ER-tethered stress sensor CREBH regulates mitochondrial unfolded protein response to maintain energy homeostasis.

The Mitochondrial Unfolded Protein Response (UPR), a mitochondria-originated stress response to altered mitochondrial proteostasis, plays important roles in various pathophysiological processes. In this study, we revealed that the endoplasmic reticulum (ER)-tethered stress sensor CREBH regulates UPR to maintain mitochondrial homeostasis and function in the liver. CREBH is enriched in and required for hepatic Mitochondria-Associated Membrane (MAM) expansion induced by energy demands.

Discovery of Two Novel Immunoepitopes and Development of a Peptide-based Sarcoidosis Immunoassay.

Sarcoidosis is a systemic granulomatous disorder associated with hypergammaglobulinemia and the presence of autoantibodies. The specific antigens initiating granulomatous inflammation in sarcoidosis are unknown, and there is no specific test available to diagnose sarcoidosis. To discover novel sarcoidosis antigens, we developed a high-throughput T7 phage display library derived from the sarcoidosis cDNA and identified numerous clones differentiating sarcoidosis from other respiratory diseases.

MIF modulates p38/ERK phosphorylation via MKP-1 induction in sarcoidosis.

Macrophage migration inhibitory factor (MIF) is a versatile cytokine that influences a variety of cellular processes important for immune regulation and tissue homeostasis. Sarcoidosis is a granulomatous disease characterized by extensive local inflammation and increased T helper cell mediated cytokines. We have shown that MIF has a modulatory role in cytokine networks in sarcoidosis.

Risk Indicators of Sarcoidosis Evolution-Unified Protocol (RISE-UP): protocol for a multi-centre, longitudinal, observational study to identify clinical features that are predictive of sarcoidosis progression.

Introduction: Sarcoidosis is a pulmonary and systemic granulomatous disease with a wide range of potential outcomes, from spontaneous resolution to end-stage organ damage and death. Currently, clinicians have no easy-to-use risk stratification tools for important clinical outcomes in sarcoidosis, such as progressive lung disease. This study will address two clinical practice needs: (1) development of a risk calculator that provides an estimate of the likelihood of pulmonary progression in sarcoidosis patients during the follow-up period and (2) determine the optimal interval for serial clinical monitoring (eg, 6, 12, 18 months) using these risk prediction tools.

Discovery of Novel Transketolase Epitopes and the Development of IgG-Based Tuberculosis Serodiagnostics.

Despite advances in rapid molecular techniques for tuberculosis (TB) diagnostics, there is an unmet need for a point-of-care, nonsputum-based test. Previously, through a T7 phage antigen display platform and immunoscreening, we identified that the serum IgGs of active TB patients differentially bind to several antigen-clones and that this immunoreactivity discriminates TB from other respiratory diseases. One of these high-performance clones has some homology to the transketolase of Mycobacterium tuberculosis ( TKT).

Modulatory role of macrophage migration inhibitory factor on cytokines and clinical features of sarcoidosis.

Sarcoidosis is a systemic granulomatous disease of unknown etiology with significant heterogeneity in organ manifestations and clinical course. Subjects with sarcoidosis share several features such as, non-necrotizing granuloma, hypergammaglobulinemia, increased local and circulating inflammatory cytokines. Macrophage migration inhibitory factor (MIF) is a pluripotent chemokine modulating cellular function.

Incidence and risk factors of COVID-19 associated pneumothorax.

Background: Pneumothorax has been increasingly observed among patients with coronavirus disease-2019 (COVID-19) pneumonia, specifically in those patients who develop acute respiratory distress syndrome (ARDS). In this study, we sought to determine the incidence and potential risk factors of pneumothorax in critically ill adults with COVID-19.

Method: This retrospective cohort study included adult patients with laboratory-confirmed SARS-CoV-2 infection admitted to one of the adult intensive care units of a tertiary, academic teaching hospital from May 2020 through May 2021.

Autoantibodies against cytoskeletons and lysosomal trafficking discriminate sarcoidosis from healthy controls, tuberculosis and lung cancers.

Sarcoidosis is a systemic granulomatous disease of unknown etiology. Hypergammaglobulinemia and the presence of autoantibodies in sarcoidosis suggest active humoral immunity to unknown antigen(s). We developed a complex cDNA library derived from tissues of sarcoidosis patients.

MKP-1 modulates ubiquitination/phosphorylation of TLR signaling.

Ubiquitination and phosphorylation are reversible posttranslational protein modifications regulating physiological and pathological processes. MAPK phosphatase (MKP)-1 regulates innate and adaptive immunity. The multifaceted roles of MKP-1 were attributed to dephosphorylation of p38 and JNK MAPKs.

Sarcoidosis and neuroendocrine tumours: case report and literature review.

Rare cases of co-existing sarcoidosis and carcinoid tumour have been previously reported in the literature. Both diseases may have vague and overlapping clinical presentations that can lead to delayed or missed diagnosis. To avoid this diagnostic pitfall, we discuss and compare the clinical presentations of all reported cases in the literature including our case.

Antiphospholipid antibodies in COVID-19: a meta-analysis and systematic review.

Background: Many studies reported high prevalence of antiphospholipid antibodies (aPL) in patients with COVID-19 raising questions about its true prevalence and its clinical impact on the disease course.

Methods: We conducted a meta-analysis and a systematic review to examine the prevalence of aPL and its clinical impact in patients with COVID-19.

Results: 21 studies with a total of 1159 patients were included in our meta-analysis.

The Role of Using Red-Topped - Non-Additive-Containing - Collecting Tube in Diagnosing Pseudohyperkalemia in Chronic Lymphocytic Leukemia.

Pseudohyperkalemia in the context of chronic lymphocytic leukemia (CLL) is becoming a common clinical presentation in our daily practice, yet the recognition and the overall approach to this condition remains a challenge as clinicians ponder on whether it's a true rise of serum potassium or not, weighing the risk-benefit ratio of giving the full anti-hyperkalemia measures, dreading the potential iatrogenic hypokalemia if it proves to be a pseudohyperkalemia instead.

Burden and impact of arrhythmias in asthma-related hospitalizations: Insight from the national inpatient sample.

Background: This study aimed to analyze the burden and impact of cardiac arrhythmias in adult patients hospitalized with asthma exacerbation using the nationwide inpatient database.

Methods: We used the National Inpatient Sample (NIS) database (2010-2014) to identify arrhythmias in asthma-related hospitalization and its impact on inpatient mortality, hospital length of stay (LOS), and hospitalization charges. We also used multivariable analysis to identify predictors of in-hospital arrhythmia and mortality.

Forty-One-Year-Old Man with Pulmonary Embolism 5 Months After COVID-19.

Background: Hypercoagulation is one of the striking features of COVID-19. Patients hospitalized with COVID-19 are at high risk for venous thromboembolism. However, it is unknown if the risk for venous thromboembolism persists after discharge.

Regulation of hepatic circadian metabolism by the E3 ubiquitin ligase HRD1-controlled CREBH/PPARα transcriptional program.

Objective: The endoplasmic reticulum (ER)-resident E3 ligase HRD1 and its co-activator Sel1L are major components of ER-associated degradation (ERAD) machinery. Here, we investigated the molecular mechanism and functional significance underlying the circadian regulation of HRD1/Sel1L-mediated protein degradation program in hepatic energy metabolism.

Methods: Genetically engineered animal models as well as gain- and loss-of-function studies were employed to address the circadian regulatory mechanism and functional significance.

The impact of coronavirus disease 2019 (COVID-19) response on central-line-associated bloodstream infections and blood culture contamination rates at a tertiary-care center in the Greater Detroit area.

We conducted a comparative retrospective study to quantify the impact of coronavirus disease 2019 (COVID-19) on patient safety. We found a statistically significant increase in central-line-associated bloodstream infections and blood culture contamination rates during the pandemic. Increased length of stay and mortality were also observed during the COVID-19 pandemic.

Platelets and renal failure in the SARS-CoV-2 syndrome.

The coronavirus disease 19 (COVID-19) is a highly transmittable viral infection caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 utilizes metallocarboxyl peptidase angiotensin receptor (ACE) 2 to gain entry into human cells. Activation of several proteases facilitates the interaction of viral spike proteins (S1) and ACE2 receptor.

Coronavirus Disease 2019 in Immunocompromised Organ Transplant Recipients: A Case Report and Review of the Literature.

Coronavirus disease 2019 (COVID-19) is an ongoing pandemic caused by a novel coronavirus called severe acute respiratory syndrome coronavirus 2. Our understanding of this new disease continues to grow. The impact of the disease on immunocompromised transplant recipients is largely unknown.

ACE2, Much More Than Just a Receptor for SARS-COV-2.

The rapidly evolving pandemic of severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection worldwide cost many lives. The angiotensin converting enzyme-2 (ACE-2) has been identified as the receptor for the SARS-CoV-2 viral entry. As such, it is now receiving renewed attention as a potential target for anti-viral therapeutics.

Derangement of Metabolic and Lysosomal Gene Profiles in Response to Dexamethasone Treatment in Sarcoidosis.

Glucocorticoids (GCs) play a central role in modulation of inflammation in various diseases, including respiratory diseases such as sarcoidosis. Surprisingly, the specific anti-inflammatory effects of GCs on different myeloid cells especially in macrophages remain poorly understood. Sarcoidosis is a systemic granulomatous disease of unknown etiology that occurs worldwide and is characterized by granuloma formation in different organs.

MKP-1 Modulates Mitochondrial Transcription Factors, Oxidative Phosphorylation, and Glycolysis.

Sepsis is the leading cause of death in the world. Recent reports suggest that in response to sepsis, metabolism of macrophages switches from oxidative phosphorylation to aerobic glycolysis. MAPK phosphatase (MKP)-1 (also known as DUSP1) localized in the nucleus and preferentially dephosphorylates p38 and JNK.

Management of repository corticotrophin injection therapy for pulmonary sarcoidosis: a Delphi study.

In patients treated with repository corticotrophin injection (RCI) for pulmonary sarcoidosis, effective management of adverse events may improve adherence. However, management of adverse events may be challenging due to limitations in real-world clinical experience with RCI and available published guidelines.We surveyed 12 physicians with a modified Delphi process using three questionnaires.