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© 2015 Leeman et al.; licensee BioMed Central. Background: Numerous agencies are providing training, technical assistance, and other support to build community-based practitioners' capacity to adopt and implement evidence-based prevention interventions. Yet, little is known about how best to design capacity-building interventions to optimize their effectiveness. Wandersman et al. (Am J Community Psychol.50:445-59, 2102) proposed the Evidence-Based System of Innovation Support (EBSIS) as a framework to guide research and thereby strengthen the evidence base for building practitioners' capacity. The purpose of this review was to contribute to further development of the EBSIS by systematically reviewing empirical studies of capacity-building interventions to identify (1) the range of strategies used, (2) variations in the way they were structured, and (3) evidence for their effectiveness at increasing practitioners' capacity to use evidence-based prevention interventions. Methods: PubMed, EMBASE, and CINAHL were searched for English-language articles reporting findings of empirical studies of capacity-building interventions that were published between January 2000 and January 2014 and were intended to increase use of evidence-based prevention interventions in non-clinical settings. To maximize review data, studies were not excluded a priori based on design or methodological quality. Using the EBSIS as a guide, two researchers independently extracted data from included studies. Vote counting and meta-summary methods were used to summarize findings. Results: The review included 42 publications reporting findings from 29 studies. In addition to confirming the strategies and structures described in the EBSIS, the review identified two new strategies and two variations in structure. Capacity-building interventions were found to be effective at increasing practitioners' adoption (n = 10 of 12 studies) and implementation (n = 9 of 10 studies) of evidence-based interventions. Findings were mixed for interventions' effects on practitioners' capacity or intervention planning behaviors. Both the type and structure of capacity-building strategies may hav e influenced effectiveness. The review also identified contextual factors that may require variations in the ways capacity-building interventions are designed. Conclusions: Based on review findings, refinements are suggested to the EBSIS. The refined framework moves the field towards a more comprehensive and standardized approach to conceptualizing the types and structures of capacity-building strategies. This standardization will assist with synthesizing findings across studies and guide capacity-building practice and research.

OBJECTIVE: To investigate the association between theoretically grounded psychosocial motivators and the sun safety practice intentions of rural youth. METHODS: A survey was given to 219 members of FFA (Future Farmers of America) at high schools in the rural Midwest (average age = 16). RESULTS: Perceived self-efficacy, peer norms, response efficacy, and susceptibility predicted protective clothing and sunscreen use intentions. Among boys, perceived norms among same-sex peers; but among girls, norms among both same- and opposite-sex peers, were significant. CONCLUSIONS: Self-efficacy should be an important component of sun safety education for rural youth. Gender-specific peer norms should also be addressed. [ABSTRACT FROM AUTHOR]

The Centers for Disease Control and Prevention (CDC) is committed to achieving true improvements in people's health. In chronic disease prevention and health promotion, we have a good deal of evidence about which intervention strategies work in clinics and in communities to improve health, but we need to accelerate translating that evidence into practice. This paper provides an overview of initial efforts of the National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP) within the CDC to identify and organize the fundamental elements of translation, with the goal of understanding what our constituents need for success and to identify key issues to consider in translation. [ABSTRACT FROM AUTHOR]

PURPOSE: To compare adolescents' report of topics they wanted to discuss with their providers with what they actually discussed, and whether they talked to their providers about their self-reported health risks. METHODS: We analyzed the 1997 Commonwealth Fund Survey of the Health of Adolescent Girls, a nationally representative sample of 6728 in-school adolescent boys and girls in 5th through 12th grade. Respondents reported on health risks, whether they believed their provider should discuss certain topics, and whether their provider did talk about health-related topics. Logistic regression was used to compare proportions and assess the associations among variables. RESULTS: Adolescents most frequently discussed healthy dietary habits (49%), weight (43%), and exercise (41%) with their clinicians but most frequently wanted to discuss drugs (65%), smoking (59%), and healthy dietary habits (57%). Overall, 70.9% of the sample reported at least one of eight potential health risks, but 63% of these adolescents had not spoken to their doctor about any of these risks. Using logistic regression models, having a female provider (odds ratio [OR] 1.41), obtaining health care information from a doctor (OR 1.72) and from the Internet (OR 1.50), speaking privately with their provider (OR 1.45), and reporting more total risk factors (OR 1.59) were each associated with having discussed any risks. CONCLUSIONS: Adolescents want and need to discuss health care issues with their providers but often do not. Providing quality preventive care to adolescents will require increased physician screening and counseling about these issues. [ABSTRACT FROM AUTHOR]

Objective: To assess the quality of life and functional status of patients who have undergone hemimandibulectomy based on the type of reconstructive procedure performed.Study Design: Survey, retrospective.Methods: Twenty-one patients who had undergone hemimandibulectomy and had similar defects were divided into two groups based on the reconstructive technique utilized. Eleven patients were placed in the soft tissue reconstruction group. Ten patients were placed in the mandible reconstruction group. All patients were assessed for: function, utilizing the Performance Status Scale, and quality of life, using a general cancer questionnaire (FACT-G) and a series of questions specific for head and neck cancer patients.Results: Mandible reconstruction produced a perceived better physical appearance (P = .02), better eating ability (P = .04), and a better overall quality of life (P = .002). The mandible reconstruction cohort consistently outscored the soft tissue cohort on all questionnaires.Conclusion: Restoration of mandibular continuity after hemimandibulectomy leads to improved function and a superior quality of life in appropriately selected patients. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To explore adolescents' knowledge of and beliefs about dietary supplements, including herbs, and over-the-counter (OTC) medications. METHODS: Eighteen focus groups with 81 adolescents in Monroe County, New York, explored teens' familiarity with and beliefs about CAM, specifically dietary supplements. We asked about general health beliefs and opinions of OTC medications to provide a framework for understanding how dietary supplements are conceptualized. Groups were conducted with suburban adolescents, urban minority adolescents, adolescents with chronic illness, (asthma, eating disorders, and diabetes), and patients of complementary/alternative practitioners ('CAM practitioners'). Transcripts were analyzed for themes relating to prevention ('staying healthy') and treatment of illness ('getting better'); direct quotations are used to illustrate adolescents' views. RESULTS: Most adolescents are familiar with 'herbal medicine,' 'herbal remedies,' or 'nutritional supplements,' and are able to name specific products or complementary/alternative medicine (CAM) therapies; however, many are unfamiliar with the term 'alternative medicine.' Adolescents are more familiar with remedies or CAM therapies commonly used by people from their own cultural or ethnic background. Older suburban females and those with chronic illnesses are more familiar with herbs and supplements than other adolescents. Most supplement use is conceptually linked with treating illness rather than with preventive care. CONCLUSIONS: Most adolescents are familiar with culturally based herbal products and nutritional supplements, used for treatment of illnesses, and not for preventive care. Providers and researchers should consider chronic illness status and culture/family tradition, and clarify terms, when asking adolescents about self-care, OTCs, or CAM. [ABSTRACT FROM AUTHOR]

Most major medical organizations recommend routine screening for breast, cervical, and colorectal cancers. Screening can lead to early detection of these cancers, resulting in reduced mortality. Yet not all people who should be screened are screened, either regularly or, in some cases, ever. This report presents the results of systematic reviews of effectiveness, applicability, economic efficiency, barriers to implementation, and other harms or benefits of interventions designed to increase screening for breast, cervical, and colorectal cancers by increasing community access to these services. Evidence from these reviews indicates that screening for breast cancer (by mammography) has been increased effectively by reducing structural barriers and by reducing out-of pocket client costs, and that screening for colorectal cancer (by fecal occult blood test) has been increased effectively by reducing structural barriers. Additional research is needed to determine whether screening for cervical cancer (by Pap test) can be increased by reducing structural barriers and by reducing out-of-pocket costs, whether screening for colorectal cancer (fecal occult blood test) can be increased by reducing out-of-pocket costs, and whether these interventions are effective in increasing the use of other colorectal cancer screening procedures (i.e., flexible sigmoidoscopy, colonoscopy, double contrast barium enema). Specific areas for further research are also suggested in this report. [ABSTRACT FROM AUTHOR]

Most major medical organizations recommend routine screening for breast, cervical, and colorectal cancers. Screening can lead to early detection of these cancers, resulting in reduced mortality. Yet not all people who should be screened are screened, either regularly or, in some cases, ever. This report presents the results of systematic reviews of effectiveness, applicability, economic efficiency, barriers to implementation, and other harms or benefits of interventions designed to increase screening for breast, cervical, and colorectal cancers by increasing community demand for these services. Evidence from these reviews indicates that screening for breast cancer (mammography) and cervical cancer (Pap test) has been effectively increased by use of client reminders, small media, and one-on-one education. Screening for colorectal cancer by fecal occult blood test has been increased effectively by use of client reminders and small media. Additional research is needed to determine whether client incentives, group education, and mass media are effective in increasing use of any of the three screening tests; whether one-on-one education increases screening for colorectal cancer; and whether any demand-enhancing interventions are effective in increasing the use of other colorectal cancer screening procedures (i.e., flexible sigmoidoscopy, colonoscopy, double contrast barium enema). Specific areas for further research are also suggested in this report. [ABSTRACT FROM AUTHOR]

The onset of parental care is associated with shifts in parents' perception of sensory stimuli from infants, mediated by neural plasticity in sensory systems. In new mothers, changes in auditory and olfactory processing have been linked to plasticity at several points along both sensory pathways, including cortical changes that are modulated, at least in part, by oxytocin. In males of biparental species, vasopressin, in addition to oxytocin, is important for modulating parental behavior; however, little is known about sensory plasticity in new fathers. We examined variation in the mRNA expression of oxytocin and vasopressin receptors (Oxtr and Avpr1a) in sensory cortices of virgin males, paired nonbreeding males, and new fathers in the biparental California mouse (Peromyscus californicus), and variation among cortices using the visual cortex for comparison. Reproductive status did not affect gene expression for either receptor, but compared to the visual cortex, expression of both receptors was higher in the left auditory cortex and lower in the anterior olfactory nucleus. Additionally, expression for both receptors was higher in the left auditory cortex compared to the right auditory cortex. While oxytocin and vasopressin receptor expression may remain stable across reproductive stages in male California mice, our findings provide support for auditory cortex lateralization, with the left auditory cortex possibly displaying higher sensitivity to both oxytocin and vasopressin compared to the right., (Copyright © 2024 Elsevier Inc. All rights reserved.)

An approach is described for high-throughput quality assessment of drug candidate libraries using high-resolution acoustic ejection mass spectrometry (AEMS). Sample introduction from 1536-well plates is demonstrated for this application using 2.5 nL acoustically dispensed sample droplets into an Open Port Interface (OPI) with pneumatically assisted electrospray ionization at a rate of one second per sample. Both positive and negative ionization are shown to be essential to extend the compound coverage of this protease inhibitor-focused library. Specialized software for efficiently interpreting this data in 1536-well format is presented. A new high-throughput method for quantifying the concentration of the components (HTQuant) is proposed that neither requires adding an internal standard to each well nor further encumbers the high-throughput workflow. This approach for quantitation requires highly reproducible peak areas, which is shown to be consistent within 4.4 % CV for a 1536-well plate analysis. An approach for troubleshooting the workflow based on the background ion current signal is also presented. The AEMS data is compared to the industry standard LC/PDA/ELSD/MS approach and shows similar coverage but at 180-fold greater throughput. Despite the same ionization process, both methods confirmed the presence of a small percentage of compounds in wells that the other did not. The data for this relatively small, focused library is compared to a larger, more chemically diverse library to indicate that this approach can be more generally applied beyond this single case study. This capability is particularly timely considering the growing implementation of artificial intelligence strategies that require the input of large amounts of high-quality data to formulate predictions relevant to the drug discovery process. The molecular structures of the 872-compound library analyzed here are included to begin the process of correlating molecular structures with ionization efficiency and other parameters as an initial step in this direction., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Published by Elsevier Inc.)

The economic, socio-political, and cultural significance of camelids in the Andean region is well-recognized, yet an understanding of their management evolution over pre-historical periods remains limited. This study aims to fill this gap by conducting the first cross-regional assessment of camelid pastoralism in Peru from 900 BCE to 1470 CE, using stable carbon and nitrogen isotopic compositions from the bone collagen and fibers of 577archaeological camelids across 21 sites. This research investigates the spatio-temporal shifts in camelid dietary habits, focusing on how the rise of intensive agriculture may have influenced change and led to the evolution of distinct roles for camelids in coastal versus non-coastal Andean economies. Our analysis indicates an increase in δ13C values over time on the coast, suggesting a shift towards maize-based camelid diets. Conversely, δ13C values decrease over time in highland environments, suggesting camelids consumed relatively more wild C3 forage and/or cultivated crops such as tubers. The study also reveals a significant positive relationship between latitude and δ15N values, suggesting increasing environmental aridity enriches δ15N in bone collagen. After controlling for this latitudinal effect, we observe a rise in δ15N values in both coastal and non-coastal camelids, suggesting that in later periods camelids may have been foddered in agricultural fields that were enriched with guano or dung fertilizer used to intensify production. Importantly, this research uncovers a distinct dietary divergence between coastal and inland camelids. The observed divergence in diets suggests contrasting socio-economic uses of camelids, where coastal camelids were predominantly involved in ceremonial and political activities, while those in non-coastal areas were crucial to the subsistence economy., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Noe et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC) is an inherited cancer syndrome caused by germline pathogenic variants in the fumarate hydratase (FH) gene. Affected individuals are at risk for developing cutaneous and uterine leiomyomas and aggressive FH-deficient renal cell carcinoma (RCC) with a papillary histology. Due to a disrupted TCA cycle, FH-deficient kidney cancers rely on aerobic glycolysis for energy production, potentially creating compensatory metabolic vulnerabilities. This study conducted a high-throughput drug screen in HLRCC cell lines, which identified a critical dependency on nicotinamide adenine dinucleotide (NAD), a redox cofactor produced by the biosynthetic enzyme nicotinamide phosphoribosyltransferase (NAMPT). Human HLRCC tumors and HLRCC-derived cell lines exhibited elevated NAMPT expression compared to controls. FH-deficient HLRCC cells, but not FH-restored HLRCC or normal kidney cells, were sensitive to NAMPT inhibition. HLRCC cell line viability was significantly decreased in both 2D and 3D in vitro cultures in response to the clinically relevant NAMPT inhibitor OT-82. NAMPT inhibition in vitro significantly decreased the total amount of NAD+, NADH, NADP, NADPH, and PAR levels and the effects of NAMPT inhibition could be rescued by the downstream NAD precursor nicotinamide mononucleotide, confirming the on-target activity of OT-82. Moreover, NAMPT inhibition by OT-82 in two HLRCC xenograft models resulted in severely reduced tumor growth. OT-82 treatment of HLRCC xenograft tumors in vivo inhibited glycolytic flux as demonstrated by reduced lactate/pyruvate ratio in hyperpolarized 13C-pyruvate magnetic resonance spectroscopic imaging experiments. Overall, our data define NAMPT inhibition as a potential therapeutic approach for FH-deficient HLRCC-associated renal cell carcinoma.

Chemical screens across hundreds of cell lines have shown that the drug sensitivities of human cancers can vary by genotype or lineage. However, most drug discovery studies have relied on culture media that poorly reflect metabolite levels in human blood. Here, we perform drug screens in traditional and Human Plasma-Like Medium (HPLM). Sets of compounds that show conditional anticancer activity span different phases of global development and include non-oncology drugs. Comparisons of the synthetic and serum-derived components that comprise typical media trace sets of conditional phenotypes to nucleotide synthesis substrates. We also characterize a unique dual mechanism for brivudine, a compound approved for antiviral use. Brivudine selectively impairs cell growth in low folate conditions by targeting two enzymes involved in one-carbon metabolism. Cataloged gene essentiality data further suggest that conditional phenotypes for other compounds are linked to off-target effects. Our findings establish general strategies for identifying drug-nutrient interactions and mechanisms of action by exploiting conditional lethality in cancer cells.

Background: Sickle cell disease (SCD) is a prevalent autosomal recessive hemoglobinopathy affecting millions worldwide, particularly individuals of African ancestry. Sickle cell disease is a lifelong condition associated with a negative impact on quality of life and mortality, causing complications such as painful vaso-occlusive episodes, acute chest syndrome, stroke, long-term anemia, and end-organ damage. Currently, there are 4 U.S. Food and Drug Administration (FDA)-approved drugs, including hydroxyurea, l-glutamine, voxelotor, and crizanlizumab, which work to alleviate symptoms and prevent complications associated with SCD, albeit without addressing the underlying cause of SCD. Allogeneic hematopoietic stem cell transplant (HSCT) has shown promise as a curative approach to SCD but is limited by donor availability and associated complications. This paper aims to review the efficacy and safety of exagamglogene autotemcel and lovotibeglogene autotemcel for managing patients with SCD, including their place in therapy, cost, and accessibility in clinical care. Data Sources: The authors searched PubMed and Medline from 2017 to 2024, for primary literature on both exagamglogene autotemcel and lovotibeglogene autotemcel. Results: The authors identified relevant studies and summarized the data on the two gene therapies. Conclusion: Exagamglogene autotemcel and lovotibeglogene autotemcel are two management strategies that address the underlying cause of SCD and provide curative potential for patients with SCD., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Background: Unplanned return to the operating room (uROR) is associated with worse outcomes and increased mortality. Little is known regarding intraoperative factors associated with uROR after emergent surgery in trauma patients. The objective of this study was to identify intraoperative factors associated with uROR after emergent hemorrhage control procedures in bleeding trauma patients., Methods: We used anesthetic record of intraoperative management to perform a retrospective study (2017-2022) of bleeding trauma patients who were taken for an emergent hemorrhage control operation., Results: A total of 225 patients met the inclusion criteria, 46 (20%) had uROR, and 181 (80%) did not. While there was no difference in demographics, mechanism, admission physiology, or time from emergency department to operating room, the uROR patients had a higher Injury Severity Score (30 vs. 25, p = 0.007). While there was no difference in volume of crystalloid infused (3,552 ± 2,279 mL vs. 2,977 ± 2,817 mL, p = 0.20), whole blood (2.2 ± 0.9 vs. 2.0 ± 0.5, p = 0.20), or platelets (11.6 ± 8.6 vs. 9.2 ± 9.0, p = 0.14), the uROR group received more packed red blood cells (11.5 ± 10.6 vs. 7.8 ± 7.5, p = 0.006) and plasma (9.6 ± 8.3 vs. 6.5 ± 6.6, p = 0.01), and more uROR patients received ≥10 U of packed red blood cells (48% vs. 27%, p = 0.006). Damage-control surgery (DCS) was more common in uROR patients (78% vs. 45%, p < 0.0001). After logistic regression, ≥10 U of packed cells in the operating room (4.3 [1.5-12.8], p = 0.009), crystalloid (1.0 [1.0-1.001], p = 0.009), International Normalized Ratio (INR) (7.6 [1.3-45.7], p = 0.03), and DCS (5.7 [1.7-19.1], p = 0.005) were independently associated with uROR., Conclusion: Massive transfusion, crystalloid resuscitation, persistent coagulopathy, and DCS are the most significant risk factors for uROR. During hemorrhage control surgery in bleeding trauma patients who receive ≥10 U of blood, providers must maintain a keen focus on minimizing crystalloid and ongoing balanced resuscitation, particularly during damage-control procedures., Level of Evidence: Retrospective/Descriptive; Level IV., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Fabry Registry data were analyzed among 83 agalsidase beta-treated patients with Fabry disease who switched to migalastat. Outcomes (estimated glomerular filtration rate [eGFR], urine protein-creatinine ratio [UPCR], plasma globotriaosylceramide [GL-3], plasma globotriaosylsphingosine [lyso-GL-3], interventricular septal wall thickness [IVST], left posterior wall thickness [LPWT], left ventricular mass index [LVMI]) were assessed using linear mixed models to estimate annual change over time in the pre- and postswitch periods. eGFR decreased throughout both periods (preswitch: -0.85 mL/min/1.73 m 2 /year; postswitch: -1.96 mL/min/1.73 m 2 /year; both p < 0.0001), with steeper decline postswitch (p pre/post  = 0.01) in both classic and late-onset patients. UPCR increased significantly postswitch (p pre/post  = 0.003) among classic patients and was stable in both periods among late-onset patients. GL-3 trajectories worsened postswitch across phenotypes (p pre/post  = 0.0005 classic, 0.02 late-onset). LPWT was stable preswitch (0.07 mm/year, p = 0.25) and decreased postswitch (-0.51 mm/year, p = 0.0005; p pre/post  = 0.0009), primarily among late-onset patients. IVST and LVMI slopes varied significantly by phenotype. Among classic patients, IVST and LVMI were stable and decreasing, respectively preswitch and increasing postswitch (p pre/post  = 0.02 IVST, 0.01 LVMI). Among late-onset patients, IVST significantly decreased postswitch (p pre/post  = 0.0003); LVMI was stable over time (p pre/post  = 0.89). Ultimately, eGFR and GL-3 trajectories worsened postswitch across phenotypes, while UPCR and cardiac measures worsened among classic and stabilized/improved among late-onset patients. These findings indicate variability in long-term outcomes after switching from ERT to migalastat, underscoring the importance of careful monitoring., (© 2024 The Author(s). Journal of Inherited Metabolic Disease published by John Wiley & Sons Ltd on behalf of SSIEM.)

Background: COVID-19 can cause profound inflammation and coagulopathy, and while many mechanisms have been proposed, there is no known common pathway leading to a prothrombotic state., Objectives: From the beginning of the COVID-19 pandemic, elevated levels of extracellular histones have been found in plasma of patients infected with SARS-CoV-2. We hypothesized that platelet activation triggered by extracellular histones might represent a unifying mechanism leading to increased thrombin generation and thrombosis., Methods: We utilized blood samples collected from an early clinical trial of hospitalized COVID-19 patients (NCT04360824) and recruited healthy subjects as controls. Using plasma samples, we measured the procoagulant and prothrombotic potential of circulating extracellular histones and extracellular vesicles (EVs). Platelet prothrombotic activity was assessed via thrombin generation potential and platelet thrombus growth. Circulating EVs were assessed for thrombin generation potential in vitro in plasma and enhancement of thrombotic susceptibility in vivo in mice., Results: Compared with controls, COVID-19 patients had elevated plasma levels of citrullinated histone H3, cell-free DNA, nucleosomes, and EVs. Plasma from COVID-19 patients promoted platelet activation, platelet-dependent thrombin generation, thrombus growth under venous shear stress, and release of platelet-derived EVs. These prothrombotic effects of COVID-19 plasma were inhibited by an RNA aptamer that neutralizes both free and DNA-bound histones. EVs isolated from COVID-19 plasma enhanced thrombin generation in vitro and potentiated venous thrombosis in mice in vivo., Conclusion: We conclude that extracellular histones and procoagulant EVs drive the prothrombotic state in COVID-19 and that histone-targeted therapy may prove beneficial., Competing Interests: Declaration of competing interests There are no competing interests to disclose., (Published by Elsevier Inc.)

Background: Chronic respiratory insufficiency from progressive muscle weakness causes morbidity and mortality in late-onset Pompe disease (LOPD). Previous Pompe Registry (NCT00231400) analyses for ≤ 5 years' alglucosidase alfa treatment showed a single linear time trend of stable forced vital capacity (FVC) % predicted., Methods: To assess longer term Pompe Registry data, piecewise linear mixed model regression analyses estimated FVC% predicted trajectories in invasive-ventilator-free patients with LOPD aged ≥ 5 years. We estimated annual FVC change 0-6 months, > 6 months-5 years, and > 5-13 years from treatment initiation, adjusting for baseline age, sex, and non-invasive ventilation., Findings: Among 485 patients (4612 FVC measurements; 8.3 years median follow-up), median ages at symptom onset, diagnosis, and alglucosidase alfa initiation were 34.3, 41.1, and 44.9 years, respectively. FVC% increased during the first 6 months' treatment (slope 1.83%/year; 95% confidence interval: 0.66, 3.01; P = 0.0023), then modestly declined -0.54%/year (-0.79, -0.30; P < 0.0001) during > 6 months-5 years, and -1.00%/year (-1.36, -0.63; P < 0.0001) during > 5-13 years. The latter two periods' slopes were not significantly different from each other (P difference  = 0.0654) and were less steep than published natural history slopes (-1% to -4.6%/year). Estimated individual slopes were ≥ 0%/year in 96.1%, 30.3%, and 13.2% of patients during the 0-6 month, > 6 month-5 year, and > 5-13 year periods, respectively., Conclusion: These real-world data indicate an alglucosidase alfa benefit on FVC trajectory that persists at least 13 years compared with published natural history data. Nevertheless, unmet need remains since most individuals demonstrate lung function decline 5 years after initiating treatment. Whether altered FVC trajectory impacts respiratory failure incidence remains undetermined., Trial Registration: This study was registered (NCT00231400) on ClinicalTrials.gov on September 30, 2005, retrospectively registered., (© 2024. The Author(s).)

Background: Higher coffee intake has been associated with reduced risk of prostate cancer, particularly aggressive forms. The activation of the phosphoinositide 3-kinase (PI3K) signaling pathway plays an important role in prostate carcinogenesis., Objective: To evaluate associations between prediagnostic coffee intake and a PI3K activation score, the expression/presence of PI3K regulators, and downstream effectors in tumor tissue from men with prostate cancer in the Health Professionals Follow-Up Study, a prospective cohort study conducted in the United States., Design: A case-only study design was applied. Coffee intake was assessed using validated food frequency questionnaires completed in 1986 and every 4 years thereafter until prostate cancer diagnosis., Participants Setting: Study participants comprised 1242 men diagnosed with prostate cancer from 1986 to 2009 and with tumor markers assessed from tissue microarrays constructed from tumor specimens., Main Outcome Measures: The outcomes include the PI3K activation score; expression of insulin receptor and insulin-like growth factor 1 receptor; angiogenesis markers; and presence of the tumor suppressor phosphatase and tensin homolog, chronic and acute inflammation, simple atrophy, and post-atrophic hyperplasia., Statistical Analyses Performed: Multivariable linear or logistic regression was conducted to estimate associations between coffee intake and tumor marker expression/presence., Results: Among coffee drinkers (86.6% of the population), median (25th, 75th percentile) coffee intake was 2 c/day (1, 3 c/day). The associations between coffee consumption and the tumor markers of interest were generally weak with modest precision. When comparing men who drank >3 c/day coffee with nondrinkers, the absolute percent difference in the PI3K activation score and angiogenesis markers ranged from 0.6% to 3.6%. The odds ratios for phosphatase and tensin homolog loss, insulin-like growth factor 1 receptor and insulin receptor expression, and presence of chronic and acute inflammation, simple atrophy, and postatrophic hyperplasia also were not statistically significant, were imprecise, and ranged from 0.82 to 1.58., Conclusions: Coffee intake was not observed to be associated with PI3K activation, related regulators, and several effectors in prostate tumor tissue. Studies exploring alternative pathways or earlier steps in carcinogenesis are needed to investigate the underlying mechanisms of the coffee and prostate cancer association., (Copyright © 2024. Published by Elsevier Inc.)

AbstractDevelopmental plasticity allows organisms to increase the fit between their phenotype and their early-life environment. The extent to which such plasticity also enhances adult fitness is not well understood, however, particularly when early-life and adult environments differ substantially. Using a cross-factorial design that manipulated diet at two life stages, we examined predictions of major hypotheses-silver spoon, environmental matching, and thrifty phenotype-concerning the joint impacts of early-life and adult diets on adult morphology/display traits, survival, and reproductive allocation. Overall, results aligned with the silver spoon hypothesis, which makes several predictions based on the premise that development in poor-quality environments constrains adult performance. Males reared and bred on a low-protein diet had lower adult survivorship than other male treatment groups; females' survivorship was higher than males' and not impacted by early diet. Measures of allocation to reproduction primarily reflected breeding diet, but where natal diet impacted reproduction, results supported the silver spoon. Both sexes showed reduced expression of display traits when reared on a low-protein diet. Results accord with other studies in supporting the relevance of the silver spoon hypothesis to birds and point to significant ramifications of sex differences in early-life viability selection on the applicability/strength of silver spoon effects.

Introduction: With increasing tobacco product varieties, understanding tobacco use (TU) profiles and their associations with tobacco dependence (TD) has also become increasingly challenging., Aims and Methods: We aimed to identify TU profiles and their associations with TD over time, and to identify subgroups with high risk of TD. We included 3463 adult recent tobacco users who had complete TU and TD data across waves 1-4 of the Population Assessment of Tobacco and Health (PATH) study. We used a composite index of TD and a summed TD score from an established 16-item TD measure. We applied a latent class analysis to identify TU profiles based on participants' usage of eight common tobacco product groups at each survey wave and to check the stability of the TU profiles over time. We then used generalized estimating equations regressions to evaluate the longitudinal TU-TD association, adjusting for potential confounders., Results: We identified three distinct TU profiles that remained consistent across four survey waves: Dominant cigarette users (62%-68%), poly users with high propensity of using traditional cigarettes, e-cigarettes, and cigars (24%-31%), and dominant smokeless product users (7%-9%). Covariate-adjusted models showed that TD was significantly lower among the poly users and the dominant smokeless users, compared to that among the dominant cigarette users., Conclusions: Both TU profiles and their associations with TD were stable over time at the population level. Poly users and smokeless product users were consistently associated with lower TD than cigarette-dominant users, suggesting the need for tailored tobacco cessation interventions for users with different TU profiles., Implications: The finding of consistent TU profiles across four survey waves extends the current literature in capturing TU patterns in an evolving tobacco product landscape. The finding of the overall higher level of TD among the cigarette-dominant users compared to the other TU latent profiles (the Cig+eCig+Cigar dominant poly users and the dominant smokeless product users) can help identify high-risk groups for potential interventions. Our application of innovative statistical methods to high-quality longitudinal data from the PATH study helps improve the understanding of the dynamic TU-TD relationship over time., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)