Understanding the experiences of transition for newly qualified mental health nurses and their potential to stay in the role: A qualitative exploration.

AIM: To understand the experiences of transition from the perspective of newly qualified mental health nurses and the impact this may have on their potential to remain in the role. BACKGROUND: During the transitional period following registration newly qualified nurses experience feelings of being overwhelmed and shock. Internationally there is limited research on factors influencing transitional experiences in the field of mental health. DESIGN: A qualitative exploration was conducted using thematic content analysis to analyse the data gathered from semi-structured interviews METHOD: 18 Newly qualified mental health nurses from two NHS Mental Health trusts were interviewed, all within 18 months of registration. Data were analysed and themes generated addressing the research aim. RESULTS/FINDINGS: Five themes were co-created using this inductive technique: 'Transition to new role', 'Support for new role', 'Professional identity', 'Role development' and 'Working environment'. These themes are representative headings with the sub-themes making up the contributory content. Themes highlighted issues concerning newly qualified nurses and the transition which included aspects of anxiety and feeling overwhelmed initially. This highlighted the feelings associated with transition and progression through the process of liminality. Supervision was identified in the context of formal support, the presence of which is conducive to a positive transition. Imposter syndrome and experiencing reality shock were common aspects of role development and acknowledging the sense of responsibility gained once registered. Safety was highlighted as many experienced their first role on in-patient environments which was busy and potentially hostile. CONCLUSION: The transition of newly qualified nurses in mental health services can prove to be a difficult experience, therefore it requires acknowledgment and careful consideration. Understanding the liminal process may allow staff to appreciate the effect of the transition and to understand that the NQN will face overwhelming and unfamiliar responsibilities. Despite the demands to boost the workforce in mental health services there is a need to understand how best to integrate NQN's into their role during this transition. Caution must be used if we are not to lose more NQN's, as despite concerns there are still NQN's looking to mental health nursing as their future and chosen career.

Are Hydroxyl Radicals Spontaneously Generated in Unactivated Water Droplets?

Spontaneous ionization/breakup of water at the surface of aqueous droplets has been reported with evidence ranging from formation of hydrogen peroxide and hydroxyl radicals, indicated by ions at m/z 36 attributed to OH•-H3O+ or (H2O-OH2)+• as well as oxidation products of radical scavengers in mass spectra of water droplets formed by pneumatic nebulization. Here, aqueous droplets are formed both by nanoelectrospray, which produces highly charged nanodrops with initial diameters ~100 nm, and a vibrating mesh nebulizer, which produces 2 - 20 µm droplets that are less highly charged. The lifetimes of these droplets range from 10s of µs to 560 ms and the surface-to-volume ratios span ~100-fold range. No ions at m/z 36 are detected with pure water, nor are significant oxidation products for the two radical scavengers that were previously reported to be formed in high abundance. These and other results indicate that prior conclusions about spontaneous hydroxyl radical formation in unactivated water droplets are not supported by the evidence and that water appears to be stable at droplet surfaces over a wide range of droplet size, charge and lifetime.

Population-based anti-Müllerian hormone reference intervals help define gonadal status in the bitch.

OBJECTIVE: To establish statistically valid, population-based reference intervals (RIs) for canine anti-Müllerian hormone (AMH) and define changes in AMH and inhibin-B in bitches during breeding cycles. METHODS: A homologous canine ELISA was used to measure AMH in serum samples (collected between May 2019 and July 2024) from 102 intact and 78 reportedly ovariohysterectomized (OVH) bitches and 8 bitches before and after ovariohysterectomy, and in longitudinal samples from 24 bitches undergoing breeding management. Established 95% RIs were used in a retrospective assessment of 3,193 clinical submissions. Cyclic variation of AMH and inhibin-B (heterologous ELISA) were regressed with time and normalized to the rise in progesterone in samples from breeding bitches. RESULTS: Intact and OVH RIs for AMH were calculated with and without inclusion of 7 samples from reportedly OVH bitches that had AMH concentrations in the intact RI. Anti-Müllerian hormone and inhibin-B were positively correlated, and AMH was 3 times higher in proestrus than in estrus. Retrospectively, of 3,193 samples submitted for clinical AMH testing, 41% to 56% were in or above the intact AMH interval, 37% to 44% were within the OVH interval, and < 10% were inconclusive, depending on how RIs were defined. CONCLUSIONS: Statistically valid, population-based RIs establish a sound basis for interpreting results of clinical submissions requesting AMH to assess gonadal status in the bitch. CLINICAL RELEVANCE: Confirmation of cyclic variation in AMH (and, for the first time, inhibin-B) reaffirms proestrus as the optimum time to draw samples, and ≤ 10% of samples submitted for determination of gonadal status are expected to fall in an inconclusive AMH RI.

Lack of genetic association of non-melanoma skin cancer and pseudoexfoliative glaucoma.

BACKGROUND: Prior research has shown a positive association of pseudoexfoliative glaucoma (PXG) in patients with non-melanoma skin cancer (NMSC), likely due to an increase in ultraviolet exposure associated with both. However, the role of NMSC as a genetic risk factor for PXG has not been examined. Thus, the goal of this study is to utilize Mendelian randomization with genome-wide association studies to evaluate for genetic causality while controlling for environmental confounders. METHODS: We conducted a MR using the inverse variance weighted method (MR-IVW) as our primary analysis. Genomic data was sourced from GWASs for patients with NMSC (10,382 cases, 208,410 controls) and PXG (1,515 cases and 210,201 controls), originating from the FinnGen Biobank. RESULTS: Despite previous association of history of NMSC with occurrence of PXG, we found no evidence for a causal association between SNPs associated with NMSC and risk of PXG following MR analysis (MR-IVW, odds ratio (OR): 0.98, 95% CI: 0.85-1.14, P = 0.87). CONCLUSION: Here, we found no evidence for a causal association between SNPs associated with NMSC and the risk of PXG following a MR analysis.

Are large language models a useful resource to address common patient concerns on hallux valgus? A readability analysis.

BACKGROUND: This study evaluates the accuracy and readability of Google, ChatGPT-3.5, and 4.0 (two versions of an artificial intelligence model) responses to common questions regarding bunion surgery. METHODS: A Google search of "bunionectomy" was performed, and the first ten questions under "People Also Ask" were recorded. ChatGPT-3.5 and 4.0 were asked these ten questions individually, and their answers were analyzed using the Flesch-Kincaid Reading Ease and Gunning-Fog Level algorithms. RESULTS: When compared to Google, ChatGPT-3.5 and 4.0 had a larger word count with 315 ± 39 words (p < .0001) and 294 ± 39 words (p < .0001), respectively. A significant difference was found between ChatGPT-3.5 and 4.0 compared to Google using Flesch-Kincaid Reading Ease (p < .0001). CONCLUSIONS: Our findings demonstrate that ChatGPT provided significantly lengthier responses than Google and there was a significant difference in reading ease. Both platforms exceeded the seventh to eighth-grade reading level of the U.S. LEVEL OF EVIDENCE: N/A.

General Skills Amidst the Details: Alternative Learning Objectives and a Framework of Competencies for Human Anatomy.

The field of anatomy is often seen by non-anatomists as concerned primarily with the tasks of locating, naming, and describing structures; these tasks, in turn, are often assumed to require only lower-order cognitive skills (LOCS), i.e., the Knowledge or Comprehension levels of Bloom's taxonomy. Many non-anatomists may thus believe that studying anatomy does not develop transferable higher-order cognitive skills. Published lists of anatomy learning objectives (LOs) might reinforce this view by focusing attention on numerous details of specific structures and regions. To explore this issue further, we have analyzed the structure of published peer-reviewed LOs by characterizing their organization (single-tiered or multi-tiered), inclusion of function, use of action verbs, and dependence on or independence of context. Our results suggest that previously published LO lists, despite their value, may not fully showcase opportunities for students to develop higher-order skills. In the hope of stimulating further discussion and scholarship, we present here a two-tiered framework of human anatomy competencies, i.e., generalizable skills beyond straightforward recognition and memorization. This framework, which is intended to be both student-facing and faculty-facing, illustrates how anatomy courses may be reframed as opportunities to think critically and develop sophisticated, professionally relevant skills.

Long-term patient-reported values following cancer surgery: A global survey study.

BACKGROUND AND OBJECTIVES: We evaluated the long-term quality of life (QOL) and priorities of an international cohort of cancer surgery survivors. METHODS: Patients were surveyed through online support groups. We utilized the Short Form-12 questionnaire to evaluate QOL and a novel survey to assess the relative importance of longevity, experience, and costs. RESULTS: A total of 592 patients from six continents responded. They were 58 ± 12 years old, 70% female, and 92% White. Patients averaged 37 months from their initial cancer diagnosis, with a maximum survivorship of 46 years. Across 17 disease sites, respondents generally ranked longevity, functional independence, and emotional well-being most important, while treatment experience and costs were ranked least important (W = 33.6%, p < 0.001). However, a subset of respondents ranked costs as significantly important. There were no differences in QOL based on demographics, except patients with higher education and income reported better QOL scores. Despite improvements in QOL throughout survivorship, both physical-QOL (41.1 ± 11.1 at 1 year vs. 42.3 ± 12.6 at 5 years, p = 0.511) and mental-QOL (41.3 ± 13.4 at 1 year vs. 44.6 ± 13.9 at 5 years, p = 0.039) remained below that of the general population (50 ± 10; both p < 0.001). CONCLUSIONS: Cancer survivors experience enduring physical and mental impairment throughout survivorship. Future efforts should aim to provide sustained support across varied socioeconomic groups, ensuring equitable care and enhancement of QOL postcancer treatment.

Primary adrenal sarcomas: A national analysis of epidemiological trends, treatment patterns, and outcomes.

BACKGROUND AND OBJECTIVES: Primary adrenal sarcoma (PAS) is an exceedingly rare malignancy with limited data available on its epidemiology, management, and outcomes. This study aimed to characterize the national incidence, treatment patterns, and survival of PAS utilizing a National Cancer Database. METHODS: The National Cancer Database was queried for patients diagnosed with primary adrenal tumors from 2004 to 2019. Cases with sarcoma histology were identified as PAS. Annual incidence trends, histological distribution, treatment modalities (surgery, chemotherapy, radiation therapy), perioperative outcomes, and overall survival (OS) were analyzed. RESULTS: Of 7213 primary adrenal tumor cases, 332 (4.6%) were PAS. The most common histological subtypes were leiomyosarcoma (37.3%), hemangiosarcoma (27.1%), and sarcoma not otherwise specified (6.0%). Most cases (71.7%) presented as locoregional disease. Treatment included surgery alone (47.8%), surgery plus chemotherapy and/or radiation (27.1%), chemotherapy/radiation alone (13.3%), or no treatment (13.9%). For surgical cases, the median length of stay was 5 days, the 30-day readmission rate was 3.36%, and the 30/90-day mortality rates were 3.65% and 9.90%, respectively. The 5-year OS rate for surgery alone was 43%, with a median OS of 34.6 months. For surgery with radiation/chemotherapy, the 5-year OS rate was 37.3%, with a median OS of 35.4 months. CONCLUSIONS: This largest analysis of PAS to date demonstrates that most cases present as locoregional disease amenable to surgical resection, with favorable outcomes. The role of adjuvant therapy remains unclear, as no significant survival difference was observed between surgery alone and multimodal treatment.

Square Parametric Excitation: A Digital Resonant Method for the Quadrupole Ion Trap.

Digital ion trap technology is an alternate method for driving quadrupole ion traps and mass filters using variable frequency, fixed amplitude RF square waves in place of variable amplitude, fixed frequency RF sine waves. This technique offers some advantages such as an increase in the high mass analysis range by varying frequency and lower overall voltage requirements. Here, we present a complex square waveform developed for resonant parametric excitation in a quadrupole linear ion trap. Unlike traditional resonance methods, the driving RF square wave and auxiliary square wave are coupled using the same digital circuitry without the need for transformer coupling. In this work, we use this complex waveform to selectively excite the first order parametric resonances of ion motion. The square parametric excitation method presented here employs a simple and repetitive circuit design consisting of a low-voltage waveform generator followed by a series of high-voltage MOSFET switches. This design allows for resonance methods to be easily implemented in the all-digital quadrupole. The complex square waveform can perform the same useful functions as sine wave auxiliary signals, such as selective mass elimination and mass isolation. We also demonstrate that the mass resolution performance and S/N of our digital mass spectrometer is improved by applying the complex square waveform during ion ejection.

Tirzepatide and blood pressure reduction: stratified analyses of the SURMOUNT-1 randomised controlled trial.

BACKGROUND: Treating obesity may be a pathway to prevent and control hypertension. In the SURMOUNT-1 trial in people with obesity or overweight with weight-related complications, 72-week tirzepatide treatment led to clinically meaningful body weight and blood pressure reduction. Post hoc analyses were conducted to further explore the effects of tirzepatide on the pattern of blood pressure reduction and whether the effects were consistent across various subgroups. METHODS: The mixed effect for repeated measure model was used to compare changes in overall blood pressure, across demographic and clinical subgroups, baseline blood pressure subgroups and hypertension categories between SURMOUNT-1 participants randomised to treatment with tirzepatide and placebo. The association between weight changes and blood pressure and adverse events associated with low blood pressure were also evaluated by mediation analysis. RESULTS: Tirzepatide treatment was associated with a rapid decline in systolic and diastolic blood pressure over the first 24 weeks, followed by blood pressure stabilisation until the end of the observation period, resulting in a significant net reduction by 72 weeks of 6.8 mm Hg systolic and 4.2 mm Hg diastolic blood pressure versus placebo. Participants randomly assigned to any tirzepatide group were more likely than those assigned to placebo to have normal blood pressure at week 72 (58.0% vs 35.2%, respectively). The effects were broadly consistent across baseline blood pressure subgroups, shifting the blood pressure distribution curve to lower blood pressure levels. The mediation analysis indicated that weight loss explained 68% of the systolic and 71% of the diastolic blood pressure reduction. Low blood pressure adverse events were infrequent, but the rate was higher in the tirzepatide group. CONCLUSIONS: In these post hoc analyses, in participants with obesity or overweight, tirzepatide was associated with reduced blood pressure consistently across participant groups primarily via weight loss, with relatively few blood pressure-related adverse events. TRIAL REGISTRATION NUMBER: NCT04184622.

Leaning in and moving forward: a call to action and review of diversity initiatives in SAGES.

BACKGROUND: Diversity, equity, and inclusion have been an intentional focus for SAGES well before the COVID-19 pandemic and the coincident societal recognition of social injustices and racism. Longstanding inequities within our society, healthcare, and the surgery profession have come to light in the aftermath of events that rose to attention around the time of Covid. In so doing, they have brought into focus disparities, injustices, and inequalities that have long been present in the field of surgery, selectively affecting the most vulnerable. METHODS: This White paper examines the current state of diversity within the field of surgery and SAGES (Society of American Gastrointestinal and Endoscopic Surgeons) approach and effort to pave the way forward to meaningful change. We delineate the imperative for diversity, equity, and inclusion for all. By all, we mean to be inclusive of the diversity of gender and sexual orientation, race, ethnicity, geography, sex, and disability in the field of surgery. RESULTS: SAGES is an organization that lives at the intersection of education and innovation. It has a vital role in assisting the surgical profession in addressing these issues and needs and being a force alongside others for sustained and necessary change. SAGES can only realize these goals through a commitment across all aspects of the organization to embed diversity, equity, and inclusion into our very fabric. CONCLUSION: True diversity, equity, and inclusion within a surgical organization is vital for its longevity, growth, relevance, and impact. Unfortunately, the absence of DEI limits opportunity, robs the organization of collective intelligence in an environment in which its presence is critical, contributes to health inequities, and impoverishes all within the society and its value to all with whom it interfaces. SAGES is an organization that lives at the intersection of education and innovation. It has a vital role in assisting the surgical profession in addressing these issues and needs and being a force alongside others for sustained and necessary change. SAGES can only realize these goals through a commitment across all aspects of the organization to embed diversity, equity, and inclusion into our very fabric. Strategies like those highlighted in this White Paper, may be within our grasp and we can learn yet more if we remain in a place of humility and teachability in the future.

Adult-born granule cells modulate CA2 network activity during retrieval of developmental memories of the mother.

Adult-born granule cells (abGCs) project to the CA2 region of the hippocampus, but it remains unknown how this circuit affects behavioral function. Here, we show that abGC input to the CA2 of adult mice is involved in the retrieval of remote developmental memories of the mother. Ablation of abGCs impaired the ability to discriminate between a caregiving mother and a novel mother, and this ability returned after abGCs were regenerated. Chemogenetic inhibition of projections from abGCs to the CA2 also temporarily prevented the retrieval of remote mother memories. These findings were observed when abGCs were inhibited at 4-6 weeks old, but not when they were inhibited at 10-12 weeks old. We also found that abGCs are necessary for differentiating features of CA2 network activity, including theta-gamma coupling and sharp wave ripples, in response to novel versus familiar social stimuli. Taken together, these findings suggest that abGCs are necessary for neuronal oscillations associated with discriminating between social stimuli, thus enabling retrieval of remote developmental memories of the mother by their adult offspring.

RNA Isolation from Human Stem Cell-Derived Retinal Organoids.

RNA isolation is an essential first step for many types of molecular analyses, including reverse transcription PCR (RT-PCR)/quantitative RT-PCR (qRT-PCR), Northern blotting, microarrays, and RNA-sequencing. While many RNA purification methods have been reported, it can be challenging to extract sufficient quantity, and suitable quality, of RNA from very small amounts of tissue and/or samples containing low numbers of cells. Here we outline a total RNA isolation method that reproducibly yields high-quality RNA from human stem cell-derived retinal organoids for downstream transcriptomic analysis.

Speckle-free coherent imaging through deep turbulence.

We develop and validate a model-based iterative reconstruction framework for digitally correcting coherent images corrupted by deep turbulence. In general, this framework is applicable to coherent-imaging approaches that gain access to the complex-optical field; however, we demonstrate our approach with multi-shot digital holography data. To test our image correction framework, we generate calibrated deep-turbulence conditions from our laboratory testbed. Using the resulting data, we demonstrate groundbreaking performance in terms of speckle-free image correction in deep-turbulence conditions.

A comparison of dementia diagnoses and cognitive function measures in Medicare claims and the Minimum Data Set.

BACKGROUND: Gold standard dementia assessments are rarely available in large real-world datasets, leaving researchers to choose among methods with imperfect but acceptable accuracy to identify nursing home (NH) residents with dementia. In healthcare claims, options include claims-based diagnosis algorithms, diagnosis indicators, and cognitive function measures in the Minimum Data Set (MDS), but few studies have compared these. We evaluated the proportion of NH residents identified with possible dementia and concordance of these three. METHODS: Using a 20% random sample of 2018-2019 Medicare beneficiaries, we identified MDS admission assessments for non-skilled NH stays among individuals with continuous enrollment in Medicare Parts A, B, and D. Dementia was identified using: (1) Chronic Conditions Warehouse (CCW) claims-based algorithm for Alzheimer's disease and non-Alzheimer's dementia; (2) MDS active diagnosis indicators for Alzheimer's disease and non-Alzheimer's dementias; and (3) the MDS Cognitive Function Scale (CFS) (at least mild cognitive impairment). We compared the proportion of admissions with evidence of possible dementia using each criterion and calculated the sensitivity, specificity, and agreement of the CCW claims definition and MDS indicators for identifying any impairment on the CFS. RESULTS: Among 346,013 non-SNF NH admissions between 2018 and 2019, 57.2% met criteria for at least one definition (44.7% CFS, 40.7% CCW algorithm, 26.0% MDS indicators). The MDS CFS uniquely identified the greatest proportion with evidence of dementia. The CCW claims algorithm had 63.7% sensitivity and 78.1% specificity for identifying any cognitive impairment on the CFS. Active diagnosis indicators from the MDS had lower sensitivity (47.0%), but higher specificity (91.0%). CONCLUSIONS: Claims- and MDS-based methods for identifying NH residents with possible dementia have only partial overlap in the cohorts they identify, and neither is an obvious gold standard. Future studies should seek to determine whether additional functional assessments from the MDS or prescriptions can improve identification of possible dementia in this population.

Activation of Hepatocyte Growth Factor/MET Signaling as a Mechanism of Acquired Resistance to a Novel YAP1/TEAD Small Molecule Inhibitor.

Many tumor types harbor alterations in the Hippo pathway, including mesothelioma, where a high percentage of cases are considered YAP1/TEAD dependent. Identification of autopalmitoylation sites in the hydrophobic palmitate pocket of TEADs, which may be necessary for YAP1 protein interactions, has enabled modern drug discovery platforms to generate compounds that allosterically inhibit YAP1/TEAD complex formation and transcriptional activity. We report the discovery and characterization of a novel YAP1/TEAD inhibitor MRK-A from an aryl ether chemical series demonstrating potent and specific inhibition of YAP1/TEAD activity. In vivo, MRK-A showed a favorable tolerability profile in mice and demonstrated pharmacokinetics suitable for twice daily oral dosing in preclinical efficacy studies. Importantly, monotherapeutic targeting of YAP1/TEAD in preclinical models generated regressions in a mesothelioma CDX model; however, rapid resistance to therapy was observed. RNA-sequencing of resistant tumors revealed mRNA expression changes correlated with the resistance state and a marked increase of hepatocyte growth factor (HGF) expression. In vitro, exogenous HGF was able to fully rescue cytostasis induced by MRK-A in mesothelioma cell lines. In addition, co-administration of small molecule inhibitors of the MET receptor tyrosine kinase suppressed the resistance generating effect of HGF on MRK-A induced growth inhibition. In this work, we report the structure and characterization of MRK-A, demonstrating potent and specific inhibition of YAP1/TAZ-TEAD-mediated transcriptional responses, with potential implications for treating malignancies driven by altered Hippo signaling, including factors resulting in acquired drug resistance.

Broad proteomics analysis of seeding-induced aggregation of α-synuclein in M83 neurons reveals remodeling of proteostasis mechanisms that might contribute to Parkinson's disease pathogenesis.

Aggregation of misfolded α-synuclein (α-syn) is a key characteristic feature of Parkinson's disease (PD) and related synucleinopathies. The nature of these aggregates and their contribution to cellular dysfunction is still not clearly elucidated. We employed mass spectrometry-based total and phospho-proteomics to characterize the underlying molecular and biological changes due to α-syn aggregation using the M83 mouse primary neuronal model of PD. We identified gross changes in the proteome that coincided with the formation of large Lewy body-like α-syn aggregates in these neurons. We used protein-protein interaction (PPI)-based network analysis to identify key protein clusters modulating specific biological pathways that may be dysregulated and identified several mechanisms that regulate protein homeostasis (proteostasis). The observed changes in the proteome may include both homeostatic compensation and dysregulation due to α-syn aggregation and a greater understanding of both processes and their role in α-syn-related proteostasis may lead to improved therapeutic options for patients with PD and related disorders.

Genetic Predisposition to Sarcoma: What Should Clinicians Know?

OPINION STATEMENT: Pathogenic germline variants in the setting of several associated cancer predisposition syndromes (CPS) may lead to the development of sarcoma. We would consider testing for a CPS in patients with a strong family history of cancer, multiple primary malignancies, and/or pediatric/adolescent/young adult patients diagnosed with other malignancies strongly associated with CPS. When a CPS is diagnosed in a patient with sarcoma, additional treatment considerations and imaging options for those patients are required. This applies particularly to the use of radiation therapy, ionizing radiation with diagnostic imaging, and the use of alkylating chemotherapy. As data and guidelines are currently lacking for many of these scenarios, we have adopted a shared decision-making process with patients and their families. If the best chance for cure in a patient with CPS requires utilization of radiation therapy or alkylating chemotherapy, we discuss the risks with the patient but do not omit these modalities. However, if there are treatment options that yield equivalent survival rates, yet avoid these modalities, we elect for those options. Considering staging imaging and post-therapy evaluation for sarcoma recurrence, we avoid surveillance techniques that utilize ionizing radiation when possible but do not completely omit them when their use is indicated.