Protocol for live neuron imaging analysis of basal surface fraction and dynamic availability of the dopamine transporter using DAT-pHluorin.

Surface availability of the dopamine (DA) transporter (DAT) critically influences DA transmission. Here, we present a protocol that describes the preparation of mouse ventral midbrain neurons, the expression of a new optical sensor, DAT-pHluorin, and the utilization of this sensor to analyze the surface availability of DAT in live neurons via fluorescent microscopy. This approach allows quantitative measures of basal surface DAT fraction under genetic backgrounds of interest and live trafficking of DAT in response to psychoactive substances.

Blood pressure control in pregnant patients with chronic hypertension and diabetes: should <130/80 be the target?

Background: The Chronic Hypertension and Pregnancy Study demonstrated that a target blood pressure of <140/90 mm Hg during pregnancy is associated with improved perinatal outcomes. Outside of pregnancy, pharmacologic therapy for patients with diabetes and hypertension is adjusted to a target blood pressure of <130/80 mm Hg. During pregnancy, patients with both diabetes and chronic hypertension may also benefit from tighter control with a target blood pressure <130/80 mm Hg.

Effects of Antihypertensive Therapy During Pregnancy on Postpartum Blood Pressure Control.

Objective: To compare differences in postpartum blood pressure (BP) control (BP below 140/90 mm Hg) for participants with hypertension randomized to receive antihypertensive treatment compared with no treatment during pregnancy.

Methods: This study was a planned secondary analysis of a multicenter, open-label, randomized controlled trial (The CHAP [Chronic Hypertension and Pregnancy] trial). Pregnant participants with mild chronic hypertension (BP below 160/105 mm Hg) were randomized into two groups: active (antihypertensive treatment) or control (no treatment unless severe hypertension, BP 160/105 mm Hg or higher).

High-Dose Propranolol for Severe and Chronic Aggression in Autism Spectrum Disorder: A Pilot, Double-Blind, Placebo-Controlled, Randomized Crossover Study.

Background: Despite the use of behavioral interventions and psychotropic medications, many individuals with autism spectrum disorder (ASD) who engage in severe aggression remain refractory to conventional treatment. Propranolol, a beta-blocker, has accumulated much anecdotal evidence as a promising option. However, well-designed studies are rare, and the apprehension about cardiovascular side effects from large doses continues to exist.

Parkinson's disease gene, Synaptojanin1, dysregulates the surface maintenance of the dopamine transporter.

Missense mutations of PARK20/SYNJ1 (synaptojanin1/Synj1) were found in complex forms of familial Parkinsonism. However, the Synj1-regulated molecular and cellular changes associated with dopaminergic dysfunction remain unknown. We now report a fast depletion of evoked dopamine and impaired maintenance of the axonal dopamine transporter (DAT) in the Synj1 haploinsufficient (Synj1+/-) neurons.

A Diagnostic Stewardship Intervention to Improve Utilization of 1,3 β-D-Glucan Testing at a Single Academic Center: Five-Year Experience.

Background: (1,3)- β-D-glucan (BDG) testing is one of the noninvasive tests to aid diagnosis of invasive fungal infections (IFIs). The study results have been heterogenous, and diagnostic performance varies depending on the risks for IFI. Thus, it is important to select appropriate patients for BDG testing to prevent false-positive results.

Optimal Timing of Delivery for Pregnant Individuals With Mild Chronic Hypertension.

Objective: To investigate the optimal gestational age to deliver pregnant people with chronic hypertension to improve perinatal outcomes.

Methods: We conducted a planned secondary analysis of a randomized controlled trial of chronic hypertension treatment to different blood pressure goals. Participants with term, singleton gestations were included.

Pregnancy Outcomes of Nifedipine Compared With Labetalol for Oral Treatment of Mild Chronic Hypertension.

Objective: To evaluate maternal and neonatal outcomes by type of antihypertensive used in participants of the CHAP (Chronic Hypertension in Pregnancy) trial.

Methods: We conducted a planned secondary analysis of CHAP, an open-label, multicenter, randomized trial of antihypertensive treatment compared with standard care (no treatment unless severe hypertension developed) in pregnant patients with mild chronic hypertension (blood pressure 140-159/90-104 mm Hg before 20 weeks of gestation) and singleton pregnancies. We performed three comparisons based on medications prescribed at enrollment: labetalol compared with standard care, nifedipine compared with standard care, and labetalol compared with nifedipine.

1 Patient With Single Coronary Artery, Giant Coronary Artery Aneurysm, Contained Rupture, and Fistula.

Single coronary artery, giant coronary artery aneurysm, and coronary cameral fistula are rare congenital anomalies, and can cause a range of presentations. To our knowledge, this is the first reported case of all 3 entities occurring simultaneously in 1 patient, with largely unknown implications. Multimodal imaging was essential in prompt diagnosis and management.

A conserved inhibitory interdomain interaction regulates DNA-binding activities of hybrid two-component systems in .

Unlabelled: Hybrid two-component systems (HTCSs) comprise a major class of transcription regulators of polysaccharide utilization genes in . Distinct from classical two-component systems in which signal transduction is carried out by intermolecular phosphotransfer between a histidine kinase (HK) and a cognate response regulator (RR), HTCSs contain the membrane sensor HK and the RR transcriptional regulator within a single polypeptide chain. Tethering the DNA-binding domain (DBD) of the RR with the dimeric HK domain in an HTCS could potentially promote dimerization of the DBDs and would thus require a mechanism to suppress DNA-binding activity in the absence of stimulus.

Sleep quality differences among caregivers for persons living with and without dementia.

Objectives: This study examined the relationship between caring for a person with/without dementia and caregiver sleep quality, and analyzed the extent to which perceived benefits of caregiving and assessments of caregiver-recipient relationship quality explain the relationship between care recipient dementia status and caregiver sleep quality.

Method: Data were analyzed from caregivers for persons with no or probable dementia who participated in the 2017 National Study of Caregiving (NSOC) and National Health and Aging Trends Study. Caregiver sleep quality was measured using NSOC time diary interview.

Mean Arterial Pressure and Neonatal Outcomes in Pregnancies Complicated by Mild Chronic Hypertension.

Objective: To estimate the association between mean arterial pressure during pregnancy and neonatal outcomes in participants with chronic hypertension using data from the CHAP (Chronic Hypertension and Pregnancy) trial.

Methods: A secondary analysis of the CHAP trial, an open-label, multicenter randomized trial of antihypertensive treatment in pregnancy, was conducted. The CHAP trial enrolled participants with mild chronic hypertension (blood pressure [BP] 140-159/90-104 mm Hg) and singleton pregnancies less than 23 weeks of gestation, randomizing them to active treatment (maintained on antihypertensive therapy with a goal BP below 140/90 mm Hg) or standard treatment (control; antihypertensives withheld unless BP reached 160 mm Hg systolic BP or higher or 105 mm Hg diastolic BP or higher).

Parkinson's disease gene, Synaptojanin1, dysregulates the surface maintenance of the dopamine transporter.

Missense mutations of PARK20/ (synaptojanin1/Synj1) have been linked to complex forms of familial parkinsonism, however, the molecular and cellular changes associated with dopaminergic dysfunction remains unknown. We now report fast depletion of evoked dopamine (DA) and altered maintenance of the axonal dopamine transporter (DAT) in the neurons. While Synj1 has been traditionally known to facilitate the endocytosis of synaptic vesicles, we demonstrated that axons of cultured neurons exhibit an increase of total DAT but a reduction of the surface DAT, which could be exacerbated by neuronal activity.

Fibrinolysis-Mediated Pathways in Acute Liver Injury.

Acute liver injury (ALI), that is, the development of reduced liver function in patients without preexisting liver disease, can result from a wide range of causes, such as viral or bacterial infection, autoimmune disease, or adverse reaction to prescription and over-the-counter medications. ALI patients present with a complex coagulopathy, characterized by both hypercoagulable and hypocoagulable features. Similarly, ALI patients display a profound dysregulation of the fibrinolytic system with the vast majority of patients presenting with a hypofibrinolytic phenotype.

Removal of pomt1 in zebrafish leads to loss of α-dystroglycan glycosylation and dystroglycanopathy phenotypes.

Biallelic mutations in Protein O-mannosyltransferase 1 (POMT1) are among the most common causes of a severe group of congenital muscular dystrophies (CMDs) known as dystroglycanopathies. POMT1 is a glycosyltransferase responsible for the attachment of a functional glycan mediating interactions between the transmembrane glycoprotein dystroglycan and its binding partners in the extracellular matrix (ECM). Disruptions in these cell-ECM interactions lead to multiple developmental defects causing brain and eye malformations in addition to CMD.

Management of sleep disorders in autism spectrum disorder with co-occurring attention-deficit hyperactivity disorder: update for clinicians.

Aims: To update and examine available literature germane to the recognition, assessment and treatment of comorbid autism spectrum disorder (ASD), attention-deficit hyperactivity disorder (ADHD) and sleep disruption, with a predominant focus on children, adolescents and emerging adults.

Background: Considerable overlaps exist among ASD, ADHD and sleep disruption. Literature and guidance for clinicians, administrators, policy makers and families have been limited, as such deliberations were rarely considered until 2013.