Myxovirus resistance,osteopontin and suppressor of cytokine signaling 3 polymorphisms predict hepatitis C virus therapy response in an admixed patient population: comparison with IL28B

OBJECTIVES:

Suppressor of cytokine signaling 3, myxovirus resistance protein and osteopontin gene polymorphisms may influence the therapeutic response in patients with chronic hepatitis C, and an association with IL28 might increase the power to predict sustained virologic response. Our aims were to evaluate the association between myxovirus resistance protein, osteopontin and suppressor of cytokine signaling 3 gene polymorphisms in combination with IL28B and to assess the therapy response in hepatitis C patients treated with pegylated-interferon plus ribavirin.

METHOD:

Myxovirus resistance protein, osteopontin, suppressor of cytokine signaling 3 and IL28B polymorphisms were analyzed by PCR-restriction fragment length polymorphism, direct sequencing and real-time PCR. Ancestry was determined using genetic markers.

RESULTS:

We analyzed 181 individuals, including 52 who were sustained virologic responders. The protective genotype frequencies among the sustained virologic response group were as follows: the G/G suppressor of cytokine signaling 3 (rs4969170) (62.2%); T/T osteopontin (rs2853744) (60%); T/T osteopontin (rs11730582) (64.3%); and the G/T myxovirus resistance protein (rs2071430) genotype (54%). The patients who had ≥3 of the protective genotypes from the myxovirus resistance protein, the suppressor of cytokine signaling 3 and osteopontin had a greater than 90% probability of achieving a sustained response (p<0.0001). The C/C IL28B genotype was present in 58.8% of the subjects in this group. The sustained virological response rates increased to 85.7% and 91.7% by analyzing C/C IL28B with the T/T osteopontin genotype at rs11730582 and the G/G suppressor of cytokine signaling 3 genotype, respectively. Genetic ancestry analysis revealed an admixed population.

CONCLUSION:

Hepatitis C genotype 1 patients who were responders to interferon-based therapy had a high frequency of multiple protective polymorphisms in the myxovirus resistance protein, osteopontin and suppressor of cytokine signaling 3 genes. The combined analysis of the suppressor of cytokine signaling 3 and IL28B genotypes more effectively predicted sustained virologic response than IL28B analysis alone.     

Effects of Estrogen Deficiency and/or Caffeine Intake on Alveolar Bone Loss,Density, and Healing: A Study in Rats

Background: The aim of this study is to evaluate the effects of caffeine and/or estrogen deficiency on ligature‐induced bone loss (BL), trabecular bone area (TBA), and postextraction bone healing (BH). Methods: Rats were assigned into one of the following groups (15 each): 1) control = non‐ingestion of caffeine/sham surgery; 2) caffeine = ingestion of caffeine/sham surgery); 3) ovariectomized (OVX) = non‐ingestion of caffeine/ovariectomy; or 4) caffeine/OVX = ingestion of caffeine/ovariectomy. The rats were under caffeine administration for 65 days and/or estrogen deficiency for 51 days. On day 21 after ovariectomy, one first mandibular molar received a ligature and the contralateral tooth was not ligated. The first maxillary molars were extracted 8 days before sacrifice. BL, TBA, the positive cells for tartrate‐resistant acid phosphatase (TRAP), receptor activator of nuclear factor‐κB ligand (RANKL), and osteoprotegerin (OPG) were analyzed in the furcation area of mandibular molars. Histometric BH and gene expression of bone morphogenetic protein (BMP)‐2, BMP‐7, osteopontin, and bone sialoprotein were evaluated in alveolar sockets. Results: The caffeine group presented the greatest BL and the OVX group the highest number of TRAP‐positive (TRAP⁺) cells around ligated teeth (P <0.05). The control group presented higher TBA and BH than the other groups (P <0.05). All test groups presented higher RANKL/OPG⁺ cells than the control group around ligated/unligated teeth. The OVX and caffeine/OVX groups presented a greater number of TRAP⁺ cells around unligated teeth than the control group (P <0.05). There were no differences among groups for gene expression (P >0.05). Conclusions: Caffeine increased BL in ligated teeth. Caffeine and/or estrogen deficiency decreased TBA in the unligated teeth and reduced BH after tooth extraction.     

A Simplified Palatal Lift Prosthesis for Neurogenic Velopharyngeal Incompetence

Velopharyngeal incompetence is a contributing factor to speech disorders and implies the presence of hypernasality, inappropriate nasal escape, and decreased air pressure during speech. One prosthetic treatment is a rehabilitative procedure employing a palatal lift prosthesis (PLP), which reduces hypernasality by approximating the incompetent soft palate to the posterior pharyngeal wall and consists of two parts, the anterior denture base and the palatal lifting plate, which are connected with steel wires; however, it seems difficult to reproduce the mobility of the soft palate in speaking, and it is therefore likely that the palatal lifting plate stimulates or oppresses the tissue of the soft palate and hinders rather than assists articulatory function. To avoid these disturbances we devised an adjustable PLP with a flexible conjunction between the denture base and the palatal lifting plate to obtain the optimal vertical lifting angle. The palatal plate was adapted to conform in a passive manner to the soft palate with light‐cured resin. The designed PLP simplified the procedure and reduced the number of adjustments and visits.     

Cardiac 123I-MIBG scintigraphy and arrhythmic risk in left ventricular noncompaction

Left ventricular noncompaction is an unusual but increasingly recognized cardiomyopathy, the etiology of which is still not definitely established. Clinical presentation includes a wide spectrum of scenarios, including heart failure, thromboembolism and malignant arrhythmias, with half of deaths occurring suddenly. Early detection of LVNC is therefore essential to prevent sudden cardiac death. To our knowledge, this is the first report of the presence of cardiac sympathetic nervous dysfunction, assessed by 123iodine-metaiodobenzylguanidine myocardial scintigraphy, in a patient with LVNC, preserved left ventricular systolic function and exercise-induced nonsustained ventricular tachycardia. This finding may be related to the increased arrhythmic risk observed in this cardiomyopathy, giving a new insight into the pathophysiology of LVNC.     

Anxiety,depression and suicidal ideation in patients with rheumatoid arthritis in use of methotrexate,hydroxychloroquine, leflunomide and biological drugs

Objective

This paper aims to investigate the prevalence of anxiety, depression and suicidal ideation in patients with rheumatoid arthritis taking different drugs to control the disease.

Methods

The study included 105 patients with rheumatoid arthritis who were treated with methotrexate, leflunomide, hydroxychloroquine and biological drugs. All patients were assessed using the Mini International Neuropsychiatric Interview, the Beck Scale for Suicide Ideation and the Hospital Anxiety and Depression Scale.

Results

Difference was statistically significant (p < 0.001) for both depression and anxiety as to suicidal ideation among groups of patients according to the medication used. Furthermore, the value reached by those patients taking biological drugs was alarming with higher scores for all measures, including suicide ideation. The patients using methotrexate and leflunomide reported lower scores on suicidal ideation than those using hydroxychloroquine and biological drugs. Patients using leflunomide showed less mental health impairment than other groups.

Conclusion

Greater scores for depression, as a comorbidity of rheumatoid arthritis, increase the rate of suicidal ideation and depression also can worsen general pain, hardships, treatment denial, and prognosis, as well as cause a faster reduction in quality of life. Patients taking biologic DMARDs (drugs known as disease-modifying drugs) had the highest rates of depression, anxiety and suicidal ideation among all patients studied. The current analysis showed that psychiatric aspects such as depression, anxiety and even suicide ideation, may differ between groups of patients with arthritis according to the drug used, serving as an alert to the importance of considering also this factors in therapeutic decisions.     

Sickle cell disease does not predispose to caries or periodontal disease

This study investigated the prevalence of dental caries and periodontal condition in a population with sickle cell disease (SCD), analyzing some associations with disease severity. The Decayed, Missing and Filled Teeth index (DMFT) and Community Periodontal Index (CPI) were recorded for 99 individuals with SCD and 91 matched controls. Socio-demographic status, oral health behaviors, and history of clinical severity of SCD were assessed. Statistical comparisons were performed between the group with SCD and the control group, as well as multivariate logistic regression analyses with DMFT index and CPI as the dependent variables. The mean number of decayed teeth was significantly higher in individuals with HbSS. Older age, female gender, and daily smoking were identified as risk factors for higher DMFT, while older age and absence of daily use of dental floss were risk factors for the development of periodontal disease. In conclusion, risk factors known to cause caries and periodontal disease had more influence on oral health than the direct impact of SCD.     

Switching cell penetrating and CXCR4-binding activities of nanoscale-organized arginine-rich peptides

Arginine-rich protein motifs have been described as potent cell-penetrating peptides (CPPs) but also as rather specific ligands of the cell surface chemokine receptor CXCR4, involved in the infection by the human immunodeficiency virus (HIV). Polyarginines are commonly used to functionalize nanoscale vehicles for gene therapy and drug delivery, aimed to enhance cell penetrability of the therapeutic cargo. However, under which conditions these peptides do act as either unspecific or specific ligands is unknown. We have here explored the cell penetrability of differently charged polyarginines in two alternative presentations, namely as unassembled fusion proteins or assembled in multimeric protein nanoparticles. By this, we have observed that arginine-rich peptides switch between receptor-mediated and receptor-independent mechanisms of cell penetration. The relative weight of these activities is determined by the electrostatic charge of the construct and the oligomerization status of the nanoscale material, both regulatable by conventional protein engineering approaches.