KDM6A Demethylase Regulates Renal Sodium Excretion and Blood Pressure.

BACKGROUND: KDM6A (Lysine-Specific Demethylase 6A) is a specific demethylase for histone 3 lysine (K) 27 trimethylation (H3K27me3). The purpose of this study is to investigate whether KDM6A in renal tubule cells plays a role in the regulation of kidney function and blood pressure. METHODS: We first crossed Ksp-Cre+/- and KDM6Aflox/flox mice for generating inducible kidney-specific deletion of KDM6A gene. RESULTS: Notably, conditional knockout of KDM6A gene in renal tubule cells (KDM6A-cKO) increased H3K27me3 levels which leads to a decrease in Na excretion and elevation of blood pressure. Further analysis showed that the expression of NKCC2 (Na-K-2Cl cotransporter 2) and NCC (Na-Cl cotransporters) was upregulated which contributes to impaired Na excretion in KDM6A-cKO mice. The expression of AQP2 (aquaporin 2) was also increased in KDM6A-cKO mice, which may facilitate water reabsorption in KDM6A-cKO mice. The expression of Klotho was downregulated while expression of aging markers including p53, p21, and p16 was upregulated in kidneys of KDM6A-cKO mice, indicating that deletion of KDM6A in the renal tubule cells promotes kidney aging. Interestingly, KDM6A-cKO mice developed salt-sensitive hypertension which can be rescued by treatment with Klotho. KDM6A deficiency induced salt-sensitive hypertension likely through downregulation of the Klotho/ERK (extracellular signal-regulated kinase) signaling and upregulation of the WNK (with-no-lysine kinase) signaling. CONCLUSIONS: This study provides the first evidence that KDM6A plays an essential role in maintaining normal tubular function and blood pressure. Renal tubule cell specific KDM6A deficiency causes hypertension due to increased H3K27me3 levels and the resultant downregulation of Klotho gene expression which disrupts the Klotho/ERK/NCC/NKCC2 signaling.

Increased anxiety symptoms in pediatric type 1 diabetes during the acute phase of COVID-19 lockdown.

OBJECTIVES: The prevalence of mental health issues has increased at an alarming rate during the COVID-19 pandemic. Furthermore, an exacerbated psychosocial burden in populations with chronic disease is observed. This cross-sectional study evaluated the psychosocial factors of pediatric type 1 diabetes (T1D) during the COVID-19 pandemic. METHODS: During April 2020, 15 min phone interviews were performed for pediatric T1D group (n=100) and healthy comparison group (n=93) to assess psychosocial functioning during the acute lockdown phase of the pandemic. The patient health questionnaire-4 was utilized to assess anxiety and depressive symptoms. An additional questionnaire to assess specific concerns related to T1D and COVID-19 was administered to the T1D group to explore potential causes for increased psychosocial burden. RESULTS: T1D was associated with a five-times higher risk of anxiety symptoms. Increased anxiety symptoms in T1D group appear to be, at least in part, due to fear of higher risk of severe COVID-19 infection and uncertainty regarding access to diabetes supplies. CONCLUSIONS: This study provides a snapshot of mental well-being in a diverse population of patients with T1D in the acute phase of a crisis and underscores the need for timely, accurate medical information and distribution of medical resources for pediatric T1D population.

Hemiparesis With Hypoglycemia in a Child With Hypopituitarism Involving LHX4 Gene Deletion.

We report a case of a 17-month-old boy with developmental delay who presented with acute-onset right-sided hemiparesis and hypoglycemia. Severe hypotension developed during his sedation for MRI and magnetic resonance angiography. Imaging revealed a hypoplastic pituitary gland within a shallow sella turcica and findings suggestive of moyamoya syndrome. Hemiparesis resolved 5 hours after correction of hypoglycemia with dextrose infusion, and severe hypotension improved with crystalloid fluids and vasopressors. Magnetic resonance angiography repeated 24 hours later revealed resolution of the vascular finding. Additional biochemical testing was consistent with hypopituitarism, and genetic evaluation revealed that the patient had a microdeletion including the LHX4 gene, which has been implicated in combined pituitary hormone deficiency type IV. Hypoglycemia frequently presents with autonomic or neuroglycopenic symptoms. However, when hypoglycemia presents with an isolated neurologic deficit like hemiparesis with preservation of alertness, it can be challenging to differentiate a cerebrovascular event from hypoglycemia-induced symptoms, leading to a delay in endocrine evaluation. Hypoglycemic hemiparesis is rare in childhood and is reported in children with diabetes mellitus or hyperinsulinism. This case expands the clinical spectrum of hemiparesis as a presenting sign of hypoglycemia in growth hormone and adrenocorticotropic hormone/cortisol deficiencies.

Pediatric diabetic ketoacidosis presenting with Streptococcus intermedius brain abscess.

OBJECTIVES: Report a novel case of new-onset type 1 diabetes in a pediatric patient presenting with DKA and concurrent Streptococcus intermedius brain abscess. CASE PRESENTATION: The following case report is that of a previously healthy 12 year-old girl presenting with new-onset type 1 diabetes with mild diabetic ketoacidosis and subsequently found to have a brain abscess. Over the course of her hospital stay, she developed seizures and was found to have a 1.3 × 1.0 × 1.2 cm right frontal parasagittal mass culture-positive for S. intermedius. Neurologic symptoms were unmasked once insulin treatment was initiated and ketosis improved, supporting the relationship between therapeutic ketosis and the management of medication-refractory epilepsy. CONCLUSIONS: This case both supports the relationship between therapeutic ketosis and the management of medication-refractory epilepsy and highlights the need to carefully consider comorbid conditions in patients with DKA and new onset neurological symptoms.

Association of Sleep Duration with Stroke in Diabetic Patients: Analysis of the National Health Interview Survey.

BACKGROUND: Habitual sleep duration is increasingly being recognized as an important risk factor for stroke. We sought to describe the association between sleep duration and stroke in a cohort of individuals with diabetes. METHODS: Data from the National Health Interview Survey for the years 2004-2013 were used. Only those answering "yes" to the question "Have you EVER been told by a doctor or other health professional that you have diabetes or sugar diabetes?" were included in the analysis. Sleep duration was categorized as short (≤6 hours), normal (7-8 hours), or long (≥9 hours). Self-reported diagnosis of stroke was the main outcome of interest. FINDINGS: A total number of 26,364 self-reported diabetic individuals provided data for analysis. Stroke was reported in 9.1% of short sleepers, 16.1% of long sleepers, and 8.3% of normative sleepers (P < .05). In the unadjusted model, short and long sleepers had an increased odds of stroke compared to normal sleepers (odds ratio [OR] = 1.12, 95% confidence interval [CI]: 1.02-1.23, P = .01; and OR = 2.18, 95% CI: 1.96-2.42, P = .01; respectively), but the association between short sleep and stroke became nonsignificant after multivariate adjustment (OR = 1.15, 95% CI: .95-1.40, P = .16) except in white participants. The association between long sleep duration and stroke persisted (OR = 1.46, 95% CI: 1.16-1.84, P = .01), especially in males (OR = 1.62, 95% CI: 1.14-2.28) and in white participants (OR = 1.97, 95% CI: 1.47-2.65). CONCLUSION: In diabetic patients, abnormal sleep duration was associated with increased risk of stroke, and this association varied among different sex and ethnic groups.

Right Atrial Myxoma and Syncope.

BACKGROUND: Right atrial myxoma accounts for 15-20% of cardiac myxomas and syncope is a very rare manifestation. We present the case of an 89-year-old man with right atrial myxoma and syncope, and discuss the role of cardiac magnetic resonance imaging (MRI) in the diagnosis of myxomas. CASE REPORT: An 89-year-old man with a history of hypertension, hyperlipidemia, chronic kidney disease stage 4, mild dementia, and benign prostatic hyperplasia presented to the emergency department with an episode of syncope. Physical examination demonstrated normal and regular heart sounds, and normal respiratory rate and oxygen saturation. Echocardiogram described a well-circumscribed echo-dense mass in the right atrial cavity, which was attached to the septum but not obstructing the tricuspid annulus, measuring 1.7×2.2 cm at its widest diameter. Cardiac MRI revealed a mass with dark intensity which enhanced heterogeneously following intravenous administration of gadolinium-chelate, consistent with a myxoma. The location of this myxoma, coupled with the presence of a stalk allowing mobility, provides a clue to how this patient experienced transient obstruction of the tricuspid valve leading to syncope. CONCLUSIONS: Right heart tumors should be considered in the differential diagnosis of unexplained syncope. Cardiac MRI with gadolinium-chelate administration can help differentiate this tumor from a right-sided atrial thrombus, which can pose a diagnostic challenge.