Evaluation of Hepatic Steatosis and Fibrosis Using Transient Elastography in Patients With Obstructive Sleep Apnea.

Objectives: Obstructive sleep apnea (OSA) is an independent risk factor for non-alcoholic fatty liver disease. This study was planned to assess proportion of patients with OSA that have hepatic steatosis and fibrosis, as measured by transient elastography, to explore variables influencing their development and to find out the polysomnography parameters that predict the need for transient elastography screening in OSA. Methods: Consecutive participants having polysomnography proven OSA were included in the study after screening for eligibility criteria. Data of the polysomnography were scored manually following standard criteria. Participants were subjected to transient elastography (Fibroscan®) and serum investigations after diagnostic polysomnography. The polysomnography, fibroscan®, and laboratory data were tabulated and analyzed. Results: A total of 71 participants were enrolled. 16.9% participants had mild OSA, 28.2% had moderate OSA, and remaining participants had severe OSA. Liver steatosis was found in 63.4% participants while hepatic fibrosis was noted in 9.9%. Oxygen desaturation index (ODI), apnea-hypopnea index (AHI), and percentage of sleep spent below 90% oxygen saturation (T90) were significantly associated with the presence of hepatic steatosis and fibrosis. Receiver operating curve (ROC) showed that at the cut-offs of 73 events/hr, 13% and 72.2 events/hr, AHI, T90 and ODI, predicted hepatic fibrosis with area under ROC of 0.960, 0.944, and 0.933, respectively (P < 0.001). Conclusions: Patients with OSA are at increased risk for development of hepatic steatosis and fibrosis. ODI, AHI, and T90 during polysomnography predict the presence of underlying hepatic fibrosis.

Voltage-dependent anion channel 3 (VDAC3) mediates P. syringae induced ABA-SA signaling crosstalk in Arabidopsis thaliana.

Pathogen severely affects plant mitochondrial processes including respiration, however, the roles and mechanism of mitochondrial protein during the immune response remain largely unexplored. The interplay of plant hormone signaling during defense is an outcome of plant pathogen interaction. We recently discovered that the Arabidopsis calcineurin B-like interacting protein kinase 9 (AtCIPK9) interacts with the voltage-dependent anion channel 3 (AtVDAC3) and inhibits MV-induced oxidative damage. Here we report the characterization of AtVDAC3 in an antagonistic interaction pathway between abscisic acid (ABA) and salicylic acid (SA) signaling in Pseudomonas syringae -Arabidopsis interaction. In this study, we observed that mutants of AtVDAC3 were highly susceptible to Pseudomonas syringae infection as compared to the wild type (WT) Arabidopsis plants. Transcripts of VDAC3 and CIPK9 were inducible upon ABA application. Following pathogen exposure, expression analyses of ABA and SA biosynthesis genes indicated that the function of VDAC3 is required for isochorisimate synthase 1 (ICS1) expression but not for Nine-cis-epoxycaotenoid dioxygenase 3 (NCED3) expression. Despite the fact that vdac3 mutants had increased NCED3 expression in response to pathogen challenge, transcripts of ABA sensitive genes such as AtRD22 and AtRAB18 were downregulated even after exogenous ABA application. VDAC3 is required for ABA responsive genes expression upon exogenous ABA application. We also found that Pseudomonas syringae-induced SA signaling is downregulated in vdac3 mutants since overexpression of VDAC3 resulted in hyperaccumulation of Pathogenesis related gene1 (PR1) transcript. Interestingly, ABA application prior to P. syringae inoculation resulted in the upregulation of ABA responsive genes like Responsive to ABA18 (RAB18) and Responsive to dehydration 22 (RD22). Intriguingly, in the absence of AtVDAC3, Pst challenge can dramatically increase ABA-induced RD22 and RAB18 expression. Altogether our results reveal a novel Pathogen-SA-ABA interaction pathway in plants. Our findings show that ABA plays a significant role in modifying plant-pathogen interactions, owing to cross-talk with the biotic stress signaling pathways of ABA and SA.

Predictors of Poor Outcome in Patients with COVID-19 associated Respiratory Failure: A Retrospective Observational Study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is majorly known to cause mild to moderate disease, but a small fraction of patients may develop respiratory failure due to diffuse lung injury, requiring management in the intensive care unit (ICU). This study attempts to identify factors that can predict unfavorable outcomes in moderate to severe COVID-19 patients. METHODS: Hospital records of 120 COVID-19 patients admitted to the ICU were retrospectively analyzed and data pertaining to demographic, clinical, and laboratory parameters were obtained. These data were then compared with outcome parameters like survival, duration of hospital stay, and various adverse events. RESULTS: Out of 120 patients, 70% were male, with a mean age of 54.44 years [standard deviation (SD) ± 14.24 years]. Presenting symptoms included breathlessness (100%), cough (94.17%), fever (82.5%), and sore throat (10.83%). Diabetes, hypertension, and chronic obstructive pulmonary disease (COPD) were the common comorbidities associated. Increased serum D-dimer, ferritin, interleukin-6 (IL-6) levels, and unvaccinated status were associated with higher mortality. Overall, 25.83% of patients survived, 24.41% of patients developed septic shock, and 10.6% of patients were discharged on oxygen. World Health Organization (WHO) clinical progression scale score ≥ 6 had 57 and 82% sensitivity and 83 and 77% specificity on days 7 and 14 after admission, respectively, for predicting mortality. A baseline National Early Warning Score 2 (NEWS 2) ≥ 9 had 48% sensitivity and 88% specificity for predicting mortality. CONCLUSION: Advanced age and associated comorbidities are linked to adverse outcomes in moderate to severe COVID-19. Persistently high D-dimer levels, despite standard treatment, may also contribute to increased mortality. WHO clinical progression scale and NEWS 2 have high specificity for predicting mortality.

Protein phosphatases and their targets: Comprehending the interactions in plant signaling pathways.

Protein phosphorylation is a vital reversible post-translational modification. This process is established by two classes of enzymes: protein kinases and protein phosphatases. Protein kinases phosphorylate proteins while protein phosphatases dephosphorylate phosphorylated proteins, thus, functioning as 'critical regulators' in signaling pathways. The eukaryotic protein phosphatases are classified as phosphoprotein phosphatases (PPP), metallo-dependent protein phosphatases (PPM), protein tyrosine (Tyr) phosphatases (PTP), and aspartate (Asp)-dependent phosphatases. The PPP and PPM families are serine (Ser)/threonine (Thr) specific phosphatases (STPs) that dephosphorylate Ser and Thr residues. The PTP family dephosphorylates Tyr residues while dual-specificity phosphatases (DsPTPs/DSPs) dephosphorylate Ser, Thr, and Tyr residues. The composition of these enzymes as well as their substrate specificity are important determinants of their functional significance in a number of cellular processes and stress responses. Their role in animal systems is well-understood and characterized. The functional characterization of protein phosphatases has been extensively covered in plants, although the comprehension of their mechanistic basis is an ongoing pursuit. The nature of their interactions with other key players in the signaling process is vital to our understanding. The substrates or targets determine their potential as well as magnitude of the impact they have on signaling pathways. In this article, we exclusively overview the various substrates of protein phosphatases in plant signaling pathways, which are a critical determinant of the outcome of various developmental and stress stimuli.

Overexpression of ARM repeat/U-box containing E3 ligase, PUB2 positively regulates growth and oxidative stress response in Arabidopsis.

Plant growth and development are governed by selective protein synthesis and degradation. Ubiquitination mediated protein degradation is governed by activating enzyme E1 followed by conjugating enzyme E2 and E3 ligase. Plant Armadillo (ARM) repeat/U-box (PUB) protein family is one of the important classes of E3 ligase. We studied the function of AtPUB2 by loss-of-function (knockout and knock down mutants) and gain-of-function (CaMV 35S promoter driven overexpression lines) approach in Arabidopsis. Under normal growth condition, we observed that loss-of-function mutant plants did not show any significant difference in growth when compared with wild-type possibly due to functional redundancy between PUB2 and PUB4. However, AtPUB2-OE lines exhibit early flowering and improved vegetative growth. Also, AtPUB2-OE seedlings showed sensitive phenotype in the presence of exogenous cytokinin. We found that AtPUB2 expression is induced under oxidative stress. Subcellular localization analysis shows that AtPUB2 is predominantly localized in the nucleus. We performed the phenotypic analysis under oxidative stress condition induced by methyl viologen (MV) and observed that overexpression lines display tolerance to oxidative stress in light and dark conditions. Furthermore, we found less amount of ROS accumulation, enhanced proline accumulation and decreased levels of MDA after MV treatment in AtPUB2-OE lines. PUB2-OE lines showed enhanced oxidative stress marker genes expression. By in vitro auto-ubiquitination assay, we also show that it possesses the E3 ligase activity. Overall, our findings suggest the possible role of AtPUB2 in plants ability to tolerate oxidative stress by enhancing the activity of antioxidant enzymes, which in turn improves ROS scavenging activity and homeostasis.

An Atypical Case of Mounier-Kuhn Syndrome: Time to Change the Diagnostic Approach?

Mounier-Kuhn syndrome (MKS) is a rare disease of unknown etiology characterized by abnormal pathologic dilatation of tracheabronchial tree. The diagnosis of MKS is normally made on CT scan of chest on the basis of enlarged diameters of trachea and main stem bronchi. We are presenting histologically confirmed case of MKS, where the diameter of right main bronchus is below minimum diameter (mean+3 SD) required for the diagnosis. We suggest that the diagnosis of MKS should not be solely based on fixed criteria such as the diameter of airways, but on the basis of the overall clinical, pathologic, and radiologic profile.