Transient Ischaemic Attack in a Patient With Conn Syndrome: A Case Report and Literature Review on the Importance of Identifying Secondary Hypertension.

Background/aim: Transient ischaemic attack (TIA) is characterised by a temporary neurological dysfunction resulting from focal ischaemia in the brain, spinal cord or retina without acute infarction. These episodes typically last less than 24 hours and are significant predictors of subsequent ischaemic strokes. Hypertension is a major risk factor for cerebrovascular events, and primary aldosteronism (PA) is recognised as a common cause of secondary hypertension.

Multilayer network analysis in patients with end-stage kidney disease.

This study aimed to investigate alterations in a multilayer network combining structural and functional layers in patients with end-stage kidney disease (ESKD) compared with healthy controls. In all, 38 ESKD patients and 43 healthy participants were prospectively enrolled. They exhibited normal brain magnetic resonance imaging (MRI) without any structural lesions.

Improving diagnosis of primary aldosteronism through education: a modified Delphi study to identify key learning points.

Background: Primary aldosteronism (PA) is the most common endocrine cause of secondary hypertension and can be effectively managed, or even cured, with targeted treatment. Despite this, it remains largely undiagnosed leaving a significant patient population with resistant hypertension and modifiable cardiovascular risk.

Objective: To determine expert consensus on key information about PA that should ideally be taught to medical students as a step toward improving the detection of this common, underdiagnosed, and often easily treated condition.

A technique to enhance the gingival esthetics of a prototype complete arch fixed implant-supported prototype prosthesis using a 3D printed gingival veneer.

An important step in the workflow for a complete arch fixed implant-supported prosthesis is the fabrication of a prototype resin prosthesis to allow the patient to visualize the definitive treatment outcome and also to use as an interim prosthesis. Producing a prototype prosthesis with the natural appearance of the gingival color and contour has been challenging. Current methods include painted stains, manually applied pink composite resin or autopolymerizing acrylic resin, and multicolored resin blocks, but these are all relatively expensive, have less than optimal esthetics, and are labor-intensive and time-consuming.

Mild autonomous cortisol secretion leads to reduced volumetric BMD at lumbar spine in patients with primary aldosteronism.

Objectives: Glucocorticoid cosecretion is more common in primary aldosteronism (PA) than previously thought. Chronic subtle cortisol excess in patients with mild autonomous cortisol secretion (MACS) negatively affects bone health. This study aimed to evaluate the impact of MACS on bone density and turnover markers in PA patients.

Functional connectivity abnormalities in clinical variants of progressive supranuclear palsy.

Progressive supranuclear palsy (PSP) can present with different clinical variants which show distinct, but partially overlapping, patterns of neurodegeneration and tau deposition in a network of regions including cerebellar dentate, superior cerebellar peduncle, midbrain, thalamus, basal ganglia, and frontal lobe. We sought to determine whether disruptions in functional connectivity within this PSP network measured using resting-state functional MRI (rs-fMRI) differed between PSP-Richardson's syndrome (PSP-RS) and the cortical and subcortical clinical variants of PSP. Structural MRI and rs-fMRI scans were collected for 36 PSP-RS, 25 PSP-cortical and 34 PSP-subcortical participants who met the Movement Disorder Society PSP clinical criteria.

Discovery of 4-(5-Membered)Heteroarylether-6-methylpicolinamide Negative Allosteric Modulators of Metabotropic Glutamate Receptor Subtype 5.

This Letter details our efforts to develop novel, non-acetylene-containing metabotropic glutamate receptor subtype 5 (mGlu) negative allosteric modulators (NAMs) with improved pharmacological properties. This endeavor involved replacing the ether-linked pyrimidine moiety, a metabolic liability, with various 5-membered heterocycles. From this exercise, we identified , a highly brain penetrant and selective mGlu NAM which displayed moderate potency against both human and rat mGlu.

Impact of confirmatory test results on subtype classification and biochemical outcome following unilateral adrenalectomy in patients with primary aldosteronism.

Context: Primary aldosteronism (PA) is the most common form of endocrine hypertension. According to the Endocrine Society Practice Guidelines, the diagnosis of PA requires a pathological screening test result and non-suppressible aldosterone levels during confirmatory testing. Sequential testing with more than one confirmatory test may result in discordant test results.

Hippocampal connectivity dynamics and volumetric alterations predict cognitive status in migraine: A resting-state fMRI study.

The etiology of cognitive decline linked to migraine remains unclear, with a growing recurrence rate and potential increased dementia risk among sufferers. Cognitive dysfunction has recently gained attention as a significant problem among migraine sufferers that can be related to alterations in hippocampal function and structure. This study explores hippocampal subfield connectivity and volume changes in migraine patients.

Discovery of VU6024578/BI02982816: An mGlu Positive Allosteric Modulator with Efficacy in Preclinical Antipsychotic and Cognition Models.

Herein, we report progress toward a metabotropic glutamate receptor subtype 1 (mGlu) positive allosteric modulator (PAM) clinical candidate and the discovery of VU6024578/BI02982816. From a weak high-throughput screening hit (VU0538160, EC > 10 μM, 71% Glu), optimization efforts improved functional potency over 185-fold to deliver the selective (inactive on mGlu) and CNS penetrant (rat K = 0.99, K = 0.

Discovery of VU0467319: an M Positive Allosteric Modulator Candidate That Advanced into Clinical Trials.

Herein we detail the of VU0467319 (VU319), an M Positive Allosteric Modulator (PAM) clinical candidate that successfully completed a Phase I Single Ascending Dose (SAD) clinical trial. VU319 () is a moderately potent M PAM (M PAM EC = 492 nM ± 2.9 nM, 71.

Sinusitis and rhinitis among US veterans deployed to Southwest Asia and Afghanistan after September 11, 2001.

Background: Post-9/11 veterans were exposed to environmental and occupational pollutants during deployment.

Objective: Our aim was to determine associations between deployment-related exposures and sinusitis and rhinitis.

Methods: Between April 2018 and March 2020, veterans with land-based deployment after 9/11 who were living within 25 miles of 6 Department of Veteran Affairs medical centers were randomly chosen by using a Defense Manpower Data Center roster.

A Single Center Experience of Special Cases: Isolated Adrenal Myelolipoma and Adrenocortical Adenoma with Myelolipomatous Component.

Objective: Isolated adrenal myelolipoma (IAM) is an uncommon, nonfunctioning tumour of the adrenal gland, primarily composed of adipose tissue and hematopoietic trilinear cells. The etiopathogenesis and clinical relevance of this neoplasm remain poorly understood. However, similar myelolipomatous alterations can also occur within adrenocortical adenomas.

Canadian Clinical Guidelines on Social Isolation and Loneliness in Older Adults.

Background: Preventing and addressing social isolation and loneliness among older adults is important because of the known associations with negative health outcomes. The Canadian Coalition for Seniors' Mental Health (CCSMH) took on the task of creating clinical guidelines.

Method: A multidisciplinary working group was established.

Midterm survival, clinical, and hemodynamic outcomes of a novel mechanical mitral valve prosthesis.

Objective: To evaluate the midterm survival, clinical, and hemodynamic outcomes of the On-X mechanical mitral valve, based on the 5-year results of the Prospective Randomized On-X Anticoagulation Clinical Trial (PROACT).

Method: PROACT Mitral was a multicenter study evaluating 401 patients who underwent mitral valve replacement (MVR) with either Standard or Conform-X On-X mitral valves, comparing low-dose and standard-dose warfarin. Here we report prespecified secondary outcomes of survival, New York Heart Association (NYHA) functional classification, and valve hemodynamics as assessed by core lab-adjudicated echocardiography at 1, 3, and 5 years in the pooled population.

Determination of MexXY-OprM substrate profile in a major efflux knockout system reveals distinct antibiotic substrate classes.

Defining the substrates of Resistance-Nodulation-Division (RND) systems is often complicated by the presence of multiple systems in a single bacterial species. Using a major efflux knockout strain, we developed a system that enables controlled expression of MexXY-OprM in the absence of background efflux complexes with overlapping substrate profiles. This system identified three groups of potential substrates: substrates, partial substrates, and nonsubstrates, and defined trimethoprim as a new substrate for MexXY-OprM.