Comparison of the BASDAI and the miniBASDAI in assessing disease activity in patients with ankylosing spondylitis

The BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) is the most widely used instrument for the assessment of disease activity in ankylosing spondylitis (AS). Objective. The aims to investigate whether the alternative BASDAI, here termed as the miniBASDAI [(Question (Q) 1 fatigue + Q2 spinal pain) + mean of (Q5 strength morning stiffness + Q6 duration morning stiffness)] / 3], measures disease activity more accurately in the subgroup of AS patients without peripheral manifestations. One hundred and ten patients were included in this cross-sectional study according to the modified New York criteria for AS. Clinical and biological parameters were evaluated. The disease activity was evaluated by the BASDAI. We calculated the miniBASDAI by omitting both the peripheral joints and the enthesitis questions: questions 3 and 4. Patients were dichotomized into a “P+” group if peripheral manifestations were present (at least arthritis or enthesitis) and a “P−” group, the subgroup without peripheral involvement (with either arthritis or enthesitis). Correlation of the BASDAI and miniBASDAI with other disease parameters were examined with the Spearman's rank correlation analysis. One hundred and ten patients were recruited. The percentage of patients with pure axial disease manifestation without peripheral involvement “P − group” was 42.7%. We found a similarly good correlation of the miniBASDAI with patient global, physician on disease activity, BASFI, ESR and CRP if compared to the correlation of the original BASDAI with these disease parameters, also in the group without peripheral involvement. Our study suggests that the BASDAI remains valid in assessing disease activity in AS patients with and without peripheral manifestations.     

Left and right ventricular function and volume assessment in young thalassemia major patients with no related myocardial iron overload

Thalassemia major (TM) patients have altered ventricular volumes and ejection fraction compared to normals, although evidence for these findings stem from restricted patient groups and has never been reproduced. We sought to evaluate cardiac parameters by cardiovascular magnetic resonance (CMR) in a group of young TM patients not covered by previous studies that are more representative of the TM population in many countries. Seventy patients including 40 TM with normal myocardial iron concentrations, and 30 age- and gender-matched normal (NL) volunteers underwent a CMR study for assessment of left and right ventricle volumes and function using a 1.5-T scanner. Left and right ventricle ejection fraction, indexed systolic and diastolic volumes, and indexed mass were compared between the two groups. Mean age of TM patients was 18.2?±?7.1 versus 17.5?±?8.5?years in NL with no significant differences (P?=?0.73). There was no difference in left ventricular (LV) ejection fraction between the groups (TM 64.9?±?5.7?%, NL 64.9?±?5.2?%; P?=?0.97). LV normalized end-diastolic and end-systolic volumes were significantly higher in patients with TM compared to NL volunteers (76.8?±?19.4 versus 66.6?±?11.7?mL/m², P?=?0.008, and 27.0?±?8.8 versus 23.6?±?5.0?mL/m², P?=?0.045). LV indexed mass was also higher in TM patients compared to NL (51.2?±?11.9 versus 42.0?±?8.5?g/m², P?<?0.001). No significant differences were observed in right ventricular parameters. In conclusion, younger patients with TM do not present different left or right ventricular function values compared to normal controls despite having increased left ventricular volumes and mass.     

Evaluation of acetylcholinesterase in an animal model of mania induced by d-amphetamine

The present study aims to investigate the effects of mood stabilizers, lithium (Li) and valproate (VPA), on acetylcholinesterase (AChE) activity in the brains of rats subjected to an animal model of mania induced by d-amphetamine (d-AMPH). In the reversal treatment, Wistar rats were first given d-AMPH or saline (Sal) for 14 days. Between days 8 and 14, the rats were treated with Li, VPA, or Sal. In the prevention treatment, rats were pretreated with Li, VPA, or Sal. AChE activity was measured in the brain structures (prefrontal cortex, hippocampus, and striatum). Li, alone in reversion and prevention treatments, increased AChE activity in the brains of rats. VPA, alone in prevention treatment, increased AChE activity in all brain regions evaluated; in the reversion, only in the prefrontal. However, d-AMPH decreased activity of AChE in the striatum of rats in both the reversion and prevention treatments. VPA was able to revert and prevent this AChE activity alteration in the rat striatum. Our findings further support the notion that the mechanisms of mood stabilizers also involve changes in AChE activity, thus reinforcing the need for more studies to better characterize the role of acetylcholine in bipolar disorder.     

Cognitive impairments in patients with cerebrovascular risk factors: A comparison of Mini Mental Status Exam and Montreal Cognitive Assessment

Objective and background

Recent evidence suggests that cerebrovascular risk factors are contributing factors, not only to vascular cognitive decline, but also for Alzheimer's disease. The study aim was to compare Montreal Cognitive Assessment (MoCA) and MMSE tests in subjects with cerebrovascular risk factors.

Patients and methods

Fifty patients with cerebrovascular risk factors were administrated the MMSE and MoCA tests. Data collected for all subjects and the results were compared.

Results

Cognitive impairments revealed on both tests were more frequent in females, and correlated with the level of education (for MoCA r = 0.75, p = 0.001 and for MMSE r = 0.662, p = 0.001). Mean values of MoCA score were significantly lower in patients with two or more cerebrovascular risk factors compared with those with only one risk factor (19.92 ± 5.99 versus 23.81 ± 4.06; p = 0.049), a finding that was not evidenced by MMSE.

Conclusions

The most frequent impaired domain in MMSE (for scores both less and more than 26) was attention; but in MoCA the most frequent impaired domains were delayed recall (for scores above 26), and visuo-executive (for scores ≤26), which is a common domain involved in vascular cognitive decline. MoCA may be superior to MMSE in early detection of cognitive decline in patients with vascular risk factors.     

A new mutation identified in <Emphasis Type="Italic">SPATA16</Emphasis> in two globozoospermic patients

Purpose

The aim of this study is to identify potential genes involved in human globozoopsermia.

Methods

Nineteen globozoospermic patients (previously screened for DPY19L2 mutations with no causative mutation) were recruited in this study and screened for mutations in genes implicated in human globozoospermia SPATA16 and PICK1. Using the candidate gene approach and the determination of Spata16 partners by Glutathione S-transferase (GST) pull-down four genes were also selected and screened for mutations.

Results

We identified a novel mutation of SPATA16: deletion of 22.6 Kb encompassing the first coding exon in two unrelated Tunisian patients who presented the same deletion breakpoints. The two patients shared the same haplotype, suggesting a possible ancestral founder effect for this new deletion. Four genes were selected using the candidate gene approach and the GST pull-down (GOPC, PICK1, AGFG1 and IRGC) and were screened for mutation, but no variation was identified.

Conclusions

The present study confirms the pathogenicity of the SPATA16 mutations. The fact that no variation was detected in the coding sequence of AFGF1, GOPC, PICK1 and IRGC does not mean that they are not involved in human globozoospermia. A larger globozoospermic cohort must be studied in order to accelerate the process of identifying new genes involved in such phenotypes. Until sufficient numbers of patients have been screened, AFGF1, GOPC, PICK1 and IRGC should still be considered as candidate genes.

     

Real-time quantitative PCR for assessment of antiviral drug effects against Epstein-Barr virus replication and EBV late mRNA expression

This study assesses the ability of quantitative real-time PCR to measure the effects of virus DNA polymerase inhibitors on EBV DNA and late mRNAs syntheses in EBV-producing cell lines. In-house real-time quantitative PCRs were used to measure EBV DNA (thymidine kinase) and mRNAs (BLLF1 gene/gp350/220, BVRF2 gene/protease) in P3HR-1 and B95-8 cells induced for EBV production by PMA and exposed to ganciclovir, cidofovir and foscarnet. The calculated 50% effective concentrations (EC(50)) for viral DNA replication inhibition in P3HR-1 cells after 7 days of drug exposure were 0.28+/-0.06, 0.29+/-0.01 and 13.6+/-0.17 microg/mL for ganciclovir, cidofovir and foscarnet, respectively. The EC(50) for B95-8 cells were 0.44+/-0.02, 0.70+/-0.06 and 46.8+/-0.5 microg/mL, respectively. The quantitation of the late viral mRNAs showed a decrease of 79-89% in the mRNA amount after 4 days of antiviral treatment. Nevertheless, a substantial amount of mRNA still remained detectable after drug exposure. The real-time PCR is an improvement in the attempt to simplify EBV DNA-quantitation for antiviral assays. The quantitation of late mRNA does not appear as more informative than DNA quantitation for the assessment of the DNA polymerase inhibitor activity, but it may be useful to assess the antiviral activity of drugs acting by another mechanism.     

Facilitators and barriers in implementing the Minimum Initial Services Package (MISP) for reproductive health in Nepal post-earthquake

Background

Following the Nepal earthquake in April 2015, UNFPA estimated that 1.4 million women of reproductive age were affected, with approximately 93,000 pregnant and 28,000 at risk of sexual violence. A set of priority reproductive health (RH) actions, the Minimum Initial Services Package (MISP), was initiated by government, international and local actors. The purpose of this study was to identify the facilitators and barriers affecting the implementation of priority RH services in two districts.

Methods

In September 2015, a mixed methods study design was used in Kathmandu and Sindhupalchowk districts to assess the implementation of the priority RH services five months post-earthquake. Data collection activities included 32 focus group discussions with male and female participants aged 18–49; 26 key informant interviews with RH, gender-based violence (GBV), and human immunodeficiency virus (HIV) experts; and 17 health facility assessments.

Results

The implementation of priority RH services was achieved in both districts. In Kathmandu implementation of emergency RH services started within days of the earthquake. Facilitating factors for successful implementation included disaster preparedness; leadership and commitment among national, international, and district level actors; resource mobilization; strong national level coordination; existing reproductive and child health services and community outreach programs; and supply chain management. Barriers included inadequate MISP training for RH coordinators and managers; weak communication between national and district level stakeholders; inadequate staffing; under-resourced and fewer facilities in rural areas; limited attention given to local GBV and HIV organizations; low availability of clinical management of rape services; and low awareness of GBV services and benefits of timely care.

Conclusion

Ensuring RH is included in emergency preparedness and immediate response efforts and is continued through the transition to comprehensive care is critical for national governments and humanitarian response agencies. The MISP for RH remains a critical component of response efforts, and the humanitarian community should consider these learnings in future emergency response.

     

Antioxidant treatment prevented late memory impairment in an animal model of sepsis

OBJECTIVE: Assess the effect of antioxidant treatment on late memory impairment and early hippocampus oxidative stress after cecal ligation and perforation. SUBJECTS: Male Wistar rats. INTERVENTIONS: Rats underwent sham operation or cecal ligation and perforation. Animals that underwent cecal ligation and perforation were divided into groups: 1) treated with basic support (50 mL/kg saline, 30 mg/kg ceftriaxone, and 25 mg/kg clindamycin every 6 hrs), 2) treated with basic support plus N-acetylcysteine (20 mg/kg N-acetylcysteine at 3, 6, 12, 18, and 24 hrs after cecal ligation and perforation), 3) treated with basic support plus deferoxamine (20 mg/kg deferoxamine at 3 and 24 hrs after cecal ligation and perforation), 4) treated with basic support plus N-acetylcysteine and deferoxamine, or 5) treated with N-acetylcysteine plus deferoxamine. MEASUREMENTS AND MAIN RESULTS: On days 10 and 30 after surgery, the animals underwent behavioral tasks: inhibitory avoidance task, habituation to an open field, and continuous multiple-trials step-down inhibitory avoidance task. The sepsis group showed significantly decreased performance in latency retention compared with the sham group in the inhibitory avoidance task. In the open-field task, the sepsis group presented memory impairment after sepsis. In the continuous multiple-trials step-down inhibitory avoidance task, the sepsis group showed a significant increase in the number of training trials required to reach the acquisition criterion. All these memory impairments were prevented by N-acetylcysteine plus deferoxamine treatment, but not its isolate use. In addition, the combined use of antioxidants attenuated oxidative damage in hippocampus 6 hrs after sepsis induction. CONCLUSIONS: Antioxidant treatment prevented the development of late cognitive deficits in an animal model of sepsis.     

Factors modulating the delivery and effect of enzymatic cargo conjugated with antibodies targeted to the pulmonary endothelium.

Vascular drug targeting may improve therapies, yet a thorough understanding of the factors that regulate effects of drugs directed to the endothelium is needed to translate this approach into the clinical domain. To define factors modulating the efficacy and effects of endothelial targeting, we used a model enzyme (glucose oxidase, GOX) coupled with monoclonal antibodies (anti-TM(34) or anti-TM(201)) to distinct epitopes of thrombomodulin, a surface determinant enriched in the pulmonary endothelium. GOX delivery results in conversion of glucose and oxygen into H(2)O(2) leading to lung damage, a clear physiologic endpoint. Results of in vivo studies in mice showed that the efficiency of cargo delivery and its effect are influenced by a number of factors including: 1) The level of pulmonary uptake of the targeting antibody (anti-TM(201) was more efficient than anti-TM(34)); 2) The amount of an active drug delivered to the target; 3) The amount of target antigen on the endothelium (animals with suppressed TM levels showed less targeting); and, 4) The substrate availability for the enzyme cargo in the target tissue (hyperoxia augmented GOX-induced injury). Therefore, both activities of the conjugates and biological factors control targeting and effects of enzymatic cargo. Understanding the nature of such "modulating biological factors" will hopefully allow optimization and ultimately applications of drug targeting for "individualized" pharmacotherapy.