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Malte Baldewig,1 Olaf Goldbaum,2 Christiane Richter-Landsberg,2 Andreas Weyland,1 Carsten Bantel1 1Department of Anesthesiology, Klinikum Oldenburg, Oldenburg, Germany; 2Molecular Neurobiology, Department of Neuroscience, University of Oldenburg, Oldenburg, Germany Purpose: Gabapentinoids are currently the mainstay of pharmacological treatments for patients with neuropathic pain. Little is known about the effects of this therapy on the integrity of neuronal networks, especially in patients with an already-damaged nervous system. Since gabapentinoids can worsen cognitive functions and recent studies have shown alterations in the brains of patients with neuropathic pain, it may be possible that these drugs have neurotoxic effects.Methods: Rat clonal PC12 pheochromocytoma (autonomic) and primary sensory dorsal-root ganglion (DRG) neurons from newborn Wistar rats were employed for this study. To mimic neuronal damage, cells were exposed to cytotoxins using either hydrogen peroxide (H2O2) or vincristine.Results: No direct cytotoxic effects were observed after incubating PC12 cells for 24 hours with increasing concentrations of gabapentin or pregabalin using MTT cytotoxicity assays. Even a 7-day incubation did not cause cellular damage. Furthermore, in preinjured PC12 and DRG neurons, neither gabapentin nor pregabalin prevented or enhanced the cytotoxic effects of H2O2 or vincristine after incubation for 24 hours and 7 days, respectively. Cell morphology and integrity of the cytoskeleton assessed by employing immunostaining of cytoskeletal proteins (α-tubulin, neurofilament L) remained intact and were not altered by gabapentinoids.Conclusion: Based on these results, gabapentinoids are unlikely to be neurotoxic in cultured autonomic (PC12) and sensory DRG cells, even when cells are preinjured. These results are of high clinical relevance, as it seems unlikely that the morphological changes recently observed in the brains of neuropathic pain patients are caused or worsened by gabapentinoids. Keywords: gabapentin, pregabalin, cytotoxicity, cytoskeleton, neuropathic pain

BackgroundMultiple stressors as well as health-and quality-impairing effects of strain in the nursing profession require the systematic acquisition of competence in dealing with these demands, starting at the stage of initial vocational training. This study investigates whether an instructional design, which merges didactic principles of nursing education with concepts and training measures from stress psychology, promotes the acquisition of stress coping competence more effectively than regular teaching on the relevant curricular field at nursing schools.MethodsThe quasi-experimental study design, based on the Solomon four-group plan, included 332 trainees in Germany. The assessment of stress coping competence at the beginning and at the end of the intervention provided a video-stimulated situational judgment test covering nursing-specific stressful situations. All were validated by field experts. Complementing group comparisons, regression analyses examined intervention effects at the individual level while controlling for other predictors of learning success.ResultsThe highest solution rates for the two basic dimensions of stress coping competence, i.e., (1) situation assessment and (2) strategy selection and justification, occurred in the treatment classes without a pretest. At the individual level, treatment effects were confirmed for the first dimension. Students with a migration background showed lower competence gains than other students.ConclusionThe instructional design and the competence test provide valuable foundations for promoting and for diagnosing coping skills. Nevertheless, subsequent studies should examine adaptive support for different learner groups. Furthermore, additional observational phases should focus on the deliberate practice of acquired coping strategies in the practical training settings of nursing education.

MAGUK p55 subfamily member 7, a part of the membrane palmitoylated protein subfamily, is an essential adapter that promotes epithelial cell polarity and has increasing significance in multiple cancers, including esophageal cancer, clear cell renal cell carcinoma, breast cancer, and pancreatic ductal adenocarcinoma. This paper aims to determine the effect of the MAGUK p55 subfamily member 7 in various tumor types using The Cancer Genome Atlas and Genotype-Tissue Expression database. A variety of software and web platforms, such as cBioPortal, GEPIA2, TIMER2, UALCAN, R, STRING, and DAVID, were used to obtain and analyze data. Notably, low expression of MAGUK p55 subfamily member 7 was observed in most cancers. In addition, low expression of MAGUK p55 subfamily member 7 predicted poor prognoses in cancer patients. Mutation was the most frequent genetic alteration type in MAGUK p55 subfamily member 7, with the phosphorylation sites identified as S412 and S490 in various cancers. Furthermore, expression of MAGUK p55 subfamily member 7 was associated with cancer-related fibroblasts and CD8+ T cells. Gene enrichment analysis indicated that MAGUK p55 subfamily member 7 influences cancer through the Rap1 signaling pathway. This paper elucidates the biological significance of MAGUK p55 subfamily member 7 in human pan-cancer prognosis and immune response.

In 2022, we monitored the Western Snowy Plover (WSP) population at Coal Oil Point Reserve as in previous years. The number of breeding adults was 52, higher than the average of 37 for our site. The wintering population size was 183, also above the average of 167. Skunk predation was the primary cause of nest failure. In response to the high levels of predation by skunks and the failure to trap them, all nests present on or laid after April 29th and before May 31st were collected, incubated until near the hatching date, and then returned to the parents. The real eggs were replaced with wooden eggs so that the parents would continue incubating. 35 nests (34%) of nests this season were replaced using this method. The hatching and fledging success rates in this report reflect those that hatched and fledged naturally and exclude nests that had eggs replaced. Hatching rate (28%) was lower than average (53%) and the fledging rate (74%) was higher than average (62%). The number of fledged chicks per male (1.0) met our site's recovery goal of 1.0 fledged chicks per male. 92% of nests (94) were initiated on the beach, and 8% (8) were initiated on the mudflats of the slough (delta).

In many autistic children, speech onset is delayed and expressive language emerges after 3 years of age. We qualitatively and quantitatively describe oral productions of autistic preschoolers, including many non- or minimally speaking, recorded during interactions with a caregiver and with an experimenter. Data clustering on manually coded oral production samples indicates five validated linguistic profiles of oral production in this diverse and inclusive sample (n = 59) of 3- to 5-year-old autistic children with highly variable expressive language abilities. These profiles are then compared on a series of demographic (age, socioeconomic status) and psychometric (autism severity, nonverbal and verbal IQ) measures, as well as on additional measures of language (expressive vocabulary, phonetic inventories). Two clusters are composed of speaking autistic children, while the three others comprise non- or minimally speaking children with qualitatively different patterns of vocal productions. The five-profile division suggests that traditional binary division of speaking vs nonspeaking children does not do justice to the complexity of early expressive language in autism.

Introduction There is an ongoing scientific discussion, that anti-cancer effects induced by radiofrequency (RF)-hyperthermia might not be solely attributable to subsequent temperature elevations at the tumor site but also to non-temperature-induced effects. The exact molecular mechanisms behind said potential non-thermal RF effects remain largely elusive, however, limiting their therapeutical targetability.Objective Therefore, we aim to provide an overview of the current literature on potential non-temperature-induced molecular effects within cancer cells in response to RF-electromagnetic fields (RF-EMF).Material and Methods This literature review was conducted following the PRISMA guidelines. For this purpose, a MeSH-term-defined literature search on MEDLINE (PubMed) and Scopus (Elsevier) was conducted on March 23rd, 2024. Essential criteria herein included the continuous wave RF-EMF nature (3 kHz − 300 GHz) of the source, the securing of temperature-controlled circumstances within the trials, and the preclinical nature of the trials.Results Analysis of the data processed in this review suggests that RF-EMF radiation of various frequencies seems to be able to induce significant non-temperature-induced anti-cancer effects. These effects span from mitotic arrest and growth inhibition to cancer cell death in the form of autophagy and apoptosis and appear to be mostly exclusive to cancer cells. Several cellular mechanisms were identified through which RF-EMF radiation potentially imposes its anti-cancer effects. Among those, by reviewing the included publications, we identified RF-EMF-induced ion channel activation, altered gene expression, altered membrane potentials, membrane oscillations, and blebbing, as well as changes in cytoskeletal structure and cell morphology.Conclusion The existent literature points toward a yet untapped therapeutic potential of RF-EMF treatment, which might aid in damaging cancer cells through bio-electrical and electro-mechanical molecular mechanisms while minimizing adverse effects on healthy tissue cells. Further research is imperative to definitively confirm non-thermal EMF effects as well as to determine optimal cancer-type-specific RF-EMF frequencies, field intensities, and exposure intervals.

Background: Studies attempting to distinguish suicide attempters from ideators have found that impulsivity is consistently associated with attempts across the spectrum of suicidal behavior from self-harm to lethal suicidal behavior. Impulsivity is readily assessed using complementary clinical and laboratory measures, making it a viable target for pharmacological strategies to prevent suicide risk. Lithium reduces suicidal behavior across diagnoses, and has been implicated in the reduction of impulsivity triggered by stress mediated phosphatidylinositol turnover. We used a placebo controlled cross-over design to study the effects of repeated lithium dosing on risk factors predisposing to suicidal behavior. Methods: 15 patients with a recent (past year) medically severe suicide attempt (MSSA) (37.5% male, 40.13 ± 13.66 years) received lithium carbonate and matching pill placebo separately in a randomized double-blind crossover design administered six weeks apart. To test the effect of lithium on measures of impulsivity and arousal, participants completed the Immediate Memory Task (IMT), Internal State Scale (ISS), and the Time Perception Task (TPT). We conducted separate analyses for each variable using repeated measures analysis of covariance. Results: Lithium dosing was associated with increased IMT response latency (p = .017, pη2 = 0.23), and decision bias (p = .048, pη2 = 0.21). Lithium did not significantly alter time perception or activation. Conclusions: Our results suggest that lithium may reduce risk in MSSA survivors by increasing the response latency and increasing conservative response bias during decision-making. Future studies should conduct long-term follow-ups with adjunct behavioral therapy with lithium on factors contributing to suicidal behavior.

The integration of digital interventions in health rehabilitation offers promising opportunities to improve patient outcomes. However, empirical studies comparing the effectiveness of digital and traditional rehabilitation interventions remain scarce. This study was designed to evaluate the impact of a digital aftercare program, compared to traditional aftercare and a control group, on both psychological and physical health outcomes in individuals undergoing orthopedic rehabilitation. Additionally, the study also aimed to examine the moderating effects of age and gender. The study employed a partially controlled trial design, engaging a cohort of 805 orthopedic patients, divided into: digIRENA (n = 323, digital aftercare), IRENA (n = 252, traditional aftercare), and a control group (n = 230, without organized aftercare). Measurements took place at four different time points: baseline (start of the rehabilitation program), T1 (13 weeks after the start of rehabilitation, marking the midpoint of aftercare), T2 (26 weeks, marking the end of aftercare), and T3 (43 weeks, to assess the sustainability of aftercare effects). The SF-12 Health Survey was the primary data collection instrument for measuring trends in physical and mental health outcomes over these intervals using repeated measures ANOVA. The results show that rehabilitants in the digIRENA group participated for a longer period of time than rehabilitants in the IRENA group, while the two groups did not differ in terms of motivation at T0 and organized physical activity outside of aftercare at T3. A significant improvement in physical health outcomes was observed in all groups across time, with digIRENA participants showing the greatest improvement. For mental health, all groups showed initial improvements, with the digIRENA group showing the most pronounced increase at T2. Overall, there was a decline in the effects achieved 4 months after the end of aftercare. When age and gender were included as covariates, the time effect for mental health disappeared, showing a significant time * gender interaction due to significantly lower baseline scores of women compared to men. The results of the study show that digital interventions, in particular the digIRENA program, contribute to improving health rehabilitation outcomes. The digIRENA program and similar digital health interventions may offer potential for improving health rehabilitation aftercare.