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College students report high psychological distress, mental health problems and anxiety. Research indicates that faculty and staff can help support these students in crisis, but there is limited trauma-informed training for higher education professionals who are not mental health counselors. This study explored an evidence-based online training program designed to help faculty/staff members facilitate well-being and resilience among college students. To test the training, a systematic program evaluation was conducted. Prior to completing the training, participants (n = 52) took a pretest. Then, after completing the training, they took a posttest. Results indicated a significant difference between pre and posttest. There were more positive attitudes toward trauma-informed approaches and resilience resources; stronger beliefs about prevalence and effects of psychological trauma; greater self-efficacy to perform trauma-informed approaches; and greater confidence in trauma-informed knowledge. Additionally, participants reported they were likely to use tools learned during the training. Thus, indicating that a self-paced, convenient, and culturally sensitive training may be beneficial for faculty and staff as they aid in student success. Practical implications, participant comments and specific suggestions for colleges are also discussed.

Potassium channel mutations play an important role in neurological diseases, such as spinocerebellar ataxia (SCA). SCA is a heterogeneous autosomal-dominant neurodegenerative disorder with multiple sub-entities, such as SCA13, which is characterized by mutations in the voltage-gated potassium channel Kv3.3 (KCNC3). In this study, we present a rare and atypical case of SCA13 with a predominant episodic central rotational vertigo, while the patient suffered only from mild progressive cerebellar symptoms, such as dysarthria, ataxia of gait and stand, and recently a cognitive impairment. In this patient, we identified a heterozygous variant in KCNC3 (c.2023G > A, p.Glu675Lys) by next-generation sequencing. This Kv3.3E675K variant was studied using voltage-clamp recordings in Xenopus oocytes. While typical SCA13 variants are dominant-negative, show shifts in the voltage-dependence of activation or an altered TBK1 regulation, the Kv3.3E675K variant caused only a reduction in current amplitude and a more pronounced cumulative inactivation. Thus, the differences to phenotypes observed in patients with classical SCA13 mutations may be related to the mechanism of the observed Kv3.3 loss-of-function. Treatment of our patient with riluzole, a drug that is known to also activate potassium channels, turned out to be partly beneficial. Strikingly, we found that the Kv3.3 and Kv3.3E675K inactivation and the frequency-dependent cumulative inactivation was antagonized by increased extracellular potassium levels. Thus, and most importantly, carefully elevated plasma potassium levels in the physiological range, or novel drugs attenuating Kv3.3 inactivation might provide novel therapeutic approaches to rescue potassium currents of SCA13 variants per se. In addition, our findings broaden the phenotypic spectrum of Kv3.3 variants, expanding it to atypical phenotypes of Kv3.3-associated neurological disorders.

Abstract Introduction CRC with liver metastases is a major contributor to cancer-related mortality. Despite advancements in liver resection techniques, patient survival remains a concern due to high recurrence rates. This study seeks to uncover prognostic biomarkers that predict overall survival in patients undergoing curative hepatic resection for CRC liver metastases. Methods Prospectively collected serum samples from a cohort of 49 patients who received curative hepatic resection for CRC liver metastases were studied. The patients are part of a cohort, previously analyzed for perioperative complications (see methods). Various preoperative serum markers, clinical characteristics, and factors were analyzed. Univariate and multivariate Cox regression analyses were conducted to determine associations between these variables and disease-free survival as well as overall survival. Results For disease-free survival, univariate analysis highlighted the correlation between poor outcomes and advanced primary tumor stage, high ASA score, and synchronous liver metastases. Multivariate analysis identified nodal-positive primary tumors and synchronous metastases as independent risk factors for disease-free survival. Regarding overall survival, univariate analysis demonstrated significant links between poor survival and high preoperative IL-8 levels, elevated neutrophil–lymphocyte ratio (NLR), and presence of metastases in other organs. Multivariate analysis confirmed preoperative IL-8 and having three or more liver metastases as independent risk factors for overall survival. The impact of IL-8 on survival was particularly noteworthy, surpassing the influence of established clinical factors. Conclusion This study establishes preoperative IL-8 levels as a potential prognostic biomarker for overall survival in patients undergoing curative liver resection for CRC liver metastases. This study underscores the importance of incorporating IL-8 and other biomarkers into clinical decision-making, facilitating improved patient stratification and tailored treatment approaches. Further research and validation studies are needed to solidify the clinical utility of IL-8 as a prognostic marker.

Objective: This study explored how college freshmen, particularly those affected by health inequities, are affected by COVID-19 and whether they would use a university-created online wellness intervention for help. Participants: Nine-hundred and eighty-nine freshmen at a large southeastern university. Method: Students responded to an online survey regarding their anxiety, worry, number of life disruptions, perceived resilience and their use of the online intervention during the pandemic (June to mid-September 2020). Results: During COVID-19, Latinx, Black, women and non-heterosexual students reported significantly greater worry, daily life disruptions than their non-Latinx, white, male and heterosexual counterparts. Women and non-heterosexual students also reported greater anxiety and less resilience. Additionally, Latinx students reported using the university's online intervention for help during COVID-19 more than others. Overall, freshmen, especially Black and women students, reported the online intervention would help them with struggles. Conclusions: Universities should identify unique worries faced by students during a health crisis and provide institutional support. Practical implications are discussed.

Severe acute respiratory syndrome corona virus 2 (SARS CoV-2) is the cause of Corona virus disease 2019 (COVID-19), which turned into a pandemic in late 2019 and early 2020. SARS CoV-2 causes endothelial cell destruction and swelling, microthrombosis, constriction of capillaries, and malfunction of pericytes, all of which are detrimental to capillary integrity, angiogenesis, and healing processes. Cytokine storming has been connected to COVID-19 disease. Hypoxemia and tissue hypoxia may arise from impaired oxygen diffusion exchange in the lungs due to capillary damage and congestion. This personal view will look at how inflammation and capillary damage affect blood and tissue oxygenation, cognitive function, and the duration and intensity of COVID-19 disease. The general effects of microvascular injury, hypoxia, and capillary damage caused by COVID-19 in key organs are also covered in this point of view. Once initiated, this vicious cycle leads to diminished capillary function, which exacerbates inflammation and tissue damage, and increased inflammation due to hypoxia. Brain damage may result from low oxygen levels and high cytokines in brain tissue. In this paper we give a summary in this direction with focus on the role of the neuropeptide Substance P. On the basis of this, we discuss selected approaches to the question: “How Substance P is involved in the etiology of the COVID-19 and how results of our research could improve the prevention or therapy of corona? Thereby pointing out the role of Substance P in the post-corona syndrome and providing novel concepts for therapy and prevention.

Purpose: Passive tibiofemoral anterior-posterior (AP) laxity has been extensively investigated after posterior cruciate ligament (PCL) single-bundle reconstruction. However, the PCL also plays an important role in providing rotational stability in the knee. Little is known in relation to the effects of PCL single-bundle reconstruction on passive tibiofemoral rotational laxity. Gait biomechanics after PCL reconstruction are even less understood. The aim of this study was a comprehensive prospective biomechanical in vivo analysis of the effect of PCL single-bundle reconstruction on passive tibiofemoral rotational laxity, passive anterior-posterior laxity, and gait pattern.Methods: Eight patients undergoing PCL single-bundle reconstruction (seven male, one female, mean age 35.6 ± 6.6 years, BMI 28.0 ± 3.6 kg/m2) were analyzed preoperatively and 6 months postoperatively. Three of the eight patients received additional posterolateral corner (PLC) reconstruction. Conventional stress radiography was used to evaluate passive translational tibiofemoral laxity. A previously established rotometer device with a C-arm fluoroscope was used to assess passive tibiofemoral rotational laxity. Functional gait analysis was used to examine knee kinematics during level walking.Results: The mean side-to-side difference (SSD) in passive posterior translation was significantly reduced postoperatively (12.1 ± 4.4 mm vs. 4.3 ± 1.8 mm; p < 0.01). A significant reduction in passive tibiofemoral rotational laxity at 90° knee flexion was observed postoperatively (27.8° ± 7.0° vs. 19.9° ± 7.5°; p = 0.02). The range of AP tibiofemoral motion during level walking was significantly reduced in the reconstructed knees when compared to the contralateral knees at 6-month follow-up (16.6 ± 2.4 mm vs. 13.5 ± 1.6 mm; p < 0.01).Conclusion: PCL single-bundle reconstruction with optional PLC reconstruction reduces increased passive tibiofemoral translational and rotational laxity in PCL insufficient knees. However, increased passive tibiofemoral translational laxity could not be fully restored and patients showed altered knee kinematics with a significantly reduced range of tibiofemoral AP translation during level walking at 6-month follow-up. The findings of this study indicate a remaining lack of restoration of biomechanics after PCL single-bundle reconstruction in the active and passive state, which could be a possible cause for joint degeneration after PCL single-bundle reconstruction.

Thousands of industrial sites were found to be correlated with contaminated sites in the Arctic. Between 13,000 and 20,000 contaminated sites are likely to exist in the permafrost region, 26% of which will be affected by permafrost thaw before 2100.

White light refracted by a glass edge or a prism might be split into the colors of the rainbow but, when restricted by a suitable arrangement of edges, might also yield a sequence of colors complementary to the rainbow. We studied the creation of these color fields experimentally with a setup consisting of RGB light-emitting diodes that cover all color combinations of the three primary colors red, green, and blue. These light fields were projected through a prism onto a screen or a camera to generate various color fields by refraction. Applying the rules of additive color mixing, a simple RGB model based on the slit spectrum of the light convincingly reproduces the observed color patterns. The parallel use of model and experiment enables a clear recognition of unusual spectra from particularly combined light fields and yields an explanation of their origin.

Background The Bergen Growth Study 2 (BGS2) aims to characterise somatic and endocrine changes in healthy Norwegian children using a novel methodology. Subjects and methods A cross-sectional sample of 1285 children aged 6–16 years was examined in 2016 using novel objective ultrasound assessments of breast developmental stages and testicular volume in addition to the traditional Tanner pubertal stages. Blood samples allowed for measurements of pubertal hormones, endocrine disruptive chemicals, and genetic analyses. Results Ultrasound staging of breast development in girls showed a high degree of agreement within and between observers, and ultrasound measurement of testicular volume in boys also showed small intra- and interobserver differences. The median age was 10.4 years for Tanner B2 (pubertal onset) and 12.7 years for menarche. Norwegian boys reached a pubertal testicular volume at a mean age of 11.7 years. Continuous reference curves for testicular volume and sex hormones were constructed using the LMS method. Conclusions Ultrasound-based assessments of puberty provided novel references for breast developmental stages and enabled the measurement of testicular volume on a continuous scale. Endocrine z-scores allowed for an intuitive interpretation of changing hormonal levels during puberty on a quantitative scale, which, in turn, provides opportunities for further analysis of pubertal development using machine-learning approaches.

Chemotherapy resistance is a persistent clinical problem in relapsed high‐risk neuroblastomas. We tested a panel of 15 drugs for sensitization of neuroblastoma cells to the conventional chemotherapeutic vincristine, identifying tariquidar, an inhibitor of the transmembrane pump P‐glycoprotein (P‐gp/ABCB1), and the ERBB family inhibitor afatinib as the top resistance breakers. Both compounds were efficient in sensitizing neuroblastoma cells to vincristine in trypan blue exclusion assays and in inducing apoptotic cell death. The evaluation of ERBB signaling revealed no functional inhibition, that is, dephosphorylation of the downstream pathways upon afatinib treatment but direct off‐target interference with P‐gp function. Depletion of ABCB1, but not ERRB4, sensitized cells to vincristine treatment. P‐gp inhibition substantially broke vincristine resistance in vitro and in vivo (zebrafish embryo xenograft). The analysis of gene expression datasets of more than 50 different neuroblastoma cell lines (primary and relapsed) and more than 160 neuroblastoma patient samples from the pediatric precision medicine platform INFORM (Individualized Therapy For Relapsed Malignancies in Childhood) confirmed a pivotal role of P‐gp specifically in neuroblastoma resistance at relapse, while the ERBB family appears to play a minor part.

Abstract The international precision oncology program INFORM enrolls relapsed/refractory pediatric cancer patients for comprehensive molecular analysis. We report a two-year pilot study implementing ex vivo drug sensitivity profiling (DSP) using a library of 75–78 clinically relevant drugs. We included 132 viable tumor samples from 35 pediatric oncology centers in seven countries. DSP was conducted on multicellular fresh tumor tissue spheroid cultures in 384-well plates with an overall mean processing time of three weeks. In 89 cases (67%), sufficient viable tissue was received; 69 (78%) passed internal quality controls. The DSP results matched the identified molecular targets, including BRAF, ALK, MET, and TP53 status. Drug vulnerabilities were identified in 80% of cases lacking actionable (very) high-evidence molecular events, adding value to the molecular data. Striking parallels between clinical courses and the DSP results were observed in selected patients. Overall, DSP in clinical real-time is feasible in international multicenter precision oncology programs.

Abstract Background PET nuclides can have a considerable influence on the spatial resolution and image quality of PET/CT scans, which can influence diagnostics in oncology, for example. The individual impact of the positron energy of 18F, 68Ga, and 64Cu on spatial resolution and image quality was compared for PET/CT scans acquired using a clinical, digital scanner. Methods A Jaszczak phantom and a NEMA PET body phantom were filled with 18F-FDG, 68Ga-HCl, or 64Cu-HCl, and PET/CT scans were performed on a Siemens Biograph Vision. Acquired images were analyzed regarding spatial resolution and image quality (recovery coefficients (RC), coefficient of variation within the background, contrast recovery coefficient (CRC), contrast–noise ratio (CNR), and relative count error in the lung insert). Data were compared between scans with different nuclides. Results We found that image quality was comparable between 18F-FDG and 64Cu-HCl PET/CT measurements featuring similar maximal endpoint energies of the positrons. In comparison, RC, CRC, and CNR were degraded in 68Ga-HCl data despite similar count rates. In particular, the two smallest spheres of 10 mm and 13 mm diameter revealed lower RC, CRC, and CNR values. The spatial resolution was similar between 18F-FDG and 64Cu-HCl but up to 18% and 23% worse compared with PET/CT images of the NEMA PET body phantom filled with 68Ga-HCl. Conclusions The positron energy of the PET nuclide influences the spatial resolution and image quality of a digital PET/CT scan. The image quality and spatial resolution of 68Ga-HCl PET/CT images were worse than those of 18F-FDG or 64Cu-HCl despite similar count rates.

To reduce costs and effort, experiments in human-robot interaction can be carried out in Virtual Reality (VR) or in screen-based (SB) formats. However, it is not well examined whether robots are perceived and experienced in the same way in VR and SB as they are in the physical world. This study addresses this topic in a between-subjects experiment, measuring trust and engagement of an interaction with a mobile service robot in a museum scenario. Measures were made in three different settings, either the real world, in VR or in a game-like SB and then compared with an ANOVA. The results indicate, that neither trust nor engagement differ dependent on the experimental setting. The results imply that both VR and SB are eligible ways to explore the interaction with a mobile service robot, if some peculiarities of each medium are taken into account.

Background: The combination of platinum-containing cytostatic drugs with different radiation qualities has been studied for years. Despite their massive side effects, these drugs still belong to the therapeutic portfolio in cancer treatment. To overcome the disadvantages of cisplatin, our study investigated the cytotoxic effects of combining radionuclides with cisplatin. Methods: FaDu cells were treated with cisplatin (concentration ≈ 2 µM) and additionally irradiated after two hours with the alpha-emitter 223Ra, the beta-emitter 188Re as well as external X-rays using dose ranges of 2–6 Gy. Cell survival was followed by colony formation assays and plotted against cisplatin concentration and radiation dose. The results were interpreted by isobolograms. Results: Isobolographic analyses revealed a supra-additive cytotoxic effect for the combination of cisplatin and 223Ra. A sub-additive effect was observed for the combination of cisplatin and 188Re, whereas a protective effect was found for the combination with X-rays. Conclusions: The combination of cisplatin and 223Ra may have the potential to create a successfully working therapy scheme for various therapy approaches, whereas the combination with 188Re as well as single-dose X-ray treatment did not lead to a detectable radiosensitizing effect. Thus, the combination with alpha-emitters might be advantageous and, therefore, should be followed in future studies when combined with cytostatic drugs.

We previously reported that L-DOPA effects on reward-based decision-making in a randomized, placebo-controlled, double-blind, crossover study were consistent with an inverted U-shaped function whereby both low and high extremes of dopamine signaling are associated with high-impulsive choice. To test this hypothesis, we performed [18F]DOPA positron emission tomography in 60 of the 87 participants in that study, and measured the effective distribution volume ratio (EDVR) of [18F]DOPA influx rate to [18F]dopamine washout rate, an index of presynaptic dopaminergic function. Participants with higher baseline EDVR self-reported lower impulsivity, and discounted rewards as a function of delay more strongly after receiving L-DOPA, whereas the opposite was detected for those with lower baseline EDVR. Our findings support a relationship of striatal dopaminergic activity to trait impulsivity, and the view that there is a non-linear, possibly inverted U-shaped relationship of striatal dopaminergic function with delay discounting. Individuals with optimal dopamine signaling would become more impulsive when receiving dopamine-enhancing drugs, whereas those with suboptimal dopaminergic signaling would benefit and exhibit less impulsive choice. Consideration of differences in endogenous dopamine signaling and possibly also other neurotransmitter activity may be crucial to advance understanding of the neurobiochemical mechanisms of impulsive decision-making and related mental disorders.

Abstract Passive translational tibiofemoral laxity has been extensively examined in posterior cruciate ligament (PCL) insufficient patients and belongs to the standard clinical assessment. However, objective measurements of passive rotational knee laxity, as well as range of tibiofemoral motion during active movements, are both not well understood. None of these are currently quantified in clinical evaluations of patients with PCL insufficiency. The objective of this study was to quantify passive translational and rotational knee laxity as well as range of anterior–posterior and rotational tibiofemoral motion during level walking in a PCL insufficient patient cohort as a basis for any later clinical evaluation and therapy. The laxity of 9 patient knees with isolated PCL insufficiency or additionally posterolateral corner (PLC) insufficiency (8 males, 1 female, age 36.78 ± 7.46 years) were analysed and compared to the contralateral (CL) knees. A rotometer device with a C-arm fluoroscope was used to assess the passive tibiofemoral rotational laxity while stress radiography was used to evaluate passive translational tibiofemoral laxity. Functional gait analysis was used to examine the range of anterior–posterior and rotational tibiofemoral motion during level walking. Passive translational laxity was significantly increased in PCL insufficient knees in comparison to the CL sides (15.5 ± 5.9 mm vs. 3.7 ± 1.9 mm, p

Substance P (SP) has been a great interest for scientists due to its unique properties and involvement in various physiological and pathological phenomenon. It took almost a century for the current understanding of this peptide so far. Its role in brain and gut were initially discussed and later on it was widely studied and observed in cardiovascular system, asthma, traumatic brain injury, immune response, vasodilation, behavior, inflammation, arthritis, cancer, airway hyper responsiveness and respiratory disorders. Involvement of SP in sudden perinatal death and COVID-19 has also been discussed which shed light on its vital role in respiratory rhythm regulation and initiation of cytokine storming in COVID-19. This article will provide a comprehensive overview of the researches done to understand the basic functions and involvement of SP in different processes of cell and its association with various diseases. This article describes the historical and scientific journey of SP from its discovery until today, including its future perspectives.

Objective: To investigate the effects of an online wellness intervention on college students' self-efficacy, intentions to seek help, general resilience and whether adverse childhood experiences (ACEs) act as a moderating variable. Participants: Three-hundred and eighty-two undergraduate students. Method: Students were assigned to two conditions: treatment or control. The treatment group participated in an online intervention designed to enhance student wellness, the control group did not. Both groups completed an online questionnaire. Results: Students exposed to the intervention reported greater self-efficacy, a higher likelihood to engage in self-help activities and greater intention to use campus resources. Additionally, among students with more ACEs, those who were exposed to the site were more likely to recommend resources. Conclusion: The online intervention presented here may be an effective tool to reduce barriers for students seeking help for mental health and may increase student wellness.