Abstract
Pulmonary hypertension secondary to left‐sided valvular disease (VHD‐PH) is associated with high morbidity and mortality. Angiotensin‐receptor neprilysin inhibitor (ARNI) is a novel ...pharmacotherapy, which reduces afterload with natriuresis and peripheral vasodilation. Our cases demonstrate that ARNI may also have a role in the treatment of combined pre‐ and postcapillary pulmonary hypertension that is independent of its effect on pulmonary capillary wedge pressure and cardiac output. Future prospective trials are needed to evaluate role of ARNIs in treatment of VHD‐PH.
The burden of financial hardship among individuals with chronic kidney disease (CKD) has not been extensively studied. Therefore, we describe the scope and determinants of financial hardship among a ...nationally representative sample of adults with CKD.
Cross-sectional.
Nonelderly adults with CKD from the 2014-2018 National Health Interview Survey.
Sociodemographic and clinical characteristics.
Financial hardship based on medical bills and consequences of financial hardship (high financial distress, food insecurity, cost-related medication nonadherence, delayed/forgone care due to cost). Financial hardship was categorized into 3 levels: no financial hardship, financial hardship but able to pay bills, and unable to pay bills at all. Financial hardship was then modeled in 2 different ways: (1) any financial hardship (regardless of ability to pay) versus no financial hardship and (2) inability to pay bills versus no financial hardship and financial hardship but able to pay bills.
Nationally representative estimates of financial hardship from medical bills were computed. Multivariable logistic regression models were used to examine the associations of sociodemographic and clinical factors with the outcomes of financial hardship based on medical bills.
A total 1,425 individuals, representing approximately 2.1 million Americans, reported a diagnosis of CKD within the past year, of whom 46.9% (95% CI, 43.7%-50.2%) reported experiencing financial hardship from medical bills; 20.9% (95% CI, 18.5%-23.6%) reported inability to pay medical bills at all. Lack of insurance was the strongest determinant of financial hardship in this population (odds ratio, 4.06 95% CI, 2.18-7.56).
Self-reported nature of CKD diagnosis.
Approximately half the nonelderly US population with CKD experiences financial hardship from medical bills that is associated strongly with lack of insurance. Evidence-based clinical and policy interventions are needed to address these hardships.
Nonalcoholic fatty liver disease affects 30% of the United States population and its progression can lead to nonalcoholic steatohepatitis (NASH), and increased risks for cirrhosis and hepatocellular ...carcinoma. NASH is characterized by a highly heterogeneous liver microenvironment created by the fibrotic activity of hepatic stellate cells (HSCs). While HSCs have been widely studied in 2D, further advancements in physiologically relevant 3D culture platforms for the in vitro modeling of these heterogeneous environments are needed. In this study, the use of stiffness‐variable, extracellular matrix (ECM) protein‐conjugated polyethylene glycol microgels as 3D cell culture scaffolds to modulate HSC activation is demonstrated. These microgels as a high throughput ECM screening system to identify HSC matrix remodeling and metabolic activities in distinct heterogeneous microenvironmental conditions are further employed. The 6 kPa fibronectin microgels are shown to significantly increase HSC matrix remodeling and metabolic activities in single or multiple‐component microenvironments. Overall, heterogeneous microenvironments consisting of multiple distinct ECM microgels promoted a decrease in HSC matrix remodeling and metabolic activities compared to homogeneous microenvironments. The study envisions this ECM screening platform being adapted to a broad number of cell types to aid the identification of ECM microenvironments that best recapitulate the desired phenotype, differentiation, or drug efficacy.
The development and utility of stiffness‐variable, ECM protein‐conjugated polyethylene glycol microgels as 3D cell culture scaffolds to modulate human hepatic stellate cell activation is demonstrated. The study envisions this ECM screening platform being adapted to a broad number of cell types to aid the identification of ECM microenvironments that best recapitulate the desired phenotype, differentiation, or drug efficacy.
Cellular phenotypes and functional responses are modulated by the signals present in their microenvironment, including extracellular matrix (ECM) proteins, tissue mechanical properties, soluble ...signals and nutrients, and cell–cell interactions. To better recapitulate and analyze these complex signals within the framework of more physiologically relevant culture models, high throughput culture platforms can be transformative. High throughput methodologies enable scientists to extract increasingly robust and broad datasets from individual experiments, screen large numbers of conditions for potential hits, better qualify and predict responses for preclinical applications, and reduce reliance on animal studies. High throughput cell culture systems require uniformity, assay miniaturization, specific target identification, and process simplification. In this review, we detail the various techniques that researchers have used to face these challenges and explore cellular responses in a high throughput manner. We highlight several common approaches including two‐dimensional multiwell microplates, microarrays, and microfluidic cell culture systems as well as unencapsulated and encapsulated three‐dimensional high throughput cell culture systems, featuring multiwell microplates, micromolds, microwells, microarrays, granular hydrogels, and cell‐encapsulated microgels. We also discuss current applications of these high throughput technologies, namely stem cell sourcing, drug discovery and predictive toxicology, and personalized medicine, along with emerging opportunities and future impact areas.
Visits to the emergency department (ED) for use of illicit drugs and opioids have increased in the past decade. In the ED, little is known about how gender may play a role in drug-related visits and ...referrals to treatment. This study performs gender-based comparison analyses of drug-related ED visits nationwide.
We performed a cross-sectional analysis with data collected from 2004 to 2011 by the Drug Abuse Warning Network (DAWN). All data were coded to capture major drug categories and opioids. We used logistic regression models to find associations between gender and odds of referral to treatment programs. A second set of models were controlled for patient "seeking detox," or patient explicitly requesting for detox referral.
Of the 27.9 million ED visits related to drug use in the DAWN database, visits by men were 2.69 times more likely to involve illicit drugs than visits by women (95% CI 2.56, 2.80). Men were more likely than women to be referred to detox programs for any illicit drugs (OR 1.12, 95% CI 1.02-1.22), for each of the major illicit drugs (e.g., cocaine: OR 1.27, 95% CI 1.15-1.40), and for prescription opioids (OR 1.30, 95% CI 1.17-1.43). This significant association prevailed after controlling for "seeking detox."
Women are less likely to receive referrals to detox programs than men when presenting to the ED regardless of whether they are "seeking detox." Future research may help determine the cause for this gender-based difference and its significance for healthcare costs and health outcomes.
The study of the liver progenitor cell microenvironment has demonstrated the important roles of both biochemical and biomechanical signals in regulating the progenitor cell functions that underlie ...liver morphogenesis and regeneration. While controllable two-dimensional
in vitro
culture systems have provided key insights into the effects of growth factors and extracellular matrix composition and mechanics on liver differentiation, it remains unclear how microenvironmental signals may differentially affect liver progenitor cell responses in a three-dimensional (3D) culture context. In addition, there have only been limited efforts to engineer 3D culture models of liver progenitor cells through the tunable presentation of microenvironmental stimuli. We present an
in vitro
model of 3D liver progenitor spheroidal cultures with integrated polyethylene glycol hydrogel microparticles for the internal presentation of modular microenvironmental cues and the examination of the combinatorial effects with an exogenous soluble factor. In particular, treatment with the growth factor TGFβ1 directs differentiation of the spheroidal liver progenitor cells toward a biliary phenotype, a behavior which is further enhanced in the presence of hydrogel microparticles. We further demonstrate that surface modification of the hydrogel microparticles with heparin influences the behavior of liver progenitor cells toward biliary differentiation. Taken together, this liver progenitor cell culture system represents an approach for controlling the presentation of microenvironmental cues internalized within 3D spheroidal aggregate cultures. Overall, this strategy could be applied toward the engineering of instructive microenvironments that control stem and progenitor cell differentiation within a 3D context for studies in tissue engineering, drug testing, and cellular metabolism.
Past studies on pediatric HIV disclosure have not investigated the variations across childcare settings. This study explored pediatric HIV disclosure for children living in the community with their ...birthparents or relatives and those living in orphanages in Addis Ababa, Ethiopia, to highlight the variations in reasons, processes and outcomes of disclosure across childcare settings. Semi-structured interviews were conducted with children and their caregivers attending an HIV clinic in Addis Ababa, Ethiopia. Among children living in orphanages, the proportion with disclosure was significantly higher (p < 0.001) and age at disclosure was younger (p = 0.09). Although the proportions of children with unplanned disclosure were similar in orphanages and the community, there were notable differences between children's experiences. Children living in the community often found out their status alone through exposure to antiretroviral therapy advertisements in the media, unbeknownst to their caregivers and healthcare providers and suffered silently without any support. Orphans, on the other hand, experienced unplanned disclosure after the death of their birthparents and subsequently received significant emotional support. Healthcare professionals need to consider these variations with childcare settings in disclosure processes. Practices in orphanages may be important models for developing adequate support system for caregivers and children in the community.
To investigate the effects of customized biomechanical foot orthosis (BFO) on kinematic data during gait in patients with hallux valgus (HV) deformities and compare the results with those of a normal ...control group.
Ten patients with HV deformities and 10 healthy volunteers were enrolled in this study. HV deformity was diagnosed using biomechanical and radiological assessments by a rehabilitation physician. Patients received the customized BFO manufactured at a commercial orthosis laboratory (Biomechanics, Goyang, South Korea) according to the strictly defined procedure by a single experienced technician. The spatiotemporal and kinematic data acquired by the Vicon 3D motion capture system (Oxford Metrics, Oxford, UK) were compared between the intervention groups (control vs. HV without orthosis) and between the HV groups (with vs. without orthosis).
The temporal-spatial and kinematic parameters of the HV group were significantly different from those of the control group. After applying BFO to the HV group, significantly increased ranges of plantar flexion motion and hindfoot inversion were observed. Furthermore, the HV group with BFO showed improved gait cadence, walking speed, and stride length, although the results were not statistically significant.
Our results suggest that it is imperative to understand the pathophysiology of HV, and the application of customized BFO can be useful for improving kinematics in HV deformities.
The aim of this study was to compare the clinical effectiveness of robot-assisted therapy with that of conventional occupational therapy according to the onset and severity of stroke.
In this ...multicenter randomized controlled trial, stroke patients were randomized (1:1) to receive robot-assisted therapy or conventional occupational therapy. The robot-assisted training group received 30 min of robot-assisted therapy twice and 30 min of conventional occupational therapy daily, while the conventional therapy group received 90 min of occupational therapy. Therapy was conducted 5 days/week for 4 weeks. The primary outcome was the Wolf Motor Function Test (WMFT) score after 4 and 8 weeks of therapy.
Overall, 113 and 115 patients received robot-assisted and conventional therapy, respectively. The WMFT score after robot-assisted therapy was not significantly better than that after conventional therapy, but there were significant improvements in the Motricity Index (trunk) and the Fugl-Meyer Assessment. After robot-assisted therapy, wrist strength significantly improved in the subacute or moderate-severity group of stroke patients.
Robot-assisted therapy improved the upper-limb functions and activities of daily living (ADL) performance as much as conventional occupational therapy. In particular, it showed signs of more therapeutic effectiveness in the subacute stage or moderate-severity group.
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