Circulating insulin-like growth factor-I (IGF-I) is associated with the risk of several cancers. Dietary protein intake, particularly dairy protein, may increase circulating IGF-I; however, ...associations with different protein sources, other macronutrients, and fibre are inconclusive. To investigate the associations between intake of protein, macronutrients and their sources, fibre, and alcohol with serum IGF-I concentrations.
A total of 11,815 participants from UK Biobank who completed ≥4 24-h dietary assessments and had serum IGF-I concentrations measured at baseline were included. Multivariable linear regression was used to assess the cross–sectional associations of macronutrient and fibre intake with circulating IGF-I concentrations.
Circulating IGF-I concentrations were positively associated with intake of total protein (per 2.5% higher energy intake: 0.56 nmol/L (95% confidence interval: 0.47, 0.66)), milk protein: 1.20 nmol/L (0.90, 1.51), and yogurt protein: 1.33 nmol/L (0.79, 1.86), but not with cheese protein: −0.07 nmol/L (−0.40, 0.25). IGF-I concentrations were also positively associated with intake of fibre (per 5 g/day higher intake: 0.46 nmol/L (0.35, 0.57)) and starch from wholegrains (Q5 vs. Q1: 1.08 nmol/L (0.77, 1.39)), and inversely associated with alcohol consumption (>40 g/day vs <1 g/day: −1.36 nmol/L (−1.00, −1.71)).
These results show differing associations with IGF-I concentrations depending on the source of dairy protein, with positive associations with milk and yogurt protein intake but no association with cheese protein. The positive association of fibre and starch from wholegrains with IGF-I warrants further investigation.
To explore the link between companies investing in the health and well-being programs of their employees and stock market performance.
Stock performance of C. Everett Koop National Health Award ...winners (n = 26) was measured over time and compared with the average performance of companies comprising the Standard and Poor's (S&P) 500 Index.
The Koop Award portfolio outperformed the S&P 500 Index. In the 14-year period tracked (2000-2014), Koop Award winners' stock values appreciated by 325% compared with the market average appreciation of 105%.
This study supports prior and ongoing research demonstrating a higher market valuation--an affirmation of business success by Wall Street investors--of socially responsible companies that invest in the health and well-being of their workers when compared with other publicly traded firms.
The antibody-drug conjugate (ADC) is a well-validated modality for the cell-specific delivery of small molecules with impact expanding rapidly beyond their originally-intended purpose of treating ...cancer. However, antibody-mediated delivery (AMD) remains inefficient, limiting its applicability to targeting highly potent payloads to cells with high antigen expression. Maximizing the number of payloads delivered per antibody is one key way in which delivery efficiency can be improved, although this has been challenging to carry out; with few exceptions, increasing the drug-to-antibody ratio (DAR) above ∼4 typically destroys the biophysical properties and
efficacy for ADCs. Herein, we describe the development of a novel bioconjugation platform combining cysteine-engineered (THIOMAB) antibodies and recombinant XTEN polypeptides for the unprecedented generation of homogeneous, stable "TXCs" with DAR of up to 18. Across three different bioactive payloads, we demonstrated improved AMD to tumors and
bacteria for high-DAR TXCs relative to conventional low-DAR ADCs.
Objective: Comorbidity is the rule and not the exception among veterans with posttraumatic stress disorder (PTSD). Examining comorbidities in a veteran population allows us to better understand ...veterans' symptoms and recognize when mental health treatment may need to be tailored to other co-occurring issues. This article evaluates comorbid mood and anxiety disorders and PTSD symptom severity in a large sample of veterans from multiple eras of service, including the recent wars in Iraq and Afghanistan. Method: The current study used data from veterans who sought treatment for PTSD at a VA PTSD Clinical Team from 2005 to 2013. Veterans were assessed for PTSD, mood, and anxiety disorders using a structured clinical interview and completed self-report symptom measures as part of the PTSD clinic intake procedure. A total of 2,460 veterans were evaluated, and 867 met diagnostic criteria for PTSD. Results: Veterans with PTSD were significantly more likely than those without PTSD to be diagnosed with social anxiety disorder and obsessive-compulsive disorder, but significantly less likely to be diagnosed with depression. In addition, veterans who had at least one comorbid diagnosis in addition to PTSD reported significantly higher PTSD symptom severity than veterans with PTSD alone. PTSD symptom severity also varied by era of service. Conclusion: These results suggest that among veterans seeking treatment for PTSD, comorbid mood and anxiety disorders may be associated with greater severity of PTSD symptoms. Future work is needed to determine the impact of specific comorbidities on trauma-focused treatment outcomes.
Clinical Impact Statement
Many veterans with posttraumatic stress disorder (PTSD) also have other psychological disorders, such as depression and anxiety. In this study, veterans at a PTSD clinic were evaluated for PTSD and mood and anxiety disorders. Veterans who had at least one diagnosis in addition to PTSD had more severe PTSD symptoms than veterans with PTSD alone. Veterans from different eras of service also had different symptom profiles. It is important to understand the impact of being diagnosed with a mood or anxiety disorder in addition to PTSD to tailor treatment to the individual.
Prior studies have demonstrated that an intake of foods rich in dietary fiber is associated with a favorable impact on health status and body weight. However, the association between fiber intake and ...weight loss has not been well-studied in employer settings. This research aimed to assess the relationship between dietary fiber and weight loss among individuals participating in the Full Plate Living (FPL) program.
The 16-week plant-predominant fiber-rich eating program was delivered to 72 employers, primarily in the Southwest U.S., over 3 years (2017-2019). Participants received weekly video lessons, FPL materials, and additional online resources. A retrospective analysis of repeated measures was conducted using participant data obtained from 4,477 participants, of which 2,792 (62.5%) reduced body weight. Analysis of variance with
analysis was used to assess the statistical significance of the changes between baseline and follow-up measures of dietary fiber intake in each of the food categories, specifically the relationship between changes in individual and combined (composite) daily servings of fruits, vegetables, whole grains, beans, and nuts on body weight measures among three groups at follow-up: those who lost, maintained, or gained weight. Multilevel modeling was used to test the hypothesis that increased intake of fiber was associated with greater weight loss.
The mean weight loss for the weight loss group was 3.28 kg. As compared to the two other groups, the intake of whole fiber-rich foods at follow-up was significantly higher among the weight loss group with fruits (2.45 servings), vegetables (2.99 servings), beans (1.03 servings), and total fiber composites (9.07 servings;
< 0.001). A significant increase in servings of grains was also noted (
< 0.05). Multilevel modeling demonstrated that a higher total fiber composite (Model 1), as well as higher intakes of either vegetables or fruits (Model 2), resulted in greater weight loss.
Our findings indicate that the FPL program can be a part of a lifestyle medicine approach to healthy eating and weight loss. Delivering the program in clinical, community, and workplace settings can increase its reach as an effective and low-cost offering.
To examine the treatment recommendation patterns among urologists and radiation oncologists, the level of concordance or discordance between physician recommendations, and the association between ...physician recommendations and the treatment that patients received.
The study was a secondary analysis of data from a randomized clinical trial conducted November 2010 to April 2014 (NCT02053389). Eligible participants were patients from the trial who saw both specialists. The primary outcome was physician recommendations that were scored using an adapted version of the validated PhyReCS coding system. Secondary outcomes included concordance between physician recommendations and the treatment patients received.
Participants were 108 patients (Mean age 61.9 years; range 43-82; 87% non-Hispanic White). Urologists were more likely to recommend surgery (79% of recommendations) and radiation oncologists were more likely to recommend radiation (68% of recommendations). Recommendations from the urologists and radiation oncologists were concordant for only 33 patients (30.6%). Most patients received a treatment that both physicians recommended (59%); however, 35% received a treatment that only one of their physicians recommended. When discordant, urologists more often recommended surgery and radiation oncologists recommended radiation and surgery as equally appropriate options.
Urologists and radiation oncologists are more likely to differ than agree in their treatment recommendations for the same patients with clinically localized prostate cancer and more likely to favor treatment aligned with their specialty. Additional studies are needed to better understand how patients make decisions after meeting with two different specialists to inform the development of best practices within oncology clinics.
Introduction: The coronavirus 2019 pandemic caused a shortage of disposable N95 respirators, prompting healthcare entities to extend the use of these masks beyond their intended single-use ...manufacturer recommendation with a paucity of supporting research. Methods: We performed a prospective cohort study of ED healthcare workers (HCW) (“subjects”) required to use respirators at an academic, Level I trauma center. Subjects had been previously fit tested and assigned an appropriately sized N95 mask per hospital protocol. Per study protocol, subjects were fit tested periodically throughout their shifts and on multiple shifts over the eight-week study period. Data points collected included the age of the mask, subjective assessment of mask seal quality, and fit test results. We analyzed the data using Fisher’s exact test, and calculated odds ratios (OR) to determine the failure rate of disposable N95 masks following reuse. Results: A total of 130 HCWs underwent fit testing and 127 were included for analysis. Mask failure rate climbed after day 2 of use, with 33.3% of masks failing at day 3, 42.9% at day 4, and 50% at ≥ day 5. Categorizing the masks into those being used for two or fewer days vs those in use for three or more, failure was more common on day 3 of use or older compared to those in the first two days of use (41.8% vs 8.3%, P < 0.0001) with an OR of failure with an older mask of 7.9 (confidence interval CI, 2.8-22.3). The healthcare workers’ assessment of poor seal was 33.3% sensitive (CI, 18.6-51.9) and 95.7% specific (CI, 88.8-98.6) for fit test failure. Conclusion: Disposable N95 masks have significant failure rates following reuse in clinical practice. Healthcare personnel also performed poorly in assessing the integrity of the seal of their disposable respirators.
Key defining attributes of an antibody-drug conjugate (ADC) include the choice of the targeting antibody, linker, payload, and the drug-to-antibody ratio (DAR). Historically, most ADC platforms have ...used the same DAR for all targets, regardless of target characteristics. However, recent studies and modeling suggest that the optimal DAR can depend on target expression level and intratumoral heterogeneity, target internalization and trafficking, and characteristics of the linker and payload. An ADC platform that enables DAR optimization could improve the success rate of clinical candidates. Here we report a systematic exploration of DAR across a wide range, by combining THIOMAB protein engineering technology with Dolasynthen, an auristatin-based platform with monomeric and trimeric variants. This approach enabled the generation of homogeneous, site-specific ADCs spanning a discrete range of DARs 2, 4, 6, 12, and 18 by conjugation of trastuzumab IgG1 THIOMAB constructs with 1, 2, or 3 engineered cysteines to monomeric or trimeric Dolasynthen. All ADCs had physicochemical properties that translated to excellent in vivo pharmacology. Following a single dose of ADCs in a HER2 xenograft model with moderate antigen expression, our data demonstrated comparable pharmacokinetics for the conjugates across all DARs and dose-dependent efficacy of all test articles. These results demonstrate that the Dolasynthen platform enables the generation of ADCs with a broad range of DAR values and with comparable physiochemical, pharmacologic, and pharmacokinetics profiles; thus, the Dolasynthen platform enables the empirical determination of the optimal DAR for a clinical candidate for a given target.
This study aimed to evaluate the effect of nurse and doctor height on occupational dose to the temple during fluoroscopically guided cardiovascular procedures. Additionally, an evaluation of the ...relationship between doctor height and table height was performed. Staff exposed during fluoroscopic procedures may be at elevated risk of cardiovascular damage or oncogenesis and have demonstrated a higher incidence of subscapular cataracts. The heads of taller staff may be exposed to reduced levels of radiation due to the increased distance from the area of highest intensity X-ray scatter. Limited research has been performed investigating height as a predictor of head dose to nursing staff. The level of radiation dose at the level of the temple to the doctor (n = 25), scrub (n = 28), and scout nurse (n = 29) was measured in a prospective single-center, observational study using Philips DoseAware badges. Procedural characteristics were recorded for vascular and cardiac cases performed in three dedicated angiography suites. Data were also collected to investigate relationships between doctor height and table height. Data were collected for 1585 cardiac and 294 vascular procedures. Staff height was a statistically significant predictor of temple dose for doctors, scrub, and scout nurses when considering the full data sample. The log temple dose demonstrated an inverse relationship to staff height during cardiac procedures, but a positive relationship for scrub and scout nurses during vascular studies. This observational study has demonstrated that taller staff are exposed to less cranial exposure dose during fluoroscopically guided cardiac examinations but has revealed a positive correlation between height and temple dose during vascular procedures. It was also determined that doctor height was correlated with average procedural table height and that vascular access point influences the choice of table elevation.
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