Kinetics of free and ligand-bound atacicept in human serum.

BAFF (B cell activation factor of the TNF family/B lymphocyte stimulator, BLyS) and APRIL (a proliferation-inducing ligand) are targeted by atacicept, a decoy receptor consisting of the extracellular domain of TACI (transmembrane activator and calcium-modulator and cyclophilin (CAML) interactor) fused to the Fc portion of human IgG1. The purpose of the study was to characterize free and ligand-bound atacicept in humans. Total and active atacicept in serum of healthy volunteers receiving a single dose of subcutaneous atacicept or in patients treated weekly for one year were measured by ELISA, Western blot, or cell-based assays. Pharmacokinetics of free and bound atacicept were predicted based on total atacicept ELISA results. Persistence of complexes of purified atacicept bound to recombinant ligands was also monitored in mice. Results show that unbound or active atacicept in human serum exceeded 0.1 µg/ml for one week post administration, or throughout a 1-year treatment with weekly administrations. After a single administration of atacicept, endogenous BAFF bound to atacicept was detected after 8 h then increased about 100-fold within 2 to 4 weeks. Endogenous heteromers of BAFF and APRIL bound to atacicept also accumulated, but atacicept-APRIL complexes were not detected. In mice receiving intravenous injections of purified complexes pre-formed in vitro, atacicept-BAFF persisted longer (more than a week) than atacicept-APRIL (less than a day). Thus, only biologically inactive BAFF and BAFF-APRIL heteromers accumulate on atacicept in vivo. The measure of active atacicept provides further support for the once-weekly dosing regimen implemented in the clinical development of atacicept

Dietary phytochemical index and overweight/obesity in children: A cross-sectional study

Objective: The aim of the present study was to examine the relationship between the dietary phytochemical index (DPI) and overweight/obesity in children. This cross-sectional study was comprised of 356 children aged 7 to 10 years-old study in the city of Tehran, Iran. The dietary intake of participants was collected using a validated food frequency questionnaire. The DPI was calculated based on the daily energy derived from phytochemical-rich foods. The definition of overweight and obesity was based on the criteria developed by the US Chronic Disease Center for prevention and health promotion. Results: The overall prevalence of overweight/obesity was 35.1. The mean (standard deviation) of the DPI was 14.25 (4.13), 24.12 (2.64), 35.41 (3.62) and 61.52 (16.47) in the first, second, third and fourth quartiles (Q), respectively. Subjects in the higher quartiles of DPI had a significantly higher intake of dietary fiber, vitamin C, and potassium compared to those in the lower quartiles. In the multiple regression analysis, subjects in the highest quartile of DPI had significantly lower odds of being overweight/obese compared to those in the first quartile odds ratio and 95% confidence intervals for Q4 vs. Q1: 0.47 (0.25, 0.87); P for trend = 0.02. © 2020 The Author(s)

Extra-hepatic fascioliasis with peritoneal malignancy tumor feature

Fascioliasis is a zoonose parasitic disease caused by Fasciola hepatica and Fasciola gigantica and is widespread in most regions of the world. Ectopic fascioliasis usually caused by juvenile Fasciola spp., but in recent years a few cases of tissue-embedded ova have been reported from different endemic areas. A 79-year-old Iranian man resident in Eird-e-Mousa village from Ardabil Province, north-west of Iran, complained with abdominal pain, nausea, and intestinal obstruction symptoms referred to Ardabil Fatemi hospital. In laparotomy multiple intestinal masses with peritoneal seeding resembling of a malignant lesion were seen. After appendectomy and peritoneal mass biopsy with numerous intraperitoneal adenopathy, paraffin embedded blocks were prepared from each tissues. A blood sample was taken from the patient 5 months later for serological diagnosis. Histopathological examination of sections showed fibrofatty stroma with dense mixed inflammatory cells infiltration and fibrosis in peritoneal masses. Large numbers of ova of Fasciola spp. were noted with typical circumscribed granulomas. Despite of anti-fasciola treatment, IHA test for detecting anti F. hepatica antibodies was positive 5 months after surgery with a titer of 1/128. Due to multiple clinical manifestation of extra-hepatic fascioliasis, its differential diagnosis from intraperitoneal tumors or other similar diseases should be considered

Gene delivery to in situ veins: Differential effects of adenovirus and adeno-associated viral vectors

AbstractPurpose: Gene transfer offers the potential to modify vein graft biology at the time of surgical implantation. Efficiency of gene delivery, stability of expression, and host responses are critical parameters for candidate vectors. We compared the effects of intraluminal exposure with adenovirus (AD) and adeno-associated virus (AAV) vectors on transgene expression and monocyte adhesion (MA) in treated vein segments. Methods: Adult New Zealand white rabbits (N = 51) were anesthetized, and the jugular veins were cannulated bilaterally. Veins were gently distended with either vector (2·108 to 1·1010 infective particles/mL) or vehicle (control) for 30 minutes, after which venous flow was restored. AD and AAV vectors encoding for the marker genes β-galactosidase (LacZ) and green fluorescent protein (GFP) were used. Vessels were explanted 2 to 40 days postinfection for analysis of gene expression (X-gal staining, reverse transcriptase-polymerase chain reaction), MA, and immunohistochemistry. Ex vivo adhesion assays used 51Cr-labeled THP-1 cells. Statistical significance was tested by using analysis of variance with a P value less than.05. Results: All animals survived, and all treated veins were patent at sacrifice. Intraluminal exposure to AD at a titer of 1·109 resulted in near complete transduction of the endothelium at 2 days, with no detectable expression by day 14. At an equal titer of infectious particles, transgene expression was markedly less for AAV at 2 to 7 days, but improved at 2 weeks and persisted to 40 days. MA was significantly increased 2 days after AD exposure (2.7-fold vs control, *P <.002); AAV treatment had no discernible effect on MA. Conclusion: AD-mediated gene transfer to vein segments resulted in robust, transient gene expression that disappeared after 2 weeks. In comparison, AAV-mediated gene delivery was less efficient, but resulted in delayed onset, persistent expression beyond 30 days. AD exposure induced an early increase in MA to the vein surface that was not seen with AAV treatment. Current generations of both AD and AAV vectors have significant, albeit different, limitations for vascular gene therapy. (J Vasc Surg 2000;31:1149-59.

The relationship between household food insecurity and depressive symptoms among pregnant women: A cross sectional study

Objective: There is growing evidence suggesting that household food insecurity (HFI) is associated with adverse outcomes on mental health; however, limited evidence exists for pregnant women. This study was conducted to determine the relationship between HFI and depressive symptoms among a sample of pregnant women. Method: This cross sectional study was performed on 394 pregnant women referring to the health centers located in Qom, Iran, from October 2017 to March 2019. HFI was evaluated using an 18-item US Household Food Security Survey Module. The Beck Depression Inventory-II questionnaire was applied to determine the severity of depressive symptoms. Logistic regression analysis was used to determine the factors associated with elevated depressive symptoms in the study population. Results: The mean (± standard deviation) age of the study population was 28.59 ± 7.28 years. Almost 48 of participants were food insecure, and 37 experienced elevated levels of depressive symptoms during pregnancy. The prevalence of elevated depressive symptoms was significantly higher in food-insecure (P < 0.001) and unemployed (P = 0.02) women, while it was significantly lower in women with higher education levels (P < 0.001). In the adjusted model, it was revealed that HFI was significantly associated with the higher likelihood of having elevated depressive symptoms (OR = 3.31, 95 CI = 2.07, 5.29), while the higher level of education was negatively associated with the levels of depressive symptoms (OR = 0.40, 95 CI = 0.20, 0.79). Conclusion: HFI was positively associated with the severity of depressive symptoms in a sample of pregnant women. Further studies are needed to confirm this finding. Meanwhile, routine screening of HFI for all pregnant women in the community health centers is recommended. © 2020 Tehran University of Medical Sciences. All rights reserved

BAFF 60-mer, and Differential BAFF 60-mer Dissociating Activities in Human Serum, Cord Blood and Cerebrospinal Fluid.

B cell activation factor of the TNF family (BAFF/BLyS), an essential B cell survival factor of which circulating levels are elevated in several autoimmune disorders, is targeted in the clinic for the treatment of systemic lupus erythematosus (SLE). The soluble form of BAFF can exist as 3-mer, or as 60-mer that results from the ordered assembly of twenty 3-mers and that can be obtained from naturally cleaved membrane-bound BAFF or made as a recombinant protein. However, which forms of soluble BAFF exist and act in humans is unclear. In this study, BAFF 3-mer and 60-mer in biological fluids were characterized for size, activity and response to specific stimulators or inhibitors of BAFF. Human cerebrospinal fluids (CSF) from patients with multiple sclerosis and adult human sera contained exclusively BAFF 3-mer in these assays, also when BAFF concentrations were moderately SLE or highly (BAFFR-deficient individual) increased. Human sera, but not CSF, contained a high molecular weight, saturable activity that dissociated preformed recombinant BAFF 60-mer into 3-mer. This activity was lower in cord blood. Cord blood displayed BAFF levels 10-fold higher than in adults and consistently contained a fair proportion of active high molecular weight BAFF able to dissociate into 3-mer but not endowed with all properties of recombinant BAFF 60-mer. If BAFF 60-mer is produced in humans, it is dissociated, or at least attenuated in the circulation

Relationship between household food insecurity and food and nutrition literacy among children of 9-12 years of age: a cross-sectional study in a city of Iran

Objective: The aim of this study was to assess the relationship between household food insecurity (HFI) with food and nutrition literacy (FNLIT) in a sample of Iranian children. This cross sectional study was performed on 315 children aged 9 to 12 years recruited from the primary schools throughout Mashhad, Iran. The Household Food Insecurity Access Scale (HFIAS) was used to assess the HFI. Also, overall FNLIT score and its sub-categories were evaluated using a validated 40-item questionnaire. Results: The prevalence of HFI in the total sample was about 56. Also, almost 14 of students had a low FNLIT score. Food insecure children had significantly lower levels of FNLT and some subscales including nutrition knowledge, food choice literacy, and food label literacy than the food-secure subjects, moreover, they had a higher likelihood of having low FNLIT score (OR = 2.89, CI 1.03-8.09; p = 0.04). In conclusion, there is a negative association between HFI and FNLIT in children. Further studies to confirm this finding are needed. © 2020 The Author(s)

Safety of medication use in primary care

© 2014 Royal Pharmaceutical Society.BACKGROUND: Medication errors are one of the leading causes of harmin health care. Review and analysis of errors have often emphasized their preventable nature and potential for reoccurrence. Of the few error studies conducted in primary care to date, most have focused on evaluating individual parts of the medicines management system. Studying individual parts of the system does not provide a complete perspective and may further weaken the evidence and undermine interventions.AIM AND OBJECTIVES: The aim of this review is to estimate the scale of medication errors as a problem across the medicines management system in primary care. Objectives were: To review studies addressing the rates of medication errors, and To identify studies on interventions to prevent medication errors in primary care.METHODS: A systematic search of the literature was performed in PubMed (MEDLINE), International Pharmaceutical Abstracts (IPA), Embase, PsycINFO, PASCAL, Science Direct, Scopus, Web of Knowledge, and CINAHL PLUS from 1999 to November, 2012. Bibliographies of relevant publications were searched for additional studies.KEY FINDINGS: Thirty-three studies estimating the incidence of medication errors and thirty-six studies evaluating the impact of error-prevention interventions in primary care were reviewed. This review demonstrated that medication errors are common, with error rates between 90%, depending on the part of the system studied, and the definitions and methods used. The prescribing stage is the most susceptible, and that the elderly (over 65 years), and children (under 18 years) are more likely to experience significant errors. Individual interventions demonstrated marginal improvements in medication safety when implemented on their own.CONCLUSION: Targeting the more susceptible population groups and the most dangerous aspects of the system may be a more effective approach to error management and prevention. Co-implementation of existing interventions at points within the system may offer time- and cost-effective options to improving medication safety in primary care.Peer reviewe