The voice of the second-level regulated nursing role: a qualitative approach.

BACKGROUND: With an international nursing shortage, there is a need to navigate towards an improved nursing workforce structure where each nursing role is valued and recognised for the work they contribute. The second-level regulated nursing role is seen as integral; however, there is role confusion, especially with the registered nurse, and high attrition. To implement strategies to retain an integral nursing workforce, there is a need to better understand the role from the experiences and expectations of the second-level regulated nursing role. AIM: To gain a better understanding of the second-level regulated nursing role in the Australian nursing workforce. DESIGN: Qualitative descriptive study from a larger mixed methods study. METHOD: Five focus groups in 2018. The findings were analysed through the lens of organisational behaviour. RESULTS: The findings identified that enrolled nurses' intrinsic and extrinsic motivators influenced levels of job satisfaction and sense of feeling valued. The findings also identified key determinants that influence job satisfaction and occupational stress: enrolled nurses' understanding of their role and scope of practice; the registered nurses' understanding of the enrolled nurses' role and their role when working with the enrolled nurse; and the organisation's understanding and recognition of their role. When these determinants align, there is job satisfaction, less occupational stress and enrolled nurses feel valued. At a professional level, the title does not reflect the role, and there are no career pathways. CONCLUSION: This study explained why recurrent challenges impact the role and what contributes to those in the role feeling valued. Challenges that affect job satisfaction and occupational stress for the second-level (enrolled) nurse are related to the working environment and with whom the nurse works. From a professional level, there are limited career opportunities that recognise and retain the enrolled nurse in their role.

Identification of LY3522348: A Highly Selective and Orally Efficacious Ketohexokinase Inhibitor.

The identification of clinical candidate LY3522348 (compound 23) is described. LY3522348 is a highly selective, oral dual inhibitor of human ketohexokinase isoforms C and A (hKHK-C, hKHK-A). Optimization began with highly efficient (S)-2-(2-methylazetidin-1-yl)-6-(1H-pyrazol-4-yl)-4-(trifluoromethyl)nicotinonitrile (3). Efforts focused on developing absorption, distribution, metabolism, potency, and in vitro safety profiles to support oral QD dosing in patients. Structure-based design leveraged vectors for substitution of the pyrazole ring, which provided an opportunity to interact with several different proximal amino acid residues in the protein. LY3522348 displayed a robust pharmacodynamic response in a mouse model of fructose metabolism and was advanced into clinical trials.

Asking for less (but receiving more): Women avoid impasses and outperform men when negotiators have weak alternatives.

Both research and conventional wisdom suggest that, due to their relational orientation, women are less likely than men to engage in agentic and assertive behaviors, leading them to underperform in zero-sum, distributive negotiations where one party's gain is equivalent to the other party's loss. However, past research tends to neglect the costs of reaching impasse by excluding impasses from measures of negotiation performance. Departing from this convention, we incorporate the economic costs of impasses into measures of negotiation performance to provide a more holistic examination of negotiation outcomes. In so doing, we reveal a reversal of the oft-cited male performance advantage when obtaining an impasse is especially economically costly (as is the case when negotiators have weak negotiation alternatives). Specifically, we predicted that female negotiators would make less assertive first offers than men due to their more relational orientation and that these gender differences in offer assertiveness should result in women avoiding impasse more often than men. Since avoiding impasses should improve negotiation performance when negotiators are able to obtain a deal that is more valuable than their negotiation alternative, women's tendency to avoid impasses should improve their performance when negotiators have weak (vs. strong) alternatives. These predictions were supported in eight studies (three preregistered) across various negotiation contexts, comprising data from the television show Shark Tank (Study 1), four incentive-compatible negotiation simulations (Studies 2 and 3, Supplemental Studies), and a multistudy causal experimental chain (Supplemental Studies 4a-c). (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Tying the value of goals to social class.

Although everyone strives toward valued goals, we suggest that not everyone will be perceived as doing so equally. In this research, we examine the tendency to use social class as a cue to understand the importance of others' goals. Six studies find evidence of a goal-value bias: Observers perceive goals across a variety of domains as more valuable to higher class than to lower class individuals (Studies 1-6). These perceptions do not appear to reflect reality (pilot study), and those who are strongly motivated to justify inequality show the bias to a greater extent (Studies 5 and 6), suggesting a motivated pathway. We also explore implications of the bias, finding that Americans tend to offer better opportunities to, and prefer to collaborate with, higher class than lower class others, revealing discriminatory outcomes that are partially driven by perceived goal value (Studies 2, 3, 4, 6). Results suggest that Americans expect higher class individuals to value achieving goals more than their lower class counterparts, fueling increased support for those who are already ahead. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Experiences of registered nurses supporting nursing students during clinical placement using a facility-based model: A mixed methods study.

BACKGROUND: An ageing workforce and increased vacancies has seen a steady growth in nursing student enrolments. This has created a need to re-think how to optimise existing clinical placement opportunities while ensuring quality student experiences and staff satisfaction in their support role. OBJECTIVES: To provide insights into the experiences and satisfaction levels of Registered Nurses who supported nursing students during clinical placement using a facility-based model. DESIGN: A quasi-experimental design. SETTINGS: Three wards in an acute care facility and Primary and Community Health within the Southwest of Sydney, New South Wales, Australia. PARTICIPANTS: Participants included Registered Nurses/Midwives, Facility-based liaison support staff, and Nurse Managers. INTERVENTION: Within the 24/7 facility-based model, each nursing student was allocated to one Registered Nurse for the duration of the clinical placement period. The pair was rostered to complete the same day, evening, night, and weekend shifts. METHODS: A cross-sectional survey related to staff satisfaction was administered to participants at two time points: (a) prior to the commencement of the intervention (baseline survey); and (b) at the completion of the intervention. Following the intervention participants were invited to a focus group or an individual interview. RESULTS: There were no statistically significant changes in the levels of staff satisfaction from baseline to post-intervention; with personal fulfilment scoring the highest and workload the lowest. Staff who worked in the Primary and Community Health settings were less satisfied with this model of student support. Overall, most participants reported high personal satisfaction, professional growth and development opportunities yet acknowledged this came at a cost, with an increased workload. CONCLUSIONS: Participants were satisfied with the facility-based model in supporting student learning on clinical placement. The model is fit for purpose however it does need to be tailored to the contextual needs of nurses working in Primary and Community settings.

Developing a self-administered questionnaire: methods and considerations.

BACKGROUND: Using a structured process to develop a self-administered questionnaire provides a robust tool for collecting data that enhances the credibility of the results. Describing this process mitigates any complexity and confusion for the nurse researcher which can be generated by many sources of information that either lack detail or have complex statistical approaches. AIM: To discuss the development of a self-administered questionnaire with a focus on face, content, construct validity and reliability testing. DISCUSSION: Adopting a well-established, sequential, five-step approach ensures that important concepts of questionnaire development are addressed: assessing existing tools and qualitative data, if available; drafting of the questionnaire with consideration for question styles, comprehension, acquiescent bias and face validity; expert panel review to establish content validity and inter-rater reliability; pilot testing to assess construct validity; and exploratory factor analysis to establish reliability testing. This approach results in a robust and credible tool for collecting data. CONCLUSION: This article provides nurse researchers with a structured process for developing self-administered questionnaires. IMPLICATIONS FOR PRACTICE: Investing time and effort to assess a newly developed questionnaire for validity and reliability and consider question styles, comprehension and acquiescent bias results in an improved and strengthened tool for collecting data. This in turn enhances the quality and credibility of a study's findings.

Exploring the role of the second-level regulated nurse in the Australian nursing workforce: an integrative review.

BACKGROUND: The enrolled nurse is the second-level regulated nursing role in Australia and internationally. Reports and research indicate that the nursing profession requires greater understanding of the role, so it can be utilised to its potential. AIM: To explore issues that may impact the EN role in the Australian nursing workforce. DESIGN: An integrative review. METHODS: A seven-step framework was used to review scholarly papers, government documents, and grey literature. RESULTS: Three themes from 24 documents were identified: understanding the EN's scope of practice, standardised practice, and career development. DISCUSSION: A lack of understanding of their scope of practice creates role confusion and a lack of standardised practice, with an expected progression to become a registered nurse. These factors contribute to ENs' not feeling valued. CONCLUSION: The nursing profession do not understand the enrolled nurse role, and further work is required to value its place in the Australian nursing workforce.

"They're Everywhere!": Symbolically Threatening Groups Seem More Pervasive Than Nonthreatening Groups.

The meaning of places is socially constructed, often informed by the groups that seem pervasive there. For instance, the University of Pennsylvania is sometimes pejoratively called "Jew-niversity of Pennsylvania," and the city of Decatur, Georgia, is disparagingly nicknamed "Dyke-atur," connoting the respective pervasiveness of Jewish students and gay residents. Because these pervasiveness perceptions meaningfully impact how people navigate the social world, it is critical to understand the factors that influence their formation. Across surveys, experiments, and archival data, six studies (N = 3,039 American adults) revealed the role of symbolic threat (i.e., perceived differences in values and worldviews). Specifically, holding constant important features of the group and context, we demonstrated that groups higher in symbolic threat are perceived as more populous in a place and more associated with that place than groups lower in symbolic threat. Ultimately, this work reveals that symbolic threat can both distort how people understand their surroundings and shape the meaning of places.

Teleworking from home experiences during the COVID-19 pandemic among public health workers (TelEx COVID-19 study).

BACKGROUND: When working from home (WFH) became temporarily necessary for staff as a result of the COVID-19 pandemic in 2020, it had to be implemented without significant organisational experience or understanding of WFH and its complexities. This study aims to determine the impacts experienced by staff who have undertaken WFH during the COVID-19 pandemic. METHODS: This was an observational cross-sectional study using survey with a purposive sampling strategy for staff from corporate and non-clinical departments. These staff undertook WFH during COVID-19 pandemic in 2020. None of these staff had any direct operational roles in a hospital facility and clinical service. Participants' self-reports of their mood while working in their normal workplace and while WFH were collected via the Scale of Positive and Negative Experience (SPANE), a validated affect balance questionnaire. The responses from the open-ended question were analysed using thematic analysis approach. RESULTS: A total of 143 participants completed the survey responses. Majority (61%) WFH for four or more months as a result of the COVID-19 pandemic. Participants rated their skills very highly on the technologies with an average rating of 9 (out of 10) for computer skills, smartphones and videoconferencing/teleconferencing applications. Participants felt WFH was an improvement on normal working, in particular in relation to their ability to concentrate and be productive. The "SPANE" relating to affect balance while WFH was completed by 124 participants (85.7%), resulting in a mean score of 5.45 (S.D. 2.98). The SPANE relating to normal working conditions was completed by 127 participant (88.8%) resulting in a mean score of 2.70 (S.D 3.69). This indicated that while participants' positive emotions typically predominated in both situations, they felt slightly more positive on average with WFH. Over 90% participants reported that they would take the opportunity to WFH again if it were offered. Data obtained from the open-ended questions had complimented the findings of the structure close-ended questions in the benefits of remote working and support for their health and wellbeing. The open-ended questions had provided additional information on challenges which the participants encountered during the WFH experience and their suggested preference to sustain this workplace practice. CONCLUSIONS: This study highlighted factors that impacted workers' work processes, productivity, physical and mental health well-being while WFH and provided a foundation for considering how to best support a positive WFH experience.

Chemical Proteomic Characterization of a Covalent KRASG12C Inhibitor.

The KRASG12C protein product is an attractive, yet challenging, target for small molecule inhibition. One option for therapeutic intervention is to design small molecule ligands capable of binding to and inactivating KRASG12C via formation of a covalent bond to the sulfhydryl group of cysteine 12. In order to better understand the cellular off-target interactions of Compound 1, a covalent KRASG12C inhibitor, we have completed a series of complementary chemical proteomics experiments in H358 cells. A new thiol reactive probe (TRP) was designed and used to construct a cellular target occupancy assay for KRASG12C. In addition, the thiol reactive probes allowed us to profile potential off-target interactions of Compound 1 with over 3200 cysteine residues. In order to complement the TRP data we designed Compound 2, an alkyne containing version of Compound 1, to serve as bait in competitive chemical proteomics experiments. Herein, we describe and compare data from both the TRP and the click chemistry probe pull down experiments.

Somatostatin analogue-induced pancreatic exocrine insufficiency in patients with neuroendocrine tumors: results of a prospective observational study.

BACKGROUND: Patients with advanced well-differentiated neuroendocrine tumours (Wd-NETs) are commonly treated with somatostatin analogues (SSAs). Some patients may develop SSA-related side effects such as pancreatic exocrine insufficiency (PEI). METHODS: In this prospective, observational study, the frequency of SSA-induced PEI in 50 sequential patients with advanced Wd-NETs treated with SSAs was investigated. Toxicity was assessed monthly and faecal elastase-1 (FE1) and quality of life (QoL) were assessed 3-monthly. RESULTS: The median age was 65.8 years, 58% were male and the majority (92%) of patients had metastatic disease; patients received 4-weekly long acting octreotide (60%) or lanreotide (40%). Twelve patients (24%) developed SSA-related PEI after a median of 2.9 months from SSA initiation; FE1 was a reliable screening tool for PEI, especially in symptomatic (abdominal bloating, flatulence and/or diarrhea) patients (risk ratio 8.25 (95% confidence interval 1.15-59.01)). Most of these patients (11/12; 92%) required PERT. Other SSA-related adverse events (any grade) included flatulence (50%), abdominal pain (32%), diarrhoea (30%) and fatigue (20%). Development of PEI did not significantly worsen overall QoL, however gastrointestinal symptoms and diarrhoea were increased. CONCLUSION: This study demonstrated that PEI occurs at a higher rate than previously reported; clinicians need to diagnose and treat this SSA-related adverse-event which occurs in 1 in 4 patients with Wd-NETs treated with SSAs. Screening with FE1 in symtomatic patients is recommend.

Striatal oligodendrogliogenesis and neuroblast recruitment are increased in the R6/2 mouse model of Huntington's disease.

The subventricular zone (SVZ) is one of the two major neurogenic regions in the adult mammalian brain. Its close proximity to the striatum suggests that a cell-based therapeutic strategy for the treatment of Huntington's disease (HD) is possible. To achieve this, it is important to understand how adult cell production, migration and differentiation may be altered in the HD brain. In this study, we quantified the number of adult-born striatal cells and characterized their fate in the R6/2 transgenic mouse model of HD. We found that the number of new striatal cells was approximately two-fold greater in R6/2 vs. wild type mice, while SVZ cell proliferation was not affected. Using cell-type specific markers, we demonstrated that the majority of new striatal cells were mature oligodendrocytes or oligodendroglial precursors that were intrinsic to the striatum. We also detected a significant increase in the number of migrating neuroblasts that appeared to be recruited from the SVZ to the striatum. However, these neuroblasts did not mature into neurons and most were lost between 1 and 2 weeks of cell age. Crossing the R6/2 mice with mice the over-expressing brain-derived neurotrophic factor in the striatum increased the numbers of neuroblasts that survived to 2 weeks, but did not promote their differentiation. Together, our data indicate that the potential treatment of HD based on manipulating endogenous progenitor cells should take into consideration the apparent enhancement in striatal oligodendrogliogenesis and the limited ability of recruited SVZ neuroblasts to survive long-term and differentiate in the diseased striatum.

Palmitoylation and trafficking of GAD65 are impaired in a cellular model of Huntington's disease.

HD (Huntington's disease) is caused by an expanded polyQ (polyglutamine) repeat in the htt (huntingtin protein). GABAergic medium spiny neurons in the striatum are mostly affected in HD. However, mhtt (mutant huntingtin)-induced molecular changes in these neurons remain largely unknown. The present study focuses on the effect of mhtt on the subcellular localization of GAD (glutamic acid decarboxylase), the enzyme responsible for synthesizing GABA (γ-aminobutyric acid). We report that the subcellular distribution of GAD is significantly altered in two neuronal cell lines that express either the N-terminus of mhtt or full-length mhtt. GAD65 is predominantly associated with the Golgi membrane in cells expressing normal htt; however, it diffuses in the cytosol of cells expressing mhtt. As a result, vesicle-associated GAD65 trafficking is impaired. Since palmitoylation of GAD65 is required for GAD65 trafficking, we then demonstrate that palmitoylation of GAD65 is reduced in the HD model. Furthermore, overexpression of HIP14 (huntingtin-interacting protein 14), the enzyme responsible for palmitoylating GAD65 in vivo, could rescue GAD65 palmitoylation and vesicle-associated GAD65 trafficking. Taken together, our data support the idea that GAD65 palmitoylation is important for the delivery of GAD65 to inhibitory synapses and suggest that impairment of GAD65 palmitoylation by mhtt may lead to altered inhibitory neurotransmission in HD.

BimEL as a possible molecular link between proteasome dysfunction and cell death induced by mutant huntingtin.

Huntington's disease (HD) is a devastating neurodegenerative disorder caused by an expanded polyglutamine repeat within the N-terminus of the huntingtin protein. It is characterized by a selective loss of medium spiny neurons in the striatum. It has been suggested that impaired proteasome function and endoplasmic reticulum (ER) stress play important roles in mutant huntingtin (mHtt)-induced cell death. However, the molecular link involved is poorly understood. In the present study, we identified the essential role of the extra long form of Bim (Bcl-2 interacting mediator of cell death), BimEL, in mHtt-induced cell death. BimEL protein expression level was significantly increased in cell lines expressing the N-terminus of mHtt and in a mouse model of HD. Although quantitative RT-PCR analysis indicated that BimEL mRNA was increased in cells expressing mHtt, we provided evidence showing that, at the post-translational level, phosphorylation of BimEL played a more important role in regulating BimEL expression. Up-regulation of BimEL facilitated the translocation of Bax to the mitochondrial membrane, which further led to cytochrome c release and cell death. On the other hand, knocking down BimEL expression prevented mHtt-induced cell death. Taken together, these findings suggest that BimEL is a key element in regulating mHtt-induced cell death. A model depicting the role of BimEL in linking mHtt-induced ER stress and proteasome dysfunction to cell death is proposed.

Post-MPTP treatment with granulocyte colony-stimulating factor improves nigrostriatal function in the mouse model of Parkinson's disease.

The neuroprotective effects of granulocyte colony-stimulating factor (G-CSF) were reported in several neurological disease models, including Parkinson's disease (PD). In the present study, we investigated the therapeutic effect of G-CSF after the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD was established. G-CSF was subcutaneously administered into C57BL/6 mice that had undergone systemic MPTP injections. We found that G-CSF treatment markedly increased the number of dopaminergic neurons in the substantia nigra pars compacta (SNpc) of the G-CSF-treated group. Consistent with this finding, we found a significant increase in dopamine release under high K(+) stimulation in the striatum of the G-CSF-treated animals compared to the MPTP-exposed mice. Finally, we observed a persistent recovery of locomotor function in the G-CSF-treated animals. These results suggest the potential therapeutic value of G-CSF in treating PD. However, our bromodeoxyuridine labeling experiment failed to identify any newly generated dopaminergic neurons in SNpc. This might indicate an indirect effect of G-CSF on cell proliferation. The underlying mechanism of G-CSF is under further investigation.

Protective function of taurine in glutamate-induced apoptosis in cultured neurons.

Previously, we showed that taurine protects neurons against glutamate-induced excitotoxicity by inhibiting the glutamate-induced increase of [Ca2+](i). In this study, we report that taurine prevents glutamate-induced chromosomal condensation, indicating that taurine inhibits glutamate-induced apoptosis. We found that Bcl-2 was down-regulated while Bax was up-regulated by glutamate treatment, and these changes were prevented in the presence of taurine. We have also shown that taurine inhibits glutamate-induced activation of calpain. Furthermore, calpastatin, a specific calpain inhibitor, also prevented glutamate-induced cell death. Here we propose the mechanisms underlying glutamate-induced apoptosis and taurine's inhibition of glutamate-induced apoptosis to be as follows: glutamate stimulation induces [Ca2+](i) elevation, which in turn activates calpain; activation of calpain leads to a reduction of Bcl-2:Bax ratios; with decreased Bcl-2:Bax ratios Bax homodimers form, Bax homodimerization, and translocation to the mitochondria result in the release of cytochrome c; released cytochrome c in turn activates a downstream caspase cascade leading to apoptosis. The antiapoptotic function of taurine is due to its inhibition of glutamate-induced membrane depolarization.

cT3N0 rectal cancer: potential overtreatment with preoperative chemoradiotherapy is warranted.

PURPOSE: Although combined-modality therapy (CMT) is the preferred treatment for T3 and/or lymph node (LN)-positive rectal cancer, the German rectal cancer study published in 2004 demonstrated that 18% of patients deemed suitable for preoperative CMT by endorectal ultrasound (ERUS) may be overstaged. Because data also suggest that LN-negative rectal cancer after total mesorectal excision may not require radiotherapy, it is reasonable to consider omitting radiotherapy for the cT3N0 subset. We therefore determined the accuracy of pre-CMT ERUS or magnetic resonance imaging (MRI) staging, to explore the validity of a nonpreoperative CMT approach for cT3N0 disease. PATIENTS AND METHODS: One hundred eighty-eight ERUS-/MRI-staged T3N0 rectal cancer patients received preoperative CMT (fluorouracil based and 45-50.4 Gy) followed by radical resection. Rates of pathologic complete response (pCR) and mesorectal LN involvement were determined. RESULTS: Tumors were located a median of 5 cm from the anal verge. Sphincter-preserving surgery was performed in 143 patients (76%). Overall pCR was 20%, and 41 patients (22%) had pathologically positive mesorectal LNs. The incidence of positive LNs significantly increased with T stage: ypT0, 3%; ypT1, 7%; ypT2, 20%; ypT3-4, 36% (P = .001). CONCLUSION: The accuracy of preoperative ERUS/MRI for staging mid to distal cT3N0 rectal cancer is limited because 22% of patients have undetected mesorectal LN involvement despite CMT. Therefore, ERUS-/MRI-staged T3N0 rectal cancer patients should continue to receive preoperative CMT. Although 18% may be overstaged and therefore overtreated, our data suggest that an even larger number would be understaged and require postoperative CMT, which is associated with significantly inferior local control, higher toxicity, and worse functional outcome.