Maternal nano-titanium dioxide inhalation exposure alters placental cyclooxygenase and oxidant balance in a sexually dimorphic manner.

The placenta plays a critical role in nutrient-waste exchange between the maternal and fetal circulation, and thus impacts fetal growth and development. We have previously shown that nano-titanium dioxide (nano-TiO2) inhalation exposure during gestation decreased fetal female pup and placenta mass [1], which persists in the following generation [2]. In utero exposed females, once mated, their offspring's placentas had increased capacity for H2O2 production. Generation of oxidants such as hydrogen peroxide (H2O2), have been shown to impact cyclooxygenase activity, specifically metabolites such as prostacyclin (PGI2) or thromboxane (TXA2). Therefore, we hypothesized that maternal nano-TiO2 inhalation exposure during gestation results in alterations in placental production of prostacyclin and thromboxane mediated by enhanced H2O2 production in a sexually dimorphic manner. Pregnant Sprague-Dawley rats were exposed to nano-TiO2 aerosols or filtered air (sham--control) from gestational day (GD) 10-19. Dams were euthanized on GD 20, and fetal serum and placental tissue were collected based on fetal sex. Fetal placental zones (junctional zone (JZ) and labyrinth zone (LZ)) were assessed for xanthine oxidoreductase (XOR) activity, H2O2, and catalase activity, as well as 6-keto-PGF1α and TXB2 levels. Nano-TiO2 exposed fetal female LZ demonstrated significantly greater XOR activity compared to exposed males. Exposed fetal female LZ also demonstrated significantly diminished catalase activity compared to sham-control females. Exposed fetal female LZ had significantly increased abundance of 6-keto-PGF1α compared to sham-control females and increased TXB2 compared to exposed males. In the aggregate these data indicate that maternal nano-TiO2 inhalation exposure has a greater impact on redox homeostasis and PGI2/TXA2 balance in the fetal female LZ. Future studies need to address if treatment with an XO inhibitor during gestation can prevent diminished fetal female growth during maternal nano-TiO2 inhalation exposure.

AIDS-Related Kaposi Sarcoma Associated with Steroid-Unresponsive Periorbital Lymphedema that Responded to Chemotherapy.

BACKGROUND As an AIDS-defining illness, the neoplasm Kaposi sarcoma (KS) classically presents as cutaneous lesions that are often associated with periorbital edema. This association with KS is important because it frequently leads to the misuse of steroids in HIV-infected patients. This report presents 2 cases of AIDS-related Kaposi sarcoma (AIDS-KS) associated with severe steroid-unresponsive periorbital lymphedema that responded to chemotherapy. CASE REPORT Case 1: A 30-year-old African-American man with KS-related periorbital edema suffered progression after receiving multiple corticosteroids for a presumed hypersensitivity reaction. After multiple hospitalizations, the patient's KS had disseminated, and he eventually opted for hospice. Case 2: A 29-year-old White male with recurrent facial edema had been repeatedly treated with corticosteroids for impending anaphylaxis reactions. He had multiple admissions with similar presentations, and it was found that his KS had progressed. After receiving chemotherapy, his facial edema has not recurred. CONCLUSIONS The failure to recognize periorbital edema as tumor-associated edema has direct consequences for the management of AIDS-KS. In addition to a delay in administering chemotherapy, the mischaracterization of periorbital edema as a hypersensitivity/allergic reaction often prompts the use of corticosteroids, potentially exacerbating the underlying AIDS-KS. Despite the current evidence, clinicians continue to order steroids in advanced AIDS-KS patients presenting with periorbital edema. Although that management is started with the best intentions and done with concerns for airway compromise, this anchoring bias could lead to devastating consequences and a rather poor prognosis.

NUDT7 regulates total hepatic CoA levels and the composition of the intestinal bile acid pool in male mice fed a Western diet.

Nudix hydrolase 7 (NUDT7) is an enzyme that hydrolyzes CoA species, is highly expressed in the liver, and resides in the peroxisomes. Peroxisomes are organelles where the preferential oxidation of dicarboxylic fatty acids occurs and where the hepatic synthesis of the primary bile acids cholic acid and chenodeoxycholic acid is completed. We previously showed that liver-specific overexpression of NUDT7 affects peroxisomal lipid metabolism but does not prevent the increase in total liver CoA levels that occurs during fasting. We generated Nudt7-/- mice to further characterize the role that peroxisomal (acyl-)CoA degradation plays in the modulation of the size and composition of the acyl-CoA pool and in the regulation of hepatic lipid metabolism. Here, we show that deletion of Nudt7 alters the composition of the hepatic acyl-CoA pool in mice fed a low-fat diet, but only in males fed a Western diet does the lack of NUDT7 activity increase total liver CoA levels. This effect is driven by the male-specific accumulation of medium-chain dicarboxylic acyl-CoAs, which are produced from the ß-oxidation of dicarboxylic fatty acids. We also show that, under conditions of elevated synthesis of chenodeoxycholic acid derivatives, Nudt7 deletion promotes the production of tauromuricholic acid, decreasing the hydrophobicity index of the intestinal bile acid pool and increasing fecal cholesterol excretion in male mice. These findings reveal that NUDT7-mediated hydrolysis of acyl-CoA pathway intermediates in liver peroxisomes contributes to the regulation of dicarboxylic fatty acid metabolism and the composition of the bile acid pool.

A Comprehensive COVID-19 Daily News and Medical Literature Briefing to Inform Health Care and Policy in New Mexico: Implementation Study.

BACKGROUND: On March 11, 2020, the New Mexico Governor declared a public health emergency in response to the COVID-19 pandemic. The New Mexico medical advisory team contacted University of New Mexico (UNM) faculty to form a team to consolidate growing information on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its disease to facilitate New Mexico's pandemic management. Thus, faculty, physicians, staff, graduate students, and medical students created the "UNM Global Health COVID-19 Intelligence Briefing." OBJECTIVE: In this paper, we sought to (1) share how to create an informative briefing to guide public policy and medical practice and manage information overload with rapidly evolving scientific evidence; (2) determine the qualitative usefulness of the briefing to its readers; and (3) determine the qualitative effect this project has had on virtual medical education. METHODS: Microsoft Teams was used for manual and automated capture of COVID-19 articles and composition of briefings. Multilevel triaging saved impactful articles to be reviewed, and priority was placed on randomized controlled studies, meta-analyses, systematic reviews, practice guidelines, and information on health care and policy response to COVID-19. The finalized briefing was disseminated by email, a listserv, and posted on the UNM digital repository. A survey was sent to readers to determine briefing usefulness and whether it led to policy or medical practice changes. Medical students, unable to partake in direct patient care, proposed to the School of Medicine that involvement in the briefing should count as course credit, which was approved. The maintenance of medical student involvement in the briefings as well as this publication was led by medical students. RESULTS: An average of 456 articles were assessed daily. The briefings reached approximately 1000 people by email and listserv directly, with an unknown amount of forwarding. Digital repository tracking showed 5047 downloads across 116 countries as of July 5, 2020. The survey found 108 (95%) of 114 participants gained relevant knowledge, 90 (79%) believed it decreased misinformation, 27 (24%) used the briefing as their primary source of information, and 90 (79%) forwarded it to colleagues. Specific and impactful public policy decisions were informed based on the briefing. Medical students reported that the project allowed them to improve on their scientific literature assessment, stay current on the pandemic, and serve their community. CONCLUSIONS: The COVID-19 briefings succeeded in informing and guiding New Mexico policy and clinical practice. The project received positive feedback from the community and was shown to decrease information burden and misinformation. The virtual platforms allowed for the continuation of medical education. Variability in subject matter expertise was addressed with training, standardized article selection criteria, and collaborative editing led by faculty.