Single-cell reconstruction and mutation enrichment analysis identifies dysregulated cardiomyocyte and endothelial cells in congenital heart disease.

Congenital heart disease (CHD) is one of the most prevalent neonatal congenital anomalies. To catalog the putative candidate CHD risk genes, we collected 16,349 variants [single-nucleotide variants (SNVs) and Indels] impacting 8,308 genes in 3,166 CHD cases for a comprehensive meta-analysis. Using American College of Medical Genetics (ACMG) guidelines, we excluded the 0.

Cell-specific MAPT gene expression is preserved in neuronal and glial tau cytopathologies in progressive supranuclear palsy.

Microtubule-associated protein tau (MAPT) aggregates in neurons, astrocytes and oligodendrocytes in a number of neurodegenerative diseases, including progressive supranuclear palsy (PSP). Tau is a target of therapy and the strategy includes either the elimination of pathological tau aggregates or reducing MAPT expression, and thus the amount of tau protein made to prevent its aggregation. Disease-associated tau affects brain regions in a sequential manner that includes cell-to-cell spreading.

Analyzing single cell transcriptome data from severe COVID-19 patients.

We describe the protocol for identifying COVID-19 severity specific cell types and their regulatory marker genes using single-cell transcriptomics data. We construct COVID-19 comorbid disease-associated gene list using multiple databases and literature resources. Next, we identify specific cell type where comorbid genes are upregulated.

Detection of copy number variants and genes by chromosomal microarray in an Emirati neurodevelopmental disorders cohort.

Copy number variations (CNVs) are highly implicated in the etiology of neurodevelopmental disorders (NDDs), and chromosomal microarray analysis (CMA) has been recommended as a first-tier test for many NDDs. We undertook a study to identify clinically relevant CNVs and genes in an ethnically homogenous population of the United Arab Emirates. We genotyped 98 patients with NDDs using genome-wide chromosomal microarray analysis, and observed 47.

Single-cell transcriptome identifies molecular subtype of autism spectrum disorder impacted by de novo loss-of-function variants regulating glial cells.

Background: In recent years, several hundred autism spectrum disorder (ASD) implicated genes have been discovered impacting a wide range of molecular pathways. However, the molecular underpinning of ASD, particularly from the point of view of 'brain to behaviour' pathogenic mechanisms, remains largely unknown.

Methods: We undertook a study to investigate patterns of spatiotemporal and cell type expression of ASD-implicated genes by integrating large-scale brain single-cell transcriptomes (> million cells) and de novo loss-of-function (LOF) ASD variants (impacting 852 genes from 40,122 cases).

Single-cell transcriptome identifies upregulated subtype of alveolar macrophages in patients with critical COVID-19.

Understanding host cell heterogeneity is critical for unraveling disease mechanism. Utilizing large-scale single-cell transcriptomics, we analyzed multiple tissue specimens from patients with life-threatening COVID-19 pneumonia, compared with healthy controls. We identified a subtype of monocyte-derived alveolar macrophages (MoAMs) where genes associated with severe COVID-19 comorbidities are significantly upregulated in bronchoalveolar lavage fluid of critical cases.

Reversible Blindness as Presenting Manifestation of Severe Diabetic Ketoacidosis.

The presenting symptoms of diabetic ketoacidosis (DKA) include abdominal pain, polyuria and nausea. Diabetes has well known chronic ocular complications like glaucoma, cataracts and retinopathy. We report a case of reversible blindness as a presenting manifestation of DKA that has been reported in literature only 3 times previously.

Bronchoscopic advances in the management of aerodigestive fistulas.

Malignant aerodigestive fistula (ADF) is an uncommon condition complicating thoracic malignancies. It results in increased morbidity and mortality and warrants therapeutic intervention. The management approach depends on symptoms, configuration, location, and extent of the fistula.

Whole lung lavage-technical details, challenges and management of complications.

Pulmonary alveolar proteinosis (PAP) is a rare disease characterized by alveolar accumulation of surfactant material with resulting hypoxemia and reduced lung function. Whole lung lavage (WLL) to physically remove the proteinaceous material from the affected lung is the standard treatment. Since its original description in 1964, there have been increasing numbers of WLL procedures done worldwide and the technique has been variously refined and modified.

Radial Probe Ultrasound-Guided Cryobiopsy.

Fluoroscopy-guided transbronchial forceps biopsy has a low diagnostic yield in patients with radiographic suspicion of interstitial lung disease. Cryobiopsy has a higher diagnostic yield likely due to preserved lung architecture and larger biopsies; however, there is an increased risk of major airway bleeding and pneumothorax. Simultaneous use of endobronchial balloon blocker allows for containment of bleeding after cryobiopsy to the affected lobe.

Stenting of critical tracheal stenosis with adjuvant cardio-pulmonary bypass.

Severe and critical central airway obstruction causing impaired ventilation and/or oxygenation can impose tremendous challenges on the interventional pulmonologist. Near total airway obstruction can rapidly evolve into potentially fatal complete airway occlusion during bronchoscopic airway manipulation under moderate sedation; as well as during the induction of the general anesthesia. Although there are currently interventional pulmonary procedures available to tackle the critical airway obstruction in extreme situations, cardio-pulmonary bypass should be considered prior to the intervention to maintain the adequate gas exchange during the procedure.

Euglycemic Diabetic Ketoacidosis in a Patient with Cocaine Intoxication.

Diabetic ketoacidosis (DKA) is characterized by elevated anion gap metabolic acidosis, hyperglycemia, and elevated ketones in urine and blood. Hyperglycemia is a key component of DKA; however, a subset of DKA patients can present with near-normal blood glucose, an entity described as "euglycemic DKA." This rare phenomenon is thought to be due to starvation and food restriction in insulin dependent diabetic patients.

Pancreaticopericardial Fistula: A Case Report and Literature Review.

Purpose. Pancreaticopericardial fistula (PPF) is an extremely rare complication of acute or chronic pancreatitis. This paper presents a rare case of PPF and provides systematic review of existing cases from 1970 to 2014.

Review and Outcome of Prolonged Cardiopulmonary Resuscitation.

The maximal duration of cardiopulmonary resuscitation (CPR) is unknown. We report a case of prolonged CPR. We have then reviewed all published cases with CPR duration equal to or more than 20 minutes.

STOP-BANG questionnaire as a screening tool for diagnosis of obstructive sleep apnea by unattended portable monitoring sleep study.

The Snoring, Tiredness, Observed apnea, high blood Pressure (STOP)-Body mass index (BMI), Age, Neck circumference, and Gender (BANG) questionnaire is a well validated screening tool for diagnosis of Obstructive sleep apnea (OSA) by an in- lab sleep study. However, performance of STOP-BANG as a screening tool for diagnosis of OSA in patients undergoing portable monitoring (PM) sleep study has not been well validated. We conducted a retrospective chart review of patients older than 18 years who had unattended portable monitoring sleep study done at a VA medical center between June 2012 and October 2014.

Sleep, immunity and inflammation in gastrointestinal disorders.

Sleep disorders have become a global issue, and discovering their causes and consequences are the focus of many research endeavors. An estimated 70 million Americans suffer from some form of sleep disorder. Certain sleep disorders have been shown to cause neurocognitive impairment such as decreased cognitive ability, slower response times and performance detriments.

Pulmonary involvement in patients with thrombotic thrombocytopenic purpura.

Objectives: To determine the frequency of pulmonary involvement in patients with thrombotic thrombocytopenic purpura (TTP).

Methods: The experience of the Oklahoma TTP-HUS (hemolytic-uremic syndrome) Registry, a population-based cohort of consecutive patients without selection or referral bias, 1995-2012, was analyzed. Evidence for pulmonary involvement in patients with TTP was also documented with a systematic review of published reports.

Bronchial responsiveness in patients with restrictive spirometry.

Background: Improvement in PFT after bronchodilators is characteristic of obstructive airway diseases such as COPD. However, improvement in patients with restrictive pattern is occasionally seen. We aim to determine the clinical significance of a bronchodilator responsive restrictive defect.

False-negative PET scan with bronchioloalveolar carcinoma: an important diagnostic caveat.

Positron emission tomography (PET) is becoming widely accepted as a powerful diagnostic tool for the diagnosis of lung cancer, but it has very poor sensitivity for the detection of bronchioloalveolar carcinoma (BAC) and adenocarcinoma with BAC pattern, the less common form of pulmonary neoplasia. We present a case of a patient with a negative PET scan who might have been followed by observation but was found to have bronchioloalveolar carcinoma at thoracotomy. PET has a reported sensitivity of over 98% in most series but misses almost two-thirds of BAC lesions, which might delay invasive testing and early diagnosis of this potentially lethal cancer.

Activated protein C improves survival in severe sepsis patients with elevated troponin.

Objective: Multiple studies in sepsis have demonstrated that elevated troponin is associated with poor outcome. The elevated troponin in this situation is thought to be secondary to microthrombi. We hypothesized that recombinant human activated protein C (APC) treatment would improve outcomes in severe sepsis patients who have elevated troponin.