The lncRNA ALPHA specifically targets chikungunya virus to control infection.

Arthropod-borne viruses, including the alphavirus chikungunya virus (CHIKV), cause acute disease in millions of people and utilize potent mechanisms to antagonize and circumvent innate immune pathways including the type I interferon (IFN) pathway. In response, hosts have evolved antiviral counterdefense strategies that remain incompletely understood. Recent studies have found that long noncoding RNAs (lncRNAs) regulate classical innate immune pathways; how lncRNAs contribute to additional antiviral counterdefenses remains unclear. Using high-throughput genetic screening, we identified a cytoplasmic antiviral lncRNA that we named antiviral lncRNA prohibiting human alphaviruses (ALPHA), which is transcriptionally induced by alphaviruses and functions independently of IFN to inhibit the replication of CHIKV and its closest relative, O'nyong'nyong virus (ONNV), but not other viruses. Furthermore, we showed that ALPHA interacts with CHIKV genomic RNA and restrains viral RNA replication. Together, our findings reveal that ALPHA and potentially other lncRNAs can mediate non-canonical antiviral immune responses against specific viruses.

Reestablishment of spermatogenesis after more than 20 years of cryopreservation of rat spermatogonial stem cells reveals an important impact in differentiation capacity.

Treatment of cancer in children is increasingly successful but leaves many prepubertal boys suffering from infertility or subfertility later in life. A current strategy to preserve fertility in these boys is to cryopreserve a testicular biopsy prior to treatment with the expectation of future technologies allowing for the reintroduction of stem cells and restoration of spermatogenesis. Spermatogonial stem cells (SSCs) form the basis of male reproduction, differentiating into all germ cell types, including mature spermatozoa and can regenerate spermatogenesis following transplantation into an infertile testis. Here, we demonstrate that rat SSCs frozen for more than 20 years can be transplanted into recipient mice and produce all differentiating germ cell types. However, compared with freshly isolated cells or those frozen for a short period of time, long-frozen cells do not colonize efficiently and showed reduced production of spermatids. Single-cell RNA sequencing revealed similar profiles of gene expression changes between short- and long-frozen cells as compared with fresh immediately after thawing. Conversely, following transplantation, long-frozen samples showed enhanced stem cell signaling in the undifferentiated spermatogonia compartment, consistent with self-renewal and a lack of differentiation. In addition, long-frozen samples showed fewer round spermatids with detectable protamine expression, suggesting a partial block of spermatogenesis after meiosis resulting in a lack of elongating spermatids. These findings strongly suggest that prolonged cryopreservation can impact the success of transplantation to produce spermatogenesis, which may not be revealed by analysis of the cells immediately after thawing. Our analysis uncovered persistent effects of long-term freezing not found in other cryopreservation studies that lacked functional regeneration of the tissue and this phenomenon must be accounted for any future therapeutic application.

Geriatric Motorcycle-Related Outcomes: A Pennsylvania Multicenter Study.

INTRODUCTION: Geriatric patients (GeP) often experience increased morbidity and mortality following traumatic insult and as a result, require more specialized care due to lower physiologic reserve and underlying medical comorbidities. Motorcycle injuries (MCCI) occur across all age groups; however, no large-scale studies evaluating outcomes of GeP exist for this particular subset of patients. Data thus far are limited to elderly participation in recreational activities such as water and alpine skiing, snowboarding, equestrian, snowmobiles, bicycles, and all-terrain vehicles. We hypothesized that GeP with MCCI will have a higher rate of mortality when compared with their younger counterparts despite increased helmet usage. METHODS: We performed a multicenter retrospective review of MCCI patients at three Pennsylvania level I trauma centers from January 2016 to December 2020. Data were extracted from each institution's electronic medical records and trauma registry. GeP were defined as patients aged more than or equal to 65 y. The primary outcome was mortality. Secondary outcomes included ventilator days; hospital, intensive care unit, and intermediate unit length of stays; complications; and helmet use. 3:1 nongeriatric patients (NGeP) to GeP propensity score matching (PSM) was based on sex, abbreviated injury scale (AIS), and injury severity score (ISS). P ≤ 0.05 was considered significant. RESULTS: One thousand five hundred thirty eight patients were included (GeP: 7% [n = 113]; NGP: 93% [n = 1425]). Prior to PSM, GeP had higher median Charlson Comorbidity Index (GeP: 3.0 versus NGeP: 0.0; P ≤ 0.001) and greater helmet usage (GeP: 73.5% versus NGeP: 54.6%; P = 0.001). There was a statistically significant difference between age cohorts in terms of ISS (GeP: 10.0 versus NGeP: 6.0, P = 0.43). There was no significant difference for any AIS body region. Mortality rates were similar between groups (GeP: 1.7% versus NGeP: 2.6%; P = 0.99). After PSM matching for sex, AIS, and ISS, GeP had significantly more comorbidities than NGeP (P ≤ 0.05). There was no difference in trauma bay interventions or complications between cohorts. Mortality rates were similar (GeP: 1.8% versus NGeP: 3.2%; P = 0.417). Differences in ventilator days as well as intensive care unit length of stay, intermediate unit length of stay, and hospital length of stay were negligible. Helmet usage between groups were similar (GeP: 64.5% versus NGeP: 66.8%; P = 0.649). CONCLUSIONS: After matching for sex, ISS, and AIS, age more than 65 y was not associated with increased mortality following MCCI. There was also no significant difference in helmet use between groups. Further studies are needed to investigate the effects of other potential risk factors in the aging patient, such as frailty and anticoagulation use, before any recommendations regarding management of motorcycle-related injuries in GeP can be made.

PROSPECTIVE POSTMORTEM ASSESSMENT OF THE INCIDENCE OF MAMMARY NEOPLASIA IN CHIMPANZEES (PAN TROGLODYTES).

When evaluating the last 25 yr of morbidity and mortality from adult chimpanzees managed within the Association of Zoo and Aquarium Chimpanzee Species Survival Plan® for North American zoos, only two female chimpanzees were diagnosed with mammary neoplasia: one incidentally antemortem and one with a terminal metastatic neoplasia. When comparing this observation of prevalence of mammary neoplasia to humans, a substantial disparity is apparent. Mammary neoplasia is the second most common cancer in adult female humans, with a lifetime risk of 1:8 in the United States. The reason for the disparity between humans and chimpanzees, as closely related species, is unknown. The true prevalence in chimpanzees may be higher than currently noted, because routine examination of mammary tissue in chimpanzees is generally less complete than for other tissues postmortem, and antemortem assessment is generally limited to mammary palpation. This study was performed on intact, bilateral mammary glands harvested at postmortem examination of adult female chimpanzees (n = 7) from six institutions. With mammography, complete histopathologic sectioning, and genetic evaluation, the risk of mammary neoplasia was evaluated more thoroughly than during a typical postmortem exam in zoo populations during 2017-2019. No chimpanzees in the study were diagnosed with mammary neoplasia. Overall, this study supports the previous impression that chimpanzees do not develop mammary neoplasia at a similar rate as humans, even when comparable diagnostic modalities for evaluation are used.

Identification of genetic loci shared between Alzheimer's disease and hypertension.

Alzheimer's disease (AD) and high blood pressure (BP) are prevalent age-related diseases with significant unexplained heritability. A thorough analysis of genetic pleiotropy between AD and BP will lay a foundation for the study of the associated molecular mechanisms, leading to a better understanding of the development of each phenotype. We used the conditional false discovery rate (cFDR) method to identify novel genetic loci associated with both AD and BP. The cFDR approach improves the effective sample size for association testing by combining GWAS summary statistics for correlated phenotypes. We identified 50 pleiotropic SNPs for AD and BP, 7 of which are novel and have not previously been reported to be associated with either AD or BP. The novel SNPs located at STK3 are particularly noteworthy, as this gene may influence AD risk via the Hippo signaling network, which regulates cell death. Bayesian colocalization analysis demonstrated that although AD and BP are associated, they do not appear to share the same causal variants. We further performed two sample Mendelian randomization analysis, but could not detect a causal effect of BP on AD. Despite the inability to establish a causal link between AD and BP, our findings report some potential novel pleiotropic loci that may influence disease susceptibility. In summary, we identified 7 SNPs that annotate to 4 novel genes which have not previously been reported to be associated with AD nor with BP and discuss the possible role of one of these genes, STK3 in the Hippo signaling network.

Methods to quantify heat stress in ruminants: Current status and future prospects.

The physiology of hyperthermia or heat stress in mammals is complex. It is a totally systemic condition that in varying degrees involves all organs, tissues and body fluid compartments. The nature and magnitude of the response is influenced by animal specific characteristics (e.g. age, diet, body condition, gender, reproductive stage), environment and animal management. Given the multifaceted nature of heat stress, and the varied ruminant production systems based in varied geoclimatic zones, it has been difficult to find appropriate measures of heat stress for production ruminants. This has become an urgent challenge as production systems intensify globally in a warming climate. Bioclimatic indices such as the Temperature-Humidity Index (THI) have evolved to incorporate some measure of animal physiology. However, these indices do not have strong relationships with core temperature trajectories and altered respiratory dynamics of animals with excessive heat load. In recent decades, the careful physiology studies of the 1950-80s, have given way to numerous studies trialling a plethora of new technologies and computational approached to measure heat stress. Infrared thermography of body surface temperatures, automated measures of respiration rate and radiotelemetry of internal body temperatures are the most intensively researched. The common goal has been to find the 'holy grail' decision-making threshold or timepoint as to the animal's wellbeing. Are we making any progress?

Most Facial Fractures Do Not Require Surgical Intervention.

PURPOSE: Literature describing the number of patients that had a facial fracture that required surgical intervention in the United States is very limited. The purpose of this study was to evaluate the percentage of patients who required surgical intervention after presenting to a Level 1 Trauma Center with 1 or more facial fractures. MATERIALS AND METHODS: This was a retrospective cross-sectional study of all patients who presented with facial fracture(s) to University Hospital, a Level 1 Trauma Center (San Antonio, Texas), over a 5-year period from July 2015 to July 2020. Patients' charts that had 1 or more International Classification of Diseases 10 codes pertaining to facial fractures were collected. Cases were subdivided by fracture location: mandible, midface, upper face, or a combination of any of the aforementioned locations (predictor variables). After subdividing based on location, each chart was then reviewed and separated based on whether or not surgical intervention was provided (primary outcome variable). Data were tabulated and analyzed with descriptive and inferential statistics. RESULTS: Over the 5-year period, 3,416 patients presented with facial fractures. Of the 3,126 patients who survived their injuries and were not lost to follow-up, the vast majority (80.9%) did not require surgical intervention for their facial fractures. Mandible fractures required surgical intervention, whether isolated or in combination, much more frequently than in patients who did not have any type of mandible fracture (RR 8.01, 95% CI 6.92-9.27, P < .05 and RR 4.60, 95% CI 3.42-6.18, P < .05, respectively). Patients aged 50 years or less were also more likely to receive surgical intervention than those aged 51 years and more (RR 1.98 95% CI 1.63-2.41, P < .05). CONCLUSIONS: The vast majority of facial fractures that present to a Level 1 Trauma Center do not require surgical intervention. Patients who present with any type of mandible fracture and are aged 50 years or less are more likely to need surgical intervention.

Monitoring spatial and temporal soundscape features within ecologically significant U.S. National Marine Sanctuaries.

The U.S. National Oceanic and Atmospheric Administration's Office of National Marine Sanctuaries manages a system of marine protected areas encompassing more than 2,000,000 km2 . U.S. National Marine Sanctuaries (NMS) have been designated to provide protection for their conservation, recreational, ecological, historical, scientific, cultural, archaeological, educational, or aesthetic qualities. Due to the large variability of attributes among NMS, designing coordinated system-wide monitoring to support diverse resource protection goals can be challenging. Underwater sound monitoring is seeing increasing application to marine protected area management because it is able to support this wide variety of information needs. Passive acoustics are providing invaluable autonomous information regarding habitat associations, identifying species spatial and temporal use, and highlighting patterns in conditions that are otherwise difficult to survey. Using standardized equipment and analysis methods this study collected ambient underwater sound data and derived measurements to investigate temporal changes in sound pressure levels and power spectral density, identify presence of select species of importance and support within and among site comparison of ambient underwater sound among eight sites within four U.S. NMS. Broadband sound pressure levels of ambient sound (10-24,000 Hz) varied as much as 24 dB re 1 µPa (max difference 100-124 dB re 1 µPa) among the recording sites, sanctuaries, and seasons. Biotic signals, such as snapping shrimp snaps and vocalizations of fishes, exhibited distinct diel and seasonal patterns and showed variation among sites. Presence of anthropogenic signals, such as vessel passage, also varied substantially among sites, ranging from on average 1.6-21.8 h/d. The study identified measurements that effectively summarized baseline soundscape attributes and prioritized future opportunities for integrating non-acoustic and acoustic variables in order to inform area-specific management questions within four ecologically varying U.S. National Marine Sanctuaries.

Intra-articular therapy with methotrexate or tumor necrosis factor inhibitors in rheumatoid arthritis: a systematic review.

BACKGROUND: Persistent monoarthritis in otherwise well-controlled rheumatoid arthritis presents a therapeutic challenge. Intra-articular (IA) steroids are a mainstay of treatment, though some have queried whether IA disease modifying anti-rheumatic drugs (DMARD) and biologics can be used in those who fail steroid injections. METHODS: A systematic literature review was conducted using four medical databases to identify randomized, controlled trials assessing IA therapies in RA patients. Included studies underwent Cochrane Risk of Bias 2 assessment for quality. RESULTS: Twelve studies were included, 6 of which examined intra-articular (IA) TNF inhibitors (TNFi), and 6 studies evaluating IA methotrexate. Of those evaluating IA TNFi, one study reported statistical improvement in TNFi therapy when compared with placebo. The remaining 5 studies compared IA TNFi therapy with steroid injections. IA TNFi had statistically improved symptom scores and clinical assessments comparable with IA steroid treatments. In the 6 studies evaluating IA methotrexate, the addition of methotrexate to steroid intra-articular therapy was not found to be beneficial, and singular methotrexate injection was not superior to the control arms (saline or triamcinolone). Risk-of-bias (ROB) assessment with the Revised Cochrane ROB tool indicated that 2 of 6 TNFi studies were at some risk or high risk for bias, compared with 5 out of 6 methotrexate studies. CONCLUSION: For persistent monoarthritis in rheumatoid arthritis, IA methotrexate was not found to have clinical utility. Intra-articular TNFi therapy appears to have equal efficacy to IA steroids, though the optimal dose and frequency of injections is yet unknown.

Syndecan-1 facilitates breast cancer metastasis to the brain.

PURPOSE: Although survival rates for patients with localized breast cancer have increased, patients with metastatic breast cancer still have poor prognosis. Understanding key factors involved in promoting breast cancer metastasis is imperative for better treatments. In this study, we investigated the role of syndecan-1 (Sdc1) in breast cancer metastasis. METHODS: To assess the role of Sdc1 in breast cancer metastasis, we silenced Sdc1 expression in the triple-negative breast cancer human MDA-MB-231 cell line and overexpressed it in the mouse mammary carcinoma 4T1 cell line. Intracardiac injections were performed in an experimental mouse metastasis model using both cell lines. In vitro transwell blood-brain barrier (BBB) and brain section adhesion assays were utilized to specifically investigate how Sdc1 facilitates brain metastasis. A cytokine array was performed to evaluate differences in the breast cancer cell secretome when Sdc1 is silenced. RESULTS: Silencing expression of Sdc1 in breast cancer cells significantly reduced metastasis to the brain. Conversely, overexpression of Sdc1 increased metastasis to the brain. We found that silencing of Sdc1 expression had no effect on attachment of breast cancer cells to brain endothelial cells or astrocytes, but migration across the BBB was reduced as well as adhesion to the perivascular regions of the brain. Loss of Sdc1 also led to changes in breast cancer cell-secreted cytokines/chemokines, which may influence the BBB. CONCLUSIONS: Taken together, our study demonstrates a role for Sdc1 in promoting breast cancer metastasis to the brain. These findings suggest that Sdc1 supports breast cancer cell migration across the BBB through regulation of cytokines, which may modulate the BBB. Further elucidating this mechanism will allow for the development of therapeutic strategies to combat brain metastasis.

Update: Interim Guidance for Health Care Providers for Managing Patients with Suspected E-cigarette, or Vaping, Product Use-Associated Lung Injury - United States, November 2019.

CDC, the Food and Drug Administration (FDA), state and local health departments, and public health and clinical stakeholders are investigating a nationwide outbreak of e-cigarette, or vaping, product use-associated lung injury (EVALI) (1). CDC has published recommendations for health care providers regarding EVALI (2-4). Recently, researchers from Utah and New York published proposed diagnosis and treatment algorithms for EVALI (5,6). EVALI remains a diagnosis of exclusion because, at present, no specific test or marker exists for its diagnosis, and evaluation should be guided by clinical judgment. Because patients with EVALI can experience symptoms similar to those associated with influenza or other respiratory infections (e.g., fever, cough, headache, myalgias, or fatigue), it might be difficult to differentiate EVALI from influenza or community-acquired pneumonia on initial assessment; EVALI might also co-occur with respiratory infections. This report summarizes recommendations for health care providers managing patients with suspected or known EVALI when respiratory infections such as influenza are more prevalent in the community than they have been in recent months (7). Recommendations include 1) asking patients with respiratory, gastrointestinal, or constitutional symptoms about the use of e-cigarette, or vaping, products; 2) evaluating those suspected to have EVALI with pulse oximetry and obtaining chest imaging, as clinically indicated; 3) considering outpatient management for clinically stable EVALI patients who meet certain criteria; 4) testing patients for influenza, particularly during influenza season, and administering antimicrobials, including antivirals, in accordance with established guidelines; 5) using caution when considering prescribing corticosteroids for outpatients, because this treatment modality has not been well studied among outpatients, and corticosteroids could worsen respiratory infections; 6) recommending evidence-based treatment strategies, including behavioral counseling, to help patients discontinue using e-cigarette, or vaping, products; and 7) emphasizing the importance of annual influenza vaccination for all persons aged ≥6 months, including patients who use e-cigarette, or vaping products.

MR imaging appearance of noncalcified and calcified DCIS.

To evaluate the MR appearance of noncalcified ductal carcinoma in situ (DCIS), with comparison to calcified DCIS. A retrospective, IRB-approved review of all DCIS diagnosed via MR biopsy between 2007 and 2011 was performed. DCIS was categorized as noncalcified based on the absence of calcifications on mammography and specimen radiography. MR morphology (focus, mass, nonmass enhancement [NME]) and enhancement kinetics (initial and delayed) for noncalcified DCIS were recorded and compared based on nuclear grade (1-3), size (<1.5 cm, 1.5-5 cm, >5 cm), and presence of necrosis. Imaging features of noncalcified and calcified DCIS were also compared. 115 cases of MR biopsy-proven DCIS were identified: 65 (56%) noncalcified and 50 (44%) calcified. For noncalcified DCIS, NME morphology was more common than mass or focus (60% vs 30.8% and 9.2%). There was a significant association between morphology and enhancement kinetics, with NME more likely demonstrating medium and persistent kinetics, and foci or masses demonstrating rapid and plateau or washout kinetics (P < .05). There was also a significant association between morphology and nuclear grade, with NME more likely seen with grade 3 DCIS (P = .024), and between size and initial enhancement, with lesions <1.5 cm more likely to have rapid initial enhancement (P = .0036). No significant difference was identified between calcified and noncalcified DCIS in terms of morphology, enhancement characteristics, nuclear grade, or presence of necrosis. The MR appearance of noncalcified DCIS closely mirrors that of calcified DCIS. Recognizing these imaging features may allow for improved identification of this MRI-detected abnormality, even in the absence of calcifications.

Effect of feeding slowly fermentable grains on productive variables and amelioration of heat stress in lactating dairy cows in a sub-tropical summer.

Feeding low-fiber and high-energy diets to dairy cows is one approach to ameliorate heat stress (HS) by reducing heat increment (HI) during digestion. However, rapidly and slowly fermentable cereal grains differ in their HI. The aim of this experiment was to quantify if feeding slowly fermentable grains ameliorated the physiological responses to HS and improved milk production (MP) in dairy cows. Holstein-Friesian lactating dairy cows were housed in shaded pens and were fed either a total mixed ration (TMR) plus wheat (TMRW), a TMR plus wheat treated with 2% of a commercial starch-binding agent (TMRB), or a TMR plus corn (TMRC) (n = 8 cows per diet) during summer in Queensland, Australia. Respiration rate (RR) and panting score (PS) were measured four times a day; rumen temperature (RuT) was recorded every 20 min, and rectal temperature (RT) and milk samples were obtained every 4 days. Cows fed slowly fermentable grains had higher milk production (MP) than cows fed TMRW, and cows fed TMRC had lower RT than those fed TMRW and TMRB (P < 0.001). Rumen temperature was positively correlated with temperature-humidity index and negatively correlated with MP (P < 0.05). In summary, feeding TMRC ameliorated HS as indicated by lower RT and improved MP in dairy cows. Milk production was improved with starch-binding agents; however, this was not associated with efficient thermoregulatory responses. Furthermore, determination of RuT enabled the prediction of changes in physiological variables and productive responses due to HS in lactating dairy cows.

Overexpression of lipid metabolism genes and PBX1 in the contralateral breasts of women with estrogen receptor-negative breast cancer.

Risk biomarkers for estrogen receptor (ER)-negative breast cancer have clear value for breast cancer prevention. We previously reported a set of lipid metabolism (LiMe) genes with high expression in the contralateral unaffected breasts (CUBs) of ER-negative cancer cases. We now further examine LiMe gene expression in both tumor and CUB, and investigate the role of Pre-B-cell leukemia homeobox-1 (PBX1) as a candidate common transcription factor for LiMe gene expression. mRNA was extracted from laser-capture microdissected epithelium from tumor and CUB of 84 subjects (28 ER-positive cases, 28 ER-negative cases, 28 healthy controls). Gene expression was quantitated by qRT-PCR. Logistic regression models were generated to predict ER status of the contralateral cancer. Protein expression of HMGCS2 and PBX1 was measured using immunohistochemistry. The effect of PBX1 on LiMe gene expression was examined by overexpressing PBX1 in MCF10A cells with or without ER, and by suppressing PBX1 in MDA-MB-453 cells. The expression of DHRS2, HMGCS2, UGT2B7, UGT2B11, ALOX15B, HPGD, UGT2B28 and GLYATL1 was significantly higher in ER-negative versus ER-positive CUBs, and predicted ER status of the tumor in test and validation sets. In contrast, LiMe gene expression was significantly lower in ER-negative than ER-positive tumors. PBX1 overexpression in MCF10A cells up-regulated most LiMe genes, but not in MCF10A cells overexpressing ER. Suppressing PBX1 in MDA-MB-453 cells resulted in decrease of LiMe gene expression. Four binding sites of PBX1 and cofactor were identified in three lipid metabolism genes using ChIP-qPCR. These data suggest a novel role for PBX1 in the regulation of lipid metabolism genes in benign breast, which may contribute to ER-negative tumorigenesis.

Impact of an Atrial Fibrillation Decision Support Tool on thromboprophylaxis for atrial fibrillation.

BACKGROUND: Appropriate thromboprophylaxis for patients with atrial fibrillation (AF) remains a national challenge. METHODS: We hypothesized that provision of decision support in the form of an Atrial Fibrillation Decision Support Tool (AFDST) would improve thromboprophylaxis for AF patients. We conducted a cluster randomized trial involving 15 primary care practices and 1,493 adults with nonvalvular AF in an integrated health care system between April 2014 and February 2015. Physicians in the intervention group received patient-level treatment recommendations made by the AFDST. Our primary outcome was the proportion of patients with antithrombotic therapy that was discordant from AFDST recommendation. RESULTS: Treatment was discordant in 42% of 801 patients in the intervention group. Physicians reviewed reports for 240 patients. Among these patients, thromboprophylaxis was discordant in 63%, decreasing to 59% 1 year later (P = .02). In nonstratified analyses, changes in discordant care were not significantly different between the intervention group and control groups. In multivariate regression models, assignment to the intervention group resulted in a nonsignificant trend toward decreased discordance (P = .29), and being a patient of a resident physician (P = .02) and a higher HAS-BLED score predicted decreased discordance (P = .03), whereas female gender (P = .01) and a higher CHADSVASc score (P = .10) predicted increased discordance. CONCLUSIONS: Among patients whose physicians reviewed recommendations of the decision support tool discordant therapy decreased significantly over 1 year. However, in nonstratified analyses, the intervention did not result in significant improvements in discordant antithrombotic therapy.

RANKL expression in normal and malignant breast tissue responds to progesterone and is up-regulated during the luteal phase.

The receptor activator of nuclear factor-κB ligand (RANKL) acts as a paracrine factor in progesterone-induced mammary epithelial proliferation and tumorigenesis. This evidence comes mainly from mouse models. Our aim was to examine whether RANKL expression in human normal and malignant breast is under the control of progesterone throughout the menstrual cycle. Breast epithelial samples were obtained by random fine needle aspiration (rFNA) of the contralateral unaffected breasts (CUB) of 18 breast cancer patients, with simultaneous serum hormone measurements. Genes correlated with serum progesterone levels were identified through Illumina microarray analysis. Validation was performed using qRT-PCR in rFNA samples from CUB of an additional 53 women and using immunohistochemistry in tissue microarrays of 61 breast cancer samples. Expression of RANKL, DIO2, and MYBPC1 was correlated with serum progesterone in CUB, and was significantly higher in luteal phase. RANKL and MYBPC1 mRNA expression were highly correlated between CUB and matched tumor samples. RANKL protein expression was also significantly increased in the luteal phase and highly correlated with serum progesterone levels in cancer samples, especially in hormone receptor positive tumors. The regulatory effects of progesterone on the expression of RANKL, DIO2, and MYBPC1 were confirmed in three-dimensional cultures of normal breast organoids. In normal breast and in breast cancer, RANKL mRNA and protein expression fluctuate with serum progesterone with highest levels in the luteal phase, suggesting that RANKL is a modulator of progesterone signaling in normal and malignant breast tissue and a potential biomarker of progesterone action and blockade.

Examining workplace behaviors in adult women with urinary incontinence: A pilot study.

BACKGROUND: Urinary incontinence is a growing issue among adult women globally. Limited data exist examining the impact of occupational, environmental, and behavioral factors on urinary incontinence. OBJECTIVE: This quantitative, cross-sectional pilot study examined the workplace behaviors of adult women experiencing urinary incontinence. It was hypothesized that specific jobs and work environments would be associated with increased urinary incontinence and urgency based on identified behaviors and work-related conditions. DESIGN: This study is a quantitative, cross-sectional survey. METHODS: Adult women (18 years and older) with a history of urinary incontinence were recruited from August 2022 to February 2023 to complete a one-time survey consisting of multiple-choice and short answer questions identifying specific workplace behaviors and symptoms of urinary incontinence. Descriptive statistics and data categorization were used to observe outcomes and examine relationships between urinary incontinence and particular professions. RESULTS: Urinary incontinence and urgency-related symptoms affected healthcare and business professionals at a higher prevalence. The most commonly reported behaviors across all professions consisted of withholding urine and utilizing absorbance products. CONCLUSION: The results of this study will help guide women's health practitioners in exploring current workplace behaviors that may contribute to urinary incontinence in adult women. With this knowledge, practitioners can provide meaningful education to employers and employees to prioritize toileting behaviors in the workplace.

Nailfold videocapillaroscopy in antineutrophil cytoplasmic antibody-associated vasculitis.

OBJECTIVE: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of illnesses that cause inflammation and alterations to small vessels in the body. Some of the most common and detrimental manifestations, including alveolar hemorrhage and glomerulonephritis, are caused by this capillary inflammation. We sought to clarify whether patients with AAV would have abnormal nailfold capillaries when evaluated with nailfold videocapillaroscopy. METHODS: Patients with a current diagnosis of AAV and a control group were identified for enrollment. Nailfold videocapillaroscopy images were used for a semiquantitative analysis on capillary density, morphology, dilation, and microhemorrhage after review by 2 rheumatologists. Disease characteristics, occurrence of recent disease flare, and presence of ANCA were recorded. RESULTS: Thirty-three patients with a diagnosis of AAV and 21 controls were recruited. The AAV group had a median age of 59 and 17 (52%) were women. Granulomatosis with polyangiitis was the most common diagnosis (19 [58%]), followed by eosinophilic granulomatosis with polyangiitis (7 [21%]) and microscopic polyangiitis (7 [21%]). Twenty-seven patients (82%) had positive ANCA tests. After assessment of capillary density, dilation, morphology, microhemorrhages, and disorganization, there were no statistically significant differences between the 2 groups. CONCLUSION: There was no evidence of differences in nailfold capillaroscopy abnormalities between those diagnosed with AAV and the control group. While this cohort was relatively small, we did not find a high enough prevalence or specific phenotype of capillary abnormalities that could aid in diagnosis or prognostication of these diseases in the clinical setting.

Dermatomyositis in Association With SARS-CoV-2 Infection or COVID-19 Vaccine.

OBJECTIVE: New-onset and relapsed dermatomyositis (DM) has been reported following SARS-CoV-2 infection or COVID-19 vaccination. This study aims to show the characteristics of a DM cohort after COVID-19 infection and vaccination. METHODS: A retrospective review was performed on patients treated for DM between March 1, 2020, and October 31, 2022. Charts were evaluated for the presence of new-onset DM or relapse of preexisting DM following either SARS-CoV-2 infection or COVID-19 vaccination. Data on symptom onset, timing of vaccination, type of vaccination, and disease characteristics were collected. RESULTS: Ninety-eight patients treated for DM at our institution in the Division of Rheumatology were included. In total, 12 of 98 patients (12.2%) experienced DM symptoms (either incident or relapse) following either infection or vaccination. Of the 12 patients who developed incident disease or relapse, 7 (58.3%) developed postinfection symptoms, and 8 (66.7%) developed symptoms after vaccination (3 patients had symptoms following both infection and vaccination). The mean onset of symptoms following COVID-19 infection was 3.2 days (median 0.5 days), and mean onset following COVID-19 vaccination was 5.75 days (median 3.5 days). Nine of 12 patients (75%) had a positive myositis-specific antibody, and the remaining 3 (25%) had myositis-associated antibodies. There was no predominant vaccine associated with the development of postvaccination DM symptoms. CONCLUSION: This retrospective review revealed a strong temporal relationship between DM symptoms and COVID-19 infection or vaccination in 12.2% of all patients with DM evaluated in our clinic during the pandemic. Additional studies are required to understand the possible pathophysiology behind this association.

Development and validation of a clinical breast cancer tool for accurate prediction of recurrence.

Given high costs of Oncotype DX (ODX) testing, widely used in recurrence risk assessment for early-stage breast cancer, studies have predicted ODX using quantitative clinicopathologic variables. However, such models have incorporated only small cohorts. Using a cohort of patients from the National Cancer Database (NCDB, n = 53,346), we trained machine learning models to predict low-risk (0-25) or high-risk (26-100) ODX using quantitative estrogen receptor (ER)/progesterone receptor (PR)/Ki-67 status, quantitative ER/PR status alone, and no quantitative features. Models were externally validated on a diverse cohort of 970 patients (median follow-up 55 months) for accuracy in ODX prediction and recurrence. Comparing the area under the receiver operating characteristic curve (AUROC) in a held-out set from NCDB, models incorporating quantitative ER/PR (AUROC 0.78, 95% CI 0.77-0.80) and ER/PR/Ki-67 (AUROC 0.81, 95% CI 0.80-0.83) outperformed the non-quantitative model (AUROC 0.70, 95% CI 0.68-0.72). These results were preserved in the validation cohort, where the ER/PR/Ki-67 model (AUROC 0.87, 95% CI 0.81-0.93, p = 0.009) and the ER/PR model (AUROC 0.86, 95% CI 0.80-0.92, p = 0.031) significantly outperformed the non-quantitative model (AUROC 0.80, 95% CI 0.73-0.87). Using a high-sensitivity rule-out threshold, the non-quantitative, quantitative ER/PR and ER/PR/Ki-67 models identified 35%, 30% and 43% of patients as low-risk in the validation cohort. Of these low-risk patients, fewer than 3% had a recurrence at 5 years. These models may help identify patients who can forgo genomic testing and initiate endocrine therapy alone. An online calculator is provided for further study.