Novel role of bone morphogenetic protein 9 in innate host responses to HCMV infection.

Herpesviruses modulate immune control to secure lifelong infection. The mechanisms Human Cytomegalovirus (HCMV) employs in this regard can reveal unanticipated aspects of cellular signaling involved in antiviral immunity. Here, we describe a novel relationship between the TGF-ß family cytokine BMP9 and HCMV infection. We identify a cross-talk between BMP9-induced and IFN receptor-mediated signaling, showing that BMP9 boosts the transcriptional response to and antiviral activity of IFNß, thereby enhancing viral restriction. We also show that BMP9 is secreted by human fibroblasts upon HCMV infection. However, HCMV infection impairs BMP9-induced enhancement of the IFNß response, indicating that this signaling role of BMP9 is actively targeted by HCMV. Indeed, transmembrane proteins US18 and US20, which downregulate type I BMP receptors, are necessary and sufficient to cause inhibition of BMP9-mediated boosting of the antiviral response to IFNß. HCMV lacking US18 and US20 is more sensitive to IFNß. Thus, HCMV has a mutually antagonistic relationship with BMP9, which extends the growing body of evidence that BMP signaling is an underappreciated modulator of innate immunity in response to viral infection.

Confidence-ranked reconstruction of census microdata from published statistics.

A reconstruction attack on a private dataset D takes as input some publicly accessible information about the dataset and produces a list of candidate elements of D. We introduce a class of data reconstruction attacks based on randomized methods for nonconvex optimization. We empirically demonstrate that our attacks can not only reconstruct full rows of D from aggregate query statistics Q(D)∈ℝm but can do so in a way that reliably ranks reconstructed rows by their odds of appearing in the private data, providing a signature that could be used for prioritizing reconstructed rows for further actions such as identity theft or hate crime. We also design a sequence of baselines for evaluating reconstruction attacks. Our attacks significantly outperform those that are based only on access to a public distribution or population from which the private dataset D was sampled, demonstrating that they are exploiting information in the aggregate statistics Q(D) and not simply the overall structure of the distribution. In other words, the queries Q(D) are permitting reconstruction of elements of this dataset, not the distribution from which D was drawn. These findings are established both on 2010 US decennial Census data and queries and Census-derived American Community Survey datasets. Taken together, our methods and experiments illustrate the risks in releasing numerically precise aggregate statistics of a large dataset and provide further motivation for the careful application of provably private techniques such as differential privacy.

The moral filter of patriotic prejudice: How Americans view Chinese in the COVID-19 era.

About one in six Asian Americans have fallen victim to anti-Asian racism during the COVID-19 pandemic [J. Lee, K. Ramakrishnan, aapidata.com/blog/discrimination-survey-2022/]. By examining anti-Asian racism in the United States primarily as a domestic issue, most prior studies have overlooked the connections between shifting US-China relations and Americans' prejudices against the Chinese in China and, by extension, East Asian Americans. This study investigates the patterns and perceptual bases of nationality-based prejudices against Chinese amid the COVID-19 pandemic in the United States. Our nationally representative online survey experiment reveals that Americans assess a hypothetical Chinese person in China as inferior in multiple social and psychological characteristics to an otherwise identical Japanese person in Japan or East Asian American. Furthermore, subjects who perceive China as more threatening to America's national interests assess Chinese more negatively, especially in terms of trustworthiness and morality, suggesting that perceived China threats propel Americans' negative stereotypes about Chinese. A contextual analysis further indicates that counties with a higher share of Trump voters in 2016 tend to perceive all East Asian-origin groups similarly as a racial outgroup. By contrast, residents in predominantly Democrat-voting counties tend to perceive Chinese in China more negatively relative to Asian Americans, despite broadly viewing East Asians more favorably. Overall, this study underscores the often-overlooked relationships between the prevailing anti-Asian sentiments in the United States and the US-China geopolitical tensions and America's domestic political polarization.

A practical guide for implementing omalizumab therapy for food allergy.

The recent approval of omalizumab for the treatment of IgE-mediated food allergy is an important step forward for the millions of food allergy patients in the United States. Through the depletion of circulating IgE and the subsequent reduction of FcεR1 on key effector cells, patients increase their tolerance to food allergens. However, omalizumab does not permit patients to eat foods that they are allergic to with impunity. Rather, it protects them from most accidental exposures. In addition, omalizumab does not cure food allergy and has not demonstrated true immunomodulation. Thus, omalizumab might be a lifelong therapy for some patients. Furthermore, there are many important questions and issues surrounding the appropriate administration of omalizumab to treat food allergy, which we discuss. Managing treatment of patients with disease that falls outside the dosing range, assessing treatment response or nonresponse, addressing its appropriateness for patients older than 55, and determining whether immunotherapy plus omalizumab provides any advantage over omalizumab alone all need to be examined. Identifying appropriate patients for this therapy is critical given the cost of biologics. Indeed, not all food allergy patients are good candidates for this therapy. Also, when and how to stop omalizumab therapy in patients who may have outgrown their food allergy needs to be elucidated. Thus, although this therapy provides a good option for patients with food allergies, much information is needed to determine how best to use this therapy. Despite many unanswered questions and issues, we provide clinicians with some practical guidance on implementing this therapy in their patients.

Benzoyl Chloride Derivatization Advances the Quantification of Dissolved Polar Metabolites on Coral Reefs.

Extracellular chemical cues constitute much of the language of life among marine organisms, from microbes to mammals. Changes in this chemical pool serve as invisible signals of overall ecosystem health and disruption to this finely tuned equilibrium. In coral reefs, the scope and magnitude of the chemicals involved in maintaining reef equilibria are largely unknown. Processes involving small, polar molecules, which form the majority components of labile dissolved organic carbon, are often poorly captured using traditional techniques. We employed chemical derivatization with mass spectrometry-based targeted exometabolomics to quantify polar dissolved phase metabolites on five coral reefs in the U.S. Virgin Islands. We quantified 45 polar exometabolites, demonstrated their spatial variability, and contextualized these findings in terms of geographic and benthic cover differences. By comparing our results to previously published coral reef exometabolomes, we show the novel quantification of 23 metabolites, including central carbon metabolism compounds (e.g., glutamate) and novel metabolites such as homoserine betaine. We highlight the immense potential of chemical derivatization-based exometabolomics for quantifying labile chemical cues on coral reefs and measuring molecular level responses to environmental stressors. Overall, improving our understanding of the composition and dynamics of reef exometabolites is vital for effective ecosystem monitoring and management strategies.

Recapitulation of human pathophysiology and identification of forensic biomarkers in a translational model of chlorine inhalation injury.

Chlorine gas (Cl2) has been repeatedly used as a chemical weapon, first in World War I and most recently in Syria. Life-threatening Cl2 exposures frequently occur in domestic and occupational environments, and in transportation accidents. Modeling the human etiology of Cl2-induced acute lung injury (ALI), forensic biomarkers, and targeted countermeasures development have been hampered by inadequate large animal models. The objective of this study was to develop a translational model of Cl2-induced ALI in swine to understand toxico-pathophysiology and evaluate whether it is suitable for screening potential medical countermeasures and to identify biomarkers useful for forensic analysis. Specific pathogen-free Yorkshire swine (30-40 kg) of either sex were exposed to Cl2 (≤240 ppm for 1 h) or filtered air under anesthesia and controlled mechanical ventilation. Exposure to Cl2 resulted in severe hypoxia and hypoxemia, increased airway resistance and peak inspiratory pressure, and decreased dynamic lung compliance. Cl2 exposure resulted in increased total leucocyte and neutrophil counts in bronchoalveolar lavage fluid, vascular leakage, and pulmonary edema compared with the air-exposed group. The model recapitulated all three key histopathological features of human ALI, such as neutrophilic alveolitis, deposition of hyaline membranes, and formation of microthrombi. Free and lipid-bound 2-chlorofatty acids and chlorotyrosine-modified proteins (3-chloro-l-tyrosine and 3,5-dichloro-l-tyrosine) were detected in plasma and lung tissue after Cl2 exposure. In this study, we developed a translational swine model that recapitulates key features of human Cl2 inhalation injury and is suitable for testing medical countermeasures, and validated chlorinated fatty acids and protein adducts as biomarkers of Cl2 inhalation.NEW & NOTEWORTHY We established a swine model of chlorine gas-induced acute lung injury that exhibits several features of human acute lung injury and is suitable for screening potential medical countermeasures. We validated chlorinated fatty acids and protein adducts in plasma and lung samples as forensic biomarkers of chlorine inhalation.

Suppressor analysis links trans-translation and ribosomal protein uS7 to RluD function in Escherichia coli.

The pseudouridine (ψ) synthase, RluD is responsible for three ψ modifications in the helix 69 (H69) of bacterial 23S rRNA. While normally dispensable, rluD becomes critical for rapid cell growth in bacteria that are defective in translation-termination. In slow-growing rluD- bacteria, suppressors affecting termination factors RF2 and RF3 arise frequently and restore normal termination and rapid cell growth. Here we describe two weaker suppressors, affecting rpsG, encoding ribosomal protein uS7 and ssrA, encoding tmRNA. In K-12 strains of E. coli, rpsG terminates at a TGA codon. In the suppressor strain, alteration of an upstream CAG to a TAG stop codon results in a shortened uS7 and partial alleviation of slow growth, likely by replacing an inefficient TGA stop codon with the more efficient TAG. Inefficient termination events, such as occurs in some rluD- strains, are targeted by trans-translation. Inactivation of the ssrA gene in slow-growing, termination-defective mutants lacking RluD and RF3, also partially restores robust growth, most probably by preventing destruction of completed polypeptides on ribosomes at slow-terminating stop codons. Finally, an additional role for RluD has been proposed, independent of its pseudouridine synthase activity. This is based on the observation that plasmids expressing catalytically dead (D139N or D139T) RluD proteins could nonetheless restore robust growth to an E. coli K-12 rluD- mutant. However, newly constructed D139N and D139T rluD plasmids do not have any growth-restoring activity and the original observations were likely due to the appearance of suppressors.

Gd3+ Encapsulation on 2D-g-C3N4 Nanostructure for Spintronics and Ultrasound Assisted Photocatalytic Applications: First-Principles and Experimental Studies.

Atomically thin two-dimensional (2D) semiconductors have high potential in optoelectronics and magneto-optics appliances due to their tunable band structures and physicochemical stability. The work demonstrates that Gd3+ incorporated 2D-g-C3N4 nanosheet (Gd3+/2D-g-C3N4 NS) is synthesized through chemisorption methodology for defect enrichment. The material characterizations reveal that the ion decoration enhances the surface area and defect concentration of the 2D sheet. The experimental observations have been further corroborated with the help of density functional theory (DFT) simulation. Spin asymmetry polarizations near the Fermi level, obtained through the partial density of states (PDOS) analyses, reveal the magnetic nature of the synthesized material, validating the room temperature ferromagnetism obtained through a vibrating-sample magnetometer (VSM). Gd3+/2D-g-C3N4 NS shows significant enhancement in saturation magnetization (Ms) experimentally and computationally compared to the pristine one. The magnetic catalyst shows 98% remediation efficiency for ultrasound-assisted visible-light-driven photodegradation of methyl orange (MO). The synergistic approach of liquid chromatography-mass spectrometry (LC-MS) analyses and DFT studies elucidates reaction intermediates and unveils the degradation mechanism. Post-characterization studies assure the stability of the magnetic catalyst through optical, chemical, magnetic, and microscopic analyses. So, the synthesized material can be proficiently used as a magnetic nanocatalyst in wastewater treatments and spin-electronics applications.

Pseudorabies Virus Regulates the Extracellular Translocation of Annexin A2 To Promote Its Proliferation.

Pseudorabies virus (PRV) infection causes enormous economic losses to the pork industry and severe health consequences in many hosts. Annexin A2 (ANXA2) is a membrane-associated protein with various intracellular functions associated with many viral infections. However, the role of ANXA2 in alphaherpesvirus replication is still not explored. In the present study, we identified the interaction between ANXA2 and PRV US3. The deficiency of ANXA2 significantly restricted PRV proliferation. PRV infection or US3 overexpression led to ANXA2 extracellular translocation. Furthermore, we confirmed that PRV or US3 could lead to the phosphorylation of the Tyr23 ANXA2 and Tyr419 Src kinase, which was associated with the ANXA2 cell surface transposition. US3 can also bind to Src in an ANXA2-independent manner and enhance the interaction between Src and ANXA2. Additionally, inhibitors targeting ANXA2 (A2ti-1) or Src (PP2) could remarkably inhibit PRV propagation in vitro and protect mice from PRV infection in vivo. Collectively, our findings broaden our understanding of the molecular mechanisms of ANXA2 in alphaherpesvirus pathogenicity and suggest that ANXA2 is a potential therapeutic target for treating alphaherpesvirus-induced infectious diseases. IMPORTANCE PRV belongs to the alphaherpesvirus and has recently re-emerged in China, causing severe economic losses. Recent studies also indicate that PRV may pose a potential public health challenge. ANXA2 is a multifunctional calcium- and lipid-binding protein implicated in immune function, multiple human diseases, and viral infection. Herein, we found that ANXA2 was essential to PRV efficient proliferation. PRV infection resulted in the extracellular translocation of ANXA2 through phosphorylation of ANXA2 and Src. ANXA2 and Src formed a complex with PRV US3. Importantly, inhibitors targeting ANXA2 or Src prevented PRV infection in vitro and in vivo. Therefore, our studies reveal a novel strategy by which alphaherpesvirus modifies ANXA2 to promote its replication and highlight ANXA2 as a target in developing novel promising antivirus agents in viral therapy.

Nativity differences in socioeconomic barriers and healthcare delays among cancer survivors in the All of Us cohort.

PURPOSE: We aimed to assess whether nativity differences in socioeconomic (SES) barriers and health literacy were associated with healthcare delays among US cancer survivors. METHODS: "All of Us" survey data were analyzed among adult participants ever diagnosed with cancer. A binary measure of healthcare delay (1+ delays versus no delays) was created. Health literacy was assessed using the Brief Health Literacy Screen. A composite measure of SES barriers (education, employment, housing, income, and insurance statuses) was created as 0, 1, 2, or 3+. Multivariable logistic regression model tested the associations of (1) SES barriers and health literacy with healthcare delays, and (2) whether nativity modified this relationship. RESULTS: Median participant age was 64 years (n = 10,020), with 8% foreign-born and 18% ethnic minorities. Compared to survivors with no SES barriers, those with 3+ had higher likelihood of experiencing healthcare delays (OR 2.18, 95% CI 1.84, 2.58). For every additional barrier, the odds of healthcare delays were greater among foreign-born (1.72, 1.43, 2.08) than US-born (1.27, 1.21, 1.34). For every 1-unit increase in health literacy among US-born, the odds of healthcare delay decreased by 9% (0.91, 0.89, 0.94). CONCLUSION: We found that SES barriers to healthcare delays have a greater impact among foreign-born than US-born cancer survivors. Higher health literacy may mitigate healthcare delays among US cancer survivors. Healthcare providers, systems and policymakers should assess and address social determinants of health and promote health literacy as a way to minimize healthcare delays among both foreign- and US-born cancer survivors.

Revision to the musculoskeletal domain of the BILAG-2004 index to incorporate ultrasound findings.

OBJECTIVES: To improve the definitions of inflammatory arthritis within the musculoskeletal (MSK) domain of the BILAG-2004 index by incorporating imaging findings and clinical features predictive of response to treatment. METHODS: The BILAG MSK Subcommittee proposed revisions to the BILAG-2004 index definitions of inflammatory arthritis, based on review of evidence in two recent studies. Data from these studies were pooled and analysed to determine the impact of the proposed changes on the severity grading of inflammatory arthritis. RESULTS: The revised definition for severe inflammatory arthritis includes definition of 'basic activities of daily living'. For moderate inflammatory arthritis, it now includes synovitis, defined by either observed joint swelling or MSK US evidence of inflammation in joints and surrounding structures. For mild inflammatory arthritis, the definition now includes reference to symmetrical distribution of affected joints and guidance on how US may help re-classify patients as moderate or no inflammatory arthritis. Data from two recent SLE trials were analysed (219 patients). A total of 119 (54.3%) were graded as having mild inflammatory arthritis (BILAG-2004 Grade C). Of these, 53 (44.5%) had evidence of joint inflammation (synovitis or tenosynovitis) on US. Applying the new definition increased the number of patients classified as moderate inflammatory arthritis from 72 (32.9%) to 125 (57.1%), while patients with normal US (n = 66/119) could be recategorized as BILAG-2004 Grade D (inactive disease). CONCLUSIONS: Proposed changes to the definitions of inflammatory arthritis in the BILAG-2004 index will result in more accurate classification of patients who are more or less likely to respond to treatment.

Socioeconomic Disparities Associated with Access to Oculofacial Plastic Surgeons: A Cross-Sectional Analysis of US County Demographics.

PURPOSE: To compare population demographics with the geographic distribution of oculofacial plastic surgeons (OPSs) in the United States. DESIGN: A cross-sectional study design was used to investigate demographic differences between counties with 1 or more OPSs and counties with zero OPSs. PARTICIPANTS: The number of OPSs were identified in each US county using online public databases: American Society of Ophthalmic Plastic and Reconstructive Surgeons and American Academy of Ophthalmology. Counties were categorized into 2 groups: 1 or more OPSs and zero OPSs. Demographic characteristics at the county level were obtained from the 2021 US Census Bureau Population Estimates and the American Community Survey. Cost of living was collected from the 2022 Economic Policy Institute Family Budget Calculator. MAIN OUTCOME MEASURES: Socioeconomic demographics of the US population as related to geographic OPS distribution. RESULTS: A total of 1238 OPSs were identified. States with the most OPSs per million were Hawaii (6.2), D.C. (6.0), Connecticut (5.8), Utah (5.1), and Maryland (5.0). Among 3143 counties, 2725 (86.7%) had zero OPSs and 418 (13.3%) had 1 or more OPSs. Counties with 1 or more OPSs had a higher median (standard deviation) household income versus counties with zero OPSs ($72 471 [$19 152] vs. $56 152 [$13 675]; difference $16 319; 95% confidence interval [CI], $14 300-$18 338; P < 0.001). The annual cost of living per person (standard deviation) was higher in counties with 1 or more OPSs versus counties with zero OPSs ($39 238 [$6992] vs. $36 227 [$3516]; difference $3011; 95% CI, $2328-$3694; P < 0.001). Counties with zero OPSs versus counties with 1 or more OPSs had higher proportions of persons with only Medicaid (15.6% vs. 13.6%; difference 2.0%; 95% CI, 1.4%-2.5%; P < 0.001), no health insurance (9.9% vs. 8.0%; difference 1.9%; 95% CI, 1.5%-2.4%; P < 0.001), no household internet access (17.2% vs. 9.6%; difference 7.6%; 95% CI, 7.1%-8.0%; P < 0.001), and higher proportions of persons aged 65 years or older (20.0% vs. 17.0%; difference 3.0%; 95% CI, 2.5%-3.5%; P < 0.001). CONCLUSIONS: This cross-sectional analysis of all US counties revealed socioeconomic disparities associated with access to OPSs. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Net greenhouse gas balance in U.S. croplands: How can soils be part of the climate solution?

Agricultural soils play a dual role in regulating the Earth's climate by releasing or sequestering carbon dioxide (CO2 ) in soil organic carbon (SOC) and emitting non-CO2 greenhouse gases (GHGs) such as nitrous oxide (N2 O) and methane (CH4 ). To understand how agricultural soils can play a role in climate solutions requires a comprehensive assessment of net soil GHG balance (i.e., sum of SOC-sequestered CO2 and non-CO2 GHG emissions) and the underlying controls. Herein, we used a model-data integration approach to understand and quantify how natural and anthropogenic factors have affected the magnitude and spatiotemporal variations of the net soil GHG balance in U.S. croplands during 1960-2018. Specifically, we used the dynamic land ecosystem model for regional simulations and used field observations of SOC sequestration rates and N2 O and CH4 emissions to calibrate, validate, and corroborate model simulations. Results show that U.S. agricultural soils sequestered 13.2 ± 1.16 $$ 13.2\pm 1.16 $$ Tg CO2 -C year-1 in SOC (at a depth of 3.5 m) during 1960-2018 and emitted 0.39 ± 0.02 $$ 0.39\pm 0.02 $$ Tg N2 O-N year-1 and 0.21 ± 0.01 $$ 0.21\pm 0.01 $$ Tg CH4 -C year-1 , respectively. Based on the GWP100 metric (global warming potential on a 100-year time horizon), the estimated national net GHG emission rate from agricultural soils was 122.3 ± 11.46 $$ 122.3\pm 11.46 $$ Tg CO2 -eq year-1 , with the largest contribution from N2 O emissions. The sequestered SOC offset ~28% of the climate-warming effects resulting from non-CO2 GHG emissions, and this offsetting effect increased over time. Increased nitrogen fertilizer use was the dominant factor contributing to the increase in net GHG emissions during 1960-2018, explaining ~47% of total changes. In contrast, reduced cropland area, the adoption of agricultural conservation practices (e.g., reduced tillage), and rising atmospheric CO2 levels attenuated net GHG emissions from U.S. croplands. Improving management practices to mitigate N2 O emissions represents the biggest opportunity for achieving net-zero emissions in U.S. croplands. Our study highlights the importance of concurrently quantifying SOC-sequestered CO2 and non-CO2 GHG emissions for developing effective agricultural climate change mitigation measures.

US businesses engaged in direct-to-consumer marketing of perinatal stem cell interventions following the Food and Drug Administration's enforcement discretion era.

BACKGROUND AIMS: The goal of this study was to analyze online marketing representations made by 300 US businesses selling allogeneic perinatal stem cell products. The study was conducted after a period of enforcement discretion by the US Food and Drug Administration (FDA). METHODS: Data mining and content analysis were used to identify, analyze and categorize marketing claims made on the websites of 300 businesses selling perinatal stem cell interventions. RESULTS: The study identified types of perinatal interventions companies advertised, geographic locations of clinics selling such products, types of companies operating in this space, diseases and injuries such businesses claim to treat, prices companies charge for such interventions, brand names of advertised perinatal cell products and identities of suppliers. CONCLUSIONS: A substantial number of US businesses market unapproved perinatal stem cell products for various indications. This widespread commercial activity occurred following the conclusion of a period of enforcement discretion by the FDA and suggests the need for more robust and comprehensive regulatory responses to businesses selling unapproved perinatal stem cell products.

Hospital Rating Organizations' Quality and Patient Safety Scores: Analysis of Result Discrepancies.

BACKGROUND: In the USA, multiple organizations rate hospitals based on quality and patient safety data, but few studies have analyzed and compared the rating results. OBJECTIVE: Compare the results of different US hospital-rating organizations. DESIGN: Observational data analysis of US acute care hospital ratings. PARTICIPANTS: Four rating organizations: Hospital Compare® (HC), Healthgrades® (HG), The Leapfrog Group® (Leapfrog), and US News and World Report® (USN). MAIN MEASURES: We analyzed the level of concordance (similar ranking), discordance (difference of 1 or more rankings), and severe discordance (difference of two or more rankings), as well as differences and correlations between the scores. KEY RESULTS: From Feb 1 to Oct 3, 2023, we analyzed data from 2,384 hospitals. In Leapfrog, there were 688 hospitals (29%) with Grade A, 652 (27.3%) with B, 885 (37.1%) with C, 153 (6.4%) with D, and 6 (0.3%) with F. For HC, 333 hospitals (14%) had five stars, 676 (28.4%) four, 695 (29.2%) three, 502 (21.4%) two, and 171 (7.2%) one-star. In ratings between HC and Leapfrog, discordance was 70%, and severe discordance was 25.1%. USN ranked 469 hospitals (19.7%). Within the USN-ranked hospital group, there was a 62% discordance and 19.8% severe discordance between HC and Leapfrog. The analysis of orthopedic procedures from HG and USN showed discordance ranging from 48 to 61.2%. CONCLUSION: The rating organizations' reported metrics were highly discordant. A hospital's ranking by one organization frequently did not correspond to a similar ranking by another. The methodology and included timeline and patient population can help explain the differences. However, the discordant ratings may confuse patients and customers.

Compliance with U.S. Government Nutrition Advice and Concurrent Obesity Trends Using Nurses' Health Study Data, 1980-2011.

BACKGROUND: Beginning in 1977, the U.S. Government began formally issuing dietary advice, a main objective of which was to reduce and prevent the prevalence of obesity in the American population. Concurrently, the Harvard School of Public Health began conducting dietary intake surveys and collecting body mass index (BMI) (kg/m2) data on female nurses in the Nurses' Health Study I (NHSI) and II (NHSII). OBJECTIVES: We aimed to assess whether compliance with the nutrition guidance from the U.S. Government to restrict dietary intake regarding total fat, saturated fat, and cholesterol was meaningfully associated with the prevalence of obesity. METHODS: We analyzed nutrition survey data from 1980 to 2011, grouping the sample into "compliers," those who complied with guidance on the intake of total fat, saturated fat, and cholesterol, and "noncompliers," those who did not. We then compared the means, medians, and distributions of BMI for compliers and noncompliers over the period for both the full survey population and an age-controlled sample. Finally, we plotted raw NHS data to examine respondents' Fat Proportion intake of energy and concurrent BMI. RESULTS: The mean and median BMI for both compliers and noncompliers increased throughout the sample period, and the BMI distributions shifted toward obese and severely obese overall and for an age-controlled subset compared with the 1980 NHSI and 1990 NHSII baselines. Compliers had slightly lower mean BMI increases than noncompliers but saw a relatively higher increase in the growth of the prevalence of those with BMI >30. We also found no linear relationship between Fat Proportion of energy intake and concurrent BMI. CONCLUSIONS: Guidance from the U.S. Government to limit fat, saturated fat, and cholesterol consumption was widely adopted by American female nurses during the study period. Our results show that compliance with this guidance had little if any effect in mitigating population-wide BMI increases during our study period.

Weight-related discrimination, perceived stress and psychological and physical well-being of persons with type 2 diabetes: A mediation analysis.

AIMS: The aim of the study was to examine perceived stress as a mediator of the association between weight-related discrimination and physical and psychological well-being among persons with type 2 diabetes (T2D). METHODS: Data were obtained from 5104 persons with self-reported T2D participating in the All of Us research programme in the United States. The Everyday Discrimination Scale, Cohen's Perceived Stress Scale (PSS) and PROMIS Global Health Scale were used to measure weight-related discrimination, perceived stress and health outcomes (physical and psychological), respectively. Mediation effects of PSS were tested by bootstrapping with 5000 random samples. RESULTS: Participants were, on average, 63.62 (SD 11.38) years old. Majority of them were female (55.53%), non-Hispanic White (72.61%), married or living with a partner (56.92%), had a household income of <$35,000 (31.99%) and had some college education (33.54%). We found that approximately 18% of study participants reported having experienced weight-related discrimination. We also found that weight-related discrimination was independently associated with poor physical and psychological well-being. These associations were partially mediated by perceived stress such that weight-related discrimination was associated with greater perceived stress, which was in turn associated with poorer physical and psychological well-being. CONCLUSIONS: Given that weight-related discrimination is associated with poor outcomes through elevated stress, interventions that target stress may disrupt this pathway thereby helping to reduce the health impact of weight-related discrimination. This assertion should, however, be tested in future studies.

Self-conducted sonographic monitoring of the knee in patients with haemophilia-A feasibility study.

INTRODUCTION/AIM: To evaluate whether patients with haemophilia (PwH) can be enabled to perform ultrasonography (US) of their knees without supervision according to the Haemophilia Early Arthropathy Detection with Ultrasound (HEAD-US) protocol and whether they would be able to recognize pathologies. METHODS: Five PwH (mean age 29.6 years, range 20-48 years) were taught the use of a portable US device and the HEAD-US protocol. Subsequently, the patients performed US unsupervised at home three times a week for a total of 6 weeks with a reteaching after 2 weeks. All images were checked for mapping of the landmarks defined in the HEAD-US protocol by a radiologist. In a final test after the completion of the self-sonography period, participants were asked to identify scanning plane and potential pathology from US images of other PwH. RESULTS: On the images of the self-performed scans, 82.7% of the possible anatomic landmarks could be identified and 67.5% of the requested images were unobjectionable, depicting 100% of the required landmarks. There was a highly significant improvement in image quality following reteaching after 2 weeks (74.80 ± 36.88% vs. 88.31 ± 19.87%, p < .001). In the final test, the participants identified the right scanning plane in 85.0% and they correctly identified pathology in 90.0% of images. CONCLUSION: Appropriately trained PwH can perform the HEAD-US protocol of their knee with high quality and are capable to identify pathologic findings on these standardized images. Asynchronous tele-sonography could enable early therapy adjustment and thereby possibly reduce costs.

Primary prophylaxis implementation and long-term joint outcomes in Swedish haemophilia A patients.

INTRODUCTION: Primary prophylaxis is the gold standard in severe haemophilia A (SHA) but time to escalate the prophylaxis regimen varies. AIM: Assess prophylaxis implementation and long-term joint health outcomes in SHA with primary prophylaxis. METHODS: Adult male patients born after 1980, with SHA on primary prophylaxis, started before the age of 3 years and second joint bleed, and no history of FVIII inhibitors, were enrolled. Repeated joint-health examinations were performed with HJHS or HEAD-US; VERITAS-PRO assessed adherence. RESULTS: Thirty patients were enrolled with, at inclusion, median age 33.5 years, annualized bleed rate and joint bleed rate 0, and FVIII consumption 4232 IU/kg/year, respectively. The median age was 1.2 years, at prophylaxis start once weekly with a median FVIII dose of 47.7 IU/kg, and 1.7 years, by the time escalation to a final regimen had occurred, with a median infusion frequency of thrice weekly and FVIII dose 41.7 IU/kg, respectively. Older age correlated with later transition to escalated prophylaxis (p < .001). Longer time to escalated prophylaxis correlated to more bleeds (p < .001). Median HJHS increased slowly, reaching 4 at 35-40 years. HJHS at 15-20 years correlated with higher HJHS afterwards. Median total HEAD-US score was 1 and correlated with HJHS (p < .001). Median VERITAS-PRO score was 36, indicating good treatment adherence. CONCLUSION: Primary prophylaxis is effective but does not completely prevent the gradual development of arthropathy in SHA. Joint assessments with HJHS should start at an early age, as they correlate with arthropathy in later life. Prophylaxis escalation should proceed expeditiously to prevent bleeds.

An SGO commentary: U.S. News and World Report gynecologic oncology procedural ratings-Do they reflect high-quality care?

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