Selective depletion of CD11c+CD11b+ dendritic cells partially abrogates tolerogenic effects of intravenous MOG in murine EAE

Intravenous (i.v.) injection of a soluble myelin antigen can induce tolerance, which effectively ameliorates experimental autoimmune encephalomyelitis (EAE). We have previously shown that i.v. myelin oligodendrocyte glycoprotein (MOG) induces tolerance in EAE and expands a subpopulation of tolerogenic CD11c⁺CD11b⁺ dendritic cells (DCs) with an immature phenotype having low expression of IA and co‐stimulatory molecules CD40, CD86, and CD80. Here, we further investigate the role of tolerogenic DCs in i.v. tolerance by injecting clodronate‐loaded liposomes, which selectively deplete CD11c⁺CD11b⁺ and immature DCs, but not CD11c⁺CD8⁺ DCs and mature DCs. I.v. MOG‐induced suppression of EAE was partially, yet significantly, blocked by CD11c⁺CD11b⁺ DC depletion. While i.v. MOG inhibited IA, CD40, CD80, CD86 expression and induced TGF‐β, IL‐27, IL‐10 production in CD11c⁺CD11b⁺ DCs, these effects were abrogated after injection of clodronate‐loaded liposomes. Depletion of CD11c⁺CD11b⁺ DCs also precluded i.v. autoantigen‐induced T‐cell tolerance, such as decreased production of IL‐2, IFN‐γ, IL‐17 and numbers of IL‐2⁺, IFN‐γ⁺, and IL‐17⁺ CD4⁺ T cells, as well as an increased proportion of CD4⁺CD25⁺Foxp3⁺ regulatory T cells and CD4⁺IL‐10⁺Foxp3^? Tr1 cells. CD11c⁺CD11b⁺ DCs, through low expression of IA and costimulatory molecules as well as high expression of TGF‐β, IL‐27, and IL‐10, play an important role in i.v. tolerance‐induced EAE suppression.     

Comparative Study of Apo-Cetirizine Single Therapy and Intermittent Sequential Therapy with Cetirizine,Loratadine and Chlorpheniramine in Allergic Rhinitis

There are limited numbers of articles, studying combined use of antihistamines. In this study, we compare single therapy of Apo-Cetirizine with a new regimen of intermittent sequential therapy with cetirizine, loratadine and chlorpheniramine in treatment of seasonal allergic rhinitis. This randomized clinical trial was performed between April and September at the peak prevalence of seasonal allergic rhinitis. Fifty-four eligible patients diagnosed clinically to have seasonal allergic rhinitis were randomized in two groups: 24 cases in single therapy arm, received Apo-Cetirizine 10 mg tablet daily and in other arm, 30 patients received sequential regimen of cetirizine 10 mg tablet, loratadine 10 mg tablet and chlorpheniramine 4 mg tablet, one tablet each day. Major Symptom Complex Score (MSCS) and Total Symptom Complex Score (TSCS) of patients were recorded before treatment and after 30 days of treatment in two groups. The average post-treatment MSCS and TSCS in combination therapy group showed better improvement than single therapy group but difference was not statistically significant (p value = 0.053 and p value = 0.104 respectively). Combination therapy regimen was better in improvement of nasal congestion (p value = 0.006). There were no significant difference between two groups in efficacy, side effects and patient’s satisfaction. Combination therapy would be effective on a wide spectrum of symptoms with lower price and theoretically offers lower chance of tolerance and re-appearance of complaints.     

Evaluation of Serologic Changes of IgG and IgM Antibodies Associated with SARS-COV-2 in Cancer Patients: A Cohort Seroprevalence Study

Background: While the coronavirus disease 2019 (COVID-19) pandemic spreads, there is increasing evidence to suggest the elevated risk of SARS-CoV-2 infection and following morbidity and mortality in cancer patients. Serology testing using ELISA proposes major advantages as a diagnostic and preventive tool to control the present SARS-CoV-2 outbreak. This cohort study was to determine the SARS-CoV-2 seroconversion in asymptomatic cancer patients. Methods: Patients in all age groups and with any type of cancer who have been in remission or have stable disease and received their latest anticancer therapy over 2 months ago included in the study. All patients were evaluated for COVID-19 symptoms and only asymptomatic patients were enrolled for serologic screening for SARS-CoV-2. Serum samples evaluated serologically for SARS-CoV-2 antibodies by enzyme-linked immunosorbent assay. Results: A total of 168 asymptomatic cancer patients were included in the study. Of the 168 cases with a history of cancer who were asymptomatic for Covid-19, 29 cases (17.26%) had a positive serological test. Conclusion: In conclusion, in the present study asymptomatic cancer patients revealed 17% seropositivity, approximately equal to the general population of the same age, sex, geographic region, and epidemic status. Asymptomatic infections should further be investigated and considered as playing an important role in the COVID-19 transmission chain.     

Association between intraoperative opioid administration and 30-day readmission: a pre-specified analysis of registry data from a healthcare network in New England

Background

The use of intraoperative opioids may influence the rate of postoperative complications. This study evaluated the association between intraoperative opioid dose and the risk of 30-day hospital readmission.

Institutional practice and outcome variation in the management of congenital diaphragmatic hernia and gastroschisis in Canada: a report from the Canadian Pediatric Surgery Network

Background

Perinatal management of congenital diaphragmatic hernia (CDH) and gastroschisis (GS) remains nonstandardized and institution specific. This analysis describes practice and outcome variation across a national network.

Methods

A national, prospective, disease-specific database for CDH and GS was evaluated over 4 years. Centers were evaluated individually and defined as low (low-volume center [LVC]) or high (high-volume center [HVC]) volume based on case mean.

Results

Congenital diaphragmatic hernia. Two hundred fifteen liveborn cases were studied (mean, 14.3 cases/center) across 15 centers (8 LVCs and 7 HVCs). Significant interinstitutional practice variation was noted in rates of termination (0%-40%) and cesarean delivery (0%-61%). Centers demonstrated marked variation in ventilation strategies, vasodilator and paralytic use, timing of surgery, and rates of primary closure. Overall survival was 81.4% (LVC, 76.9%; HVC, 82.4%; P = .43).Gastroschisis. Four hundred sixteen cases were investigated (mean, 26 cases/center; range, 6-72) across 16 centers (10 LVCs and 6 HVCs). Cesarean delivery rates varied widely between centers (0%-86%) as did timing of closure (early vs delayed, 1%-100%). There was no difference in length of stay, days on total parenteral nutrition, and overall survival (94.3% vs 97.2%; P = .17) between LVCs and HVCs.

Conclusions

The existence of perinatal practice and outcome variation for GS and CDH suggests targets for improved delivery of care and justifies efforts to standardize treatment on a national basis.     

Oligodendrocyte vulnerability following traumatic brain injury in rats

Experimental and clinical findings demonstrate that traumatic brain injury (TBI) results in injury to both gray and white matter structures. The purpose of this study was to document patterns of oligodendrocyte vulnerability to TBI. Sprague Dawley rats underwent sham operated procedures or moderate fluid percussion brain injury. Quantitative immunohistochemical analysis was performed on animals perfusion-fixed at 3 (n=9) or 7 (n=9) days post-surgery. Within the ipsilateral external capsule and corpus callosum, numbers of APC-CC1 immunoreactive oligodendrocytes were significantly decreased at 3 or 7 days post-TBI compared to sham rats (p<0.03). At both posttraumatic survival periods, double-labeling studies indicated that oligodendrocytes showed increased Caspase 3 activation compared to sham. These data demonstrate regional patterns of oligodendrocyte vulnerability after TBI and that oligodendrocyte cell loss may be due to Caspase 3-mediated cell death mechanisms. Further studies are needed to test therapeutic interventions that prevent trauma-induced oligodendrocyte cell death, subsequent demyelination and circuit dysfunction.