7 tesla magnetic resonance imaging: A closer look at substantia nigra anatomy in Parkinson's disease

A hallmark of Parkinson's disease (PD) is the progressive neurodegeneration of dopaminergic neurons in the substantia nigra pars compacta (SNc). Dopaminergic denervation is commonly imaged using radiotracer imaging in target structures such as the striatum. Until recently, imaging made only a modest contribution to detecting neurodegenerative changes in the substantia nigra (SN) directly. Histologically, the SN is subdivided into the ventral pars reticulata and the dorsal pars compacta, which is composed of dopaminergic neurons. In humans, dopaminergic neurons, which are known to accumulate neuromelanin, form clusters of cells (nigrosomes) that penetrate deep into the SN pars reticulata (SNr). The SNr contains higher levels of iron than the SNc in normal subjects. Neuromelanin and T2*‐weighted imaging therefore better detect the SNc and the SNr, respectively. The development of ultra‐high field 7 Tesla (7T) magnetic resonance imaging (MRI) provided the increase in spatial resolution and in contrast that was needed to detect changes in SN morphology. 7T MRI allows visualization of nigrosome‐1 as a hyperintense signal area on T2*‐weighted images in the SNc of healthy subjects and its absence in PD patients, probably because of the loss of melanized neurons and the increase of iron deposition. This review is designed to provide a better understanding of the correspondence between the outlines and subdivisions of the SN detected using different MRI contrasts and the histological organization of the SN. The recent findings obtained at 7T will then be presented in relation to histological knowledge. © 2014 International Parkinson and Movement Disorder Society     

Improved Real-World Glycemic Control With Continuous Glucose Monitoring System Predictive Alerts

Background:Most standalone real-time continuous glucose monitoring (RT-CGM) systems provide predictive low and high sensor glucose (SG) threshold alerts. The durations and risk of low and high SG excursions following Guardian™ Connect CGM system predictive threshold alerts were evaluated.Methods:Continuous glucose monitoring system data uploaded between January 2, 2017 and May 22, 2018 by 3133 individuals using multiple daily injections (MDIs) or continuous subcutaneous insulin infusion (CSII) therapy were deidentified and retrospectively analyzed. Glucose excursions were defined as SG values that went beyond a preset low or high SG threshold for ≥15 minutes. For a control group, thresholds were based on the median of the low SG threshold limit (70 mg/dL) and the high SG threshold limit (210 mg/dL) preset by all system users. During periods when alerts were not enabled, timestamps were identified when a predictive alert would have been triggered. The time before low horizon was 17.5 minutes and the time before high horizon was 15 minutes, of all users who enabled alerts. Excursions occurring after a low SG or high SG predictive alert were segmented into prevented, ≤20, 20-60, and >60 minutes.Results:Excursions were prevented after 59% and 39% of low and high SG predictive alerts, respectively. The risk of a low or high excursion occurring was 1.9 (P < 0.001, 95% CI, 1.88-1.93) and 3.3 (P < 0.001, 95% CI, 3.20-3.30) times greater, respectively, when alerts were not enabled.Conclusions:The predictive alerts of the RT-CGM system under study can help individuals living with diabetes prevent some real-world low and high SG excursions. This can be especially important for those unable to reach or maintain glycemic control with basic RT-CGM or CSII therapy.     

How important are client characteristics to understanding treatment process in the therapeutic community?

Prior research has demonstrated that therapeutic communities (TCs) are effective at improving posttreatment outcomes for substance abusers. However, little is known about the in-treatment experience for clients with different backgrounds, experiences, and needs. The aim of this study is to examine the in-treatment experience for different clients by exploring the relationships between treatment process and client characteristics. A comprehensive measure of treatment process, operationalized as Community Environment and Personal Change and Development and change was administered to 447 adults and 148 adolescents receiving treatment at community-based TC programs in New York, California, and Texas. Data on demographic characteristics, substance use and treatment history, and client risk factors were extracted from intake interviews and analyzed separately for adolescent and adult residents. Multivariate general linear models were used to examine the effect of client variables on treatment process, after controlling for treatment duration and program effects. Within adult programs, clients who were 25 years or older, female, and had a prior drug treatment experience had higher Community Environment scores. Adolescents with one or more arrests within the past 2 years had lower scores on both process dimensions of Community Environment and Personal Development and Change. Our results indicate the need to understand why adult clients who are younger, male, and have no prior treatment history and adolescent clients with recent arrests reported lower ratings of treatment process. Future research should also examine the role of modifiable mediators so that appropriate strategies to enhance therapeutic engagement may be developed as necessary.     

Cover Image,Volume 20, Issue 6

The cover image, by Sara Charleer et al., is based on the Brief Report A vitamin Accuracy and precision of flash glucose monitoring sensors inserted into the abdomen and upper thigh compared with the upper arm, DOI: 10.1111/dom.13239 . Design Credit: Mr. Joren Polfliet.

     

A mouse model for the renal salt-wasting syndrome pseudohypoaldosteronism

Aldosterone-dependent epithelial sodium transport in the distal nephron is mediated by the absorption of sodium through the highly selective, amiloride-sensitive epithelial sodium channel (ENaC) made of three homologous subunits (α, β, and γ). In human, autosomal recessive mutations of α, β, or γENaC subunits cause pseudohypoaldosteronism type 1 (PHA-1), a renal salt-wasting syndrome characterized by severe hypovolemia, high plasma aldosterone, hyponatremia, life-threatening hyperkaliemia, and metabolic acidosis. In the mouse, inactivation of αENaC results in failure to clear fetal lung liquid at birth and in early neonatal death, preventing the observation of a PHA-1 renal phenotype. Transgenic expression of αENaC driven by a cytomegalovirus promoter in αENaC(−/−) knockout mice [αENaC(−/−)Tg] rescued the perinatal lethal pulmonary phenotype and partially restored Na⁺ transport in renal, colonic, and pulmonary epithelia. At days 5–9, however, αENaC(−/−)Tg mice showed clinical features of severe PHA-1 with metabolic acidosis, urinary salt-wasting, growth retardation, and 50% mortality. Adult αENaC(−/−)Tg survivors exhibited a compensated PHA-1 with normal acid/base and electrolyte values but 6-fold elevation of plasma aldosterone compared with wild-type littermate controls. We conclude that partial restoration of ENaC-mediated Na⁺ absorption in this transgenic mouse results in a mouse model for PHA-1.     

The effects of carbon dioxide on oxygenation and systemic, cerebral, and pulmonary vascular hemodynamics after the bidirectional superior cavopulmonary anastomosis

OBJECTIVES: We investigated the effects of different CO(2) tensions on oxygenation, pulmonary blood flow (Qp), cerebral blood flow, and systemic blood flow (Qs) after the bidirectional superior cavopulmonary anastomosis (BCPA). BACKGROUND: Hypoxemia refractory to management of a high pulmonary vascular resistance index (PVRI) may complicate recovery from the BCPA. METHODS: After BCPA, CO(2) was added to the inspired gas of mechanically ventilated patients. The Qp, Qs, PVRI, and systemic vascular resistance index (SVRI) were calculated from oxygen consumption, intravascular pressures, and oxygen saturations. Cerebral blood flow was estimated by near infrared spectroscopy and transcranial Doppler. RESULTS: In nine patients (median age 7.1, range 2 to 23 months), arterial oxygen tension increased significantly (p < 0.005) from 36 +/- 6 mm Hg to 44 +/- 6 to 50 +/- 7 mm Hg at arterial carbon dioxide tensions (PaCO(2)) of 35, 45, and 55 mm Hg, respectively and decreased to 40 +/- 8 mm Hg at PaCO(2) 40 mm Hg. At a PaCO(2) of 55 and 45 compared with 35 mm Hg, Qp, cerebral blood flow, and Qs increased significantly, PVRI, Qp/Qs, and the ratio of Qp to inferior vena caval blood flow were unchanged, but SVRI decreased. CONCLUSIONS: We have demonstrated that after the BCPA, systemic oxygenation, Qp, Qs, and cerebral blood flow increased and SVRI decreased at CO(2) tensions of 45 and 55 mm Hg compared with 35 mm Hg. We suggest that hypoxemia after the BCPA is ameliorated by a higher PaCO(2) and that low PaCO(2) or alkalosis may be detrimental. Hypercarbic management strategies may allow earlier progression to the BCPA, which may contribute to reducing the interval morbidity in patients with a functional single ventricle.     

Patient Versus Professional Based Psychosocial Risk Factor Screening for Adverse Pregnancy Outcomes

To identify Psychopathology, Psychosocial problems and substance use (PPS) as predictors of adverse pregnancy outcomes, two screen-and-advice instruments were developed: Mind2Care (M2C, self-report) and Rotterdam Reproductive Risk Reduction (R4U, professional’s checklist). To decide on the best clinical approach of these risks, the performance of both instruments was compared. Observational study of 164 pregnant women who booked at two midwifery practices in Rotterdam. Women were consecutively screened with M2C and R4U. For referral to tailored care based on specific PPS risks, inter-test agreement of single risks was performed in terms of overall accuracy and positive accuracy (risk present according to both instruments). With univariate regression analysis we explored determinants of poor agreement (<90 %). For triage based on risk accumulation and for detecting women-at-risk for adverse birth outcomes, M2C and R4U sum scores were compared. Overall accuracy of single risks was high (mean 93 %). Positive accuracy was lower (mean 46 %) with poorest accuracy for current psychiatric symptoms. Educational level and ethnicity partly explained poor accuracy (p < 0.05). Overall low PPS prevalence decreased the statistical power. For triage, M2C and R4U sum scores were interchangeable from sum scores of five or more (difference <1 %). The probability of adverse birth outcomes similarly increased with risk accumulation for both instruments, identifying 55–75 % of women-at-risk. The self-report M2C and the professional’s R4U checklist seem interchangeable for triage of women-at-risk for PPS or adverse birth outcomes. However, the instruments seem to provide complementary information if used as a guidance to tailored risk-specific care.