Effects of single and repeated shock on perceived pain and startle response in healthy volunteers

Contingent shock (CS) has been used in a number of studies to suppress health-threatening self-injurious behavior of individuals with mental retardation and autism. As sustained suppression is an issue of concern, research into procedural variables of CS is needed. In this study, clinical evidence was used to infer a variable that might be of relevance for the application of clinical contingent shock, that is, to assess the effect of single versus repeated shock at a specific location on the body. With pain intensity and startle response as dependent variables, shocks were administered to 48 healthy volunteers. Electric shocks were identical to those that used in clinical practice. The second shock in succession to the same location of the body produced higher pain intensity ratings than the first shock and that the third shock in succession to the same location of the body produced higher pain intensity ratings than the second shock in succession. Startle responses, however, failed to be affected in this direction. The latter result is consistent with a previous study. Our data suggest that repeated shock to the same location is likely to be more effective to establish suppression than repeated shock to different locations.     

Effects of IGM-enriched solution on polymorphonuclear neutrophil function, bacterial clearance, and lung histology in endotoxemia

Immunological interventions in endotoxemia and sepsis have been tested in experimental and clinical studies. Our group evaluated the effects of an immunoglobulin (Ig)M-enriched solution in an established model of Gram-negative bacteraemia. Ten New Zealand White rabbits (2-3 kg) were randomized to a treatment or control group. In both groups, LPS was infused at a rate of 40 mg kg(-1) h(-1). Immunoglobulin M-enriched solution (Pentaglobin; 2 mL kg(-1) h(-1)) was applied in the intervention group 15 min after beginning LPS infusion. 1 x 10(8) colony forming units of Escherichia coli were injected 30 min after LPS infusion was commenced. Baseline hemodynamic and respiratory parameters, blood E. coli concentration (30 min before and 1, 15, 30, 60, 90, 120, and 180 min after E. coli injection), polymorphonuclear neutrophil oxidative burst activity, and phagocytosis dead space (both 30 min before and 1, 15, 60, 120, and 180 min postinjection) were measured. Ex vivo phagocytosis activity was measured in a separate experiment and evaluated by electron microscopy. Diffuse alveolar damage (DAD) was measured. Organ colonization (kidney, lung, liver, spleen) was assessed in aseptic organ samples. Hemodynamic parameters did not differ between the two groups. Bacterial blood clearance was not influenced by application of IgM-enriched solution. Liver and spleen colonization was significantly reduced in the IgM group. Immunoglobulin M-enriched solution reduced in vitro residual phagocytosis capacity at 30, 90, and 180 min and improved respiratory burst at 180 min. Correspondingly, ex vivo phagocytosis activity as documented by electron microscopy was increased in the IgM group. The sum of all weighted DAD scores (except overdistension) was significantly better in the IgM group (23+/-5 vs. 30+/-8). Immunoglobulin M-enriched solution significantly improved six of seven DAD score parameters and reduced liver and spleen E. coli count. Residual phagocytosis capacity was significantly decreased in the IgM group, whereas burst activity was increased, pointing to an increased in vivo phagocytosis efficiency. Short-term IgM-enriched solution intervention had an especially beneficial effect on LPS-induced pulmonary histological changes.     

Vancomycin-resistant enterococcal meningitis treated with intrathecal streptomycin

Enterococcal meningitis is a rare complication of neurosurgical procedures. We present a patient who developed vancomycin-resistant enterococcal ventriculitis - meningitis after a brain tumor resection and ventriculoperitoneal shunt placement, treated successfully with intrathecal streptomycin through bilateral cerebrospinal fluid drainage catheters in addition to systemic antibiotics. This is the first report of such treatment for this resistant organism.     

Treatment of Mood and Depressive Disorders With Complementary and Alternative Medicine: Efficacy Review

There has been a steady increase in people with symptoms of depression over the past several years (since 2011). The further increase in stress and depression in the early part of the COVID-19 pandemic was accompanied by an increase in unmet mental health needs. Many have turned to complementary and alternative medicine (CAM) therapies such as bright-light therapy, yoga, meditation, and dietary supplements like St. John's wort or folic acid. The reliability of evidence for use of CAM therapies for depression has remained low. There are few randomized controlled trials (RCTs) in the current literature and poor methodology in many of the trials that are available. This state of the science review examines current published guidelines, meta-analyses, systematic reviews, and RCTs regarding use of CAM therapies in the management of depression.     

Functional characterization of novel or yet uncharacterized ATP7B missense variants detected in patients with clinical Wilson's disease

Wilson's disease (WD, MIM#277900) is an autosomal recessive disorder resulting in copper excess caused by biallelic variants in the ATP7B gene (MIM#606882) encoding a copper transporting P-type ATPase. ATP7B variants of unknown significance (VUS) are detected frequently, sometimes impeding a clear diagnosis. Functional analyses can help to classify these variants as benign or pathogenic. Additionally, variants already classified as (likely) pathogenic benefit from functional analyses to understand their pathomechanism, thus contribute to the development of personalized treatment approaches in the future. We described clinical features of six WD patients and functionally characterized five ATP7B missense variants (two VUS, three yet uncharacterized likely pathogenic variants), detected in these patients. We determined the protein level, copper export capacity, and cellular localization in an in vitro model and potential structural consequences using an ATP7B protein model based on AlphaFold. Our analyses give insight into the pathomechanism and allowed reclassification for the two VUS to likely pathogenic and for two of the three likely pathogenic variants to pathogenic.     

Carcinoma-associated fibroblasts: orchestrating the composition of malignancy

The tumor stroma is no longer seen solely as physical support for mutated epithelial cells but as an important modulator and even a driver of tumorigenicity. Within the tumor stromal milieu, heterogeneous populations of fibroblast-like cells, collectively termed carcinoma-associated fibroblasts (CAFs), are key players in the multicellular, stromal-dependent alterations that contribute to malignant initiation and progression. This review focuses on novel insights into the contributions of CAFs to disease progression, emergent events leading to the generation of CAFs, identification of CAF-specific biomarkers predictive of disease outcome, and recent therapeutic approaches aimed at blunting or reverting detrimental protumorigenic phenotypes associated with CAFs.