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Mara Bensson-Ravunniarath,1 Joanna Bryan Ringel,2 Ariel Avgar,3 Faith Wiggins,4 Ann Lee,4 Margaret V McDonald,5 Lourdes R Guerrero,6 John Kallas,3 Geoffrey Gusoff,7 Megan Shen,8 Emily Tseng,9 Nicola Dell,9 Sara Czaja,2 Lee A Lindquist,10 Madeline R Sterling2 1Department of Medicine, Massachusetts General Hospital, Boston, MA, USA; 2Department of Medicine, Weill Cornell Medicine, New York, NY, USA; 3Cornell University, School of Industrial Labor Relations, Ithaca, NY, USA; 4 1199SEIU Training and Employment Fund, New York, NY, USA; 5Center for Home Care Policy & Research, VNS Health, New York, NY, USA; 6Department of Neurosciences, UC San Diego, San Diego, CA, USA; 7Department of Family Medicine, UCLA, Los Angeles, CA, USA; 8Clinical Research Division, Fred Hutch Cancer Center, Seattle, WA, USA; 9Cornell Tech, Cornell University, New York, NY, USA; 10Division of Geriatrics, Feinberg School of Medicine, Northwestern University, Chicago, IL, USACorrespondence: Madeline R Sterling, Department of Medicine, Division of General Internal Medicine, Weill Cornell Medicine, 420 East 70th Street, Room LH-357, New York, NY, 10021, USA, Tel +1646-962-5029, Email mrs9012@med.cornell.eduPurpose: Despite a rapidly growing need for home health aides (HHAs), turnover rates are high. While this is driven in large part by the demanding nature of their work and low wages, another factor may be that HHAs are often not considered part of the medical team which can leave them feeling unheard by other healthcare professionals. We sought to determine whether this concept, or HHAs’ perceived voice, was associated with job satisfaction.Methods and Design: This cross-sectional survey of English- and Spanish-speaking HHAs caring for adults with heart failure (HF) was conducted from June 2020 to July 2021 in New York, NY in partnership with a labor management fund of a large healthcare union that provides benefits and training to HHAs. Voice was assessed with a validated 5-item scale (total score range 5 to 25). Job Satisfaction was assessed with the 5-item Work Domain Satisfaction Scale (total score range 5 to 35). Multivariable linear regression analysis was used to examine the association between voice and job satisfaction.Results: A total of 413 HHAs employed by 56 unique home care agencies completed the survey; they had a mean age of 48 years, 97.6% were female, 60.2% were Hispanic, and they worked as HHAs for a median of 10 years (IQR, 5, 17). They had a median Voice score of 18 (IQR 15– 20) and mean job satisfaction score of 26.4 (SD 5.6). Higher levels of voice (1.75 [0.46– 3.04]) were associated with greater job satisfaction (p=0.008). When adjusting for Race/Ethnicity, HF training, and HF knowledge, the association between Voice and job satisfaction remained significant ((1.77 [0.40– 3.13])Conclusion: HHAs with a voice in the care of their patients experienced greater job satisfaction. Voice may be an important target for interventions aiming to improve HHAs’ retention in the field.Keywords: long-term care, home health aide, communication, healthcare team

Guanidinoacetic acid (GAA) plays an important role in cellular energy use and protein synthesis. The objectives of this study were to determine the optimal level of dietary GAA regarding the growth performance and fillet characteristics of rainbow trout ( Oncorhynchus mykiss ). A total of 300 trout (initial weight, 66.84 ± 7.82 g) were fed isonitrogenous (34%) and isocaloric (20.6 MJ kg -1 ) diets with increasing levels of GAA (0.00, 0.06, 0.12, 0.18%) for 90 days. The results showed that trout fed GAA (either 0.06, 0.12, or 0.18%) yielded better ( p < 0.05) performance (BW, BWG, FCR, and SGR) than trout fed the control diet (0.00% GAA inclusion). No differences ( p > 0.05) were observed for BW, BWG, nor FCR among trout fed GAA. Nonetheless, trout fed a diet with a 0.12% GAA inclusion had the highest ( p < 0.01) SGR. Fillet quality was not affected by GAA supplementation ( p > 0.05) for cook loss, shear force, nor colour. Trout fed 0.06% GAA inclusion tended ( p = 0.08) to have a higher WHC. Moreover, trout fed 0.12 and 0.18% GAA had lower ( p < 0.05) pH values than trout fed the control diet and 0.06% GAA. Our findings give insights for the growth promotion and fillet quality of trout fed diets supplemented with GAA, especially at the level of 0.12%.

Heart failure (HF) affects six million people in the U.S., is associated with high morbidity, mortality, and healthcare utilization. (1, 2) Despite a decade of innovation, the majority of interventions aimed at reducing hospitalization and readmissions in HF have not been successful. (3-7) One reason may be that most have overlooked the role of home health aides and attendants (HHAs), who are often highly involved in HF care. (8-13) Despite their contributions, studies have found that HHAs lack specific HF training and have difficulty reaching their nursing supervisors when they need urgent help with their patients. Here we describe the protocol for a pilot randomized control trial (pRCT) assessing a novel stakeholder-engaged intervention that provides HHAs with a) HF training (enhanced usual care arm) and b) HF training plus a mobile health application that allows them to chat with a nurse in real-time (intervention arm). In collaboration with the VNS Health of New York, NY, we will conduct a single-site parallel arm pRCT with 104 participants (HHAs) to evaluate the feasibility, acceptability, and effectiveness (primary outcomes: HF knowledge; HF caregiving self-efficacy) of the intervention among HHAs caring for HF patients. We hypothesize that educating and better integrating HHAs into the care team can improve their ability to provide support for patients and outcomes for HF patients as well (exploratory outcomes include hospitalization, emergency department visits, and readmission). This study offers a novel and potentially scalable way to leverage the HHA workforce and improve the outcomes of the patients for whom they care. Clinical trial.gov registration: NCT04239911., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Importance: Home health aides and attendants (HHAs) provide essential care to older adults and those with chronic conditions in the home. However, some HHAs struggle with poor mood and stress, which may have been exacerbated by the COVID-19 pandemic., Objective: To elicit HHAs' perspectives toward mental health and well-being, including how their job influences both and how to better support the workforce in the future., Design, Setting, and Participants: For this qualitative study, focus groups and interviews with HHAs were facilitated in English and Spanish from August 17, 2022, to February 9, 2023, in partnership with the 1199SEIU Training and Employment Fund, a benefit fund of the 1199SEIU United Healthcare Workers East and the largest health care union in the US. Included were HHAs at risk for poor mental health and well-being, which were defined as having at least mild or more symptoms on either the 8-item Personal Health Questionnaire depression scale, the 4-item Cohen Perceived Stress Scale, or the University of California, Los Angeles Loneliness Scale., Exposure: Mental health and well-being of HHAs., Main Outcomes and Measures: Focus groups and interviews were audio recorded, professionally transcribed, and translated. A thematic analysis was performed that was informed by Pender's Health Promotion Model and the National Institute for Occupational Safety and Health's Total Worker Health model., Results: A total of 28 HHAs from 14 different agencies participated (mean [SD] age, 54.3 [10.8] years; 26 female [93%]). Seventeen participants (61%) spoke Spanish at home. Five key themes emerged: (1) HHAs' attitudes toward mental health and well-being were influenced by a variety of personal and cultural factors; (2) HHAs' relationships with their patients impacted their mood in both positive and negative ways; (3) structural and organizational aspects of the job, alongside the COVID-19 pandemic, impacted HHAs' mood and stress levels; (4) HHAs used a variety of strategies to cope with their emotions; and (5) HHAs were eager for interventions that can improve their mood, particularly those that bring them closer to their colleagues., Conclusions and Relevance: These findings suggest that HHAs' mental health and well-being may be influenced by both personal and occupational factors. Interventions and policies to better support their emotional well-being on the job are warranted.

Background: Despite their unique contributions to heart failure (HF) care, home healthcare workers (HHWs) have unmet educational needs and many lack HF caregiving self-efficacy. To address this, we used a community-partnered approach to develop and pilot a HF training course for HHWs., Methods: We partnered with the Training and Employment Fund, a benefit fund of the largest healthcare union in the United States, to develop a 2-hour virtual HF training course that met HHWs' job-specific needs. English and Spanish-speaking HHWs interested in HF training, with access to Zoom, were eligible. We used a mixed methods design with pre/postsurveys and semi-structured interviews to evaluate the course: (a) feasibility, (b) acceptability, and (c) effectiveness (change in knowledge [Dutch Heart Failure Knowledge Scale range 0-15] and caregiving self-efficacy [HF Caregiver Self-efficacy Scale range 0-100])., Results: Of the 210 HHWs approached, 100 were eligible and agreed, and 70 enrolled. Of them, 53 (employed by 15 different home care agencies) participated. Posttraining data showed significant improvements (pretraining mean [SD] versus posttraining mean [SD]; P value) in HF knowledge (11.21 [1.90] versus 12.21 [1.85]; P =0.0000) and HF caregiving self-efficacy (75.21 [16.57] versus 82.29 [16.49]; P =0.0017); the greatest gains occurred among those with the lowest pre-training scores. Participants found the course engaging, technically feasible, and highly relevant to their scope of care., Conclusions: We developed and piloted the first HF training course for HHWs, which was feasible, acceptable, and improved their HF knowledge and caregiving self-efficacy. Our findings warrant scalability to the workforce at large with a train-the-trainer model.

Background: We sought to better understand patterns of potentially inappropriate medications (PIMs) from the Beers criteria among older adults hospitalized with heart failure (HF). This observational study of hospitalizations was derived from the geographically diverse REasons for Geographic and Racial Differences in Stroke cohort., Methods and Results: We examined participants aged 65 years and older with an expert-adjudicated hospitalization for HF. The Beers criteria medications were abstracted from medical records. The prevalence of PIMs was 61.1% at admission and 64.0% at discharge. Participants were taking a median of 1 PIM (interquartile range [IQR] 0-1 PIM) at hospital admission and a median of 1 PIM (IQR 0-2 PIM) at hospital discharge. Between admission and discharge, 19.1% of patients experienced an increase in the number of PIMs, 15.1% experienced a decrease, and 37% remained on the same number between hospital admission and discharge. The medications with the greatest increase from admission to discharge were proton pump inhibitors (32.6% to 38.6%) and amiodarone (6.2% to 12.2%). The strongest determinant of potentially harmful prescribing patterns was polypharmacy (relative risk 1.34, 95% confidence interval 1.16-1.55, P < .001)., Conclusions: PIMs are common among older adults hospitalized for HF and may be an important target to improve outcomes in this vulnerable population., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The study of interface states and bulk traps and their connection to device instability is highly demanded to achieve reliable β-Ga2O3 metal-oxide-semiconductor (MOS) devices. However, a comprehensive analysis of the capture/emission behavior of interface states and bulk traps can be challenging due to widespread time constant distribution. In this study, using capacitance transient measurement tools, trap states of the ZrO2/β-Ga2O3 MOS gate stack were explicitly investigated, particularly its bias- and temperature-dependent relaxation kinetics. As forward bias is enlarged, it is observed that the interface state density (Dit) increases by 12.6%. Two bulk traps with discrete levels identified as 0.43 eV (E1) and 0.74 eV (E2) below the conduction band minimum were extracted by deep-level transient spectroscopy. It is further revealed that the emission processes of E1 and E2 are thermally enhanced, while the capture processes remain insensitive to temperature. The electric-field dependence of E1 indicates that the dominant mechanism follows the rule of Poole–Frenkel emission. The capacitance–voltage (C–V) hysteresis deteriorated at a higher forward bias due to the higher trap density and increased population of trapped charges. These findings provide an important framework for future device optimization to improve the reliability and performance of β-Ga2O3 MOS devices. [ABSTRACT FROM AUTHOR]

In this work, three atomic layer deposition (ALD) approaches are used to deposit an Al2O3 gate insulator on n-GaN for application in vertical GaN power switches: thermal ALD (ThALD), plasma-enhanced ALD (PEALD), and their stacked combination. The latter is a novel method to yield the most ideal insulating layer. Also, the influence of an in situ NH3 or H2 plasma pre-treatment is studied. Planar MIS capacitors are used to investigate the electrical properties and robustness of the gate insulators. In vacuo x-ray photoelectron spectroscopy (XPS) is used to study the changes in chemical composition after every surface treatment. XPS shows that all plasma pre-treatments efficiently remove all carbon contamination from the surface, but only NH3 plasma is observed to additionally remove the native oxide from the n-GaN surface. The water precursor step in the ThALD process does not completely remove the CH3 ligands of the trimethylaluminum precursor step, which might electrically be associated with a reduced forward bias robustness. The O2 plasma step in the PEALD process is associated with the removal of carbon and a tremendous increase of the O content in the GaN surface region. Electrically, this strongly correlates to an enhanced forward bias robustness and an increased forward bias hysteresis, respectively. The ThALD/PEALD stack method mitigates the shortcomings of both ALD processes while maintaining its advantages. Electrical measurements indicate that the stack method alongside NH3 plasma pretreatment provides the best characteristics in terms of hysteresis, threshold voltage, forward bias robustness, and interface trap density of states. [ABSTRACT FROM AUTHOR]

We investigate the sub-bandgap optical absorption (SOA) in 300-nm-thick Al1−xInxN alloys used in cladding layers of edge-emitting laser diodes and distributed Bragg reflectors of vertical-cavity surface-emitting lasers. Al1−xInxN alloys, with indium content x ranging from 0.114 to 0.185, were grown by metal-organic chemical vapor deposition on a c-plane GaN/sapphire template. SOAs on 300-nm-thick thin films were characterized using photothermal deflection spectroscopy (PDS). Thermal emission, such as nonradiative recombination with phonon emission, is the dominant energy relaxation process occurring after SOA in Al1−xInxN alloys. The absorption coefficient of the SOA was estimated to be 0.6–7.0 × 103 cm−1 in these samples by combining PDS and spectroscopic ellipsometry. The drastic increase in the SOA, when x exceeded the lattice-matched composition of the GaN/sapphire template, indicates that impurities, vacancy-type defects, and their complexes with increasing x are possible candidates that result in SOA in Al1−xInxN alloys. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to investigate the association between high-sensitivity C-reactive protein (hsCRP) levels and hepatic fibrosis in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) and assess its predictive efficacy. Methods: The study included 1,477 participants from the United States and 1,531 from China diagnosed with MASLD. Liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) were assessed by vibration-controlled transient elastography (VCTE) to evaluate the presence and degree of hepatic fibrosis and steatosis. The relationship between hsCRP levels and hepatic fibrosis in MASLD patients was examined using multivariable-adjusted and restricted cubic spline (RCS) models. Additionally, subgroup analyses were conducted to investigate the potential heterogeneity among different characteristic subgroups. Results: The results demonstrated a significant correlation between elevated hsCRP levels and an increased risk of significant fibrosis, advanced fibrosis, and cirrhosis in the US cohort of MASLD patients (OR 2.22, 1.69, and 2.85, respectively; all P <0.05). The results of the Chinese cohort were consistent with those of the US cohort, and there was a significant and positive correlation between hsCRP levels and the risk of hepatic fibrosis in patients with MASLD (OR 2.53, 3.85, and 3.78, respectively, all P <0.001). The RCS analysis revealed a significant non-linear relationship between hsCRP levels and the degree of hepatic fibrosis, with disparate inflection point values observed across different cohorts (approximately 9 mg/L in the US cohort and 4 mg/L in the Chinese cohort). The impact of hsCRP levels on the risk of hepatic fibrosis varied across different subgroups with distinct characteristics. Conclusion: The present study demonstrated a significant correlation between hsCRP levels and the degree of hepatic fibrosis in patients with MASLD, with notable dose-response relationships and subgroup differences. [ABSTRACT FROM AUTHOR]

Background/Objectives: Fragile X syndrome (FXS) is one of the most common genetic causes of intellectual developmental disability and autism spectrum disorder (ASD), second only to Down's syndrome and associated with a broad range of neurodevelopmental, behavioral, and psychiatric challenges. FXS may be present in infants or young children with characteristic dysmorphic features, developmental delays, and behavioral challenges. The diagnosis of FXS is confirmed by the molecular genetic testing of the FMR1 gene encoding fragile X messenger RNA-binding protein (FMRP), involved in regulating the translation of multiple mRNAs which play a key role in neuronal development and synaptic plasticity. Understanding the genetic cause, pathophysiology, and natural history of FXS is crucial for identifying commonly associated comorbidities, instituting effective therapeutic interventions, and improving long-term outcomes. Methods: This systematic review employed a comprehensive literature search using multiple electronic databases including PubMed, Web of Science, and Scopus with keywords related to fragile X syndrome, lifespan, genetics, neurodevelopmental, behavioral, and psychiatric disorders. Results: FXS is associated with an increased risk for specific neurodevelopmental, or psychiatric disorders. Symptoms and challenges associated with FXS vary based on multiple factors, including genetic differences, age, sex, comorbid conditions, various environmental influences, the availability of support, and opportunities for therapeutic interventions. Knowledge of these associations helps guide caregivers and clinicians in identifying potentially treatable conditions that can help to improve the lives of affected patients and their families. Conclusions: The focus of this article is to explore and describe the genetic underpinnings of FXS, identify associated developmental, behavioral, and psychiatric conditions over the lifespan, and provide a review of clinical features, therapeutic interventions including investigational treatments, and current research updates. [ABSTRACT FROM AUTHOR]

Despite the potential of paid caregivers (e.g., home health aides and other home care workers) to improve their clients' health-related outcomes, paid caregivers are rarely integrated in the healthcare team. Geriatrician's perspective on paid caregivers can inform healthcare team approaches that leverage the paid caregiver role to improve older adult health. This secondary qualitative analysis (n = 9 geriatricians, n = 27 interviews) used thematic analysis to identify geriatrician perceptions of when paid caregivers do the most to support the health of older adults. Geriatricians perceived that paid caregiver contributions were greatest in the care of high-needs older adults (e.g., dementia) and that paid caregivers stepped up to fill healthcare gaps when families could not provide all needed support (e.g., no family). Future work should consider how to best integrate paid caregivers who are already providing health-related support into the care team and explore barriers to paid caregiver participation in health-related care more generally. [ABSTRACT FROM AUTHOR]

Introduction: Home care workers (HCWs) are paid caregivers who provide support to patients with chronic conditions and functional limitations. Additionally, they provide emotional support to patients and familial support. Although several qualitative studies have been conducted on HCWs, they focused more on studying prevalently the lived experiences about the workplace violence, the end of life, stressor and resilience, during the COVID-19 pandemic or focused more in dementia and heart failure, but not on feelings and working conditions. Methods: The study was carried out using Cohen's phenomenological methodology. The subjects were enrolled in several cities of Central Italy and interviewed with open questions to allow them full freedom of expression and asked to describe their lived experience of HCWs who helped people with chronic diseases. Each interview was recorded audio and lasted between 20 and 60 min. Researchers involved in the analysis were independently immersed in the data by reading and rereading the transcripts to gain a sense of the entire data set. The extrapolation of the themes followed. The individual researchers compared the various extrapolated themes. Results: Seventeen HCWs, all women, with a mean age of 54 years were enrolled in this study. All had more than a year (from 4 to 26 years) of experience in Italy, and almost the whole sample lived with the person they were assisting. Three themes were identified in the interviews: (1) feeling inadequate as a nurse, (2) feeling valued in this role, and (3) uncertain future. Feeling inadequate due to lack of training, difficulties related to the Italian language, or uncertainty about their future were topics identified by the HCWs. Conclusions: Since HCWs represent an important resource which, if properly trained, could positively influence the quality of life of the elderly population and a valid support for their families, understanding the lived experience can suggest interventions that could be implemented by a health care professional and provide evidence to inform political decision makers to increase the support for HCWs. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC) driven by the KRAS-G12D mutation presents a formidable health challenge because of limited treatment options. MRTX1133 is a highly selective and first-in-class KRAS-G12D inhibitor under clinical development. Here, we report that the advanced glycosylation end product–specific receptor (AGER) plays a key role in mediating MRTX1133 resistance in PDAC cells. The up-regulation of AGER within cancer cells instigates macropinocytosis, facilitating the internalization of serum albumin and subsequent amino acid generation. These amino acids are then used to synthesize the antioxidant glutathione, leading to resistance to MRTX1133 treatment due to the inhibition of apoptosis. The underlying molecular mechanism involves AGER's interaction with diaphanous-related formin 1 (DIAPH1), a formin protein responsible for driving Rac family small GTPase 1 (RAC1)–dependent macropinosome formation. The effectiveness and safety of combining MRTX1133 with pharmacological inhibitors of the AGER-DIAPH1 complex (using RAGE299) or macropinocytosis (using EIPA) were confirmed in patient-derived xenografts, orthotopic models, and genetically engineered mouse PDAC models. This combination therapy also induces high-mobility group box 1 (HMGB1) release, resulting in a subsequent antitumor CD8+ T cell response in immunocompetent mice. Collectively, the study findings underscore the potential to enhance the efficacy of KRAS-G12D blockade therapy by targeting AGER-dependent macropinocytosis. Editor's summary: Selective KRAS-G12D inhibitors have become an important treatment option for patients with KRAS-G12D–driven cancers, but the development of drug resistance can limit their efficacy. In this study by Li et al., the authors found that advanced glycosylation end product–specific receptor (AGER) contributed to MRTX1133 resistance in pancreatic ductal adenocarcinoma (PDAC) through modulation of macropinocytosis and glutathione synthesis using patient-derived xenografts and orthotopic and genetically engineered mouse models. The combination of MRTX1133 with inhibition of AGER or macropinocytosis improved survival and reduced tumor burden in a CD8+ T cell–dependent manner. These results suggest that this combination treatment may be an effective strategy to improve MRTX1133 efficacy in KRAS-G12D–driven PDAC and related cancers. —Allison Williams [ABSTRACT FROM AUTHOR]

Marfan syndrome (MFS) is an inherited disorder that affects the connective tissues and mainly presents in the bones, eyes, and cardiovascular system, etc. Aortic pathology is the leading cause of death in patients with Marfan syndrome. The fibrillin-1 gene (FBN1) is a major gene involved in the pathogenesis of MFS. It has been shown that the aortic pathogenesis of MFS is associated with the imbalances of the transforming growth factor-beta (TGF-β) signaling pathway. However, the exact molecular mechanism of MFS is unclear. Animal models may partially mimic MFS and are vital to the study of MFS. Several species of animals have been used for MFS studies, including chicks, cattle, mice, pigs, zebrafishes, Caenorhabditis elegans , and rabbits. These models were developed spontaneously or in combination with genetic engineering techniques. This review is to describe the TGF-β signaling pathway in MFS and the potential application of animal models to provide new therapeutic strategies for patients with MFS. [ABSTRACT FROM AUTHOR]

Simple Summary: The use of feed additives has been increasing in the aquaculture feed industry due to their potential to enhance production and profitability through physiological benefits, such as increased growth rates and fillet quality. Guanidinoacetic acid is a promising feed additive due to its physiological role as creatine precursor and its heat stability during feed manufacturing. The current study was designed to evaluate the effect of increasing doses of guanidinoacetic acid (0.00, 0.06, 0.12, and 0.18%) in rainbow trout (Oncorhynchus mykiss) growth, weight gain, and meat quality. We hypothesised that trout fed with the feed additive would have better performance, reaching its optimal physiological response at 0.12%. The results showed that trout fed guanidinoacetic acid presented better weight gain than trout 0.00%, with an optimal growth rate when fed 0.12%. Nonetheless, the level used was not enough to affect fillet quality. This study contributes to the aquaculture industry by determining the optimal level of guanidinoacetic acid for trout performance and its effects on fillet quality. These results can later be adapted to the reality of the aquaculture feed industry to improve fish performance and, consequently, profitability. Guanidinoacetic acid (GAA) plays an important role in cellular energy use and protein synthesis. The objectives of this study were to determine the optimal level of dietary GAA regarding the growth performance and fillet characteristics of rainbow trout (Oncorhynchus mykiss). A total of 300 trout (initial weight, 66.84 ± 7.82 g) were fed isonitrogenous (34%) and isocaloric (20.6 MJ kg−1) diets with increasing levels of GAA (0.00, 0.06, 0.12, 0.18%) for 90 days. The results showed that trout fed GAA (either 0.06, 0.12, or 0.18%) yielded better (p < 0.05) performance (BW, BWG, FCR, and SGR) than trout fed the control diet (0.00% GAA inclusion). No differences (p > 0.05) were observed for BW, BWG, nor FCR among trout fed GAA. Nonetheless, trout fed a diet with a 0.12% GAA inclusion had the highest (p < 0.01) SGR. Fillet quality was not affected by GAA supplementation (p > 0.05) for cook loss, shear force, nor colour. Trout fed 0.06% GAA inclusion tended (p = 0.08) to have a higher WHC. Moreover, trout fed 0.12 and 0.18% GAA had lower (p < 0.05) pH values than trout fed the control diet and 0.06% GAA. Our findings give insights for the growth promotion and fillet quality of trout fed diets supplemented with GAA, especially at the level of 0.12%. [ABSTRACT FROM AUTHOR]

No biomarker can effectively screen for early gastric cancer (EGC). Players in the A disintegrin and metalloproteinase (ADAM)-natural killer group 2 member D (NKG2D) receptor axis may have a role for that. As a proof-of-concept pilot study, the expression of ADAM8, ADAM9, ADAM10, ADAM12, ADAM17, and major histocompatibility complex (MHC) class I chain-related sequence A (MICA), a ligand for NKG2D, in gastric cancer was investigated in silico using The Cancer Genome Atlas (TCGA) database. Subsequently, the mRNA and protein expression levels of these markers except ADAM8 were tested in blood samples from patients with EGC and healthy controls. In the TCGA data analyses, EGC tissues (n = 57) expressed significantly higher mRNA levels of ADAM8, ADAM9, ADAM10, ADAM12, and ADAM17 than normal tissues (n = 35) (p < 0.005). In human blood sample analyses, ADAM12 (p = 0.0007), ADAM17 mRNA (p < 0.0001) and ADAM10 (p < 0.0017) protein were significantly elevated in patients with EGC (n = 27 for mRNA and n = 25 for protein) compared to the controls (n = 30 for mRNA and n = 26 for protein). Areas under the curves calculated by receiver-operating characteristic analysis for ADAM12, ADAM17 mRNA and ADAM10 protein were 0.7568 (95% confidence interval [CI]: 0.6334 to 0.8802), 0.8062 (95% CI: 0.6889 to 0.9234; p < 0.0001), and 0.8108 (95% CI: 0.6895 to 0.9320; p = 0.0001), respectively. Thus, ADAM12, ADAM17 mRNA and ADAM10 protein levels in peripheral blood could hold potential as biomarkers for screening EGC, and further investigations are required. [ABSTRACT FROM AUTHOR]

Simple Summary: Poultry are unable to synthesize arginine. Thus, it is essential to include enough arginine in poultry feed. One can save some arginine by means of providing the molecules in which arginine is needed as a building block. However, the question is how much arginine can these kinds of molecules replace in poultry feed. Herein, these questions are addressed in two trials comparing guanidinoacetic acid and arginine. Moreover, the energy-saving potential of guanidinoacetic acid is evaluated. Optimal performance in broiler chickens was achieved when birds were provided with higher dietary arginine content compared to the available recommendation tables. Supplementation of either arginine or guanidinoacetic acid with a low-arginine feed alleviated the lower performance. However, more guanidinoacetic acid was needed to provide the same level of growth attained with arginine (1 to 0.57 ratio). Reduction of dietary energy by 50 and 100 kcal/kg did not significantly influence the performance of birds at all stages of growth. Moreover, guanidinoacetic acid had no energy-sparing effect. This study helps the industry to accurately meet the arginine and energy requirements of broiler chickens. Two 35-day trials were conducted to determine the arginine (Arg) requirement of broiler chickens and the Arg and energy-sparing effects of guanidinoacetic acid (GAA). In experiment 1, a low-Arg diet (basal diet) was supplemented with increasing levels (0.06–0.61%) of L-Arg or GAA. In experiment 2, a diet meeting the energy and amino acid requirements of broiler chickens served as the positive control (PC). Two negative control (NC) groups were assigned by reducing either 50 (NC1) or 100 (NC2) kcal nitrogen-corrected metabolizable energy. Test groups were supplemented with 0.06% GAA for NC1 and 0.12% GAA for NC2 to compensate for the lower energy in the feed. The low dietary Arg concentration (starter: 1.02%, grower: 0.88%, finisher: 0.75%) significantly reduced overall performance (p < 0.05). Supplementation of either L-Arg or GAA with a low-Arg diet both alleviated the lower performance (p < 0.05). However, more GAA was needed to provide the same level of growth attained with L-Arg at an equivalency rate of 1 GAA to 0.57 Arg. Reduction of dietary energy by 50 and 100 kcal did not significantly influence the performance of birds at all stages of growth. Moreover, no effect of GAA supplementation at 0.06% or 0.12% was observed. [ABSTRACT FROM AUTHOR]

The rising prevalence of Alzheimer's disease and Alzheimer's disease–related dementias has led to renewed public discourse and policy changes in response to the care needs of persons living with dementia and their care partners. Comprehensive dementia care models are central to many recent policy initiatives, most notably the Centers for Medicare & Medicaid Services Guiding an Improved Dementia Experience model. Gerontological nursing research is uniquely positioned to design and lead research investigating the effectiveness of these initiatives, as well as the dissemination and scaling of existing comprehensive dementia care models. The current Annual State of the Science Review provides an overview of the current state of comprehensive dementia care models in the United States and relevant policies. Challenges and opportunities for nursing education, research, and implementation across the translational research continuum are also outlined. [Research in Gerontological Nursing, 18(1), 7–16.] [ABSTRACT FROM AUTHOR]

Background: Potentially inappropriate medications (PIMs) can lead to adverse outcomes. This study aimed to investigate the prevalence of PIMs in older Chinese outpatients with heart failure according to the 2019 Beers criteria and the factors associated with PIMs. Methods: A cross-sectional retrospective study was conducted using electronic medical data during January 1, 2020 to December 31, 2020 from 9 tertiary medical institutions in Chengdu, China. Outpatients aged 65 and above who were diagnosed with heart failure were included. The 2019 Beers criteria were used to evaluate the PIM status of older outpatients, and binary logistic regression was used to identify potential risk factors for PIMs. Results: There were 3626 prescriptions. The prevalence of PIMs among older outpatients with heart failure was 67.98% according to the 2019 Beers criteria. Diuretics, non-steroidal anti-inflammatory drugs (NSAIDs), benzodiazepine receptor agonist hypnotics, rivaroxaban, and dabigatran were the top five PIMs. The risks of PIMs were associated with the number of drugs prescribed and comorbidities. PIMs were shown to be more common in patients with polypharmacy (5–9 medications, OR: 10.403, 95% CI: 8.258–13.104, p < 0.001; ≥10 medications, OR: 35.018, 95% CI: 10.545-116.293, p < 0.001), valvular heart disease (OR: 1.537, 95% CI: 1.109–2.131, p = 0.010), and insomnia (OR: 2.655, 95% CI: 1.809–3.898, p < 0.001). While, medicare reimbursement (OR: 0.678, 95% CI: 0.570–0.808, p < 0.001) and visits to the geriatric departments (department of cardiology, OR: 1.687, 95% CI: 1.214–2.344, p = 0.002) were protective factors. Conclusions: The prevalence of PIMs use was high among older Chinese outpatients with heart failure, according to this study. Multidisciplinary teams should cooperate to reduce PIMs in older adults. [ABSTRACT FROM AUTHOR]

We aimed to review the association of dietary fats and risk of coronary events in adults. We searched PubMed, Embase, CENTRAL, Scopus, and Web of Sciences to April 2022 for prospective cohorts and randomized trials investigating the association of dietary intake and biomarkers of fats and fatty acid interventions and the risk of coronary events. We performed random-effects meta-analyses to estimate relative risk (RR) for the top versus bottom tertiles of exposures. One-hundered sixty-five prospective cohorts and randomized trials were included. Dietary intake and biomarkers of total fat and saturated, monounsaturated, and polyunsaturated fatty acids were not associated with the risk of coronary events. Dietary intake of trans fatty acids, palmitic acid, stearic acid, and saturated fatty acids from meat and unprocessed meat was modestly associated with a higher risk and, in contrast, intake of alpha-linolenic acid, long-chain omega-3 fatty acids, and linoleic acid was modestly associated with a lower risk. Supplementation with long-chain omega-3 fatty acids and increasing the consumption of alpha-linolenic and linoleic acids in place of saturated fats reduced the risk of coronary events. Existing evidence, in its totality, provides a modest support in favor of current recommendations suggesting replacement of saturated fats with polyunsaturated fats. [ABSTRACT FROM AUTHOR]

Background: Rearing poultry under stressful high stocking density (HSD) conditions is a common commercial practice to increase profitability, despite its negative effects on broiler physiology and welfare. Many feed additives are used to alleviate the negative impact of such practices. This study investigated the ameliorative effects of guanidinoacetic acid (GAA) on growth performance, ingestive behavior, immune response, antioxidant status, stress indicators, and intestinal histomorphometry of broilers subjected to HSD. A total of 364 male broilers were randomly allocated into four treatments with 7 replicates each in a 2 × 2 factorial arrangement: two stocking densities (SD) (10 and 16 birds/m2) and two GAA levels (0 and 0.6 g/kg feed). Results: Body weight, weight gain, feed intake, feed conversion ratio, production efficiency factor, dressing yield, and ingestive behavior were negatively affected by HSD, whereas the mortality rate was unaffected (P > 0.05). GAA improved the overall growth performance and dressing percentage (P < 0.05). In the HSD group, the immune response decreased at d 21 (P < 0.05). Creatine kinase, glutathione peroxidase (GPX), superoxide dismutase, catalase, triglycerides, and villus length and width (ileum) were reduced, whereas corticosterone (CORT) was increased (P < 0.05). Moreover, GAA increased the hemagglutination-inhibition titer at 21 days and the levels of lactate dehydrogenase, GPX, and catalase and decreased the levels of creatinine, alanine aminotransferase, nitrite, triglycerides, and CORT (P < 0.05). SD and GAA did not affect malondialdehyde or other biochemical parameters (P > 0.05). Conclusions: Dietary GAA supplementation can improve productivity and antioxidant status and reduce stress in broilers reared in a HSD environment. [ABSTRACT FROM AUTHOR]

Programmed cell death, especially programmed necrosis such as necroptosis, ferroptosis, and pyroptosis, has attracted significant attention recently. Traditionally, necrosis was thought to occur accidentally without signaling pathways, but recent discoveries have revealed that molecular pathways regulate certain forms of necrosis, similar to apoptosis. Accumulating evidence indicates that programmed necrosis is involved in the development of various diseases, including myocardial ischemia–reperfusion injury (MIRI). MIRI occurs when blood flow and oxygen return to an ischemic area, causing excessive production of reactive oxygen species. While this reperfusion is critical for treating myocardial infarction, it inevitably causes cellular damage via oxidative stress. Furthermore, this cellular damage triggers multiple forms of cardiomyocyte death, which is the primary cause of inflammation, cardiac tissue remodeling, and ensuing heart failure. Therefore, understanding the molecular mechanisms of various forms of cell death in MIRI is crucial for therapeutic target discovery. Developing therapeutic strategies to inhibit multiple cell death pathways simultaneously could provide effective protection against MIRI. In this paper, we review the fundamental molecular pathways and MIRI-specific mechanisms of apoptosis, necroptosis, ferroptosis, and pyroptosis. Additionally, we suggest that the simultaneous suppression of multiple cell death pathways could be an effective therapy and identify potential therapeutic targets for implementing this strategy. [ABSTRACT FROM AUTHOR]

Background/Objectives: Like in the general population, the prevalences of eating- and weight-related health issues in the armed forces are increasing. Relevant medical conditions include the eating disorders (EDs) anorexia nervosa, bulimia nervosa, binge eating disorder, and avoidant restrictive food intake disorder (ARFID), as well as body dysmorphic disorder, muscle dysmorphia, and the relative energy deficiency in sport (RED-S) syndrome. Methods: We performed a narrative literature review on eating- and weight-related disorders in the armed forces. Results: Entry standards might exclude people with obesity, with EDs, or at high risk for EDs from entering the armed forces for military reasons and to protect the individual's health. Relevant potential risk factors of eating- and weight-related disorders in the military are the emphasis on appearance and fitness in the military, high levels of stress, military sexual trauma, post-traumatic stress disorder, deployment, relocation, long commutes, consumption of ultra-processed foods and beverages, limitations on food selection and physical exercise, and intensive combat training and field exercises. Eating- and weight-related disorders negatively impact professional military appearance and lead to problems with cardiorespiratory and neuromuscular fitness; daytime sleepiness; and a higher risk of musculoskeletal injuries, and other physical and mental health problems. Current and potential future therapeutic options include occupational health measures, psychosocial therapies, neuromodulation, and drug treatments. Conclusions: Even though randomized controlled trials (RCTs) have been performed to test treatments for obesity in the armed forces, RCTs for the treatment of EDs, body dysmorphic disorder, muscle dysmorphia, and RED-S syndrome are lacking in the military context. [ABSTRACT FROM AUTHOR]

This study leverages the theories of racialized and gendered organizations as frameworks to examine a Southeastern school district's aspiring leadership program and hiring practices to determine the extent to which they produce and reproduce gender and race-based norms that promote workplace exclusion for women and people of color interested in the school principalship. Data were obtained from interviews with district administrators, school administrators, and teachers (n = 12). Findings provide support that the district operates in a manner consistent with a racialized and gendered organization. Results are discussed, and implications for improvement are provided. [ABSTRACT FROM AUTHOR]

The living lab (LL) concept has a significant potential to drive sustainable development, particularly in the bioeconomy sector, by assisting communities in improving their quality of life whilst also considering the environmental impact. In this context, the main research question was the following: is there any specific mechanism through which living labs operate under the sustainable development concept? We reviewed 120 papers addressing this topic and performed a bibliometric analysis on the linkage between sustainability and living labs by applying the methodology of a systematic review. We concluded that living labs can drive innovation and experimentation in sustainability, which can be transposed into tangible solutions to economic, environmental, and social problems. The role of living labs in the transition to a bioeconomy is discussed and further research directions are presented. [ABSTRACT FROM AUTHOR]

Social isolation and loneliness are associated with negative health outcomes, and these outcomes are exacerbated among older adults who are homebound. To address this issue, Meals on Wheels programs increasingly provide social connection services to clients in addition to home-delivered meals. This descriptive qualitative study examines the impact of three types of social connection programs on the well-being of homebound older adult clients, as well as on the volunteers and staff members who deliver the programs. Thematic analysis of semi-structured interviews conducted with 117 clients, volunteers, and staff in six Meals on Wheels social connection programs across the United States indicated that program participation was associated with substantial benefits. Benefits included the development of supportive friendships, reduced feelings of loneliness, and an improved overall sense of well-being. Insights from this study may inform the development, expansion, and sustainability of social connection programs provided by community-based organizations. [ABSTRACT FROM AUTHOR]

Background: Globally, diabetic kidney disease (DKD) has become the leading cause of end-stage renal disease, imposing substantial social and economic costs. This meta-analysis was designed to provide valuable insights into gene-disease interactions by investigating the potential association between lipid metabolism gene polymorphisms and the risk of DKD. Methods: An electronic literature search was conducted on MEDLINE Complete, Web of Science, Embase, and PubMed. A total of 18 studies on the peroxisome proliferator-activated receptor γ (PPARγ) Pro12Ala variant and 20 publications concerning apolipoprotein E (ApoE) gene polymorphism were included in the meta-analysis. Results: Overall, the PPARγ Pro12Ala polymorphism was found to be significantly associated with a decreased DKD risk (OR = 0.74, 95% CI: 0.62–0.88). In subgroup analysis, Ala carriers were less susceptible to DKD than Pro homozygotes among Asian (OR = 0.73, 95% CI: 0.56–0.95) and Caucasian populations (OR = 0.74, 95% CI: 0.59–0.93). Subgroup analysis stratified by albuminuria categories showed that the PPARγ Pro12Ala polymorphism reduced the risk of both microalbuminuria and macroalbuminuria with corresponding ORs of 0.58 (95% CI: 0.43–0.78) and 0.68 (95% CI: 0.53–0.86). Sensitivity analysis confirmed the robustness of the meta-analysis results. However, publication bias was identified in the subgroup analysis of the Caucasian population. The primary analysis of the ApoE gene polymorphism yielded significant findings, indicating that ApoE ε2/ε2, ApoE ε2/ε3, and ApoE ε2/ε4 genotypes increase the risk of DKD (ε2/ε2 vs. ε3/ε3: OR = 1.93, 95% CI: 1.03–3.61; ε2/ε3 vs. ε3/ε3: OR = 1.63, 95% CI: 1.19–2.25; ε2/ε4 vs. ε3/ε3: OR = 1.87, 95% CI: 1.37–2.55). However, sensitivity analysis suggested that influential and Hardy-Weinberg equilibrium (HWE)-violating studies may impact the overall effect estimates. Conclusions: A meta-analysis showed that PPARγ gene polymorphism may be a protective factor for DKD, whereas the ApoE ε2/ε2, ApoE ε2/ε3, and ApoE ε2/ε4 genotypes are associated with an increased risk of DKD. However, the role of ApoE gene polymorphism in susceptibility to DKD is less certain and requires further evaluation. [ABSTRACT FROM AUTHOR]

This experiment aimed to study the effects of guanidine acetic acid (GAA) on reproductive performance, lactation performance and blood biochemical indices of sows, as well as the performance of offspring piglets. A total of 20 sows (Landrace × Yorkshire, parity 4) were used. Half of the sows in each parity were fed a control diet (CG; basic diet, n = 10) or GAA diet (basic diet +1 g/kg GAA, n = 10) from the 85th day of gestation until weaning. The study results are presented as follows: Supplementation of GAA from late gestation to lactation did not adversely affect sow feed intake, backfat thickness, or blood routine indexes (p > 0.05). GAA supplementation showed a tendency to increase the number of healthy piglets and their birth activity (p = 0.06; p = 0.08), while significantly increasing the IUGR score of piglets (p < 0.05). GAA supplementation significantly increased colostrum protein content (p < 0.05) and tended to increase daily milk yield in sows (p = 0.07). GAA supplementation increased the level of immunoglobulin A in sow colostrum (p < 0.05) and showed a tendency to increase proline content (p = 0.10). GAA supplementation significantly decreased triglyceride content in sow cord blood (p < 0.05), with no significant effects observed on HDL-C, LDL-C, TC, and GLU (p > 0.05). GAA supplementation significantly increased eNOS levels in sow cord blood (p < 0.05), while showing no significant effects on IL-6 and IL-10 (p > 0.05). GAA supplementation did not significantly affect the α diversity of sow intestinal flora (ACE, Shannon, Chao1, Simpson, observed_otus, pielou_e, and good_cover), but PCoA analysis revealed differences in intestinal flora structure between groups. Additionally, GAA decreased the relative abundance of Sarciha and unidentified_ruminococcaceae and increased the relative abundance of Lactobacillus , Parabacteroides , and Pedobacter in the gut. GAA boosts nitric oxide synthase in sows' umbilical cord blood, enhancing placental blood vessel development. This improves piglet health and vitality, increases beneficial gut bacteria (Lactobacillus , Parabacteroides , Pedobacter), and raises colostrum protein levels and lactation volume, leading to better piglet growth and performance. [ABSTRACT FROM AUTHOR]

The mineralocorticoid system, comprising the renin-angiotensin-aldosterone system (RAAS) and associated receptors, is traditionally viewed as a regulator of sodium and fluid balance and blood pressure (BP), with the main mineralocorticoid hormone aldosterone acting via the mineralocorticoid receptor (MR) in distal renal tubules. Over the past few decades, there has been a wider understanding of the role of the mineralocorticoid system in regulating both classical BP-dependent and non-BP-dependent systemic effects. Mounting evidence indicates the novel role of the mineralocorticoid system in cardiometabolic health, with excess mineralocorticoid system activity being associated with adiposity, diabetes, insulin resistance and cardiovascular diseases independent of its effect on BP, and RAAS blockade and MR antagonists offering protection against cardiometabolic dysfunction. The metabolic manifestations of mineralocorticoid system overactivation are mainly mediated by their interactions with adipose tissue, which orchestrates energy, lipids, and glucose homeostasis via effects on the functions of brown and white adipocytes and immune cells. Adipose tissue can, in turn, influence mineralocorticoid system activity by harboring its own RAAS system and by releasing mineralocorticoid-secretory factors/adipokines, resulting in further progression of cardiometabolic dysfunction. This article discusses the interplay between the mineralocorticoid system and adipose tissue in the pathophysiology of cardiometabolic diseases. [ABSTRACT FROM AUTHOR]

When domestic violence first became recognized as a social problem, services (e.g., hotlines, medical accompaniment, and emergency shelters) focused largely on meeting victims' needs during crisis. Research documenting the process survivors go through to end abusive relationships and to establish a new, safe life shows that the challenges they face go well beyond the initial crisis. In contrast to standard practices, the Chesapeake Crisis to Self-Sufficiency Model (CCSSM) provides a continuum of holistic, survivor-centered services to support the transition from crisis to self-sufficiency. Staff interviews reveal that the CCSSM grew out of recognizing clients' needs postcrisis. Establishing service continuums in critical areas such as housing, legal assistance, and economic empowerment creates customizable pathways for clients to follow. Administrative data for 464 survivors receiving services under the traditional model and 607 served under the CCSSM show that the CCSSM cohort worked with the agency for significantly more months and received a broader array of services. These data suggest that the comprehensive service model provides survivors with much needed services beyond the initial crisis and may ultimately increase their chances of leaving an abusive relationship. Future research should explore if the CCSSM leads to increased survivor safety and movement toward self-sufficiency and if the model decreases the odds that survivors will return to an abusive partner. [ABSTRACT FROM AUTHOR]

Multiple cancers, including colorectal cancer (CRC), are more frequent and often more aggressive in individuals with obesity. Here, we showed that macrophages accumulated within tumors of patients with obesity and CRC and in obese CRC mice and that they promoted accelerated tumor growth. These changes were initiated by oleic acid accumulation and subsequent tumor cell–derived acid production and were driven by macrophage signaling through the acid-sensing receptor GPR65. We found a similar role for GPR65 in hepatocellular carcinoma (HCC) in obese mice. Tumors in patients with obesity and CRC or HCC also exhibited increased GPR65 expression, suggesting that the mechanism revealed here may contribute to tumor growth in a range of obesity-associated cancers and represent a potential therapeutic target. Editor's summary: Obesity is a risk factor for the development of several types of cancer, but how obesity contributes to tumorigenesis remains incompletely understood. Using a mouse model of colon cancer, Bagchi et al. found that tumor-associated macrophages (TAMs) accumulate and drive tumor growth in obese mice. Obesity-associated accumulation of oleic acid enhanced tumor acidity and suppressed TAM inflammatory responses. During obesity, TAMs up-regulated the acid-sensing receptor GPR65, which promoted growth of both colon and liver tumors. Together, these findings identify tumor acidity and GPR65-mediated TAM adaptations as drivers of tumor growth in obesity-associated cancers. —Claire Olingy [ABSTRACT FROM AUTHOR]

Ovarian cancer (OvCa) is the gynaecological disorder with the poorest prognosis due to the fast development of chemoresistance. We sought to connect chemoresistance and cancer cell-derived extracellular vesicles (EV). The mechanisms of how chemoresistance is sustained by EV remained elusive. One potentially contributing factor is A Disintegrin and Metalloprotease 17 (ADAM17)-itself being able to promote chemoresistance and inducing tumour cell proliferation and survival via the Epidermal Growth Factor Receptor (EGFR) pathway by shedding several of its ligands including Amphiregulin (AREG). We now demonstrate that upon chemotherapeutic treatment, proteolytically active ADAM17 is released in association with EV from OvCa cells. In terms of function, we show that patient-derived EV induce AREG shedding and restore chemoresistance in ADAM17-deficient cells. Confirming that ADAM17-containing EV transmit chemoresistance in OvCa, we propose that ADAM17 levels (also on EV) might serve as an indicator for tumour progression and the chemosensitivity status of a given patient., (© 2023 The Authors. Journal of Extracellular Vesicles published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles.)

The impact of 1.8 MeV proton irradiation on metalorganic chemical vapor deposition grown (010) β -Ga2O3 Schottky diodes is presented. It is found that after a 10.8 × 10 13 cm − 2 proton fluence the Schottky barrier height of (1.40 ± 0.05 eV) and the ideality factor of (1.05 ± 0.05) are unaffected. Capacitance–voltage extracted net ionized doping curves indicate a carrier removal rate of 268 ± 10 cm − 1 . The defect states responsible for the observed carrier removal are studied through a combination of deep level transient and optical spectroscopies (DLTS/DLOS) as well as lighted capacitance–voltage (LCV) measurements. The dominating effect on the defect spectrum is due to the EC - 2.0 eV defect state observed in DLOS and LCV. This state accounts for ∼ 75 % of the total trap introduction rate and is the primary source of carrier removal from proton irradiation. Of the DLTS detected states, the EC - 0.72 eV state dominated but had a comparably smaller contribution to the trap introduction. These two traps have previously been correlated with acceptor-like gallium vacancy-related defects. Several other trap states at E C -0.36, E C -0.63, and E C -1.09 eV were newly detected after proton irradiation, and two pre-existing states at E C -1.2 and E C -4.4 eV showed a slight increase in concentration after irradiation, together accounting for the remainder of trap introduction. However, a pre-existing trap at EC - 0.40 eV was found to be insensitive to proton irradiation and, therefore, is likely of extrinsic origin. The comprehensive defect characterization of 1.8 MeV proton irradiation damage can aid the modeling and design for a range of radiation tolerant devices. [ABSTRACT FROM AUTHOR]

Site-specific conjugation approaches are of great importance in drug discovery, notably for the synthesis of biochemical probes or molecular conjugates for targeted delivery. Herein, we report a mild ionic liquid (IL)-mediated thiolation technique that relies on the use of 1,3-ethyl-methyl imidazolium acetate, [C 2 mim][OAc] as a solvent and precursor to generate activated IL, as well as a solvent for the conjugation reaction. First, a focused library of active ILs was prepared for functionalizing/conjugating cysteine-containing small molecules and unprotected peptides. Interestingly, a bifunctional active IL could also be successfully employed as a linker for the conjugation of peptides lacking Cys. This study sets the ground for further investigation of the use of active ILs for modifying, labeling or conjugating larger and more complex therapeutic modalities such as proteins and antibodies., (© 2023 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

Media narratives employed in contemporary journalism, including data journalism, are critical in shaping public understanding of the complex systems that affect our lives. Depicting a chain of events in a "story" format, narratives are constructed with detailed, precise, and well-researched information based on character identification, human emotions, and real social problems. In many ways, they are indispensable intermediaries of practiced judgment and expertise that guide the public to meaningfully engage with evidence-based understanding of our world and how we can act upon it. DMDU narratives suggest that we can act to shape the future toward our liking even when we cannot predict what that future will be, that we need to simultaneously consider multiple rather than a single future, and that the quest for prediction can interfere with the task of identifying the best actions. DMDU practice relies on substantive stakeholder interaction, and it is supported by vast amounts of empirical evidence. This perspective discusses how media narratives intersect with DMDU to informand to leverage the complexities ofmodern contemporary public challenges. We first explore how uncertainty might be actionable, as opposed to fearful. Next, while acknowledging limitations on transference of information during the journalistic process, we address the challenges and best strategies to distill information to the public to maintain and build trust about uncertainty. Next, we discuss how journalistic practices could be useful for disseminating more broadly findings of DMDU analyses. [ABSTRACT FROM AUTHOR]

Ecological design is crucial in shaping contemporary, resilient, and livable cities. The Santa Cruz de Tenerife Refinery, a prominent landmark in the Mid-Atlantic, serves as an exemplary case study for understanding advanced metropolitan processes and integrating trans-scalar, transdisciplinary, and nature-based solutions (NBS) practices into urban contexts. This article explores the challenges of transforming obsolete industrial areas, including the refinery's decommissioning process, its port, and industrial heritage value, and their relationship with the sea, into vibrant urban cores. It examines innovative strategies for land use, decontamination, and urban resilience, which are vital for fostering adaptability and recovery from natural and anthropogenic disasters. By emphasizing the refinery's connection to Santa Cruz de Tenerife and its metropolitan area, as well as its coastal interface, this study proposes a comprehensive methodology to assess the territorial impacts of urban processes and guide project decisions toward enhancing the quality of life for the region's residents. [ABSTRACT FROM AUTHOR]

Older adults are a high in risk of severe COVID-19 disease outcomes and experience "vaccine hesitancy." Guided by health communication models such as the Reasoned Action Approach and the Extended Parallel Process Model, online surveys designed to inform statewide public health communication efforts were administered in West Virginia, a primarily rural and fully Appalachian state, in Winter 2021 (n = 272) and Fall 2022 (n = 248). Adults ages 50+ years (N = 520) reported attitudes, intentions, and behaviors regarding COVID-19 vaccination and their related patient-provider communication. Vaccine usefulness/safety, perceived effectiveness, and subjective norms predicted behavior while perceived severity, efficacy, and usefulness/safety predicted intention to get a booster, specifically the updated Fall 2022 Omicron (bivalent) booster. As patient-provider communication (which a minority reported receiving) was a strong predictor of behavioral outcomes, characteristics of effective healthcare provider communication and considerations for public message construction are discussed. [ABSTRACT FROM AUTHOR]

Home care aides play a critical role in the care of older adults, but they do this under difficult working conditions. The COVID-19 pandemic exacerbated aides' stress and worsened their mental health, raising the question of how agencies can better support aides. We explore how home care industry leaders in New York perceived and addressed home care aides' mental health and well-being prior to and during the pandemic through in-depth interviews conducted in 2019 (n = 8 agencies) and 2022 (n = 14 agencies). We found that these topics became more central in leaders' thinking, reflected in a range of new internally and externally funded agency actions, albeit limited by ongoing financial constraints. Maintaining a skilled and reliable aide workforce is critical to societal health but will remain challenging without continued investment in aide support of the kind described in the Surgeon General's Framework for Workplace Mental Health and Well-Being. [ABSTRACT FROM AUTHOR]

CD8+ T cell activation leads to the rapid proliferation and differentiation of effector T cells (Teffs), which mediate antitumor immunity. Although aerobic glycolysis is preferentially activated in CD8+ Teffs, the mechanisms that regulate CD8+ T cell glucose uptake in the low-glucose and acidic tumor microenvironment (TME) remain poorly understood. Here, we report that the abundance of the glucose transporter GLUT10 is increased during CD8+ T cell activation and antitumor immunity. Specifically, GLUT10 deficiency inhibited glucose uptake, glycolysis, and antitumor efficiency of tumor-infiltrating CD8+ T cells. Supplementation with glucose alone was insufficient to rescue the antitumor function and glucose uptake of CD8+ T cells in the TME. By analyzing tumor environmental metabolites, we found that high concentrations of lactic acid reduced the glucose uptake, activation, and antitumor effects of CD8+ T cells by directly binding to GLUT10's intracellular motif. Disrupting the interaction of lactic acid and GLUT10 by the mimic peptide PG10.3 facilitated CD8+ T cell glucose utilization, proliferation, and antitumor functions. The combination of PG10.3 and GLUT1 inhibition or anti–programmed cell death 1 antibody treatment showed synergistic antitumor effects. Together, our data indicate that GLUT10 is selectively required for glucose uptake of CD8+ T cells and identify that TME accumulated lactic acid inhibits CD8+ T cell effector function by directly binding to GLUT10 and reducing its glucose transport capacity. Last, our study suggests disrupting lactate-GLUT10 binding as a promising therapeutic strategy to enhance CD8+ T cell–mediated antitumor effects. Editor's summary: CD8+ T cells are a critical part of antitumor immunity and depend on metabolites including glucose to maintain their function. Here, Liu et al. have evaluated targeting glucose transport 10 (GLUT10) as a way to increase CD8+ T cell function by disrupting the competitive binding of lactic acid that increased glucose uptake, thereby increasing proliferation and antitumor capacity. Authors developed a mimic peptide, PG10.3, to treat mouse models alone or in combination with anti–programmed cell death 1 to improve antitumor effects. This represents a new potential therapeutic option to improve outcomes for patients undergoing immunotherapy that will require further study. —Dorothy Hallberg [ABSTRACT FROM AUTHOR]