledge and doing their own research. Despite its widespread availability, only 24.2% of women preferred the internet as an information source. Poor communication and inadequate information provision were identified as barriers to information access. Statistically significant associations were identified between location of residence, education level, year of birth, diagnostic group and health information preferences. Recommendations from women included improved communication strategies, system changes and provision of individualized information. CONCLUSION: Health professionals are central to women accessing information about gynaecological diagnoses. Areas for improvement include communication strategies, facilitating access to internet-based resources for information and consideration of women's preferences when providing health information. IMPLICATIONS FOR THE PROFESSION AND PATIENT CARE: Consumer co-design of gynaecological health information and communication training for health professionals is recommended. Improved communication and facilitated use of internet-based resources may improve women's understanding of information. IMPACT: This study explored gynaecological patients' preferences and satisfaction regarding information provision, exploring enablers and barriers to information access. It was found that gynaecological patients preferred individualized information provided to them directly by health professionals and despite its widespread availability, the internet is an underutilized health information resource. These findings are applicable to health professionals and patients utilizing tertiary gynaecological health services in Australia but may be generalized if demographic data aligns with other jurisdictions. REPORTING METHOD: The STROBE reporting method was used in the preparation of the manuscript. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.


Assuntos
Comunicação , Preferência do Paciente , Humanos , Feminino , Estudos Transversais , Austrália , Pessoal de Saúde
4.
Artigo em Inglês | MEDLINE | ID: mdl-39097983

RESUMO

ISSUE ADDRESSED: Sexual and reproductive health (SRH) knowledge influences health literacy and promotes positive health behaviours. This scoping review explores the SRH knowledge of women in Australia and reports on knowledge assessment, ways of learning, enablers and barriers, and interventions to improve knowledge. METHODS: Seven databases were searched for eligible articles published in English between 2012 and 2022. RESULTS: Eighty-five sources were included for analysis. Data were mapped by knowledge topic and population group and charted against four review objectives. Assessment of knowledge was the primary focus in 59% of sources. Two sources used a validated knowledge assessment tool. Knowledge was assessed using self-assessment, a measurement of correctness, or both. Women learnt about SRH through a range of sources, including healthcare providers, peers, family, internet, and school. Enablers and barriers spanned information content, delivery, timing, accessibility, interactions with those providing information, cultural and gendered norms, pre-migration experiences, and functional health literacy. Nine sources reported on interventions to facilitate SRH knowledge. CONCLUSIONS: This review identified topics, population groups, and gaps in assessment of SRH knowledge of women in Australia. Overall, the measurement of women's SRH knowledge is largely conducted using unvalidated tools focusing on specific topics. SO WHAT?: It is recommended a validated tool be developed to comprehensively assess the SRH knowledge of women in Australia allowing for intersectional population analysis and exploration of knowledge conceptualisation. This would enable assessment of interventions aiming to improve SRH knowledge thereby facilitating improved health literacy and outcomes.

5.
J Am Chem Soc ; 145(14): 8218-8230, 2023 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-36996286

RESUMO

The discovery of novel large band gap two-dimensional (2D) materials with good stability and high carrier mobility will innovate the next generation of electronics and optoelectronics. A new allotrope of 2D violet phosphorus P11 was synthesized via a salt flux method in the presence of bismuth. Millimeter-sized crystals of violet-P11 were collected after removing the salt flux with DI water. From single-crystal X-ray diffraction, the crystal structure of violet-P11 was determined to be in the monoclinic space group C2/c (no. 15) with unit cell parameters of a = 9.166(6) Å, b = 9.121(6) Å, c = 21.803(14)Å, ß = 97.638(17)°, and a unit cell volume of 1807(2) Å3. The structure differences between violet-P11, violet-P21, and fibrous-P21 are discussed. The violet-P11 crystals can be mechanically exfoliated down to a few layers (∼6 nm). Photoluminescence and Raman measurements reveal the thickness-dependent nature of violet-P11, and exfoliated violet-P11 flakes were stable in ambient air for at least 1 h, exhibiting moderate ambient stability. The bulk violet-P11 crystals exhibit excellent stability, being stable in ambient air for many days. The optical band gap of violet-P11 bulk crystals is 2.0(1) eV measured by UV-Vis and electron energy-loss spectroscopy measurements, in agreement with density functional theory calculations which predict that violet-P11 is a direct band gap semiconductor with band gaps of 1.8 and 1.9 eV for bulk and monolayer, respectively, and with a high carrier mobility. This band gap is the largest among the known single-element 2D layered bulk crystals and thus attractive for various optoelectronic devices.

6.
Immunol Cell Biol ; 101(7): 590-597, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37227221

RESUMO

In biomedical research, there is no situation where public engagement (PE) and public involvement (PI) are not possible, important or even expected. Whether we work in the clinic or in the laboratory, all researchers have a duty to reach out, demonstrate the added value that science brings to society, and make a real difference to the way research is done. Here we outline the benefits of PE and PI for individual researchers and their employers, for members of the public, and for society at large. We offer solutions to overcome major challenges, including a step-by-step guide for researchers to embrace PE and PI in their career, and make a call to action for a cultural shift towards embedding PE and PI in our modern academic environment.


Assuntos
Pesquisa Biomédica
7.
BMC Med ; 21(1): 176, 2023 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-37158942

RESUMO

BACKGROUND: Childhood obesity is a global health concern and can lead to lifetime cardiometabolic disease. New advances in metabolomics can provide biochemical insights into the early development of obesity, so we aimed to characterize serum metabolites associated with overweight and adiposity in early childhood and to stratify associations by sex. METHODS: Nontargeted metabolite profiling was conducted in the Canadian CHILD birth cohort (discovery cohort) at age 5 years (n = 900) by multisegment injection-capillary electrophoresis-mass spectrometry. Clinical outcome was defined using novel combined measures of overweight (WHO-standardized body mass index ≥ 85th percentile) and/or adiposity (waist circumference ≥ 90th percentile). Associations between circulating metabolites and child overweight/adiposity (binary and continuous outcomes) were determined by multivariable linear and logistic regression, adjusting for covariates and false discovery rate, and by subsequent sex-stratified analysis. Replication was assessed in an independent replication cohort called FAMILY at age 5 years (n = 456). RESULTS: In the discovery cohort, each standard deviation (SD) increment of branched-chain and aromatic amino acids, glutamic acid, threonine, and oxoproline was associated with 20-28% increased odds of overweight/adiposity, whereas each SD increment of the glutamine/glutamic acid ratio was associated with 20% decreased odds. All associations were significant in females but not in males in sex-stratified analyses, except for oxoproline that was not significant in either subgroup. Similar outcomes were confirmed in the replication cohort, where associations of aromatic amino acids, leucine, glutamic acid, and the glutamine/glutamic acid ratio with childhood overweight/adiposity were independently replicated. CONCLUSIONS: Our findings show the utility of combining measures of both overweight and adiposity in young children. Childhood overweight/adiposity at age 5 years has a specific serum metabolic phenotype, with the profile being more prominent in females compared to males.


Assuntos
Sobrepeso , Obesidade Infantil , Criança , Pré-Escolar , Humanos , Feminino , Masculino , Sobrepeso/epidemiologia , Adiposidade , Estudos Transversais , Obesidade Infantil/epidemiologia , Glutamina , Canadá/epidemiologia , Aminoácidos Aromáticos , Metaboloma , Glutamatos
8.
BMC Med Res Methodol ; 23(1): 234, 2023 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-37838681

RESUMO

BACKGROUND: The COVID-19 pandemic resulted in major disruption to healthcare delivery worldwide causing medical services to adapt their standard practices. Learning how these adaptations result in unintended patient harm is essential to mitigate against future incidents. Incident reporting and learning system data can be used to identify areas to improve patient safety. A classification system is required to make sense of such data to identify learning and priorities for further in-depth investigation. The Patient Safety (PISA) classification system was created for this purpose, but it is not known if classification systems are sufficient to capture novel safety concepts arising from crises like the pandemic. We aimed to review the application of the PISA classification system during the COVID-19 pandemic to appraise whether modifications were required to maintain its meaningful use for the pandemic context. METHODS: We conducted a mixed-methods study integrating two phases in an exploratory, sequential design. This included a comparative secondary analysis of patient safety incident reports from two studies conducted during the first wave of the pandemic, where we coded patient-reported incidents from the UK and clinician-reported incidents from France. The findings were presented to a focus group of experts in classification systems and patient safety, and a thematic analysis was conducted on the resultant transcript. RESULTS: We identified five key themes derived from the data analysis and expert group discussion. These included capitalising on the unique perspective of safety concerns from different groups, that existing frameworks do identify priority areas to investigate further, the objectives of a study shape the data interpretation, the pandemic spotlighted long-standing patient concerns, and the time period in which data are collected offers valuable context to aid explanation. The group consensus was that no COVID-19-specific codes were warranted, and the PISA classification system was fit for purpose. CONCLUSIONS: We have scrutinised the meaningful use of the PISA classification system's application during a period of systemic healthcare constraint, the COVID-19 pandemic. Despite these constraints, we found the framework can be successfully applied to incident reports to enable deductive analysis, identify areas for further enquiry and thus support organisational learning. No new or amended codes were warranted. Organisations and investigators can use our findings when reviewing their own classification systems.


Assuntos
COVID-19 , Segurança do Paciente , Humanos , Pandemias , Erros Médicos , COVID-19/epidemiologia , Gestão de Riscos
9.
Child Dev ; 94(5): 1319-1329, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36967654

RESUMO

This study examined 4- and 5-year-olds' incremental interpretation of size adjectives, focusing on whether contrastive inferences are modulated by speaker behavior. Children (N = 120, 59 females, mostly White, tested between July, 2018 and August, 2019) encountered either a conventional or unconventional speaker who labeled objects in a correspondingly typical or atypical way. Critical utterances contained size adjectives (e.g., "Look at the big duck"). With conventional speakers, gaze measures indicated that children rapidly used the adjective to differentiate members of a contrasting pair, indicating that even 4-year-olds derive contrastive inferences. With unconventional speakers, contrastive inferences were delayed in processing. The findings demonstrate that preschoolers adjust their use of pragmatic cues when presented with evidence disconfirming their default assumptions about a speaker.


Assuntos
Compreensão , Idioma , Criança , Feminino , Humanos , Pré-Escolar , Desenvolvimento da Linguagem , Sinais (Psicologia)
10.
Reprod Health ; 20(Suppl 1): 20, 2023 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-36694182

RESUMO

BACKGROUND: Availability of quality-assured medical abortion medicines plays a crucial role in providing comprehensive abortion care. However, access to these medicines is still restricted for many abortion seekers. Increasing availability of affordable, quality-assured mifepristone and misoprostol is important to improve access to safe medical abortion services. Driven by the outcomes of a global consultation hosted by the World Health Organization and the Swedish International Development Cooperation Agency in 2018, we decided to holistically examine access to medical abortion medicines from supply to demand. The overarching principle of the national landscape assessments was to generate evidence to support policy dialog and policymaking that is contextual to the needs of the country. This paper aims to describe the framework and methodological approach used in the World Health Organization landscape assessments of medical abortion medicines at country-level. METHODS: A country assessment protocol was developed to guide the methodology of the World Health Organization landscape assessments. The assessment protocol included adaptation of an existing availability framework, an online desk review and literature review for existing data available for the country of interest, country-level key informant interviews, and analysis of the data to identify barriers and opportunities to improve medical abortion availability. CONCLUSION: The availability framework and methodology will allow the identification of key barriers that limit readiness of medical abortion medicines, and the development of opportunities to overcome those barriers. The national landscape assessments will provide directions for future investments and offer guidance for policy and programming on medical abortion care.


Increasing availability of affordable, safe, and effective medical abortion medicines is necessary to improve access to safe medical abortion services. Driven by the results of a meeting hosted by the World Health Organization and the Swedish International Development Cooperation Agency in 2018, we decided to examine access to medical abortion medicines from supply to demand in selected countries. The overarching goal of the national landscape assessments was to generate evidence to support advocacy efforts and policymaking that is appropriate to the needs of the country. This paper aims to describe the assessment protocol and the steps taken in the World Health Organization landscape assessments of medical abortion medicines at country-level. The assessment allows for a determination of the enabling environment surrounding the provision of medical abortion services. This in turn allows for the identification of key barriers that limit availability of abortion medicines, and the identification of opportunities to overcome those barriers. The availability framework includes both supply and demand sides of commodity availability, considering factors from product introduction to use. This approach can be used for future national assessments for any health commodity or service. The assessment findings will be informative to policymakers and programme managers in developing plans to safeguard availability of safe and effective medical abortion medicines.


Assuntos
Aborto Induzido , Aborto Espontâneo , Misoprostol , Gravidez , Feminino , Humanos , Mifepristona , Organização Mundial da Saúde
11.
Reprod Health ; 20(Suppl 1): 58, 2023 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-37041543

RESUMO

BACKGROUND: In recent years a growing number of manufacturers and medical abortion products have entered country markets and health systems, with varying degrees of quality and accessibility. An interplay of factors including pharmaceutical regulations, abortion laws, government policies and service delivery guidelines and provider's knowledge and practices influence the availability of medical abortion medicines. We assessed the availability of medical abortion in eight countries to increase understanding among policymakers of the need to improve availability and affordability of quality-assured medical abortion products at regional and national levels. METHODS: Using a national assessment protocol and an availability framework, we assessed the availability of medical abortion medicines in Bangladesh, Liberia, Malawi, Nepal, Nigeria, Rwanda, Sierra Leone and South Africa between September 2019 and January 2020. RESULTS: Registration of abortion medicines-misoprostol or a combination of mifepristone and misoprostol-was established in all countries assessed, except Rwanda. Mifepristone and misoprostol regimen for medical abortion was identified on the national essential medicines list/standard treatment guidelines for South Africa as well as in specific abortion care service and delivery guidelines for Bangladesh, Nepal, Nigeria, and Rwanda. In Liberia, Malawi, and Sierra Leone-countries with highly restrictive abortion laws and no abortion service delivery guidelines or training curricula-no government-supported training on medical abortion for public sector providers had occurred. Instead, training on medical abortion was either limited in scope to select private sector providers and pharmacists or prohibited. Community awareness activities on medical abortion have been limited in scope across the countries assessed and where abortion is broadly legal, most women do not know that it is an option. CONCLUSION: Understanding the factors that influence the availability of medical abortion medicines is important to support policymakers improve availability of these medicines. The landscape assessments documented that medical abortion commodities can be uniquely impacted by the laws, policies, values, and degree of restrictions placed on service delivery programs. Results of the assessments can guide actions to improve access.


Unsafe abortion is a leading cause of death and disability among women of reproductive age. Medical management of abortion with mifepristone and misoprostol pills, or just misoprostol, is a safe and effective way to end a pregnancy. Owing to an increase in the number of medical abortion products that have entered country health systems, we examined access to these medicines from supply to demand in selected countries. The overarching goal of the national landscape assessments was to produce evidence to support advocacy efforts and policymaking for improved access to quality medical abortion products that is appropriate to the needs of the country. This paper aims to describe key findings across eight country settings on the availability of medical abortion medicines and identify key opportunities to improve access to them across countries.


Assuntos
Abortivos , Aborto Induzido , Acessibilidade aos Serviços de Saúde , Internacionalidade , Feminino , Humanos , Gravidez , Aborto Induzido/legislação & jurisprudência , Aborto Induzido/métodos , Mifepristona , Misoprostol , África do Sul , Indústria Farmacêutica/legislação & jurisprudência , Internacionalidade/legislação & jurisprudência , Acessibilidade aos Serviços de Saúde/legislação & jurisprudência
12.
Nano Lett ; 22(11): 4501-4508, 2022 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-35609247

RESUMO

The surface functionalization of two-dimensional (2D) materials with organic electron donors (OEDs) is a powerful tool to modulate the electronic properties of the material. Here we report a novel molecular dopant, Me-OED, that demonstrates record-breaking molecular doping to MoS2, achieving a carrier density of 1.10 ± 0.37 × 1014 cm-2 at optimal functionalization conditions; the achieved carrier density is much higher than those by other OEDs such as benzyl viologen and an OED based on 4,4'-bipyridine. This impressive doping power is attributed to the compact size of Me-OED, which leads to high surface coverage on MoS2. To confirm, we study tBu-OED, which has an identical reduction potential to Me-OED but is significantly larger. Using field-effect transistor measurements and spectroscopic characterization, we estimate the doping powers of Me- and tBu-OED are 0.22-0.44 and 0.11 electrons per molecule, respectively, in good agreement with calculations. Our results demonstrate that the small size of Me-OED is critical to maximizing the surface coverage and molecular interactions with MoS2, enabling us to achieve unprecedented doping of MoS2.

13.
BMC Nurs ; 22(1): 461, 2023 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-38057825

RESUMO

BACKGROUND: To maintain and improve the quality of the cancer nursing workforce, it is crucial to understand the factors that influence retention and job satisfaction. We aimed to investigate the characteristics of cancer nurses in Australia and identify predictors of job satisfaction. METHODS: We analysed data from an anonymous cross-sectional survey distributed through the Cancer Nurses Society Australia membership and social media platforms from October 2021 to February 2022. The survey was compared to national nursing registration data. Data were analysed with non-parametric tests, and a stepwise, linear regression model was developed to best predict job satisfaction. RESULTS: Responses were received from 930 cancer nurses. Most respondents (85%) described themselves as experienced nurses, and more than half had post-graduate qualifications. We identified individual, organizational, and systemic factors that contribute to job satisfaction and can impact in workforce shortages. The findings include strategies to address and prioritize workforce challenges. There were 89 different titles for advanced practice nursing roles. Managing high workload was a reported challenge by 88%. Intention to stay less than 10 years was reported by nearly 60%; this was significantly correlated with job satisfaction and age. Significantly higher scores for job satisfaction were associated with those who had career progression opportunities, career development opportunities, adequate peer support and a clearly defined scope of role. Conversely, job satisfaction scores decreased the more people agreed there was a lack of leadership and they had insufficient resources to provide quality care. CONCLUSION: Cancer nurses are critical to the delivery of cancer care however, the workforce faces multiple challenges. This study provides an understanding of the Australian cancer nursing workforce characteristics, their roles and activities, and highlights important considerations for retaining nurses in the profession.

14.
Bioconjug Chem ; 33(3): 486-495, 2022 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-35139308

RESUMO

Targeted delivery of chemotherapeutic drugs can improve their therapeutic efficiency by localizing their toxic effects at the diseased site. This is often achieved either by direct conjugation of drugs to antibodies targeting overexpressed receptors on cancer cells (antibody-drug conjugates/ADCs) or by conjugating antibodies to nanoparticles bearing drugs (antibody-nanoparticle conjugates/ANCs). Here, we report a platform for utilizing hinge cysteines on antigen-binding fragment (Fab') of an anti-CD4 antibody for site-specific conjugation to nanoparticles giving rise to anti-CD4 Fab'-nanoparticle conjugates (Fab'-NCs). We demonstrate a convenient route for obtaining functional anti-CD4 Fab' from full-length antibody and examine the targeted delivery efficiencies of anti-CD4 Fab'-NCs vs ANCs for selective delivery to CD4high mT-ALL cells. Our results indicate that higher avidity of full-length anti-CD4 antibody, i.e., protein alone translated to higher binding ability to CD4high mT-ALL cells in comparison with anti-CD4 Fab' alone. However, the targeted delivery efficiency of anti-CD4 Fab'-NCs was comparable to ANCs indicating that the avidity of Fab' is restored in a nanoparticle-conjugate format. Fab'-NCs are equally capable of achieving targeted drug delivery to CD4high T-cells as ANCs and are a versatile alternative to ANCs by offering site-selective modification strategy while retaining their advantages.


Assuntos
Imunoconjugados , Nanopartículas , Anticorpos Monoclonais , Linfócitos T CD4-Positivos , Fragmentos Fab das Imunoglobulinas
15.
Phys Rev Lett ; 129(8): 081102, 2022 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-36053687

RESUMO

Gravitational waves (GWs) from inspiraling neutron stars afford us a unique opportunity to infer the as-of-yet unknown equation of state of cold hadronic matter at supranuclear densities. During the inspiral, the dominant matter effects arise due to the star's response to their companion's tidal field, leaving a characteristic imprint in the emitted GW signal. This unique signature allows us to constrain the cold neutron star equation of state. At GW frequencies above ≳800 Hz, however, subdominant tidal effects known as dynamical tides become important. In this Letter, we demonstrate that neglecting dynamical tidal effects associated with the fundamental (f) mode leads to large systematic biases in the measured tidal deformability of the stars and hence in the inferred neutron star equation of state. Importantly, we find that f-mode dynamical tides will already be relevant for Advanced LIGO's and Virgo's fifth observing run (∼2025)-neglecting dynamical tides can lead to errors on the neutron radius of O(1 km), with dramatic implications for the measurement of the equation of state. Our results demonstrate that the accurate modeling of subdominant tidal effects beyond the adiabatic limit will be crucial to perform accurate measurements of the neutron star equation of state in upcoming GW observations.

16.
J Am Acad Dermatol ; 87(1): 103-109, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-32763326

RESUMO

BACKGROUND: Although lasers have been the criterion standard for tattoo removal, selecting the best modality can be challenging because of the varying efficacies and adverse effects. OBJECTIVE: To evaluate all lasers used to remove tattoos and assess their efficacies and adverse effects. METHODS: Our systematic review searched PubMed, MEDLINE, Embase, Scopus, CINAHL, Cochrane Central Register of Trials, and ClinicalTrials.gov for all laser treatments. The outcomes measured included laser parameters, treatment methods, patient and tattoo characteristics, clearance rate, and adverse effect rate. The quality of the included articles was appraised by using specific assessment tools and given a high, moderate, or low risk of bias. RESULTS: Our search led to 3037 studies, with 36 being included in the systematic review (7 randomized controlled trials, 2 nonrandomized controlled trials, and 27 case series). Although quality-switched neodymium-doped yttrium-aluminum-garnet lasers are safe and effective, picosecond lasers have shown superiority with blue, green, and yellow tattoo pigments. Both are safe and effective for black tattoos. LIMITATIONS: Variability among studies. CONCLUSIONS: Picosecond lasers show superiority when treating blue, green, and yellow tattoos. The R20 and R0 novel techniques can effectively reduce treatment time. Further randomized controlled trials are required to make a more definitive recommendation.


Assuntos
Terapia a Laser , Lasers de Estado Sólido , Tatuagem , Humanos , Terapia a Laser/efeitos adversos , Terapia a Laser/métodos , Lasers de Estado Sólido/efeitos adversos
17.
BMC Med ; 19(1): 292, 2021 11 26.
Artigo em Inglês | MEDLINE | ID: mdl-34823524

RESUMO

BACKGROUND: Defining the metabolic syndrome (MetS) in children remains challenging. Furthermore, a dichotomous MetS diagnosis can limit the power to study associations. We sought to characterize the serum metabolite signature of the MetS in early childhood using high-throughput metabolomic technologies that allow comprehensive profiling of metabolic status from a biospecimen. METHODS: In the Family Atherosclerosis Monitoring In earLY life (FAMILY) prospective birth cohort study, we selected 228 cases of MetS and 228 matched controls among children age 5 years. In addition, a continuous MetS risk score was calculated for all 456 participants. Comprehensive metabolite profiling was performed on fasting serum samples using multisegment injection-capillary electrophoresis-mass spectrometry. Multivariable regression models were applied to test metabolite associations with MetS adjusting for covariates of screen time, diet quality, physical activity, night sleep, socioeconomic status, age, and sex. RESULTS: Compared to controls, thirteen serum metabolites were identified in MetS cases when using multivariable regression models, and using the quantitative MetS score, an additional eight metabolites were identified. These included metabolites associated with gluconeogenesis (glucose (odds ratio (OR) 1.55 [95% CI 1.25-1.93]) and glutamine/glutamate ratio (OR 0.82 [95% CI 0.67-1.00])) and the alanine-glucose cycle (alanine (OR 1.41 [95% CI 1.16-1.73])), amino acids metabolism (tyrosine (OR 1.33 [95% CI 1.10-1.63]), threonine (OR 1.24 [95% CI 1.02-1.51]), monomethylarginine (OR 1.33 [95% CI 1.09-1.64]) and lysine (OR 1.23 [95% CI 1.01-1.50])), tryptophan metabolism (tryptophan (OR 0.78 [95% CI 0.64-0.95])), and fatty acids metabolism (carnitine (OR 1.24 [95% CI 1.02-1.51])). The quantitative MetS risk score was more powerful than the dichotomous outcome in consistently detecting this metabolite signature. CONCLUSIONS: A distinct metabolite signature of pediatric MetS is detectable in children as young as 5 years old and may improve risk assessment at early stages of development.


Assuntos
Síndrome Metabólica , Coorte de Nascimento , Estudos de Casos e Controles , Criança , Pré-Escolar , Estudos de Coortes , Humanos , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/epidemiologia , Estudos Prospectivos
18.
Am J Obstet Gynecol ; 224(6): 597.e1-597.e14, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33309562

RESUMO

BACKGROUND: Contraceptive method choice is often strongly influenced by the experiences and opinions of one's social network. Although social media, including Twitter, increasingly influences reproductive-age individuals, discussion of contraception in this setting has yet to be characterized. Natural language processing, a type of machine learning in which computers analyze natural language data, enables this analysis. OBJECTIVE: This study aimed to illuminate temporal trends in attitudes toward long- and short-acting reversible contraceptive methods in tweets between 2006 and 2019 and establish social media platforms as alternate data sources for large-scale sentiment analysis on contraception. STUDY DESIGN: We studied English-language tweets mentioning reversible prescription contraceptive methods between March 2006 (founding of Twitter) and December 2019. Tweets mentioning contraception were extracted using search terms, including generic or brand names, colloquial names, and abbreviations. We characterized and performed sentiment analysis on tweets. We used Mann-Kendall nonparametric tests to assess temporal trends in the overall number and the number of positive, negative, and neutral tweets referring to each method. The code to reproduce this analysis is available at https://github.com/hms-dbmi/contraceptionOnTwitter. RESULTS: We extracted 838,739 tweets mentioning at least 1 contraceptive method. The annual number of contraception-related tweets increased considerably over the study period. The intrauterine device was the most commonly referenced method (45.9%). Long-acting methods were mentioned more often than short-acting ones (58% vs 42%), and the annual proportion of long-acting reversible contraception-related tweets increased over time. In sentiment analysis of tweets mentioning a single contraceptive method (n=665,064), the greatest proportion of all tweets was negative (65,339 of 160,713 tweets with at least 95% confident sentiment, or 40.66%). Tweets mentioning long-acting methods were nearly twice as likely to be positive compared with tweets mentioning short-acting methods (19.65% vs 10.21%; P<.002). CONCLUSION: Recognizing the influence of social networks on contraceptive decision making, social media platforms may be useful in the collection and dissemination of information about contraception.


Assuntos
Atitude Frente a Saúde , Anticoncepção/psicologia , Anticoncepção/tendências , Opinião Pública , Mídias Sociais , Tomada de Decisões , Feminino , Humanos , Masculino , Processamento de Linguagem Natural
19.
Matern Child Health J ; 25(4): 510-520, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33389587

RESUMO

PURPOSE: Breastfeeding and responsive feeding are important practices that support the health of infants and women. In the United States, breastfeeding continuation rates remain lower than recommended, and working women face additional challenges with breastfeeding continuation. Providers in a family child care setting are uniquely positioned to support and provide important resources to families in their breastfeeding and infant feeding practices. METHODS: The Go NAP SACC program was designed to improve the nutrition and physical activity environments and practices in child care settings serving infants and young children. This evaluation focuses on Breastfeeding and Infant Feeding in Nebraska Family Child Care Homes (FCCH). ASSESSMENT: Paired-sample t-tests were used to examine differences in pre-post evaluation scores. A repeated measure ANCOVA was used to examine differences between rural-urban settings. Nebraska FCCH met recommendations at pre-test, and exceeded recommendations at post-test (p < .05). Rural and urban FCCH performed equally well in 18 of 22 items, indicating little difference in the ability to provide supportive environments and adhere to best practices in both settings. Improvement in family engagement items were significant at the p < .001 level. Family engagement in FCCH is an important area for intervention that was well-received by provider participants. CONCLUSION: This evaluation shows that the Go NAP SACC program improves breastfeeding and infant feeding environments and practices in rural and urban FCCH. Interventions should continue to focus on basic and practical education and professional development for FCCH providers, with emphasis on intentional family engagement and support.


Assuntos
Aleitamento Materno , Cuidado da Criança , Criança , Creches , Saúde da Criança , Pré-Escolar , Comportamento Alimentar , Feminino , Humanos , Lactente , Estados Unidos
20.
Neurosurg Focus ; 50(5): E5, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33932935

RESUMO

OBJECTIVE: Frailty is recognized as an important consideration in patients with cancer who are undergoing therapies, including spine surgery. The definition of frailty in the context of spinal metastases is unclear, and few have studied such markers and their association with postoperative outcomes and survival. Using national databases, the metastatic spinal tumor frailty index (MSTFI) was developed as a tool to predict outcomes in this specific patient population and has not been tested with external data. The purpose of this study was to test the performance of the MSTFI with institutional data and determine whether machine learning methods could better identify measures of frailty as predictors of outcomes. METHODS: Electronic health record data from 479 adult patients admitted to the Massachusetts General Hospital for metastatic spinal tumor surgery from 2010 to 2019 formed a validation cohort for the MSTFI to predict major complications, in-hospital mortality, and length of stay (LOS). The 9 parameters of the MSTFI were modeled in 3 machine learning algorithms (lasso regularization logistic regression, random forest, and gradient-boosted decision tree) to assess clinical outcome prediction and determine variable importance. Prediction performance of the models was measured by computing areas under the receiver operating characteristic curve (AUROCs), calibration, and confusion matrix metrics (positive predictive value, sensitivity, and specificity) and was subjected to internal bootstrap validation. RESULTS: Of 479 patients (median age 64 years [IQR 55-71 years]; 58.7% male), 28.4% had complications after spine surgery. The in-hospital mortality rate was 1.9%, and the mean LOS was 7.8 days. The MSTFI demonstrated poor discrimination for predicting complications (AUROC 0.56, 95% CI 0.50-0.62) and in-hospital mortality (AUROC 0.69, 95% CI 0.54-0.85) in the validation cohort. For postoperative complications, machine learning approaches showed a greater advantage over the logistic regression model used to develop the MSTFI (AUROC 0.62, 95% CI 0.56-0.68 for random forest vs AUROC 0.56, 95% CI 0.50-0.62 for logistic regression). The random forest model had the highest positive predictive value (0.53, 95% CI 0.43-0.64) and the highest negative predictive value (0.77, 95% CI 0.72-0.81), with chronic lung disease, coagulopathy, anemia, and malnutrition identified as the most important predictors of postoperative complications. CONCLUSIONS: This study highlights the challenges of defining and quantifying frailty in the metastatic spine tumor population. Further study is required to improve the determination of surgical frailty in this specific cohort.


Assuntos
Fragilidade , Neoplasias da Coluna Vertebral , Adulto , Feminino , Fragilidade/diagnóstico , Humanos , Aprendizado de Máquina , Masculino , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos , Complicações Pós-Operatórias/etiologia , Neoplasias da Coluna Vertebral/cirurgia
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