Contactins in the central nervous system: role in health and disease

Contactins are a group of cell adhesion molecules that are mainly expressed in the brain and play pivotal roles in the organization of axonal domains, axonal guidance, neuritogenesis, neuronal development, synapse formation and plasticity, axo-glia interactions and neural regeneration. Contactins comprise a family of six members. Their absence leads to malformed axons and impaired nerve conduction. Contactin mediated protein complex formation is critical for the organization of the axon in early central nervous system development. Mutations and differential expression of contactins have been identified in neuro-developmental or neurological disorders. Taken together, contactins are extensively studied in the context of nervous system development. This review summarizes the physiological roles of all six members of the Contactin family in neurodevelopment as well as their involvement in neurological/neurodevelopmental disorders.     

Radiographic evaluation of ventral instability in lumbar spondylolisthesis: do we need extension radiographs in routine exams?

Purpose

To determine the usefulness of acquiring extension radiographs for the evaluation of the degree of spondylolisthesis.

Methods

Routine radiographs of the lumbar spine were retrospectively evaluated in 87 patients (mean-age 63, range 32–86) by two independent radiologists. All patients received radiographs in standing neutral, flexion and extension position. Vertebral body depth, sagittal translational displacement and lordosis angle were measured and slip percentage (SP) was calculated on standing neutral, flexion and extension radiographs. Statistical analysis was performed with a two-sided t test. Inter- and intraobserver reliability was assessed using the kappa-coefficient.

Results

There was no statistically significant SP-difference between neutral standing and extension images. Ventral instability was diagnosed in 25–34 % (cut-off >8 % SP-difference) for neutral versus flexion comparison. The detection rate of flexion–extension radiographs representing the extremes of motion was lower with 15–22 %. Inter- and intraobserver reliability was good to excellent.

Conclusion

Slip percentage in routine standing extension radiography ultimately does not differ from that obtained in a static neutral standing view. Extension radiography may therefore be omitted in a routine work-up of ventral instability in lumbar spondylolisthesis.     

Amhezole,A Novel Fungal Secondary Metabolite from Aspergillus terreus for Treatment of Microbial Mouth Infection

Bio‐guided fractionation of Aspergillus terreus extract leads to isolation of a novel terpenoidal secondary metabolite. The isolated compound and the total alcoholic extract of Aspergillus terreus showed a remarkable activity against microbial mouth infections; namely, Candida albicans, Lactobacillus acidophilus, Streptococcus gordonii, and S. mutan. Moreover, the Minimum Inhibitory Concentration of the isolated compound was determined and showed low values. The combination of each of the alcoholic extract of A. terreus and the isolated compound Coe‐Comfort tissue conditioner inhibited the growth of Candida albicans at concentrations of 500 and 7.81 µg/mL, respectively, Lactobacillus acidophilus at concentrations of 250 and 7.81 µg/mL, respectively, Streptococcus gordonii at concentrations of 1000 and 62.50 µg/mL, respectively, and S. mutans at concentrations of 1000 and 125 µg/mL, respectively. The oral dosing of the extract and the isolated compound did not show any significant effect on the activity of alanine aminotransferase, aspirate aminotransferase, and the levels of blood urea and serum creatinine. Copyright © 2017 John Wiley & Sons, Ltd.     

A fuzzy logic model for differential diagnosis of lower urinary tract dysfunctions

Lower urinary tract dysfunctions (LUTD) restrict quality of life, resulting in decreased work productivity and emotional well‐being. However, most people are not diagnosed because they do not seek medical treatment. In addition, some facilities do not adequately train health professionals in the evaluation, diagnosis and treatment of these conditions. The study's objective was to develop a decision support system modelled on fuzzy logic that defines LUTD using the terminology of the International Continence Society. This methodological study aimed to develop a model that uses the maximum–minimum composition (max–min) of fuzzy relations that can perform differential diagnoses of LUTD. The model was tested in 100 cases (50 men and 50 women), and the data were obtained from medical records containing the clinical data and results of urodynamic studies. All medical records were reviewed by a specialist in urology. The model was capable of determining a diagnosis in full (62%) or partial (36%) agreement with the medical report. Agreement between the model and the medical report was excellent (kappa = 0·98, p ? 0·001, CI = 0·88–1) or substantial (kappa = 0·53, p ? 0·001, CI = 0·45–0·60), considering overestimative accordance (where accordance is assumed when at least one diagnosis is equal) and underestimative accordance (where accordance is assumed when all diagnoses are equal), respectively. The proposed model based on the max–min composition of fuzzy relationships is very simple and performed well. However, more tests are recommended before the model is used as a decision support system.     

Cross-presentation of glycoprotein 96-associated antigens on major histocompatibility complex class I molecules requires receptor-mediated endocytosis

Heat shock proteins (HSPs) like glycoprotein (gp)96 (glucose-regulated protein 94 [grp94]) are able to induce specific cytotoxic T lymphocyte (CTL) responses against cells from which they originate. Here, we demonstrate that for CTL activation by gp96-chaperoned peptides, specific receptor-mediated uptake of gp96 by antigen-presenting cells (APCs) is required. Moreover, we show that in both humans and mice, only professional APCs like dendritic cells (DCs), macrophages, and B cells, but not T cells, are able to bind gp96. The binding is saturable and can be inhibited using unlabeled gp96 molecules. Receptor binding by APCs leads to a rapid internalization of gp96, which colocalizes with endocytosed major histocompatibility complex (MHC) class I and class II molecules in endosomal compartments. Incubation of gp96 molecules isolated from cells expressing an adenovirus type 5 E1B epitope with the DC line D1 results in the activation of E1B-specific CTLs. This CTL activation can be specifically inhibited by the addition of irrelevant gp96 molecules not associated with E1B peptides. Our results demonstrate that only receptor-mediated endocytosis of gp96 molecules leads to MHC class I-restricted re-presentation of gp96-associated peptides and CTL activation; non-receptor-mediated, nonspecific endocytosis is not able to do so. Thus, we provide evidence on the mechanisms by which gp96 is participating in the cross-presentation of antigens from cellular origin.     

ANTIBODY RESPONSES TO ANTIGENIC DETERMINANTS OF INFLUENZA VIRUS HEMAGGLUTININ : I. Thymus Dependence of Antibody Formation and Thymus Independence of Immunological Memory

Using immunodiffusion methods it has been shown that purified hemagglutinin (HA) extracted from two related strains of influenza A viruses (A/PR8/34 and A/FM1/47) have two distinct antigenic determinants, or groups of determinants. One determinant is cross-reactive while the other is strain-specific. Antisera raised in normal mice against HA were shown to contain two populations of antibody molecules, each directed against one of the determinants. Immunization of thymus-deprived (TXBM) mice showed a strong thymus dependence of antibody formation to HA. However, the thymus dependence of antibody formation against the cross-reactive determinant could be overcome by repeated inoculations of HA in TXBM mice, indicating a different handling of two portions of the same molecule by the immunological system. Strong, secondary-type responses to the strain-specific determinant were observed in primed thymus-deprived mice after reconstitution with virgin thymus cells, showing that specific immunological memory was elicited by this determinant despite the absence of detectable antibody secretion. These findings are interpreted as examples of immunological recognition and memory mediated by B lymphocytes and discussed in terms of mechanisms of T and B lymphocyte co-operation. It is suggested that the helper effect of T lymphocytes is exerted at a late stage in the differentiation of specific populations of B cells into antibody-secreting cells.     

Multifocal pyomyositis: report of two cases

Pyomyositis is a primary infection of the striated muscles. We describe the clinical and imaging features of pyomyositis in two patients, one diabetic and the other immunocompetent. Treatment with incision, drainage and antibiotics was successful and resulted in full recovery. Increased awareness, especially in immuno‐competent patients, should lead to earlier diagnosis, correct treatment and a better outcome.     

Analysis of upper extremity movement in four sitting positions: a comparison of persons with and without cerebral palsy

The purposes of this study were to compare the arm movements of persons with and without cerebral palsy and to determine if the alteration of the seat angle of a chair affected the quality of those movements. Twelve subjects--3 men and 3 women with spastic cerebral palsy and 3 men and 3 women without any known anomalies that could affect arm movements--were studied. The number of movement elements constituting a reach was used to measure the quality of movements. The findings demonstrated significant differences in the number of movement elements used by the subjects with and without cerebral palsy regardless of position. No significant differences could be attributed to the seating positions. Implications are discussed in relation to the method used in the analysis of movements and the effect of the findings for research and treatment.     

Effects of a 24‐hr‐shift‐related short‐term sleep deprivation on cardiac function: A cardiac magnetic resonance‐based study

Fatigue and sleep deprivation are common phenomena, especially among medical professionals and shift workers. Studies have proven that short episodes of sleep deprivation can lead to sympathetic hyperactivity with an elevation in blood pressure, heart rate, and an increased secretion of stress hormones (e.g. cortisol, noradrenaline, thyroid hormones). In this study investigating cardiac strain in 20 healthy subjects undergoing short‐term sleep deprivation, it could be shown for the first time that 24‐hr‐shift‐related short‐term sleep deprivation leads to a significant increase in cardiac contractility, blood pressure, heart rate and stress hormone secretion. These findings may help better understand how workload and shift duration affect public health, and lay the foundation for further investigations.