Heart failure with preserved ejection fraction (HFpEF) is a challenging disease state that has long been plagued by heterogeneity in diagnostic criteria and underlying etiologies. Due in part to the ...complexity of defining this disease and the simplistic approach of only studying medications that have shown significant improvement in heart failure with reduced ejection fraction, there have been a multitude of negative trials in this population. In the past few years, however, there have been medications that have finally shown to benefit patients with HFpEF. In particular, the blockbuster class of medications called SGLT2 inhibitors have provided a treatment option that improves outcomes in this group of patients. There is increasing focus on HFpEF research that aims to improve the phenotyping of these patients to more successfully tailor therapy and improve patient outcomes.
Early detection of HIV has great potential to reduce transmission, especially when newly diagnosed individuals are treated early. Early treatment and suppression of viral loads is known to ...effectively attenuate HIV transmission. However, little is known about whether persons at high risk for HIV are being appropriately tested during healthcare encounters according to national guidelines. Specifically, the at-risk adolescent population may be under tested and are not routinely monitored by state-level surveillance system. This study reviewed HIV testing rates for at-risk adolescents from 2005-2012 at the main tertiary care and pediatric center in Rhode Island. While the absolute number of HIV tests for at-risk adolescents continued to increase, the HIV testing rates for this population decreased during the seven year period. Increasing awareness of HIV testing for patients, their families, and physicians may improve the HIV testing rate among at-risk adolescents in Rhode Island.
BACKGROUNDHeart failure (HF) poses a substantial economic burden on the United States (US) health care system. In contrast, little is known about the financial challenges faced by patients with HF. ...In this study, we examined the scope and sociodemographic predictors of subjective financial hardship due to medical bills incurred by patients with HF. METHODSIn the Medical Expenditure Panel Survey (MEPS; years 2014--2018), a US nationally representative database, we identified all patients who reported having HF. Any subjective financial hardship due to medical bills was assessed based on patients' reporting either themselves or their families (1) having difficulties paying medical bills in the past 12 months, (2) paying bills late or (3) being unable to pay bills at all. Logistic regression was used to evaluate independent predictors of financial hardship among patients with HF. All analyses took into consideration the survey's complex design. RESULTSA total of 116,563 MEPS participants were included in the analysis, of whom 858 (0.7%) had diagnoses of HF, representing 1.8 million (95% CI 1.6-2.0) patients annually. Overall, 33% (95% CI 29%-38%) reported any financial hardship due to medical bills, and 13.2% were not able to pay bills at all. Age ≤ 65 years and lower educational attainment were independently associated with higher odds of subjective financial hardship due to medical bills. CONCLUSIONSubjective financial hardship is a prevalent issue for patients with HF in the US, particularly those who are younger and have lower educational attainment. There is a need for policies that reduce out-of-pocket costs for the care of HF, an enhanced identification of this phenomenon in the clinical setting, and approaches to help minimize financial toxicity in patients with HF while ensuring optimal quality of care.
Intercellular communication through secreted proteins is necessary in essential processes such as embryo and limb development, disease progression, and immune responses. There exist many techniques ...to study bulk solution protein concentrations, but there is a limited set of tools to study the concentrations of cell-secreted proteins in situ within diverse cell platforms while retaining spatial information. In this study, we have developed a microgel system that is able to quantitatively measure the cell-secreted protein concentration within defined three-dimensional culture configurations with single-cell spatial resolution, called μGeLISA (microgel-linked immunosorbent assay). This system, which is based on the surface modification of polyethylene glycol microgels, was able to detect interleukin 6 (IL-6) concentrations of 2.21–21.86 ng/mL. Microgels were also able to detect cell spheroid-secreted IL-6 and distinguish between low- and high-secreting single cells. The system was also adapted to measure the concentration of cell-secreted matrix metalloproteinase-2 (MMP-2). μGeLISA represents a highly versatile system with a straightforward fabrication process that can be adapted toward the detection of secreted proteins within a diverse range of cell culture configurations.
Liver fibrosis is a common feature of progressive liver disease and is manifested as a dynamic series of alterations in both the biochemical and biophysical properties of the liver. Hepatic stellate ...cells (HSCs) reside within the perisinusoidal space of the liver sinusoid and are one of the main drivers of liver fibrosis, yet it remains unclear how changes to the sinusoidal microenvironment impact HSC phenotype in the context of liver fibrosis. Cellular microarrays were used to examine and deconstruct the impacts of bio-chemo-mechanical changes on activated HSCs in vitro. Extracellular matrix (ECM) composition and stiffness were found to act individually and in combination to regulate HSC fibrogenic phenotype and proliferation. Hyaluronic acid and collagen III promoted elevated collagen I expression while collagen IV mediated a decrease. Previously activated HSCs exhibited reduced lysyl oxidase (Lox) expression as array substrate stiffness increased, with less dependence on ECM composition. Collagens III and IV increased HSC proliferation, whereas hyaluronic acid had the opposite effect. Meta-analysis performed on these data revealed distinct phenotypic clusters (e.g. low fibrogenesis/high proliferation) as a direct function of their microenvironmental composition. Notably, soft microenvironments mimicking healthy tissue (1 kPa), promoted higher levels of intracellular collagen I and Lox expression in activated HSCs, compared to stiff microenvironments mimicking fibrotic tissue (25 kPa). Collectively, these data suggest potential HSC functional adaptations in response to specific bio-chemo-mechanical changes relevant towards the development of therapeutic interventions. These findings also underscore the importance of the microenvironment when interrogating HSC behavior in healthy, disease, and treatment settings.
In this work we utilized high-throughput cellular microarray technology to systematically interrogate the complex interactions between HSCs and their microenvironment in the context of liver fibrosis. We observed that HSC phenotype is regulated by ECM composition and stiffness, and that these phenotypes can be classified into distinct clusters based on their microenvironmental context. Moreover, the range of these phenotypic responses to microenvironmental stimuli is substantial and a direct consequence of the combinatorial pairing of ECM protein and stiffness signals. We also observed a novel role for microenvironmental context in affecting HSC responses to potential fibrosis therapeutics.
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We develop magnetic cytoskeleton affinity (MiCA) purification, which allows for rapid isolation of molecular motors conjugated to large multivalent quantum dots, in miniscule quantities, which is ...especially useful for single-molecule applications. When purifying labeled molecular motors, an excess of fluorophores or labels is usually used. However, large labels tend to sediment during the centrifugation step of microtubule affinity purification, a traditionally powerful technique for motor purification. This is solved with MiCA, and purification time is cut from 2 h to 20 min, a significant time-savings when it needs to be done daily. For kinesin, MiCA works with as little as 0.6 μg protein, with yield of ∼27%, compared to 41% with traditional purification. We show the utility of MiCA purification in a force-gliding assay with kinesin, allowing, for the first time, simultaneous determination of whether the force from each motor in a multiple-motor system drives or hinders microtubule movement. Furthermore, we demonstrate rapid purification of just 30 ng dynein-dynactin-BICD2N-QD (DDB-QD), ordinarily a difficult protein-complex to purify.
The objective of this study is to investigate the prevalence of substance use disorder among college youth receiving treatment for psychiatric illness and the impact of this comorbidity on ...educational disruption and functional outcomes. 113 college students treated at a hospital-based outpatient psychiatric program in Rhode Island from July 2012 to July 2013. Chart reviews yielded demographic information, psychiatric diagnoses, Global Assessment of Functioning (GAF) scores at initial evaluation, and occurrence of medical leave. Rates of medical leave and significant impairment (GAF ≤ 60) in participants with and without substance use disorders were analyzed with odds ratios adjusting for age and gender. Cannabis use (23.9%) and alcohol use (17.7%) disorders were significantly associated with lower GAF scores and medical leave for psychiatric illness. These associations were greater for cannabis use disorder. College students in psychiatric care could benefit from improved screening and treatment for both alcohol and cannabis use disorders.
We adopt the concerns‐based adoption model as an analytical lens to explore how Korean teachers perceive the mandated changes brought about by the policy to teach software (SW) education. The ...research questions are (a) How can teachers be grouped according to their perceived SW knowledge/skills and pedagogical beliefs? (b) What are the overall trends in teachers' stages of concern about SW education? and (c) How are the stages of concern about SW education distributed according to the different teacher types? The participants were 207 teachers who completed the online survey. Data were collected about their perceived SW knowledge/skills, pedagogical beliefs, and the seven stages of concern related to SW education. First, K‐means clustering was performed to categorize teachers into four types based on their SW knowledge/skills and pedagogical beliefs. Overall, our findings indicate that 40% of the participants belonged to Type I, who have high SW knowledge/skills and pedagogical beliefs. Second, the concerns profile in Type I showed an M pattern in which they hold both self and impact concerns. Types II–IV showed a similar trend, such that the trends peak at Stage 0 (Awareness) and the intense concerns at the self‐level (Stage 1, Informational and Stage 2, Personal). All types demonstrated a tailing up phenomenon at Stage 6 (Refocusing). This study has implications for the design of concern‐based interventions and makes suggestions to enable teachers to move toward more advanced levels to adopt computational thinking‐based pedagogy in SW education.
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