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Purpose: Given the implementation of a new Certified Public Accountant (CPA) licensure exam and the CPA Evolution Model Curriculum, accounting educators must integrate more advanced skills in their coursework. We illustrate how a commonly-used project in accounting classes, which teaches technical accounting content, can address skills and competencies identified by the Pathways Commission and the American Institute of Certified Public Accountants (AICPA) and, as a result, enhance skills all business school graduates need in the workplace. Design/methodology/approach: We incorporate a financial statement analysis research project under a group work format in three levels of financial accounting classes. Using both quantitative and qualitative analysis, we evaluate changes in student perceptions of skills and competencies important for business graduates. Findings: We find students perceive improvement in critical thinking, problem-solving, the ability to work with other people, their understanding of the course material, and data analysis abilities after completion of the project. We also find statistically significant increases pre-to post-project in student perceptions of their knowledge, confidence, competence, and enthusiasm with respect to accounting material. Originality/value: We provide an example of how educators can align a commonly-used project with the CPA Evolution Model Curriculum, yet still meet the needs of non-accounting majors and prepare all students for future business careers. Group work has been studied and similar financial statement analysis projects have been implemented in the classroom for years. We contribute by not only extending and updating this research, but also by re-evaluating a project to determine whether it meets the shifting needs of a rapidly changing profession. By doing so, we answer recent researchers' call for research in higher education that addresses employability and workplace skills.

Abstract We report time resolved observations of the crystallization from liquid hydrogen, supercooled to temperatures below the melting point, using 11.2 keV X-ray diffraction from the Linac Coherent Light Source (LCLS). Changes to the metastable solid and liquid structure factors have been dynamically measured. This allows for a direct determination of the lowest energy crystal polymorphs, the stacking probabilities, as well as the liquid and solid densities and temperatures. Such measurements provide experimental evidence of an Arrhenius-like growth kinetics along the stacking direction during supercooling.

Background: Serous endometrial carcinoma (SEC) is a high-risk subtype of endometrial cancer. The effectiveness of multiple adjuvant therapies, namely chemotherapy (CT), radiotherapy (RT), and sequential/concurrent chemotherapy with radiotherapy (CRT), have previously been investigated. However, optimal management of early-stage SEC remains unclarified. Methods: All cases of early-stage SEC (FIGO 2009 stages I–II) treated in our institution from 2002 to 2019 were identified. Patient data were documented until September 2023. Overall survival (OS) and disease-free survival (DFS) were computed using Kaplan–Meier estimates and Cox’s proportional hazard model; descriptive statistical analysis was performed. Results: A total of 50 patients underwent total hysterectomy-bilateral salpingo-oophorectomy and omentectomy, displaying stage IA (60%), IB (24%), and II (16%) disease. The median follow-up was 90.9 months. Patients underwent adjuvant CRT (n = 36, 72%), CT (n = 6, 12%), or RT (n = 6, 12%). Two patients were observed and excluded from analyses. The 42 patients who received radiotherapy had pelvic external beam radiotherapy (n = 10), vaginal brachytherapy (n = 21), or both (n = 11). CRT had better OS (HR 0.14, 95%CI 0.04–0.52, p < 0.005) and DFS (HR 0.25, 95%CI 0.07–0.97, p = 0.05) than CT alone. RT displayed no OS or DFS benefits compared to CT/CRT. Recurrences were mostly distant. Acute and late G3-4 toxicities were primarily hematologic. Conclusions: Our data underline the challenge of treating SEC. CRT appears to be superior to CT alone but not to RT. Most recurrences were distant, highlighting the need for optimized systemic treatment options.

Introdução: O emprego de fluorescência bacteriana (FB) para demarcação de áreas de maior carga microbiana torna a coleta de amostras direcionada. A biópsia dos tecidos (BT) da ferida é considerada o padrão-ouro para coleta de material para a identificação microbiológica, entretanto a pução aspirativa (PA) por agulha é proposta como um método seguro e eficaz para este mesmo fim. Objetivo: Avaliar a concordância da identificação microbiológica PA em relação à BT. Método: Estudo prospectivo conduzido entre maio/2022 e aneiro/2023 no Hospital do Servidor Público Estadual (IAMSPE). Foram incluídos pacientes com diagnóstico de infecção de ferida submetidos à PA e à BT. A concordância da identificação microbiológica entre os métodos foi mensurada pelo Coeficiente Kappa de Cohen. O Teste do Sinal e o Teste Exato de Fisher foram aplicados, ambos com significância quando p < .05. Resultados: Foram incluídos 40 pacientes. A maioria foi do gênero masculino (53%) com média de 70,4 ± 14,9 anos de idade. As comorbidades mais frequentes foram Hipertensão Arterial Sistêmica (70%), Diabetes Mellitus (43%) e Insuficiência Venosa Crônica (43%). Os microrganismos mais frequentemente identificados foram S. aureus (18%), P. aeruginosa (14%) e E. coli (10%). A concordância ocorreu em 75% dos casos e resultou em um κ = 0,36 (IC 95%, 0,0-0,7). A sensibilidade foi de 90% para BT e 85% para PA. A sensibilidade da combinação BT-PA foi de 100%, um incremento significativo de 11% em comparação com BT isoladamente (p = 0,04). A identificação média de microrganismos foi de 1,5 para BT e 1,2 para PA. A identificação média de microrganismos com a combinação BT-PA foi de 1,9 microrganismos, um incremento significativo em comparação com BT isoladamente (p < 0,01). Conclusão: O κ = 0,36 indicou uma ''concordância razoável'', isto é, a PA isolada é insuficientemente comparável à BT e, portanto, aquele método não deve substituir rotineiramente o último na prática clínica. No entanto, a combinação BT-PA mostrou um aumento significativo tanto na sensibilidade quanto na identificação microbiológica média, o que indica que PA pode ser um método confirmatório para a BT ao oferecer uma segunda modalidade para coleta de amostra para culturas. Além disso, em casos selecionados em que BT não é viável, a PA permite a identificação microbiológica em até 63% dos casos.

Introdução: O uso prolongado de antimicrobianos em infecção osteoarticular (IOA) é uma prática comum e o tempo do tratamento depende do tipo da infecção. A redução do tempo de tratamento tem sido uma prática comum e a racionalização dos antimicrobianos é uma medida necessária. Objetivo: Avaliar o impacto da redução do tempo do tratamento das IOA num hospital com protocolo de supressão prolongada de antimicrobianos. Comparar agentes etiológicos na ocorrência de recidiva de IOA. Método: Estudo retrospectivo observacional de 2018 a 2019 em Hospital de ensino. Todos os pacientes com infecção sem implante foram tratados por 6 semanas e com implante por 12 semanas. Após completar o tratamento todos foram acompanhados por 1 ano para avaliar recidiva. Os agentes etiológicos foram comparados com aqueles que tiveram recidiva. Foi considerado como recidiva todo paciente que após completar o tratamento apresentou sinais e sintomas sugestivos de IOA após 30 dias do término do tratamento. Resultados: De 106 pacientes: 5 evoluíram a óbito e foram excluídos do estudo, mas nenhum com mortalidade relacionada a infecção óssea. A idade mínima foi de 21 e a máxima de 89 anos, com média de 64, sendo 54 (53,47%) mulheres; 47 (46,53%) homens. Em relação à classificação, 47,0% Infecção Relacionada a Fratura; 29,0% Infecção de Artroplastia; 14,0%, Osteomielite crônica; 5,0% Infecção de material de síntese; 3,0% osteomielite por contiguidade e 2,0% Espondilodiscite. Os principais agentes foram: S. aureus (29,1%), seguido de P. aeruginosa (13,6%), E. cloacae (8,7%), K. pneumoniae (6,8%), S. marcescens (6,8%), E. faecalis (5,8%) e Acinetobacter spp (4,9%). O tempo mínimo de tratamento foi de 28 dias e o máximo de 84, com média de 58. Na redução de uma média prévia de 1 ano para uma média de 58 dias houve uma economia de 307 dias de uso de antimicrobiano. A economia de 307 dias corresponderia a aproximadamente o tratamento de mais 5 pacientes. Dos 101 pacientes, apenas 11,11% apresentaram recidiva. Todos apresentaram cultura positiva no primeiro episódio. Na recidiva, apenas 6 pacientes apresentaram cultura positiva. Dos 6 pacientes, 5 com agentes etiológicos diferente do primeiro episódio e 1 foi a mesma espécie, contudo com perfil de sensibilidade diferente. Conclusão: A redução do tempo do uso do antimicrobiano nas IOA teve um baixo percentual de recidiva (11,11%), sendo que a maior parte apresentou outro agente etiológico ou perfil de sensibilidade diferente.

Introdução: A incidência da infecção relacionada à fratura (IRF) pode variar de 0,4 a 32%, sendo ainda maior em fraturas expostas. Os principais patógenos descritos são os cocos Gram-positivo (CGP), em especial o S. aureus. Entretanto, estudos que avaliam informações epidemiológicas e microbiológicas nas IRF são escassos no Brasil. Objetivo: Os objetivos deste trabalho são descrever a incidência de IRF e os dados clínico-microbiológicos em um serviço ortopédico. Método: Estudo prospectivo com análise de dados coletados entre março de 2020 e março de 2023, unicêntrico, conduzido em serviço multidisciplinar de Ortopedia e Infectologia, o qual incluiu pacientes maiores de 18 anos com fraturas fechadas e expostas submetidos à fixação interna com implantes como tratamento cirúrgico definitivo. Resultados: Do total de 462 pacientes incluídos, 71,6% foram do sexo masculino com média de idade de 47,6 anos (DP±20,8). As principais comorbidades foram Hipertensão Arterial Sistêmica (19,3%), tabagismo (19,3%) e etilismo (17,3%). As fraturas expostas foram 25,1% dos casos, sendo a classificação de Gustilo-Anderson do tipo 3-A a mais frequente (69,8%). A incidência global de IRF, em fraturas fechadas, e em fraturas expostas foi de 19,7%, 16,5%, e 29,3% respectivamente. A principal profilaxia cirúrgica foi uma cefalosporina de 1a ou 2a geração (84,6%) associada a um aminoglicosídeo (44,6%) ou isolada (43,1%). Os principais patógenos identificados foram S. aureus (22,1%), K. pneumoniae (11,6%), S. epidermidis (10,5%), demais Staphylococcus coagulase-negativo (10,5%), E. coli (6,3%), P. aeruginosa (5,3%), Streptococcus spp beta-hemolítico (4,2%), outros CGP (9,5%) e outros bacilos Gram-negativo (BGN) (20,0%). A resistência à meticilina foi identificada em 60% das cepas do gênero Staphylococcus e a multidroga resistência (MDR) foi identificada em 53,7% dos BGN. Conclusão: A incidência de IRF global e em fraturas expostas foi elevada, assim como em fraturas fechadas nas quais menores valores são esperados visto o menor dano tecidual e a adoção sistemática da profilaxia antimicrobiana cirúrgica. A elevada frequência de BGN (43,2%) demonstrando perfil de MDR (53,7%) associada a uma alta resistência à meticilina do gênero Staphylococcus (60%) apontam para uma mudança no perfil epidemiológico de IRF e sugerem a revisão da profilaxia antimicrobiana em cirurgias ortopédicas com implantes no Brasil.

Heart failure with preserved ejection fraction (HFpEF) is commonly found in persons living with HIV (PLWH) even when antiretroviral therapy suppresses HIV viremia. However, studying this condition has been challenging because an appropriate animal model is not available. In this article, we studied calcium transient in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) in culture to simulate the cardiomyocyte relaxation defect noted in PLWH and HFpEF and assess whether various drugs have an effect. We show that treatment of hiPSC-CMs with inflammatory cytokines (such as interferon-γ or TNF-α) impairs their Ca2+ uptake into sarcoplasmic reticulum and that SGLT2 inhibitors, clinically proven as effective for HFpEF, reverse this effect. Additionally, treatment with mitochondrial antioxidants (like mito-Tempo) and certain antiretrovirals resulted in the reversal of the effects of these cytokines on calcium transient. Finally, incubation of hiPSC-CMs with serum from HIV patients with and without diastolic dysfunction did not alter their Ca2+-decay time, indicating that the exposure to the serum of these patients is not sufficient to induce the decrease in Ca2+ uptake in vitro. Together, our results indicate that hiPSC-CMs can be used as a model to study molecular mechanisms of inflammation-mediated abnormal cardiomyocyte relaxation and screen for potential new interventions.

A growing number of general circulation models are adapting interactive sulfur and aerosol schemes to improve the representation of relevant physical and chemical processes and associated feedbacks. They are motivated by investigations of climate response to major volcanic eruptions and potential solar geoengineering scenarios. However, uncertainties in these schemes are not well constrained. Stratospheric sulfate is modulated by emissions of sulfur-containing species of anthropogenic and natural origin, including volcanic activity. While the effects of volcanic eruptions have been studied in the framework of global model intercomparisons, the background conditions of the sulfur cycle have not been addressed in such a way. Here, we fill this gap by analyzing the distribution of the main sulfur species in nine global atmospheric aerosol models for a volcanically quiescent period. We use observational data to evaluate model results. Overall, models agree that the three dominant sulfur species in terms of burdens (sulfate aerosol, OCS, and SO2) make up about 98 % stratospheric sulfur and 95 % tropospheric sulfur. However, models vary considerably in the partitioning between these species. Models agree that anthropogenic emission of SO2 strongly affects the sulfate aerosol burden in the northern hemispheric troposphere, while its importance is very uncertain in other regions, where emissions are much lower. Sulfate aerosol is the main deposited species in all models, but the values deviate by a factor of 2. Additionally, the partitioning between wet and dry deposition fluxes is highly model dependent. Inter-model variability in the sulfur species is low in the tropics and increases towards the poles. Differences are largest in the dynamically active northern hemispheric extratropical region and could be attributed to the representation of the stratospheric circulation. The differences in the atmospheric sulfur budget among the models arise from the representation of both chemical and dynamical processes, whose interplay complicates the bias attribution. Several problematic points identified for individual models are related to the specifics of the chemistry schemes, model resolution, and representation of cross-tropopause transport in the extratropics. Further model intercomparison research is needed with a focus on the clarification of the reasons for biases, given the importance of this topic for the stratospheric aerosol injection studies.

Abstract The aim of this study is to determine if extended‐release, bioabsorbable, subcutaneous naltrexone (NTX) implants can mitigate respiratory depression after an intravenous injection (IV) of fentanyl. Six different BIOabsorbable Polymeric Implant Naltrexone (BIOPIN) formulations, comprising combinations of Poly‐d,l‐Lactic Acid (PDLLA) and/or Polycaprolactone (PCL‐1 or PCL‐2), were used to create subcutaneous implants. Both placebo and naltrexone implants were implanted subcutaneously in male dogs. The active naltrexone implants consisted of two doses, 644 mg and 1288 mg. A challenge with IV fentanyl was performed in 33 male dogs at 97–100 days after implantation. Following the administration of a 30 μg/kg intravenous fentanyl dose, the placebo cohort manifested a swift and profound respiratory depression with a ~50% reduction in their pre‐dose respiratory rate (RR). The BIOPIN NTX‐implanted dogs were exposed to escalating doses of intravenous fentanyl (30 μg/kg, 60 μg/kg, 90 μg/kg, and 120 μg/kg). In contrast, the dogs implanted with the BIOPIN naltrexone implants tolerated doses up to 60 μg/kg without significant respiratory depression (

Abstract Introduction The rapid development of artificial intelligence (AI) in healthcare has exposed the unmet need for growing a multidisciplinary workforce that can collaborate effectively in the learning health systems. Maximizing the synergy among multiple teams is critical for Collaborative AI in Healthcare. Methods We have developed a series of data, tools, and educational resources for cultivating the next generation of multidisciplinary workforce for Collaborative AI in Healthcare. We built bulk‐natural language processing pipelines to extract structured information from clinical notes and stored them in common data models. We developed multimodal AI/machine learning (ML) tools and tutorials to enrich the toolbox of the multidisciplinary workforce to analyze multimodal healthcare data. We have created a fertile ground to cross‐pollinate clinicians and AI scientists and train the next generation of AI health workforce to collaborate effectively. Results Our work has democratized access to unstructured health information, AI/ML tools and resources for healthcare, and collaborative education resources. From 2017 to 2022, this has enabled studies in multiple clinical specialties resulting in 68 peer‐reviewed publications. In 2022, our cross‐discipline efforts converged and institutionalized into the Center for Collaborative AI in Healthcare. Conclusions Our Collaborative AI in Healthcare initiatives has created valuable educational and practical resources. They have enabled more clinicians, scientists, and hospital administrators to successfully apply AI methods in their daily research and practice, develop closer collaborations, and advanced the institution‐level learning health system.

The Goddard Chemistry Aerosol Radiation and Transport (GOCART) model, which controls the sources, sinks, and chemistry of aerosols within the Goddard Earth Observing System (GEOS), recently underwent a major refactoring and update, including a revision of the emissions datasets and the addition of brown carbon. A 4-year benchmark simulation utilizing the new version of the model code, termed GOCART Second Generation (GOCART-2G) and coupled to the Goddard Earth Observing System (GEOS) model, was evaluated using in situ and spaceborne measurements to develop a baseline and prioritize future development. A comparison of simulated aerosol optical depth between GOCART-2G and MODIS retrievals indicates the model captures the overall spatial pattern and seasonal cycle of aerosol optical depth but overestimates aerosol extinction over dusty regions and underestimates aerosol extinction over Northern Hemisphere boreal forests, requiring further investigation and tuning of emissions. This MODIS-based analysis is corroborated by comparisons to MISR and selected AERONET stations; however, discrepancies between the Aqua and Terra satellites indicate there is a diurnal component to biases in aerosol optical depth over southern Asia and northern Africa. Despite the underestimate of aerosol optical depth in biomass burning regions in GEOS, there is an overestimate in the surface mass of organic carbon in the United States, especially during the summer months. Over Europe, GOCART-2G is unable to match the summertime peak in aerosol optical depth, opposing the observed late fall and early spring peaks in surface mass concentration. A comparison of the vertical profile of attenuated backscatter to observations from CALIPSO indicates the GEOS model is capable of capturing the vertical profile of aerosol; however, the mid-troposphere plumes of dust in the North Atlantic and smoke in the southeastern Atlantic are perhaps too low in altitude. The results presented highlight priorities for future development with GOCART-2G, including improvements for dust, biomass burning aerosols, and anthropogenic aerosols.

Abstract Background Coronavirus disease COVID-19 is a heterogeneous condition caused by SARS-CoV-2 infection. Generally, it is characterized by interstitial pneumonia that can lead to impaired gas-exchange, acute respiratory failure, and death, although a complex disorder of multi-organ dysfunction has also been described. The pathogenesis is complex, and a variable combination of factors has been described in critically ill patients. COVID-19 is a particular risk for older persons, particularly those with frailty and comorbidities. Blood bacterial DNA has been reported in both physiological and pathological conditions and has been associated with some haematological and laboratory parameters but, to date, no study has characterized it in hospitalized old COVID-19 patients The present study aimed to establish an association between blood bacterial DNA (BB-DNA) and clinical severity in old COVID-19 patients. Results BB-DNA levels were determined, by quantitative real-time PCRs targeting the 16S rRNA gene, in 149 hospitalized older patients (age range 65–99 years) with COVID-19. Clinical data, including symptoms and signs of infection, frailty status, and comorbidities, were assessed. BB-DNA was increased in deceased patients compared to discharged ones, and Cox regression analysis confirmed an association between BB-DNA and in-hospital mortality. Furthermore, BB-DNA was positively associated with the neutrophil count and negatively associated with plasma IFN-alpha. Additionally, BB-DNA was associated with diabetes. Conclusions The association of BB-DNA with mortality, immune-inflammatory parameters and diabetes in hospitalized COVID-19 patients suggests its potential role as a biomarker of unfavourable outcomes of the disease, thus it could be proposed as a novel prognostic marker in the assessment of acute COVID-19 disease.

Marfan Syndrome (MFS) is an autosomal dominant disease caused in most cases by mutations in the FNB1 gene, which encodes for fibrillin 1. MFS does not alway shows typical phenotypic signs. Indeed, the occurrence of sudden death of unknown cause is increasingly seen in young adults without ante mortem preexisting pathology to explain the event. In many cases the diagnosis of Marfan Syndrome (MFS) is carried out post mortem, especially in cases where the disease’s external phenotype is absent. Here is reported a case of a young woman who died during a twin pregnancy investigated with medico-legal and forensic anthropological procedures. The autopsy showed the absence of a typical marfanoid habitus and the presence of a dissecting aneurysm of the aorta with histopathological degeneration of the aortic elastic fibers. The genetic investigation revealed two previously undetected de novo mutations of the FBN1 gene: c.T6181C: p.C2061R and c.G1415A: p.C472Y. This new mutations, together with a comprehensive analysis, demonstrates the existence of a causal relationship between these mutations and the dissecting aneurysm of the aorta. This also stresses the importance of a combined multidisciplinary approach to this condition which includes morphological and genetic studies.

This article is an update to a previous article on the online embedded librarian program at Athens State University. It examines the nature of embedded librarianship at Athens State University and how it has grown and evolved over the past fifteen years. The authors review the literature and provide definitions and best practices associated with embedded librarianship as well as various levels of embedded librarian involvement. They also provide suggestions for those involved in embedded librarianship.

The coexistence allows the adaptation of the aggressors and assaulted in school communities through artistic interaction techniques. Due to its transformational value, artivist education allows students to be involved in raising awareness of their environment as well as themselves. For this reason, the interest of the research was to determine the benefits of artivism in school coexistence. Three studies based on sustainability, school exchange and meaning analysis were carried out in 80 fifth and sixth grade primary students. Measurement scales and the log of experiences were used, from whose data it was obtained that there was greater sustainability of direct and democratic coexistence from the fourth month of experimentation with activities based on artivist education (Experiment 1), as well as effects on school exchange with greater emphasis on the democratic component (Experiment 2). The conclusions of the research invited to deduce that artivist education allowed coexistence to be made more sustainable through the strategies that subjects adopted from their peers, in turn, direct interaction allowed to propose a formative process of adaptation between assaulted and aggressors. As a contribution, the research highlights the adoption of new forms of student interaction with power groups to the extent of how and how they establish acceptability behaviors in the shared context.

Malaysia and ASEAN society are rich with a variety of traditional games and usually played during leisure time. 'Tossing the Stones' or Batu Seremban was chosen in this survey. Using a purposive sampling technique, respondents from Malaysia, Philippines, Indonesia and Thailand went through the game intervention and answered the questionnaires provided. The goal was to understand how they perceived wellness while playing this game, after identifying the frequency of Traditional Games engagement. Results showed that Batu Seremban gave high wellness scores such as; M=4.16, SD=0.722. The physical, intellectual, social and emotional elements identified in 'Tossing the Stones' showed that strong educational elements identified in the traditional leisure game can also be used to teach children and young adults through integration in the curriculum. Suggestions on how the game can be used in classrooms were made based on the findings.

Abstract Background Immediate initiation of antiretroviral treatment (iART) is a proven intervention that significantly decreases time to viral suppression and increases patient retention. iART involves starting medication as early as possible, often after a reactive rapid HIV test or re-engagement in care, although it does not have a universal definition. We aimed to understand iART from an implementation science perspective in a wide range of New York City (NYC) clinics providing HIV primary care, including staff knowledge, attitudes, and practices, as well as clinic barriers and facilitators to iART. Methods We used a mixed-methods, convergent study design, with a quantitative survey and in-depth interview (IDI), to understand individual-level knowledge, attitudes, and practices, as well as clinic-level barriers and facilitators to iART. We recruited at least one medical and non-medical staff member from a diverse purposive sample of 30 NYC clinics. In quantitative analyses, we used separate binomial logistic regression models to estimate odds ratios (OR) and 95% confidence intervals (95% CI). In qualitative analyses, we used codebooks created by thematic analyses structured using a Framework Model to develop descriptive analytic memos. Results Recruited staff completed 46 surveys and 17 IDIs. We found high levels of awareness of the viral suppression and retention in care benefits of iART. Survey respondents more commonly reported medication starts within three to four days of a reactive rapid HIV test rather than same-day initiation. Among survey respondents, compared to medical staff, non-medical staff were more likely to agree that medication should only be initiated after receiving confirmatory HIV test results (OR: 0.2, 95% CI: 0.06–0.8). Additionally, survey respondents from clinics serving a majority people of color were less likely to report iART on the same day as a reactive rapid HIV test (OR: 0.2, 95% CI: 0.02–1.0, p-value

Fentanyl is an opioid with powerful analgesic effects and a high speed of action. Due to its pharmacological properties, this molecule has therapeutic application as an anesthetic in surgery or as palliative therapy for cancer patients. Unfortunately, in recent years, the easy availability of this substance, the low cost and the illegal online market have favored the large-scale diffusion of fentanyl. Fentanyl is available in different forms, including nasal spray, oral patches, soluble capsules, aerosol or the new version of fentanyl mixed with other drugs, making its use very widespread. Subjects of various ages are involved in fentanyl consumption, including minors that have not yet reached adolescence. In this work, we performed a literature review using the search engines PubMed NCBI and SCOPUS regarding episodes of acute fentanyl intoxication occurring in those of a pediatric age using the Mesh Terms “fentanyl” AND “overdose” AND “children”. The inclusion criteria were English papers published in the last 10 years regarding the cases of children under the age of 10. We evaluated the most frequent methods of intake and the circumstances of such episodes. In cases of death, we analyzed the autopsy, the toxicological findings and the investigations carried out. The review results show that in this age group (under < 10 y.o. s), it is possible to identify the risk factors for fentanyl intake, such as the presence of this molecule within the family unit due to drug addiction or medical therapy. The results also demonstrate a significant risk of underestimation of this phenomenon, since the molecule is often not investigated through adequate toxicological analysis. These results, therefore, suggest always carrying out toxicological investigations in the case of suspected fentanyl intoxication, both on patients or cadavers. The investigations must always include a urinary screening for opiates, and the request for a second level analysis with molecule dosage in cases of positivity or in cases of strong suspicion for assumption. In cases of intoxication in a family context of drug addiction, it is necessary to investigate the chronicity of the intake through hair analysis and evaluate the possible co-administration of other drugs. In conclusion, we suggest a protocol, applicable both on patients or cadavers, which can be useful for physicians and forensic pathologists in order to promptly identify these cases and allow for the reporting of them to the judicial authorities with the adoption of strict prevention and control measures.

With the widespread phenomenon of antibiotic resistance and the diffusion of multiple drug-resistant bacterial strains, enormous efforts are being conducted to identify suitable alternative agents against pathogenic microorganisms. Since an association between biofilm formation and antibiotic resistance phenotype has been observed, a promising strategy pursued in recent years focuses on controlling and preventing this formation by targeting and inhibiting the Quorum Sensing (QS) system, whose central role in biofilm has been extensively demonstrated. Therefore, the research and development of Quorum Quenching (QQ) compounds, which inhibit QS, has gradually attracted the attention of researchers and has become a new strategy for controlling harmful microorganisms. Among these, a number of both natural and synthetic compounds have been progressively identified as able to interrupt the intercellular communication within a microbial community and the adhesion to a surface, thus disintegrating mature/preformed biofilms. This review describes the role played by QS in the formation of bacterial biofilms and then focuses on the mechanisms of different natural and synthetic QS inhibitors (QSIs) exhibiting promising antibiofilm ability against Gram-positive and Gram-negative bacterial pathogens and on their applications as biocontrol strategies in various fields.

At many crime scenes, investigators are able to trace and find traces of blood. For many years, it was believed that such traces could only be subjected to genetic investigations, such as those aimed at comparing DNA profiling with a suspect to verify his identity, and that it was therefore not possible to backdate the traces. In recent years, various works have used experimental models to investigate the possibility of identifying markers and methodologies for estimating the time since deposition (TSD) of bloodstains. Despite the results, these methods are still not part of standard procedures, and there is no univocal analysis methodology. In this work we carried out a systematic literature review of all the papers published in the last ten years on this topic, comparing the experimental models created. This review demonstrates the potential that different molecular approaches, such as transcriptomics, metabolomics, proteomics, and spectrometry, can have in the analysis of TSD, with notable sensitivity and specificity. This paper also analyzes the intrinsic and extrinsic limits of these models and emphasizes the need to continue research work on this topic, considering the importance that this parameter can assume in forensic investigations against a suspect.

The spread of antibiotic-resistant pathogens has prompted the development of novel approaches to identify molecules that synergize with antibiotics to enhance their efficacy. This study aimed to investigate the effects of ten Essential Oils (EOs) on the activity of nine antibiotics in influencing growth and biofilm formation in Escherichia coli, Pseudomonas aeruginosa, and Enterococcus faecalis. The effects of the EOs alone and in combination with antibiotics on both bacterial growth and biofilm formation were analyzed by measuring the MIC values through the broth microdilution method and the crystal violet assay, respectively. All EOs inhibited the growth of E. coli (1.25 ≤ MIC ≤ 5 mg/mL) while the growth of P. aeruginosa and E. faecalis was only affected by EOs from Origanum vulgare, (MIC = 5 mg/mL) and O. vulgare (MIC = 1.25 mg/mL) and Salvia rosmarinus (MIC = 5 mg/mL), respectively. In E. coli, most EOs induced a four- to sixteen-fold reduction in the MIC values of ampicillin, ciprofloxacin, ceftriaxone, gentamicin, and streptomycin, while in E. faecalis such a reduction is observed in combinations of ciprofloxacin with C. nepeta, C. bergamia, C. limon, C. reticulata, and F. vulgare, of gentamicin with O. vulgare, and of tetracycline with C. limon and O. vulgare. A smaller effect was observed in P. aeruginosa, in which only C. bergamia reduced the concentration of tetracycline four-fold. EO-antibiotic combinations also inhibit the biofilm formation. More precisely, all EOs with ciprofloxacin in E. coli, tetracycline in P. aeruginosa, and gentamicin in E. faecalis showed the highest percentage of inhibition. Combinations induce up- and down-methylation of cytosines and adenines compared to EO or antibiotics alone. The study provides evidence about the role of EOs in enhancing the action of antibiotics by influencing key processes involved in resistance mechanisms such as biofilm formation and epigenetic changes. Synergistic interactions should be effectively considered in dealing with pathogenic microorganisms.

Abstract Femtosecond pump-probe spectroscopy using ultrafast optical and infrared pulses has become an essential tool to discover and understand complex electronic and structural dynamics in solvated molecular, biological, and material systems. Here we report the experimental realization of an ultrafast two-color X-ray pump X-ray probe transient absorption experiment performed in solution. A 10 fs X-ray pump pulse creates a localized excitation by removing a 1s electron from an Fe atom in solvated ferro- and ferricyanide complexes. Following the ensuing Auger–Meitner cascade, the second X-ray pulse probes the Fe 1s → 3p transitions in resultant novel core-excited electronic states. Careful comparison of the experimental spectra with theory, extracts +2 eV shifts in transition energies per valence hole, providing insight into correlated interactions of valence 3d with 3p and deeper-lying electrons. Such information is essential for accurate modeling and predictive synthesis of transition metal complexes relevant for applications ranging from catalysis to information storage technology. This study demonstrates the experimental realization of the scientific opportunities possible with the continued development of multicolor multi-pulse X-ray spectroscopy to study electronic correlations in complex condensed phase systems.

Introduction: Postural instability (PI) is a common disabling symptom in Parkinson’s disease (PD) patients, but the brain alterations underlying this sign are not fully understood yet. This study aimed to investigate the association between PI and callosal damage in PD and progressive supranuclear palsy (PSP) patients, using multimodal MR imaging. Methods: One-hundred and two PD patients stratified according to the presence/absence of PI (PD-steady N=58; PD-unsteady N=44), 69 PSP patients, and 38 healthy controls (HC) underwent structural and diffusion 3T brain MRI. Thickness, fractional anisotropy (FA) and mean diffusivity (MD) were calculated over 50 equidistant points covering the whole midsagittal profile of the corpus callosum (CC) and compared among groups. Associations between imaging metrics and postural instability score were investigated using linear regression. Results: Both PSP and PD-unsteady patient groups showed CC involvement in comparison with HC, while no difference was found between PD-steady patients and controls. The CC damage was more severe and widespread in PSP than in PD patients. The CC genu was the regions most damaged in PD-unsteady patients compared with PD-steady patients, showing significant microstructural alterations of MD and FA metrics. Linear regression analysis pointed at the MD in the CC genu as the main contributor to PI among the considered MRI metrics. Conclusion: This study identified callosal microstructural alterations associated with PI in unsteady PD and PSP patients, which provide new insights on PI pathophysiology and might serve as imaging biomarkers for assessing postural instability progression and treatment response.

We established consensus on practice-based metrics that characterize quality of care for older primary care patients and can be examined using secondary health administrative data. We conducted a two-round RAND/UCLA Appropriateness Method (RAM) study and recruited 10 Canadian clinicians and researchers with expertise relevant to the primary care of elderly patients. Informed by a literature review, the first RAM round evaluated the appropriateness and importance of candidate quality measures in an online questionnaire. Technical definitions were developed for each endorsed indicator to specify how the indicator could be operationalized using health administrative data. In a virtual synchronous meeting, the expert panel offered feedback on the technical specifications for the endorsed indicators. Panelists then completed a second (final) questionnaire to rate each indicator and corresponding technical definition on the same criteria (appropriateness and importance). We used statistical integration to combine technical expert panelists' judgements and content analysis of open-ended survey responses. Our literature search and internal screening resulted in 61 practice-based quality indicators for rating. We developed technical definitions for indicators endorsed in the first questionnaire (n = 55). Following the virtual synchronous meeting and second questionnaire, we achieved consensus on 12 practice-based quality measures across four Priority Topics in Care of the Elderly. The endorsed indicators provide a framework to characterize practice- and population-level encounters of family physicians delivering care to older patients and will offer insights into the outcomes of their care provision. This study presented a case of soliciting expert feedback to develop measurable practice-based quality indicators that can be examined using administrative data to understand quality of care within population-based data holdings. Future work will refine and operationalize the technical definitions established through this process to examine primary care provision for older adults in a particular context (Ontario, Canada).

Introduction: In postmenopausal women, vitamin D deficiency has been associated with disability, low muscle mass and fractures. Irisin is an important myokine that may contribute to the maintenance of muscle and bone density. Vitamin D is associated with the growth and function of muscle tissue through interactions between the vitamin D receptor and PGC-1α and activation of p38/MAPK (mitogen-activated protein kinase) in muscle, a mechanism similar to irisin action. The aim of this pilot study was to evaluate the effects of cholecalciferol supplementation on serum irisin levels in sedentary postmenopausal women with hypovitaminosis D (25(OH)D

Natural α-glucosidase inhibitors from plant-based foods such as catechins offer an attractive strategy for their potential anti-diabetic effects. In this study, infusions of three different tea types (green, white, and oolong) were investigated for their total phenolic (TPC) and catechins (EGCG, ECG, EGC, and EC) content, and for their α-glucosidase inhibitory activities. We observed that the level of TPC in white tea was significantly higher compared to oolong and green tea, which suggests higher content of EGCG and ECG catechins in fresh young leaves. Our findings showed that the higher content of such catechins in the infusion of white tea well correlated with a strong inhibition of α-glucosidase, and such inhibition was demonstrated to be more effective than the FDA-approved drug acarbose. Then, we computationally explored the molecular requirements for enzyme inhibition, especially for the most active catechins EGCG and ECG, as well as their disposition/stability within the active site.

Objetivo: As infecções relacionadas aos implantes ortopédicos (IRI), que abrange às infecções relacionadas às fraturas (IRF) e às infecções de próteses ortopédicas (IPO), persiste como uma complicação comum após procedimentos cirúrgicos ortopédicos para estabilização de fraturas. Mesmo durante a COVID-19, com a redução dos casos de traumatismo, as taxas de IRI permaneceram elevadas em nossa instituição. O presente estudo teve como objetivo investigar as características epidemiológicas e microbiológicas das IRI em um centro ortopédico terciário brasileiro entre 2020 e 2022. Método: Estudo de coorte retrospectivo em um único centro, envolvendo todos os pacientes submetidos a cirurgia ortopédica para estabilização de fraturas. O diagnóstico de IRF e IPO foi realizado de acordo com os critérios da EBJIS. Foram analisados 402 pacientes que passaram por algum tipo de correção cirúrgica de fratura, sendo incluídos na análise aqueles que desenvolveram IRF e IPO. Os patógenos foram isolados a partir de culturas de tecido peri-implante e fluido de sonicação, e identificados por meio de MALDI-TOF. Resultados: Um total de 65 pacientes com IRI foram incluídos, resultando em uma incidência de infecção de 16,1% (65/402). Os pacientes masculinos representaram 73,8% da amostra, com média de idade de 48,5 ± 18,6 anos. As fraturas fechadas corresponderam a 60% dos casos. Em relação ao mecanismo de trauma, quedas foram responsáveis por 43,1% dos casos, seguidas por acidentes automobilísticos (26,6%). Os sítios de infecção mais frequentemente afetados foram tíbia (26,2%) e quadril (12,3%). Observou-se que 86,2% dos casos correspondiam a IRF e 12,3% a IPO, enquanto infecções após instrumentação da coluna vertebral foram diagnosticadas em 1,5% dos casos. Entre os pacientes com culturas bacterianas positivas, 68,9% apresentaram bactérias gram-positivas e 31% bactérias gram-negativas, sendo o Staphylococcus aureus o patógeno mais prevalente em todos os sítios de infecção. Infecções polimicrobianas (24,1%), principalmente envolvendo bacilos gram-negativos, foram menos comuns do que infecções monomicrobianas (75,8%). Conclusão: Este estudo evidenciou que a incidência de IRI permaneceu alta durante a COVID-19, sendo as infecções monomicrobianas, incluindo espécies de Staphylococcus, as predominantes. A identificação da epidemiologia das vítimas de traumatismo ortopédico e da prevalência microbiológica constitui o primeiro passo em direção ao planejamento terapêutico bem-sucedido.

Introdução: A incidência da infecção relacionada à fratura (IRF) pode variar de 0,4 a 32%, sendo ainda maior em fraturas expostas. Os principais patógenos descritos são os cocos Gram-positivo (CGP), em especial o S. aureus. Entretanto, estudos que avaliam informações epidemiológicas e microbiológicas nas IRF são escassos no Brasil. Este estudo descreve a incidência de IRF e os patógenos associado em um hospital público terciário universitário brasileiro ao longo de 3 anos de coleta de dados. Métodos: Estudo transversal, unicêntrico, com dados coletados entre março de 2020 e março de 2023 de pacientes maiores de 18 anos com fraturas ósseas fechadas e expostas submetidas à fixação ortopédica, exceto próteses articulares. Para o diagnóstico de IRF foi utilizada a definição proposta por METSEMAKERS et al (2017). Resultados: Do total de 462 pacientes incluídos, 71,6% foram do sexo masculino com média de idade de 47,6 anos (DP±20,8). As principais comorbidades foram Hipertensão Arterial Sistêmica (19,3%), tabagismo (19,3%) e etilismo (17,3%). As fraturas expostas foram 25,1% dos casos, sendo a classificação de Gustilo-Anderson do tipo 3-A a mais frequente (69,8%). A incidência global de IRF, em fraturas fechadas, e em fraturas expostas foi de 19,7%, 16,5%, e 29,3% respectivamente. A principal profilaxia cirúrgica foi uma cefalosporina de 1a ou 2a geração (84,6%) associada a um aminoglicosídeo (44,6%) ou isolada (43,1%). Os principais patógenos identificados foram S. aureus (22,1%), K. pneumoniae (11,6%), S. epidermidis (10,5%), demais Staphylococcus coagulase-negativo (10,5%), E. coli (6,3%), P. aeruginosa (5,3%), Streptococcus spp beta-hemolítico (4,2%), outros CGP (9,5%) e outros bacilos Gram-negativo (BGN) (20,0%). A resistência à meticilina foi identificada em 60% das cepas do gênero Staphylococcus e a multidroga resistência (MDR) foi identificada em 53,7% dos BGN. Conclusão: A incidência de IRF global e em fraturas expostas foi elevada, assim como em fraturas fechadas nas quais menores valores são previstos devido à adoção sistemática da profilaxia antimicrobiana cirúrgica. A elevada frequência de BGN (43,2%) demonstrando perfil de MDR (53,7%) associada a uma alta resistência à meticilina do gênero Staphylococcus (60%) apontam para uma mudança no perfil epidemiológico de IRF e sugerem a revisão da profilaxia antimicrobiana em cirurgias ortopédicas com implantes no Brasil.

Introdução: O tratamento ideal da osteomielite ainda é um motivo importante de debate na literatura. Devido à dificuldade de erradicar o biofilme, um dos tratamentos preconizados envolve desbridamento e terapia local com a colocação de espaçadores de polimetilmetacrilato carregado de antibiótico (PMMA+ATB). Há ainda dúvidas se a permanência in situ prolongada do PMMA+ATB no paciente causaria eventos adversos. O objetivo deste estudo foi investigar se a permanência de culturas positivas de fluido de sonicação de PMMA+ATB in situ alteram o desfecho clínico de pacientes com osteomielite crônica. Metodologia: Realizamos estudo preliminar em uma série de casos de 13 pacientes que possuíam diagnóstico de osteomielite em um hospital universitário de São Paulo no período entre 2021 e 2022. Todos receberam tratamento antimicrobiano sistêmico e local com PMMA eluído de Vancomicina e/ou Gentamicina. As culturas de tecido infectado do paciente; o tempo de retenção do PMMA+ATB maior que 4 semanas; e as culturas do fluido de sonicação do PMMA+ATB foram comparados ao sucesso terapêutico destes pacientes avaliados após 6 meses e um ano do tratamento local. O desfecho clínico “sucesso terapêutico” foi definido como ausência de: necessidade de novas terapias antimicrobianas sistêmicas; necessidade de reabordagem cirúrgica; sinais clínicos de osteomielite ativa; e morte relacionada ao procedimento ortopédico. Resultados: As culturas do fluido de sonicação de PMMA+ATB foram positivas em 54% (7/13) dos pacientes. Destes, 100% tiveram sucesso terapêutico após 6 meses. Após um ano, foi possível avaliar o desfecho de 9 pacientes, e 44% (4/9) possuíam cultura de fluido de sonicação de PMMA+ATB positiva. Entretanto, o sucesso terapêutico foi atingido em 78% destes. O tempo de permanência in situ do PMMA+ATB variou de 1,5 a 37 semanas (média= 9 semanas; mediana= 5 semanas). Após 6 meses de seguimento, não houve diferença nas taxas de sucesso de tratamento nos pacientes que mantiveram PMMA+ATB in situ por mais (78%) ou menos (75%) de 4 semanas. Conclusão: A terapia com PMMA+ATB parece ser uma forma efetiva de tratamento de osteomielite crônica. A positividade das culturas em fluido de sonicação de PMMA+ATB após a retirada cirúrgica não parecem estar correlacionadas ao desfecho clínico de sucesso terapêutico após 6 meses e um ano.

Introdução: A infecção relacionada à fratura (IRF) pode ocorrer em taxas elevadas e a maioria causada por Staphylococcus aureus. Contudo, agentes etiológicos podem variar com a localização anatômica e geográfica, mecanismo de trauma e fatores do hospedeiro, sendo importante determinar os patógenos dominantes locais e suas implicações no desfecho do tratamento clínico e cirúrgico. O objetivo deste estudo foi caracterizar o perfil microbiológico nas IRF e associar a falha do tratamento aos patógenos encontrados. Métodos: Estudo observacional, do tipo coorte prospectiva, em pacientes maiores de 18 anos com IRF, conforme critérios de Metsemakers et al (2017), internados entre 2020 e 2023 em hospital terciário de São Paulo. Falha do tratamento de IRF foi definido como necessidade de reoperação ou reinício da terapia antibiótica para o mesmo patógeno, amputação ou óbito. Proporções das variáveis categóricas foram associadas utilizando o teste qui-quadrado ou exato de Fisher. Resultados: Foram avaliados 65 casos de IRF com diagnóstico microbiológico. A média de idade na população foi 44,41 (± 16,7) anos e 46 pacientes eram do sexo masculino (70,8%). Falha de tratamento ocorreu em 27 (41,5%) casos e 6 (9,2%) perderam seguimento após 6 meses de acompanhamento médio. O microrganismo mais frequente nos casos de falha foi o S. aureus (n = 9; 33,3%), K. pneumoniae (n = 6; 22,2%), S. epidermidis (n = 4; 14,8%), E. coli (n = 4; 14,8%) e P. aeruginosa (n = 4; 14,8%). Na análise por grupos houve risco maior de falha nas IRF por bacilos gram-negativo (BGN) não fermentadores [Incidência: 52,9% vs. 42,9%; RR: 1,24 (intervalo de confiança (IC)95% = 0,70-2,18)], S. aureus [Incidência: 50,0% vs. 43,9%; RR:1,14 (IC95% = 0,64-2,03)] e BGN fermentadores [Incidência: 50,0% vs. 45,5%; RR: 1,10 (IC95% = 0,40-3,06)]. Houve menor risco de falha no grupo de Staphylococcus coagulase-negativos [Incidência: 41,2% vs. 47,6%; RR: 0,86 (IC95% = 0,45-1,66)]. Em relação à resistência antimicrobiana, 60% dos Staphylococcus foram resistentes à meticilina (MRSA) e 53,7% dos BGN foram multidrogas resistentes (MDR). Conclusões: Este estudo evidencia altas taxas de falha de tratamento nas IRF, provavelmente associados a bactérias multirresistentes, incluindo o MRSA e BGN-MDR. S. aureus foi a etiologia mais prevalente, contudo, BGNs não fermentadores cursaram com maior risco de falha terapêutica, o que está de acordo a incidência crescente desses patógenos em infecções associadas à assistência à saúde no Brasil.

Introdução: O tratamento antimicrobiano sistêmico empírico ou dirigido por cultura para as infecções ósseas tem classicamente demonstrado altas taxas de falha. Por outro lado, a terapia antibiótica local associada a um biomaterial com o cimento ortopédico ou polimetilmetacrilato (PMMA), tem progressivamente mostrado altas taxas de resolutividade e poucos eventos adversos locais e sistêmicos. Este estudo avalia o desfecho de sobrevida livre de infecção após a terapia antibiótica local no tratamento das osteomielites crônicas e infecções associadas à fratura (IAF). Método: Estudo de série de casos com seguimento ambispectivo para avaliar a taxa de controle de infecção óssea em pacientes com osteomielite crônica cavitaria e IAF que foram tratados com terapia antibiótica local associado à PMMA, e acompanhados no Grupo de Infecções Musculoesqueléticas de um Hospital Universitário Terciário, de abril de 2020 a maio de 2023. Foram excluídos os pacientes com artroplastias infectadas. Resultados: No total, oito pacientes com osteomielite e 13 com IAF foram avaliados, sendo 15 (71%) homens, com média de idade de 42 anos (DP+- 18-72). A comorbidade mais comum foi o tabagismo (23%). Infecção em tíbia e fêmur foram predominantes (90%), seguido de coluna e úmero. Em 20 pacientes (95%) foi usado o PMMA como veículo para o antibiótico e em 1 (5%), biocerâmica. O cimento foi diluído apenas com vancomicina em 15 casos (71%) e em associação com gentamicina em 6 (28%). Dezesseis pacientes (76%) receberam tratamento sistêmico, enquanto 6 (28%) receberam apenas tratamento local. Foram identificados microrganismos em 95% dos casos, sendo metade infecção polimicrobiana. Trinta e sete patógenos foram isolados em culturas ósseas e de fluido de sonicação, 15 (41%) eram Staphylococcus coagulase negativos, 13 Staphylococcus aureus, 4 Bacilos Gram-negativos, 3 Streptococcus spp. e 2 Enterococcus faecalis. O tempo médio de seguimento foi de 9 meses (2 – 19 meses). Três pacientes (15%) tiveram recorrência de sintomas, enquanto 18 (85%) permanecem assintomáticos. Todos os 3 receberam também terapia antimicrobiana sistêmica. Conclusão: O tratamento para osteomielite com terapia antibiótica associado ao PMMA e outros biomateriais se mostrou eficiente como terapia adjuvante. Mais estudos são necessários para padronização de materiais e doses.

Merkel cell carcinoma is a rare and aggressive cutaneous neuroendocrine cancer that occurs in the photodamaged skin of white and elderly patients, usually presenting as a solitary plaque or nodule in the head and neck region. When located in the lower palpebral area, reconstructing the defect resulting from its excision can become challenging for the dermatological surgeon due to the local cosmetic and functional peculiarity. We report the use of a bilobed flap for lower eyelid reconstruction with a satisfactory result, both in terms of aesthetics and the resulting functionality.

AimThis prospective pilot study evaluated inflammatory and intestinal barrier biomarkers and the effects of a synbiotic in obese adolescents.MethodsEighteen obese and 20 eutrophic adolescents were evaluated for body composition using bioimpedance analysis (BIA), body mass index (BMI), IL-6 and lipopolysaccharide (LPS) serum levels, CD4 and FoxP3 Treg lymphocytes and monocytes. Synbiotic supplementation for 60 days was also evaluated for these parameters only in obese adolescents.ResultsWe observed an increase in CD4 lymphocyte (18.0 ± 12.4 vs. 8.9 ± 7.5; p

Introduction Older adults have high rates of primary care utilisation, and quality primary care has the potential to address their complex medical needs. Family physicians have different levels of knowledge and skills in caring for older patients, which may influence the quality of care delivery and resulting health outcomes. In this study, we aim to establish consensus on practice-based metrics that characterise quality of care for older primary care patients and can be examined using secondary, administrative data.Methods and analysis We describe a two-round RAND/UCLA Appropriateness Method (RAM) study to assess the consensus of a technical expert panel. We will recruit pan-Canadian experts who demonstrate excellence in clinical practice or scholarship related to the primary care of older adults. A literature review will generate a candidate list of practice-based quality indicators. The first round aims to evaluate the appropriateness and importance of candidate indicators through an online questionnaire. We will then develop technical definitions for each endorsed indicator using ICES data holdings. Panellists will offer feedback on the technical definitions in a virtual synchronous meeting and provide ratings on the same criteria in a second questionnaire.Ethics and dissemination Our study has been approved by the Hamilton Integrated Research Ethics Board (Project ID #15545). Findings will be disseminated via manuscripts, presentations and the lead author’s thesis.Trial registration number ISRCTN17074347

Rape and sexual violence occur in all social classes and societies. In most cases, the sexual offenders are known to the victim and the majority of rapes happen in intimate relationships. Children are particularly vulnerable to sexual abuse, in particular, the female sex. The sexual abuse of minors is defined as “any sexual activities that an adult carries on or with a person under the age of consent.” Literature evidence that the prevalence of any type of violence among women with disabilities varies between 26.0% and 90.0%, compared to nondisabled women, showing that people with disabilities have an increased risk of suffering physical and sexual violence. Children with intellectual disabilities (ID) show a high risk of sexual victimization. The World Health Organization presently defines mental retardation as “a significantly reduced ability to understand new or complex information and to learn and apply new skills (impaired intelligence). This results in a reduced ability to cope independently (impaired social functioning), and begins before adulthood, with a lasting effect on development.” The aim of this study is to investigate the correct identification of sexual abuse and severe mental retardation through the collaboration of a team of experts (forensic pathologist, psychiatrist, psychologist, gynecologist, pediatrician, and social worker). We present a case of a 12-year-old female child, who suffers from severe mental retardation and was the victim of rape by a 79-year-old man. The study shows the difficulties in discovering episodes of sexual abuse among children affected by ID by evidencing the importance of adequate analysis through a multidisciplinary approach. The work focuses on the need to improve knowledge about medical and forensic investigations through proper protocols, for early recognition and appropriate management of these complicated cases.

Abstract The overall estimated risk of recurrence after an apparently complete thyroid cancer resection ranges from 5% CTCs (p = 0.09) and with >30% S‐phase cells at baseline (p = 0.0015), predicting ≤1 year relapsing lesion event. These results suggest a new intriguing frontier of precision oncology forefront cytology‐based liquid biopsy.

Metabolic reprogramming is an emerging hallmark of cancer, involving the overexpression of metabolism-related proteins, such as glucose and monocarboxylate transporters and intracellular glycolytic enzymes. The biology of testicular germ cell tumors (TGCTs) is very complex, and although their metabolic profile has been scantily explored, some authors have recently reported that the metabolic rewiring of cancer cells resulted in an association with aggressive clinicopathological characteristics. In this study we have investigated, by immunohistochemical analysis, the expression of key proteins sustaining the hyperglycolytic phenotype in pure seminoma (SE, nr. 35), pure embryonal carcinoma (EC, nr. 17) tissues samples, and normal testes (nr. 5). GLUT1, CD44, PFK-1, MCT1, MCT4, LDH-A, and PDH resulted in more expression in EC cells compared to SE cells. TOM20 was more expressed in SE than in EC. GLUT1, MCT1, and MCT4 expression showed a statistically significant association with SE histology, while for EC, the association resulted in being significant only for GLUT1 and MCT4. Finally, we observed that EC resulted as negative for p53, suggesting that the GLUT1 and MTC overexpression observed in EC could be also attributed to p53 downregulation. In conclusion, our findings evidenced that EC exhibits a higher expression of markers of active aerobic glycolysis compared to SE, suggesting that the aggressive phenotype is associated with a higher glycolytic rate. These data corroborate the emerging evidence on the involvement of metabolic reprogramming in testicular malignancies as well, highlighting that the metabolic players should be explored in the future as promising therapeutic targets.

Abstract Background AQUILA (NCT03470103) was a prospective, observational, 12-month cohort study evaluating treatment patterns, clinical effectiveness, and safety of intravitreal aflibercept (IVT-AFL) in patients from Latin America with neovascular age-related macular degeneration (nAMD). Methods Treatment-naïve and previously treated (switching to IVT-AFL) patients (aged ≥ 55 years) were enrolled from March 2018, with a primary completion date of September 2020, from Argentina, Colombia, Costa Rica, and Mexico. Patients received IVT-AFL in a routine clinical practice setting. Results Of 274 patients in the full analysis set, 201 were treatment-naïve and 73 had received previous treatment. The mean ± standard deviation number of IVT-AFL injections received by month 12 was 4.2 ± 1.9 (treatment-naïve) and 5.2 ± 2.7 (previously treated). The median duration from diagnosis to IVT-AFL treatment was 1.2 months (treatment-naïve) and 19.5 months (previously treated). Mean best-corrected visual acuity (BCVA) (Early Treatment Diabetic Retinopathy Study [ETDRS] letters) improved from baseline to month 12 by + 5.2 ± 18.3 (treatment-naïve; baseline: 48.2 ± 23.5) and + 3.1 ± 15.3 letters (previously treated; baseline: 47.7 ± 21.4). Conclusion AQUILA is the first study to assess the use of IVT-AFL in routine clinical practice in Latin America. Mean BCVA and other visual acuity outcomes improved in both treatment groups, despite many patients not receiving the IVT-AFL label-recommended regimen of three initial monthly doses, or seven or more injections in 12 months. Patients who did receive the label-recommended number of injections had numerically greater improvements in visual acuity outcomes. Patients with nAMD treated regularly and more frequently with IVT-AFL, therefore, have the potential to achieve outcomes consistent with those observed in interventional studies. Trial registration: Clinicaltrials.gov, NCT03470103. Registered February 5, 2018, https://clinicaltrials.gov/ct2/show/NCT03470103

Abstract We have coupled the GEOS‐Chem tropospheric‐stratospheric chemistry mechanism and the Community Aerosol and Radiation Model for Atmospheres (CARMA), a sectional aerosol microphysics module, within the NASA Goddard Earth Observing System Chemistry‐Climate Model (GEOS CCM) in order to simulate the interactions between stratospheric chemistry and aerosol microphysics. We use observations of the 1991 Mount Pinatubo volcanic cloud to evaluate this new version of the GEOS CCM. The GEOS‐Chem chemistry module is used to simulate the oxidation of sulfur dioxide (SO2) more realistically than assuming hydroxyl radical (OH) fields are constant, as OH concentrations in the plume decrease dramatically in the weeks following the eruption. CARMA simulates sulfate aerosols with dynamic microphysical and optical properties. The CARMA‐calculated aerosol surface area is coupled to the chemistry module from GEOS‐Chem for the calculation of heterogeneous chemistry. We use a set of observational and theoretical constraints for Pinatubo to evaluate the performance of this new version of the GEOS CCM. These simulations are specifically compared with satellite and in‐situ observations and provide insights into the connections between the gas‐phase chemistry and the aerosol microphysics of the early plume and how they impact the climatic and chemical changes following a large volcanic eruption. A second, smaller eruption is also included in these simulations, the 15 August 1991, eruption of Cerro Hudson in Chile, which we find essential in explaining the aerosol optical depth in the Southern Hemisphere in 1991.

ABSTRACT Adaptive antibiotic resistance is a transient metabolic adaptation of bacteria limiting their sensitivity to low, progressively increased, concentrations of antibiotics. Unlike innate and acquired resistance, adaptive resistance is dependent on the presence of antibiotics, and it disappears when the triggering factor is removed. Low concentrations of antibiotics are largely diffused in natural environments, in the food industry or in certain body compartments of humans when used therapeutically, or in animals when used for growth promotion. However, molecular mechanisms underlying this phenomenon are still poorly characterized. Here, we present experiments suggesting that epigenetic modifications, triggered by low concentrations of ampicillin, gentamicin, and ciprofloxacin, may modulate the sensitivity of bacteria to antibiotics. The epigenetic modifications we observed were paralleled by modifications of the expression pattern of many genes, including some of those that have been found mutated in strains with permanent antibiotic resistance. As the use of low concentrations of antibiotics is spreading in different contexts, our findings may suggest new targets and strategies to avoid adaptive antibiotic resistance. This might be very important as, in the long run, this transient adaptation may increase the chance, allowing the survival and the flourishing of bacteria populations, of the onset of mutations leading to stable resistance. IMPORTANCE In this study, we characterized the modifications of epigenetic marks and of the whole transcriptome in the adaptive response of Escherichia coli cells to low concentrations of ampicillin, gentamicin, and ciprofloxacin. As the transient adaptation does increase the chance of permanent resistance, possibly allowing the survival and flourishing of bacteria populations where casual mutations providing resistance may give an immediate advantage, the importance of this study is not only in the identification of possible molecular mechanisms underlying adaptive resistance to antibiotics, but also in suggesting new strategies to avoid adaptation.

Dynamic digital radiography (DDR) is a high-resolution radiographic imaging technique using pulsed X-ray emission to acquire a multiframe cine-loop of the target anatomical area. The first DDR technology was orthostatic chest acquisitions, but new portable equipment that can be positioned at the patient’s bedside was recently released, significantly expanding its potential applications, particularly in chest examination. It provides anatomical and functional information on the motion of different anatomical structures, such as the lungs, pleura, rib cage, and trachea. Native images can be further analyzed with dedicated post-processing software to extract quantitative parameters, including diaphragm motility, automatically projected lung area and area changing rate, a colorimetric map of the signal value change related to respiration and motility, and lung perfusion. The dynamic diagnostic information along with the significant advantages of this technique in terms of portability, versatility, and cost-effectiveness represents a potential game changer for radiological diagnosis and monitoring at the patient’s bedside. DDR has several applications in daily clinical practice, and in this narrative review, we will focus on chest imaging, which is the main application explored to date in the literature. However, studies are still needed to understand deeply the clinical impact of this method.