The negative outlook: Long-term follow up of ThyroSeq negative and low-risk nodules.

BACKGROUND: Molecular testing of thyroid nodules is an essential tool to help risk stratify nodules with indeterminate cytology. Although ThyroSeq testing has been around for over a decade, there is a paucity of long-term follow-up data on cytologically indeterminate nodules that are determined to be molecularly negative or low-risk. The objective of this study is to assess the outcomes of nodules with indeterminate cytology (Bethesda III or IV) and negative or low-risk ThyroSeq results. METHODS: This is a single academic institution retrospective cohort study. Patients with at least one thyroid nodule sampled with fine-needle aspiration who underwent ThyroSeq testing from 2012 to 2018 and had negative or low-risk ThyroSeq results on a cytologically indeterminate sample (n = 159 patients, 167 nodules) were included in the study. Outcomes include the false-negative rate and negative predictive value of each test version, as well as follow-up length for each nodule. RESULTS: There were 159 patients with a mean age of 58 years (7-84 years) included in this study; the majority were female (81.8%). The mean follow-up was 4.0 years. Of 167 nodules, three were found to be malignant on resection (1.8%). The negative predictive value for the entire cohort was 98.2% and it was 89.3% for the surgical series. CONCLUSION: ThyroSeq testing has good negative predictive value and can help risk stratify cytologically indeterminate nodules. Routine follow-up allows for safe monitoring of nodules for features suggestive of malignancy.

Authenticity, Well-Being, and Minority Stress in LGB Individuals: A Scoping Review.

In general (i.e. in heteronormative and cisgendered samples), authenticity appears protective against threats to well-being. Authenticity may also, in part, protect well-being against the minority stressors experienced by sexually minoritized (LGB; lesbian, gay, and bisexual) individuals. In this scoping review, we examined the relation between authenticity and well-being in LGB samples experiencing minority stress. We hypothesized that (i) LGB minority stress relates to decreased authenticity (i.e. inauthenticity), (ii) authenticity relates to increased well-being, and (iii) authenticity influences the relation between LGB minority stress and well-being. We identified 17 studies (N = 4,653) from systematic searches across Medline, ProQuest, PsycINFO, and Scopus using terms related to sexual identity, minority stress, authenticity, and well-being. In almost all studies, proximal (but not distal) stress was associated with inauthenticity, and inauthenticity with decreased well-being. In all but one study, the association between proximal stress and well-being was associated with inauthenticity. Although these results are consistent with our hypotheses, the included studies were limited in scope and heterogenous in their methods, instruments, and samples, restricting conclusions regarding mediation or moderation. The results require replication, well-powered direct comparisons between LGB and non-LGB samples, and consideration of the varied ways authenticity can be conceptualized and measured.

The Impact of Donor History of Sleep Apnea on Corneal Tissue Evaluation Parameters.

PURPOSE: The goal of this study was to explore whether the donor history of sleep apnea affects corneal tissue evaluation parameters. METHODS: This was a retrospective study assessing the impact of donor history of sleep apnea in a dataset obtained from the Eversight Eye Bank. Comparative analysis and multivariate regression were used to assess differences in key parameters including endothelial cell density (ECD) and central corneal thickness. RESULTS: Data analyzed consisted of 50,170 tissues from 25,399 donors with no history of sleep apnea and 5473 tissues from 2774 donors with a history of sleep apnea. Tissue from donors with a history of sleep apnea showed lower ECD than those from donors with no history of sleep apnea (-51 cells/mm2, P < 0.001). Multivariate linear regression demonstrated that history of sleep apnea was a predictor of lower ECD by 13.72 cells/mm2 (P = 0.0264). Secondary analysis demonstrated that underweight and obese body mass indexes were significant predictors of increased ECD in donors with no history of sleep apnea (P < 0.0001, P = 0.025, respectively). Body mass index category was not a significant predictor of ECD in donors with a history of sleep apnea. In a smaller subset of 10,756 tissues, sleep apnea was not a significant predictor of central corneal thickness. CONCLUSIONS: This is the first study to demonstrate that a donor's history of sleep apnea is associated with a lower ECD in a large eye bank dataset. Future studies are needed to investigate whether history of sleep apnea affects posttransplantation outcomes.

'Nostalgic food heals for us': A qualitative exploration of experiences with nostalgia, food, and mood.

ISSUE ADDRESSED: Nostalgia-the bittersweet reliving of the past-has been linked to social connection and psychological wellbeing. Although food consumption is often an intrinsically social experience, relatively little research has examined how individuals experience and understand how food consumption relates to feelings of nostalgia, food and mood. METHODS: In the current study, semi-structured interviews were conducted with eight Australians from varying cultural backgrounds to explore their experiences with nostalgia, food and mood. RESULTS: Reflexive thematic analysis identified three key themes from the data: (i) The bittersweet experiences of food-evoked nostalgia-individuals' descriptions of food-evoked nostalgia and how it impacted their mood both positively and negatively (ii) social connection and identity continuity-participants' description of food-evoked nostalgia and how this provides an opportunity for social connection and identity continuity throughout life, which positively influences mood, and (iii) the role and relationship of food-evoked nostalgia and mood-individual descriptions of the important role that nostalgic food plays in their life, in addition to their relationship with food, and how this impacts mood. CONCLUSIONS: Understanding the positive component of nostalgic foods allowed individuals to bolster positive mood states with food-evoked nostalgia, increasing their quality of life. SO WHAT?: Understanding the link between food-evoked nostalgia and mood has significant implications, suggesting that negative mood states altered by nostalgic foods may result in positive mood states. Appropriate use of food-evoked nostalgia may increase the quality of life for individuals experiencing low mood states.

The Top 50 Articles and Authors of the New Millennium in Psychiatry: A Bibliometric Analysis.

The field of psychiatry faces significant challenges in the new millennium, marked by a surge in mental health diagnoses coupled with barriers to accessing adequate care. Despite obstacles, notable advancements have been achieved throughout the field, including the release of DSM-5, the introduction of esketamine, and the development of innovative assessment tools. This study aims to comprehensively analyze recent advances in psychiatry by examining the top 50 most cited articles and authors since 2000, addressing a gap in the literature left by previous subfield-focused bibliometric studies. Utilizing the Web of Science (WOS) database, this bibliometric analysis examined all publications in psychiatric journals from January 1, 2000, to September 18, 2022. The top 50 most cited articles and authors were identified and characterized based on various metrics, including times cited, article type, and institutional affiliations. WOS extracted 699,005 articles, with authors from the United States contributing the highest number of publications. The top 50 articles spanned a variety of formats, with cross-sectional studies, new measures, literature reviews, and randomized controlled trials being the most prevalent. The American Journal of Psychiatry emerged as the leading journal, hosting eight of the top 50 articles. Among the top 50 authors, female representation was limited, comprising 24% of first authors and 22% overall. Institutional affiliations revealed a majority of top authors worked at universities affiliated with the top 40 NIH-funded departments of psychiatry, with those affiliated with Harvard University leading in authorship contributions. This study sheds light on recent advancements in psychiatry, emphasizing the underrepresentation of female authors and the prevalence of top authors affiliated with major NIH-funded programs. This bibliometric analysis provides a comprehensive overview of recent advances and the top recent contributors in the field, fostering a deeper understanding of the evolving landscape of psychiatry in the new millennium.

Impact of comorbid opioid use disorder and major depressive disorder on healthcare utilization outcomes in patients with peripheral artery disease: A National Readmission Database analysis.

BACKGROUND: Prior research has demonstrated that individuals with peripheral artery disease (PAD) often have comorbid opioid use disorder (OUD) and major depressive disorder (MDD), with limited data regarding their impact on readmission outcomes, length of stay, and cost. This study aimed to investigate these healthcare utilization outcomes in patients with PAD who have comorbid OUD and MDD. METHODS: Data were obtained from the National Readmission Database from 2011 through 2018. The study population included all hospitalizations with PAD as the primary or secondary diagnosis, from which hospitalizations with OUD and MDD were extracted using appropriate ICD-9/10 diagnosis codes. Primary outcomes were 30-day and 90-day readmission, total cost, and total length of stay within the calendar year. We created hierarchical multivariable logistic regression models examining OUD with and without MDD, with a random effect for healthcare facility location. RESULTS: From 2011 to 2018, 13,265,817 weighted admissions with PAD were identified. These admissions were segmented into four categories: No OUD/No MDD (12,056,466), OUD/No MDD (323,762), No OUD/MDD (867,641), and OUD/MDD (17,948). The group with No OUD/No MDD was used as the reference group for all subsequent comparisons. Regarding 30-day and 90-day readmissions, patients with OUD/MDD had odds of 1.14 (95% CI 1.10, 1.18) and 1.09 (95% CI 1.06, 1.13), respectively. Patients with OUD/No MDD bore the highest median cost of $64,354 (IQR $30,797-137,074), and patients with OUD/MDD marked the lengthiest median stay of 6.01 days (IQR 2.01-13.30). CONCLUSION: This study found a significant association between these comorbidities and outcomes and therefore calls for targeted interventions and pain management strategies.

Comparison of industry payments to psychiatrists and psychiatric advanced practice clinicians in the USA, 2021: a cross-sectional study.

OBJECTIVES: To compare industry payment patterns among US psychiatrists and psychiatric advanced practice clinicians (APCs) and determine how scope of practice laws has influenced these patterns. DESIGN: Cross-sectional study. SETTING: This study used the publicly available US Centers for Medicare and Medicaid Services Sunshine Act Open Payment database and the National Plan and Provider Enumeration System (NPPES) database for the year 2021. PARTICIPANTS: All psychiatrists and psychiatric APCs (subdivided into nurse practitioners (NPs) and clinical nurse specialists (CNSs)) included in either database. PRIMARY AND SECONDARY OUTCOME MEASURES: Number and percentage of clinicians receiving industry payments and value of payments received. Total payments and number of transactions by type of payment, payment source and clinician type were also evaluated. RESULTS: A total of 85 053 psychiatric clinicians (61 011 psychiatrists (71.7%), 21 895 NPs (25.7%), 2147 CNSs (2.5%)) were reviewed; 16 240 (26.6%) psychiatrists received non-research payment from industry, compared with 10 802 (49.3%) NPs and 231 (10.7%) CNSs (p<0.001) for pairwise comparisons). Psychiatric NPs were significantly more likely to receive industry payments compared with psychiatrists (incidence rate ratio (IRR), 1.85 (95% CI 1.81 to 1.88); p<0.001)). Compared with psychiatrists, NPs were more likely to receive payments of > United States Dollars (US) $) 100 (33.9% vs 14.6%; IRR, 2.14 (2.08 to 2.20); p<0.001) and > US$ 1000 (5.3% vs 4.1%; IRR, 1.29 (1.20 to 1.38); p<0.001) but less likely to receive > US$ 10 000 (0.4% vs 1.0%; IRR, 0.39 (0.31 to 0.49); p<0.001). NPs in states with 'reduced' or 'restricted' scope of practice received more frequent payments (reduced: IRR, 1.22 (1.18 to 1.26); restricted: IRR, 1.26 (1.22 to 1.30), both p<0.001). CONCLUSIONS: Psychiatric NPs were nearly two times as likely to receive industry payments as psychiatrists, while psychiatric CNSs were less than half as likely to receive payment. Stricter scope of practice laws increases the likelihood of psychiatric NPs receiving payment, the opposite of what was found in a recent specialty agnostic study.

Occurrence and characteristics of extended-spectrum-ß-lactamase- and pAmpC-producing Klebsiella pneumoniae isolated from companion animals with urinary tract infections.

This study examined 70 Klebsiella pneumoniae isolates derived from companion animals with urinary tract infections in Taiwan. Overall, 81% (57/70) of the isolates carried extended-spectrum ß-lactamase (ESBL) and/or plasmid-encoded AmpC (pAmpC) genes. ESBL genes were detected in 19 samples, with blaCTX-M-1, blaCTX-M-9, and blaSHV being the predominant groups. pAmpC genes were detected in 56 isolates, with blaCIT and blaDHA being the predominant groups. Multilocus sequence typing revealed that sequence types (ST)11, ST15, and ST655 were prevalent. wabG, uge, entB, mrkD, and fimH were identified as primary virulence genes. Two isolates demonstrated a hypermucoviscosity phenotype in the string test. Antimicrobial susceptibility testing exhibited high resistance to ß-lactams and fluoroquinolones in ESBL-positive isolates but low resistance to aminoglycosides, sulfonamides, and carbapenems. Isolates carrying pAmpC genes exhibited resistance to penicillin-class ß-lactams. These findings provide valuable insights into the role of K. pneumoniae in the context of the concept of One Health.

Systems-level analyses dissociate genetic regulators of reactive oxygen species and energy production.

Respiratory chain dysfunction can decrease ATP and increase reactive oxygen species (ROS) levels. Despite the importance of these metabolic parameters to a wide range of cellular functions and disease, we lack an integrated understanding of how they are differentially regulated. To address this question, we adapted a CRISPRi- and FACS-based platform to compare the effects of respiratory gene knockdown on ROS to their effects on ATP. Focusing on genes whose knockdown is known to decrease mitochondria-derived ATP, we showed that knockdown of genes in specific respiratory chain complexes (I, III, and CoQ10 biosynthesis) increased ROS, whereas knockdown of other low ATP hits either had no impact (mitochondrial ribosomal proteins) or actually decreased ROS (complex IV). Moreover, although shifting metabolic conditions profoundly altered mitochondria-derived ATP levels, it had little impact on mitochondrial or cytosolic ROS. In addition, knockdown of a subset of complex I subunits-including NDUFA8, NDUFB4, and NDUFS8-decreased complex I activity, mitochondria-derived ATP, and supercomplex level, but knockdown of these genes had differential effects on ROS. Conversely, we found an essential role for ether lipids in the dynamic regulation of mitochondrial ROS levels independent of ATP. Thus, our results identify specific metabolic regulators of cellular ATP and ROS balance that may help dissect the roles of these processes in disease and identify therapeutic strategies to independently target energy failure and oxidative stress.

High Prevalence of Anorectal Dysfunction in Ambulatory Patients with Chronic Constipation, Regardless of Colon Transit Time.

BACKGROUND: Classification of chronic constipation (CC) into its three subtypes of slow transit constipation, defecation disorder and normal transit constipation, may improve its multifaceted management. We assessed the merits of the London classification in patients with CC, who were studied by both wireless motility capsule (WMC) and high-resolution anorectal manometry (HR-ARM), examining their relative utilities in decision-making.s PATIENTS AND METHODS: Retrospective, community-based study of prospectively collected data on patients with CC by Rome IV criteria, who underwent WMC and HR-ARM, Balloon Expulsion Test, and Rectal Sensory Testing. Clinical assessment was made by standard questionnaires. On WMC, standard criteria for colonic transit time (CTT) were used (normal CTT < 59 h). The hierarchical London classification was used for HR-ARM analyses. RESULTS: Of 1261 patients with CC, 166 (91 M; ages 22-86) received technically satisfactory WMC and HR-ARM, formed the analyzed study cohort, of whom 84 had normal CTT and 82 had prolonged CTT (> 59 h). Patients with slow CTT were significantly older and had longer duration and more severe disease. Using the London classification criteria for disorders of anorectal function, we noted a high prevalence of anorectal dysfunction, regardless of CTT. Except for lower rate of anal hypertonicity in patients with slow CTT, disorders of recto-anal coordination, and rectal sensation were seen at a comparable rate in patients with CC, regardless of CTT. CONCLUSION: There is a significant overlap of anorectal disorders in patients with slow CTT. There is questionable specificity and utility of WMC and HR-ARM in assessing patients with CC. More work is needed to demonstrate the value of these studies as surrogate markers of the disease and its response to multifaceted therapy.

Distribution of CARES Act Provider Relief Funding to Psychiatric Care Organizations.

More than $100 billion in Coronavirus Aid, Relief, and Economic Security (CARES) Act funding was intended to support financially stressed health care providers during the COVID-19 pandemic. The distribution of the CARES Act's Provider Relief Fund among psychiatrists is poorly understood. Analyzing funding received by 2,593 psychiatric care organizations (PCOs), the authors found that funding was more equally distributed across care organizations of different sizes in psychiatry versus other specialties. Substantially less relief funding was received by PCOs per provider relative to other specialties. This disparity in relief funding is surprising given that specific earmarks of the CARES Act were intended to improve U.S. mental health care capacity, meriting further attention.

Investigating the gastrointestinal physiology of mature horses with and without a history of cribbing behavior in response to feeding a digestive support supplement.

Cribbing, a stereotypic oral behavior observed in horses, involves placing incisors on a fixed object, arching the neck, pulling against the object, and emitting an audible grunt. This behavior has been associated with gastrointestinal (GI) dysfunction and gastric ulceration. In this randomized crossover study, we investigated the impact of a GI support supplement (SPL) on the GI environment and physiology of four cribbing (CB) and four non-cribbing horses (NCB). Mature Quarter Horses, acclimated to individual stalls for 16 hours daily with paddock turnout in pairs for 8 hours per day, were randomly assigned to receive either the SPL or placebo for 21 days, followed by a 2-week washout period. Fecal and gastric samples were collected for pH determination and blood samples were analyzed for serum cortisol and gastrin levels. Endoscopic examinations assessed gastric ulcer severity, and cribbing frequency and bouts were recorded via video surveillance. Data were analyzed using a mixed-model ANOVA. Results showed no differences in fecal and gastric pH between cribbing statuses. However, an interaction between supplementation and cribbing status was observed for squamous mucosa ulcer scores (P=0.003). There were no differences in glandular mucosa ulcer scores, serum cortisol, serum gastrin, and crib-bite count between CB and NCB horses or between supplementation groups. Crib-bout duration did not differ with supplementation, but differences were found between periods (P<0.05) and hour ranges (P<0.001). Our findings suggest that the GI support supplement may not effectively address cribbing behavior or alter the GI environment in NCB or CB horses.

Systems-level analyses dissociate genetic regulators of reactive oxygen species and energy production.

Respiratory chain dysfunction can decrease ATP and increase reactive oxygen species (ROS) levels. Despite the importance of these metabolic parameters to a wide range of cellular functions and disease, we lack an integrated understanding of how they are differentially regulated. To address this question, we adapted a CRISPRi- and FACS- based platform to compare the effects of respiratory gene knockdown on ROS to their effects on ATP. Focusing on genes whose knockdown is known to decrease mitochondria-derived ATP, we showed that knockdown of genes in specific respiratory chain complexes (I, III and CoQ10 biosynthesis) increased ROS, whereas knockdown of other low ATP hits either had no impact (mitochondrial ribosomal proteins) or actually decreased ROS (complex IV). Moreover, although shifting metabolic conditions profoundly altered mitochondria-derived ATP levels, it had little impact on mitochondrial or cytosolic ROS. In addition, knockdown of a subset of complex I subunits-including NDUFA8, NDUFB4, and NDUFS8-decreased complex I activity, mitochondria-derived ATP and supercomplex level, but knockdown of these genes had differential effects on ROS. Conversely, we found an essential role for ether lipids in the dynamic regulation of mitochondrial ROS levels independent of ATP. Thus, our results identify specific metabolic regulators of cellular ATP and ROS balance that may help dissect the roles of these processes in disease and identify therapeutic strategies to independently target energy failure and oxidative stress.

A systematic review of influences and outcomes of body image in postpartum via a socioecological framework.

BACKGROUND: Women in the postpartum period come under multi-level pressure to return to pre-pregnancy body shape and size. This pressure can lead to reduced body image satisfaction, self-esteem, and mood. In this systematic review we explored the influences and outcomes of body dissatisfaction during the postpartum period. METHODS: Four databases were searched using keywords: postpart* OR postnatal OR peripart* OR 'new mother' OR 'breast feed*' AND 'body image' OR 'body dissatisf*' OR 'body satisf*' OR 'body attitude' OR 'body shape'. RESULTS: The influences and outcomes of body image dis/satisfaction in the postpartum period from 55 international studies were found to align within four of the five factors of the socioecological model. Intrapersonal factors: weight and body shape concerns, mental health and stressors, attitudes and behaviours, and protective coping skills and interventions. Interpersonal factors: social support (partner, family, and friends) and sexual functioning. Institutional factors: experiences with the healthcare system and returning to work. Societal factors: culture and ethnicity, media influences and social norms such as the thin ideal. CONCLUSIONS: A focus on intrapersonal factors alone is insufficient to understand women's experiences of body dis/satisfaction during the postpartum period. This suggests a need for better education and policy practices in pre-natal and postpartum care directed at body image and education to dispel societal norms such as the thin ideal. Doing so shifts the focus to include interpersonal, institutional, and societal influences alongside intrapersonal experiences. Research is needed to explore the utility and efficacy of broader approaches for women during this vulnerable life period.

Personalized Tacrolimus Dosing After Liver Transplantation: A Randomized Clinical Trial.

Background: Inter- and intra-individual variability in tacrolimus dose requirements mandates empirical clinician-titrated dosing that frequently results in deviation from a narrow target range. Improved methods to individually dose tacrolimus are needed. Our objective was to determine whether a quantitative, dynamically-customized, phenotypic-outcome-guided dosing method termed Phenotypic Personalized Medicine (PPM) would improve target drug trough maintenance. Methods: In a single-center, randomized, pragmatic clinical trial ( NCT03527238 ), 62 adults were screened, enrolled, and randomized prior to liver transplantation 1:1 to standard-of-care (SOC) clinician-determined or PPM-guided dosing of tacrolimus. The primary outcome measure was percent days with large (>2 ng/mL) deviation from target range from transplant to discharge. Secondary outcomes included percent days outside-of-target-range and mean area-under-the-curve (AUC) outside-of-target-range per day. Safety measures included rejection, graft failure, death, infection, nephrotoxicity, or neurotoxicity. Results: 56 (29 SOC, 27 PPM) patients completed the study. The primary outcome measure was found to be significantly different between the two groups. Patients in the SOC group had a mean of 38.4% of post-transplant days with large deviations from target range; the PPM group had 24.3% of post-transplant days with large deviations; (difference -14.1%, 95% CI: -26.7 to -1.5 %, P=0.029). No significant differences were found in the secondary outcomes. In post-hoc analysis, the SOC group had a 50% longer median length-of-stay than the PPM group [15 days (Q1-Q3: 11-20) versus 10 days (Q1-Q3: 8.5-12); difference 5 days, 95% CI: 2-8 days, P=0.0026]. Conclusions: PPM guided tacrolimus dosing leads to better drug level maintenance than SOC. The PPM approach leads to actionable dosing recommendations on a day-to-day basis. Lay Summary: In a study on 62 adults who underwent liver transplantation, researchers investigated whether a new dosing method called Phenotypic Personalized Medicine (PPM) would improve daily dosing of the immunosuppression drug tacrolimus. They found that PPM guided tacrolimus dosing leads to better drug level maintenance than the standard-of-care clinician-determined dosing. This means that the PPM approach leads to actionable dosing recommendations on a day-to-day basis and can help improve patient outcomes.

Effects of pregnancy and lactation on muscle-tendon morphology.

Pregnancy and lactation hormones have been shown to mediate anatomical changes to the musculoskeletal system that generates animal movement. In this study, we characterize changes in the medial gastrocnemius muscle, its tendon and aponeuroses that are likely to have an effect on whole animal movement and energy expenditure, using the rat model system, Rattus norvegicus. We quantified muscle architecture (mass, cross-sectional area, and pennation angle), muscle fiber type and diameter, and Young's modulus of stiffness for the medial gastrocnemius aponeuroses as well as its contribution to Achilles tendon in three groups of three-month-old female rats: virgin, primiparous pregnant, and primiparous lactating animals. We found that muscle mass drops by 23% during lactation but does not change during pregnancy. We also found that during pregnancy muscle fibers switch from Type I to IIa and during lactation from Type IIb to Type I. The stiffness of connective tissues that has a demonstrated role in locomotion, the aponeurosis and tendon, also changed. Pregnant animals had a significantly less stiff aponeurosis. However, tendon stiffness was most affected during lactation, with a significant drop in stiffness and interindividual variation. We propose that the energetic demands of locomotion may have driven the evolution of these anatomical changes in muscle-tendon units during pregnancy and lactation to ensure more energy can be allocated to fetal development and lactation.

Lower extremity symptoms and ankle-brachial index screening as predictors of cardiovascular outcomes in Black adults.

BACKGROUND: The prevalence of peripheral artery disease (PAD) and leg symptoms are higher in Black than White adults. We studied the effects of self-reported lower extremity symptoms and ankle-brachial indices (ABI) groups on outcomes. METHODS: Black participants in the Jackson Heart Study with baseline ABI and PAD symptom assessments (exertional leg pain by the San Diego Claudication questionnaire) were included. Abnormal ABI was < 0.90 or > 1.40. Participants were divided into (1) normal ABI, asymptomatic, (2) normal ABI, symptomatic, (3) abnormal ABI, asymptomatic, and (4) abnormal ABI, symptomatic to examine their associations with MACE (stroke, myocardial infarction, fatal coronary heart disease) and all-cause mortality, using Kaplan-Meier survival curves and stepwise Cox proportional hazard models adjusting for Framingham risk factors. RESULTS: Of 4586 participants, mean age was 54.6 ± 12.6 years, with 63% women. Compared with participants with normal ABI who were asymptomatic, participants with abnormal ABI and leg symptoms had highest risk of MACE (adjusted HR 2.28; 95% CI 1.62, 3.22) and mortality (aHR 1.82; 95% CI 1.32, 2.56). Participants with abnormal ABI without leg symptoms had higher risk for MACE (aHR 1.49; 95% CI 1.06, 2.11) and mortality (aHR 1.44; 95% CI 1.12, 1.99). Participants with normal ABI and no leg symptoms did not have higher risks. CONCLUSION: Among Black adults, the highest risk for adverse outcomes were in symptomatic participants with abnormal ABIs, followed by asymptomatic participants with abnormal ABIs. These findings underscore the need for further studies to screen for PAD and develop preventative approaches in Black adults with asymptomatic disease.

Activin A-Expressing Polymorphonuclear Myeloid-Derived Suppressor Cells Infiltrate Skeletal and Cardiac Muscle and Promote Cancer Cachexia.

Cachexia is a major cause of death in cancer and leads to wasting of cardiac and skeletal muscle, as well as adipose tissue. Various cellular and soluble mediators have been postulated in driving cachexia; however, the specific mechanisms behind this muscle wasting remain poorly understood. In this study, we found polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) to be critical for the development of cancer-associated cachexia. Significant expansion of PMN-MDSCs was observed in the cardiac and skeletal muscles of cachectic murine models. Importantly, the depletion of this cell subset, using depleting anti-Ly6G Abs, attenuated this cachectic phenotype. To elucidate the mechanistic involvement of PMN-MDSCs in cachexia, we examined major mediators, that is, IL-6, TNF-α, and arginase 1. By employing a PMN-MDSC-specific Cre-recombinase mouse model, we showed that PMN-MDSCs were not maintained by IL-6 signaling. In addition, PMN-MDSC-mediated cardiac and skeletal muscle loss was not abrogated by deficiency in TNF-α or arginase 1. Alternatively, we found PMN-MDSCs to be critical producers of activin A in cachexia, which was noticeably elevated in cachectic murine serum. Moreover, inhibition of the activin A signaling pathway completely protected against cardiac and skeletal muscle loss. Collectively, we demonstrate that PMN-MDSCs are active producers of activin A, which in turn induces cachectic muscle loss. Targeting this immune/hormonal axis will allow the development of novel therapeutic interventions for patients afflicted with this debilitating syndrome.

A longitudinal analysis of Australian women's fruit and vegetable consumption and depressive symptoms.

BACKGROUND: In Australia, women report higher rates of depressive symptoms than men. Research suggests that dietary patterns rich in fresh fruit and vegetables could protect against depressive symptoms. The Australian Dietary Guidelines suggest that consuming two servings of fruit and five serves of vegetables per day is optimal for overall health. However, this consumption level is often difficult for those experiencing depressive symptoms to achieve. AIMS: This study aims to compare diet quality and depressive symptoms in Australian women over time using (I) two serves of fruit and five serves of vegetables per day (FV7), and (ii) two serves of fruit and three serves of vegetables per day (FV5). MATERIALS AND METHODS: A secondary analysis was conducted using data from the Australian Longitudinal Study on Women's Health over 12 years at three time points 2006 (n = 9145, Mean age = 30.6, SD = 1.5), 2015 (n = 7186, Mean age = 39.7, SD = 1.5), and 2018 (n = 7121, Mean age = 42.4, SD = 1.5). RESULTS: A linear mixed effects model found, after adjusting for covarying factors, a small significant inverse association between both FV7 (b = -.54, 95% CI = -.78, -.29) and FV5 (b = -.38, 95% CI = -.50, -.26) in depressive symptoms. DISCUSSION: These findings suggest an association between fruit and vegetable consumption and decreased depressive symptoms. The small effect sizes indicate caution should be taken in interpreting these results. The findings also suggest that current Australian Dietary Guideline recommendations need not be prescriptive to two fruit and five vegetables for impact on depressive symptoms. CONCLUSIONS: Future research could evaluate reduced vegetable consumption (three serves per day) in identifying the protective threshold for depressive symptoms.