Toward an understanding of the interaction between filarial parasites and host antigen-presenting cells

Summary: Lymphatic filarial infection, from an immunologic point of view, is one of the most complex parasite infections. Not only are there different clinical manifestations that reflect differing immune responses, but the parasite's multiple stages, each with distinct anatomic tropism, add a compartmental layer of complexity to an already complicated process. Moreover, these parasites have finely tuned immune evasion strategies that enable escape from the innate immune system. As different stages of the parasite interact with different types of antigen‐presenting cells that, in turn, may play a significant role in shaping the subsequent adaptive immune response, the focus of this review is to provide insight into the interaction between filarial parasites and antigen‐presenting cells with an eye toward understanding how they influence parasite antigen‐driven T‐cell responses.     

Protocolized Laboratory Screening for the Medical Clearance of Psychiatric Patients in the Emergency Department: A Systematic Review

Objective

Emergency department (ED) patients with psychiatric chief complaints undergo medical screening to rule out underlying or comorbid medical illnesses prior to transfer to a psychiatric facility. This systematic review attempts to determine the clinical utility of protocolized laboratory screening for the streamlined medical clearance of ED psychiatric patients by determining the clinical significance of individual laboratory results.

Methods

We searched PubMed, Embase, and Scopus using the search terms “emergency department, psychiatry, diagnostic tests, laboratories, studies, testing, screening, and clearance” up to June 2017 for studies on adult psychiatric patients. This systematic review follows the recommendations of Meta‐analysis of Observational Studies in Epidemiology (MOOSE) statement. The quality of each study was rated according to the Newcastle‐Ottawa quality assessment scale.

Results

Four independent reviewers identified 2,847 publications. We extracted data from three studies (n = 629 patients). Included studies defined an abnormal test result as any laboratory result that falls out of the normal range. A laboratory test result was deemed as “clinically significant” only when patient disposition or treatment plan was changed because of that test result. Across the three studies the prevalence of clinically significant results were low (0.0%–0.4%).

Conclusions

The prevalence of clinically significant laboratory test results were low, suggesting that according to the available literature, routine laboratory testing does not significantly change patient disposition. Due to the paucity of available research on this subject, we could not determine the clinical utility of protocolized laboratory screening tests for medical clearance of psychiatric patients in the ED. Future research on the utility of routine laboratory testing is important in a move toward shared decision making and patient‐centered health care.

     

Is High Preprocedural Renal Resistive Index Sensitive Enough to Predict Iodine Contrast-Induced Nephropathy in Patients Receiving Intra-Arterial Iodinate Contrast?

PurposeRenal Resistive Index (RRI) is a newly introduced sonographic index in predicting contrast-induced nephropathy (CIN) development. It has been suggested that RRI > 0.69 should be considered as a risk factor for CIN development. The present study aimed to calculate the predictive value of RRI using a cutoff point of 0.69.MethodsA total of 90 patients who were a candidate for coronary vessels angiography were enrolled in this study. Color Doppler ultrasonography was performed and RRI was measured. Patients were followed up for 48 hours after contrast media exposure for the CIN development. The diagnosis of CIN was based on a 25% relative rise or 0.5 mg/dL absolute rise in creatinine level. The predictive values of RRI were measured using 0.69 as a cutoff point.ResultsOut of 90 patients, CIN developed in 3 patients and 17 patients had preprocedural RRI > 0.69. Of 3 patients with CIN, 1 had RRI > 0.69. Using 0.69 as the cutoff point, the measured sensitivity and specificity of RRI were 33.3% and 83.9%, respectively.ConclusionsRRI > 0.69 is not a sensitive index in predicting the CIN development and cannot be used as an independent factor.     

Isfahan Healthy Heart Programme: a comprehensive integrated community-based programme for cardiovascular disease prevention and control. Design,methods and initial experience

The Isfahan Healthy Heart Programme (IHHP) is a five to six year comprehensive integrated community-based programme for cardiovascular diseases (CVD) prevention and control via reducing CVD risk factors and improvement of cardiovascular healthy behaviour in a target population. IHHP started late in 1999 and will be finished in 2005-2006. A primary survey was done to collect baseline data from interventional (Isfahan and Najaf-Abad) and reference (Arak) communities. In a two-stage sampling method, we randomly selected 5 to 10 percent of households from randomly selected clusters. Then individuals aged > or = 19 years were selected for the survey. This way, data from 12,600 individuals (6300 in interventional counties and 6300 in the reference county) was collected and stratified according to living area (urban vs. rural) and different age and sex groups. The samples underwent a 30-minute interview to complete validated questionnaires containing questions on demography, socioeconomic status, smoking behaviour, physical activity, nutritional habits and other behaviour regarding CVD. Blood pressure and body mass index (BMI) measurements were done and fasting blood samples were taken for two hours post load plasma glucose (2 hpp), serum (total, HDL and LDL) cholesterol and triglyceride levels. A twelve-lead electrocardiogram was recorded in all persons above 35 years of age. Community-wide surveillance of deaths, hospital discharges, myocardial infarction and stroke registry was carried out in the intervention and control areas. Four to five years of interventions based on different categories such as mass media, community partnerships, health system involvement and policy and legislation have started in the intervention area while Arak will be followed without intervention. Considering the results of the baseline surveys, (assessments needed, the objectives, existing resources and the possibility of national implementation) the interventions were planned. They were set based on specific target groups like school children, women, work-site, health personnel, high-risk persons, and community leaders were actively engaged as decision makers. A series of teams was arranged for planning and implementation of the intervention strategies. Monitoring will be done on small samples to assess the effect of different interventions in the intervention area. While four periodic surveys will be conducted on independent samples to assess health behaviours related to CVD risk factors in the intervention and reference areas, the original pre-intervention subjects aged more than 35 years will be followed in both areas to assess the individual effect of interventions and outcomes like sudden death, fatal and nonfatal MI and stroke. The whole baseline survey will be repeated on the original and an independent sample in both communities at the end of the study.     

A longitudinal study of family structure in Swedish persons with haemophilia

Haemophilia is an X‐linked inherited rare bleeding disorder affecting mainly men. The treatment consists of replacement therapy that has been associated with severe side effects, such as blood transmitted viral infections, but has markedly improved over the last decades. The aim of this study was to study family structure over time among Swedish persons with haemophilia (PWH), focusing on children, siblings and marital status. PWH A or B were identified from the haemophilia centres and the national Patient Registry. Each PWH was compared to five age‐ and gender‐matched controls. The national Multi‐Generation Registry was used to identify children and siblings. A total of 1365 children with a father suffering from haemophilia A or B and 1938 siblings of the PWH were identified. Having one or more children was significantly less common (P = 0.003) for PWH than for controls. Significantly lower rates of having a child were also found for the subgroups of persons suffering from severe haemophilia and those infected with HIV (P < 0.001). A higher proportion of PWH, with or without HIV and/or viral hepatitis had siblings compared to the controls (P < 0.001). However, the mean number of siblings was significantly lower for persons with severe haemophilia (P = 0.001). The number of marriages and divorces did not differ between PWH and controls. Our data indicate a negative impact of HIV and viral hepatitis on family structure for PWH despite the relatively good access to treatment in Sweden over the last few decades. This was particularly true for those with a severe form of haemophilia.     

Mutation in Osteoactivin Decreases Bone Formation in Vivo and Osteoblast Differentiation in Vitro

We have previously identified osteoactivin (OA), encoded by Gpnmb, as an osteogenic factor that stimulates osteoblast differentiation in vitro. To elucidate the importance of OA in osteogenesis, we characterized the skeletal phenotype of a mouse model, DBA/2J (D2J) with a loss-of-function mutation in Gpnmb. Microtomography of D2J mice showed decreased trabecular mass, compared to that in wild-type mice [DBA/2J-Gpnmb⁺/SjJ (D2J/Gpnmb⁺)]. Serum analysis showed decreases in OA and the bone-formation markers alkaline phosphatase and osteocalcin in D2J mice. Although D2J mice showed decreased osteoid and mineralization surfaces, their osteoblasts were increased in number, compared to D2J/Gpnmb⁺ mice. We then examined the ability of D2J osteoblasts to differentiate in culture, where their differentiation and function were decreased, as evidenced by low alkaline phosphatase activity and matrix mineralization. Quantitative RT-PCR analyses confirmed the decreased expression of differentiation markers in D2J osteoblasts. In vitro, D2J osteoblasts proliferated and survived significantly less, compared to D2J/Gpnmb⁺ osteoblasts. Next, we investigated whether mutant OA protein induces endoplasmic reticulum stress in D2J osteoblasts. Neither endoplasmic reticulum stress markers nor endoplasmic reticulum ultrastructure were altered in D2J osteoblasts. Finally, we assessed underlying mechanisms that might alter proliferation of D2J osteoblasts. Interestingly, TGF-β receptors and Smad-2/3 phosphorylation were up-regulated in D2J osteoblasts, suggesting that OA contributes to TGF-β signaling. These data confirm the anabolic role of OA in postnatal bone formation.Osteoporosis is a growing public health problem, in part because of the increasing numbers of people living beyond the age of 65 years.¹ It is characterized by low bone mass due to increased bone resorption by osteoclasts and decreased bone formation by osteoblasts, with significant deterioration in the bone microarchitecture leading to high bone fragility and increased fracture risk.^1,2 The net effect of osteoporosis is low bone mass.¹ There is an increasing demand for identifying novel bone anabolic factors with potential therapeutic benefits in treating generalized bone loss, such as osteoporosis and/or major skeletal fracture.Osteoactivin is a novel glycoprotein first identified in natural mutant osteopetrotic rats.³ The same protein has been identified and named separately in several other species: as dendritic cell heparan sulfate proteoglycan integrin dependent ligand (DCHIL) in mouse dendritic cells,⁴ as transmembrane glycoprotein NMB (GPNMB) in human melanoma cell lines and melanocytes,⁵ and as hematopoietic growth factor inducible neurokinin (HGFIN) in human tumor cells.⁶ The current recommended name for the protein encoded by Gpnmb in mouse is transmembrane glycoprotein NMB (http://www.ncbi.nlm.nih.gov/protein/Q99P91.2); here, we continue to use osteoactivin (OA) for the protein and Gpnmb for the gene. OA is a type I transmembrane protein that consists of multiple domains, including an extracellular domain, transmembrane domain, and protein sorting signal sequence.⁷ Within the C-terminal domain, OA has an RGD motif, predicting an integrin attachment site.^3,7–9Our research group initially reported on the novel role of OA in osteoblast differentiation and function.^7–10 We demonstrated that OA expression has a temporal pattern during osteoblast differentiation, being highest during matrix maturation and culture mineralization in vitro.^7–11 Using loss-of–function and gain-of–function approaches in osteoblasts, we reported that OA overexpression increases osteoblast differentiation and function and that OA down-regulation decreases nodule formation, alkaline phosphatase (ALP) activity, osteocalcin (OC) production, and matrix mineralization in vitro.⁷ We also reported on the positive role of OA in mesenchymal stem cell (MSCs) differentiation into osteoblasts in vitro.¹² In another study, we showed that recombinant OA protein induces higher osteogenic potential of fetal-derived MSCs, compared with bone marrow–derived MSCs¹³ and its osteogenic effects in the mouse C3H10T1/2 MSC cell line were similar to those of recombinant BMP-2.¹² We also localized OA protein as associated predominately with osteoblasts lining trabecular bones in vivo,¹¹ and showed that local injection of recombinant OA increased bone mass in a rat model.¹⁴ Moreover, in a fracture repair model OA expression increased over time, reaching a maximum 2 weeks after fracture.¹¹ In a parallel study, recombinant OA supported bone regeneration and formation in a rat critical-size calvarial defect model.¹⁵ Others have shown that OA is highly expressed by osteoclasts in vitro, suggesting that it may regulate osteoclast formation and activity.¹⁶There is urgent need for an animal model to fully examine the role of OA in osteogenesis. Interestingly, a natural mutation of the Gpnmb gene has been identified in the DBA/2J (D2J) mouse strain.¹⁷ These mice exhibit high-frequency hearing loss, which begins at the time of weaning and becomes severe by 2 to 3 months of age.^18,19 Aged D2J mice also develop progressive eye abnormalities that closely mimic human hereditary glaucoma. The onset of disease symptoms falls roughly between 3 and 4 months of age, and disease becomes severe by 6 months of age.^5,20 D2J mice are homozygous for a nonsense mutation in the Gpnmb gene sequence that induces an early stop codon, generating a truncated protein sequence of 150 amino acids (aa) instead of the full-length 562-aa OA protein.⁵ The control for the D2J mouse is the wild-type DBA/2J-Gpnmb⁺/SjJ mouse (D2J/Gpnmb⁺), homozygous for the wild-type Gpnmb gene.²¹ These Gpnmb wild-type mice do not develop glaucoma, as D2J mice do, although they exhibit mild iris stromal atrophy.²¹In the present study, we used Gpnmb mutant (D2J) and Gpnmb wild-type (D2J/Gpnmb⁺) mice to gain insight into the role of OA in osteogenesis and in osteoblast differentiation and function. Here, we report that loss-of–function mutation of Gpnmb suppresses bone formation by directly affecting osteoblast proliferation and survival, leading to a decreased number of differentiated osteoblasts with suppressed activity in bone mineralization. Thus, our data point to OA as a novel and positive regulator of postnatal bone formation.     

Comparative evaluation of effects of different surface treatment methods on bond strength between fiber post and composite core

PURPOSE

Debonding of a composite resin core of the fiber post often occurs at the interface between these two materials. The aim of this study was to evaluate the effects of different surface treatment methods on bond strength between fiber posts and composite core.

MATERIALS AND METHODS

Sixty-four fiber posts were picked in two groups (Hetco and Exacto). Each group was further divided into four subgroups using different surface treatments: 1) silanization; 2) sandblasting; 3) Treatment with 24% H₂O₂, and 4) no treatment (control group). A cylindrical plexiglass matrix was placed around the post and filled with the core resin composite. Specimens were stored in 5000 thermal cycles between 5℃ and 55℃. Tensile bond strength (TBS) test and evaluation using stereomicroscope were performed on the specimen and the data were analyzed using two-way ANOVA, Post Hoc Scheffe tests and Fisher''s Exact Test (α=.05).

RESULTS

There was a significant difference between the effect of different surface treatments on TBS (P<.001) but different brands of post (P=.743) and interaction between the brand of post and surface treatment (P=.922) had no significant effect on TBS. Both silanization and sandblasting improved the bonding strength of fiber posts to composite resin core, but there were not any significant differences between these groups and control group.

CONCLUSION

There was not any significant difference between two brands of fiber posts that had been used in this study. Although silanization and sandblasting can improve the TBS, there was not any significant differences between surface treatments used.     

Prooxidant-Antioxidant Balance and Antioxidized LDL Antibody Level Values and Cardiac Function in Patients with Coronary Artery Disease

Objectives: We studied the association between the prooxidant-antioxidant balance (PAB), anti-malondialdehyde-modified low-density lipoprotein (oxidized LDL, ox-LDL) IgG antibody and indices of cardiac function (systolic and diastolic function) in patients with coronary artery disease (CAD). Methods: Fifty-five patients with established CAD were selected, and serum levels of anti-ox-LDL IgG and PAB values were measured and compared with 40 matched healthy controls. Systolic and diastolic functions were determined for all patients. Results: PAB values were significantly higher in patients than in controls (p < 0.001), whilst serum anti-ox-LDL concentrations were not statistically different between the 2 groups (p = 0.821). However, after adjustment for high-density lipoprotein cholesterol, the patients had higher anti-ox-LDL levels (p = 0.04). Total PAB values were inversely associated with ejection fraction (r = -0.326, p = 0.031), but this was not the case for anti-ox-LDL in either group (p > 0.05). Conclusion: Serum concentrations of a marker of oxidative stress (PAB values) are inversely associated with cardiac function. PAB is a relatively simple index that could be incorporated into risk assessment in CAD patients. Anti-ox-LDL IgG antibody concentration does not appear to reflect total oxidative stress as assessed by PAB.