Early use of MRI improves diagnostic accuracy in young adults with stroke

ObjectivesThe misdiagnosis of acute ischemic stroke in young adults is a significant problem since patients may have many decades of potential disability. Also, proven therapies for acute stroke may not be administered if there is an initial misdiagnosis. We assessed the hypothesis that early use of MRI, arrival by ambulance, and presentation to a Primary Stroke Center (PSC) would be associated with a reduced rate of misdiagnosis.MethodsA prospective database of young adults (ages 16–49 years) with ischemic stroke (final diagnosis provided by vascular neurologists) was reviewed. We collected information on several variables, including age, race, arrival by ambulance, whether brain MRI was performed within 48 h, and initial presentation to a PSC. Variables were tested against emergency department (ED) misdiagnosis using univariate and multivariate methods.Results77 patients with a mean age of 37.9 years were reviewed. 48.3% of patients arrived by ambulance, 53.2% had a brain MRI within 48 h, and 23.4% initially presented to a PSC. The overall rate of ED misdiagnosis was 14.5%. In multivariate testing, performance of MRI within 48 h (p = 0.023) was associated with a lower rate of misdiagnosis and age < 35 years was linked with greater likelihood of misdiagnosis (p = 0.047).ConclusionsEarly performance of MRI leads to greater accuracy of stroke diagnosis in young adults presenting to the ED. Patients less than age 35 years have a greater risk of misdiagnosis. ED physicians and neurologists should consider early use of MRI in young adults with stroke-like deficits and diagnostic uncertainty.     

Risk factors for maternal mortality in Delhi slums: a community-based case-control study

BACKGROUND: In order to develop, implement and evaluate policy for reducing maternal mortality, it is essential to study the risk factors associated with maternal deaths. AIMS: The study aims to determine the epidemiological risk factors and its related causes associated with maternal deaths in Delhi slums. MATERIALS AND METHODS: A community-based case-control study was designed, wherein snowball-sampling method was used to identify the maternal deaths (cases) in the community and circular systematic random sampling procedure was used to select the controls from the same area where a maternal death was found. STATISTICAL ANALYSIS: Data on 70 cases and 384 controls that had live births as the outcome of the pregnancy were analyzed. Logistic regression was applied to identify the risk factors. RESULTS: In the study population, most of the deliveries were conducted at home by untrained 'dais.' Cases were mostly illiterate, young, having high parity and no antenatal care taken during pregnancy (P CONCLUSIONS: The study findings suggest that women should be educated about the importance of antenatal registration and regular checkups. Untrained 'dais' should be trained to recognize the obstetric complications at an early stage and refer high-risk cases for adequate management. These preventive measures could help in reducing maternal mortality at the community level.     

microMRI-HREM pipeline for high-throughput, high-resolution phenotyping of murine embryos

Rapid and precise phenotyping analysis of large numbers of wild-type and mutant mouse embryos is essential for characterizing the genetic and epigenetic factors regulating embryogenesis. We present a novel methodology that permits precise high-throughput screening of the phenotype of embryos with both targeted and randomly generated mutations. To demonstrate the potential of this methodology we show embryo phenotyping results produced in a large-scale ENU-mutagenesis study. In essence this represents an analysis pipeline, which starts with simultaneous micro-magentic resonance imaging (microMRI) screening (voxel size: 25.4 x 25.4 x 24.4 microm) of 32 embryos in one run. Embryos with an indistinct phenotype are then cut into parts and suspect organs and structures are analysed with HREM (high-resolution episcopic microscopy). HREM is an imaging technique that employs 'positive' eosin staining and episcopic imaging for generating three-dimensional (3D) high-resolution (voxel size: 1.07 x 1.07 x 2 microm) digital data of near histological contrast and quality. The results show that our method guarantees the rapid availability of comprehensive phenotype information for high numbers of embryos in, if necessary, histological quality and detail. The combination of high-throughput microMRI with HREM provides an alternative screening pipeline with advantages over existing 3D phenotype screening methods as well as traditional histology. Thus, the microMRI-HREM phenotype analysis pipeline recommends itself as a routine tool for analysing the phenotype of transgenic and mutant embryos.     

Disseminated nodular granulomatous perifolliculitis

Nodular granulomatous perifolliculitis is a well-recognized infection of the dermal and subcutaneous tissue caused by dermatophytes, which normally do not invade beyond the epidermis. We report here one such case that occurred in an immunosuppressed individual. The patient was a 35-year-old farmer who presented with small pruritic eruption that had initially appeared on the lower leg and then had gradually spread to hair-bearing areas of the body, finally producing nodular and pustular inflammatory lesions with exacerbations and remissions. Fungal examination by direct potassium hydroxide mount and culture revealed Trichophyton rubrum. Granulomatous changes were seen on histopathological examination. The patient completely responded to systemic antifungal therapy.     

A class of Covariate-Adjusted Response-Adaptive Allocation Designs for Multitreatment Binary Response Trials

A class of covariate-adjusted response-adaptive randomization procedures is developed for binary treatment outcomes in a phase III clinical trial set up involving multiple treatments. The target allocation is developed by combining the ethical aspects with statistical precision under the existence of treatment covariate interaction. Relevant measures of the performance for the proposed allocation designs are studied and compared.     

Molecular Motions in Sucrose-PVP and Sucrose-Sorbitol Dispersions—II. Implications of Annealing on Secondary Relaxations

Purpose

To determine the effect of annealing on the two secondary relaxations in amorphous sucrose and in sucrose solid dispersions.

Methods

Sucrose was co-lyophilized with either PVP or sorbitol, annealed for different time periods and analyzed by dielectric spectroscopy.

Results

In an earlier investigation, we had documented the effect of PVP and sorbitol on the primary and the two secondary relaxations in amorphous sucrose solid dispersions (1). Here we investigated the effect of annealing on local motions, both in amorphous sucrose and in the dispersions. The average relaxation time of the local motion (irrespective of origin) in sucrose, decreased upon annealing. However, the heterogeneity in relaxation time distribution as well as the dielectric strength decreased only for β₁- (the slower relaxation) but not for β₂-relaxations. The effect of annealing on β₂-relaxation times was neutralized by sorbitol while PVP negated the effect of annealing on both β₁- and β₂-relaxations.

Conclusions

An increase in local mobility of sucrose brought about by annealing could be negated with an additive.     

Characterization of the GBoV1 Capsid and Its Antibody Interactions

Human bocavirus 1 (HBoV1) has gained attention as a gene delivery vector with its ability to infect polarized human airway epithelia and 5.5 kb genome packaging capacity. Gorilla bocavirus 1 (GBoV1) VP3 shares 86% amino acid sequence identity with HBoV1 but has better transduction efficiency in several human cell types. Here, we report the capsid structure of GBoV1 determined to 2.76 Å resolution using cryo-electron microscopy (cryo-EM) and its interaction with mouse monoclonal antibodies (mAbs) and human sera. GBoV1 shares capsid surface morphologies with other parvoviruses, with a channel at the 5-fold symmetry axis, protrusions surrounding the 3-fold axis and a depression at the 2-fold axis. A 2/5-fold wall separates the 2-fold and 5-fold axes. Compared to HBoV1, differences are localized to the 3-fold protrusions. Consistently, native dot immunoblots and cryo-EM showed cross-reactivity and binding, respectively, by a 5-fold targeted HBoV1 mAb, 15C6. Surprisingly, recognition was observed for one out of three 3-fold targeted mAbs, 12C1, indicating some structural similarity at this region. In addition, GBoV1, tested against 40 human sera, showed the similar rates of seropositivity as HBoV1. Immunogenic reactivity against parvoviral vectors is a significant barrier to efficient gene delivery. This study is a step towards optimizing bocaparvovirus vectors with antibody escape properties.