Current Use and Barriers to Point-of-Care Ultrasound in Rheumatology: A National Survey of VA Medical Centers.

INTRODUCTION: Point-of-care ultrasound (POCUS) can assist rheumatologists in monitoring disease activity, establishing diagnoses, and guiding procedural interventions. POCUS use has been increasing, but little is known about current use and barriers among rheumatologists. The purpose of this study was to characterize current POCUS use, training needs, and barriers to use among rheumatologists in practice. METHODS: A prospective observational study of all Veterans Affairs (VA) medical centers was conducted using a web-based survey sent to all chiefs of staff and rheumatology chiefs about current POCUS use, training needs, barriers, and policies. RESULTS: All chiefs of staff (n = 130) and rheumatology chiefs at VA medical centers (n = 95) were surveyed with 100% and 84% response rates, respectively. The most common diagnostic POCUS applications were evaluation of synovitis, joint effusion, tendinopathies, bursitis, and rotator cuff. The most common procedural applications were arthrocentesis and joint, bursa, and tendon injection. Most rheumatology chiefs (69%) expressed interest in training for their group. The most common barriers to POCUS use were lack of trained providers (68%), funding for training (54%), training opportunities (38%), funding for travel (38%), and ultrasound equipment (31%). Lack of POCUS infrastructure was common, and few facilities had POCUS policies (20%), image archiving (25%), or quality assurance processes (6%). CONCLUSION: Currently, half of rheumatology groups use diagnostic and procedural ultrasound applications. Most rheumatology groups desire training, and lack of training and equipment were the most common barriers to ultrasound use. Deliberate investment is needed in ultrasound training and infrastructure for systematic adoption of POCUS in rheumatology. Graphical Abstract available for this article. TRIAL REGISTRATION: NCT03296280.

Fulminant Celiac Disease Presenting in the Postpartum Period.

Celiac disease (CD) is an immune-mediated disorder of the small intestine triggered by dietary exposure to gluten in genetically susceptible individuals. Adult CD usually has an insidious onset with gastrointestinal symptoms, most often diarrhea and weight loss. The association between CD and reproductive abnormalities has been well described in the literature, but it is uncommon for CD to initially manifest during pregnancy or the postpartum period. We report a case of adult CD in a previously healthy woman with a life-threatening presentation during the postpartum period.

Arabidopsis FIBRILLIN6 influences carotenoid biosynthesis by directly promoting phytoene synthase activity.

Carotenoids are health-promoting plastidial isoprenoids with essential functions in plants as photoprotectants and photosynthetic pigments in chloroplasts. They also accumulate in specialized plastids named chromoplasts, providing color to non-photosynthetic tissues such as flower petals and ripe fruit. Carotenoid accumulation in chromoplasts requires specialized structures and proteins such as fibrillins (FBNs). The FBN family includes structural components of carotenoid sequestering structures in chromoplasts and members with metabolic roles in chloroplasts and other plastid types. However, the association of FBNs with carotenoids in plastids other than chromoplasts has remained unexplored. Here, we show that Arabidopsis (Arabidopsis thaliana) FBN6 interacts with phytoene synthase (PSY), the first enzyme of the carotenoid pathway. FBN6, but not FBN4 (a FBN that does not interact with PSY), enhances the activity of plant PSY (but not of the bacterial PSY crtB) in Escherichia coli cells. Overexpression of FBN6 in Nicotiana benthamiana leaves results in a higher production of phytoene, the product of PSY activity, whereas loss of FBN6 activity in Arabidopsis mutants dramatically reduces the production of carotenoids during seedling de-etiolation and after exposure to high light. Our work hence demonstrates that FBNs promote not only the accumulation of carotenoids in chromoplasts but also their biosynthesis in chloroplasts.

Different effects of four rest periods after the last weekly training session on young male professional soccer players' physical performance.

The main aim of this study was to analyze the optimal pre-competitive recovery period for young male professional soccer players to be in the best conditions to achieve a higher physical performance. Seventeen young male professional soccer players (age: 20.7 ± 1.0 years) who participated in the Tunisian soccer league participated in this study. Players underwent a fitness test battery after four different recovery periods: 12, 24, 36, and 48h following their last training session. The battery fitness test included a linear sprint test (i.e., 5 and 20m distances), squat jumps (SJ), countermovement jumps (CMJ), ball shooting test, a Yo-yo endurance intermittent test (YYIRT-1) and a 15-m ball dribbling agility test (Ag). The main findings indicated that the 12h recovery period resulted in better performance in the 5m sprint test compared to 36h, as well as in the SJs and CMJs as compared to the 48h recovery period. Additionally, the 24h recovery period showed significantly better results in the 20-m sprint test compared to all other recovery periods, as well as in the SJ and Ag tests compared to the 48h recovery period. In practical terms, these findings suggest that coaches should consider scheduling the last training session for soccer players 12-24h before the match to enhance their physical performance, particularly in linear sprinting, vertical jumps, and agility variables. However, in situations where it is not possible to adjust the timing of the last training session, an alternative approach is to incorporate "priming-day" exercises on the match day, around 6-8h prior to the competition.

Evaluation of health literacy and its predictive formative factors among Spanish military personnel.

Health literacy (HL) is an aspect that has been widely studied. However, in the military population there are hardly any studies on the influence of educational variables. Knowing the level of health literacy of military professionals is important as it has an impact on adequate health decision making, avoids the abuse of health services and makes it possible to ask for help when needed, especially in aspects related to mental health. The aim of this study was to measure the level of literacy, as well as its association with other training variables in a sample of military personnel. The study was carried out in 695 military personnel of the Spanish Army. A cross-sectional observational design was used, using a survey with the HLS-EU-Q47 scale. Among the results, it stands out that the level of health literacy of the military is high compared to the rest of the population. The results showed that the level of HL does not seem to be influenced by the level of languages, nor by the degree they hold, nor by experiences abroad. On the other hand, it was observed that the performance of professional internships and work in multidisciplinary teams, extracurricular training, does influence the level of HL, especially in the dimension related to health promotion. This fact seems to mean that the military have learned during these experiences to keep abreast of health-related issues, to understand, to value and to form a considered opinion on health-related information.

Functional Foods in Dermatology.

Functional foods, defined as whole foods that provide health benefits beyond their nutritional value, may provide multiple dermatologic benefits. Research studies have documented multiple benefits, including enhanced skin barrier function, improved wound healing, radiance, photoprotection, and hormonal regulation. Although the majority of research to date has involved small-scale human interventions or animal models, promising findings have been noted. A number of potential molecular mechanisms have been described, such as the ability of some foods to combat oxidative stress and thus reduce visible and histologic skin changes in response to UV radiation. Additional mechanisms have been described for wound healing, photo-carcinogenesis, and other outcomes. In this review, we discuss the potential dermatologic role of functional foods in order to advocate for larger-scale, evidence-based, human studies to expand this promising field.

The relationships between body mass index, reciprocal ponderal index, waist-to-height ratio, and fitness in young adult males.

Background: Anthropometric measures such as the body mass index (BMI), reciprocal ponderal index (RPI), and waist-to-height ratio (WHR) have been proposed as predictors of physical fitness. This study aimed to identify the differences in explanatory capacity and fit of BMI, RPI, and WHR on physical fitness, which involves jumping, sprinting, change of direction, and aerobic capacity, by adjusting the polynomial regression. Methods: A sample of 297 healthy, recreationally active male university students between 18 and 20 years old was recruited for this study. Anthropometric measurements (height: 174.09 ± 6.27 cm, weight: 78.98 ± 20.27 kg, waist circumference: 93.74 ± 14.56 cm) were taken for each participant. Jumping tests (squat jump, countermovement jump), sprinting tests (20 m sprint), agility tests (agility T-test), and aerobic/endurance tests (6 min walk test, VAM-EVAL test) were performed. Nonlinear quadratic regression models were used to assess the relationship between the jump, sprint, and fitness test scores and the anthropometric indices. The models were compared based on R-squares and Bayesian Information Criterion (BIC). The significance level was set at p < 0.05. Results: The results showed that all the indices predicted a portion of the variance because all variables and index relationships were significant. Regarding the fitted models, the Bayesian Information Criterion showed that BMI was the best indicator of performance, although the RPI was better for VO2max. Conclusion: These findings may be of great interest to practitioners because it appears that anthropometric measures can be used to predict physical fitness in certain tests although the accuracy raises any concerns.

Home care/outpatient versus hospital admission in mild acute pancreatitis: protocol of a multicentre, randomised controlled trial (PADI_2 trial).

INTRODUCTION: Acute pancreatitis (AP) is the third most common gastrointestinal disease resulting in hospital admission, with over 70% of AP admissions being mild cases. In the USA, it costs 2.5 billion dollars annually. The most common standard management of mild AP (MAP) still is hospital admission. Patients with MAP usually achieve complete recovery in less than a week and the severity predictor scales are reliable. The aim of this study will be to compare three different strategies for the management of MAP. METHODS/DESIGN: This is a randomised, controlled, three-arm multicentre trial. Patients with MAP will be randomly assigned to group A (outpatient), B (home care) or C (hospital admission). The primary endpoint of the trial will be the treatment failure rate of the outpatient/home care management for patients with MAP compared with that of hospitalised patients. The secondary endpoints will be pain relapse, diet intolerance, hospital readmission, hospital length of stay, need for intensive care unit admission, organ failure, complications, costs and patient satisfaction. The general feasibility, safety and quality checks required for high-quality evidence will be adhered to. ETHICS AND DISSEMINATION: The study (version 3.0, 10/2022) has been approved by the Scientific and Research Ethics Committee of the 'Institut d'Investigació Sanitaria Pere Virgili-IISPV' (093/2022). This study will provide evidence as to whether outpatient/home care is similar to usual management of AP. The conclusions of this study will be published in an open-access journal. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT05360797).

Pancreatic Cancer Surveillance in Carriers of a Germline Pathogenic Variant in CDKN2A.

Three percent of patients with pancreatic ductal adenocarcinoma (PDAC) present a germline pathogenic variant (GPV) associated with an increased risk of this tumor, CDKN2A being one of the genes associated with the highest risk. There is no clear consensus on the recommendations for surveillance in CDKN2A GPV carriers, although the latest guidelines from the International Cancer of the Pancreas Screening Consortium recommend annual endoscopic ultrasound (EUS) or magnetic resonance imaging (MRI) regardless of family history. Our aim is to describe the findings of the PDAC surveillance program in a cohort of healthy CDKN2A GPV heterozygotes. This is an observational analysis of prospectively collected data from all CDKN2A carriers who underwent screening for PDAC at the high-risk digestive cancer clinic of the "Hospital Clínic de Barcelona" between 2013 and 2021. A total of 78 subjects were included. EUS or MRI was performed annually with a median follow-up of 66 months. Up to 17 pancreatic findings were described in 16 (20.5%) individuals under surveillance, although most of them were benign. No significant precursor lesions were identified, but an early PDAC was detected and treated. While better preventive strategies are developed, we believe that annual surveillance with EUS and/or MRI in CDKN2A GPV heterozygotes may be beneficial.

Pharmacokinetics of cefiderocol during extracorporeal membrane oxygenation: A case report.

Patients with extracorporeal membrane oxygenation (ECMO) support do frequently receive broad-spectrum antibiotics, due to the high frequency of infection by multidrug resistant microorganisms. The extracorporeal circuit can alter the pharmacokinetics (PK) of administered drugs, and in the case of antibiotics this may lead to treatment failure. Cefiderocol is a new cephalosporin that exhibits excellent in vitro activity against many multidrug-resistant (MDR) microorganisms, but there is no published data about the modifications of its PK in patients with ECMO support. Herein we report the results of a pharmacokinetic investigation of cefiderocol in a critically ill patient receiving extracorporeal respiratory support.

Environmentally driven transcriptomic and metabolic changes leading to color differences in "Golden Reinders" apples.

Apple is characterized by its high adaptation to diverse growing environments. However, little is still known about how different environments can regulate at the metabolic or molecular level specific apple quality traits such as the yellow fruit peel color. In this study, changes in carotenoids and chlorophylls, antioxidants as well as differences in the transcriptome were investigated by comparing the peel of "Golden Reinders" apples grown at different valley and mountain orchards. Mountain environment favored the development of yellow color, which was not caused by an enhanced accumulation of carotenoids but rather by a decrease in the chlorophyll content. The yellow phenotype was also associated to higher expression of genes related to chloroplast functions and oxidative stress. Time-course analysis over the last stages of apple development and ripening, in fruit from both locations, further revealed that the environment differentially modulated isoprenoids and phenylpropanoid metabolism and pointed out a key role for H2O2 in triggering apple peel degreening. Overall, the results presented herein provide new insights into how different environmental conditions regulate pigment and antioxidant metabolism in apple leading to noticeable differences in the apple peel color.

Immune Response to Natural and Experimental Infection of Panulirus argus Virus 1 (PaV1) in Juveniles of Caribbean Spiny Lobster.

Experimental infections have been used to better comprehend the immune system of organisms, and to probe for additives that generate greater resistance and help reduce antibiotic use in aquaculture. We compared the immune response of juveniles of the Caribbean spiny lobster, Panulirus argus, infected naturally with Panulirus argus virus 1 (PaV1) versus organisms infected experimentally, to determine the analogy between both infectious processes. The immunological response was measured by hemagglutination activity, hemocyte count, and total phenoloxidase activity in plasma and hemocytes in 211 individuals that were either naturally infected (110), or had been injected with viral inoculum and followed for six months (101). The samples were classified into the following four groups according to the severity of the infection: 0, uninfected; 1, lightly; 2, moderately; and 3, severely infected), which was determined on the basis of PCR and histological criteria. A permutational MANOVA showed that both the origin (natural and experimental), and the severity of the infection contributed significantly to explain the variation in the immune response of lobsters. The lack of significance of the interaction term indicated that the immunological response changed with the severity of the infection in a similar way, regardless of its origin. The results of the present study suggest that the experimental viral infection of PaV1 produces a defense response similar to the natural pathways of contagion, and provides the bases to validate an immunological challenge protocol for the first time in crustaceans. The discussion includes the perspective of the conceptual models of immune response within an ecological context.

Oocytes maintain ROS-free mitochondrial metabolism by suppressing complex I.

Oocytes form before birth and remain viable for several decades before fertilization1. Although poor oocyte quality accounts for most female fertility problems, little is known about how oocytes maintain cellular fitness, or why their quality eventually declines with age2. Reactive oxygen species (ROS) produced as by-products of mitochondrial activity are associated with lower rates of fertilization and embryo survival3-5. Yet, how healthy oocytes balance essential mitochondrial activity with the production of ROS is unknown. Here we show that oocytes evade ROS by remodelling the mitochondrial electron transport chain through elimination of complex I. Combining live-cell imaging and proteomics in human and Xenopus oocytes, we find that early oocytes exhibit greatly reduced levels of complex I. This is accompanied by a highly active mitochondrial unfolded protein response, which is indicative of an imbalanced electron transport chain. Biochemical and functional assays confirm that complex I is neither assembled nor active in early oocytes. Thus, we report a physiological cell type without complex I in animals. Our findings also clarify why patients with complex-I-related hereditary mitochondrial diseases do not experience subfertility. Complex I suppression represents an evolutionarily conserved strategy that allows longevity while maintaining biological activity in long-lived oocytes.

The Lack of Alternative Oxidase 1a Restricts in vivo Respiratory Activity and Stress-Related Metabolism for Leaf Osmoprotection and Redox Balancing Under Sudden Acute Water and Salt Stress in Arabidopsis thaliana.

In plants salt and water stress result in an induction of respiration and accumulation of stress-related metabolites (SRMs) with osmoregulation and osmoprotection functions that benefit photosynthesis. The synthesis of SRMs may depend on an active respiratory metabolism, which can be restricted under stress by the inhibition of the cytochrome oxidase pathway (COP), thus causing an increase in the reduction level of the ubiquinone pool. However, the activity of the alternative oxidase pathway (AOP) is thought to prevent this from occurring while at the same time, dissipates excess of reducing power from the chloroplast and thereby improves photosynthetic performance. The present research is based on the hypothesis that the accumulation of SRMs under osmotic stress will be affected by changes in folial AOP activity. To test this, the oxygen isotope-fractionation technique was used to study the in vivo respiratory activities of COP and AOP in leaves of wild-type Arabidopsis thaliana plants and of aox1a mutants under sudden acute stress conditions induced by mannitol and salt treatments. Levels of leaf primary metabolites and transcripts of respiratory-related proteins were also determined in parallel to photosynthetic analyses. The lack of in vivo AOP response in the aox1a mutants coincided with a lower leaf relative water content and a decreased accumulation of crucial osmoregulators. Additionally, levels of oxidative stress-related metabolites and transcripts encoding alternative respiratory components were increased. Coordinated changes in metabolite levels, respiratory activities and photosynthetic performance highlight the contribution of the AOP in providing flexibility to carbon metabolism for the accumulation of SRMs.

Do You Know How to Assess Risks Posed by Over-the-Counter Vitamin A Supplements?

Dietary supplements are regulated as foods by the US Food and Drug Administration (FDA) and, despite their potentially harmful effects, are not subject to labeling rules that apply to prescription medications. This commentary responds to a case about vitamin A supplement safety. The commentary compares regulation of vitamin A-derivative prescription medications, such as isotretinoin, to regulation of high-dose vitamin A supplements, illuminating both products' potential for causing birth defects. Label analysis is key to educating patients about risks of vitamin A-containing supplements. The commentary also suggests the need for more FDA oversight of the dietary supplement industry.

Epigenome-Wide DNA Methylation Profiling of Normal Mucosa Reveals HLA-F Hypermethylation as a Biomarker Candidate for Serrated Polyposis Syndrome.

Serrated polyposis syndrome (SPS) is associated with a high risk for colorectal cancer. Intense promoter hypermethylation is a frequent molecular finding in the serrated pathway and may be present in normal mucosa, predisposing to the formation of serrated lesions. To identify novel biomarkers for SPS, fresh-frozen samples of normal mucosa from 50 patients with SPS and 19 healthy individuals were analyzed by using the 850K BeadChip Technology (Infinium). Aberrant methylation levels were correlated with gene expression using a next-generation transcriptome profiling tool. Two validation steps were performed on independent cohorts: first, on formalin-fixed, paraffin-embedded tissue of the normal mucosa; and second, on 24 serrated lesions. The most frequently hypermethylated genes were HLA-F, SLFN12, HLA-DMA, and RARRES3; and the most frequently hypomethylated genes were PIWIL1 and ANK3 (Δß = 10%; P < 0.05). Expression levels of HLA-F, SLFN12, and HLA-DMA were significantly different between SPS patients and healthy individuals and correlated well with the methylation status of the corresponding differentially methylated region (fold change, >20%; r > 0.55; P < 0.001). Significant hypermethylation of CpGs in the gene body of HLA-F was also found in serrated lesions (Δß = 23%; false discovery rate = 0.01). Epigenome-wide methylation profiling has revealed numerous differentially methylated CpGs in normal mucosa from SPS patients. Significant hypermethylation of HLA-F is a novel biomarker candidate for SPS.

Demographics of Dietary Supplement Use for Skin: An Analysis of NHANES Cross-Sectional Data.

Dietary supplement use is common, with reported use by over half of US adults. This cross-sectional study utilized 2015–2016 National Health and Nutrition Examination Survey data. A total of 9971 respondents were surveyed, of which 3704 reported taking dietary supplements for "healthy skin, hair, and nails." Of those reporting skin supplement use, the majority had health insurance and some college education or above. Many respondents were 19 or younger, were of non-Hispanic White race, had a household income of more than $100,000 per year, and some were pregnant. More than two-thirds of the respondents decided to take the supplements on their own rather than at the advice of a healthcare professional, which is quite alarming. This study helps identify demographic groups more likely to consume skin, hair, and nail supplements. Overall, physicians should educate their patients on dietary supplements to avoid drug-supplement interactions and address the factors that influence the use of over-the-counter skin supplements. J Drugs Dermatol. 2022;21(4):434-436.doi:10.36849/JDD.5744.

Understanding Retinoblastoma Post-Translational Regulation for the Design of Targeted Cancer Therapies.

The retinoblastoma protein (Rb1) is a prototypical tumor suppressor protein whose role was described more than 40 years ago. Together with p107 (also known as RBL1) and p130 (also known as RBL2), the Rb1 belongs to a family of structurally and functionally similar proteins that inhibits cell cycle progression. Given the central role of Rb1 in regulating proliferation, its expression or function is altered in most types of cancer. One of the mechanisms underlying Rb-mediated cell cycle inhibition is the binding and repression of E2F transcription factors, and these processes are dependent on Rb1 phosphorylation status. However, recent work shows that Rb1 is a convergent point of many pathways and thus the regulation of its function through post-translational modifications is more complex than initially expected. Moreover, depending on the context, downstream signaling can be both E2F-dependent and -independent. This review seeks to summarize the most recent research on Rb1 function and regulation and discuss potential avenues for the design of novel cancer therapies.