Negative Association of Plasma Levels of Vitamin D and miR-378 With Viral Load in Patients With Chronic Hepatitis B Infection

Background:

Chronic Hepatitis B (CHB) is accompanied by inflammation of liver because of infection with Hepatitis B Virus (HBV). Previous studies revealed an inverse association between vitamin D and HBV DNA levels.

Objectives:

The current study aimed to investigate the levels of 25 (OH) D3 (the steady form of vitamin D), miR-378 and HBV DNA in the patients with CHB.

Patients and Methods:

One hundred and seventy three patients with HBeAg negative CHB were recruited for the study. Plasma levels of HBVDNA and 25 (OH) D3 were quantified. The expression level of miR-378 in plasma was measured by a relative quantitative Real Time Polymerase Chain Reaction (qRT-PCR) assay.

Results:

In the pathway regression analysis, the plasma level of 25 (OH) D3 showed a significant inverse correlation with plasma levels of HBV DNA (-0.198, P = 0.008) and direct correlation with miR-378 (0.188, P = 0.013). Similarly plasma level of miR-378 had inverse association with HBV DNA level (-0.177, P = 0.020).

Conclusions:

These results suggest that vitamin D could involve in a miRNA- mediated regulatory pathway in control of HBV replication. Further studies are recommended to understand the effects of miR-378 and anti-infective action of vitamin D on Hepatitis B Virus.     

Correlates of basal insulin persistence among insulin-naïve people with type 2 diabetes: results from a multinational survey

Background and objective: People with T2DM who initiate basal insulin therapy often stop therapy temporarily or permanently soon after initiation. This study analyzes the reasons for and correlates of stopping and restarting basal insulin therapy among people with T2DM.

Methods: An online survey was completed by 942 insulin-naïve adults with self-reported T2DM from Brazil, France, Germany, Japan, Spain, UK, and US. Respondents had initiated basal insulin therapy within the 3–24 months before survey participation and met criteria for one of three persistence groups: continuers had no gaps of ≥7 days in basal insulin treatment; interrupters had at least one gap in insulin therapy of ≥7 days within the first 6 months after initiation and had since restarted basal insulin; and discontinuers stopped using basal insulin within the first 6 months after initiation and had not restarted.

Results: Physician recommendations and cost were strongly implicated in patients stopping and not resuming insulin therapy. Continuous persistence was lower for patients with more worries about insulin initiation, greater difficulties and weight gain while using insulin, and higher for those using pens and perceiving their diabetes as severe. Repeated interruption of insulin therapy was associated with hyperglycemia and treatment burden while using insulin. Resumption and perceived likelihood of resumption were associated with hyperglycemia upon insulin cessation. Perceived likelihood of resumption among discontinuers was associated with perceived benefits of insulin.

Conclusion: Better understanding of the risk factors for patient cessation and resumption of basal insulin therapy may help healthcare providers improve persistence with therapy.     

Ocular Manifestations,Conventional Fundus Fluorescein Angiographic Findings,and Relationship Between Angiographic Findings and Visual Acuity in Behçet’s Disease

Purpose: Evaluating the ocular manifestation and fundus fluorescein angiography (FA) findings of patients with Behçet’s disease as well as the relationship between visual acuity and angiographic findings. Methods: Retrospective chart review of patients with Behçet’s disease seen at the Farabi Eye Hospital. Results: Forty-six patients (92 eyes) with mean age of 33.41 ± 10.67 were included. The most frequent presenting symptom and sign were reduced vision (76%) and uveitis (87%), respectively. Panuveitis was the most frequent type of uveitis (76%). Among patients with FA, vasculitis was the most common finding (87%) and it was significantly more severe among patients with visual acuity less than 20/200. Macular leakage (P = 0.001), arterial narrowing (P = 0.000), and posterior retinal vasculitis (P = 0.002) on FA were all associated with worsening final visual acuity. Conclusion: The most common ocular findings in Behçet’s disease were panuveitis and vasculitis. Location of vasculitis, arterial narrowing, and macular leakage on initial FA may predict visual prognosis.     

Treatment of COVID‐19 with pentoxifylline: Could it be a potential adjuvant therapy?

The world is facing a viral pandemic of a new coronavirus called COVID‐19. Pentoxifylline is a methyl‐xanthine derivative and it inhibits the phosphodiesterase IV (PDE IV). This drug is known for its unique features as an immunomodulatory and anti‐inflammatory agent, also it could have antiviral affects. This is a scoping review, in which all related articles on COVID‐19 and the probable benefits of Pentoxifylline against COVID‐19 pathogenesis, in Medline, Scopus, Web of Sciences, and Google Scholar up to 20 March 2020 with proper keywords including: pentoxifylline, Pentoxil, COVID‐19, coronavirus, treatment, anti‐inflammatory, immunomodulatory, antifibrosis, oxygenation, circulation, bronchodilator, ARDS, and organ failure. We found many confirmatory data on proper efficacy of pentoxifylline on controlling COVID‐19 and its consequences. The antiviral, anti‐inflammatory, anti‐oxidative, immune‐modulatory, bronchodilator and respiratory supportive effects and protective roles in organ failures of PTX, along with its main functions means better circulation‐oxygenation properties, low price and safety, make it a promising drug to be considered for COVID‐19 treatment, especially as an adjuvant therapy in combination with other drugs.     

Characteristics of the swallowing sounds recorded in the ear, nose and on trachea

The various malfunctions and difficulties of the swallowing mechanism necessitate various diagnostic techniques to address those problems. Swallowing sounds recorded from the trachea have been suggested as a noninvasive method of swallowing assessment. However, acquiring signals from the trachea can be difficult for those with loose skin. The objective of this pilot study was to explore the viability of using the ear and nose as alternative recording locations for recording swallowing sounds. We recorded the swallowing and breathing sounds of five healthy young individuals from the ear, nose and trachea, simultaneously. We computed time-frequency features and compared them for the different locations of recording. The features included the peak and the maximum frequencies of the power spectrum density, average power at different frequency bands and the wavelet coefficients. The average power calculated over the 4 octave bands between 150 and 2,400 Hz showed a consistent trend with less than 20 dB difference for the breath sounds of all the recording locations. Thus, analyzing breath sounds recorded from the ear and nose for the purpose of aspiration detection would give similar results to those from tracheal recordings; thus, ear and nose recording may be a viable alternative when tracheal recording is not possible.     

Improvement of a Dendritic Cell-Based Therapeutic Cancer Vaccine with Components of Toxoplasma gondii

The use of dendritic cells (DCs) as a cellular adjuvant is a promising approach to the immunotherapy of cancer. It has previously been demonstrated that DCs pulsed ex vivo with Toxoplasma gondii antigens trigger a systemic Th1-biased specific immune response and induce protective and specific antitoxoplasma immunity. In the present study, we demonstrate that tumor antigen-pulsed DCs matured in the presence of Toxoplasma gondii components induce a potent antitumor response in a mouse model of fibrosarcoma. Bone-marrow derived DCs (BMDCs) were cultured in the presence of granulocyte-macrophage colony-stimulating factor and interleukin-4. After 5 days, tumor lysates with or without the T. gondii lysate were added to the culture for another 2 days. The cytokine production in the BMDC culture and the coculture supernatants of DCs and splenic cells was evaluated. For immunization, 7 days after tumor challenge, different groups of BALB/c mice received different kinds of DCs subcutaneously around the tumor site. Tumor growth was monitored, and 2 weeks after DC immunotherapy, the cytotoxic activity and the infiltration of CD8⁺ T cells were monitored in different groups. According to the findings, immunotherapy with T. gondii-matured DCs led to a significant increase in the activity of cytotoxic T cells and decreased the rate of growth of the tumor in immunized animals. Immature DCs did not cause any change in cytotoxic activity or the tumor growth rate compared to that in the healthy controls. The current study suggests that a specific antitumor immune response can be induced by DCs matured with T. gondii components and provide the basis for the use of T. gondii in DC-targeted clinical therapies.Dendritic cells (DCs) efficiently induce T-cell activation in the secondary lymphoid organs (3, 4, 25). The Th1 arm of the immune response is very important in the battle against cancer (17). Evidence indicates that DCs play an important role in determining the type of immune response generated against antigens. Several factors can influence the development of polarized immune responses, such as the DC lineage and its activation status. Some studies have shown that distinct DC subsets are able to promote different types of responses, depending on the pathogen-derived signals and the host-derived cytokines present in the microenvironment (13, 23, 24, 37).In microbial infections, certain molecular patterns of microbial components directly stimulate immature DCs in the periphery to differentiate into mature DCs by binding to pattern recognition receptors, such as Toll-like receptors (TLRs), which play a critical role in the innate immunity of mammals. The stimulation of TLR signaling in DCs causes an increase in the surface expression of the major histocompatibility complex (MHC) peptide for T-cell recognition, the upregulation of costimulatory molecules important for T-cell clonal expansion, and the secretion of immunomodulatory cytokines, which direct T-lymphocyte differentiation into effector cells. Remarkably, the ligation of distinct TLRs can trigger the production of different cytokines by a single DC type or result in different cytokines in distinct DC subtypes. Studying the complexity of the DC responses to TLR ligands illuminates the link between the innate and the adaptive arms of the immune system (1, 5, 36).Toxoplasma gondii is an obligate intracellular parasite. Immunity to this organism is accomplished by the high-level production of type 1 cytokines such as gamma interferon (IFN-γ). Both interleukin-12 (IL-12) and IFN-γ are essential for resistance to this opportunistic pathogen (10, 12, 21, 31, 38). T. gondii is a potent stimulus for IL-12 production, which in turn is required to skew the immune response toward Th1 (16, 33). Innate immune cells, such as polymorphonuclear neutrophils, DCs, and macrophages, are important sources of IL-12 during T. gondii infection (7). TLR2 and myeloid differentiation factor 88 are critical for protective immunity against T. gondii infection (27). In recent years, TLR4 has also been found to be essential in the T. gondii-induced activation of DCs (2).The present study was designed on the basis of the role of T. gondii in the induction of Th1 (cellular arm) immune responses and the importance of this arm in anticancer immunity. In the present study, the maturation state and the cytokine production capabilities of T. gondii-treated DCs, as well as their potential adjuvant effect on tumor immunotherapy of an experimental model, were evaluated.     

Proliferating progenitor cells: a required cellular element for induction of ischemic tolerance in the brain.

Permanent cerebral blood flow reduction results in brain injury (stroke), whereas transient ischemic stress results in preconditioning, which can ameliorate the extent of irreversible brain injury from subsequent ischemia-the phenomena of ischemic tolerance. Neurogenesis in the brain occurs after both ischemic injury and the brief ischemia resulting in preconditioning. As neurogenesis is regarded as having an intrinsic neuroprotective role in the brain, we investigated the possible role of these endogenous progenitor cells in the induction of ischemic tolerance. Methylazoxymethanol acetate (MAM) was injected in wild-type mice to attenuate precursor cell proliferation and ganciclovir was used to diminish newly generated cells in GFAP/HSV-TK mice. Both MAM and ganciclovir significantly attenuated ischemia-induced progenitor cell proliferation in the subventricular zone, dentate gyrus, penumbra, and corpus callosum as quantified by 5-bromo-2'-deoxyuridine- or Ki-67-positive cells. Attenuation of ischemia-induced progenitor cell proliferation in the brain blocked the induction of ischemic tolerance. Further the number of TUNEL (TdT-mediated dUTP nick end labeling)-positive cells was considerably increased in MAM-treated animals, whereas MAM did not cause cell death in sham-operated controls. The results of this study suggest a role for endogenous progenitors in the protective effect of ischemic tolerance.     

Transfusion associated in-hospital mortality and morbidity in isolated Coronary Artery Bypass Graft surgery

Transfusion after cardiac surgery is very common. This rate varies between institutions and has remained high despite established transfusion guidelines. We analyzed our database of patients who underwent isolated CABG (Coronary Artery Bypass Graft) to determine the predictive factors of homologous transfusion and associated postoperative morbidity, mortality and resource utilization. All 14,152 patients who underwent first-time isolated CABG, with or without cardiopulmonary bypass (CPB) who had postoperative homologous transfusion between February 2002 and March 2008 in Tehran Heart Center, were evaluated retrospectively. Overall, 16.5% of patients received transfusion. Transfused patients demonstrated a significantly higher incidence of postoperative complications (cardiac, infectious, ischemic, reoperation) and mortality (p<0.001). Homologous blood transfusion effect on mortality, morbidity and resource utilization. By Multivariable logistic regression analysis adjusted for confounders: Homologous blood transfusion effect on Mortality (30-days) (OR=3.976, p<0.0001), Prolonged ventilation hours (OR=4.755, p<0.0001), Total ICU hours (β =14.599, p<0.0001), Hospital length of stay (β =1.141, p<0.0001), Post surgery length of stay (β =0.955, p<0.0001). We conclude that the isolated CABG patients receiving blood transfusion have significantly higher mortality, morbidity and resource utilization. Homologous blood transfusion is an independent factor of increased resource utilization, morbidity and mortality.     

A novel Fontan Y-graft for interrupted inferior vena cava and azygos continuation

Open in a separate window OBJECTIVESTo evaluate the hemodynamicdynamic advantage of a new Fontan surgical template that is intended for complex single-ventricle patients with interrupted inferior vena cava-azygos and hemi-azygos continuation. The new technique has emerged from a comprehensive pre-surgical simulation campaign conducted to facilitate a balanced hepatic flow and somatic Fontan pathway growth after Kawashima procedure.METHODSFor 9 patients, aged 2 to18 years, majority having poor preoperative oxygen saturation, a pre-surgical computational fluid dynamics customization is conducted. Both the traditional Fontan pathways and the proposed novel Y-graft templates are considered. Numerical model was validated against in vivo phase-contrast magnetic resonance imaging data and in vitro experiments.RESULTSThe proposed template is selected and executed for 6 out of the 9 patients based on its predicted superior hemodynamic performance. Pre-surgical simulations performed for this cohort indicated that flow from the hepatic veins (HEP) do not reach to the desired lung. The novel Y-graft template, customized via a right- or left-sided displacement of the total cavopulmonary connection anastomosis location resulted a drastic increase in HEP flow to the desired lung. Orientation of HEP to azygos direct shunt is found to be important as it can alter the flow pattern from 38% in the caudally located direct shunt to 3% in the cranial configuration with significantly reversed flow. The postoperative measurements prove that oxygen saturation increased significantly (P-value = 0.00009) to normal levels in 1 year follow-up.CONCLUSIONSThe new Y-graft template, if customized for the individual patient, is a viable alternative to the traditional surgical pathways. This template addresses the competing hemodynamic design factors of low physiological venous pressure, high postoperative oxygen saturation, low energy loss and balanced hepatic growth factor distribution possibly assuring adequate lung development.Date and number of IRB approval25 October 2019, 280011928-604.01.01.