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We identified 2 cases of Salmonella enterica serovar Vitkin infection linked by whole-genome sequencing in infants in Ontario, Canada, during 2022. Both households of the infants reported having bearded dragons as pets. The outbreak strain was also isolated from an environmental sample collected from a patient's bearded dragon enclosure. Twelve cases were detected in the United States, and onset dates occurred during March 2021-September 2022 (isolates related to isolates from Canada within 0-9 allele differences by core-genome multilocus sequence typing). Most US patients (66.7%) were <1 year of age, and most (72.7%) had reported bearded dragon exposure. Hospitalization was reported for 5 (38.5%) of 13 patients. Traceback of bearded dragons identified at least 1 potential common supplier in Southeast Asia. Sharing rare serovar information and whole-genome sequencing data between Canada and the United States can assist in timely identification of outbreaks, including those that might not be detected through routine surveillance.
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Lagartos , Salmonella , Lactente , Animais , Humanos , Estados Unidos/epidemiologia , Ontário , Alelos , Surtos de Doenças , HospitalizaçãoRESUMO
BACKGROUND: Rectal tumors display varying degrees of response to total neoadjuvant therapy (TNT). We evaluated the performance of a convolutional neural network (CNN) in interpreting endoscopic images of either a non-complete response to TNT or local regrowth during watch-and-wait surveillance. METHODS: Endoscopic images from stage II/III rectal cancers treated with TNT from 2012 to 2020 at a single institution were retrospectively reviewed. Images were labelled as Tumor or No Tumor based on endoscopy timing (before, during, or after treatment) and the tumor's endoluminal response. A CNN was trained using ResNet-50 architecture. The area under the curve (AUC) was analyzed during training and for two test sets. The main test set included images of tumors treated with TNT. The other contained images of local regrowth. The model's performance was compared to sixteen surgeons and surgical trainees who evaluated 119 images for evidence of tumor. Fleiss' kappa was calculated by respondent experience level. RESULTS: A total of 2717 images from 288 patients were included; 1407 (51.8%) contained tumor. The AUC was 0.99, 0.98, and 0.92 for training, main test, and local regrowth test sets. The model performed on par with surgeons of all experience levels for the main test set. Interobserver agreement was good ( k = 0.71-0.81). All groups outperformed the model in identifying tumor from images of local regrowth. Interobserver agreement was fair to moderate ( k = 0.24-0.52). CONCLUSIONS: A highly accurate CNN matched the performance of colorectal surgeons in identifying a noncomplete response to TNT. However, the model demonstrated suboptimal accuracy when analyzing images of local regrowth.
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Black/African American and Hispanic Americans experience significant HIV-related disparities. Substance use might be a contributing factor to these disparities, but there is limited research on this topic. This study investigated various substance use risks by HIV status and race/ethnicity (Black, Hispanic, White) among U.S. adults. We used data from the 2005-2019 National Survey on Drug Use and Health (N = 541,921). In each racial/ethnic group, the prevalence rates of past-year and past-month tobacco, alcohol, cannabis, and cocaine use, and past-year alcohol and illicit drug use disorders were estimated by HIV status. A series of logistic regressions with the interaction term of HIV x race/ethnicity were performed to examine race/ethnicity's moderating effect on the HIV-substance use associations, while controlling for sociodemographic factors and survey year. Moderation analysis showed that HIV status's association with the risks of past-year tobacco use (AOR = 1.67, 95% CI = 1.01-2.75), past-year cocaine use (AOR = 3.80, 95% CI = 1.91-7.57), past-month cocaine use (AOR = 5.34, 95% CI = 2.10-13.60), and past-year alcohol use disorder (AOR = 2.52, 95% CI = 1.29-4.92) differed significantly between Black and White adults. Between the Hispanic and White groups, HIV status's association with the risks of past-year alcohol use (AOR = 2.00, 95% CI = 1.09-3.69), past-year cocaine use (AOR = 2.40, 95% CI = 1.06-5.39), and past-month cocaine use (AOR = 3.69, 95% CI = 1.36-10.02) also differed significantly. It is well-established that individuals with HIV face an elevated risk of substance use. Our study added valuable insights by highlighting that this phenomenon is particularly more significant among Black and Hispanic adults for several substances when compared to White adults. Implications for practice are discussed.
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Negro ou Afro-Americano , Infecções por HIV , Hispânico ou Latino , Transtornos Relacionados ao Uso de Substâncias , Brancos , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Negro ou Afro-Americano/estatística & dados numéricos , Negro ou Afro-Americano/psicologia , Etnicidade/estatística & dados numéricos , Disparidades nos Níveis de Saúde , Hispânico ou Latino/estatística & dados numéricos , Infecções por HIV/etnologia , Infecções por HIV/epidemiologia , Prevalência , Fatores de Risco , Fatores Socioeconômicos , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/etnologia , Estados Unidos/epidemiologia , População Branca/estatística & dados numéricosRESUMO
BACKGROUND: Lack of standardized assessments that explicitly quantify performance during prosthetic grip selection poses difficulty determining whether efforts to improve the design of multi-grip hands and their control approaches are successful. In this study, we developed and validated a novel assessment of multi-grip prosthetic performance: The Coffee Task. METHODS: Individuals without limb loss completed the Box and Block Test and two versions of the Coffee Task - Continuous and Segmented - with a myoelectric prosthetic emulator. On different days, participants selected prosthetic grips using pattern recognition and trigger control. Outcomes of the Continuous and Segmented Coffee Task were completion time and number of errors, respectively. Two independent raters assessed outcomes of the Coffee Task using video recordings to determine inter-rater reliability. Known-group validity was assessed by comparing outcomes with the emulator to those with an intact limb. Convergent validity was assessed through the correlation of the Coffee Task outcomes and those of the Box and Blocks Test. Responsiveness to changes with practice and control approach were assessed using the standardized response mean (SRM). RESULTS: Inter-rater reliability was high for both versions of the Coffee Task (Intra-class coefficient > 0.981). Coffee Task outcomes were moderately correlated with the Box and Blocks outcomes (|r| ≥ 0.412, p ≤ 0.007). Participants completed the Coffee Task faster with their intact limb than with the emulator (p < 0.001). Both versions of the Coffee Task were responsive to changes with training (SRM ≥ 0.81) but not control approach (SRM ≤ 0.12). CONCLUSIONS: The Coffee Task is reliable, has good known-group and convergent validity, and is responsive to changes due to practice. Future work should assess whether the Coffee Task is feasible and reliable for people with upper limb loss who use multi-grip prostheses.
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Membros Artificiais , Café , Humanos , Reprodutibilidade dos Testes , Extremidade Superior , Força da MãoRESUMO
BACKGROUND: Patient access to body-powered and myoelectric upper limb prostheses in the United States is often restricted by a healthcare system that prioritizes prosthesis prescription based on cost and perceived value. Although this system operates on an underlying assumption that design differences between these prostheses leads to relative advantages and disadvantages of each device, there is limited empirical evidence to support this view. MAIN TEXT: This commentary article will review a series of studies conducted by our research team with the goal of differentiating how prosthesis design might impact user performance on a variety of interrelated domains. Our central hypothesis is that the design and actuation method of body-powered and myoelectric prostheses might affect users' ability to access sensory feedback and account for device properties when planning movements. Accordingly, other domains that depend on these abilities may also be affected. While our work demonstrated some differences in availability of sensory feedback based on prosthesis design, this did not result in consistent differences in prosthesis embodiment, movement accuracy, movement quality, and overall kinematic patterns. CONCLUSION: Collectively, our findings suggest that performance may not necessarily depend on prosthesis design, allowing users to be successful with either device type depending on the circumstances. Prescription practices should rely more on individual needs and preferences than cost or prosthesis design. However, we acknowledge that there remains a dearth of evidence to inform decision-making and that an expanded research focus in this area will be beneficial.
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Membros Artificiais , Desenho de Prótese , Extremidade Superior , Humanos , Extremidade Superior/fisiologia , Eletromiografia/instrumentação , Retroalimentação Sensorial/fisiologia , Fenômenos BiomecânicosRESUMO
BACKGROUND: During inpatient rehabilitation, physical therapists (PTs) often need to manually advance patients' limbs, adding physical burden to PTs and impacting gait retraining quality. Different electromechanical devices alleviate this burden by assisting a patient's limb advancement and supporting their body weight. However, they are less ideal for neuromuscular engagement when patients no longer need body weight support but continue to require assistance with limb advancement as they recover. The objective of this study was to determine the feasibility of using a hip flexion exosuit to aid paretic limb advancement during inpatient rehabilitation post-stroke. METHODS: Fourteen individuals post-stroke received three to seven 1-hour walking sessions with the exosuit over one to two weeks in addition to standard care of inpatient rehabilitation. The exosuit assistance was either triggered by PTs or based on gait events detected by body-worn sensors. We evaluated clinical (distance, speed) and spatiotemporal (cadence, stride length, swing time symmetry) gait measures with and without exosuit assistance during 2-minute and 10-meter walk tests. Sessions were grouped by the assistance required from the PTs (limb advancement and balance support, balance support only, or none) without exosuit assistance. RESULTS: PTs successfully operated the exosuit in 97% of sessions, of which 70% assistance timing was PT-triggered to accommodate atypical gait. Exosuit assistance eliminated the need for manual limb advancement from PTs. In sessions with participants requiring limb advancement and balance support, the average distance and cadence during 2-minute walk test increased with exosuit assistance by 2.2 ± 3.1 m and 3.4 ± 1.9 steps/min, respectively (p < 0.017). In sessions with participants requiring balance support only, the average speed during 10-meter walk test increased with exosuit by 0.07 ± 0.12 m/s (p = 0.042). Clinical and spatiotemporal measures of independent ambulators were similar with and without exosuit (p > 0.339). CONCLUSIONS: We incorporated a unilateral hip flexion exosuit into inpatient stroke rehabilitation in individuals with varying levels of impairments. The exosuit assistance removed the burden of manual limb advancement from the PTs and resulted in improved gait measures in some conditions. Future work will understand how to optimize controller and assistance profiles for this population.
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Exoesqueleto Energizado , Estudos de Viabilidade , Reabilitação do Acidente Vascular Cerebral , Humanos , Reabilitação do Acidente Vascular Cerebral/métodos , Reabilitação do Acidente Vascular Cerebral/instrumentação , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Transtornos Neurológicos da Marcha/reabilitação , Transtornos Neurológicos da Marcha/etiologia , Acidente Vascular Cerebral/complicações , Marcha/fisiologia , Adulto , Paresia/reabilitação , Paresia/etiologia , Pacientes InternadosRESUMO
The current study tests the Motivational Interviewing (MI) technical and relational hypotheses in a sample of Hispanic/Latinx adults (N = 276) who engage in heavy alcohol consumption. MI causal theory hypothesizes that therapist use of MI consistent skills (i.e., technical hypothesis) and embodiment of the MI Spirit (i.e., relational hypothesis) will elicit client change talk, which is a putative mechanism of positive client outcome after the session. We tested these associations in a rigorous parallel process latent growth curve mediation modeling framework. The data are from a completed randomized clinical trial of a culturally-adapted (CAMI) versus un-adapted MI targeting hazardous alcohol use and consequences. Results. The unconditional growth models for the mediator (i.e., proportion of change talk relative to sustain talk) and two study outcomes (i.e., percent of heavy drinking days; alcohol-related consequences) showed a linear effect over a 12-month period with a slower rate of growth at later timepoints. Contrary to expectations, the latent growth mediation models did not show relationships between MI-consistent skills (i.e., technical predictor) or latent MI Spirit (i.e., relational indicator) and the slope factor for proportion change talk. The slope factor for proportion change talk was also not associated with the slope factors for percent heavy drinking and consequences over follow-up. Conclusions. In this novel population for MI process analysis, the technical and relational hypotheses were not supported. Studies that are exploratory may be needed to further investigate the causal model in populations that are not often represented in MI process research.
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While healthy individuals have redundant degrees of freedom of the joints, they coordinate their multi-joint movements such that the redundancy is effectively reduced. Achieving high inter-joint coordination may be difficult for upper limb prosthesis users due to the lack of proprioceptive feedback and limited motion of the terminal device. This study compared inter-joint coordination between prosthesis users and individuals without limb loss during different upper limb activities of daily living (ADLs). Nine unilateral prosthesis users (five males) and nine age- and sex-matched controls without limb loss completed three unilateral and three bilateral ADLs. Principal component analysis was applied to the three-dimensional motion trajectories of the trunk and arms to identify coordinative patterns. For each ADL, we quantified the cumulative variance accounted for (VAF) of the first five principal components (pcs), which was the lowest number of pcs that could achieve 90% VAF in control limb movements across all ADLs (5 ≤ n ≤ 9). The VAF was lower for movements involving a prosthesis compared to those completed by controls across all ADLs (p < 0.001). The pc waveforms were similar between movements involving a prosthesis and movements completed by control participants for pc1 (r > 0.78, p < 0.001). The magnitude of the relationship for pc2 and pc3 differed between ADLs, with the strongest correlation for symmetric bilateral ADLs (0.67 ≤ r ≤ 0.97, p < 0.001). Collectively, this study demonstrates that activities of daily living were completed with distinct coordination strategies in prosthesis users compared to individuals without limb loss. Future work should explore how device features, such as the availability of sensory feedback or motorized wrist joints influence multi-joint coordination.
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Atividades Cotidianas , Membros Artificiais , Análise de Componente Principal , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Fenômenos Biomecânicos , Extremidade Superior , Idoso , Desempenho Psicomotor/fisiologia , AmputadosRESUMO
Summary: Neonatal adrenal hemorrhage (NAH) occurs in up to 3% of infants and is the most common adrenal mass in newborns. The most common presentation of NAH is an asymptomatic palpable flank mass which resolves over time without intervention. In rare cases, NAH can present as hemorrhage, shock, or adrenal insufficiency. This case describes a preterm infant born with severe anemia in the setting of bilateral adrenal hemorrhages with resulting adrenal insufficiency. The infant was successfully treated with blood transfusions and steroids. This is a unique presentation of NAH as it was bilateral, presented with severe anemia, and resulted in prolonged adrenal insufficiency. Learning points: Consider adrenal hemorrhage for cases of severe anemia at birth. Adrenal insufficiency is a rare complication of adrenal hemorrhage. Adrenal recovery can take months, if not years.
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(1) Background: Irritable bowel syndrome (IBS) is a highly prevalent disorder of gut-brain interaction (DGBI) that is known to reduce the quality of life and raise healthcare costs. The aim of this study was to describe the epidemiology of IBS in a large multiracial academic safety-net hospital. (2) Methods: An electronic query was performed using ICD-9 codes to identify 740 IBS outpatients seen at the Boston Medical Center (BMC) between 1 January 2005 and 30 September 2007. Demographic data were collected from electronic medical records. Bivariate analyses using chi-square tests and ANOVA were used to calculate the significance of categorical and continuous dependent variables, respectively. (3) Results: Compared with the general BMC outpatient population, the IBS cohort consisted of significantly higher proportions of White and Asian patients and lower proportions of Black and Hispanic patients (p < 0.0001). White and Asian patients predominantly had private insurance, while Black and Hispanic patients mostly had government/state-funded or no insurance (p < 0.0001). The IBS subgroup frequencies were similar across racial groups; however, Hispanic patients had IBS with constipation (32%, p < 0.02) more often compared to non-Hispanic patients. (4) Conclusions: Significant differences were found across the racial groups studied in this large outpatient IBS cohort. These findings are likely attributed to racial and socioeconomic disparities in healthcare access and utilization.
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Introduction: Irritable bowel syndrome (IBS) is a disorder of gut-brain interaction (DGBI), and associated co-morbidities worsen quality of life. Research concerning IBS co-morbidities in different racial/ethnic groups is very sparse. This study aimed to determine the prevalence rates of co-morbidities and possible differences in a multiracial/ethnic IBS cohort. Methods: Based on ICD-9-coded IBS diagnosis, 740 outpatients (≥18 years) were included in this retrospective study at Boston Medical Center. Demographics and ICD-9-coded co-morbidities were extracted from electronic records. Descriptive statistics and multiple logistic regression were used for data analyses. Results: The most prevalent co-morbidities in this IBS cohort included gastroesophageal reflux disorder (GERD) (30%), depression (27%), anxiety (23%), (chronic obstructive pulmonary disease) COPD/asthma (16%), and obesity (10%). GERD was more prevalent in Hispanics and Blacks (p = 0.0005), and non-ulcer dyspepsia (NUD) was more prevalent in Blacks and Asians (p = 0.003). Higher rates of diabetes mellitus type 2 (DMT2) (p = 0.0003) and depression (p = 0.03), but not anxiety (p = 0.9), were present in Blacks and Hispanics. GERD was significantly associated with Hispanics (p = 0.003), dependent on age, overweight, and obesity. NUD was significantly associated with Blacks (p = 0.01) and Asians (p = 0.006), independent of sex, age, and BMI. Cancer of the thyroid, ovaries, and testis occurred at a five-fold higher rate than expected. Conclusions: Significant racial/ethnic differences exist for IBS co-morbidities in this study cohort, including depression, DMT2, GERD, and NUD. Certain cancers were found to be more frequent in this IBS sample as compared with the general population.
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BACKGROUND: Utilization of palliative care remains low among surgical patients. We aim to characterize general surgeons' perceptions of barriers to access palliative care in British Columbia (BC). METHODS: Semi-structured interviews were carried out with a total of 11 surgeons in BC. Interviews were transcribed for thematic analysis via interpretive description. Dominant themes were identified and agreed upon between the authors. RESULTS: Several barriers were identified, which include system and institution, communication and surgical workflow barriers. At the system and institutional level, there were difficulties accessing patient information and continuity of care. Themes in the communication included patient misconceptions about palliative care and communication challenges with consulting services. Surgical workflow barriers influenced the overall perceived role of surgeons when caring for patients with palliative care needs. CONCLUSION: Understanding surgeons' perspectives on barriers to palliative care is an important step in changing management. This can aid in the development of strategies that ease access to palliative care.
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INTRODUCTION: Discrimination is linked to alcohol use severity among Latinx adults, who also show high prevalence rates of PTSD compared to non-Latinx adults. We know little about whether PTSD symptoms affects the relationship between discrimination and alcohol use severity. We hypothesized that the association between discrimination and alcohol use severity might differ by level of PTSD symptom severity. METHODS: This is a secondary cross-sectional analysis of data collected at baseline from a completed randomized clinical trial testing the relative efficacy of a culturally adapted motivational interview designed to address discrimination and drinking behavior against an unadapted motivational interview for Latinx adults. Eligible participants screened positive for the NIAAA Single Alcohol Screening Question for heavy drinking days, identified as Latinx, and were 18-65 years old. We assessed the Everyday Discrimination Scale, Primary Care PC-PTSD screener, Alcohol Use Disorder Identification Test, and the Short Acculturation Scale for Hispanics. The study analyzed the main and interactive effects of discrimination and PTSD symptoms on alcohol use severity, while controlling for age, sex, household income, and acculturation. RESULTS: After controlling for covariates in model 2, the interaction of discrimination and PTSD symptoms was significantly related to alcohol use severity. Simple slopes analysis indicated that discrimination was positively related to alcohol use severity among those with high (1 SD above the mean) but not low (1 SD below the mean) levels of PTSD symptoms. CONCLUSIONS: Evidence suggests that the experiences of discrimination were associated with alcohol use severity among those who reported more PTSD symptoms. Specifically, discrimination may have a stronger effect on alcohol use severity among Latinx adults who report more PTSD symptoms. Screening Latinx adults for heavy drinking days, discrimination, and PTSD symptoms is clinically important. Culturally adapted alcohol interventions that target discrimination may be particularly effective for Latinx individuals with more PTSD symptoms.
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Intoxicação Alcoólica , Transtornos de Estresse Pós-Traumáticos , Adolescente , Adulto , Idoso , Humanos , Pessoa de Meia-Idade , Adulto Jovem , Consumo de Bebidas Alcoólicas/epidemiologia , Estudos Transversais , Hispânico ou Latino , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Despite the re-emergence of the pioneering "Coley's toxin" concept in anti-cancer immune therapies highlighted by check-point inhibitors and CAR-T approaches, fundamental mechanisms responsible for the immune-enhancing efficacy of low-dose "Coley's toxin" remain poorly understood. This study examines the novel reprogramming of immune-enhancing neutrophils by super-low dose endotoxin conducive for anti-cancer therapies. Through integrated analyses including scRNAseq and functional characterizations, we examined the efficacy of reprogrammed neutrophils in treating experimental cancer. We observed that neutrophils trained by super-low dose endotoxin adopt a potent immune-enhancing phenotype characterized by CD177loCD11bloCD80hiCD40hiDectin2hi. Both murine and human neutrophils trained by super-low dose endotoxin exhibit relieved suppression of adaptive T cells as compared to un-trained neutrophils. Functionally, neutrophils trained by super-low dose endotoxin can potently reduce tumor burden when transfused into recipient tumor-bearing mice. Mechanistically, Super-low dose endotoxin enables the generation of immune-enhancing neutrophils through activating STAT5 and reducing innate suppressor IRAK-M. Together, our data clarify the long-held mystery of "Coley's toxin" in rejuvenating anti-tumor immune defense, and provide a proof-of-concept in developing innate neutrophil-based anti-tumor therapeutics.
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Endotoxinas , Neutrófilos , Neutrófilos/imunologia , Animais , Camundongos , Humanos , Neoplasias/imunologia , Neoplasias/terapia , Neoplasias/tratamento farmacológico , Camundongos Endogâmicos C57BL , Fator de Transcrição STAT5/metabolismo , Linhagem Celular TumoralRESUMO
Leprosy was one of the most outwardly visible diseases in the European Middle Ages, a period during which leprosaria were founded to provide space for the sick. The extant documentary evidence for leprosy hospitals, especially in relation to diet, therapeutic, and medical care, is limited. However, human dental calculus stands to be an important source of information as it provides insight into the substances people were exposed to and accumulated in their bodies during their lives. In the present study, microremains and DNA were analysed from the calculus of individuals buried in the late medieval cemetery of St Leonard, a leprosarium located in Peterborough, England. The results show the presence of ginger (Zingiber officinale), a culinary and medicinal ingredient, as well as evidence of consumption of cereals and legumes. This research suggests that affected individuals consumed ingredients mentioned in medieval medical textbooks that were used to treat regions of the body typically impacted by leprosy. To the authors' knowledge, this is the first study which has identified Zingiber officinale in human dental calculus in England or on the wider European continent.
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Hanseníase , Zingiber officinale , Humanos , Cálculos Dentários , Inglaterra , Hanseníase/tratamento farmacológico , DietaRESUMO
Clostridioides difficile (C. difficile) is the predominant causative agent of nosocomial diarrhea worldwide. Infection with C. difficile occurs due to the secretion of large glycosylating toxin proteins, which can lead to toxic megacolon or mortality in susceptible hosts. A critical aspect of C. difficile's biology is its ability to persist asymptomatically within the human host. Individuals harboring asymptomatic colonization or experiencing a single episode of C. difficile infection (CDI) without recurrence exhibit heightened immune responses compared to symptomatic counterparts. The significance of these immune responses cannot be overstated, as they play critical roles in the development, progression, prognosis, and outcomes of CDI. Nonetheless, our current comprehension of the immune responses implicated in CDI remains limited. Therefore, further investigation is imperative to elucidate their underlying mechanisms. This review explores recent advancements in comprehending CDI pathogenesis and how the host immune system response influences disease progression and severity, aiming to enhance our capacity to develop immunotherapy-based treatments for CDI.
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BACKGROUND AND AIMS: Patients with severely reduced kidney function have been excluded from randomized controlled trials and data on the safety and efficacy of direct oral anticoagulants (DOACs) according to kidney function remain sparse. The aim was to evaluate the safety and efficacy of the DOACs across subgroups of kidney function. METHODS: Using multiple Danish nationwide registers and laboratory databases, we included patients initiated on oral anticoagulants (OACs) with atrial fibrillation and available creatinine level and followed patients for 2 years to evaluate occurrence of stroke/thromboembolism (TE) and major bleeding. RESULTS: Among 26 686 included patients, 3667 (13.7%) had an estimated glomerular filtration rate (eGFR) of 30-49 mL/min/1.73 m2 and 596 (2.2%) had an eGFR below 30 mL/min/1.73 m2. We found no evidence of differences regarding the risk of stroke/TE between the OACs (P-value interaction >0.05 for all). Apixaban was associated with a lower 2-year risk of major bleeding compared to vitamin K antagonists (VKA) [hazard ratio 0.79, 95% confidence interval (CI) 0.67-0.93], and the risk difference was significantly larger among patients with reduced kidney function (P-value interaction 0.018). Rivaroxaban was associated with a higher risk of bleeding compared to apixaban (hazard ratio 1.78, 95%CI 1.32-2.39) among patients with eGFR 30-49 mL/min/1.73 m2. CONCLUSIONS: Overall, we found no differences regarding the risk of stroke/TE, but apixaban was associated with a 21% lower relative risk of major bleeding compared to VKA. This risk reduction was even greater when comparing apixaban to VKA among patients with eGFR 15-30 mL/min/1.73 m2, and when comparing apixaban to dabigatran and rivaroxaban among patients with eGFR 30-49 mL/min/1.73 m2.
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Fibrilação Atrial , Taxa de Filtração Glomerular , Hemorragia , Rim , Sistema de Registros , Acidente Vascular Cerebral , Humanos , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/fisiopatologia , Fibrilação Atrial/complicações , Masculino , Feminino , Taxa de Filtração Glomerular/efeitos dos fármacos , Idoso , Administração Oral , Hemorragia/induzido quimicamente , Hemorragia/epidemiologia , Acidente Vascular Cerebral/prevenção & controle , Acidente Vascular Cerebral/epidemiologia , Dinamarca/epidemiologia , Rim/fisiopatologia , Rim/efeitos dos fármacos , Resultado do Tratamento , Fatores de Risco , Medição de Risco , Fatores de Tempo , Anticoagulantes/efeitos adversos , Anticoagulantes/administração & dosagem , Idoso de 80 Anos ou mais , Tromboembolia/prevenção & controle , Tromboembolia/epidemiologia , Inibidores do Fator Xa/efeitos adversos , Inibidores do Fator Xa/administração & dosagem , Pessoa de Meia-Idade , Piridonas/efeitos adversos , Piridonas/administração & dosagem , Pirazóis/efeitos adversos , Pirazóis/administração & dosagemRESUMO
Stress granule formation is triggered by the release of mRNAs from polysomes and is promoted by the action of the RNA-binding proteins G3BP1/2. Stress granules have been implicated in several disease states, including cancer and neurodegeneration. Consequently, compounds that limit stress granule formation or promote their dissolution have potential as both experimental tools and novel therapeutics. Herein, we describe two small molecules, G3BP inhibitor a and b (G3Ia and G3Ib), designed to bind to a specific pocket in G3BP1/2 that is targeted by viral inhibitors of G3BP1/2 function. In addition to disrupting the co-condensation of RNA, G3BP1, and caprin 1 in vitro, these compounds inhibit stress granule formation in cells treated prior to or concurrent with stress and dissolve pre-existing stress granules. These effects are consistent across multiple cell types and a variety of initiating stressors. Thus, these compounds represent powerful tools to probe the biology of stress granules and hold promise for therapeutic interventions designed to modulate stress granule formation.
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DNA Helicases , RNA Helicases , Grânulos de Estresse , DNA Helicases/genética , Proteínas de Ligação a Poli-ADP-Ribose/genética , RNA Helicases/genética , Proteínas com Motivo de Reconhecimento de RNA/genéticaRESUMO
Introduction: The current study presents the development of a scale to assess drinking behavior in response to acculturation and immigration stress. Methods: The 19-item Measure of Immigration and Acculturation Stressors (MIAS) and a parallel assessment, a Measure of Drinking in Response to Immigration and Acculturation Stressors (MDRIAS), were administered at baseline, 6 months, and 12 months in a completed randomized controlled trial testing culturally adapted motivational interviewing to reduce heavy drinking and related problems in Latinx individuals who met criteria for heavy drinking (n=149). Results: Exploratory factor analysis of the MIAS showed best fit for a four-factor solution (Relational Stress, Perceived Ethnic Discrimination, Attenuated Aspirations, and Sense of Alienation) with 15 items. The MIAS subscales and the four corresponding MDRIAS subscales were shown to have good reliability (i.e., internal consistency, intercorrelations, and test-retest) and criterion-related validity (i.e., concurrent, convergent, and predictive). Conclusions: These findings suggest that the MIAS can be used to assess different types of immigration and acculturation stressors for Latinx adults and the MDRIAS can be used to assess drinking in response to those experiences. The MIAS and MDRIAS could be used in the future to adapt alcohol interventions to relevant stressors that contribute to Latinx adults' alcohol use.