Denying Death: The Terminally Critically Ill.

We describe a subgroup of the Chronically Critically Ill (CCI) we call the Terminally Critically Ill as demonstrated by terminally ill cancer patients. These cancer patients, though clearly terminally ill and with relatively short prognoses, can be kept alive for extended periods with medical interventions aimed at treating the complications of the cancer and cancer treatment. Such interventions can be painful, exhausting, costly and may interfere with attending to end of life concerns. We present a typical (composite) case and discuss ethical concerns regarding this growing subgroup of the chronically critically ill patients for whom death is routinely denied and delayed for extended periods.

Impacts of livestock grazing on the probability of burning in wildfires vary by region and vegetation type in California.

Wildfire activity has recently increased in California, impacting ecosystems and human well-being. California's rangelands are complex social-ecological systems composed of multiple ecosystems and the people who live and work in them. Livestock grazing has been proposed as a tool for reducing wildfire activity. Here, we explore how grazing affects wildfire at large spatial scales, assessing burn probability on rangelands with different grazing levels. We collected grazing data by surveying 140 large private landowners in three social-ecological regions: California's North Bay, Central Coast, and Central Valley and Foothills. Using pre-regression matching and mixed effects regression, we calculate the burn probability from 2001 to 2017 in points sampled from grazed and ungrazed properties in each region in grasslands, shrub/scrublands, and forests. We find that in the Central Coast and North Bay, annual burn probability decreases as stocking levels increase across all vegetation types, with reductions of 0.008-0.036. In the Central Valley and Foothills, the relationship is complex, with burn probability increasing over some grazing levels and variations in the effect of higher stocking densities. Our results indicate that livestock grazing may reduce annual burn probability in some regions and ecosystems in California, providing the first large-scale assessment of this relationship.

Self-Resolving Vulvar Breast Tissue Arising in the Post-Partum Setting: A Case Report and Review of Literature.

INTRODUCTION: During the postpartum period, breast engorgement in preparation for lactation may trigger the onset of vulvar labial nodules that present with pain and discomfort. These labial nodules may originate from ectopic breast tissue and can rarely present in women during the postpartum period in the labia majora. MAIN ISSUE: A 37-year-old African American female, gravida 1 para 1, presented to the Loma Linda University Medical Center with complaints of new onset labial swelling worsening 6 days following her full term spontaneous vaginal delivery. Additionally, our respondent complained of difficulty breastfeeding due to intermittent lack of milk production. She reported bilateral breast engorgement with tenderness, despite frequent attempts at breastfeeding. The respondent's presentation did not meet the criteria for other common differentials due to the physical characteristics of the nodules. The location of the nodules along the milk line led physicians to believe that the respondent was presenting with engorged extra-mammary breast tissue in the labia majora. MANAGEMENT: The participant was told to observe her course over the next few days as she began to have milk production and ejection. The respondent was seen in clinic for her 6-week postpartum visit, and was no longer complaining of difficulty with breastfeeding. The labial nodules had resolved spontaneously. CONCLUSION: A literature search yielded no case reports that described a case of an extra-mammary vulvar mass that self-resolved with resolution of breast engorgement. The infrequent presentation of extra-mammary vulvar tissue makes it difficult to conclude a guideline for diagnosis and management.

An Algorithmic Approach to Patients Who Refuse Care But Lack Medical Decision-Making Capacity.

Situations in which patients lack medical decision-making (MDM) capacity raise ethical challenges, especially when the patients decline care that their surrogate decision makers and/or clinicians agree is indicated. These patients are a vulnerable population and should receive treatment that is the standard of care, in line with their the values of their authentic self, just as any other patient would. But forcing treatment on patients who refuse it, even though they lack capacity, carries medical and psychological risks to the patients and the hospital staff. It is also often impractical to force some treatments, especially in the long term. For example, independent of the ethical "should" question, how would one force hemodialysis for the rest of a patient's life, or force a surgery that requires weeks of post-operative physical therapy? In this article we present a novel algorithm that can help clinicians with ethical and practical decision making, with the goals of achieving the best outcomes for patients and reducing moral distress for their caretakers and clinicians.

High-density lipoprotein metabolism in human apolipoprotein B(100) transgenic/brown adipose tissue deficient mice: a model of obesity-induced hyperinsulinemia.

Obese and diabetic humans display decreased plasma high-density lipoprotein cholesterol (HDL-C) concentrations and an increased risk for coronary heart disease. However, investigation on HDL metabolism in obesity with a particular emphasis on hepatic ATP-binding cassette transporter A1 (ABCA1), the primary factor for HDL formation, has not been well studied. Human apolipoprotein B(100) transgenic (hApoB(tg)) and brown adipose tissue deficient (BATless) mice were crossed to generate hApoB(tg)/BATless mice. Male and female hApoB(tg) and hApoB(tg)/BATless mice were maintained on either a regular rodent chow diet or a diet high in fat and cholesterol until 24 weeks of age. The hApoB(tg)/BATless mice that were fed a HF/HC diet became obese, developed hepatic steatosis, and had significantly elevated plasma insulin levels compared with their hApoB(tg) counterparts, but plasma concentrations of total cholesterol, HDL-C, triglycerides, and free fatty acids and lipoprotein distribution between genotypes were not significantly different. Hepatic expression of genes encoding HDL-modifying factors (e.g., scavenger receptor, class B, type I, hepatic lipase, lecithin:cholesterol acyltransferase, and phospholipid transfer protein) was either altered significantly or showed a trend of difference between 2 genotypes of mice. Importantly, hepatic protein levels of ABCA1 were significantly lowered by ∼35% in male obese hApoB(tg)/BATless mice with no difference in mRNA levels compared with hApoB(tg) counterparts. Despite reduced hepatic ABCA1 protein levels, plasma HDL-C concentrations were not altered in male obese hApoB(tg)/BATless mice. The result suggests that hepatic ABCA1 may not be a primary contributing factor for perturbations in HDL metabolism in obesity-induced hyperinsulinemia.

Cortical mechanics and meiosis II completion in mammalian oocytes are mediated by myosin-II and Ezrin-Radixin-Moesin (ERM) proteins.

Cell division is inherently mechanical, with cell mechanics being a critical determinant governing the cell shape changes that accompany progression through the cell cycle. The mechanical properties of symmetrically dividing mitotic cells have been well characterized, whereas the contribution of cellular mechanics to the strikingly asymmetric divisions of female meiosis is very poorly understood. Progression of the mammalian oocyte through meiosis involves remodeling of the cortex and proper orientation of the meiotic spindle, and thus we hypothesized that cortical tension and stiffness would change through meiotic maturation and fertilization to facilitate and/or direct cellular remodeling. This work shows that tension in mouse oocytes drops about sixfold during meiotic maturation from prophase I to metaphase II and then increases ∼1.6-fold upon fertilization. The metaphase II egg is polarized, with tension differing ∼2.5-fold between the cortex over the meiotic spindle and the opposite cortex, suggesting that meiotic maturation is accompanied by assembly of a cortical domain with stiffer mechanics as part of the process to achieve asymmetric cytokinesis. We further demonstrate that actin, myosin-II, and the ERM (Ezrin/Radixin/Moesin) family of proteins are enriched in complementary cortical domains and mediate cellular mechanics in mammalian eggs. Manipulation of actin, myosin-II, and ERM function alters tension levels and also is associated with dramatic spindle abnormalities with completion of meiosis II after fertilization. Thus, myosin-II and ERM proteins modulate mechanical properties in oocytes, contributing to cell polarity and to completion of meiosis.

A review of fatty acid profiles and antioxidant content in grass-fed and grain-fed beef.

Growing consumer interest in grass-fed beef products has raised a number of questions with regard to the perceived differences in nutritional quality between grass-fed and grain-fed cattle. Research spanning three decades suggests that grass-based diets can significantly improve the fatty acid (FA) composition and antioxidant content of beef, albeit with variable impacts on overall palatability. Grass-based diets have been shown to enhance total conjugated linoleic acid (CLA) (C18:2) isomers, trans vaccenic acid (TVA) (C18:1 t11), a precursor to CLA, and omega-3 (n-3) FAs on a g/g fat basis. While the overall concentration of total SFAs is not different between feeding regimens, grass-finished beef tends toward a higher proportion of cholesterol neutral stearic FA (C18:0), and less cholesterol-elevating SFAs such as myristic (C14:0) and palmitic (C16:0) FAs. Several studies suggest that grass-based diets elevate precursors for Vitamin A and E, as well as cancer fighting antioxidants such as glutathione (GT) and superoxide dismutase (SOD) activity as compared to grain-fed contemporaries. Fat conscious consumers will also prefer the overall lower fat content of a grass-fed beef product. However, consumers should be aware that the differences in FA content will also give grass-fed beef a distinct grass flavor and unique cooking qualities that should be considered when making the transition from grain-fed beef. In addition, the fat from grass-finished beef may have a yellowish appearance from the elevated carotenoid content (precursor to Vitamin A). It is also noted that grain-fed beef consumers may achieve similar intakes of both n-3 and CLA through the consumption of higher fat grain-fed portions.

A role for the C. elegans L1CAM homologue lad-1/sax-7 in maintaining tissue attachment.

The L1 family of cell adhesion molecules (L1CAMs) is important for neural development. Mutations in one of the human L1CAM genes, L1, can result in several neurological syndromes, the symptoms of which are variably penetrant. The physiological cause of these symptoms, collectively termed CRASH, is not clear. Caenorhabditis elegans animals genetically null for the L1CAM homologue LAD-1, exhibit variably penetrant pleiotropic phenotypes that are similar to the CRASH symptoms; thus the C. elegans lad-1 mutant provides an excellent model system to study how disruption of L1 leads to these abnormalities. These phenotypes include uncoordinated movements, variable embryonic lethality, and abnormal neuronal distribution and axon trajectories. Our analysis revealed that many of these phenotypes are likely a result of tissue detachment.