Symptoms During or Shortly After Isolated Carpal Tunnel Release and Problems Within 24?hours After Surgery

This study used the National Survey of Ambulatory Surgery (NSAS) database to measure the incidence of and risk factors for symptoms in the ambulatory surgery center and problems within 24 h after isolated carpal tunnel release (CTR). The NSAS contained records on 400,000 adult patients with carpal tunnel syndrome who were treated with CTR in 2006, based on ICD-9 codes. The type of anesthesia used and factors associated with symptoms and problems were sought in bivariate and multivariable statistical analyses. The mean duration of the procedure was 16 ± 8.8 min. Only 5 % were performed under local anesthesia without sedation, 45 % with IV sedation, 28 % regional anesthesia, and 19 % general anesthesia. Symptoms in the ambulatory surgery center or a problem within 24 h after discharge were recorded in 10 % of patients, all of them minor and transient, including difficulties with pain and its treatment. The strongest risk factors were male sex, age of 45 years and older, and participation of an anesthesiologist. Local anesthesia and regional anesthesia were associated with more perioperative symptoms and postoperative problems. Most CTR are performed with some sedation in the United States. CTR is a safe procedure: one in 10 patients will experience a minor issue in the perioperative or immediate postoperative period.     

Neutralization of Mitochondrial Superoxide by Superoxide Dismutase 2 Promotes Bacterial Clearance and Regulates Phagocyte Numbers in Zebrafish

Mitochondria are known primarily as the location of the electron transport chain and energy production in cells. More recently, mitochondria have been shown to be signaling centers for apoptosis and inflammation. Reactive oxygen species (ROS) generated as by-products of the electron transport chain within mitochondria significantly impact cellular signaling pathways. Because of the toxic nature of ROS, mitochondria possess an antioxidant enzyme, superoxide dismutase 2 (SOD2), to neutralize ROS. If mitochondrial antioxidant enzymes are overwhelmed during severe infections, mitochondrial dysfunction can occur and lead to multiorgan failure or death. Pseudomonas aeruginosa is an opportunistic pathogen that can infect immunocompromised patients. Infochemicals and exotoxins associated with P. aeruginosa are capable of causing mitochondrial dysfunction. In this work, we describe the roles of SOD2 and mitochondrial ROS regulation in the zebrafish innate immune response to P. aeruginosa infection. sod2 is upregulated in mammalian macrophages and neutrophils in response to lipopolysaccharide in vitro, and sod2 knockdown in zebrafish results in an increased bacterial burden. Further investigation revealed that phagocyte numbers are compromised in Sod2-deficient zebrafish. Addition of the mitochondrion-targeted ROS-scavenging chemical MitoTEMPO rescues neutrophil numbers and reduces the bacterial burden in Sod2-deficient zebrafish. Our work highlights the importance of mitochondrial ROS regulation by SOD2 in the context of innate immunity and supports the use of mitochondrion-targeted ROS scavengers as potential adjuvant therapies during severe infections.     

Checkpoint-blocker-induced autoimmunity is associated with favourable outcome in metastatic melanoma and distinct T-cell expression profiles

Background Immune checkpoint blockers (ICBs) activate CD8⁺ T cells, eliciting both anti-cancer activity and immune-related adverse events (irAEs). The relationship of irAEs with baseline parameters and clinical outcome is unclear.Methods Retrospective evaluation of irAEs on survival was performed across primary (N = 144) and secondary (N = 211) independent cohorts of patients with metastatic melanoma receiving single agent (pembrolizumab/nivolumab—sICB) or combination (nivolumab and ipilimumab—cICB) checkpoint blockade. RNA from pre-treatment and post-treatment CD8⁺ T cells was sequenced and differential gene expression according to irAE development assessed.Results 58.3% of patients developed early irAEs and this was associated with longer progression-free (PFS) and overall survival (OS) across both cohorts (log-rank test, OS: P < 0.0001). Median survival for patients without irAEs was 16.6 months (95% CI: 10.9–33.4) versus not-reached (P = 2.8 × 10⁻⁶). Pre-treatment monocyte and neutrophil counts, but not BMI, were additional predictors of clinical outcome. Differential expression of numerous gene pathway members was observed in CD8⁺ T cells according to irAE development, and patients not developing irAEs demonstrating upregulated CXCR1 pre- and post-treatment.Conclusions Early irAE development post-ICB is associated with favourable survival in MM. Development of irAEs is coupled to expression of numerous gene pathways, suggesting irAE development in-part reflects baseline immune activation.Subject terms: Immunotherapy, Melanoma     

Structured Sequence Learning: Animal Abilities,Cognitive Operations,and Language Evolution

Human language is a salient example of a neurocognitive system that is specialized to process complex dependencies between sensory events distributed in time, yet how this system evolved and specialized remains unclear. Artificial Grammar Learning (AGL) studies have generated a wealth of insights into how human adults and infants process different types of sequencing dependencies of varying complexity. The AGL paradigm has also been adopted to examine the sequence processing abilities of nonhuman animals. We critically evaluate this growing literature in species ranging from mammals (primates and rats) to birds (pigeons, songbirds, and parrots) considering also cross‐species comparisons. The findings are contrasted with seminal studies in human infants that motivated the work in nonhuman animals. This synopsis identifies advances in knowledge and where uncertainty remains regarding the various strategies that nonhuman animals can adopt for processing sequencing dependencies. The paucity of evidence in the few species studied to date and the need for follow‐up experiments indicate that we do not yet understand the limits of animal sequence processing capacities and thereby the evolutionary pattern. This vibrant, yet still budding, field of research carries substantial promise for advancing knowledge on animal abilities, cognitive substrates, and language evolution.     

The Venom of Philippine Tarantula (Theraphosidae) Contains Peptides with Pro-Oxidative and Nitrosative-Dependent Cytotoxic Activities against Breast Cancer Cells (MCF-7) In Vitro

Background: Breast cancer is a multifactorial disease that affects women worldwide. Its progression is likely to be executed by oxidative stress wherein elevated levels of reactive oxygen and nitrogen species drive several breast cancer pathologies. Spider venom contains various pharmacological peptides which exhibit selective activity to abnormal expression of ion channels on cancer cell surface which can confer potent anti-cancer activities against this disease. Methods: Venom was extracted from a Philippine tarantula by electrostimulation and fractionated by reverse phase-high performance liquid chromatography (RP-HPLC). Venom fractions were collected and used for in vitro analyses such as cellular toxicity, morphological assessment, and oxidative stress levels. Results: The fractionation of crude spider venom generated several peaks which were predominantly detected spectrophotometrically and colorimetrically as peptides. Treatment of MCF-7 cell line of selected spider venom peptides induced production of several endogenous radicals such as hydroxyl radicals (•OH), nitric oxide radicals (•NO), superoxide anion radicals (•O2−) and lipid peroxides via malondialdehyde (MDA) reaction, which is comparable with the scavenging effects afforded by 400 µg/mL vitamin E and L-cysteine (p<0.05). Concomitantly, the free radicals produced decrease the mitochondrial membrane potential and metabolic activity as detected by rhodamine 123 and tetrazolium dye respectively (p>0.05). This is manifested by cytotoxicity in MCF-7 cells as seen by increase in membrane blebbing, cellular detachment, caspase activity and nuclear fragmentation. Conclusion: These data suggest that the Philippine tarantula venom contains peptide constituents exhibiting pro-oxidative and nitrosative-dependent cytotoxic activities against MCF-7 cells and can indicate mechanistic insights to further explore its potential application as prooxidants in cancer therapy.     

Untergrenzen oder Personalbemessung in der Pflege

Die Onkologie - Die Pflegepersonaluntergrenzen als rote Linien zur Abgrenzung einer gefährlichen Pflegepraxis sind nicht geeignet, die dringend benötigte Trendwende einzuleiten und...