Optical coherence tomography angiography features of optic nerve head drusen and nonarteritic anterior ischemic optic neuropathy

ObjectiveTo evaluate the optic disc microvasculature in optic nerve head drusen (ONHD) vasculature in comparison to acute nonarteritic anterior ischemic optic neuropathy (NAION) and normal eyes using optical coherence tomography angiography (OCT-A).MethodsTen eyes with ONHD, 10 eyes with acute NAION, and 10 healthy eyes were included in this prospective, comparative, observational case series. OCT-A imaging was performed on the optic discs. Qualitative grading was performed for dilation and tortuosity of the peripapillary vessels by 3 graders. Quantitative comparison was performed for peripapillary and inside disc vessel densities in nerve head (NH) and retinal peripapillary capillary (RPC) slabs.ResultsThe intergrader agreement for dilation and tortuosity of the peripapillary vessels was poor (0.313 and 0.182 for vascular dilation in nerve head and radial peripapillary capillary enface images, respectively, and 0.478 and 0.490 for vascular tortuosity in nerve head and radial peripapillary capillary enface images, respectively). In NH en face images, the vessel density measurements were statistically significantly different between the 3 groups (all p < 0.05). In RPC en face images, the vessel density measurements were statistically significantly different between the 3 groups (all p < 0.05) except for nasal peripapillary sector (0.08).Conclusion: Despite poor intergrader agreement in qualitative analysis, quantitative OCT-A evaluation may differentiate optic disc edema due to NAION from pseudodisc edema due to ONHD.     

Understanding epidemic data and statistics: A case study of COVID-19

The 2019 novel-coronavirus (COVID-19) has affected 181 countries with approximately 1197405 confirmed cases (by 5th April). Understanding the transmission dynamics of the infection in each country which got affected on a daily basis and evaluating the effectiveness of control policies are critical for our further actions. To date, the statistics of COVID-19 reported cases show that more than 80% of infected are mild cases of disease, around 14% of infected have severe complications, and about 5% are categorized as critical disease victims. Today's report (5th April 2020; daily updates in the prepared website) shows that the confirmed cases of COVID-19 in the United States, Spain, Italy, and Germany are 308850, 126168, 124632, and 96092, respectively. Calculating the total case fatality rate (CFR) of Italy (4th April 2020), about 13.3% of confirmed cases have passed away. Compared with South Korea's rate of 1.8% (seven times lower than Italy) and China's 4% (69% lower than Italy), the CFR of Italy is too high. Some effective policies that yielded significant changes in the trend of cases were the lockdown policy in China, Italy, and Spain (the effect observed after some days), the shutdown of all nonessential companies in Hubei (the effect observed after 5 days), combined policy in South Korea, and reducing working hours in Iran.     

C5aR and C5L2 act in concert to balance immunometabolism in adipose tissue

Recent studies suggested that the immunometabolic receptors; C5aR and C5L2, constitutively self-associate into homo-/heterodimers and that acylation stimulating protein (ASP/C3adesArg) or C5a treatment of adipocytes increased their colocalization. The present study evaluates the C5aR contribution in adipocytes to the metabolic and immune responses elicited by ligand stimulation.     

Contribution of EVX1 in Aggressiveness of Esophageal Squamous Cell Carcinoma

Homeobox genes play an overruling role in the regional cell fate determination during development. EVX1 is known as a new target gene of BMP signaling pathway, a group of morphogens which are making the largest subset within the transformation growth factor beta (TGF-β) superfamily. In this study, we aimed to enlighten the expression level of EVX1 in esophageal squamous cell carcinoma (ESCC) and to disclose its apparent roles in maintenance and progression of the disease. The expression level of EVX1 was analyzed in fresh tumoral tissues in comparison with distant tumor-free tissues of 50 ESCC patients using relative comparative real-time PCR. The importance of EVX1 in development and cancer was also reviewed. EVX1 was underexpressed in 70 % of tumor samples. There was a significant correlation between down-regulation of EVX1 and lymph node metastasis of tumor cells (p = 0.027). Furthermore, EVX1 underexpression was significantly correlated with depth of tumor cell invasion (P = 0.037). To the best of our knowledge, this is the first report highlighting EVX1 expression in ESCC to date. The clinicopathological relevance of EVX1 mRNA expression in ESCC targeted this gene as a new independent molecular marker for advanced tumor, which determine the characteristics and behavior of aggressive ESCC.     

Identification of a mammalian glycerol-3-phosphate phosphatase: Role in metabolism and signaling in pancreatic β-cells and hepatocytes

Obesity, and the associated disturbed glycerolipid/fatty acid (GL/FA) cycle, contribute to insulin resistance, islet β-cell failure, and type 2 diabetes. Flux through the GL/FA cycle is regulated by the availability of glycerol-3-phosphate (Gro3P) and fatty acyl-CoA. We describe here a mammalian Gro3P phosphatase (G3PP), which was not known to exist in mammalian cells, that can directly hydrolyze Gro3P to glycerol. We identified that mammalian phosphoglycolate phosphatase, with an uncertain function, acts in fact as a G3PP. We found that G3PP, by controlling Gro3P levels, regulates glycolysis and glucose oxidation, cellular redox and ATP production, gluconeogenesis, glycerolipid synthesis, and fatty acid oxidation in pancreatic islet β-cells and hepatocytes, and that glucose stimulated insulin secretion and the response to metabolic stress, e.g., glucolipotoxicity, in β-cells. In vivo overexpression of G3PP in rat liver lowers body weight gain and hepatic glucose production from glycerol and elevates plasma HDL levels. G3PP is expressed at various levels in different tissues, and its expression varies according to the nutritional state in some tissues. As Gro3P lies at the crossroads of glucose, lipid, and energy metabolism, control of its availability by G3PP adds a key level of metabolic regulation in mammalian cells, and G3PP offers a potential target for type 2 diabetes and cardiometabolic disorders.The glycerolipid/fatty acid (GL/FA) cycle, which is central to energy homeostasis, balances glucose and lipid metabolism (1, 2), and generates metabolic signals (3, 4). This cycle is deregulated in obesity and type 2 diabetes. Under conditions of fuel surfeit with excessive glucose and free fatty acid (FFA) supply, a substantial portion of glucose is used in mammalian cells via formation of glycerol-3-phosphate (Gro3P) and its incorporation into GL via GL/FA cycle (4, 5). The cycle consists of lipogenesis and lipolysis segments and generates intermediates for the synthesis of various types of complex lipids, but also signals that control many biological processes, including insulin secretion and action (3, 6, 7). The proper operation of this cycle possibly protects β-cells and other cell types from glucolipotoxicity and metabolic stress (4, 8, 9).Lipogenesis, i.e., the successive esterification of glycolysis-derived Gro3P with fatty acyl-CoA (FA-CoA), produces triglyceride (TG), which can be stored as lipid droplets (10). Lipolysis of TG is initiated by adipose TG lipase to generate diacylglycerol (DAG), which is hydrolyzed by hormone sensitive lipase to give rise to monoacylglycerol (MAG). MAG hydrolysis by classical MAG lipase or by α/β-hydrolase domain-6 (ABHD6) to glycerol and FFA completes the lipolytic segment of the GL/FA cycle (2, 3).Presently glycerol release from mammalian cells is thought to occur exclusively from the lipolytic segment of the GL/FA cycle, and glycerol production is considered to reflect lipolysis flux. We proposed earlier that, at high glucose concentrations, the release of glycerol by β-cells, which do not express glycerokinase that transforms glycerol to Gro3P (4), is a mechanism of “glucolipodetoxification,” and that this process is dependent on the lipolysis segment of GL/FA cycle (3, 4). Indeed, mammalian cells are not known to harbor a Gro3P phosphatase (G3PP) (11), which could directly generate glycerol from Gro3P. In an earlier study on mass isotopomer distribution analysis of glucose labeling from [¹³C]glycerol in the liver, Gro3P hydrolysis activity was speculated but was not directly demonstrated (12). Thus, the fate of Gro3P in mammalian cells is thought to be its conversion to dihydroxyacetone phosphate (DHAP) or lysophosphatidate, the first intermediate of the lipogenic arm of the cycle. However, many microbes (13–15) and plants (16) harbor a G3PP. We now describe that a previously known phosphoglycolate phosphatase (PGP) (17) with an uncertain function in mammalian cells acts as a specific G3PP and plays a pivotal role in the regulation of glucose and lipid metabolism and signaling, as well as in the response to metabolic stress.     

Low dose ribavirin for treatment of hepatitis C virus infected thalassemia major patients; new indications for combination therapy

Background

Treatment guidelines contraindicate ribavirin for treatment of hepatitis C virus (HCV) infection in thalassemia major patients. Nevertheless, the current evidence suggests that ribavirin might be tolerated by these patients.

Objectives

Despite this evidence, low dose ribavirin combination therapy has not been compared with peginterferon monotherapy in these patients so far.

Patients and Methods

Two hundred eighty thalassemia patients with detectable HCV-RNA PCR (≥ 50 IU/mL) and liver histology consistent with chronic HCV infection were self-assigned to receive peginterferon alfa-2a (n = 81) monotherapy or its combination therapy with ribavirin, 600-800 mg QD, according to hemoglobin levels (n = 199). Treatment experienced patients were eligible for this study.

Results

Sustained virological response (SVR) was significantly higher in patients who received ribavirin (51 % vs. 38 % P = 0.02). In multivariate regression, OR of ribavirin for prediction of SVR was 2.2 (95 % CI 1.24-3.91). The SVR was significantly higher in the ribavirin group in subgroups of patients with more than 24 years of age, elevated ALT, ferritin < 2006 ng/mL, previous treatment failure, genotype 1, positive history of splenectomy, fibrosis score of 0-4 HAI and viral load < 600,000 IU/mL. Treatment discontinuations due to the safety concerns were comparable between the treatment groups (6.5 and 8 %). Furthermore, transfusion intervals were almost halved in patients who received low dose ribavirin.

Conclusions

According to the present study, adult thalassemia patients with HCV infection can be treated successfully with low dose ribavirin. Hence, we strongly advise combination therapy in thalassemia patients with aforementioned clinical characteristics. Moreover, ribavirin does not seem to be beneficial in thalassemia patients below 18 years of age.     

Injectable soft tissue filler infection with a similar appearance to an odontogenic abscess

Infection of an injectable soft tissue filler may involve fascial spaces and appears similar to an odontogenic abscess. This case report addresses a 32‐year‐old female patient with facial swelling who was referred to the department of endodontics for the treatment of a suspected odontogenic infection.     

Gastroprotective effect of sumatriptan against indomethacin-, stress- and ethanol-induced gastric damage in male rats: Possible modulatory role of 5-hydroxytryptamine 1B/1D receptors and pro-inflammatory cytokines

The current study was aimed to investigate the beneficial effect of sumatriptan, a 5-hydroxytryptamine 1B/1D (5HT_1B/1D) receptor agonist, on gastric ulcer in rats via stimulating 5HT_1B/1D receptors and suppressing pro-inflammatory cytokines. Rats were allocated into three models of gastric ulcer: indomethacin (30 mg/kg, PO), water immersion restraint stress (WRS) and ethanol (5 ml/kg PO). Animals were administered with sumatriptan (0.01, 0.1, 0.3 and 1 mg/kg, i.p) 30 min before gastric ulcer induction. GR-127935 (0.01 mg/kg, i.p, a selective 5HT_1B/1D antagonist) was administered 30 min before sumatriptan (0.1 mg/kg) injection. Macroscopic assessments (J-score), ELISA analysis of tumour necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1β) and histopathological changes were performed on the rat's stomach tissues. Gastric ulcer induction in three models caused an increase in J-score, TNF-α, IL-1β and microscopic features. Sumatriptan (0.1 mg/kg) significantly improved gastric injury induced by indomethacin, WRS and ethanol through the reduction in the J-score, TNF-α, IL-1β and microscopic lesions. Concurrent administration of GR-127935 (0.01 mg/kg) with sumatriptan (0.1 mg/kg) reversed the gastroprotective effect of sumatriptan in three models. Sumatriptan possessed gastroprotective effects on indomethacin-, WRS- and ethanol-induced gastric damage in rats via the possible involvement of the 5HT_1B/1D receptors.