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1.
Artigo em Inglês | MEDLINE | ID: mdl-36124734

RESUMO

BACKGROUND: Frailty is a complex, dynamic geriatric condition, but limited evidence has shown how genes and environment may contribute to its longitudinal changes. We sought to investigate sources of individual differences in the longitudinal trajectories of frailty, considering potential selection bias when including a sample of oldest-old twins. METHODS: Data were from two Swedish twin cohort studies: a younger cohort comprising 1,842 adults aged 29-96 years followed up to 15 waves, and an older cohort comprising 654 adults aged ≥79 years followed up to five waves. Frailty was measured using the frailty index (FI). Age-based latent growth curve models were used to examine longitudinal trajectories, and extended to a biometric analysis to decompose variability into genetic and environmental etiologies. RESULTS: A bilinear model with an inflection point at age 75 best described the data, indicating a four- to five-fold faster FI increase after 75 years. Twins from the older cohort had significantly higher mean FI at baseline but slower rate of increase afterwards. FI level at age 75 was moderately heritable in both men (42%) and women (55%). Genetic influences were relatively stable across age for men and increasing for women, although the most salient amplification in FI variability after age 75 was due to individual-specific environmental influences for both men and women; conclusions were largely consistent when excluding the older cohort. CONCLUSION: Increased heterogeneity of frailty in late life is mainly attributable to environmental influences, highlighting the importance of targeting environmental risk factors to mitigate frailty in older adults.

2.
PLoS One ; 17(8): e0272370, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35925951

RESUMO

Hospitals acquire and maintain long-term operating assets such as land, buildings, and equipment. In this study, we analyzed hospitals' long-term assets acquisitions data extracted from the Medicare Cost Report, a mandatory annual filing for all Medicare-certified hospitals. The first objective of this study is to examine the time trend of land, buildings, and equipment acquisitions of all general acute care hospitals in the U.S. from 2005 to 2019 to understand the relative magnitude and temporal changes for the operating assets. The second objective is to examine the 15-year accumulated acquisitions of land, buildings, and equipment per capita in each state to understand the variations of potential access to hospital operating resources across states. To understand the longitudinal changes in acquisitions of operating assets for each year from 2005 to 2019, we calculated the total acquisition amounts across all hospitals for land, buildings, and equipment, respectively, and adjusted the amounts to 2019 dollars based on the consumer price index (CPI). For each state (including Washington D.C.) and the whole nation, the 15-year accumulated CPI-adjusted acquisition amounts per capita for land, buildings, and equipment were also calculated, respectively. The nationwide acquisitions of those operating assets grew rapidly from 2005 to 2008 followed by a negative overall growth from 2008 to 2014 and since 2015, started increasing steadily again. In 2019, U.S. general acute care hospitals acquired $3.0 billion of land, $44.6 billion of buildings, and $33.9 billion of equipment. Huge geographical variation in per capita cumulative total asset investment were also found with the first place North Dakota having a per capita investment that is almost four times higher than that in the lowest ranked state of Alabama.


Assuntos
Investimentos em Saúde , Medicare , Alabama , Hospitais , North Dakota , Estados Unidos
3.
Sensors (Basel) ; 22(15)2022 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-35957225

RESUMO

The traditional optical fiber-based twist sensing has the disadvantage of low sensitivity and difficulty of distinguishing the twist direction. Moreover, chiral isomerism may lead to sensing errors. In this paper, a six-hole helical microstructured optical fiber (HMSF) with a thin-gold-film-coat based on the surface plasmon resonance (SPR) effect was designed. The twist sensing characteristics of this fiber were further analyzed. Numerical calculation and analysis show that the combination of helical effect and SPR effect can design an HMSF-based sensor that is very sensitive to distortion. In the torsion range of ±300°, the distortion sensitivity can reach 2470.7 pm/(rad/m), and the linear correlation coefficient is 0.99996. Based on the special sensing mechanism, it has a good linear coefficient over a large range. Additionally, the direction of the twist can be easily discerned. The HMSF in this work not only has high sensitivity, high linearity, high fault tolerance rate, and a wide range of measurement, but is also easy to manufacture. Therefore, it is promising in the field of twist sensing and has a good application prospect.

4.
Res Social Adm Pharm ; 18(11): 3995-4002, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35934666

RESUMO

Pharmacy Benefit Managers (PBMs) originated in the 1960s to address a market need providing services to insurance companies in managing the newly introduced prescription drug benefits. Since then, PBMs have been expanding their roles in the prescription drug supply chain and have come under scrutiny. As of November 2021, all 50 states have enacted some form of regulation on PBMs. These state-level regulations focus on a variety of different policy levers, many of which align with advocacy efforts led by community pharmacists that focus on business transactions between pharmacies and PBMs without evidence supporting how these policies would enhance the patient experience, improve population health, lower costs, or improve the experience of health care providers. Many state policies could help increase transparency, prevent anticompetitive behavior between PBM-owned and independently-owned pharmacies, and increased accountability of PBMs to plan sponsors. However, there were no direct mechanisms to ensure that the potential benefits of these policies would ultimately be realized as savings for the health care system or consumers, improved health outcomes, or increased quality of care.

5.
JAMA Health Forum ; 3(5): e220888, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35977258

RESUMO

This economic evaluation examines the magnitude and trend of prescription drug rebates in commercial markets from 2015 to 2019 and identifies insurance plan factors associated with rebates.


Assuntos
Medicamentos sob Prescrição , Seguro Saúde , Prescrições
6.
JAMA Health Forum ; 3(5): e221018, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35977260

RESUMO

Importance: The COVID-19 pandemic has had a negative association with hospital operations. To help health care facilities and clinicians stay financially viable during the COVID-19 pandemic, Congress provided $175 billion in subsidies. It remains unclear how much financial losses hospitals incurred owing to operational disruptions during the COVID-19 pandemic and whether subsidies were sufficient to offset the financial losses. Objective: To assess changes in the operational financial performance and overall financial viability of hospitals during the COVID-19 pandemic. Design Setting and Participants: This cross-sectional study included 1378 US hospitals whose fiscal years began in January and 785 hospitals whose fiscal years began in July (all with continuous observations from 2016 through 2020). RAND Hospital Data, a compiled and processed version of Medicare Cost Reports, were used. The data were analyzed on March 12, 2022. Exposures: The operational disruptions experienced and relief funds received by US hospitals during the COVID-19 pandemic. Main Outcomes and Measures: A hospital's annual operating margin, overall profit margin, and other nonoperating income as a share of total revenue from January 2016 to December 2020. Results: Among the 1378 hospitals with fiscal years beginning in January, the mean operating margin declined from -1.0% (95% CI,-1.9% to -0.1%) in 2019 to -7.4% (95% CI, -8.5% to -6.3%) in 2020. The mean share of other nonoperating income grew from 4.4% (95% CI, 4% to 4.7%) in 2019 to 10.3% (95% CI, 9.9% to 10.8%) in 2020. The mean overall profit in 2020 (6.7%; 95% CI, 5.4% to 8.1%) remained as stable as prior years. Government, rural, and smaller hospitals showed higher mean overall profit margins in 2020 than in 2019 (7.2% vs 3.7%, 7.5% vs 1.9%, and 6.7% vs 3.5%, respectively). These results remained consistent when hospitals whose fiscal years began in July were examined. Conclusions and Relevance: The results of this cross-sectional study suggest that although hospitals experienced a sizeable reduction in operating margins in 2020, their overall profit margins remained similar to those in prior years, suggesting that the COVID-19 relief fund effectively offset the financial losses for hospitals during the COVID-19 pandemic. Government, rural, and smaller hospitals, which were supported by some targeted fund allocations, generated higher overall profit margins during 2020 than in prior years.


Assuntos
COVID-19 , Idoso , COVID-19/epidemiologia , Estudos Transversais , Hospitais Privados , Humanos , Medicare , Pandemias , Estados Unidos/epidemiologia
7.
BMC Genomics ; 23(1): 483, 2022 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-35780101

RESUMO

BACKGROUND: Zinc finger protein 143(ZNF143), a member of the Krüppel C2H2-type zinc finger protein family, is strongly associated with cell cycle regulation and cancer development. A recent study suggested that ZNF143 plays as a transcriptional activator that promotes hepatocellular cancer (HCC) cell proliferation and cell cycle transition. However, the exact biological role of ZNF143 in liver regeneration and normal liver cell proliferation has not yet been investigated. METHODS: In our study, we constructed a stable rat liver cell line (BRL-3A) overexpressing ZNF143 and then integrated RNA-seq and Cleavage Under Targets and Tagmentation (CUT&Tag) data to identify the mechanism underlying differential gene expression. RESULTS: Our results show that ZNF143 expression is upregulated during the proliferation phase of liver regeneration after 2/3 partial hepatectomy (PH). The cell counting kit-8 (CCK-8) assay, EdU staining and RNA-seq data analyses revealed that ZNF143 overexpression (OE) significantly inhibited BRL-3A cell proliferation and cell cycle progression. We then performed CUT&Tag assays and found that approximately 10% of ZNF143-binding sites (BSs) were significantly changed genome-wide by ZNF143 OE. However, CCCTC-binding factor (CTCF) binding to chromatin was not affected. Interestingly, the integration analysis of RNA-seq and CUT&Tag data showed that some of genes affected by ZNF143 differential BSs are in the center of each gene regulation module. Gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses indicated that these genes are critical in the maintenance of cell identity. CONCLUSION: These results indicated that the expression level of ZNF143 in the liver is important for the maintenance of cell identity. ZNF143 plays different roles in HCC and normal liver cells and may be considered as a potential therapeutic target in liver disease.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Animais , Proliferação de Células/genética , Ratos , Transativadores/genética , Transativadores/metabolismo
8.
J Agric Food Chem ; 70(27): 8458-8468, 2022 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-35786884

RESUMO

Hydrophilic ß-sitosterol sugar esters were synthesized by a two-step biocatalytic approach using ß-sitosterol vinyl adipate as an intermediate. The maximum conversion (above 90%) of ß-sitosterol vinyl adipate was achieved using the saccharides glucose, sucrose, and raffinose. The chemical structure of the synthesized esters was confirmed by various techniques. The investigation of physical properties revealed that ß-sitosterol sugar esters had enhanced water solubility (3.0-8.0 mM at 35 °C), reduced crystallinity, and high wettability. Their lyotropic liquid crystal properties were observed by polarized light microscopy. Furthermore, ß-sitosterol sugar esters could be hydrolyzed into ß-sitosterol adipate under simulated intestinal conditions at a low rate (2.83-18.14%). Most ß-sitosterol sugar esters probably entered into intestinal bile salt micelles with ester bonds intact and showed up to 10-fold higher in vitro bioaccessibility than free ß-sitosterol in non-fat systems. The excellent physical and functional characteristics of ß-sitosterol sugar esters suggested their great potential application in the food industry.


Assuntos
Ésteres , Açúcares , Adipatos , Colesterol/química , Digestão , Ésteres/química , Sitosteroides
9.
Animals (Basel) ; 12(13)2022 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-35804617

RESUMO

The objective of the study was to elucidate the stearoyl-coenzyme A desaturase (SCD1)-dependent gene network of c9, t11-CLA biosynthesis in MAC-T cells from an energy metabolism perspective. The cells were divided into the CAY group (firstly incubated with CAY10566, a chemical inhibitor of SCD1, then incubated with trans-11-octadecenoic acid, (TVA)), the TVA group (only TVA), and the control group (without CAY, TVA). The c9, t11-CLA, and TVA contents were determined by gas chromatography. The mRNA levels of SCD1 and candidate genes were analyzed via real-time PCR. Tandem mass tag (TMT)-based quantitative proteomics, bioinformatic analysis, parallel reaction monitoring (PRM), and small RNA interference were used to explore genes involved in the SCD1-dependent c9, t11-CLA biosynthesis. The results showed that the SCD1 deficiency led by CAY10566 blocked the biosynthesis of c9, t11-CLA. In total, 60 SCD1-related proteins mainly involved in energy metabolism pathways were primarily screened by TMT-based quantitative proteomics analysis. Moreover, 17 proteins were validated using PRM analysis. Then, 11 genes were verified to have negative relationships with SCD1 after the small RNA interference analysis. Based on the above results, we concluded that genes involved in energy metabolism pathways have an impact on the SCD1-dependent molecular mechanism of c9, t11-CLA biosynthesis.

10.
BMJ Open ; 12(7): e060501, 2022 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-35820764

RESUMO

OBJECTIVE: This study aims to characterise and evaluate the largest 100 hospitals in the USA that have adopted aggressive collection tactics to pursue patients with unpaid medical bills, such as lawsuits, wage garnishments and liens. DESIGN: Cross-sectional study. SETTING: We examined state and county court record systems to measure the magnitude and prevalence of these practices at the largest 100 hospitals in the UA between 1 January 2018 and 31 July 2020. MAIN OUTCOMES MEASURES: The main outcome of this study was the number of lawsuits, wage garnishments and liens. A secondary outcome was the characterisation of a hospital's safety, charitability, size and financial practices. RESULTS: Between 1 January 2018 and 31 July 2020, 26 hospitals filed 38 965 court actions (lawsuits, wage garnishments and liens) against patients for unpaid medical debt. For 16 of 26 hospitals, the dollar amount pursued in the court claim was available for 100% of cases, totalling US$71.8 million. The average aggregate amount sought by hospital lawsuits during the study period was US$4.5 million. Three hospitals filed US$56.2 million in amounts pursued in court, or 78.3% of the total amount pursued by all hospitals in the sample. In the remaining 74 hospitals, the study team did not identify extraordinary collection actions through the court system. CONCLUSIONS: Standardised medical debt collections best practices and metrics of medical debt collections quality are needed to increase public accountability for hospitals, particularly non-profit hospitals. There is a need to re-evaluate Internal Revenue Service rules pertaining to non-profit hospitals' tax-exempt status to ensure tax-exempt hospitals provide community benefits commensurate with the value of tax exemption.


Assuntos
Hospitais , Isenção Fiscal , Estudos Transversais , Humanos
11.
Front Microbiol ; 13: 879321, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35711756

RESUMO

Our previous work have shown that certain subpopulations of Klebsiella pneumoniae exhibit significant phenotypic changes under simulated microgravity (SMG), including enhanced biofilm formation and cellulose synthesis, which may be evoked by changes in gene expression patterns. It is well known that prokaryotic cells genomic DNA can be hierarchically organized into different higher-order three-dimensional structures, which can highly influence gene expression. It is remain elusive whether phenotypic changes induced by SMG in the subpopulations of K. pneumoniae are driven by genome higher-order structural changes. Here, we investigated the above-mentioned issue using the wild-type (WT) K. pneumoniae (WT was used as a control strain and continuously cultivated for 2 weeks under standard culture conditions of normal gravity) and two previous identified subpopulations (M1 and M2) obtained after 2 weeks of continuous incubation in a SMG device. By the combination of genome-wide chromosome conformation capture (Hi-C), RNA-seq and whole-genome methylation (WGS) analyses, we found that the along with the global chromosome interactions change, the compacting extent of M1, M2 subpopulations were much looser under SMG and even with an increase in active, open chromosome regions. In addition, transcriptome data showed that most differentially expressed genes (DEGs) were upregulated, whereas a few DEGs were downregulated in M1 and M2. The functions of both types DEGs were mainly associated with membrane fractions. Additionally, WGS analysis revealed that methylation levels were lower in M1 and M2. Using combined analysis of multi-omics data, we discovered that most upregulated DEGs were significantly enriched in the boundary regions of the variable chromosomal interaction domains (CIDs), in which genes regulating biofilm formation were mainly located. These results suggest that K. pneumoniae may regulate gene expression patterns through DNA methylation and changes in genome structure, thus resulting in new phenotypes in response to altered gravity.

13.
Food Chem ; 394: 133412, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-35728468

RESUMO

The lipid matrix plays a key role in solid lipid nanoparticles (SLNs) embedding active ingredients. To investigate the influence of lipid matrix structure on arrangement, release, and stability of solid lipid nanoparticles, three phytosterols formulations with different carrier glycerides [glycerol monostearate (GMS), glycerol distearate (GDS), and glycerol tristearate (GTS)] were prepared and evaluated. X-ray diffraction and differential scanning calorimetry revealed the lowest crystallinity of phytosterols in the GMS matrix, corresponding to the maximum bioaccessibility (40.2%) in vitro experiments. Sustained release and better stability were observed from GDS and GTS matrices, which could be attributed to strong molecular interactions or a core-rich structure inside the nanoparticles. Molecular dynamics simulations demonstrated that the affinity between phytosterols and glycerides decreased in the order GDS > GTS > GMS, as well as explaining the release and storage capacities of the three nanoparticles. This study would facilitate the rational design of SLNs in functional foods.


Assuntos
Nanopartículas , Fitosteróis , Varredura Diferencial de Calorimetria , Portadores de Fármacos/química , Glicerídeos/química , Glicerol , Lipídeos/química , Lipossomos , Nanopartículas/química , Tamanho da Partícula
14.
J Texture Stud ; 2022 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-35661160

RESUMO

Freezing is a way to preserve the quality of fruit for a long time. Nanguo pear stored at low temperature is prone to browning and lignification. In this study, freeze-thaw cycles were used to simulate the temperature fluctuation in the process, storage, and transportation. The texture properties were taken as the research focus to analyze the lignification phenomenon of Nanguo pear under freeze-thaw cycles. The results showed that freeze-thaw treatment significantly reduced the firmness and propectin content of Nanguo pear, increased the content of stone cells in the fruit, but also destroyed the size of stone cells in the fruit. However, with the increase of freezing-thawing cycles, the content of lignin, stone cell content, and PAL activity increased significantly, while the content of chlorogenic acid increased first and then decreased. These results are helpful to further understand the correlation between texture change with fruit firmness and formation mechanism of stone cells during freeze-thaw cycles of Nanguo pear.

15.
BMJ Open ; 12(5): e059041, 2022 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-35545399

RESUMO

OBJECTIVE: This study aims to characterise and evaluate the National Institutes of Health's (NIH's) grant allocation speed and pattern of COVID-19 research. DESIGN: Cross-sectional study. SETTING: COVID-19 NIH RePORTER Dataset was used to identify COVID-19 relevant grants. PARTICIPANTS: 1108 grants allocated to COVID-19 research. MAIN OUTCOMES AND MEASURES: The primary outcome was to determine the number of grants and funding amount the NIH allocated for COVID-19 by research type and clinical/scientific area. The secondary outcome was to calculate the time from the funding opportunity announcement to the award notice date. RESULTS: The NIH awarded a total of 56 169 grants in 2020, of which 2.0% (n=1108) wwas allocated for COVID-19 research. The NIH had a US$45.3 billion budget that year, of which 4.9% (US$2.2 billion) was allocated to COVID-19 research. The most common clinical/scientific areas were social determinants of health (n=278, 8.5% of COVID-19 funding), immunology (n=211, 25.8%) and pharmaceutical interventions research (n=208, 47.6%). There were 104 grants studying COVID-19 non-pharmaceutical interventions, of which 2 grants studied the efficacy of face masks and 6 studied the efficacy of social distancing. Of the 83 COVID-19 funded grants on transmission, 5 were awarded to study airborne transmission of COVID-19 and 2 grants on transmission of COVID-19 in schools. The average time from the funding opportunity announcement to the award notice date was 151 days (SD: ±57.9). CONCLUSION: In the first year of the pandemic, the NIH diverted a small fraction of its budget to COVID-19 research. Future health emergencies will require research funding to pivot in a timely fashion and funding levels to be proportional to the anticipated burden of disease in the population.


Assuntos
Pesquisa Biomédica , COVID-19 , COVID-19/epidemiologia , Estudos Transversais , Organização do Financiamento , Humanos , National Institutes of Health (U.S.) , Estados Unidos
16.
J Chromatogr Sci ; 2022 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-35567797

RESUMO

Eleven consecutive N'-n-acylnornicotines from cherry-red tobacco were structurally elucidated and quantitively analyzed using chromatography and mass spectrometry. All of these N'-n-acylnornicotines are first reported in cherry-red tobacco, whereas N'-propionylnornicotine, N'-n-valerylnornicotine, N'-n-nonanoylnornicotine and N'-n-undecanoylnornicotine are first reported in natural products. The concentration distribution of the identified N'-n-acylnornicotines was studied and it was found that N'-n-octanoylnornicotine and N'-n-hexanoylnornicotine showed the highest concentration, accounting for 94% of the detected N'-n-acylnornicotines. The cherry-red color density of the related tobacco leaves was found to be positively correlated with the concentration of the N'-n-acylnornicotines, whereas the ultraviolet-visible spectra of the N'-n-acylnornicotines showed no absorption larger than 300 nm, indicating the discovered compounds are not responsible for the cherry-red color appearance.

17.
J Anim Ecol ; 91(6): 1303-1315, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35420162

RESUMO

Organisms exist within ecological networks, connected through interactions such as parasitism, predation and mutualism which can modify their abundance and distribution within habitat patches. Differential species responses make it hard to predict the influence of climate change at the community scale. Understanding the interplay between climate and biotic interactions can improve our predictions of how ecosystems will respond to current global warming. We aim to understand how climate affects the multitrophic biotic interactions as well as the community structure using the enclosed communities of wasps associated with figs as study system. To examine the presence and strength of multitrophic species interactions, we first characterized the multitrophic community of fig wasps associated with Ficus racemosa and then applied hierarchical joint species distribution models, fitted to community monitoring data. We further evaluated the effect of climate on individual species trends as well as interspecific interactions. We found that the competitive balance shifted to favour non-pollinating galling wasps and disadvantage the dominant pollinator in suboptimal conditions. Furthermore, suboptimal conditions for galling wasps facilitated the occurrence of their specialized parasitoid, as changes cascaded across trophic levels and led to alternative community structures. Our results highlight the role of how species interactions can be modified across multiple trophic levels in a fig wasp community according to climate.


Assuntos
Ficus , Vespas , Animais , Ecossistema , Ficus/fisiologia , Polinização , Simbiose , Temperatura , Vespas/fisiologia
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