Paper Title: Colorectal cancer screening knowledge among community pharmacists: A national survey.

BACKGROUND: Colorectal cancer (CRC) screening can reduce CRC morbidity and mortality. Community pharmacies could be a viable option for delivering home-based CRC screening tests such as fecal immunochemical tests (FITs). However, little is known about community pharmacists' knowledge about CRC screening guidelines. OBJECTIVE: We assessed community pharmacists' knowledge about CRC screening to identify education and training needs for a pharmacy-based CRC screening program. METHODS: Between September 2022 and January 2023, we conducted an online national survey of community pharmacists practicing in the United States (US) (Responders were eligible if they were currently-licensed community pharmacists and currently practiced in the US. The survey assessed knowledge of national CRC screening guidelines, including recommended starting age, frequency of screening, different screening modalities, and follow-up care. Using multiple linear regression, we evaluated correlates of community pharmacists' level of CRC screening knowledge, defined as the total number of knowledge questions answered correctly from "0" (no questions correct) to "5" (all questions correct). RESULTS: 578 eligible community pharmacists completed the survey, with a response rate of 59%. Most community pharmacists correctly answered the question about the next steps following a positive FIT (87%) and the question about where a FIT can be done (84%). A minority of community pharmacists responded correctly to questions about the age to start screening with FIT (34%) and how often a FIT should be repeated (28%). Only 5% of pharmacists answered all knowledge questions correctly. Community pharmacists answered more CRC screening knowledge questions correctly as their years in practice increased. Board-certified community pharmacists answered more CRC screening knowledge questions correctly compared to those who were not board-certified. CONCLUSION: To ensure the successful implementation of a pharmacy-based CRC screening program, community pharmacists need to be educated about CRC screening and trained to ensure comprehensive patient counseling and preventive service delivery.

Intra- and Intermolecular Charge-Transfer Dynamics of Carbene-Metal-Amide Photosensitizers.

A series of steady-state and time-resolved spectroscopies were performed on a set of eight carbene-metal-amide (cMa) complexes, where M = Cu and Au, that have been used as photosensitizers for photosensitized electrocatalytic reactions. Using ps-to-ns and ns-to-ms transient absorption spectroscopies (psTA and nsTA, respectively), the excited-state kinetics from light absorption, intersystem crossing (ISC), and eventually intermolecular charge transfer were thoroughly characterized. Using time-correlated single photon counting (TCSPC) and psTA with a thermally activated delayed fluorescence (TADF) model, the variation in intersystem crossing (ISC), (S1 → T1) rates (∼3-120 × 109 s-1), and ΔEST values (73-115 meV) for these compounds were fully characterized, reflecting systematic changes to the carbene, carbazole, and metal. The psTA additionally revealed an early time relaxation (rate ∼0.2-0.8 × 1012 s-1) attributed to solvent relaxation and vibrational cooling. The nsTA experiments for a gold-based cMa complex demonstrated efficient intermolecular charge transfer from the excited cMa to an electron acceptor. Pulse radiolysis and bulk electrolysis experiments allowed us to identify the character of the transient excited states as ligand-ligand charge transfer as well as the spectroscopic signature of oxidized and reduced forms of the cMa photosensitizer.

The relationships between fear of missing out and psychological and sociocultural factors in Latinx emerging adult college students.

OBJECTIVES: The proliferation of social media has resulted in negative consequences such as fear of missing out (FoMO), the anxious feelings one has when others are having rewarding experiences. Few studies have assessed FoMO in Latinx emerging adult college students, none utilizing the socioecological framework. This study assessed the relationships between FoMO and psychological and sociocultural risk and protective factors. METHOD: Latinx college students (n = 452; Mage = 19.97 years, SD = 1.89; 77.2% female) completed an online survey assessing demographics, FoMO, social media addiction, depression, anxiety, stress, Machiavellianism, narcissism, psychopathy, familism, and acculturation. Two multiple linear regressions assessed the associations between FoMO and psychological and sociocultural factors. RESULTS: Both regressions were statistically significant. First, FoMO was positively associated with social media addiction, depression, and Machiavellianism. Second, FoMO was positively associated with familial honor and negatively associated with familial interconnectedness and ethnic social relations. CONCLUSIONS: Associations between FoMO and psychological factors are consistent with past literature, yet they highlight the need for prospective studies to assess temporality. The fact that FoMO was related uniquely to familistic attitudes suggests the importance of family in FoMO perceptions and the need to assess these associations in a more nuanced manner. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Clinical Theranostics in Recurrent Gliomas: A Review.

Gliomas represent the most commonly occurring tumors in the central nervous system and account for approximately 80% of all malignant primary brain tumors. With a high malignancy and recurrence risk, the prognosis of high-grade gliomas is poor, with a mean survival time of 12-18 months. While contrast-enhanced MRI serves as the standard diagnostic imaging modality for gliomas, it faces limitations in the evaluation of recurrent gliomas, failing to distinguish between treatment-related changes and tumor progression, and offers no direct therapeutic options. Recent advances in imaging modalities have attempted to address some of these limitations, including positron emission tomography (PET), which has demonstrated success in delineating tumor margins and guiding the treatment of recurrent gliomas. Additionally, with the advent of theranostics in nuclear medicine, PET tracers, when combined with therapeutic agents, have also evolved beyond a purely diagnostic modality, serving both diagnostic and therapeutic roles. This review will discuss the growing involvement of theranostics in diagnosing and treating recurrent gliomas and address the associated impact on quality of life and functional recovery.

Epidemiologic and tick exposure characteristics among people with reported Lyme disease - Minnesota, 2011-2019.

AIMS AND METHODS: In the United States, blacklegged Ixodes spp. ticks are the primary vector of Lyme disease. Minnesota is among the states with the highest reported incidence of Lyme disease, having an average of 1857 cases reported annually during 2011-2019. In contrast to the Northeast and mid-Atlantic United States where exposure to ticks predominately occurs around the home, the circumstances regarding risk for exposure to blacklegged ticks in Minnesota are not well understood, and risk is thought to be highest in rural areas where people often participate in recreational activities (e.g. hiking, visiting cabins). We analysed enhanced surveillance data collected by the Minnesota Department of Health during 2011-2019 to describe epidemiologic and tick exposure characteristics among people with reported Lyme disease. RESULTS: We found that younger age, male gender, residence in a county with lower Lyme disease risk, residence in the Minneapolis-St. Paul metropolitan area, and an illness onset date later in the year were independently associated with higher odds of reporting tick exposures away from the home. We also describe the range of activities associated with tick exposure away from the home, including both recreational and occupational activities. CONCLUSIONS: These findings refine our understanding of Lyme disease risk in Minnesota and highlight the need for heterogeneous public health prevention messaging, including an increased focus on peridomestic prevention measures among older individuals living in high-risk rural areas and recreational and occupational prevention measures among younger individuals living in the Minneapolis-St. Paul metropolitan area.

Exploring Sociodemographic Factors in Allergic Fungal Rhinosinusitis in a Northern California Patient Population.

BACKGROUND: Allergic fungal rhinosinusitis (AFRS) is a subtype of chronic rhinosinusitis (CRS) that has previously been associated with younger age and Black patients. However, the role of demographic and socioeconomic factors in AFRS severity remains to be fully elucidated. OBJECTIVE: The objective of this study was to determine whether demographic and socioeconomic factors are associated with incidence of AFRS, as well as with disease severity in Northern California. METHODS: A retrospective cohort study was conducted of adult patients with AFRS and CRS from 2010 to 2019. AFRS was determined by the Bent and Kuhn criteria, and severity was assessed by radiographic evidence of cranioorbital invasion and other clinical parameters. Chi-square and t-test were used to assess demographic and socioeconomic differences between AFRS and CRS cohorts, and multivariable logistic regression was used to assess risk factors for severe AFRS. RESULTS: Black patients represented 26.2% (55/210 patients) of the AFRS group and 4.9% (842/17,300 patients) of the CRS group, with pairwise comparison of race/ethnicity categories showing that the AFRS group had significantly higher proportions of Black race/ethnicity compared with other race/ethnicities (p < 0.01). AFRS and CRS groups differed significantly by age, with mean ages of 48.7 and 51.0 years, respectively (p = 0.04). There were no significant differences in gender, Medicaid status, comorbidities, and socioeconomic status measures. Multivariate logistic regression showed that Black patients had higher odds of having severe AFRS (adjusted odds ratio = 2.29; 95% confidence interval: 1.18-4.45). CONCLUSION: AFRS has a unique predilection for Black patients, and severe disease is also more likely in this population.

Health insurance among survivors of childhood cancer following affordable care act implementation.

BACKGROUND: The Affordable Care Act (ACA) increased private non-employer health insurance options, expanded Medicaid eligibility, and provided pre-existing health conditions protections. We evaluated insurance coverage among long-term adult survivors of childhood cancer pre/post-ACA implementation. METHODS: Using the multicenter Childhood Cancer Survivor Study, we included participants from two cross-sectional surveys: pre-ACA (2007-2009; survivors: N = 7,505; siblings: N = 2,175) and post-ACA (2017-2019; survivors: N = 4,030; siblings: N = 987). A subset completed both surveys (1,840 survivors; 646 siblings). Multivariable regression models compared post-ACA insurance coverage and type (private/public/uninsured) between survivors and siblings and identified associated demographic and clinical factors. Multinomial models compared gaining and losing insurance vs staying the same among survivors and siblings who participated in both surveys. RESULTS: The proportion with insurance was higher post-ACA (survivors pre-ACA 89.1% to post-ACA 92.0% [+2.9%]; siblings pre-ACA 90.9% to post-ACA 95.3% [+4.4%]). Post-ACA insurance coverage was greater among those age 18-25 (survivors: 15.8% vs < 2.3% ages 26+; siblings +17.8% vs < 4.2% ages 26+). Survivors were more likely to have public insurance than siblings post-ACA (18.4% vs 6.9%; odds ratios [OR]=1.7, 95%CI 1.1-2.6). Survivors with severe chronic conditions (OR = 4.7, 95%CI 3.0-7.3) and those living in Medicaid expansion states (OR = 2.4, 95%CI 1.7-3.4) had increased odds of public insurance coverage post-ACA. Among the subset completing both surveys, low/mid income survivors (<$60,000) experienced both insurance losses and gains in reference to highest household income survivors (≥$100,000), relative to odds of keeping the same insurance status. CONCLUSIONS: Post-ACA, more childhood cancer survivors and siblings had health insurance, although disparities remain in coverage.

PET Imaging of Metabolism, Perfusion, and Hypoxia: FDG and Beyond.

ABSTRACT: Imaging glucose metabolism with [18F]fluorodeoxyglucose positron emission tomography has transformed the diagnostic and treatment algorithms of numerous malignancies in clinical practice. The cancer phenotype, though, extends beyond dysregulation of this single pathway. Reprogramming of other pathways of metabolism, as well as altered perfusion and hypoxia, also typifies malignancy. These features provide other opportunities for imaging that have been developed and advanced into humans. In this review, we discuss imaging metabolism, perfusion, and hypoxia in cancer, focusing on the underlying biology to provide context. We conclude by highlighting the ability to image multiple facets of biology to better characterize cancer and guide targeted treatment.

Anthropogenic and climatic factors interact to influence reproductive timing and effort.

Reproduction, although absolutely essential to a species' persistence, is in itself challenging. As anthropogenic change increasingly affects every landscape on Earth, it is critical to understand how specific pressures impact the reproductive efforts of individuals, which directly contribute to the success or failure of populations. However, organisms rarely encounter a single burden at a time, and the interactions of environmental challenges can have compounding effects. Understanding environmental and physiological pressures is difficult because they are often context-dependent and not generalizable, but long-term monitoring across variable landscapes and weather patterns can improve our understanding of these complex interactions. We tested the effects of urbanization, climate, and individual condition on the reproductive investment of wild side-blotched lizards (Uta stansburiana) by measuring physiological/reproductive metrics from six populations in urban and rural areas over six consecutive years of variable precipitation. We observed that reproductive stage affected body condition, corticosterone concentration, and oxidative stress. We also observed that reproductive patterns differed between urban and rural populations depending on rainfall, with rural animals increasing reproductive investment during rainier years compared to urban conspecifics, and that reproductive decisions appeared to occur early in the reproductive process. These results demonstrate the plastic nature of a generalist species optimizing lifetime fitness under varying conditions.

Structural characterization of antibody-responses from Zolgensma treatment provides the blueprint for the engineering of an AAV capsid suitable for redosing.

Monoclonal antibodies (mAbs) are useful tools to dissect the neutralizing antibody response against the adeno-associated virus (AAV) capsids used as gene therapy delivery vectors. This study structurally characterizes the interactions of 21 human-derived antibodies from patients treated with the AAV9 vector, Zolgensma ® , utilizing high-resolution cryo-electron microscopy. The majority of the bound antibodies do not conform to the icosahedral symmetry of the capsid, thus requiring localized reconstructions. These complex structures provide unprecedented details of the mAbs binding interfaces, with some antibodies inducing structural perturbations of the capsid upon binding. Key surface capsid amino acid residues were identified facilitating the design of capsid variants with an antibody escape phenotype, with the potential to expand the patient cohort treatable with AAV9 vectors to include those that were previously excluded due to their pre-existing neutralizing antibodies, and possibly also to those requiring redosing.

Findings From a National Survey of Older US Adults on Patient Willingness to Use Telehealth Services: Cross-Sectional Survey.

BACKGROUND: Telehealth (telemedicine and telepharmacy) services increase access to patient services and ensure continuity of care. However, few studies have assessed factors that influence patients' willingness to use telehealth services, and we sought to investigate this. OBJECTIVE: This study aims to examine respondents' (aged between 45 and 75 years) willingness to use telehealth services (telepharmacy and telemedicine) and the correlates of the willingness to use telehealth services. METHODS: We administered a cross-sectional national survey of 1045 noninstitutionalized US adults aged between 45 and 75 years in March and April 2021. Multiple logistic regression analyses were used to identify demographic and health service use correlates of self-reported willingness to use telehealth services. RESULTS: Overall willingness to use telemedicine was high (674/1045, 64.5%). Adults aged 55 years and older were less willing to use telemedicine (aged between 55 and 64 years: odds ratio [OR] 0.61, 95% CI 0.42-0.86; aged 65 years or older: OR 0.33, 95% CI 0.22-0.49) than those younger than 55 years. Those with a regular provider (OR 1.01, 95% CI 1-1.02) and long travel times (OR 1.75, 95% CI 1.03-2.98) were more willing to use telemedicine compared to those without a regular provider and had shorter travel times, respectively. Willingness to use telemedicine services increased from 64.5% (674/1045) to 83% (867/1045) if the service was low-cost or insurance-covered, was with their existing health care provider, or was easy-to-use. Overall willingness to use telepharmacy was 76.7% (801/1045). Adults aged older than 55 years were less willing to use telepharmacy (aged between 55 and 64 years: OR 0.57, 95% CI 0.38-0.86; aged 65 years or older: OR 0.24, 95% CI 0.15-0.37) than those younger than 55 years. Those who rated pharmacy service quality higher were more willing to use telepharmacy (OR 1.06, 95% CI 1.03-1.09) than those who did not. CONCLUSIONS: Respondents were generally willing to use telehealth (telemedicine and telepharmacy) services, but the likelihood of their being willing to use telehealth decreased as they were older. For those initially unwilling (aged 55 years or older) to use telemedicine services, inexpensive or insurance-covered services were acceptable.

LGBTQ+ cancer: priority or lip service? A qualitative content analysis of LGBTQ+ considerations in U.S. state, jurisdiction, and tribal comprehensive cancer control plans.

The National Comprehensive Cancer Control Program, a Centers for Disease Control and Prevention funded program, supports cancer coalitions across the United States (US) in efforts to prevent and control cancer including development of comprehensive cancer control (CCC) plans. CCC plans often focus health equity within their priorities, but it is unclear to what extent lesbian, gay, bisexual, transgender, queer/questioning, plus (LGBTQ+) populations are considered in CCC plans. We qualitatively examined to what extent LGBTQ+ populations were referenced in 64 U.S. state, jurisdiction, tribes, and tribal organization CCC plans. A total of 55% of CCC plans mentioned LGBTQ+ populations, however, only one in three CCC plans mentioned any kind of LGBTQ+ inequity or LGBTQ+ specific recommendations. Even fewer plans included mention of LGBTQ+ specific resources, organizations, or citations. At the same time almost three fourths of plans conflated sex and gender throughout their CCC plans. The findings of this study highlight the lack of prioritization of LGBTQ+ populations in CCC plans broadly while highlighting exemplar plans that can serve as a roadmap to more inclusive future CCC plans. Comprehensive cancer control plans can serve as a key policy and advocacy structure to promote a focus on LGBTQ+ cancer prevention and control.

Multidimensional mass profiles increase confidence in bacterial identification when using low-resolution mass spectrometers.

Field-forward analytical technologies, such as portable mass spectrometry (MS), enable essential capabilities for real-time monitoring and point-of-care diagnostic applications. Significant and recent investments improving the features of miniaturized mass spectrometers enable various new applications outside of small molecule detection. Most notably, the addition of tandem mass spectrometry scans (MS/MS) allows the instrument to isolate and fragment ions and increase the analytical specificity by measuring unique chemical signatures for ions of interest. Notwithstanding these technological advancements, low-cost, portable systems still struggle to confidently identify clinically significant organisms of interest, such as bacteria, viruses, and proteinaceous toxins, due to the limitations in resolving power. To overcome these limitations, we developed a novel multidimensional mass fingerprinting technique that uses tandem mass spectrometry to increase the chemical specificity for low-resolution mass spectral profiles. We demonstrated the method's capabilities for differentiating four different bacteria, including attentuated strains of Yersinia pestis. This approach allowed for the accurate (>92%) identification of each organism at the strain level using de-resolved matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) data to mimic the performance characteristics of miniaturized mass spectrometers. This work demonstrates that low-resolution mass spectrometers, equipped with tandem MS acquisition modes, can accurately identify clinically relevant bacteria. These findings support the future application of these technologies for field-forward and point-of-care applications where high-performance mass spectrometers would be cost-prohibitive or otherwise impractical.

An Environmental Scan and Qualitative Inquiry of Cancer Patient Navigation Services in North Carolina.

Background and Objectives: Patient navigation services reduce barriers to accessing cancer care and lead to improved outcomes for patients. North Carolina (NC) has thousands of cancer patients seeking cancer care services each year. We sought to complete a digital environmental scan and qualitative inquiry of cancer patient navigation services throughout the state to better inform patients, hospitals administrators, and state officials about the current state of patient navigation programs for cancer patients throughout NC. Methods: For seven cancer hospitals in NC, two steps were used: an environmental scan of publicly available information on the hospitals' websites about navigation services, and key informant interviews with navigation staff at each site. Results: The website scans revealed information about navigation services was incomplete. Each hospital had a page dedicated to cancer navigation, but many did not outline the specific services available to patients. Interviews revealed that navigation services are available to cancer patients across diagnoses, although only a subset of patients receive services. Cancer navigators reported that their work includes care coordination, patient advocacy, emotional support, and addressing non-medical barriers to health care access (transportation, finances, childcare, etc.). Each navigation service had a unique configuration and referral pattern. Conclusions: Cancer hospitals throughout NC are working to address barriers to care commonly faced by patients, with some programs offering more robust services compared to others. Hospitals would benefit from updating their websites at regular intervals to fully report the services available to patients through their programs, including direct and clear patient navigation contact methods.

Tunable High Entropy Lanthanide Oxide Microspheres via Confined Electroprecipitation in Emulsion Droplet Scaffolds.

Emergent high entropy nanomaterials and their associated complex surface structure hold promise to unlock unique catalytic intermediate pathways and photonic/plasmonic interactions; however, synthetic strategies to tune the size, morphological, and stoichiometric properties remain limited. This work demonstrates a confined electro-precipitation mechanism for the formation of tunable, high-entropy oxide microspheres within emulsion droplet scaffolds. This mechanism complements a traditional confined electrodeposition mechanism and explains the previously observed anomalous formation of thermodynamically unfavorable particles, including lanthanide species. Mass transfer studies reveal that microsphere coverage over a surface may be tuned and modeled by using a time-dependent modified Levich equation. Additionally, morphological tuning was demonstrated as a function of experimental conditions, such as rotation rate and precursor concentration. Finally, extension to multimetallic species permitted the generation of high-entropy lanthanide oxide microspheres, which were confirmed to have equimolar stoichiometries via energy dispersive spectroscopy and inductively coupled plasma mass spectrometry. This novel method promises to generate tunable, complex oxides with applications to thermal catalysis, optics, and applications yet unknown.

Social jet lag impairs exercise volume and attenuates physiological and metabolic adaptations to voluntary exercise training.

Social jet lag (SJL) is a misalignment between sleep and wake times on workdays and free days. SJL leads to chronic circadian rhythm disruption and may affect nearly 70% of the general population, leading to increased risk for cardiometabolic diseases. This study investigated the effects of SJL on metabolic health, exercise performance, and exercise-induced skeletal muscle adaptations in mice. Ten-week-old C57BL/6J mice (n = 40) were allocated to four groups: control sedentary (CON-SED), control exercise (CON-EX), social jet lag sedentary (SJL-SED), and social jet lag exercise (SJL-EX). CON mice were housed under a 12:12-h light-dark cycle. SJL was simulated by implementing a 4-h phase delay for 3 days to simulate "weekends," followed by a 4-h phase advance back to "weekdays," for 6 wk. EX mice had free access to a running wheel. Graded exercise tests (GXTs) and glucose tolerance tests (GTTs) were performed at baseline and after intervention to monitor the effects of exercise and social jet lag on cardiorespiratory and metabolic health, respectively. SJL led to alterations in activity and running patterns and clock gene expression in skeletal muscle and decreased average running distance (P < 0.05). SJL-SED mice gained significantly more weight compared with CON-SED and SJL-EX mice (P < 0.01). SJL impaired fasting blood glucose and glucose tolerance compared with CON mice (P < 0.05), which was partially restored by exercise in SJL-EX mice. SJL also blunted improvements in exercise performance and mitochondrial content in the quadriceps. These data suggest that SJL blunted some cardiometabolic adaptations to exercise and that proper circadian hygiene is necessary for maintaining health and performance.NEW & NOTEWORTHY In mice, disrupting circadian rhythms with social jet lag for 6 wk caused significant weight gain, higher fasting blood glucose, and impaired glucose tolerance compared with control. Voluntary exercise in mice experiencing social jet lag prevented weight gain, though the mice still experienced increased fasting blood glucose and impaired exercise performance compared with trained mice not experiencing social jet lag. Social jet lag seems to be a potent circadian rhythm disruptor that impacts exercise-induced training adaptations.

Mycobacterial spindle cell pseudotumor of the spinal cord: Case report and literature review.

We report the first description of spinal cord mycobacterial spindle cell pseudotumor. A patient with newly diagnosed advanced HIV presented with recent-onset bilateral leg weakness and was found to have a hypermetabolic spinal cord mass on structural and molecular imaging. Biopsy and cultures from blood and cerebrospinal fluid confirmed spindle cell pseudotumor due to Mycobacterium avium-intracellulare. Despite control of HIV and initial reduction in pseudotumor volume on antiretrovirals and antimycobacterials (azithromycin, ethambutol, rifampin/rifabutin), he ultimately experienced progressive leg weakness due to pseudotumor re-expansion. Here, we review literature and discuss multidisciplinary diagnosis, monitoring and management challenges, including immune reconstitution inflammatory syndrome.

Influence of age on the efficacy of pharmacologic treatments on fracture risk reduction and increases in BMD: RCT results from the FNIH-ASBMR-SABRE project.

There is a common belief that antiosteoporosis medications are less effective in older adults. This study used data from randomized controlled trials (RCTs) to determine whether the anti-fracture efficacy of treatments and their effects on BMD differ in people ≥70 compared to those <70 yr. We used individual patient data from 23 RCTs of osteoporosis medications collected as part of the FNIH-ASBMR SABRE project. We assessed the following fractures: radiographic vertebral, non-vertebral, hip, all clinical, and all fractures. We used Cox proportional hazard regression to estimate treatment effect for clinical fracture outcomes, logistic regression for the radiographic vertebral fracture outcome, and linear regression to estimate treatment effect on 24-mo change in hip and spine BMD in each age subgroup. The analysis included 123 164 (99% female) participants; 43% being ≥70 yr. Treatment with anti-osteoporosis drugs significantly and similarly reduced fractures in both subgroups (eg, odds ratio [OR] = 0.47 and 0.51 for vertebral fractures in those below and above 70 yr, interaction P = .19; hazard ratio [HR] for all fractures: 0.72 vs 0.70, interaction P = .20). Results were similar when limited to bisphosphonate trials with the exception of hip fracture risk reduction which was somewhat greater in those <70 (HR = 0.44) vs ≥70 (HR = 0.79) yr (interaction P = .02). Allocation to anti-osteoporotic drugs resulted in significantly greater increases in hip and spine BMD at 24 mo in those ≥70 compared to those <70 yr. In summary, anti-osteoporotic medications similarly reduced the risk of fractures regardless of age, and the few small differences in fracture risk reduction by age were of uncertain clinical significance.

Medications used for osteoporosis maybe are less effective in older adults. This study used data from clinical trials to determine whether these medications work equally well in reducing the risk of fractures in people ≥70 compared to those <70 yr. The analysis included 123 164 participants with data from 23 trials. Treatment with anti-osteoporosis drugs significantly reduced fractures in both groups in a similar way. The BMD increased more in the older group.

Metabolic control of adaptive ß-cell proliferation by the protein deacetylase SIRT2.

Selective and controlled expansion of endogenous ß-cells has been pursued as a potential therapy for diabetes. Ideally, such therapies would preserve feedback control of ß-cell proliferation to avoid excessive ß-cell expansion and an increased risk of hypoglycemia. Here, we identified a regulator of ß-cell proliferation whose inactivation results in controlled ß-cell expansion: the protein deacetylase Sirtuin 2 (SIRT2). Sirt2 deletion in ß-cells of mice increased ß-cell proliferation during hyperglycemia with little effect in homeostatic conditions, indicating preservation of feedback control of ß-cell mass. SIRT2 restrains proliferation of human islet ß-cells cultured in glucose concentrations above the glycemic set point, demonstrating conserved SIRT2 function. Analysis of acetylated proteins in islets treated with a SIRT2 inhibitor revealed that SIRT2 deacetylates enzymes involved in oxidative phosphorylation, dampening the adaptive increase in oxygen consumption during hyperglycemia. At the transcriptomic level, Sirt2 inactivation has context-dependent effects on ß-cells, with Sirt2 controlling how ß-cells interpret hyperglycemia as a stress. Finally, we provide proof-of-principle that systemic administration of a GLP1-coupled Sirt2-targeting antisense oligonucleotide achieves ß-cell selective Sirt2 inactivation and stimulates ß-cell proliferation under hyperglycemic conditions. Overall, these studies identify a therapeutic strategy for increasing ß-cell mass in diabetes without circumventing feedback control of ß-cell proliferation.