Homogenates of skeletal muscle injected with snake venom inhibit myogenic differentiation in cell culture

Introduction: Viperid snakebite envenomings are characterized by muscle necrosis and a deficient regenerative response. Methods: Homogenates from gastrocnemius muscles of mice injected with the venom of the snake Bothrops asper or with 2 tissue‐damaging toxins were added to cultures of C2C12 myogenic cells. Myoblasts proliferation and fusion were assessed. Venom was detected by immunoassay in mouse muscle during the first week after injection. Results: Homogenates from venom‐injected muscle induced a drop in the number of proliferating myoblasts and a complete elimination of myotube formation. The inhibitory effect induced by homogenates from venom‐injected mice was abrogated by preincubation of the homogenate with antivenom antibodies but not with control antibodies. This finding provides evidence that the effect is due to the action of venom in the tissue. Conclusions: Our observations suggest that traces of venom in muscle tissue might inhibit myotube formation and preclude a successful regenerative response. Muscle Nerve, 2013     

Validation of Obesity Surgery Data in the Swedish National Patient Registry and Scandinavian Obesity Registry (SOReg)

Background and Aim

Swedish health registries are common sources of data for studies on the effects of obesity surgery, and there is a need to assess the quality of data in these registries. The aim of this study was to validate the registration of obesity surgery in the National Patient Registry (NPR) and the Scandinavian Obesity Surgery Registry (SOReg).

Method

We randomly selected 962 out of 8501 registrations of obesity surgery in 2011 from the NPR and SOReg. Registered surgical procedures in the NPR and SOReg were compared to the medical records, and concordance was analyzed by calculating positive predictive value (PPV) with 95 % confidence interval (CI).

Results

We received 938 (98 %) medical records for manual review. The overall PPV for obesity surgery was high in the NPR (PPV 97.0; 95 % CI 95.6–98.4) and even higher in SOReg (PPV 99.7; 95 % CI 99.3–100). Accuracy was higher for gastric bypass surgery than for other types of obesity surgery. Registrations that were misclassified as obesity surgery (n?=?44) included reoperations due to complications or reconstruction to normal anatomy after previous obesity surgery (n?=?11) and endoscopic procedures (n?=?10).

Conclusion

Obesity surgery registrations in the NPR and SOReg have high accuracy and are reliable sources of data to identify patients having undergone obesity surgery. When it is of importance to distinguish between specific surgical procedures, non-gastric bypass surgeries in the NPR should ideally be supplemented with data from other sources.

     

Axo-somatic inhibition of projection neurons in the lateral nucleus of amygdala in human temporal lobe epilepsy: an ultrastructural study

Here, we report ultrastructural alterations in the synaptic circuitry of the human amygdala related to neuronal cell densities in surgical specimens of patients suffering from temporal lobe epilepsy (TLE). The neuronal cell densities quantified in the basolateral complex of amygdala were significantly reduced only in the lateral nucleus (LA) of TLE patients as compared to autopsy or non-Ammon’s horn sclerosis (AHS) controls (Nissl staining, immunostaining against the neuronal marker NeuN). For this reason, we focussed on the LA to perform a more detailed quantitative ultrastructural analysis, which revealed an inverse correlation between the number of axo-somatic inhibitory synaptic profiles at the somata of glutamic acid decarboxylase (GAD)-negative projection neurons and the extent of perisomatic fibrillary gliosis. In contrast, the density of GAD-immunoreactive interneurons positively correlated with the number of axo-somatic inhibitory synaptic profiles. The fibrillary material in perisomatic glial cell processes was preferentially labeled by the astroglial marker S100B. In addition, a qualitative study of the dendrites of GAD- and parvalbumin (PARV)-containing interneurons showed that they were often contacted by asymmetrical excitatory synapses. Our results are in line with anatomical data from rodents and cats, which show that amygdalar interneurons form axo-somatic inhibitory synapses on GAD-negative projection neurons, whereas the interneurons themselves receive excitatory input from recurrent collaterals of projection neurons and from cortico- and thalamo-amygdalar afferents. The structural reorganization patterns observed in the GABAergic circuitry are compatible with a reduced feedback or feed forward inhibition of amygdalar projection neurons in human TLE.     

Event-related potential responses to love-related facial stimuli

In event-related potential (ERPs) studies, emotional stimuli usually elicit an enhanced late positive potential (LPP), which is assumed to reflect motivated attention. However, whether a stimulus elicits emotional responses may depend on the individual's state, such as experiencing romantic love. It has been suggested that stimuli that are related to someone's beloved will elicit increased attention in that infatuated individual. In this study, participants who were in love viewed faces of their beloved, their friend, and of an unknown, beautiful person. The friend was included to control for familiarity, and the unknown person for perceived beauty. As expected, the LPP was larger in response to the face of the beloved than to the other two emotionally significant faces. Interpreting the LPP as reflecting motivated attention, this implies that romantic love is accompanied by increased attention for the face of one's beloved.     

Cross-cultural validation of the German version of the Four-Dimensional Symptom Questionnaire (4DSQ) in multimorbid elderly people

Purpose

Psychosomatic symptoms and mental health problems are highly prevalent in multimorbid elderly people challenging general practitioners to differentiate between normal stress and psychopathological conditions. The 4DSQ is a Dutch questionnaire developed to detect anxiety, depression, somatization, and distress in primary care. This study aims to analyze measurement equivalence between a German version and the original Dutch instrument.

Methods

A Dutch and a German sample of multimorbid elderly people, matched by gender and age, were analyzed. Equivalence of scale structures was assessed by confirmatory factor analysis (CFA). To evaluate measurement equivalence across languages, differential item functioning (DIF) was analyzed using Mantel–Haenszel method and hybrid ordinal logistic regression analysis. Differential test functioning (DTF) was assessed using Rasch analysis.

Results

A total of 185 German and 185 Dutch participants completed the questionnaire. The CFA confirmed one-factor models for all scales of both 4DSQ versions. Nine items in three scales were flagged with DIF. The anxiety scale showed to be free of DIF. DTF analysis revealed negligible scale impact of DIF.

Conclusions

The German 4DSQ demonstrated measurement equivalence to the original Dutch instrument. Hence, it can be considered a valid questionnaire for the screening for mental health problems in primary care.

     

Cell surface engineering using glycosylphosphatidylinositol anchored tissue inhibitor of matrix metalloproteinase‐1 stimulates cutaneous wound healing

The balance between matrix metalloproteinases and their endogenous tissue inhibitors (TIMPs) is an important component in effective wound healing. The biologic action of these proteins is linked in part to the stoichiometry of TIMP/matrix metalloproteinases/surface protein interactions. We recently described the effect of a glycosylphosphatidylinositol (GPI) anchored version of TIMP‐1 on dermal fibroblast biology. Here, cell proliferation assays, in vitro wound healing, electrical wound, and impedance measurements were used to characterize effects of TIMP‐1‐GPI treatment on primary human epidermal keratinocytes. TIMP‐1‐GPI stimulated keratinocyte proliferation, as well as mobilization and migration. In parallel, it suppressed the migration and matrix secretion of dermal myofibroblasts, and reduced their secretion of active TGF‐β1. Topical application of TIMP‐1‐GPI in an in vivo excisional wound model increased the rate of wound healing. The agent positively influenced different aspects of wound healing depending on the cell type studied. TIMP‐1‐GPI counters potential negative effects of overactive myofibroblasts and enhances the mobilization and proliferation of keratinocytes essential for effective wound healing. The application of TIMP‐1‐GPI represents a novel and practical clinical solution for facilitating healing of difficult wounds.