The Val66Met Polymorphism at the BDNF Gene does not Influence Wisconsin Card Sorting Test Results in Children and Adolescents with Bipolar Disorder

ObjectivesTo assess the role of the Val66Met polymorphism at the brain-derived neurotrophic factor (BDNF) gene on the performance of children and adolescents with bipolar disorder [juvenile bipolar disorder (JBD)] on the Wisconsin Card Sorting Test (WCST).MethodsChildren and adolescents were assessed by the K-SADS-PL and a clinical evaluation for BD and comorbid conditions. Manic and depressive symptoms were assessed with the Young Mania Rating Scale and the Children Depression Rating Scale – Reviewed. The Val66Met polymorphism at the BDNF was genotyped from a blood sample. Patients’ IQ and executive functions were assessed by a standard cognitive flexibility test (WCST).ResultsFifty-three subjects were included in the study. No significant difference was observed between the Val/Val and Val/Met+Met/Met groups on any WCST scores in the MANCOVA (F48,5 = .76; p = .59; Perseverative Errors, p = .66; Nonperseverative Errors, p = .58; Categories Completed, p = .34; Attempts to Reach First Category, p=.64; and Percentage of Conceptual Level Responses, p = .99).ConclusionsOur findings from this sample of children and adolescents with BD do not replicate results from studies of adults and suggest the existence of differences in the neurobiology of this disorder across the life cycle. Investigations of larger samples are necessary to confirm these data.     

Blockade of CXCR1/2 chemokine receptors protects against brain damage in ischemic stroke in mice: Ischemia and Reparixin

OBJECTIVE:

Ischemic stroke may result from transient or permanent reductions of regional cerebral blood flow. Polymorphonuclear neutrophils have been described as the earliest inflammatory cells to arrive in ischemic tissue. CXCR1/2 receptors are involved in the recruitment of these cells. However, the contribution of these chemokine receptors during transient brain ischemia in mice remains poorly understood. In this work, we investigated the effects of reparixin, an allosteric antagonist of CXCR1/2 receptors, in a model of middle cerebral artery occlusion and reperfusion in mice.

METHODS:

C57BL/6J male mice treated with reparixin or vehicle were subjected to a middle cerebral artery occlusion procedure 1 h after the treatment. Ninety minutes after ischemia induction, the monofilament that prevented blood flow was removed. Twenty-four hours after the reperfusion procedure, behavioral changes, including motor signs, were analyzed with the SmithKline/Harwell/Imperial College/Royal Hospital/Phenotype Assessment (SHIRPA) battery. The animals were sacrificed, and brain tissue was removed for histological and biochemical analyses. Histological sections were stained with hematoxylin and eosin, neutrophil infiltration was estimated by myeloperoxidase activity and the inflammatory cytokine IL-1β was measured by ELISA.

RESULTS:

Pre-treatment with reparixin reduced the motor deficits observed in this model of ischemia and reperfusion. Myeloperoxidase activity and IL-1β were reduced in the reparixin-treated group. Histological analysis revealed that ischemic injury was also attenuated by reparixin pre-treatment.

CONCLUSIONS:

Our results suggest that the blockade of the CXCR1/2 receptors by reparixin promotes neuroprotective effects by reducing the levels of polymorphonuclear infiltration in the brain and the tissue damage associated with middle cerebral artery occlusion and reperfusion.     

Oral glucose for pain relief during examination for retinopathy of prematurity: a masked randomized clinical trial

OBJECTIVE:

Ophthalmologic examination for retinopathy of prematurity is a painful procedure. Pharmacological and non-pharmacological interventions have been proposed to reduce pain during eye examinations. This study aims to evaluate the analgesic effect of 25% glucose using a validated pain scale during the first eye examination for retinopathy of prematurity in preterm infants with birth weight ≤1,500 g and/or gestational age ≤32 weeks.

METHODS:

A masked, randomized clinical trial for one dose of 1 ml of oral 25% glucose solution 2 minutes before the first ophthalmologic examination for retinopathy of prematurity was conducted between March 2008 and April 2010. The results were compared to those of a control group that did not receive oral glucose solution. Pain was evaluated using a Neonatal Infant Pain Scale immediately before and immediately after the ophthalmologic examination in both groups. Clinicaltrials.gov: {"type":"clinical-trial","attrs":{"text":"NCT00648687","term_id":"NCT00648687"}}NCT00648687

RESULTS:

One hundred and twenty-four patients who were examined for the first time for retinopathy of prematurity were included. Seventy were included in the intervention group and 54 in the control group. The number of patients with pain immediately before the procedure was similar in both groups. The number of patients with pain after ophthalmologic examination was 15.7% in the intervention group and 68.5% in the control group (p<0.001).

CONCLUSIONS:

One ml of oral 25% glucose solution given 2 minutes before an ophthalmologic examination for retinopathy of prematurity was an effective measure for pain relief.     

Mutagenicity and cytotoxicity in patients submitted to ionizing radiation: A comparison between cone beam computed tomography and radiographs for orthodontic treatment

Objectives:To evaluate and compare mutagenicity (micronucleus) and cytotoxicity (karyorrhexis, pyknosis, and karyolysis) in exfoliated buccal mucosa cells of children following cone beam computed tomography (CBCT) or conventional radiograph exposure necessary for orthodontic planning.Materials and Methods:A total of 49 healthy children were submitted to CBCT or a conventional orthodontic radiographic protocol; they were divided into two groups based on exam: CBCT (n  =  24) and Radiographic Set (n  =  25) groups. The micronucleus test in the exfoliated buccal mucosa cells was applied.Results:There was not a statistically significant difference (P > .05) found between the number of micronucleated buccal mucosa cells (MNC) before and after exposure to radiation in either group, showing that neither group experienced a mutagenic effect. However, radiation did cause other nuclear alterations closely related to cytotoxicity, including karyorrhexis, pyknosis, and karyolysis, in both groups (P < .05). The CBCT group presented a greater increase in cell death than was noted in the Radiographic Set group (P < .044).Conclusion:According to the micronucleus test, mutagenicity was not induced by the CBCT or the conventional radiographs, but cytotoxicity was verified after these exams, especially after CBCT. That might have happened once the CBCT group received a greater radiation dose than the Radiographic Set group as a result of the protocols used in orthodontic planning for this study.     

Development of a measure of the patient-provider relationship in antenatal care and its importance in PMTCT

The prevention of mother-to-child HIV transmission (PMTCT) is a complex challenge in heavily affected and resource-limited settings such as South Africa. Management of PMTCT requires a cascade of interventions that need to be addressed to effectively decrease the risk of HIV transmission to infants. This PMTCT cascade includes incremental components that can be shaped and influenced by the patient-provider relationship. The relationship that a pregnant woman has with her care providers may possibly affect decisions that she makes concerning her antenatal care and may, in turn, influence the quality of the care provided. A patient-provider relationship scale (PPRS) was developed in Pretoria, South Africa with two aims: first, to quantify the patient-provider relationship in an antenatal population in a resource-limited setting and provide preliminary evidence of its reliability and validity; and second, to determine whether the patient-provider relationship has an effect on PMTCT. The instrument was administrated in a cross-sectional pilot study to a group of women at discharge after delivery (n=192) at two major hospitals in South West Tshwane. Statistical analysis of the instrument showed high reliability (α=0.91) and preliminary evidence of its validity including significant associations with participants' attitudes regarding the functioning of the clinics and a single statement (the clinic staff "know me as a person," R=0.47, p<0.001) that has been shown previously to have a significant association with adherence to antiretroviral treatment. For HIV-positive participants, the PPRS was significantly associated with statements related to important components of the PMTCT cascade. In addition, those with substantially inadequate antenatal care (≤2 visits) and those who did not initiate highly active antiretroviral therapy, although eligible, had significantly poorer PPRS scores. The PPRS is a potentially useful, context-appropriate instrument that could have an important role in future research focused on improving PMTCT and decreasing the risk of HIV infection in children.     

An open-label, sequential, dose-finding study of peginesatide for the maintenance treatment of anemia in chronic hemodialysis patients

ABSTRACT: BACKGROUND: Peginesatide is a peptide-based erythropoiesis-stimulating agent that was designed and engineered to stimulate specifically the erythropoietin receptor dimer that governs erythropoiesis. The primary objective of this phase 2 dose-finding study was to determine the once-monthly peginesatide dosing strategy that would maintain hemoglobin within [PLUS-MINUS SIGN]1.0 g/dL of baseline values after conversion from epoetin alfa; the safety of peginesatide was evaluated concurrently. METHODS: Chronic hemodialysis patients on stable regimens of epoetin alfa were sequentially assigned to cohorts that differed on (1) how the peginesatide starting dose was determined (using a single epoetin alfa--to-peginesatide dose conversion ratio or a tiered, weight-based or absolute-dose conversion table) and on (2) whether or not a 1-week erythropoiesis-stimulating agent-free interval was used. Peginesatide doses were titrated to maintain hemoglobin levels within [PLUS-MINUS SIGN]1.0 g/dL from baseline. RESULTS: A total of 164 patients were enrolled and received intravenous peginesatide every 4 weeks for up to 6 doses; the duration of the study including follow-up was [LESS-THAN OR EQUAL TO]29 weeks. Overall, the proportion of patients with hemoglobin levels within [PLUS-MINUS SIGN]1.0 g/dL of baseline increased over the course of the study from 39% (Weeks 2--13) to 54% (Weeks 18--25). Cohorts that used tiered dose conversion tables trended towards having more stable peginesatide doses than did those cohorts that used a single dose conversion ratio. Moreover, cohorts that used an erythropoiesis-stimulating agent-free interval did not have the substantial initial increase in hemoglobin levels that was seen in those cohorts that did not use such an interval. In this study, the safety profile of peginesatide was consistent with those of marketed erythropoiesis-stimulating agents. CONCLUSIONS: The results of this study were used to guide the dosing regimens used subsequently in phase 3 studies. Once-monthly peginesatide is feasible in hemodialysis patients.Trial registrationClinicalTrials.gov registration: NCT00228449.     

Osteoporosis/osteopenia as an independent factor associated with periodontitis in postmenopausal women: a case–control study

Summary

This study investigated whether osteoporosis/osteopenia has an influence on the progression of periodontitis in postmenopausal women. The findings highlight that postmenopausal women with osteoporosis/osteopenia had a greater chance of presenting periodontitis than those with normal bone mineral density, particularly among nonusers of osteoporosis medications and women with a greater number of remaining teeth, showing that osteoporosis/osteopenia has had an influence on the progression of periodontitis.

Introduction

This study investigated whether osteoporosis/osteopenia has an influence on the progression of periodontitis in postmenopausal women and explored the effects of use of osteoporosis medication and tooth loss on this association.

Methods

This case–control study involved 521 postmenopausal women, with minimum age of 50 years, in Feira de Santana, Bahia, Brazil. Sociodemographic characteristics, health conditions/medications, and lifestyle habits were recorded. A complete periodontal examination was performed and periodontitis was diagnosed. Bone mineral density was evaluated through lumbar spine and femoral bone densitometry, obtained using dual-energy X-ray absorptiometry. Logistic regression was used to calculate the strength of association between the occurrences of osteoporosis/osteopenia and periodontitis.

Results

Women with osteoporosis/osteopenia were twice as likely to present periodontitis, as were those with normal bone mineral density, even after adjusting for smoking, age, family income, and last visit to dentist (odds ratios (OR)_adjusted?=?2.24, 95 % CI [1.24–4.06], p?=?0.008). Among nonusers of osteoporosis medication (OR_adjusted?=?2.51, 95 % CI [1.33–4.73], p?=?0.004) and women with at least 10 remaining teeth (OR_adjusted?=?2.50 95 % CI [1.18–5.27], p?=?0.02), the odds ratio was higher and statistically significant.

Conclusions

These findings highlight that postmenopausal women with osteoporosis/osteopenia had a greater chance of presenting periodontitis than those with normal bone mineral density, particularly among nonusers of osteoporosis medications and women with a greater number of remaining teeth.