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Cardiovascular disease (CVD) remains the number one cause of death worldwide. Women are at increased risk of death from CVD, but the mechanisms for how and why this occurs remain elusive. One subset of women who are exceptionally vulnerable to CVD are those with rheumatic diseases (RDs). Indeed, women account for 80% of all RDs, disorders that encompass a broad range of autoimmune and autoinflammatory diseases that lead to chronic inflammation and pathology. The clear association of increased CVD risk in women with RD is thought to be mediated by a number of factors, including RD pathology itself, pharmacological induction of CVD, and/or as yet unidentified mechanisms. As such, elucidation of the causes and treatments of these pathologies has given rise to a new subspecialty of cardiology: cardio-rheumatology. Here, we review and discuss the CVD risks in patients with RDs, the associated sex disparities in RD and CVD care, as well as the current therapeutic and interventional options available to specifically help women with RDs. We hope this discussion will provide guidance and support to patients, as well as to cardio-rheumatologists, as these groups are the most uniquely positioned to radically improve CVD care in these individuals. Moreover, we are hopeful this discussion may lead to better, more efficacious approaches to treating these disorders in women in the near future., Competing Interests: Maria Irene Kontaridis has received grant funding from Onconova Therapeutics and is a consultant for BioMarin Pharmaceutical Inc.; both funding and consulting projects are independent of the work in this manuscript and have no overlap with the submitted work. Samantha Le Sommer has no competing interests to declare.

Background: Joint pain is composed of both spontaneous and movement-induced pain. In animal models, static bodyweight distribution is a surrogate for spontaneous joint pain. However, there are no commercially-available instruments that measure static bodyweight distribution in normal, pronograde rodents., New Method: We designed a Static Horizontal Incapacitance Meter (SHIM) to measure bodyweight distribution in pronograde standing rodents. We assessed the device for feasibility, repeatability, and sensitivity to quantify hindlimb bodyweight distribution. Mice and rats with unilateral inflammatory pain induced by subcutaneous injections of capsaicin or Complete Freund's Adjuvant (CFA) into the plantar surface of the left hind paw were used to measure static weight-bearing. The ability to attenuate inflammatory pain-associated weight-bearing asymmetry was tested by administering a non-steroidal anti-inflammatory drug, meloxicam., Results: The SHIM's ability to detect significant reductions in limb loading on the injected hindlimb in mice and rats was validated using both acute and sub-chronic pain models. Treatment with meloxicam partially reversed CFA-induced effects., Comparison With Existing Methods: In contrast with assays that measure kinetic or static weight-bearing forces (e.g., walking, or standing at a 45 ° incline), the SHIM allows evaluation of weight-bearing in rodents that are standing at rest in their normal pronograde position., Conclusions: The SHIM successfully detected: (a) asymmetric weight-bearing in acute and sub-chronic pain models; and (b) the analgesic effects of meloxicam. This study provides a novel tool to objectively evaluate limb use dysfunction in rodents., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Few tools are available to comprehensively describe the unique social-emotional skill profiles of youth with autism spectrum disorder (ASD). The present study describes the usability, reliability, and validity of SELweb, a normed, web-based assessment designed to measure four core social-emotional domains, when used to measure these skills in a sample of 57 well-characterized youth with ASD (ages 6-10 years with IQ ≥ 80). SELweb measures facial emotion recognition, theory of mind, social problem solving, and self-control. SELweb was well tolerated and yielded scores with reliabilities comparable to those found in normative samples. SELweb scores showed good evidence of convergent and discriminant validity for three of the four skills it was designed to assess. Mean deficits were found for theory of mind, social problem solving, and self-control, whereas no mean deficits were found for emotion recognition. Individual profiles varied considerably, suggesting the sensitivity of SELweb to the within- and between-person individual differences among youth with ASD. Findings support the usefulness and accessibility of SELweb as a tool for measuring complex social-emotional skill profiles in youth with ASD. Autism Res 2019, 12: 1260-1271. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: No single, simple, high-quality test exists that measures multiple social thinking skills directly in children with autism spectrum disorder (ASD). The present study suggests that SELweb, a web-based assessment system, is an effective and valid way to measure how children with ASD think about and understand social and emotional information, and is able to capture strengths and weaknesses experienced by children with ASD., (© 2019 International Society for Autism Research, Wiley Periodicals, Inc.)

We developed and characterized monoclonal antibodies directed against the amino-terminal and carboxy-terminal regions of human and mouse sclerostin (scl). Amino-terminal and carboxy-terminal scl peptides with limited homology to scl domain-containing protein-1 were synthesized using f-moc chemistry. The peptides were conjugated to keyhole limpet hemocyanin and the conjugates were used for immunization of mice. Monoclonal antibodies were obtained and characterized using bacterially expressed and insect cell-expressed recombinant scl. The amino-terminal (IgG 2aK) and carboxy-terminal (IgG 2bK) antibodies bound bioactive sclerostin that was expressed in an insect-cell expression system with dissociation constants in the nanomolar range. The antibodies are potentially useful agents that can be used for modulating sclerostin bioactivity.

gly96/IEX 1 is a growth- and apoptosis-regulating, immediate early gene that is widely expressed in epithelial and vascular tissues. In vascular tissues, expression of the gene is induced by mechanical stretch, and overexpression of the gene prevents injury-induced vascular smooth muscle hypertrophy and neointimal hyperplasia. We now show that deletion of the gly96/IEX-1 gene in mice is associated with development of elevated blood pressure, cardiac hypertrophy, and diminished fractional shortening of the left ventricle. Systolic blood pressure in conscious male gly96/IEX-1-/- mice is 20-25 mmHg higher than in gly96/IEX-1+/+ mice. Serum and/or urine concentrations of sodium, potassium, creatinine, angiotensin II, corticosterone, aldosterone, epinephrine, norepinephrine, prostaglandin E2, thromboxane B2, prostaglandin-6-keto-1alpha, nitrites and nitrates, cAMP, and cGMP are normal in gly96/IEX-1-/- mice. Alterations in dietary sodium intake do not alter blood pressure in gly96/IEX-1-/- mice. Aortic mRNAs for endothelial nitric oxide synthase, guanylate cyclase-alpha, and cGMP kinase-1 are increased in gly96/IEX-1-/- mice. Treatment with Nomega-nitro-L-arginine methyl ester or L-arginine does not alter blood pressure in gly96/IEX-1-/- mice. Gly96/IEX-1-/- mice respond to infused sodium nitroprusside with decrements in blood pressure similar to those seen in wild-type littermate mice. In contrast to gly96/IEX-1 transgenic mice that have abnormalities in immune function, gly96/IEX-1-/- mice have normal lymphoid tissue architecture and a normal complement of T and B cells in lymphoid tissues. Ablation of the gly96/IEX-1 gene results in hypertension and cardiac hypertrophy, suggesting a novel role for this gene in cardiovascular physiology.