The onset of presbyopia in middle adulthood results in potential losses in productivity among otherwise healthy adults if uncorrected or undercorrected. The economic burden could be significant in ...lower-income countries, where up to 94% of cases may be uncorrected or undercorrected. This study estimates the global burden of potential productivity lost because of uncorrected functional presbyopia.
Population data from the US Census Bureau were combined with the estimated presbyopia prevalence, age of onset, employment rate, gross domestic product (GDP) per capita in current US dollars, and near vision impairment disability weights from the Global Burden of Disease 2010 study to estimate the global loss of productivity from uncorrected and undercorrected presbyopia in each country in 2011. To allow comparison with earlier work, we also calculated the loss with the conservative assumption that the contribution to productivity extends only up to 50 years of age.
The economic modeling did not require the use of subjects.
We estimated the number of cases of uncorrected or undercorrected presbyopia in each country among the working-age population. The number of working-age cases was multiplied by the labor force participation rate, the employment rate, a disability weight, and the GDP per capita to estimate the potential loss of GDP due to presbyopia.
The outcome being measured is the lost productivity in 2011 US dollars resulting from uncorrected or undercorrected presbyopia.
There were an estimated 1.272 billion cases of presbyopia worldwide in 2011. A total of 244 million cases, uncorrected or undercorrected among people aged <50 years, were associated with a potential productivity loss of US $11.023 billion (0.016% of global GDP). If all those people aged <65 years are assumed to be productive, the potential productivity loss would be US $25.367 billion or 0.037% of global GDP. Correcting presbyopia to the level achieved in Europe would reduce the burden to US $1.390 billion (0.002% of global GDP).
Even with conservative assumptions regarding the productive population, presbyopia is a significant burden on productivity, and correction would have a significant impact on productivity in lower-income countries.
We previously isolated MACH-related inducer of toxicity (MRIT), a homolog of caspase 8. MRIT, also known as c-FLICE-inhibitory protein (c-FLIP), is an enzymatically inactive homolog of caspase 8 with ...homology to viral FLIP (v-FLIP). Because of this homology and resemblance to dominant negative proteins, c-FLIP is widely believed to be an antagonist to the death receptor-initiated apoptotic pathways that use caspase 8. We generated a polyclonal antibody, MAG1, and show that this antibody specifically recognizes two splice forms, long form (c-FLIP
l) and short form (c-FLIP
s). By
in situ
hybridization and immunohistochemistry, we demonstrate that c-FLIP is expressed in endothelial cells, macrophages, and smooth muscle cells (SMCs) both in human coronary arteries and in cultured cells. In an uninjured rat carotid arteries, c-FLIP protein is abundant in the vascular media. After balloon angioplasty, c-FLIP protein is rapidly down-regulated in medial SMCs for 2 weeks and regains expression by 4 weeks. In contrast, the neointima is strongly immunoreactive to c-FLIP from day 7 after the initial injury and remains strongly immunoreactive until 4 to 6 weeks. Similarly there is strong c-FLIP immunoreactivity in SMCs from nonatherosclerotic diffuse intimal thickening and in the overlying endothelial cells. In contrast, c-FLIP immunoreactivity is uneven and often absent in SMCs within the atherosclerotic plaque. Double labeling with c-FLIP antibody and terminal deoxynucleotidyltransferase-mediated UDP end labeling (TUNEL) in the injured rat common carotid artery show that TUNEL-positive cells in the first 2 days after injury lack detectable c-FLIP, suggested a role for caspase 8 in this form of death. In contrast, there is no correlation of c-FLIP with the spontaneous elevation in death of intima seen at 7 days after injury. For human atherosclerotic plaques, the majority of TUNEL-positive cells lack detectable c-FLIP. The expression pattern of c-FLIP and the relation between c-FLIP and TUNEL suggest a role for c-FLIP- and caspase 8-driven death in control of viability of the cells of the atherosclerotic intima.
COVID-19 caused by the SARS-CoV-2 virus has become a global pandemic. 3CL protease is a virally encoded protein that is essential across a broad spectrum of coronaviruses with no close human analogs. ...PF-00835231, a 3CL protease inhibitor, has exhibited potent in vitro antiviral activity against SARS-CoV-2 as a single agent. Here we report, the design and characterization of a phosphate prodrug PF-07304814 to enable the delivery and projected sustained systemic exposure in human of PF-00835231 to inhibit coronavirus family 3CL protease activity with selectivity over human host protease targets. Furthermore, we show that PF-00835231 has additive/synergistic activity in combination with remdesivir. We present the ADME, safety, in vitro, and in vivo antiviral activity data that supports the clinical evaluation of PF-07304814 as a potential COVID-19 treatment.
Subarachnoid fat is an uncommon finding that has several etiologies. It is important to determine the etiology in order to plan appropriate treatment. We present a case report of an 80-year-old ...female brought to the emergency department after a fall with complaints of headache and pain in the sacral region. Computed tomography and magnetic resonance images of the head demonstrated fat in the subarachnoid space. Computed tomography and magnetic resonance images of the sacrum demonstrated a Tarlov cyst with a sacral fracture extending into the cyst, likely representing the origin of the fat in the subarachnoid space. This case demonstrates a rare etiology of fat in the subarachnoid space.
Damage to renal tubular epithelial cells by genetic, environmental, or biological insults can initiate complex signaling mechanisms that promote kidney repair and functional recovery. In this study, ...we demonstrated that thyroid receptor interacting protein 13 (TRIP13) is a critical modulator of tubular epithelial cell repair following ischemia-reperfusion injury (IRI), a common type of renal stressor. In Trip13
hypomorph mice treated with unilateral renal IRI, persistent tubular epithelial cell damage was determined in the IRI-treated kidney throughout the 168 hours of experimental period compared to the contralateral kidneys. The damaged epithelial cells were associated with increased levels of DNA damage (ɣH2AX) and apoptotic markers (p53, cleaved caspase-7, and TUNEL-positive cells). Correspondingly, TRIP13 was found to directly interact with Tetratricopeptide Repeat Domain 5 (TTC5), a p53 co-factor, and genetic knockdown of TRIP13 in murine inner medullary collecting duct cells in the presence of hydrogen peroxide showed increased activity of p53 at Serine 15. In all, these studies suggest that insufficient TRIP13 increased the susceptibility of damaged tubular epithelial cells to progress towards apoptotic cell death.
Lipoprotein lipase (LPL), hydrolyzes the core triglycerides of lipoproteins, thereby playing a role in their maturation. LPL may be important in the metabolic pathways that lead to atherosclerosis, ...since it is secreted in vitro by both of the predominant cell types of the atherosclerotic plaque, i.e., macrophages and smooth muscle cells. Because of uncertainty concerning the primary cellular source of LPL in atherosclerotic lesions, in situ hybridization assays for LPL mRNA were performed on 12 coronary arteries obtained from six cardiac allograft recipients. Macrophages and smooth muscle cells were identified on adjacent sections with cell-specific antibodies and foam cells were identified morphologically. LPL protein was localized using a polyclonal antibody. LPL mRNA was produced by a proportion of plaque macrophages, particularly macrophage-derived foam cells, but was not detected in association with any intimal or medial smooth muscle cells. These findings were confirmed by combined immunocytochemistry and in situ hybridization on the same tissue sections. LPL protein was detected in association with macrophage-derived foam cells, endothelial cells, adventitial adipocytes, and medial smooth muscle cells, and, to a lesser extent, in intimal smooth muscle cells and media underlying well-developed plaque. These results indicate that macrophage-derived foam cells are the primary source of LPL in atherosclerotic plaques and are consistent with a role for LPL in the pathogenesis of atherosclerosis.
Imaging of Overuse Injuries of the Hip Baal, Joe D; Cecil, Katherine L; Patel, Rina ...
The Radiologic clinics of North America
61, Številka:
2
Journal Article
Recenzirano
Overuse injuries of the hip are common, and clinical diagnosis may be difficult because of overlapping and nonspecific clinical symptoms. Imaging can play an essential role in guiding diagnosis and ...management. Femoroacetabular joint structural abnormalities result in various conditions that can predispose patients to early development of osteoarthritis. Repetitive stress on the skeletally immature hip can result in apophyseal injuries. Notable nonosseous overuse hip pathologies include athletic pubalgia, trochanteric bursitis, and injuries involving the iliopsoas myotendinous unit. Timely diagnosis of overuse injuries of the hip can facilitate improved response to conservative measures and prevent irreversible damage.
ECG Interpretation Proficiency of Healthcare Professionals Kashou, Anthony H.; Noseworthy, Peter A.; Beckman, Thomas J. ...
Current problems in cardiology,
October 2023, 2023-Oct, 2023-10-00, 20231001, Letnik:
48, Številka:
10
Journal Article
Recenzirano
ECG interpretation is essential in modern medicine, yet achieving and maintaining competency can be challenging for healthcare professionals. Quantifying proficiency gaps can inform educational ...interventions for addressing these challenges. Medical professionals from diverse disciplines and training levels interpreted 30 12-lead ECGs with common urgent and nonurgent findings. Average accuracy (percentage of correctly identified findings), interpretation time per ECG, and self-reported confidence (rated on a scale of 0 not confident, 1 somewhat confident, or 2 confident) were evaluated. Among the 1206 participants, there were 72 (6%) primary care physicians (PCPs), 146 (12%) cardiology fellows-in-training (FITs), 353 (29%) resident physicians, 182 (15%) medical students, 84 (7%) advanced practice providers (APPs), 120 (10%) nurses, and 249 (21%) allied health professionals (AHPs). Overall, participants achieved an average overall accuracy of 56.4% ± 17.2%, interpretation time of 142 ± 67 seconds, and confidence of 0.83 ± 0.53. Cardiology FITs demonstrated superior performance across all metrics. PCPs had a higher accuracy compared to nurses and APPs (58.1% vs 46.8% and 50.6%; P < 0.01), but a lower accuracy than resident physicians (58.1% vs 59.7%; P < 0.01). AHPs outperformed nurses and APPs in every metric and showed comparable performance to resident physicians and PCPs. Our findings highlight significant gaps in the ECG interpretation proficiency among healthcare professionals.
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