Intestinal lymph as a readout of meal-induced GLP-1 release in an unrestrained rat model.

Intestinal lymph supposedly provides a readout for the secretion of intestinal peptides. We here assessed how mesenteric lymph duct (MLD) lymph levels of glucagon-like peptide (GLP-1), insulin, and metabolites [glucose and triglycerides (TG)] evolve after isocaloric high- and low-fat diet (HFD and LFD) meals and how they compare with hepatic portal vein (HPV) plasma levels. Moreover, we examined the effects of intraperitoneally administered GLP-1 (1 or 10 nmol/kg) on these parameters. At 20 min after the HFD meal onset, GLP-1 levels were higher in MLD lymph than in HPV plasma. No such difference occurred with the LFD meal. Intraperitoneal injections of 10 nmol/kg GLP-1 before meals enhanced the meal-induced increases in MLD lymph and HPV plasma GLP-1 levels except for the MLD lymph levels after the HFD meal. Intraperitoneal injection of 1 nmol/kg GLP-1 only increased HPV plasma GLP-1 levels at 60 min after the HFD meal. GLP-1 injections did not increase the MLD lymph or HPV plasma GLP-1 concentrations beyond the physiological range, suggesting that intraperitoneal GLP-1 injections can recapitulate the short-term effects of endogenous GLP-1. Dipeptidyl peptidase IV (DPP-IV) activity in MLD lymph was lower than in HPV plasma, which presumably contributed to the higher levels of GLP-1 in lymph than in plasma. Insulin and glucose showed similar profiles in MLD lymph and HPV plasma, whereas TG levels were higher in lymph than in plasma. These results indicate that intestinal lymph provides a sensitive readout of intestinal peptide release and potential action, in particular when fat-rich diets are consumed.

"Losing My Self": A Poet's Ironies and a Daughter's Reflections on Dementia.

What can we learn about the experience of dementia and about ways of being human when a poet describes her forgetting? My mother, the poet Shirley Kaufman, died in 2016 at the age of 93. She had dementia for many years. By her mid-80s, many of her poems probed the experience of forgetting, including questions about the nature of self, memory, and thought, and the location of the past and the future. Her experience of forgetting revealed in her ninth and last collection, the widely acclaimed Ezekiel's Wheels (2009), serves as my entry point for an exploration of the self as it becomes dislocated in time yet remains attuned to and consciously aware of that dislocation. That dual quality of my mother's experience is the central, ironic tension explored in this essay. An intimate ethnography, this essay connects my mother's late-life poetry with my own experience, both as a daughter who watched her mother's state of mind unfold and as an anthropologist with extensive experience studying aging, late-life identity, illness, and the culture of medicine. Through the insights of my mother's poetic language I show how dementia can expose ironic features of selfhood, communication, and life itself that are worth our discernment. My hope is that my analysis may focus our gaze on the inherent tension in this form of life and teach us something new about identity, memory, and what is shared among us, those with and without the condition we call dementia.

"It's not broke, so let's not try to fix it": why patients decline a cardiovascular implantable electronic device.

BACKGROUND: Few patients decline therapy of a cardiovascular implantable electronic device (CIED), and little is known about the characteristics or reasoning of those who do. Our objective was to describe the reasons why patients decline CIED implantation using qualitative methods. METHODS: Qualitative, engaging thematic analysis. Three patient focus groups led by two trained facilitators and one semi-structured interview guide. RESULTS: Of the 13 patients, two were women and all were white (median age [range], 65 [44-88] years). Five themes emerged: (1) don't mess with a good thing; (2) my health is good enough; (3) independent decision making; (4) it's your job, but it's my choice; and (5) gaps in learning. Most patients who decline CIEDs are asymptomatic. Other reasons to decline included feeling well, enjoying life, acceptance of the future, desire to try to improve health through diet and exercise, hearing of negative CIED experiences, and unwillingness to take on associated risks of CIED implantation. A medical record review showed that clinicians understand patients' reasons for declining CIED treatment. However, focus group data suggest that gaps in patients' knowledge around the purpose and function of CIEDs exist and patients may benefit from targeted education. CONCLUSIONS: Patients decline implantation of CIEDs for various reasons. Most patients who decline therapy are asymptomatic at the time of their device consult. Focus group information show data suggestive that device consultations should be enhanced to address gaps in patient learning and confirm knowledge transfer. Clinicians should revisit treatment options iteratively.

Randomized, Double-Blind, Placebo-Controlled Trial of MUC1 Peptide Vaccine for Prevention of Recurrent Colorectal Adenoma.

PURPOSE: To assess whether MUC1 peptide vaccine produces an immune response and prevents subsequent colon adenoma formation. PATIENTS AND METHODS: Multicenter, double-blind, placebo-controlled randomized trial in individuals age 40 to 70 with diagnosis of an advanced adenoma ≤1 year from randomization. Vaccine was administered at 0, 2, and 10 weeks with a booster injection at week 53. Adenoma recurrence was assessed ≥1 year from randomization. The primary endpoint was vaccine immunogenicity at 12 weeks defined by anti-MUC1 ratio ≥2.0. RESULTS: Fifty-three participants received the MUC1 vaccine and 50 placebo. Thirteen of 52 (25%) MUC1 vaccine recipients had a ≥2-fold increase in MUC1 IgG (range, 2.9-17.3) at week 12 versus 0/50 placebo recipients (one-sided Fisher exact P < 0.0001). Of 13 responders at week 12, 11 (84.6%) responded to a booster injection at week 52 with a ≥2-fold increase in MUC1 IgG measured at week 55. Recurrent adenoma was observed in 31 of 47 (66.0%) in the placebo group versus 27 of 48 (56.3%) in the MUC1 group [adjusted relative risk (aRR), 0.83; 95% confidence interval (CI), 0.60-1.14; P = 0.25]. Adenoma recurrence occurred in 3/11 (27.3%) immune responders at week 12 and week 55 (aRR, 0.41; 95% CI, 0.15-1.11; P = 0.08 compared with placebo). There was no difference in serious adverse events. CONCLUSIONS: An immune response was observed only in vaccine recipients. Adenoma recurrence was not different than placebo, but a 38% absolute reduction in adenoma recurrence compared with placebo was observed in participants who had an immune response at week 12 and with the booster injection.

Loneliness and Social Media Use Among Adolescents with Psychiatric Disorders.

Studies have demonstrated that a prolonged feeling of loneliness is a major risk factor for psychopathology among children and adolescents. The purpose of this study was to evaluate the association between patterns of social media use with loneliness and psychopathology among 65 adolescents who were diagnosed with psychiatric disorders and treated at a psychiatric outpatient clinic in Israel. Social capital (online and offline) was negatively associated with loneliness. There was no association between loneliness and patterns of social media use, age, gender, psychiatric diagnosis, or disease severity. Our findings indicate that both online and offline social capital are associated with loneliness, and highlight the importance of studying the effect of peer online social support in alleviating loneliness.

Toward a phenomenology of boundaries in medicine: chronic illness experience in the case of stroke.

In this article I explore the ambiguous nature of the boundaries of authority and responsibility in medicine by discussing two dimensions of patients' response to long-term ramifications of stroke. A phenomenological examination of the chronic illness experience is employed to identify how and the extent to which medicine's power both responds to and affects the individual sufferer. Rather than interpret the illness process as a dichotomy between medical control and patient autonomy, this article presents some assumptions about the boundaries of medical authority that are held by patients and practitioners alike. I suggest that dilemmas that patients face following a stroke are responses to medicine's limits and scope as well as reflections of medicine's goals and values. I argue that phenomenological studies of existential responses to illness are necessary in order to understand cultural sources of unmet expectations resulting from chronic conditions.

Medicare, ethics, and reflexive longevity: governing time and treatment in an aging society.

The clinical activities that constitute longevity making in the United States are perhaps the quintessential example of a dynamic modern temporality, characterized by the quest for risk reduction, the powerful progress narratives of science and medicine, and the personal responsibility of calculating the worth of more time in relation to medical options and age. This article explores how medicine materializes and problematizes time through a discussion of ethicality-in this case, the form of governance in which scientific evidence, Medicare policy and clinical knowledge and practice organize first, what becomes "thinkable" as the best medicine, and second, how that kind of understanding shapes a telos of living. Using liver disease and liver transplantation in the United States as my example, I explore the influence of Medicare coverage decisions on treatments, clinical standards, and ethical necessity. Reflexive longevity-a relentless future-thinking about life itself-is one feature of this ethicality.

Making longevity in an aging society: linking Medicare policy and the new ethical field.

Life-extending interventions for older persons are changing medical knowledge and societal expectations about longevity. Today's consciousness about growing older is partly shaped by a new form of ethics, constituted by and enabled through the routines and institutions that comprise ordinary clinical care. Unlike bioethics, whose emphasis is on clinical decision-making in individual situations, this new form of ethics is exceptionally diffuse and can be characterized as an ethical field. It is located in and shaped by health-care policies, standard technologies, and clinical evidence, and it emerges in what patients and families come to need and want. Three developments illustrate this ethical field at work: the changing nature of disease, especially the ascent of risk awareness and risk-based strategies for life extension; the role of technology in reshaping the ends of medicine; and the role of Medicare policy in creating need and ethical necessity. Medicare's expanding criteria for payment coverage of liver transplantation and implantable cardiac devices illustrate the pervasive logic of this new form of ethics. The powerful connection between the technological imperative and its ethical necessity is rarely mentioned in Medicare reform debates.

Time, clinic technologies, and the making of reflexive longevity: the cultural work of time left in an ageing society.

Developments in clinical intervention are having a profound impact on health and health behaviours in late life and on ideas about longevity and the appropriate time for death. The fact that the timing of death is even considered to be a controllable event is a relatively new cultural phenomenon. The activities that make up life extension, like other medical practices scrutinised by social scientists, constitute a site for the emergence of new forms of subjectivity. For older adults the clinical encounter forces a calculation about how much time left is wanted in relation to age. The twin dimensions of the transformation of time highlighted in this article - the control over the timing of death and the creation of time left - both contribute to and are a widespread effect of biomedicalisation in affluent sectors of society. Through three stories this paper begins to map the cultural work that the concept, time left, does, the socio-medical ways in which that notion is talked about, organised and calculated in the American clinic today. It asks, what kind of subject emerges when longevity, imbued with the technological, becomes a reflexive practice and an object of intervention and apparent choice?

Time, Clinic Technologies, and the Making of Reflexive Longevity: The cultural work of 'time left' in an aging society.

Developments in clinical intervention are having a profound impact on health and health behaviors in late life and on ideas about longevity and the appropriate time for death. The fact that the timing of death is even considered to be a controllable event is a relatively new cultural phenomenon. The activities that make up life extension, like other medical practices scrutinized by social scientists, constitute a site for the emergence of new forms of subjectivity. For older adults the clinical encounter forces a calculation about how much 'time left' is wanted in relation to age. The twin dimensions of the transformation of time highlighted in this essay -- the control over the timing of death and the creation of 'time left' -- both contribute to and are a widespread effect of biomedicalization in affluent sectors of society. Through three stories this essay begins to map the cultural work that the concept, 'time left,' does, the socio-medical ways in which that notion is talked about, organized and calculated in the American clinic today. It asks, what kind of subject emerges when longevity, imbued with the technological, becomes a reflexive practice and an object of intervention and apparent choice?

Roux-en-Y gastric bypass surgery reprograms enterocyte triglyceride metabolism and postprandial secretion in rats.

OBJECTIVE: Roux-en-Y gastric bypass (RYGB) surgery produces rapid and persistent reductions in plasma triglyceride (TG) levels associated with fewer cardiovascular events. The mechanisms of the reduction in systemic TG levels remain unclear. We hypothesized that RYGB reduces intestinal TG secretion via altered enterocyte lipid handling. METHODS: RYGB or Sham surgery was performed in diet-induced obese, insulin-resistant male Sprague-Dawley rats. First, we tested whether RYGB reduced test meal-induced TG levels in the intestinal lymph, a direct readout of enterocyte lipid secretion. Second, we examined whether RYGB modified TG enterocyte secretion at the single lipid level and in comparison to other lipid subclasses, applying mass spectrometry lipidomics to the intestinal lymph of RYGB and Sham rats (0-21 days after surgery). Third, we explored whether RYGB modulated the metabolic characteristics of primary enterocytes using transcriptional and functional assays relevant to TG absorption, reesterification, storage in lipid droplets, and oxidation. RESULTS: RYGB reduced overall postprandial TG concentrations compared to Sham surgery in plasma and intestinal lymph similarly. RYGB reduced lymphatic TG concentrations more than other lipid subclasses, and shifted the remaining TG pool towards long-chain, unsaturated species. In enterocytes of fasted RYGB rats, lipid uptake was transcriptionally (Fatp4, Fabp2, Cd36) and functionally reduced compared to Sham, whereas TG reesterification genes were upregulated. CONCLUSION: Our results show that RYGB substantially reduces intestinal TG secretion and modifies enterocyte lipid absorption and handling in rats. These changes likely contribute to the improvements in the plasma TG profile observed after RYGB in humans.

The Association Between Assisted Living Direct Care Worker End-of-Life Training and Hospice Use Patterns.

As resident acuity levels increase for those who reside in assisted living (AL), states allow for hospice care provision in AL. End-of-life care training for staff can potentially increase the awareness of benefits of hospice care for AL residents. This study examined the association between AL staff trained in end-of-life care and hospice utilization in a sample of ALs (n = 45) in Florida. The sample included ALs (n = 21) with a low percentage (≤59%) and ALs (n = 24) with a high percentage (≥60%) of staff trained in end-of-life care as reported by AL directors. Zero-inflated negative binomial regression (ZINB) indicated that ALs in the high percentage of staff trained group were associated with a 3.64% greater utilization of hospice than ALs in the low percentage of staff trained group. Implementation of required staff training specific to care for the terminally ill as required in some states could potentially improve resident access to hospice care.

Enhancing enterocyte fatty acid oxidation in mice affects glycemic control depending on dietary fat.

Studies indicate that modulating enterocyte metabolism might affect whole body glucose homeostasis and the development of diet-induced obesity (DIO). We tested whether enhancing enterocyte fatty acid oxidation (FAO) could protect mice from DIO and impaired glycemic control. To this end, we used mice expressing a mutant form of carnitine palmitoyltransferase-1a (CPT1mt), insensitive to inhibition by malonyl-CoA, in their enterocytes (iCPT1mt) and fed them low-fat control diet (CD) or high-fat diet (HFD) chronically. CPT1mt expression led to an upregulation of FAO in the enterocytes. On CD, iCPT1mt mice had impaired glycemic control and showed concomitant activation of lipogenesis, glycolysis and gluconeogenesis in their enterocytes. On HFD, both iCPT1mt and control mice developed DIO, but iCPT1mt mice showed improved glycemic control and reduced visceral fat mass. Together these data indicate that modulating enterocyte metabolism in iCPT1mt mice affects glycemic control in a body weight-independent, but dietary fat-dependent manner.

The value of "life at any cost": talk about stopping kidney dialysis.

With the trend toward an older, sicker dialysis population in the USA, discussions of ethical issues surrounding dialysis have shifted from concerns about access to and availability of the therapy, to growing unease about non-initiation and treatment discontinuation. Recent studies report treatment withdrawal as the leading cause of death among elderly dialysis patients. Yet, the actual activities that move patients toward stopping treatment often remain obscure, even to clinicians and patients themselves. This paper explores that paradox, drawing on anthropological research among patients over age 70, their families, and clinicians in two California renal dialysis units. It concludes that many older patients sacrifice a sense of choice about dialysis in the present to maintain "choice" as both value and possibility for the future. Even so, patients desire more information and communication, provided earlier in their illness, about prognosis, how long they can expect to be on dialysis, and what the impact of the treatment will be on their daily lives. That, with time, there is a transition to be made from dialysis as "treatment" to end of life care could be better explained and managed to alleviate patients' confusion and unneeded isolation.

Clinical life: expectation and the double edge of medical promise.

This article introduces the concept of clinical life to capture a form of life produced in the pursuit and wake of medically achieved longevity. Relying on the retrospective accounts of 28 individuals over age 70 who have undergone cardiac bypass surgery, angioplasty or a stent procedure, as well as interviews with their families and with clinicians, we examine three features of clinical life. First, patients do not distinguish between clinical possibility and clinical promise, and thus assume that life can and will be improved by medical intervention in late life. Rather than anticipating a range of potential treatment outcomes, patients therefore expect the best-case scenario: that medical procedures will reverse aging, disease and the march of time. Second, patients then assess the value of their post-procedure lives in accordance with that expectation. Norms regarding what life 'should be like' at particular ages are continually recalibrated to the horizon of what is clinically possible. And third, the price of living longer entails a double-edged relationship with the clinic--it generates opportunities for bodily restoration and increased self-worth but also creates ambivalence about the value of life. This latter feature of clinical life is rarely publicly acknowledged in an environment that emphasizes medical promise.

Old age, life extension, and the character of medical choice.

OBJECTIVES: This qualitative, ethnographic study explores the character and extent of medical choice for life-extending procedures on older adults. It examines the sociomedical features of treatment that shape health care provider understandings of the nature of choice, and it illustrates the effects of treatment patterns on patients' perspectives of their options for life extension. METHODS: By using participant observation in outpatient clinics and face-to-face interviews, we spoke with a convenience sample of 38 health professionals and 132 patients aged 70 or older who had undergone life-extending medical procedures. We asked providers and patients open-ended questions about their understandings of medical choice for cardiac procedures, dialysis, and kidney transplant. RESULTS: Neither patients nor health professionals made choices about the start or continuation of life-extending interventions that were uninformed by the routine pathways of treatment; the pressures of the technological imperative; or the growing normalization, ease, and safety of treating ever older patients. We found a difference among cardiac, dialysis, and transplant procedures regarding the locus of responsibility for maintaining and extending life. DISCUSSION: Provider and patient practices together reveal how the standard use of medical procedures at ever older ages trumps patient-initiated decision making.