Xylose Incorporated in Unsymmetrical Gold(I) N-Heterocyclic Carbene Complexes: Synthesis, Characterization and Antibacterial Activity.

A series of Au(I) complexes containing unsymmetrical N-heterocyclic carbene (imidazolylidene and benzimidazolylidene) functionalized with a xyloside group and an alkyl moiety (methyl and mesityl) was prepared using efficient procedures from D-xylose. Their characterization was carried out in solution by multinuclear NMR, HR-MS spectrometry and cyclic voltammetry, as well as in the solid state by means of single crystal X-ray diffraction analysis for two of them. Evaluation of their ability to inhibit bacterial growth showed a preference for a Gram-positive strain, Staphylococcus aureus, over a Gram-negative strain, Pseudomonas aeruginosa.

The Efficacy of GLP-1 Agonists in Treating Substance Use Disorder in Patients: A Scoping Review.

ABSTRACT: Substance use disorder (SUD) continues to be a leading cause of morbidity and mortality with limited treatments. There is interest in expanding the use of GLP-1 agonists in treating SUD. However, evidence for safety and efficacy in humans is limited. This review aims to bridge the existing knowledge gap by establishing a baseline of literature in this area to inform future trials and clinical practice. Our inclusion criteria were English peer-reviewed manuscripts reporting on use of GLP-1, GIP, and/or glucagon receptor agonists in treatment of SUDs, excluding case studies. The literature search was performed in accordance to PRISMA guidelines. Five studies were included in this review examining the use of this medication in tobacco use disorder, alcohol use disorder, and cocaine use disorder. No studies regarding substance withdrawal syndrome were identified. The included studies varied widely in terms of patient selection, dose/formulation of GLP-1 agonists, and follow-up. The results of this scoping review are mixed, with 3 studies demonstrating positive results and 2 studies finding no efficacy of this medication on SUD outcomes. It is premature to prescribe this medication off-label to patients. Further research is needed to determine the efficacy of GLP-1 agonists in treating SUD.

Intersectional trends in child and adolescent suicide-related emergency department encounters in Florida (2016‒2021).

Objectives: Emergency department (ED) visits resulting from suicidal thoughts and behaviors have increased at alarming rates among youth in the United States in recent years. Understanding trends among specific racial, ethnic, gender, and/or age subgroups can provide the foundation for tailored solutions for those with the greatest need for support. Methods: Using data from the Florida State Emergency Department Database from 2016 to 2021, we calculated annual rates of ED suicide-related diagnoses per 1000 young people aged 8‒21 years. We explored annual trends by age and intersectional race/ethnicity and sex subgroups. Additionally, we examined subgroup-specific stratified percent changes from 2016 to 2019 and 2016 to 2021. Results: Among 8‒12-year olds, the highest rates of suicide-related ED encounters occurred among Black males and females and this trend was steady over time. Among 13‒21-year-old patients, Black and White females displayed the highest rates of suicide-related ED encounters across 2016‒2021, and all subgroups experienced a slight decline in 2020 and 2021. Rates generally increased between 2016 and 2019, with the largest percent increase (10.6%) occurring among Black females aged 18‒21 years, whereas there was a trend of decreased rates among most subgroups between 2019 and 2021. Conclusions: Across all years and age groups, Black females showed consistently higher rates of suicide-related ED encounters than almost any other subgroup, supporting previous research that Black adolescent females may be disproportionately suffering from the mental health crisis faced by young people. Furthermore, preteen Black males need additional mental health support, as do adolescent and young adult White females.

Glucagon-like peptide-1 (GLP-1) receptor agonists for weight management: A review for the gynecologic oncologist.

The use of glucagon-like peptide-1 receptor agonists (GLP-1RA) has experienced rapid growth amidst the obesity epidemic in the United States. While originally developed for glucose control in Type 2 Diabetes Mellitus, the scope of these agents now extends to encompass weight loss and cardiovascular risk reduction. GLP-1RAs have the potential to induce significant weight loss, in combination with lifestyle modifications, among adults who are overweight or obese. Furthermore, these agents demonstrate efficacy in ameliorating hyperglycemia, enhancing insulin sensitivity, regulating blood pressure, improving cardiometabolic parameters, mitigating kidney dysfunction, and potentially reducing the risk of several obesity-related cancers. Drug-related toxicity is primarily gastrointestinal and active management can prevent drug discontinuation. Obesity is associated both with an increased incidence of malignancy but also with decreased survival. More research is needed to evaluate the potential use of GLP-1RA to modify the endocrine function of adipocytes, regulate the chronic inflammatory state associated with obesity, and prospective applications in oncology. These agents can impact patients with gynecologic malignancies both through their direct mechanism of action as well as potential drug toxicity.

Combined measures in lake restoration - A powerful approach as exemplified from Lake Groote Melanen (the Netherlands).

Controlling lake eutrophication is a challenge. A case-specific diagnostics driven approach is recommended that will guide to a suite of measures most promising in restoration of eutrophic lakes as exemplified by the case of the shallow lake Groote Melanen, The Netherlands. A lake system analysis identified external and internal nutrient load as main reasons for poor water quality and reoccurring cyanobacterial blooms in the lake. Based on this analysis, a package of restoration measures was implemented between January 2015 and May 2016. These measures included fish removal, dredging, capping of peat rich sediment with sand and an active barrier (lanthanum-modified bentonite), diversion of two inlet streams, reconstruction of banks, and planting macrophytes. Dredging and sand capping caused temporarily elevated turbidity and suspended solids concentrations, while addition of the lanthanum-modified clay caused a temporary exceedance of the Dutch La standard for freshwaters. Diversion of inflow streams caused 35 % less water inflow and larger water level fluctuations, but the lake remained water transporting with strongly improved water quality as was revealed by comparing five years pre-intervention water quality data with five years' post-intervention data. Total phosphorus concentration in the water column was reduced by 93 % from 0.47 mg P l-1 before the intervention to 0.03 mg P l-1 after the intervention, total nitrogen by 66 % from 1.27 to 0.21 mg N l-1, total chlorophyll-a by 75 % from 68 to 16 µg l-1, cyanobacteria chlorophyll-a by 88 % from 32 to 4 µg l-1. Turbidity had declined by 58 % from 23.5 FTU to on average 9.9 FTU. No cyanobacteria blooms were recorded over the entire post-intervention monitoring period (2016-2021). Submerged macrophytes increased from complete absence before intervention to around 10 %-15 % coverage after intervention. Repeated fish removal lowered the fish stock to below 100 kg ha-1 with 12 % of bream and carp remaining. Hence, the package of cohesive measures that was based on a thorough diagnosis resulted in rapidly, strongly and enduringly improved water quality. This case provides evidence for the power of combining measures in restoring eutrophic lakes.

Predictability of varicocele repair success: preliminary results of a machine learning-based approach.

Varicocele is a prevalent condition in the infertile male population. However, to date, which patients may benefit most from varicocele repair is still a matter of debate. The purpose of this study was to evaluate whether certain preintervention sperm parameters are predictive of successful varicocele repair, defined as an improvement in total motile sperm count (TMSC). We performed a retrospective study on 111 patients with varicocele who had undergone varicocele repair, collected from the Department of Endocrinology, Metabolic Diseases and Nutrition, University of Catania (Catania, Italy), and the Unit of Urology at the Selcuk University School of Medicine (Konya, Türkiye). The predictive analysis was conducted through the use of the Brain Project, an innovative tool that allows a complete and totally unbiased search of mathematical expressions that relate the object of study to the various parameters available. Varicocele repair was considered successful when TMSC increased by at least 50% of the preintervention value. For patients with preintervention TMSC below 5 × 106, improvement was considered clinically relevant when the increase exceeded 50% and the absolute TMSC value was >5 × 106. From the preintervention TMSC alone, we found a model that predicts patients who appear to benefit little from varicocele repair with a sensitivity of 50.0% and a specificity of 81.8%. Varicocele grade and serum follicle-stimulating hormone (FSH) levels did not play a predictive role, but it should be noted that all patients enrolled in this study were selected with intermediate- or high-grade varicocele and normal FSH levels. In conclusion, preintervention TMSC is predictive of the success of varicocele repair in terms of TMSC improvement in patients with intermediate- or high-grade varicoceles and normal FSH levels.

Potato soup: analysis of cultivated potato gene bank populations reveals high diversity and little structure.

Cultivated potatoes are incredibly diverse, ranging from diploid to pentaploid and encompass four different species. They are adapted to disparate environments and conditions and carry unique alleles for resistance to pests and pathogens. Describing how diversity is partitioned within and among these populations is essential to understanding the potato genome and effectively utilizing landraces in breeding. This task is complicated by the difficulty of making comparisons across cytotypes and extensive admixture within section petota. We genotyped 730 accessions from the US Potato genebank including wild diploids and cultivated diploids and tetraploids using Genotype-by-sequencing. This data set allowed us to interrogate population structure and diversity as well as generate core subsets which will support breeders in efficiently screening genebank material for biotic and abiotic stress resistance alleles. We found that even controlling for ploidy, tetraploid material exhibited higher observed and expected heterozygosity than diploid accessions. In particular group chilotanum material was the most heterozygous and the only taxa not to exhibit any inbreeding. This may in part be because group chilotanum has a history of introgression not just from wild species, but landraces as well. All group chilotanum, exhibits introgression from group andigenum except clones from Southern South America near its origin, where the two groups are not highly differentiated. Moving north, we do not observe evidence for the same level of admixture back into group andigenum. This suggests that extensive history of admixture is a particular characteristic of chilotanum.

A sociocultural approach to understanding collective trauma in Indigenous communities.

Research on the effects of collective trauma tends to take a psychocentric approach, focusing on the impact of being geographically near the traumatic event (physical proximity) or personally knowing a victim (social proximity). We theorize that this approach falls short in describing the effect of collective trauma among interdependent cultural groups, such as Indigenous Peoples, for whom the self and one's group are inextricably tied. Using a concurrent embedded mixed-methods design (N = 545), the current study explores the influence of cultural proximity (having a shared cultural connection to victims) in the wake of a fatal school shooting involving students from both a Native American tribe and a predominantly White city. After controlling for physical and social proximity, student distress behaviors and staff support behaviors, but not staff members' own psychological distress, were significantly higher in schools with higher Native student populations, where a larger proportion of students shared cultural connections with the victims. We discuss implications regarding the importance of providing adequate support for Indigenous Peoples, and interdependent cultural groups in general, following collective trauma.

Piloting Home Produce Delivery to Improve Food Security, Budget, and Diet in Families with Children: A Mixed-Methods Study.

BACKGROUND: Few children in food insecure (FI) households meet dietary recommendations for fruit and vegetables ("produce"). Barriers include affordability, accessibility, and desirability. Home produce delivery may reduce FI, increase produce consumption, and decrease budget tradeoffs. OBJECTIVE: Evaluate the acceptability and potential impact of delivering produce through home visiting programs on FI, diet, and budget tradeoffs. METHODS: In this prospective pre/post mixed methods study, 51 parents engaged in home visiting programs were enrolled. Participants completed pre- and post-program surveys on FI (18-item Food Security Scale), produce consumption, and budget tradeoffs. Pre- and post-surveys were compared using McNemar's test and weighted kappas. Interview guides were based on Social Cognitive Theory and a previously published framework. Interviews were conducted in English or Spanish; thematic analysis was completed. RESULTS: Twenty-nine (56.9%) participants completed both surveys. Most were female (96.3%) and Hispanic (79.3%) (Table 1). Food security improved in the post-period, with more participants reporting high food security (pre: 6.9%, post: 31.0%) and fewer reporting very low food security (pre: 20.7%, post: 6.9%, p<0.01) (Table 2). Budgetary tradeoffs decreased in the post-program period (pre: 71.4%, post: 48.1%, p=0.03). Fifteen participants were interviewed. Themes included 1) saved money, 2) increased fruit and vegetable consumption, and 3) interest in future participation. CONCLUSION: This pilot study found that an intervention for delivery of produce through home visiting programs was acceptable to participants and resulted in potential improvements in FI and household budgets. This supports future studies to further explore the impact of this novel intervention. WHAT'S NEW: In this prospective mixed-methods pilot, home delivered produce was acceptable and feasible with potentially improved food security and household budgets; evidence of potential change in produce consumption was mixed. Changes in budget tradeoffs is a novel outcome in food programs.

Outcomes of the Modified Dunn Procedure Versus Delayed Imhauser Osteotomy for Moderate to Severe Stable Slipped Capital Femoral Epiphysis.

BACKGROUND: Traditional management of moderate to severe stable slipped capital femoral epiphysis (SCFE) has been in situ fixation followed by reconstructive surgery if symptoms arise. This delayed approach may lead to irreversible intra-articular damage of the hip over time. The purpose of this study was to compare radiographic and clinical outcomes of the modified Dunn procedure (MDP) versus in situ fixation followed by delayed Imhauser osteotomy (DIO). METHODS: This was a retrospective study from a single institution between 2001 and 2021. Among 250 patients diagnosed with SCFE, a total of 18 (18 hips) treated with MDP and 16 (18 hips) treated with DIO for moderate to severe stable SCFE were included. Most patients who underwent DIO either had concomitant (11/18 hips) or subsequent (2/18 hips) open osteochondroplasty. Mean follow up was 4.7 years (range: 1 to 12.8 y). Radiographs were reviewed to measure Southwick angle, anteroposterior and lateral alpha (α) angles, and femoral head-neck offset ratio preoperatively and at latest follow up. Charts were reviewed for demographics, subsequent surgeries, complications, and Heyman-Herndon clinical outcomes. RESULTS: The amount of deformity correction was greater in the MDP than DIO group based on anteroposterior α angles (mean: 22.3 vs. 11.9 degrees, P=0.046) and femoral head-neck offset ratios (mean: 0.26 vs. 0.12, P=0.001). There was no significant difference in Heyman-Herndon scores (both 16/18, 88.9% good to excellent outcomes, P>0.999). Less reoperations were performed in the MDP than DIO group (2/18, 11.1% vs. 9/18, 50%; P=0.004). AVN occurred in 2/18 hips (11.1%) in the MDP group with both surgeries performed early in the series and underwent prior in situ screw fixation compared with 0/18 hips (0%) in the DIO group (P=0.486). One patient in the DIO group was later diagnosed with osteoarthritis. CONCLUSIONS: MDP resulted in more anatomic coronal and sagittal plane deformity correction, less reoperations, and similar Heyman-Herndon clinical outcomes compared with DIO. AVN occurred in the MDP group whereas osteoarthritis occurred in the DIO group. These complications must be weighed against improved long-term clinical results for patients who would otherwise be at risk for premature degenerative joint disease due to residual proximal femoral deformity. LEVEL OF EVIDENCE: Level III-retrospective comparative study.

Systematic review of mechanistic evidence for TiO2 nanoparticle-induced lung carcinogenicity.

Nano-sized titanium dioxide particles (TiO2 NPs) are a high-production volume nanomaterial widely used in the paints, cosmetics, food and photovoltaics industry. However, the potential carcinogenic effects of TiO2 NPs in the lung are still unclear despite the vast number of in vitro and in vivo studies investigating TiO2 NPs. Here, we systematically reviewed the existing in vitro and in vivo mechanistic evidence of TiO2 NP lung carcinogenicity using the ten key characteristics of carcinogens for identifying and classifying carcinogens. A total of 346 studies qualified for the quality and reliability assessment, of which 206 were considered good quality. Using a weight-of-evidence approach, these studies provided mainly moderate to high confidence for the biological endpoints regarding genotoxicity, oxidative stress and chronic inflammation. A limited number of studies investigated other endpoints important to carcinogenesis, relating to proliferation and transformation, epigenetic alterations and receptor-mediated effects. In summary, TiO2 NPs might possess the ability to induce chronic inflammation and oxidative stress, but it was challenging to compare the findings in the studies due to the wide variety of TiO2 NPs differing in their physicochemical characteristics, formulation, exposure scenarios/test systems, and experimental protocols. Given the limited number of high-quality and high-reliability studies identified within this review, there is a lack of good enough mechanistic evidence for TiO2 NP lung carcinogenicity. Future toxicology/carcinogenicity research must consider including positive controls, endotoxin testing (where necessary), statistical power analysis, and relevant biological endpoints, to improve the study quality and provide reliable data for evaluating TiO2 NP-induced lung carcinogenicity.

Educational and occupational aspirations of adolescent and young adult cancer survivors: a qualitative analysis.

PURPOSE: Adolescent and young adult cancer survivors (AYACS) are patients diagnosed with cancer between 15 and 39 years of age. AYACS are often derailed from planned educational and occupational endeavors due to disruption from cancer treatment and its consequences. The study objective was to examine how a personal cancer diagnosis impacted AYACS' experiences related to these endeavors. METHODS: Semi-structured interviews were conducted as part of a larger study assessing psychosocial challenges among a younger AYACS subset aged 15-25 years old at the time of cancer diagnosis. Interviews were coded based on responses and were used to develop themes related to educational and occupational endeavors. RESULTS: Data were collected from 35 participants. Five themes emerged: (1) Pauses in educational attainment had a detrimental effect on educational goals for some participants, but further solidified and sculpted educational plans for others; (2) Although participants experienced challenges accomplishing educational goals, supportive school environments helped surmount these challenges; (3) Participants reflected on rethinking career aspirations, though some desired to pursue the same occupation planned before cancer diagnosis; (4) Participants experienced challenges, including physical and cognitive limitations, upon returning to work; and (5) Participants valued autonomy and normalcy through work and appreciated supportive and flexible work environments. CONCLUSIONS: AYACS prioritize professional achievement, yet encounter challenges in achieving professional goals. Our findings create a foundation for developing and testing prospective interventions to promote continuance of school and work during cancer treatment when feasible, and proactive reintegration strategies for those who paused professional goals due to cancer treatment.

Mule trains to mountain roads: the role of working mules in supporting resilient communities in the Himalayas.

Working equids play a central role in mountainous communities, but their work often goes unnoticed by the wider world, with sparse documentation of their role, value, or welfare - a state which often extends to their human counterparts. Communities living in the remote Manaslu Valley, Nepal, face a number of uncertainties, including extreme weather events due to the seasonal monsoon and, more recently, the construction of a new road network. Using semi-structured interviews, questionnaires, and Equine Assessment Research and Scoping (EARS) welfare assessments, we outline the specific role of pack mules in supporting the lives of local people, explain the nuanced links between human experience and mule welfare, and gain insight into how people living in this volatile environment manage uncertainty and risk. Mule work was felt to be the 'only option' for a sustainable livelihood for most mule owners although, in some cases, mules had enabled respondents to diversify their income. Mule owners with more husbandry experience did not own mules in more positive behavioural states, which may suggest a lack of generational knowledge and support networks. Short-term ongoing risks, such as the monsoon or unstable tracks, had a larger impact both financially and emotionally than the long-term but distant implications of the road construction. Mule owners must constantly balance the risk of working during the monsoon season, when conditions are treacherous but pay was higher, with losing valuable income but keeping themselves and their mules safe; they do, however, have a more mobile option for employment than non-owners. Mules enable a level of resilience and agility for communities living with constant uncertainty and change, which is only beginning to be recognised formally within the sustainable development sphere. Integration of animal welfare into the SDGs would allow humanitarian aid initiatives to strengthen support networks around working equids, which would greatly benefit the mules and humans alike.

Exercise and PTSD.

Evidence indicating that exercise benefits mental health symptoms across a range of mental health diagnoses spans decades of scientific literature; however, fewer studies have examined the impact of exercise on posttraumatic stress disorder (PTSD). Exercise is an accessible, cost-effective, and scalable treatment option that has the potential to improve both physiological and psychological symptoms among individuals with PTSD. The purpose of this chapter is to review empirical literature on the role of exercise in the treatment of PTSD. Researchers have demonstrated that exercise improves PTSD symptoms as both a stand-alone treatment and as an adjunct to cognitive behavioral and trauma-focused therapies. Additional research is needed to clarify mechanisms that account for the impacts of exercise on PTSD and to identify which components of exercise (e.g., type of exercise, dose, intensity, frequency) are the most beneficial.

Development of a family-level intervention for families with transgender and/or nonbinary youth: Lessons and recommendations.

Family support plays an important role in promoting resilience and health among transgender and/or nonbinary youth (TNBY), but family members often experience barriers to supporting their TNBY, including minority-adjacent stress stemming from exposure to structural stigma and antitransgender legislation. TNBY and their families need effective family-level interventions developed using community-based participatory research (CBPR), which integrates community members (e.g., TNBY, family members, service providers for families with TNBY) into the intervention development process to ensure the resulting intervention is relevant and useful. Informed by findings from the Trans Teen and Family Narratives Project, we used CBPR to develop the Trans Teen and Family Narratives Conversation Toolkit, a family-level intervention designed to educate families about TNBY and facilitate conversations about gender. The toolkit was developed across 1.5 years (June 2019 to January 2021) using four integrated phases: (1) content development: digital storytelling workshop with TNBY; (2) content review: digital storyteller interviews and user focus groups; (3) content development: study team content synthesis and website development; and (4) content review: website review by TNBY, family members, and mental health providers, and intervention refinement. This article outlines the intervention development process, describes strategies employed to navigate challenges encountered along the way, and shares key learnings to inform future CBPR intervention development efforts. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Genomic and functional determinants of host spectrum in Group B Streptococcus.

Group B Streptococcus (GBS) is a major human and animal pathogen that threatens public health and food security. Spill-over and spill-back between host species is possible due to adaptation and amplification of GBS in new niches but the evolutionary and functional mechanisms underpinning those phenomena are poorly known. Based on analysis of 1,254 curated genomes from all major GBS host species and six continents, we found that the global GBS population comprises host-generalist, host-adapted and host-restricted sublineages, which are found across host groups, preferentially within one host group, or exclusively within one host group, respectively, and show distinct levels of recombination. Strikingly, the association of GBS genomes with the three major host groups (humans, cattle, fish) is driven by a single accessory gene cluster per host, regardless of sublineage or the breadth of host spectrum. Moreover, those gene clusters are shared with other streptococcal species occupying the same niche and are functionally relevant for host tropism. Our findings demonstrate (1) the heterogeneity of genome plasticity within a bacterial species of public health importance, enabling the identification of high-risk clones; (2) the contribution of inter-species gene transmission to the evolution of GBS; and (3) the importance of considering the role of animal hosts, and the accessory gene pool associated with their microbiota, in the evolution of multi-host bacterial pathogens. Collectively, these phenomena may explain the adaptation and clonal expansion of GBS in animal reservoirs and the risk of spill-over and spill-back between animals and humans.

A feasibility study assessing knowledge, vaccine hesitancy, and completion rates of free HPV vaccination in low-income uninsured adults.

Background: Human Papillomavirus (HPV) vaccination rates remain low in the U.S., particularly among minorities and low-income, uninsured patients. We report preliminary data on a pilot study program providing education and free HPV vaccination at a clinic serving low-income uninsured adults. Methods: From October 2020 through October 2022, we assessed HPV vaccination knowledge, awareness, and prevalence of hesitancy towards receiving the vaccine among low-income uninsured patients age 18-45. The Parents Attitudes about Childhood Vaccines (PACV) survey was modified and used to evaluate vaccine hesitancy. An educational video on HPV was shown to patients declining vaccination. Results: 43 patients were enrolled. 69.8% had heard of the HPV vaccine and 85.7% were non-hesitant based on PACV scores of 0-49. Black participants had a statistically significant higher PACV score (more hesitant) than White participants. Familiarity with the HPV vaccine correlated with lower PACV scores. Only 27% completed all three HPV vaccine doses. Discussion: The availability of an education program together with free HPV vaccination are not sufficient to achieve adequate vaccination rates in low-income, uninsured adults. Innovative, culturally sensitive education and supportive interventions, in addition to access to free HPV vaccination, are warranted in order to improve vaccination rates in this underserved population.

Implementing an Environmental Contaminants Deliberation Module in General Chemistry.

Placing chemistry in the context of complex societal issues is one way to help students see the application of fundamental ideas in the general chemistry curriculum. Here, we describe the impact of an in-class deliberation on environmental contaminants, which encourages students to consider different perspectives when addressing the issue of water and soil quality in communities. Student surveys were used to analyze the quality of the deliberation and several key factors regarding student attitudes before and after the activity. Students report a high-quality experience during the deliberation, wherein new ideas were introduced and they carefully considered different views on the issue at hand. Not only do students gain scientific knowledge about lead contamination, they also demonstrate statistically significant gains in their attitudes toward chemistry and their motivation to take action. As a complement to traditional teaching methods, this deliberation module can address key learning outcomes in systems thinking and the impact chemistry has on society.

Factors associated with transfer from assisted living facilities to a nursing home: National Health Aging Trends Study 2011-2019.

BACKGROUND: Residents of assisted living facilities (ALF) transfer to a nursing home when they require a higher level of care, but limited research has examined risk factors for transfer to a nursing home. The aims of this study were to identify (1) baseline factors associated with transfer to a nursing home and (2) time-varying factors associated with transfer to a nursing home over 8 years, using a national dataset from the National Health Aging Trends Study (NHATS). METHODS: NHATS participants were included in this study if they: (1) resided in ALF from Round 1 (2011) through Round 8 (2018); (2) completed the sample person (SP) interview at baseline; (3) were admitted to ALF at age 65 years or older. We conducted Cox proportional hazards regression to examine candidate predictors (difficulty with basic activities of daily living (ADL), chronic conditions, hospitalization, sleep disturbances, mental health, physical performance, self-reported health, participation in social and physical activity, and sociodemographic) associated with transfer to a nursing home. Employing backward elimination, we built parsimonious final models for analysis. RESULTS: The analytic sample included 970 participants of whom 143 transferred to nursing homes over 8 years. Those who had a better physical performance at baseline (HR = 0.83, 95% CI = 0.79-0.88) and were college educated (HR = 0.58, 95% CI = 0.36-0.92) demonstrated a significantly lower risk for transfer to a nursing home over 8 years. Residents who maintained physical activity (HR = 0.56, 95% CI = 0.37-0.86), better physical performance (HR = 0.87, 95% CI = 0.80-0.94), and difficulty with fewer basic ADLs (HR = 1.13, 95% CI = 1.02-1.26) were at lower risk for transfer to a nursing home over 8 years. CONCLUSIONS: Our findings can be used to identify older adults in ALFs at risk of transfer to a nursing home. Strategies to promote physical function and physical activity could avoid/delay the need to transfer. Helping older residents to age in place will have important health and economic benefits.

TBK1 and IKKε protect target cells from IFNγ-mediated T cell killing via an inflammatory apoptotic mechanism.

Cytotoxic T cells produce interferon gamma (IFNγ), which plays a critical role in anti-microbial and anti-tumor responses. However, it is not clear whether T cell-derived IFNγ directly kills infected and tumor target cells, and how this may be regulated. Here, we report that target cell expression of the kinases TBK1 and IKKε regulate IFNγ cytotoxicity by suppressing the ability of T cell-derived IFNγ to kill target cells. In tumor targets lacking TBK1 and IKKε, IFNγ induces expression of TNFR1 and the Z-nucleic acid sensor, ZBP1, to trigger RIPK1-dependent apoptosis, largely in a target cell-autonomous manner. Unexpectedly, IFNγ, which is not known to signal to NFκB, induces hyperactivation of NFκB in TBK1 and IKKε double-deficient cells. TBK1 and IKKε suppress IKKα/ß activity and in their absence, IFNγ induces elevated NFκB-dependent expression of inflammatory chemokines and cytokines. Apoptosis is thought to be non-inflammatory, but our observations demonstrate that IFNγ can induce an inflammatory form of apoptosis, and this is suppressed by TBK1 and IKKε. The two kinases provide a critical connection between innate and adaptive immunological responses by regulating three key responses: (1) phosphorylation of IRF3/7 to induce type I IFN; (2) inhibition of RIPK1-dependent death; and (3) inhibition of NFκB-dependent inflammation. We propose that these kinases evolved these functions such that their inhibition by pathogens attempting to block type I IFN expression would enable IFNγ to trigger apoptosis accompanied by an alternative inflammatory response. Our findings show that loss of TBK1 and IKKε in target cells sensitizes them to inflammatory apoptosis induced by T cell-derived IFNγ. Short Summary: In the absence of TBK1 and IKKε, target cells are killed by T cells in an IFNγ-dependent manner. In TBK1 and IKKε-deficient cells, IFNγ induces RIPK1-dependent death, as well as hyper-induction of NFκB-dependent inflammatory genes. This suggests that any inhibition of TBK1/IKKε to block type I IFN expression will result in the demise of the cell accompanied by an alternate inflammatory program.