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A new protocol to detect neurodegeneration in Drosophila melanogaster whole-brain mounts using sophisticated microscopy.
The rapid and selective identification in the clinical setting of pathogenic bacteria causing healthcare associated infections (HAIs) and in particular blood stream infections (BSIs) is a major challenge, as the number of people affected worldwide and the associated mortality are on the rise. In fact, traditional laboratory techniques such culture and polymerase chain reaction (PCR)-based methodologies are often associated to long turnaround times, which justify the pressing need for the development of rapid, specific and portable point of care devices. The recently discovered clustered regularly interspaced short palindromic repeat loci (CRISPR) and the new class of programmable endonuclease enzymes called CRISPR associated proteins (Cas) have revolutionised molecular diagnostics. The use of Cas proteins in optical and electrochemical biosensing devices has significantly improved the detection of nucleic acids in clinical samples. In this study, a CRISPR/Cas12a system was coupled with electrochemical impedance spectroscopy (EIS) measurements to develop a label-free biosensing assay for the detection of Escherichia coli and Staphylococcus aureus, two bacterial species commonly associated to BSI infections. The programmable Cas12a endonuclease activity, induced by a specific guide RNA (gRNA), and the triggered collateral activity were assessed in in vitro restriction analyses, and evaluated thanks to impedance measurements using a modified gold electrode. The Cas12a/gRNA system was able to specifically recognize amplicons from different clinical isolates of E. coli and S. aureus with a limit of detection of 3 nM and a short turnaround time approximately of 1.5 h. To the best of our knowledge, this is the first biosensing device based on CRISPR/Cas12a label free impedance assay.
The evidence suggests that heavy workloads, pressure to publish, lack of recognition and job insecurity has led to increased job stress among nurse academics. Lack of proper mentoring, reorientation and transition into an academic role are contributory factors towards the lack of retention and recruitment among nurse academics. Internationally, the sustainability of the nurse academic workforce is an area of great concern. AMD3100 The experiences of nurse academics have not been extensively investigated.

To explore the work experiences of nurse academics.

Qualitative Exploratory study. Data were analysed using thematic analysis.

A purposive sample of nurse academics (n=19), recruited from all states and territories of Australia, lecturer to professor level and work experiences from 2 to 30years.

Data were collected using semi-structured face to face and telephone interviews. Data were transcribed verbatim and thematically analysed based upon Braun & Clark's model. The study is reported in accordance witing, difficult, academically weak, rude, and manipulative students. The growing workload increased non-academic administrative work, and the inability to sustain newly appointed staff were areas of great concern. Doing more with less and not being recognized were pertinent factors that needed to be addressed.Occupant safety remains one of the most challenging and significant design considerations in the automotive and transportation industry. Nevertheless, independently developed active or passive safety systems may lead to unsatisfactory protective performance under the critical driving scenarios. This study aimed to conduct multiobjective optimization of the cooperative controls between autonomous emergency steering (AES) and occupant restraint system (ORS) to explore the potential occupant injury reduction capability as well as mechanisms subjected to a frontal collision. First, a multiple simulation approach comprising PreScan/Simulink, LS-DYNA, Madymo was used to correlate the control parameters of the safety systems and occupant injuries quantitatively. Then the control parameters of AES and ORS were selected as the design variables after sensitivity analysis, and injury responses of the sampling points were extracted by the multiple simulation approach. Surrogate models and multiobjective optimization algorithm were used to determine the optimum design in cooperative controls of AES and ORS maneuvers, from which in-depth effect mechanisms that contributed to the improvement of occupant protection were identified. Compared to the baseline design, the optimum control parameters of AES-ORS integration substantially decreased the occupant injuries of the head, chest and neck, and consequently led to a reduction of 33.02% in the overall injury risk. This study is anticipated to demonstrate a new design approach for the control system, thereby enhancing occupant safety.The present study, based on a cross-sectional design, was conducted in the primary care setting with patients presenting somatic symptoms suggestive of somatoform disorders (SFD). The main aim of the study was to determine whether cognitive variables could differentiate between patients with SFD alone and those who also present depressive symptoms suggestive of depression (SFD + depression). All participants (N = 796) completed validated self-report measures to assess somatic, depressive, and/or anxiety symptoms, as well as functional impairment, quality of life (QoL), and cognitive variables (worry, rumination, metacognition, cognitive distortions, and emotion regulation). Univariate and multivariate analyses (controlled for potential sociodemographic and clinical confounders) were performed. On the univariate analysis, significant differences between the SFD and SFD + depression groups were found in sociodemographic and clinical variables, functional impairment, QoL, and cognitive variables. On the multivariate analysis, the only significative variables associated with comorbid SFD + depression were anxiety (β = 0.27; p less then 0.001), physical and psychological QoL (β = -0.10; p = 0.01; and β = -0.21; p less then 0.001, respectively), and marital status (β = -65; p less then 0.05). Cognitive variables were not significantly related to depressive symptoms in patients with SFD. These findings suggest that patients with SFD - with or without comorbid depression - share common cognitive processes and thus both groups could benefit from transdiagnostic cognitive therapy.
While research demonstrates that somatisation is highly correlated with post-traumatic stress disorder (PTSD), the relationship between International Classification of Diseases 11th edition (ICD-11) PTSD, complex PTSD (CPTSD) and somatisation has not previously been determined.

To determine the relationship between frequency and severity of somatisation and ICD-11 PTSD/CPTSD.

This cross-sectional study included 222 individuals recruited to the National Centre for Mental Health (NCMH) PTSD cohort. We assessed rates of Patient Health Questionnaire 15 (PHQ-15) somatisation stratified by ICD-11 PTSD/CPTSD status. Path analysis was used to explore the relationship between PTSD/CPTSD and somatisation, including number of traumatic events, age, and gender as controls.

70% (58/83) of individuals with CPTSD had high PHQ-15 somatisation symptom severity compared with 48% (12/25) of those with PTSD (chi-square 95.1, p value <0.001). Path analysis demonstrated that core PTSD symptoms and not disturbances in self organisation (DSO) symptoms were associated with somatisation (unstandardised coefficients 0.616 (p-value 0.017) and-0.012 (p-value 0.962) respectively.

Individuals with CPTSD have higher somatisation than those with PTSD. The core features of PTSD, not the DSO, characteristic of CPTSD, were associated with somatisation.
Individuals with CPTSD have higher somatisation than those with PTSD. The core features of PTSD, not the DSO, characteristic of CPTSD, were associated with somatisation.Hydrogen peroxide (H2O2) is widely used in clinical practice due to its antiseptic properties and its ability to heal wounds. However, due to its involvement in the formation of ROS, H2O2 causes several side effects, including disorders of the metabolism of skin cells and the development of chronic inflammation mediated by oxidative stress. Therefore, this study evaluated the effects of cannabidiol (CBD), a phytocannabinoid known for its antioxidant and anti-inflammatory properties, on the proteome of keratinocyte membranes exposed to H2O2. Overall, the hydrogen peroxide caused the levels of several proteins to increase, while the treatment with CBD prevented these changes. Analysis of the protein-protein interaction network showed that the significant changes mainly involved proteins with important roles in the proteasomal activity, protein folding processes (regulatory subunit of the proteasome 26S 6A, beta proteasome subunit type 1, chaperonin 60 kDa), protein biosynthesis (40S ribosomal proteins S16, S2 and ubiquitin-S27a), regulation of the redox balance (carbonyl reductase [NADPH] 1 and NAD(P)H [quinone] 1 dehydrogenase) and cell survival (14-3-3 theta protein). Additionally, CBD reduced the total amount of MDA, 4-HNE and 4-ONE-protein adducts. Therefore, we conclude that CBD partially prevents the changes induced by hydrogen peroxide by reducing oxidative stress and maintaining proteostasis networks. Moreover, our results indicate that combination therapy with CBD may bring a promising approach in the clinical use of hydrogen peroxide by preventing its pro-oxidative and pro-inflammatory effect through potential participation of CBD in membrane mediated molecular signaling.The antioxidant function of the phospholipid hydroperoxide glutathione peroxidase (GPx4) is vital for the homeostasis of many cell types, from neoplastic cells to normal erythroid precursors. However, some functional proteins in erythroid precursors are lost during the development of red blood cells (RBCs); whether GPx4 is maintained as an active enzyme in mature RBCs has remained unclear. Our meta-analyses of existing RBC proteomics and metabolomics studies revealed the abundance of GPx4 to be correlated with lipid-anchored proteins. In addition, GPx4 anti-correlated with lyso-phospholipids and complement system proteins, further supporting the presence of active GPx4 in mature RBCs. To test the potential biological relevance of GPx4 in mature RBCs, we correlated the rate of hemolysis of human RBCs during storage with the abundance of GPx4 and other heritable RBC proteins. Of the molecules that anti-correlated with the rate of hemolysis of RBCs, proteins that mediate the cellular response to hydroperoxides, including GPx4, have the greatest enrichment. Western blotting further confirmed the presence of GPx4 antigenic protein in RBCs. Using an assay optimized to measure the activity of GPx4 in RBCs, we found GPx4 to be an active enzyme in mature RBCs, suggesting that GPx4 protects RBCs from hemolysis during blood bank storage.Cysteine sulfenic acids (Cys-SOH) are pivotal modifications in thiol-based redox signaling and central intermediates en route to disulfide and sulfinic acid states. A core mission in our lab is to develop bioorthogonal chemical tools with the potential to answer mechanistic questions involving cysteine oxidation. Our group, among others, has contributed to the development of nucleophilic chemical probes for detecting sulfenic acids in living cells. Recently, another class of Cys-SOH probes based on strained alkene and alkyne electrophiles has emerged. However, the use of different models of sulfenic acid and methodologies, has confounded clear comparison of these probes with respect to chemical reactivity, kinetics, and selectivity. Here, we perform a parallel evaluation of nucleophilic and electrophilic chemical probes for Cys-SOH. Among the key findings, we demonstrate that a probe for Cys-SOH based on the norbornene scaffold does not react with any of the validated sulfenic acid models in this study. Furthermore, we show that purported cross-reactivity of dimedone-like probes with electrophiles, like aldehydes and cyclic sulfenamides, is a not meaningful in a biological setting.
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