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RATIONALE: Characterization of Regolith And Trace Economic Resources (CRATER), an Orbitrap™-based laser desorption mass spectrometry instrument designed to conduct high-precision, spatially resolved analyses of planetary materials, is capable of answering outstanding science questions about the Moon's formation and the subsequent processes that have modified its (sub)surface. METHODS: Here, we describe the baseline design of the CRATER flight model, which requires <20 000 cm3 volume, <10 kg mass, and <60 W peak power. The analytical capabilities and performance metrics of a prototype that meets the full functionality of the flight model are demonstrated. RESULTS: The instrument comprises a high-power, solid-state, pulsed ultraviolet (213 nm) laser source to ablate the surface of the lunar sample, a custom ion optical interface to accelerate and collimate the ions produced at the ablation site, and an Orbitrap mass analyzer capable of discriminating competing isobars via ultrahigh mass resolution and high mass accuracy. The CRATER instrument can measure elemental and isotopic abundances and characterize the organic content of lunar surface samples, as well as identify economically valuable resources for future exploration. CONCLUSION: An engineering test unit of the flight model is currently in development to serve as a pathfinder for near-term mission opportunities.
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PURPOSE OF REVIEW: Many patients with migraine report their attacks are triggered by various weather anomalies. Studies have shown mixed results regarding the association of migraine to weather changes. The purpose of the current review is to compile the most up-to-date research studies on how weather may affect migraine. In addition, we explore the association between weather and other inflammatory disease states as well as neurotransmitters. RECENT FINDINGS: Migraine attacks can be related to weather variables such as barometric pressure, humidity, and wind. However, the results of recent studies are inconsistent; weathers' effect on migraine attacks is around 20%. However, very strong weather factors have a more significant effect on migraine attack variables. Many individuals identify weather as a migraine attack trigger, yet we see no causative relationship between weather and migraine patterns. The outcomes of studies indicate mixed results and reflect individual variation in how weather can impact migraine patterns. Similar relationships can be seen with other rheumatologic and pain conditions in general. Overall, the combination of weather plus other factors appears to be a more significant migraine trigger.
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Transtornos de Enxaqueca , Tempo (Meteorologia) , Humanos , Transtornos de Enxaqueca/epidemiologia , Transtornos de Enxaqueca/etiologia , Pressão AtmosféricaRESUMO
While pre-exposure prophylaxis (PrEP) has demonstrated efficacy in preventing HIV transmission, disparities in access persist in the United States, especially among Hispanic/Latinx sexual minority men (SMM). Language barriers and differences in how Latinx SMM obtain information may impact access to PrEP and HIV prevention. This study used data from the 2021 American Men's Internet Survey (AMIS) to examine differences in communication networks and PrEP use among Latinx SMM by primary language (Spanish vs. English). We examined the associations between Latinx SMM's individual- and meso-level communication networks and PrEP-related outcomes using modified Poisson regression with robust variances. Spanish-speaking Latinx SMM in the study were less likely to test for HIV, be aware of PrEP, and use daily PrEP, compared to English-speaking participants. Sexuality disclosure to a healthcare provider was positively associated with PrEP uptake among all participants and predicted STI testing over the past 12 months among English-speaking Latinx SMM. Findings highlight disparities in PrEP awareness and uptake among Latinx SMM, especially among those whose primary language is Spanish. Addressing these disparities through targeted interventions, including improved communication with healthcare providers, may help facilitate PrEP access and use in this population.
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Infecções por HIV , Hispânico ou Latino , Idioma , Profilaxia Pré-Exposição , Minorias Sexuais e de Gênero , Humanos , Masculino , Hispânico ou Latino/estatística & dados numéricos , Hispânico ou Latino/psicologia , Profilaxia Pré-Exposição/estatística & dados numéricos , Adulto , Infecções por HIV/prevenção & controle , Infecções por HIV/etnologia , Minorias Sexuais e de Gênero/estatística & dados numéricos , Minorias Sexuais e de Gênero/psicologia , Estados Unidos , Adulto Jovem , Pessoa de Meia-Idade , Adolescente , Inquéritos e Questionários , Barreiras de Comunicação , Comunicação , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde/etnologia , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Conhecimentos, Atitudes e Prática em SaúdeRESUMO
BACKGROUND AND OBJECTIVES: Poor oral health disproportionately affects low-income older adults, for whom food insecurity and poor mental health may affect dental health. We explored the associations between food insecurity, mental health, and dental health. Furthermore, we examined whether mental health impacted the associations between food insecurity and dental health. MATERIALS AND METHODS: We conducted a cross-sectional study with a convenience sample of 226 older adults (aged 50+), employing survey and dental screening data. Participants were recruited from seven community-based organisations in Washington State, USA. We calculated descriptive statistics and conducted Chi-square tests, t tests, and logistic regression analyses to assess the associations between aspects of dental health (untreated decay, gum disease, and unmet dental needs), mental health (depression and cognitive function), and food insecurity. RESULTS: In our sample, food insecurity was observed in 28.4%, 40.6% had untreated decay, 31.6% gum disease, and 42.5% unmet dental needs. Food insecurity was associated with a higher occurrence of untreated decay and unmet dental needs. Participants experiencing food insecurity had higher odds of gum disease (aOR = 2.3; 95% CI: 1.1, 5.2) and unmet dental needs (aOR = 3.2; 95% CI:1.4, 7.6). Greater gum disease due to food insecurity was observed among individuals with lower levels of cognitive impairment. CONCLUSION: Food insecurity is associated with poorer oral health among older adults and cognitive function may modify this relationship. These findings underscore the importance of addressing both food insecurity and cognitive impairment as integral components of efforts to improve the oral health of older adults.
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Nearly half of all sexually transmitted infections occur in adolescents and young adults. Among them, syphilis infections are on the rise in the United States. Sexually active adolescents, especially those who do not use condoms consistently or are men who have sex with men, are at particular risk for syphilis infection. With the rise in acquired syphilis infections, the incidence of congenital syphilis has also increased. Syphilis can have a variety of presentations based on infectious stage and central nervous system involvement. Careful physical examination and history can elicit the diagnosis. Screening with a nontreponemal test followed by treponemal testing can confirm the diagnosis, and staging is determined clinically. Testing for all sexually transmitted infections should be pursued because coinfections are common. Penicillin is the first-line treatment for syphilis, and duration of therapy depends on the presence of neurologic symptoms; all infants with possible congenital syphilis should receive treatment. Posttreatment monitoring is essential to confirm successful eradication of syphilis. All sexually active, at-risk patients, including pregnant persons, should be screened for syphilis, and those diagnosed as having syphilis should be counseled on disclosure to partners. Although not often found in a pediatric population, with the increasing incidence of syphilis infections in the United States, pediatric providers should have a low threshold for syphilis screening in adolescents and a high index of suspicion for congenital syphilis in infants.
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Sífilis , Humanos , Sífilis/diagnóstico , Sífilis/epidemiologia , Sífilis/terapia , Sífilis/tratamento farmacológico , Adolescente , Sífilis Congênita/diagnóstico , Sífilis Congênita/epidemiologia , Sífilis Congênita/prevenção & controle , Criança , Masculino , Feminino , Antibacterianos/uso terapêutico , Gravidez , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: Air pollution-induced systemic inflammation and oxidative stress are hypothesized to be the major biological mechanisms underlying pathological outcomes. We examined the association between short-term exposure to ambient air pollutants and biomarkers of inflammation and oxidative stress in 2199 general middle-aged Korean population residing in metropolitan areas. METHODS: Serum levels of inflammatory cytokines (interleukin [IL]-1ß, IL-6, IL-8, IL-10, and tumor necrosis factor [TNF]-α) and urinary levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) were measured. Daily concentrations of a series of air pollutants (particulate matter [PM]10, PM2.5, SO2, NO2, CO, and O3) were predicted using the Community Multiscale Air Quality modeling system, and participant-level pollutant exposure was determined using geocoded residential addresses. Short-term exposure was defined as the 1- to 7-day moving averages. RESULTS: The multivariable-adjusted linear models controlling for the sociodemographic, lifestyle, temporal, and meteorological factors identified positive associations of PM with IL-1ß, IL-8, IL-10, TNF-α, and 8-OHdG levels; SO2 with IL-10 levels, CO with IL-1ß, IL-10, and TNF-α levels; and O3 with IL-1ß, IL-8, and 8-OHdG levels. O3 levels were inversely associated with IL-10 levels. For each pollutant, the strongest associations were observed for the 7-day average PM and CO with IL-1ß (per 10-µg/m3 increase in PM10: 2.7%, 95% confidence interval [CI] = 0.6-4.8; per 10-µg/m3 increase in PM2.5: 6.4%, 95% CI = 2.4-10.5; per 0.1-ppm increase in CO: 3.3%, 95% CI = 0.3-6.5); the 2-day average SO2 with IL-10 levels (per 1-ppb increase in SO2: 1.1%, 95% CI = 0.1-2.1); and the 7-day average O3 with IL-8 levels (per 1-ppb increase in O3: 1.3%, 95% CI = 0.7-1.9). CONCLUSIONS: Short-term exposure to ambient air pollutants may induce oxidative damage and pro-inflammatory roles, together with counter-regulatory anti-inflammatory response.
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Poluentes Atmosféricos , Poluentes Ambientais , Pessoa de Meia-Idade , Humanos , Poluentes Atmosféricos/efeitos adversos , Poluentes Atmosféricos/análise , Estudos Transversais , Interleucina-10 , Interleucina-8 , Fator de Necrose Tumoral alfa , Material Particulado/efeitos adversos , Material Particulado/análise , Inflamação/induzido quimicamente , Inflamação/epidemiologia , Biomarcadores , Estresse OxidativoRESUMO
In this article, we investigate how the concept of Care Biography and related concepts are understood and operationalised and describe how it can be applied to advancing our understanding and practice of holistic and person-centred care. Walker and Avant's eight-step concept analysis method was conducted involving multiple database searches, with potential or actual applications of Care Biography identified based on multiple discussions among all authors. Our findings demonstrate Care Biography to be a novel overarching concept derived from the conjunction of multiple other concepts and applicable across multiple care settings. Concepts related to Care Biography exist but were more narrowly defined and mainly applied in intensive care, aged care, and palliative care settings. They are associated with the themes of Meaningfulness and Existential Coping, Empathy and Understanding, Promoting Positive Relationships, Social and Cultural Contexts, and Self-Care, which we used to inform and refine our concept analysis of Care Biography. In Conclusion, the concept of Care Biography, can provide a deeper understanding of a person and their care needs, facilitate integrated and personalised care, empower people to be in control of their care throughout their life, and help promote ethical standards of care.
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Formação de Conceito , Humanos , Assistência Centrada no Paciente/normas , EmpatiaRESUMO
Healthy social functioning has been a growing focus for understanding children's positive development and well-being. Despite the flexibility and cost-effectiveness of behavior rating scales, there has been a rising issue of concern in both practice and research applications regarding rating scales and its low cross-informant agreement. The present study aimed to analyze the extent to which caregivers and teachers agree about children's prosocial behaviors, identify whether there were differences in the degree of agreement across child welfare settings, and ultimately offer recommendations for assessing behavior for children involved with child welfare services. To do so, the reports of 1,224 children, caregivers, and teachers from the National Survey of Child and Adolescent Well-Being (NSCAW) I who have been investigated by Child Protective Services (CPS) for abuse and/or neglect have been examined. Intra-class correlation coefficients (ICCs) of caregiver and teacher assessment of children's prosocial functioning were calculated to understand the degree of agreement in their perceptions of children's prosocial behaviors. ICC values presented show that agreement was low but significant across all samples and subscales (ICC range, .11-.22). It is suggested that future researchers pursue examination of the underlying mechanisms or factors that contribute to informant discrepancies.
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Patients 80 years or older with HbA1c <7.0% (53 mmol/mol) treated with multiple daily insulin injections had low rates of rapid-acting insulin deprescription and initiation of diabetes medications with lower risk of hypoglycemia. Further investigation is needed to elucidate factors contributing to potentially inappropriately aggressive treatment of these patients.
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Diabetes Mellitus Tipo 2 , Hipoglicemia , Humanos , Idoso , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/efeitos adversos , Glicemia , Hemoglobinas Glicadas , Hipoglicemia/induzido quimicamente , Hipoglicemia/diagnóstico , Insulina/uso terapêuticoRESUMO
OBJECTIVES: This pilot study examined the association between food insecurity and edentulism among older adults in Washington State. METHODS: This study focused on adults aged 50 years and older, who were recruited through seven community-based organizations in Washington State. The exposure variable was food security level (high, marginal, and low/very low food security) assessed using the 10-item U.S. Adult Food Security Survey. The outcome was edentulism, defined as having zero natural teeth. Confounder-adjusted odds ratios (OR) and 95% confidence intervals (CIs) were generated using binary logistic regression models (α = 0.05). RESULTS: Of the 216 participants, 28.7% (n = 62) had low/very low food security and 7.9% (n = 17) had zero teeth. Older adults with low or very low food security had greater odds of being edentulous compared to those with marginal or high food security, although the difference was not statistically significant (OR: 1.39; 95% CI: 0.46, 4.20; p = 0.56). CONCLUSIONS: Future research should explore food insecurity-focused interventions aimed at preventing edentulism in older adults in a broader effort to address oral health inequities.
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OBJECTIVE: Families of critically ill patients may benefit from receiving a written update of patient care each day. Our objective was to develop a system to facilitate care provider creation of written updates and to determine the effect of implementing this process on the care provider experience. DESIGN: The experiences of ICU care providers (nurses, advanced practice providers, and physicians) were measured monthly during a 3-month pre-intervention and a 3-month intervention period. During the intervention period, written updates were sent to families each day and posted in the electronic medical record. Study investigators assisted by editing and distributing the written communication to families. SETTING: An urban academic medical center in the United States. MAIN OUTCOME MEASURES: Nurse-Physician Collaboration Scale (NPCS) and Maslach Burnout Inventory (MBI). RESULTS: Over the 3-month intervention period, care providers created written communication for families of 152 patients (average 5 ICU days per family). NPCS scores among the 65 participating care providers were significantly lower, indicating greater collaboration during the intervention vs. pre-intervention period: 49.9 (95 % CI 46.4-53.6) vs. 55.4 (95 % CI 51.5-59.3), p = 0.002. MBI scores were similar during the intervention vs. pre-intervention periods. A subset of care providers participated in individual interviews. Care providers reported that the process of creating written communication was acceptable and had clear benefits for both families and the medical team. CONCLUSIONS: Use of written communication as a supplement to verbal communication improves collaboration among ICU care providers without affecting symptoms of burnout. IMPLICATIONS FOR PRACTICE: We created a system to facilitate written communication with ICU families that was acceptable to care providers and improved aspects of their experience. In the future, use of written communication can be enhanced with refinements to the process that reduce the time spent creating written updates while highlighting the benefits to families and care providers.
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Comunicação , Unidades de Terapia Intensiva , Redação , Humanos , Unidades de Terapia Intensiva/organização & administração , Masculino , Feminino , Redação/normas , Adulto , Pessoa de Meia-Idade , Equipe de Assistência ao Paciente/normasRESUMO
PURPOSE: We recently developed an optical instrument to non-invasively detect fluorescently labeled circulating tumor cells (CTCs) in mice called 'Diffuse in vivo Flow Cytometry' (DiFC). OTL38 is a folate receptor (FR) targeted near-infrared (NIR) contrast agent that is FDA approved for use in fluorescence guided surgery of ovarian and lung cancer. In this work, we investigated the use OTL38 for in vivo labeling and detection of FR + CTCs with DiFC. PROCEDURES: We tested OTL38 labeling of FR + cancer cell lines (IGROV-1 and L1210A) as well as FR- MM.1S cells in suspensions of Human Peripheral Blood Mononuclear cells (PBMCs) in vitro. We also tested OTL38 labeling and NIR-DIFC detection of FR + L1210A cells in blood circulation in nude mice in vivo. RESULTS: 62% of IGROV-1 and 83% of L1210A were labeled above non-specific background levels in suspensions of PBMCs in vitro compared to only 2% of FR- MM.1S cells. L1210A cells could be labeled with OTL38 directly in circulation in vivo and externally detected using NIR-DiFC in mice with low false positive detection rates. CONCLUSIONS: This work shows the feasibility of labeling CTCs in vivo with OTL38 and detection with DiFC. Although further refinement of the DiFC instrument and signal processing algorithms and testing with other animal models is needed, this work may eventually pave the way for human use of DiFC.
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Camundongos Nus , Células Neoplásicas Circulantes , Animais , Células Neoplásicas Circulantes/patologia , Humanos , Linhagem Celular Tumoral , Coloração e Rotulagem , Feminino , Camundongos , Citometria de Fluxo , Leucócitos MononuclearesRESUMO
BACKGROUND: Hydrogen sulfide is a highly toxic, flammable, and colorless gas. Hydrogen sulfide has been identified as a potential terrorist chemical threat agent in mass-casualty events. Our previous studies showed that cobinamide, a vitamin B12 analog, effectively reverses the toxicity from hydrogen sulfide poisoning. In this study, we investigate the effectiveness of intratracheally administered cobinamide in treating a lethal dose hydrogen sulfide gas inhalation and compare its performance to saline control administration. METHODS: A total of 53 pathogen-free New Zealand White rabbits were used for this study. Four groups were compared: (i) received no saline solution or drug intratracheally (n = 15), (ii) slow drip saline intratracheally (n = 15), (iii) fast drip saline intratracheally (n = 15), and (iv) slow drip cobinamide intratracheally (n = 8). Blood pressure was continuously monitored, and deoxy- and oxyhemoglobin concentration changes were monitored in real-time in vivo using continuous wave near-infrared spectroscopy. RESULTS: The mean (± standard deviation) weight for all animals (n = 53) was 3.87 ± 0.10 kg. The survival rates of the slow cobinamide and the fast saline groups were 75 percent and 60 percent, respectively, while the survival rates in the slow saline and control groups were 26.7 percent and 20 percent, respectively. A log-rank (Mantel-Cox) test showed that survival in fast saline and slow cobinamide groups were significantly greater than those of no saline control and slow saline groups (P < 0.05). The slow and no saline control groups were not significantly different (P = 0.59). The slow cobinamide group did significantly better than the slow saline group (P = 0.021). DISCUSSION: The ability to use intratracheal cobinamide as an antidote to hydrogen sulfide poisoning is a novel approach to mass-casualty care. The major limitations of this study are that it was conducted in a single species at a single inhaled hydrogen sulfide concentration. Repeated investigations in other species and at varying levels of hydrogen sulfide exposure will be needed before any definitive recommendations can be made. CONCLUSIONS: We demonstrated that intratracheal cobinamide and fast saline drip improved survival for hydrogen sulfide gas inhalation in rabbit models. Although further study is required, our results suggest that intratracheal administration of cobinamide and fast saline may be useful in hydrogen sulfide mass-casualty events.
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Sulfeto de Hidrogênio , Vitamina B 12 , Coelhos , Animais , Cobamidas , Solução Salina , VitaminasRESUMO
OBJECTIVES: Registered nurse prescribing has been put forth, for decades, as an innovative approach to meet growing healthcare needs, particularly in areas of care where medications are essential and highly controlled such as for patients requiring cancer and palliative care. However, the adoption of innovative health delivery models requires acceptance by key stakeholders. This study explores cancer and palliative care nurses' attitudes toward nurse prescribing and their perceptions about educational requirements for a nurse prescriber. DATA SOURCES: A cross-sectional survey was distributed to Australian nurses between March and July 2021. Data were collected using the Advancing Implementation of Nurse Prescribing in Australia online survey. Pearson χ2 tests were used to examine associations between nurses in cancer care, palliative care, and all other specialties on demographics, attitudes to nurse prescribing, and educational perspectives to become prescribers. Of the 4,424 nurses who participated in the survey, 161 nurses identified they worked in cancer care and 109 in palliative care settings. CONCLUSION: Although nurses have a common set of core capabilities, their work contexts and their professional experiences shape their attitudes toward practice. Nurses in cancer care were significantly less certain than nurses in palliative care [χ2(2)â¯=â¯6.68, Pâ¯=â¯.04], and nurses from all other specialties [χ2(2) =13.87, Pâ¯=â¯<.01] of the benefits of nurse prescribing (ie, nurse prescribing would decrease health care system costs, reduce patient risk). Nurses in cancer care were more certain that successfully implementing nurse prescribing requires strong support from their medical and pharmacy colleagues. In addition, nurses working in cancer and palliative care agreed that improving patient care was their primary motivator for becoming a prescriber. IMPLICATIONS FOR NURSING PRACTICE: Open to expanding their role and responsibilities, nurses in cancer and palliative care settings reported that successfully adopting nurse prescribing must be supported by their other healthcare colleagues within the same environment, which demands strong interprofessional collaborative efforts.
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Neoplasias , Enfermeiras e Enfermeiros , Humanos , Atitude do Pessoal de Saúde , Cuidados Paliativos , Papel do Profissional de Enfermagem , Prescrições de Medicamentos , Estudos Transversais , Austrália , Neoplasias/tratamento farmacológicoRESUMO
BACKGROUND: Ticagrelor reduced major adverse cardiovascular events (MACE) and increased bleeding in patients with type 2 diabetes mellitus (T2DM) and coronary artery disease. Limb events including revascularization, acute limb ischemia (ALI), and amputation are major morbidities in patients with T2DM and atherosclerosis. OBJECTIVES: This study sought to determine the effect of ticagrelor on limb events. METHODS: Patients were randomized to ticagrelor or placebo on top of aspirin and followed for a median of 3 years. MACE (cardiovascular death, myocardial infarction, or stroke), limb events (ALI, amputation, revascularization), and bleeding were adjudicated by an independent and blinded clinical events committee. The presence of peripheral artery disease (PAD) was reported at baseline. RESULTS: Of 19,220 patients randomized, 1,687 (8.8%) had PAD at baseline. In patients receiving placebo, PAD was associated with higher MACE (10.7% vs 7.3%; HR: 1.48; P < 0.001) and limb (9.5% vs 0.8%; HR: 10.67; P < 0.001) risk. Ticagrelor reduced limb events (1.6% vs 1.3%; HR: 0.77; 95% CI: 0.61-0.96; P = 0.022) with significant reductions for revascularization (HR: 0.79; 95% CI: 0.62-0.99; P = 0.044) and ALI (HR: 0.24; 95% CI: 0.08-0.70; P = 0.009). The benefit was consistent with or without PAD (HR: 0.80; 95% CI: 0.58-1.11; and HR: 0.76; 95% CI: 0.55-1.05, respectively; Pinteraction = 0.81). There was no effect modification of ticagrelor vs placebo based on PAD for MACE (Pinteraction = 0.40) or TIMI major bleeding (Pinteraction = 0.3239). CONCLUSIONS: Patients with T2DM and atherosclerosis are at high risk of limb events. Ticagrelor decreased this risk, but increased bleeding. Future trials evaluating the combination of ticagrelor and aspirin would further elucidate the benefit/risk of such therapy in patients with PAD, including those without coronary artery disease. (A Study Comparing Cardiovascular Effects of Ticagrelor Versus Placebo in Patients With Type 2 Diabetes Mellitus [THEMIS]: NCT01991795).
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Aspirina , Diabetes Mellitus Tipo 2 , Inibidores da Agregação Plaquetária , Ticagrelor , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Aspirina/uso terapêutico , Aspirina/administração & dosagem , Aterosclerose/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Método Duplo-Cego , Quimioterapia Combinada , Isquemia/prevenção & controle , Doença Arterial Periférica/tratamento farmacológico , Inibidores da Agregação Plaquetária/uso terapêutico , Inibidores da Agregação Plaquetária/administração & dosagem , Ticagrelor/uso terapêutico , Ticagrelor/administração & dosagem , Resultado do TratamentoRESUMO
BACKGROUND: The identification of cancer driver genes from sequencing data has been crucial in deepening our understanding of tumor biology and expanding targeted therapy options. However, apart from the most commonly altered genes, the mechanisms underlying the contribution of other mutations to cancer acquisition remain understudied. Leveraging on our whole-exome sequencing of the largest Asian lung adenocarcinoma (LUAD) cohort (n = 302), we now functionally assess the mechanistic role of a novel driver, PARP4. METHODS: In vitro and in vivo tumorigenicity assays were used to study the functional effects of PARP4 loss and mutation in multiple lung cancer cell lines. Interactomics analysis by quantitative mass spectrometry was conducted to identify PARP4's interaction partners. Transcriptomic data from cell lines and patient tumors were used to investigate splicing alterations. RESULTS: PARP4 depletion or mutation (I1039T) promotes the tumorigenicity of KRAS- or EGFR-driven lung cancer cells. Disruption of the vault complex, with which PARP4 is commonly associated, did not alter tumorigenicity, indicating that PARP4's tumor suppressive activity is mediated independently. The splicing regulator hnRNPM is a potentially novel PARP4 interaction partner, the loss of which likewise promotes tumor formation. hnRNPM loss results in splicing perturbations, with a propensity for dysregulated intronic splicing that was similarly observed in PARP4 knockdown cells and in LUAD cohort patients with PARP4 copy number loss. CONCLUSIONS: PARP4 is a novel modulator of lung adenocarcinoma, where its tumor suppressive activity is mediated not through the vault complex-unlike conventionally thought, but in association with its novel interaction partner hnRNPM, thus suggesting a role for splicing dysregulation in LUAD tumorigenesis.
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Ribonucleoproteínas Nucleares Heterogêneas Grupo M , Neoplasias Pulmonares , Proteínas Nucleares , Animais , Humanos , Camundongos , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/metabolismo , Linhagem Celular Tumoral , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Ribonucleoproteínas Nucleares Heterogêneas Grupo M/metabolismo , Ribonucleoproteínas Nucleares Heterogêneas Grupo M/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Mutação , Ligação Proteica , Splicing de RNA , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismoRESUMO
BACKGROUND: Understanding characteristics of healthcare personnel (HCP) with SARS-CoV-2 infection supports the development and prioritization of interventions to protect this important workforce. We report detailed characteristics of HCP who tested positive for SARS-CoV-2 from April 20, 2020 through December 31, 2021. METHODS: CDC collaborated with Emerging Infections Program sites in 10 states to interview HCP with SARS-CoV-2 infection (case-HCP) about their demographics, underlying medical conditions, healthcare roles, exposures, personal protective equipment (PPE) use, and COVID-19 vaccination status. We grouped case-HCP by healthcare role. To describe residential social vulnerability, we merged geocoded HCP residential addresses with CDC/ATSDR Social Vulnerability Index (SVI) values at the census tract level. We defined highest and lowest SVI quartiles as high and low social vulnerability, respectively. RESULTS: Our analysis included 7,531 case-HCP. Most case-HCP with roles as certified nursing assistant (CNA) (444, 61.3%), medical assistant (252, 65.3%), or home healthcare worker (HHW) (225, 59.5%) reported their race and ethnicity as either non-Hispanic Black or Hispanic. More than one third of HHWs (166, 45.2%), CNAs (283, 41.7%), and medical assistants (138, 37.9%) reported a residential address in the high social vulnerability category. The proportion of case-HCP who reported using recommended PPE at all times when caring for patients with COVID-19 was lowest among HHWs compared with other roles. CONCLUSIONS: To mitigate SARS-CoV-2 infection risk in healthcare settings, infection prevention, and control interventions should be specific to HCP roles and educational backgrounds. Additional interventions are needed to address high social vulnerability among HHWs, CNAs, and medical assistants.
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Background: Stent thrombosis (ST) is an uncommon but serious complication of stent implantation. This study aimed to explore factors associated with early, late, and very late ST to help guide risk assessment and clinical decision-making on ST. Methods: The analysis included patients who received stent placement for the index acute coronary syndrome (ACS). Cumulative incidence of ST was assessed at 30 days (early ST), 31-360 days (late ST), 361-720 days (very late ST), and up to 720 days. Cox proportional hazards models were used to assess associations between ST and various factors, including patient characteristics [i.e., age, sex, ACS presentation, history of hypertension, smoking, diabetes, prior myocardial infarction (MI), heart failure, prior ischemic stroke, and cancer], laboratory tests [i.e., positive cardiac biomarker, hemoglobin, platelet count, white blood cell (WBC) count], and treatment [i.e., drug-eluting stent (DES) vs. bare-metal stent (BMS) and anticoagulant with rivaroxaban vs. placebo]. Results: Among the 8,741 stented patients, 155 ST events (2.25%) occurred by Day 720. The cumulative incidences of early, late, and very late ST were 0.80%, 0.81%, and 0.77%, respectively. After multivariable adjustment, age ≥ 75 [hazard ratio (HR) = 2.13 (95% confidence interval, CI: 1.26-3.60)], a history of prior MI [HR = 1.81 (95% CI: 1.22-2.68)], low hemoglobin level [HR = 2.34 (95% CI: 1.59-3.44)], and high WBC count [HR = 1.58 (95% CI: 1.02-2.46)] were associated with a greater risk of overall ST, whereas DES [HR = 0.56 (95% CI: 0.38-0.83)] and rivaroxaban therapy [HR = 0.63 (95% CI: 0.44-0.88)] were associated with a lower risk of overall ST up to 720 days. Low hemoglobin level and high WBC count were associated with early ST (low hemoglobin: HR = 2.35 [95% CI: 1.34-4.12]; high WBC count: HR = 2.11 [95% CI: 1.17-3.81]). Low hemoglobin level and prior MI were associated with a greater risk of late ST (low hemoglobin: HR = 2.32 [95% CI: 1.26-4.27]; prior MI: HR = 2.98 [95% CI: 1.67-5.31]), whereas DES was associated with a lower risk of late ST [HR = 0.33 (95% CI: 0.16-0.67)]. Age ≥75â years was associated with very late ST. Conclusion: The study identified positive and negative associations with early, late, and very late ST. These variables may be useful in constructing risk assessment models for ST. Clinical Trial Registration: http://www.clinicaltrials.gov, identifier NCT00809965.
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Phyllodes tumors (PT) are rare fibroepithelial lesions of the breast that commonly present as rapidly enlarging, palpable masses. Phyllodes tumors may be classified as benign, borderline, or malignant on the basis of histopathologic analysis. Although malignant PT cannot be distinguished from benign PT on the basis of imaging findings alone, studies suggest that malignant PT tend to be larger and irregular in shape, and they are less likely to have circumscribed margins. If biopsy results are indeterminate, excisional biopsy should be performed. Malignant PT can be difficult to distinguish histologically from sarcomas and spindle cell metaplastic breast carcinoma; the distinction is important for prognosis and treatment. Malignant PT are treated surgically with wide local excision, without a clear role for adjuvant radiation or chemotherapy in most cases. Nearly one-third of malignant PT recur locally, usually within a few years after initial diagnosis. Distant metastatic disease is rare, and the five-year overall survival rate of malignant PT is close to 80%. The purpose of this article is to review the clinical presentation, imaging appearance, histopathology, and management of malignant PT.