"I see it very much as an end-of-life food" - Barriers to oral nutritional supplement adherence, views from healthy older adults.

Malnutrition affects approximately one quarter of UK adults aged 65 years and over. As the global demographic shift continues, malnutrition is expected to increase. Oral nutritional supplements (ONS) are used both to prevent and to treat malnutrition. However, their effectiveness is compromised by poor adherence, and it is not well understood what contributes to this. Therefore, the current research was designed to explore ONS adherence from the parallel perspectives of ONS as a prescribed "medication" and as a food supplement/substitute. Eighteen older adults (13F, 5M; mean age = 73.4 yr; range: 70-80 yr) participated in focus groups (three in-person and one online), to investigate experiences of taking prescribed medications, including dietary supplements, and what should be factors to consider in supporting regular intake of ONS for trial development, as well as any potential improvements to products. Focus group sessions were recorded and then transcribed. Thematic Analysis was applied to the transcripts by the first author, and themes were discussed in depth, using exemplar quotes from participants. Five dominant themes were identified from the data: Disgust, Palatability and Acceptance; End-of-Life Care; Resistance to Medicines; Rituals and Reminders; and Real Food Displacement. Nutritional supplements were characterised as "disgusting", "manufactured", and associated with serious, chronic illness, as well as end-of-life care, in contrast to probiotics which were linked with health and wellness. The sweet taste of ONS was identified as a barrier to intake, given that it is generally associated with a signal to stop eating, and low hunger. As a group, participants tried to "avoid taking medicines", and viewed the need to have them negatively, yet most regularly took prescribed medication and/or vitamin supplements. Participants identified several, rituals and reminders to take medicines, including meal-based, or time-of-day-based prompts (e.g., before, with or after meals). To improve adherence, savoury products were suggested, as well as a more person-centred approach to individual nutritional needs and preferences. Overall, the group discussion mainly identified barriers to intake, but that improving taste, adding to "real food" (not replacing meals), and offering variety of flavour and form (e.g., savoury soups as well as sweet drinks) could be included in future trials to improve appeal and therefore intake. Future work should continue to explore how best to formulate, market and/or prescribe ONS, and how this might vary for malnutrition prevention vs treatment strategies.

Scurvy: A Case Report and Literature Review.

Scurvy is a rare disease which can manifest in a variety of presentations. Classically, scurvy is associated with poor dentition and bleeding diatheses. Rarely, scurvy can present with life-threatening hemodynamical instability. Herein, we report the case of a 69-year-old female with a history of hypertension and depression who presented with four months of weakness and a 20-pound weight loss. Her presentation was complicated by lower extremity bruising and myalgias over the last three weeks. The patient's blood pressure in the emergency department was 86/54 mmHg. On further examination, she had poor dentition and extensive ecchymoses in different stages of resolution over her posterior thighs and calves. The patient was also noted to have perifollicular hemorrhages. An ascorbic acid level was checked and the result was 0.0 mg/dL (normal range: 0.4 to 2.0 mg/dL). During her admission, she slowly improved with a provided diet and multivitamins. Her blood pressure consistently remained over 120/65 mmHg. The patient was advised to adjust her diet and take supplemental ascorbic acid. On a follow-up visit two weeks later, the patient endorsed an improvement in pain and exercise tolerance and was noted to have marked improvement in skin findings.  Ascorbic acid is an essential piece of multiple biochemical pathways. Humans are required to attain ascorbic acid from their diet. People who consume diets lacking in ascorbic acid develop scurvy.

A High Content Screen in Macrophages Identifies Small Molecule Modulators of STING-IRF3 and NFkB Signaling.

We screened a library of bioactive small molecules for activators and inhibitors of innate immune signaling through IRF3 and NFkB pathways with the goals of advancing pathway understanding and discovering probes for immunology research. We used high content screening to measure the translocation from the cytoplasm to nucleus of IRF3 and NFkB in primary human macrophages; these transcription factors play a critical role in the activation of STING and other pro-inflammatory pathways. Our pathway activator screen yielded a diverse set of hits that promoted nuclear translocation of IRF3 and/or NFkB, but the majority of these compounds did not cause activation of downstream pathways. Screening for antagonists of the STING pathway yielded multiple kinase inhibitors, some of which inhibit kinases not previously known to regulate the activity of this pathway. Structure-activity relationships (SARs) and subsequent chemical proteomics experiments suggested that MAPKAPK5 (PRAK) is a kinase that regulates IRF3 translocation in human macrophages. Our work establishes a high content screening approach for measuring pro-inflammatory pathways in human macrophages and identifies novel ways to inhibit such pathways; among the targets of the screen are several molecules that may merit further development as anti-inflammatory drugs.

The 5-HT2C receptor agonist meta-chlorophenylpiperazine (mCPP) reduces palatable food consumption and BOLD fMRI responses to food images in healthy female volunteers.

RATIONALE: Brain 5-HT2C receptors form part of a neural network that controls eating behaviour. 5-HT2C receptor agonists decrease food intake by activating proopiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus, but recent research in rodents has suggested that 5-HT2C receptor agonists may also act via dopaminergic circuitry to reduce the rewarding value of food and other reinforcers. No mechanistic studies on the effects of 5-HT2C agonists on food intake in humans have been conducted to date. OBJECTIVES: The present study examined the effects of the 5-HT2C receptor agonist meta-chlorophenylpiperazine (mCPP) on food consumption, eating microstructure and blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) responses to food pictures in healthy female volunteers. METHODS: In a double-blind, placebo-controlled, crossover design, participants were randomized immediately after screening to receive oral mCPP (30mg) in a single morning dose, or placebo, in a counterbalanced order. Test foods were served from a Universal Eating Monitor (UEM) that measured eating rate and fMRI BOLD signals to the sight of food and non-food images were recorded. RESULTS: mCPP decreased rated appetite and intake of a palatable snack eaten in the absence of hunger but had no significant effect on the consumption of a pasta lunch (although pasta eating rate was reduced). mCPP also decreased BOLD fMRI responses to the sight of food pictures in areas of reward-associated circuitry. A post hoc analysis identified individual variability in the response to mCPP (exploratory responder-non-responder analysis). Some participants did not reduce their cookie intake after treatment with mCPP and this lack of response was associated with enhanced ratings of cookie pleasantness and enhanced baseline BOLD responses to food images in key reward and appetite circuitry. CONCLUSIONS: These results suggest that 5-HT2C receptor activation in humans inhibits food reward-related responding and that further investigation of stratification of responding to mCPP and other 5-HT2C receptor agonists is warranted.

Endoscopic Bubble Trouble: Hyperbaric Oxygen Therapy for Cerebral Gas Embolism During Upper Endoscopy.

Gas embolism is a rare but potentially devastating complication of endoscopic procedures. We describe 3 cases of gas embolism which were associated with endoscopic procedures (esophagogastroduodenoscopy and endoscopic retrograde cholangiopancreatography). We treated these at our hyperbaric medicine center with 3 different outcomes: complete resolution, death, and disability. We review the literature regarding this unusual complication of endoscopy and discuss the need for prompt identification and referral for hyperbaric oxygen therapy. Additional adjunctive therapies are also discussed.

Standardized set-point acupuncture for migraines.

CONTEXT: Migraine headaches are common, debilitating, underdiagnosed, and undertreated, and medications are not always effective. Research has shown that acupuncture may be an effective and safe adjuvant or alternative migraine treatment. OBJECTIVE: The purpose of the current study was to evaluate whether a standardized set of acupuncture points, when used to deliver treatment over a predefined period of time, could reduce the frequency and intensity of migraines. DESIGN: This is a prospective interventional study using set point acupuncture for migraines. SETTING: The study took place at Conemaugh Memorial Medical Center in Johnstown, PA, USA. PARTICIPANTS: Participants were 59 individuals with a diagnosis of migraine. INTERVENTION: Acupuncture was administered 2 ×/wk for 4 wks, followed by 1 ×/wk for 4 more wks, using one set of acupoints. OUTCOME MEASURES: Participants collected daily headache diaries and migraine quality-of-life measurements on a personal digital assistant for 12 wks before starting the acupuncture intervention. Participants continued to record the frequency and intensity of their migraines during the intervention and for an additional 12 wks beyond the intervention. The Migraine Disability Assessment (MIDAS), Headache Impact Test (HIT-6), and Beck Depression Inventory (BDI-II) were completed 4 × during the study: 12 wks prior to the start of the intervention, immediately prior to the first acupuncture treatment, at the end of treatment, and 12 wks after the end of treatment. RESULTS: When preintervention measurements were compared to postintervention measurements, migraine frequency and pain intensity showed a significant decrease (α = 0.05) after acupuncture intervention. Results had not returned to the preintervention baseline even 12 wks after the last acupuncture session. Acupuncture significantly influenced migraine frequency and intensity in the study's participants when preintervention measurements were compared to postintervention measurements. CONCLUSIONS: These results indicate that not only did acupuncture decrease both the frequency and intensity of migraines, but also the benefit had not subsided for 12 wks after the final acupuncture session. Validated survey measurements used to assess migraine impact on quality of life showed statistically significant improvement over baseline.