There is a growing concern about the COVID-19 epidemic intensifying in rural areas in the United States (U.S.). In this study, we described the dynamics of COVID-19 cases and deaths in rural and ...urban counties in the U.S.
Using data from April 1 to November 12, 2020, from Johns Hopkins University, we estimated COVID-19 incidence and mortality rates and conducted comparisons between urban and rural areas in three time periods at the national level, and in states with higher and lower COVID-19 incidence rates.
Results at the national level showed greater COVID-19 incidence rates in urban compared to rural counties in the Northeast and Mid-Atlantic regions of the U.S. at the beginning of the epidemic. However, the intensity of the epidemic has shifted to a rapid surge in rural areas. In particular, high incidence states located in the Mid-west of the country had more than 3,400 COVID-19 cases per 100,000 people compared to 1,284 cases per 100,000 people in urban counties nationwide during the third period (August 30 to November 12).
Overall, the current epicenter of the epidemic is located in states with higher infection rates and mortality in rural areas. Infection prevention and control efforts including healthcare capacity should be scaled up in these vulnerable rural areas.
•Assessment of the patterns of COVID-19 in rural and urban counties in the United States.•COVID-19 epidemic in the United States is composed of sub-epidemics with different temporal dynamics and spatial patterns.•The current epicenter of the epidemic is located in states with higher COVID-19 infection intensity and mortality in rural areas.•Residents in areas with high burden of infection combined with lower healthcare capacity are at higher risk of COVID-19 infection and related morbidity and mortality.
The United States (U.S.) is currently experiencing a substance use disorders (SUD) crisis with an unprecedented magnitude. The objective of this study was to recognize and characterize the most ...vulnerable populations at high risk of SUD mortality in the U.S., and to identify the locations where these vulnerable population are located. We obtained the most recent available mortality data for the U.S. population aged 15-84 (2005-2017) from the Centers for Diseases and Prevention (CDC). Our analysis focused on the unintentional substance poisoning to estimate SUD mortality. We computed health-related comorbidities and socioeconomic association with the SUD distribution. We identified the most affected populations and conducted a geographical clustering analysis to identify places with increased concentration of SUD related deaths. From 2005-2017, 463,717 SUD-related deaths occurred in the United States. White population was identified with the highest SUD death proportions. However, there was a surge of the SUD epidemic in the Black male population, with a sharp increase in the SUD-related death rate since 2014. We also found that an additional average day of mental distress might increase the relative risk of SUD-related mortality by 39%. The geographical distribution of the epidemic showed clustering in the West and Mid-west regions of the U.S. In conclusion, we found that the SUD epidemic in the U.S. is characterized by the emergence of several micro-epidemics of different intensities across demographic groups and locations within the country. The comprehensive description of the epidemic presented in this study could assist in the design and implementation of targeted policy interventions for addiction mitigation campaigns.
Under the premise that in a resource-constrained environment such as Sub-Saharan Africa it is not possible to do everything, to everyone, everywhere, detailed geographical knowledge about the HIV ...epidemic becomes essential to tailor programmatic responses to specific local needs. However, the design and evaluation of national HIV programs often rely on aggregated national level data. Against this background, here we proposed a model to produce high-resolution maps of intranational estimates of HIV prevalence in Kenya, Malawi, Mozambique and Tanzania based on spatial variables. The HIV prevalence maps generated highlight the stark spatial disparities in the epidemic within a country, and localize areas where both the burden and drivers of the HIV epidemic are concentrated. Under an era focused on optimal allocation of evidence-based interventions for populations at greatest risk in areas of greatest HIV burden, as proposed by the Joint United Nations Programme on HIV/AIDS (UNAIDS) and the United States President's Emergency Plan for AIDS Relief (PEPFAR), such maps provide essential information that strategically targets geographic areas and populations where resources can achieve the greatest impact.
Sclerostin and Dickkopf-1 in Renal Osteodystrophy Cejka, Daniel; Herberth, Johann; Branscum, Adam J ...
Clinical journal of the American Society of Nephrology,
04/2011, Letnik:
6, Številka:
4
Journal Article
Recenzirano
Odprti dostop
The serum proteins sclerostin and Dickkopf-1 (Dkk-1) are soluble inhibitors of canonical wnt signaling and were recently identified as components of parathyroid hormone (PTH) signal transduction. ...This study investigated the associations between sclerostin and Dkk-1 with histomorphometric parameters of bone turnover, mineralization, and volume in stage 5 chronic kidney disease patients on dialysis (CKD-5D).
In a cross-sectional study, 60 CKD-5D patients underwent bone biopsies followed by histomorphometry. Levels of sclerostin, Dkk-1, and intact PTH (iPTH) were determined in blood.
Serum levels of sclerostin and iPTH correlated negatively. In unadjusted analyses, sclerostin correlated negatively with histomorphometric parameters of turnover, osteoblastic number, and function. In adjusted analyses, sclerostin remained a strong predictor of parameters of bone turnover and osteoblast number. An observed correlation between sclerostin and cancellous bone volume was lost in regression analyses. Sclerostin was superior to iPTH for the positive prediction of high bone turnover and number of osteoblasts. In contrast, iPTH was superior to sclerostin for the negative prediction for high bone turnover and had similar predictive values than sclerostin for the number of osteoblasts. Serum levels of Dkk-1 did not correlate with iPTH or with any histomorphometric parameter.
Our data describe a promising role for serum measurements of sclerostin in addition to iPTH in the diagnosis of high bone turnover in CKD-5D patients, whereas measurements of Dkk-1 do not seem to be useful for this purpose.
The Standards for the Reporting of Diagnostic Accuracy (STARD) statement, which was recently updated to the STARD2015 statement, was developed to encourage complete and transparent reporting of test ...accuracy studies. Although STARD principles apply broadly, the checklist is limited to studies designed to evaluate the accuracy of tests when the disease status is determined from a perfect reference procedure or an imperfect one with known measures of test accuracy. However, a reference standard does not always exist, especially in the case of infectious diseases with a long latent period. In such cases, a valid alternative to classical test evaluation involves the use of latent class models that do not require a priori knowledge of disease status. Latent class models have been successfully implemented in a Bayesian framework for over 20 years. The objective of this work was to identify the STARD items that require modification and develop a modified version of STARD for studies that use Bayesian latent class analysis to estimate diagnostic test accuracy in the absence of a reference standard. Examples and elaborations for each of the modified items are provided. The new guidelines, termed STARD-BLCM (Standards for Reporting of Diagnostic accuracy studies that use Bayesian Latent Class Models), will facilitate improved quality of reporting on the design, conduct and results of diagnostic accuracy studies that use Bayesian latent class models.
Bone marrow adipose tissue (BMAT) is hypothesized to serve as an expandable/contractible fat depot which functions, in part, to minimize energy requirements for sustaining optimal hematopoiesis. We ...investigated whether BMAT is required for immune reconstitution following injury. Male wild type (WBB6F1, WT) and BMAT-deficient WBB6F1/J-
/J (
) mice were lethally irradiated. Irradiation was followed by adoptive transfer of 1000 purified WT hematopoietic stem cells (HSCs). The extent of immune reconstitution in blood, bone marrow, and lymph nodes in the irradiated mice was determined using HSCs from green fluorescent protein (GFP)-expressing mice. We also evaluated skeletal response to treatment. Detection of GFP-positive B and T cells in peripheral blood at 4 and 9 weeks following adoptive transfer and in bone marrow and lymph nodes following necropsy revealed excellent immune reconstitution in both WT and BMAT-deficient mice. Adipocytes were numerous in the distal femur of WT mice but absent or rare in
mice. Bone parameters, including length, mass, density, bone volume, microarchitecture, and turnover balance, exhibited few differences between WT and BMAT-deficient mice. The minimal differences suggest that BMAT is not required for reconstitution of the immune system following lethal radiation and is not a major contributor to the skeletal phenotypes of kit signaling-deficient mice.
The underlying reasons behind the unprecedented increase of the mortality rates due to the opioid epidemics in the United States are still not fully uncovered. Most efforts have been focused on ...targeting opioids, but there is little information about vulnerable populations at high risk of opioid abuse and death. In this study, we used data from the Ohio Department of Health for deaths caused by prescription opioids from 2010-2017 to analyze the spatiotemporal dynamics of the opioid overdose epidemic. Our results showed a rapid increase in prescription opioid death rates among the white male population aged 30-39 but also a considerable increase among the black male population with an exponential growth trend. Our geospatial analysis suggests that the increasing rates of the opioid overdose epidemic in Ohio were driven by the epidemic hotspot areas. Our findings highlight the relevance of prioritizing public health measures targeting specific locations and vulnerable populations to mitigate the current opioids crisis.
The hypothalamus and dorsal vagal complex (DVC) are both important for integration of signals that regulate energy balance. Increased leptin transgene expression in either the hypothalamus or DVC of ...female rats was shown to decrease white adipose tissue and circulating levels of leptin and adiponectin. However, in contrast to hypothalamus, leptin transgene expression in the DVC had no effect on food intake, circulating insulin, ghrelin and glucose, nor on thermogenic energy expenditure. These findings imply different roles for hypothalamus and DVC in leptin signaling. Leptin signaling is required for normal bone accrual and turnover. Leptin transgene expression in the hypothalamus normalized the skeletal phenotype of leptin-deficient ob/ob mice but had no long-duration (≥10 weeks) effects on the skeleton of leptin-replete rats. The goal of this investigation was to determine the long-duration effects of leptin transgene expression in the DVC on the skeleton of leptin-replete rats. To accomplish this goal, we analyzed bone from three-month-old female rats that were microinjected with recombinant adeno-associated virus encoding either rat leptin (rAAV-Leptin, n = 6) or green fluorescent protein (rAAV-GFP, control, n = 5) gene. Representative bones from the appendicular (femur) and axial (3rd lumbar vertebra) skeleton were evaluated following 10 weeks of treatment. Selectively increasing leptin transgene expression in the DVC had no effect on femur cortical or cancellous bone microarchitecture. Additionally, increasing leptin transgene expression had no effect on vertebral osteoblast-lined or osteoclast-lined bone perimeter or marrow adiposity. Taken together, the findings suggest that activation of leptin receptors in the DVC has minimal specific effects on the skeleton of leptin-replete female rats.
•Leptin is important for energy balance and bone maturation.•The dorsal vagal complex (DVC) plays a role in integrating leptin signaling.•Increased leptin gene expression in the DVC had no effect on bone in rats.
Bone marrow adipose tissue (BMAT) levels are higher in distal femur metaphysis of female mice housed at thermoneutral (32°C) than in mice housed at 22°C, as are abdominal white adipose tissue (WAT) ...mass, and serum leptin levels. We performed two experiments to explore the role of increased leptin in temperature-enhanced accrual of BMAT. First, we supplemented 6-week-old female C57BL/6J (B6) mice with leptin for 2 weeks at 10 µg/d using a subcutaneously implanted osmotic pump. Controls consisted of
ad libitum
(
ad lib
) fed mice and mice pair fed to match food intake of leptin-supplemented mice. The mice were maintained at 32°C for the duration of treatment. At necropsy, serum leptin in leptin-supplemented mice did not differ from
ad lib
mice, suggesting suppression of endogenous leptin production. In support,
Ucp1
expression in BAT, percent body fat, and abdominal WAT mass were lower in leptin-supplemented mice. Leptin-supplemented mice also had lower BMAT and higher bone formation in distal femur metaphysis compared to the
ad lib
group, changes not replicated by pair-feeding. In the second experiment, BMAT response was evaluated in 6-week-old female B6 wild type (WT), leptin-deficient
ob/ob
and leptin-treated (0.3 μg/d)
ob/ob
mice housed at 32°C for the 2-week duration of the treatment. Compared to mice sacrificed at baseline (22°C), BMAT increased in
ob/ob
mice as well as WT mice, indicating a leptin independent response to increased temperature. However, infusion of
ob/ob
mice with leptin, at a dose rate having negligible effects on either energy metabolism or serum leptin levels, attenuated the increase in BMAT. In summary, increased housing temperature and increased leptin have independent but opposing effects on BMAT in mice.
The effect of diet-induced obesity on bone in rodents is variable, with bone mass increases, decreases, and no impact reported. The goal of this study was to evaluate whether the composition of ...obesogenic diet may influence bone independent of its effect on body weight. As proof-of-principle, we used a mouse model to compare the skeletal effects of a commonly used high fat ‘Western’ diet and a modified high fat diet. The modified high fat diet included ground English walnut and was isocaloric for macronutrients, but differed in fatty acid composition and contained nutrients (e.g. polyphenols) not present in the standard ‘Western’ diet. Eight-week-old mice were randomized into 1 of 3 dietary treatments (n = 8/group): (1) low fat control diet (LF; 10 % kcal fat); (2) high fat ‘Western’ diet (HF; 46 % kcal fat as soybean oil and lard); or (3) modified high fat diet supplemented with ground walnuts (HF + walnut; 46 % kcal fat as soybean oil, lard, and walnut) and maintained on their respective diets for 9 weeks. Bone response in femur was then evaluated using dual energy x-ray absorptiometry, microcomputed tomography, and histomorphometry. Consumption of both obesogenic diets resulted in increased weight gain but differed in impact on bone and bone marrow adiposity in distal femur metaphysis. Mice consuming the high fat ‘Western’ diet exhibited a tendency for lower cancellous bone volume fraction and connectivity density, and had lower osteoblast-lined bone perimeter (an index of bone formation) and higher bone marrow adiposity than low fat controls. Mice fed the modified high fat diet did not differ from mice fed control (low fat) diet in cancellous bone microarchitecture, or osteoblast-lined bone perimeter, and exhibited lower bone marrow adiposity compared to mice fed the ‘Western’ diet. This proof-of-principal study demonstrates that two obesogenic diets, similar in macronutrient distribution and induction of weight gain, can have different effects on cancellous bone in distal femur metaphysis. Because the composition of the diets used to induce obesity in rodents does not recapitulate a common human diet, our finding challenges the translatability of rodent studies evaluating the impact of diet-induced obesity on bone.
•The effect of diet-induced obesity on bone in rodents is variable.•We compared skeletal response to two high fat obesogenic diets.•Consumption of both diets resulted in increased weight gain.•The diets differed in impact on cancellous bone and adiposity in distal femur.•Diet composition has actions on bone that are not explained by changes in weight.
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