Early postpartum resting‐state functional connectivity for mothers receiving buprenorphine treatment for opioid use disorder: A pilot study

Between 1999 and 2014, the prevalence of opioid use disorder (OUD) among pregnant women quadrupled in the USA. The standard treatment for peripartum women with OUD is buprenorphine. However, the maternal behavior neurocircuit that regulates maternal behavior and mother‐infant bonding has not been previously studied for human mothers receiving buprenorphine treatment for OUD (BT). Rodent research shows opioid effects on reciprocal inhibition between maternal care and defence maternal brain subsystems: the hypothalamus and periaqueductal gray, respectively. We conducted a longitudinal functional magnetic resonance imaging (fMRI) pilot study in humans to specifically examine resting‐state functional connectivity (rs‐FC) between the periaqueductal gray and hypothalamus, as well as to explore associations with maternal bonding for BT. We studied 32 mothers who completed fMRI scans at 1 month (T1) and 4 months postpartum (T2), including seven mothers receiving buprenorphine for OUD and 25 non‐OUD mothers as a comparison group (CG). The participants underwent a 6‐minute resting‐state fMRI scan at each time point. We measured potential bonding impairments using the Postpartum Bonding Questionnaire to explore how rs‐FC with periaqueductal gray is associated with bonding impairments. Compared to CG, BT mothers differed in periaqueductal gray‐dependent rs‐FC with the hypothalamus, amygdala, insular cortex and other brain regions at T1, with many of these differences disappearing at T2, suggesting potential therapeutic effects of continuing buprenorphine treatment. In contrast, the “rejection and pathological anger” subscale of the Postpartum Bonding Questionnaire at T1 and T2 was associated with the T1‐to‐T2 increases in periaqueductal gray‐dependent rs‐FC with the hypothalamus and amygdala. Preliminary evidence links maternal bonding problems for mothers with OUD early in the postpartum to connectivity between specific care and defence maternal brain circuits, which may be mitigated by buprenorphine treatment. This exploratory study supports a potential mechanism for investigating both the therapeutic benefits and risks of opioids for maternal care and bonding with infants.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151866/1/jne12770.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151866/2/jne12770_am.pd

Simvastatin improves the sexual health-related quality of life in men aged 40 years and over with erectile dysfunction : Additional data from the Erectile Dysfunction and Statin trial

© 2014 Trivedi et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.Background: Erectile dysfunction is prevalent in men over 40 years, affecting their quality of life and that of their partners. The aims of this study were:a)To evaluate the internal reliability of the male erectile dysfunction specific quality of life (MED-QoL) scale and explore its factor structure.b)To evaluate the effect of simvastatin on subscales of the MED-QoL in men over forty years with erectile dysfunction. Methods: This is a double blind randomised controlled trial of 40 mg simvastatin or placebo given once daily for six months to men over forty years with untreated erectile dysfunction, who were not at high cardiovascular risk and were not on anti-hypertensive or lipid-lowering medication. 173 eligible men were recruited from 10 general practices in East of England. Data were collected at two points over 30 weeks. We report on the factor structure of MED-QoL, the internal reliability of the scale and the derived subscales, and the effect of simvastatin on MED-QoL subscales. Results: An initial analysis of the MED-QoL items suggested that a number of items should be removed (MED-QoL-R). Exploratory factor analysis identified three subscales within the MED-QoL-R which accounted for 96% of the variance, related to feelings of Control, initiating Intimacy, and Emotional response to erectile dysfunction. The alpha value for the revised scale (MED-Qol-R) was >0.95 and exceeded .82 for each subscale. Regression analysis showed that patients in the placebo group experienced a significantly reduced feeling of Control over erectile dysfunction than those in the statin group. Those in the placebo group had significantly lower Emotional response than those in the statin group at the close of trial, but there was no significant treatment effect on Intimacy. Conclusions: Our revised MED-QoL-R identified three subscales. Secondary analysis showed a significant improvement in sexual health related quality of life, specifically in relation to perception of control and emotional health in men with untreated erectile dysfunction given 40 mg simvastatin for six months. Trial registration: Current Controlled Trials ISRCTN66772971.Peer reviewe

Imaging Electronic Correlations in Twisted Bilayer Graphene near the Magic Angle

Twisted bilayer graphene with a twist angle of around 1.1{\deg} features a pair of isolated flat electronic bands and forms a strongly correlated electronic platform. Here, we use scanning tunneling microscopy to probe local properties of highly tunable twisted bilayer graphene devices and show that the flat bands strongly deform when aligned with the Fermi level. At half filling of the bands, we observe the development of gaps originating from correlated insulating states. Near charge neutrality, we find a previously unidentified correlated regime featuring a substantially enhanced flat band splitting that we describe within a microscopic model predicting a strong tendency towards nematic ordering. Our results provide insights into symmetry breaking correlation effects and highlight the importance of electronic interactions for all filling factors in twisted bilayer graphene.Comment: Main text 9 pages, 4 figures; Supplementary Information 25 page

Cortisol secretion after adrenocorticotrophin (ACTH) and Dexamethasone tests in healthy female and male dogs

<p>Abstract</p> <p>Background</p> <p>For the conclusive diagnosis of Cushing's Syndrome, a stimulating ACTH test or a low suppressive Dexamethasone test is used. Reports in other species than the dog indicate that plasma cortisol concentration after ACTH administration is affected by gender. We investigated the effect of gender on the cortisol response to ACTH and Dexamethasone tests in dogs.</p> <p>Methods</p> <p>Seven healthy adult Cocker Spaniels (4 females and 3 males) were assigned to a two by two factorial design: 4 dogs (2 females and 2 males) received IV Dexamethasone 0.01 mg/kg, while the other 3 dogs received an IV saline solution (control group). Two weeks later the treatments were reversed. After one month, ACTH was given IV (250 μg/animal) to 4 dogs (2 female and 2 males) while the rest was treated with saline solution (control group). Cortisol concentrations were determined by a direct solid-phase radioimmunoassay and cholesterol and triglycerides by commercial kits.</p> <p>Results and Discussion</p> <p>No effect of treatment was observed in metabolite concentrations, but females presented higher cholesterol concentrations. ACTH-treated dogs showed an increase in cortisol levels in the first hour after sampling until 3 hours post injection. Cortisol concentrations in Dexamethasone-treated dogs decreased one hour post injection and remained low for 3 hours, thereafter cortisol concentrations increased. The increase in cortisol levels from one to two hours post ACTH injection was significantly higher in females than males. In Dexamethasone-treated males cortisol levels decreased one hour post injection up to 3 hours; in females the decrease was more pronounced and prolonged, up to 5 hours post injection.</p> <p>Conclusion</p> <p>We have demonstrated that cortisol response to ACTH and Dexamethasone treatment in dogs differs according to sex.</p

Identifying patient preferences for communicating risk estimates: A descriptive pilot study

BACKGROUND: Patients increasingly seek more active involvement in health care decisions, but little is known about how to communicate complex risk information to patients. The objective of this study was to elicit patient preferences for the presentation and framing of complex risk information. METHOD: To accomplish this, eight focus group discussions and 15 one-on-one interviews were conducted, where women were presented with risk data in a variety of different graphical formats, metrics, and time horizons. Risk data were based on a hypothetical woman's risk for coronary heart disease, hip fracture, and breast cancer, with and without hormone replacement therapy. Participants' preferences were assessed using likert scales, ranking, and abstractions of focus group discussions. RESULTS: Forty peri- and postmenopausal women were recruited through hospital fliers (n = 25) and a community health fair (n = 15). Mean age was 51 years, 50% were non-Caucasian, and all had completed high school. Bar graphs were preferred by 83% of participants over line graphs, thermometer graphs, 100 representative faces, and survival curves. Lifetime risk estimates were preferred over 10 or 20-year horizons, and absolute risks were preferred over relative risks and number needed to treat. CONCLUSION: Although there are many different formats for presenting and framing risk information, simple bar charts depicting absolute lifetime risk were rated and ranked highest overall for patient preferences for format

A double blind, randomised placebo controlled trial of topical 2% viscous lidocaine in improving oral intake in children with painful infectious mouth conditions

<p>Abstract</p> <p>Background</p> <p>Painful infectious mouth conditions are a common presentation to emergency departments. Although self limiting, painful ulcerative lesions and inflamed mucosa can decrease oral intake and can lead to dehydration. Oral analgesia is of limited efficacy and is often refused by the patient. Despite widespread use of oral 2% viscous lidocaine for many years, there is little evidence for its efficacy as an analgesic and in aiding oral intake in children with painful infectious mouth conditions. This study aims to establish the effectiveness of 2% viscous lidocaine in increasing oral intake in these children by comparing it with placebo.</p> <p>Methods/Design</p> <p>This study is a randomised double-blind placebo controlled trial of children between 6 months and 8 years of age with painful infectious mouth conditions defined as gingivostomatitis (herpetic or non herpetic), ulcerative pharyngitis, herpangina and hand foot and mouth disease as assessed by the treating clinician in association with a history of poor oral fluid intake. It will be conducted at a single tertiary paediatric emergency department in Melbourne Australia.</p> <p>20 patients have already been randomised to receive 2% lidocaine or placebo in a pilot study to determine the sample size in a preplanned adaptive design. A further 80 patients will be randomised to receive either 2% lidocaine or placebo. The placebo agent is identical to lidocaine in terms of appearance, flavour and smell. All clinical and research staff involved, patients and their parents will be blinded to treatment allocation.</p> <p>The primary endpoint is the amount of fluid ingested by each child, expressed in ml/kg, within 60 minutes from the time of administration of the study mixture. Secondary endpoints are the proportion of patients ingesting 5 ml/kg and 10 ml/kg at 30 and 60 minutes after drug administration and the incidence of adverse events. Longer term outcomes will include the proportion of patients requiring hospital admission and length of emergency department stay.</p> <p>Discussion</p> <p>This trial will define the role of 2% lidocaine in the treatment of painful infectious mouth conditions</p> <p>Trial registration</p> <p>The trial is registered with the Australian and New Zealand Clinical Trials Registry - <a href="http://www.anzctr.org.au/ACTRN12609000566235.aspx">ACTRN12609000566235</a>.</p

The addition of locust bean gum but not water delayed the gastric emptying rate of a nutrient semisolid meal in healthy subjects

BACKGROUND: Most of the previous studies regarding the effects of gel-forming fibres have considered the gastric emptying of liquid or solid meals after the addition of pectin or guar gum. The influence of locust bean gum, on gastric emptying of nutrient semisolid meals in humans has been less well studied, despite its common occurrence in foods. Using a standardised ultrasound method, this study was aimed at investigating if the gastric emptying in healthy subjects could be influenced by adding locust been gum, a widely used thickening agent, or water directly into a nutrient semisolid test meal. METHODS: The viscosity of a basic test meal (300 g rice pudding, 330 kcal) was increased by adding Nestargel (6 g, 2.4 kcal), containing viscous dietary fibres (96.5%) provided as seed flour of locust bean gum, and decreased by adding 100 ml of water. Gastric emptying of these three test meals were evaluated in fifteen healthy non-smoking volunteers, using ultrasound measurements of the gastric antral area to estimate the gastric emptying rate (GER). RESULTS: The median value of GER with the basic test meal (rice pudding) was estimated at 63 %, (range 47 to 84 %), (the first quartile = 61 %, the third quartile = 69 %). Increasing the viscosity of the rice pudding by adding Nestargel, resulted in significantly lower gastric emptying rates (p < 0.01), median GER 54 %, (range 7 to 71 %), (the first quartile = 48 %, the third quartile = 60 %). When the viscosity of the rice pudding was decreased (basic test meal added with water), the difference in median GER 65 %, (range 38 to 79 %), (the first quartile = 56 %, the third quartile = 71 %) was not significantly different (p = 0.28) compared to the GER of the basic test meal. CONCLUSIONS: We conclude that the addition of locust bean gum to a nutrient semisolid meal has a major impact on gastric emptying by delaying the emptying rate, but that the addition of water to this test meal has no influence on gastric emptying in healthy subjects