CHronic hypERtension and L-citRulline studY (CHERRY): an Early-Phase Randomised Controlled Trial in Pregnancy.

Oral supplementation with L-citrulline, which is sequentially converted to L-arginine then nitric oxide, improves vascular biomarkers and reduces blood pressure in non-pregnant, hypertensive human cohorts and pregnant mice with a pre-eclampsia-like syndrome. This early-phase randomised feasibility trial assessed the acceptability of L-citrulline supplementation to pregnant women with chronic hypertension and its effects on maternal BP and other vascular outcomes. Pregnant women with chronic hypertension were randomised at 12-16 weeks to receive 3-g L-citrulline twice daily (n = 24) or placebo (n = 12) for 8 weeks. Pregnant women reported high acceptability of oral L-citrulline. Treatment increased maternal plasma levels of citrulline, arginine and the arginine:asymmetric dimethylarginine ratio, particularly in women reporting good compliance. L-citrulline had no effect on diastolic BP (L-citrulline: - 1.82 95% CI (- 5.86, 2.22) vs placebo: - 5.00 95% CI (- 12.76, 2.76)), uterine artery Doppler or angiogenic biomarkers. Although there was no effect on BP, retrospectively, this study was underpowered to detect BP changes < 9 mmHg, limiting the conclusions about biological effects. The increase in arginine:asymmetric dimethylarginine ratio was less than in non-pregnant populations, which likely reflects altered pharmacokinetics of pregnancy, and further pharmacokinetic assessment of L-citrulline in pregnancy is advised.Trial Registration EudraCT 2015-005792-25 (2017-12-22) and ISRCTN12695929 (2018-09-20).

Transplanting Microglia for Treating CNS Injuries and Neurological Diseases and Disorders, and Prospects for Generating Exogenic Microglia.

Microglia are associated with a wide range of both neuroprotective and neuroinflammatory functions in the central nervous system (CNS) during development and throughout lifespan. Chronically activated and dysfunctional microglia are found in many diseases and disorders, such as Alzheimer's disease, Parkinson's disease, and CNS-related injuries, and can accelerate or worsen the condition. Transplantation studies designed to replace and supplement dysfunctional microglia with healthy microglia offer a promising strategy for addressing microglia-mediated neuroinflammation and pathologies. This review will cover microglial involvement in neurological diseases and disorders and CNS-related injuries, current microglial transplantation strategies, and different approaches and considerations for generating exogenic microglia.

Nervonic acid limits weight gain in a mouse model of diet-induced obesity.

Lipid perturbations contribute to detrimental outcomes in obesity. We previously demonstrated that nervonic acid, a C24:1 ω-9 fatty acid, predominantly acylated to sphingolipids, including ceramides, are selectively reduced in a mouse model of obesity. It is currently unknown if deficiency of nervonic acid-sphingolipid metabolites contribute to complications of obesity. Mice were fed a standard diet, a high fat diet, or these diets supplemented isocalorically with nervonic acid. The primary objective was to determine if dietary nervonic acid content alters the metabolic phenotype in mice fed a high fat diet. Furthermore, we investigated if nervonic acid alters markers of impaired fatty acid oxidation in the liver. We observed that a nervonic acid-enriched isocaloric diet reduced weight gain and adiposity in mice fed a high fat diet. The nervonic acid enrichment led to increased C24:1-ceramides and improved several metabolic parameters including blood glucose levels, and insulin and glucose tolerance. Mechanistically, nervonic acid supplementation increased PPARα and PGC1α expression and improved the acylcarnitine profile in liver. These alterations indicate improved energy metabolism through increased ß-oxidation of fatty acids. Taken together, increasing dietary nervonic acid improves metabolic parameters in mice fed a high fat diet. Strategies that prevent deficiency of, or restore, nervonic acid may represent an effective strategy to treat obesity and obesity-related complications.

Determinants of Diuretic Responsiveness and Associated Outcomes During Acute Heart Failure Hospitalization: An Analysis From the NHLBI Heart Failure Network Clinical Trials.

BACKGROUND: Poor response to loop diuretic therapy is a marker of risk during heart failure hospitalization. We sought to describe baseline determinants of diuretic response and to further explore the relationship between this response and clinical outcomes. METHODS AND RESULTS: Patient data from the National Heart, Lung, and Blood Institute Heart Failure Network ROSE-AHF and CARRESS-HF clinical trials were analyzed to determine baseline determinants of diuretic response. Diuretic efficiency (DE) was defined as total 72-hour fluid output per total equivalent loop diuretic dose. Data from DOSE-AHF was then used to determine if these predictors of DE correlated with response to a high- versus low-dose diuretic strategy. At 72 hours, the high-DE group had median fluid output of 9071 ml (interquartile range: 7240-11775) with median furosemide dose of 320 mg (220-480) compared with 8030 ml (6300-9915) and 840 mg (600-1215) respectively for the low DE group. Cystatin C was independently associated with DE (odds ratio 0.36 per 1mg/L increase; 95% confidence interval: 0.24-0.56; P < 0.001). Independently from baseline characteristics, reduced fluid output, weight loss and DE were each associated with increased 60 day mortality. Among patients with estimated glomerular filtration rate below the median, those randomized to a high-dose strategy had improved symptoms compared with those randomized to a low-dose strategy. CONCLUSIONS: Elevated baseline cystatin C, as a biomarker of renal dysfunction, is associated with reduced diuretic response during heart failure hospitalization. Higher loop diuretic doses are required for therapeutic decongestion in patients with renal insufficiency. Poor response identifies a high-risk population.

Care of the mother-infant dyad: a novel approach to conducting and evaluating neonatal resuscitation simulation training in Bihar, India.

BACKGROUND: As the global under-five mortality rate declines, an increasing percentage is attributable to early neonatal mortality. A quarter of early neonatal deaths are due to perinatal asphyxia. However, neonatal resuscitation (NR) simulation training in low-resource settings, where the majority of neonatal deaths occur, has achieved variable success. In Bihar, India, the poorest region in South Asia, there is tremendous need for a new approach to reducing neonatal morality. METHODS: This analysis aims to assess the impact of a novel in-situ simulation training program, developed by PRONTO International and implemented in collaboration with CARE India, on NR skills of nurses in Bihar. Skills were evaluated by clinical complexity of the simulated scenario, which ranged from level 1, requiring NR without a maternal complication, to level 3, requiring simultaneous management of neonatal and maternal complications. A total of 658 nurses at 80 facilities received training 1 week per month for 8 months. Simulations were video-recorded and coded for pre-defined clinical skills using Studiocode™. RESULTS: A total of 298 NR simulations were analyzed. As simulation complexity increased, the percentage of simulations in which nurses completed key steps of NR did not change, even with only 1-2 providers in the simulation. This suggests that with PRONTO training, nurses were able to maintain key skills despite higher clinical demands. As simulation complexity increased from level 1 to 3, time to completion of key NR steps decreased non-significantly. Median time to infant drying decreased by 7.5 s (p = 0.12), time to placing the infant on the warmer decreased by 21.7 s (p = 0.27), and time to the initiation of positive pressure ventilation decreased by 20.8 s (p = 0.12). Nevertheless, there remains a need for improvement in absolute time elapsed between delivery and completion of key NR tasks. CONCLUSIONS: PRONTO simulation training enabled nurses in Bihar to maintain core NR skills in simulation despite demands for higher-level triage and management. Although further evaluation of the PRONTO methodology is necessary to understand the full scope of its impact, this analysis highlights the importance of conducting and evaluating simulation training in low-resource settings based on simultaneous care of the mother-infant dyad.

A pilot randomized controlled trial comparing prenatal yoga to perinatal health education for antenatal depression.

We conducted a pilot randomized controlled trial (RCT) comparing a prenatal yoga intervention to perinatal-focused health education in pregnant women with depression. Findings document acceptability and feasibility of the yoga intervention: no yoga-related injuries were observed, instructors showed fidelity to the yoga manual, and women rated interventions as acceptable. Although improvements in depression were not statistically different between groups, they favored yoga. This study provides support for a larger scale RCT examining prenatal yoga to improve mood during pregnancy.

The Clinical Learning Dyad Model: An Innovation in Midwifery Education.

There is a national shortage of women's health and primary care providers in the United States, including certified nurse-midwives and certified midwives. This shortage is directly related to how many students can be trained within the existing system. The current model of midwifery clinical training is based on apprenticeship, with one-on-one interaction between a student and preceptor. Thus, the number of newly trained midwifery providers is limited by the number of available and willing preceptors. The clinical learning dyad model (CLDM), which pairs 2 beginning midwifery students with one preceptor in a busy practice, addresses this problem. In addition, this model brings in a senior midwife student as a near-peer mentor when the students are first oriented into outpatient clinical practice. The model began as a pilot project to improve the quality of training and increase available student spots in clinical education. This article discusses the origins of the model, the specifics of its design, and the results of a midterm and one-year postintervention survey. Students and preceptors involved in this model identified several advantages to the program, including increased student accountability, enhanced socialization into the profession, improved learning, and reduced teaching burden on preceptors. An additional benefit of the CLDM is that students form a learning community and collaborate with preceptors to care for women in busy clinical settings. Challenges of the model will also be discussed. Further research is needed to evaluate the effectiveness of the CLDM. This article is part of a special series of articles that address midwifery innovations in clinical practice, education, interprofessional collaboration, health policy, and global health.

Rebozo Technique for Fetal Malposition in Labor.

Fetal occiput posterior position is associated with increased maternal and fetal morbidities. Currently, clinicians have limited evidence-based techniques or tools to remedy fetal occiput posterior position. The traditional Mexican rebozo technique of pelvic massage, sifting, or jiggling offers a potentially valuable tool to help correct fetal malposition. This article reviews the adaptation of 3 rebozo techniques that can be used in labor to encourage optimum fetal positioning; outlines hospital considerations for safety, fetal heart rate monitoring, and universal precautions; and reviews the implementation plan to introduce and sustain use of the rebozo in a large academic medical center.

Potential for prenatal yoga to serve as an intervention to treat depression during pregnancy.

BACKGROUND: When left untreated, antenatal depression can have a serious negative impact on maternal, and infant outcomes. Many affected women do not obtain treatment for depression owing to difficulties accessing care or because they do not find standard antidepressant treatments to be acceptable during pregnancy. This study examined the acceptability and feasibility of a gentle prenatal yoga intervention, as a strategy for treating depression during pregnancy. METHODS: We developed a 10-week prenatal yoga program for antenatal depression and an accompanying yoga instructors' manual, and enrolled 34 depressed pregnant women from the community into an open pilot trial. We measured change in maternal depression severity from before to after the intervention. RESULTS: Results suggested that the prenatal yoga intervention was feasible to administer and acceptable to the women enrolled. No study-related injuries or other safety issues were observed during the trial. On average, participants' depression severity decreased significantly by the end of the intervention based on both observed-rated and self-report depression assessment measures. CONCLUSION: The current study suggests that prenatal yoga may be a viable approach to addressing antenatal depression, one that may have advantages in terms of greater acceptability than standard depression treatments. Research and policy implications are discussed.

Clinical characteristics and outcomes with rivaroxaban vs. warfarin in patients with non-valvular atrial fibrillation but underlying native mitral and aortic valve disease participating in the ROCKET AF trial.

AIMS: We investigated clinical characteristics and outcomes of patients with significant valvular disease (SVD) in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) trial. METHODS AND RESULTS: ROCKET AF excluded patients with mitral stenosis or artificial valve prostheses. We used Cox regression to adjust comparisons for potential confounders. Among 14 171 patients, 2003 (14.1%) had SVD; they were older and had more comorbidities than patients without SVD. The rate of stroke or systemic embolism with rivaroxaban vs. warfarin was consistent among patients with SVD [2.01 vs. 2.43%; hazard ratio (HR) 0.83, 95% confidence interval (CI) 0.55-1.27] and without SVD (1.96 vs. 2.22%; HR 0.89, 95% CI 0.75-1.07; interaction P = 0.76). However, rates of major and non-major clinically relevant bleeding with rivaroxaban vs. warfarin were higher in patients with SVD (19.8% rivaroxaban vs. 16.8% warfarin; HR 1.25, 95% CI 1.05-1.49) vs. those without (14.2% rivaroxaban vs. 14.1% warfarin; HR 1.01, 95% CI 0.94-1.10; interaction P = 0.034), even when controlling for risk factors and potential confounders. In intracranial haemorrhage, there was no interaction between patients with and without SVD where the overall rate was lower among those randomized to rivaroxaban. CONCLUSIONS: Many patients with 'non-valvular atrial fibrillation' have significant valve lesions. Their risk of stroke is similar to that of patients without SVD after controlling for stroke risk factors. Efficacy of rivaroxaban vs. warfarin was similar in patients with and without SVD; however, the observed risk of bleeding was higher with rivaroxaban in patients with SVD but was the same among those without SVD. Atrial fibrillation patients with and without SVD experience the same stroke-preventive benefit of oral anticoagulants.

Spiritual well-being and spiritual practices in elderly depressed psychiatric inpatients.

This study's aims were to describe the spirituality of depressed elderly psychiatric inpatients and to examine associations among spirituality, depression, and quality of life (QOL). Forty-five persons participated. Most reported frequent, stable spiritual practices and experiencing spiritual comfort and guidance. Some reported spiritual distress and changes in spirituality. During hospitalization, participants demonstrated increased spiritual well-being (SWB) and peacefulness, and reduced hopelessness, worthlessness, and guilt. Positive associations were found between SWB and QOL and negative associations between SWB and depression.

A pilot study of spirituality and inpatient rehabilitation outcomes in persons with spinal cord dysfunction and severe neurological illnesses.

This prospective, observational pilot study was conducted on an academic inpatient rehabilitation unit. Ninety-three persons with spinal cord dysfunction or severe neurological illness participated. All completed admission surveys; 46 completed surveys six months after discharge. The aims were to describe admission and post-discharge spirituality and associations between spirituality and rehabilitation outcomes. At admission, participants reported spirituality similar to that of other samples of medical patients. After discharge, frequency of private spiritual practices increased and spiritual and existential well-being decreased. No significant associations were detected between spirituality and rehabilitation outcomes. Findings suggest the importance of spirituality to the participants and future research with a larger sample and modifications to the methodology.

Modified MyPyramid for Older Adults.

In 1999 we proposed a Modified Food Guide Pyramid for adults aged 70+ y. It has been extensively used in a variety of settings and formats to highlight the unique dietary challenges of older adults. We now propose a Modified MyPyramid for Older Adults in a format consistent with the MyPyramid graphic. It is not intended to substitute for MyPyramid, which is a multifunctional Internet-based program allowing for the calculation of individualized food-based dietary guidance and providing supplemental information on food choices and preparation. Pedagogic issues related to computer availability, Web access, and Internet literacy of older adults suggests a graphic version of MyPyramid is needed. Emphasized are whole grains and variety within the grains group; variety and nutrient density, with specific emphasis on different forms particularly suited to older adults' needs (e.g. frozen) in the vegetables and fruits groups; low-fat and non-fat forms of dairy products including reduced lactose alternatives in the milk group; low saturated fat and trans fat choices in the oils group; and low saturated fat and vegetable choices in the meat and beans group. Underlying themes stress nutrient- and fiber-rich foods within each group and food sources of nutrients rather than supplements. Fluid and physical activity icons serve as the foundation of MyPyramid for Older Adults. A flag to maintain an awareness of the potential need to consider supplemental forms of calcium, and vitamins D and B-12 is placed at the top of the pyramid. Discussed are newer concerns about potential overnutrition in the current food landscape available to older adults.

Spirituality during alcoholism treatment and continuous abstinence for one year.

OBJECTIVE: The primary aim of this prospective study was to examine the role of several aspects of spirituality in maintaining abstinence from alcohol for one year in persons treated for alcohol dependence. The roles of alcohol abstinence self-efficacy and Alcoholics Anonymous affiliation were also examined. METHOD: Seventy-four adults with alcohol dependence who had completed a three-week outpatient addiction program participated in this study. Instruments used included the Spiritual Well-Being Scale, Duke Religion Index, Brief Religious Coping Scale, Alcohol Abstinence Self-Efficacy Scale, and Alcoholics Anonymous Affiliation Scale. Abstinence data was collected from participants and collaterals three, six, and twelve months after treatment discharge. Demographics, discharge measures, and the change in scores from admission to discharge were compared between those with and without 12-month alcohol abstinence using logistic regression or Fisher's exact tests. RESULTS: Twenty-eight participants were categorized as continuously abstinent for one year. The strongest associations between 12 month abstinence and the variables of interest were discharge scores of abstinence self-efficacy and existential well-being, and increases during treatment in scores of private spiritual practices. Increased age demonstrated a significant association with positive outcome. CONCLUSION: The associations of private spiritual practices, existential well-being, and abstinence self-efficacy with one year of continuous abstinence following treatment discharge suggest the importance of addressing issues related to these variables during alcoholism treatment. More research is needed to understand the role of these variables in promoting and maintaining abstinence and to determine whether or not a related intervention would improve abstinence rates.

Complementary treatments for tobacco cessation: a survey.

Little information is available regarding the prevalence of use and interest in future use of complementary and alternative medicine (CAM) for tobacco cessation among tobacco users. We conducted a self-administered anonymous survey among 1,175 patients seen at a midwestern outpatient tobacco treatment specialty clinic between November 2003 and July 2005. Patient use of CAM for tobacco cessation, perceived efficacy of these treatments, and interest in future use of CAM were ascertained. Data were summarized using descriptive statistics, and logistic regression models were used to determine the characteristics associated with past CAM use or interest in future use of CAM for tobacco cessation. All of the patients who received the survey completed it. A total of 27% of patients reported previous use of CAM for tobacco cessation. The interventions most commonly used were hypnosis, relaxation, acupuncture, and meditation. CAM treatments most commonly perceived to be efficacious were yoga, relaxation, meditation, and massage therapy. A total of 67% of the patients reported interest in future use of CAM for tobacco cessation. The treatments of greatest interest for use in the future were hypnosis, herbal products, acupuncture, relaxation, and massage therapy. Female gender, previous use of conventional tobacco cessation products, previous use of CAM treatments, and a higher level of education were significantly associated with interest in future CAM use. The high level of interest in CAM among tobacco users underscores the need to conduct further research in this field.

Late bleb leakage after trabeculectomy with 5-fluorouracil or mitomycin C.

OBJECTIVE: To determine the prevalence of late filtering bleb leakage after trabeculectomy performed with intraoperative adjunctive use of 5-fluorouracil (5-FU) or mitomycin C. DESIGN: Case series. SETTING: Private clinic in São Paulo. PATIENTS: Forty-seven consecutive patients (47 eyes) who had previously undergone trabeculectomy with intraoperative application of either 5-FU (25 mg/mL) or mitomycin C (0.2 mg/mL) and who had functioning filtering blebs. The patients who received 5-FU had advanced primary open-angle glaucoma without previous surgery; those who received mitomycin C had either previous failed filtering surgery or refractory glaucoma. All patients had been followed for at least 6 months. OUTCOME MEASURES: Slit-lamp appearance of bleb, bleb leakage, as determined with the Seidel test. RESULTS: None of the eyes had spontaneous bleb leakage. Ten (32.2%) of the 31 eyes that received 5-FU and 5 (31.2%) of the 16 eyes that received mitomycin C had induced bleb leakage. Thirty filtering blebs were classified as transparent, 10 as vascularized and 7 as ischemic. The rates of bleb leakage for the three groups were 46.7%, 0% and 14.3% respectively (p = 0.012). CONCLUSIONS: The importance of late bleb leakage in patients who receive intraoperative 5-FU or mitomycin C in predisposing these eyes to late complications, such as endophthalmitis and hypotony, needs to be evaluated.

Mitomycin C as adjunctive therapy with glaucoma implant surgery.

Twenty-one eyes of 21 patients with refractory glaucoma underwent glaucoma surgery involving placement of a modified Molteno implant and intraoperative application of mitomycin C. Sixteen eyes (76.2%) had an intraocular pressure (IOP) of 21 mm Hg or less after a mean follow up of 9.4 +/- 6.4 months; additional medication was needed in six eyes. Major complications included early flat anterior chamber (42.9%), implant plate erosion (9.5%), tube erosion (4.8%), late hypotony (4.8%), tube-corneal touch (4.8%), and phthisis bulbi after choroidal hemorrhage (4.8%). Only one patient had a high IOP due to decreased filtration through the implant. These results suggest that glaucoma implant surgery with the adjunctive use of mitomycin C may be useful in eyes with refractory glaucoma.