Overweight or obese patients with diabetes were assigned to lifestyle intervention with a weight-loss goal of 7% or to a control program of support and education. The intervention group had sustained ...weight loss but no significant reduction in cardiovascular events at 10 years.
Weight loss is recommended for overweight or obese patients with type 2 diabetes.
1
This recommendation is based on short-term studies showing numerous benefits of weight loss, including improvements in glycemic control, risk factors for cardiovascular disease, quality of life, and other obesity-related coexisting illnesses.
2
However, it is unknown whether weight loss reduces the risk of cardiovascular morbidity and mortality in patients with type 2 diabetes. Epidemiologic studies involving patients with diabetes have had conflicting results, perhaps because of confounding from unintentional weight loss.
3
A meta-analysis
4
of cohort studies concluded that moderate intentional weight loss was associated with reduced mortality among . . .
Aspirin is a chemopreventive agent for colorectal adenoma and cancer (CRC) that, like many drugs inclusive of chemotherapeutics, has been investigated for its effects on bacterial growth and ...virulence gene expression. Given the evolving recognition of the roles for bacteria in CRC, in this work, we investigate the effects of aspirin with a focus on one oncomicrobe-
We show that aspirin and its primary metabolite salicylic acid alter
strain Fn7-1 growth in culture and that aspirin can effectively kill both actively growing and stationary Fn7-1. We also demonstrate that, at levels that do not inhibit growth, aspirin influences Fn7-1 gene expression. To assess whether aspirin modulation of
may be relevant
, we use the
mouse intestinal tumor model in which Fn7-1 is orally inoculated daily to reveal that aspirin-supplemented chow is sufficient to inhibit
-potentiated colonic tumorigenesis. We expand our characterization of aspirin sensitivity across other
strains, including those isolated from human CRC tissues, as well as other CRC-associated microbes, enterotoxigenic
, and colibactin-producing
Finally, we determine that individuals who use aspirin daily have lower fusobacterial abundance in colon adenoma tissues, as determined by quantitative PCR performed on adenoma DNA. Together, our data support that aspirin has direct antibiotic activity against
strains and suggest that consideration of the potential effects of aspirin on the microbiome holds promise in optimizing risk-benefit assessments for use of aspirin in CRC prevention and management.
There is an increasing understanding of the clinical correlations and potential mechanistic roles of specific members of the gut and tumoral microbiota in colorectal cancer (CRC) initiation, progression, and survival. However, we have yet to parlay this knowledge into better CRC outcomes through microbially informed diagnostic, preventive, or therapeutic approaches. Here, we demonstrate that aspirin, an established CRC chemopreventive, exhibits specific effects on the CRC-associated
in culture, an animal model of intestinal tumorigenesis, and in human colonic adenoma tissues. Our work proposes a potential role for aspirin in influencing CRC-associated bacteria to prevent colorectal adenomas and cancer, beyond aspirin's canonical anti-inflammatory role targeting host tissues. Future research, such as studies investigating the effects of aspirin on fusobacterial load in patients, will help further elucidate the prospect of using aspirin to modulate
for improving CRC outcomes.
Microbial populations form intricate macroscopic colonies with diverse morphologies whose functions remain to be fully understood. Despite fungal colonies isolated from environmental and clinical ...samples revealing abundant intraspecies morphological diversity, it is unclear how this diversity affects fungal fitness and disease progression. Here we observe a notable effect of oxygen tension on the macroscopic and biofilm morphotypes of the human fungal pathogen Aspergillus fumigatus. A hypoxia-typic morphotype is generated through the expression of a subtelomeric gene cluster containing genes that alter the hyphal surface and perturb interhyphal interactions to disrupt in vivo biofilm and infection site morphologies. Consequently, this morphotype leads to increased host inflammation, rapid disease progression and mortality in a murine model of invasive aspergillosis. Taken together, these data suggest that filamentous fungal biofilm morphology affects fungal-host interactions and should be taken into consideration when assessing virulence and host disease progression of an isolated strain.
Abstract
Background
Differential use of endocrine therapy (ET) by race may contribute to breast cancer outcome disparities, but racial differences in ET behaviors are poorly understood.
Methods
Women ...aged 20–74 years with a first primary, stage I–III, hormone receptor–positive (HR+) breast cancer were included. At 2 years postdiagnosis, we assessed nonadherence, defined as not taking ET every day or missing more than two pills in the past 14 days, discontinuation, and a composite measure of underuse, defined as either missing pills or discontinuing completely. Using logistic regression, we evaluated the relationship between race and nonadherence, discontinuation, and overall underuse in unadjusted, clinically adjusted, and socioeconomically adjusted models.
Results
A total of 1280 women were included; 43.2% self-identified as black. Compared to white women, black women more often reported nonadherence (13.7% vs 5.2%) but not discontinuation (10.0% vs 10.7%). Black women also more often reported the following: hot flashes, night sweats, breast sensitivity, and joint pain; believing that their recurrence risk would not change if they stopped ET; forgetting to take ET; and cost-related barriers. In multivariable analysis, black race remained statistically significantly associated with nonadherence after adjusting for clinical characteristics (adjusted odds ratio = 2.72, 95% confidence interval = 1.75 to 4.24) and after adding socioeconomic to clinical characteristics (adjusted odds ratio = 2.44, 95% confidence interval = 1.50 to 3.97) but was not independently associated with discontinuation after adjustment. Low recurrence risk perception and lack of a shared decision making were strongly predictive of ET underuse across races.
Conclusions
Our results highlight important racial differences in ET-adherence behaviors, perceptions of benefits/harms, and shared decision making that may be targeted with culturally tailored interventions.
The genus
encompasses human pathogens such as
and industrial powerhouses such as
In both cases,
biofilms have consequences for infection outcomes and yields of economically important products. ...However, the molecular components influencing filamentous fungal biofilm development, structure, and function remain ill defined. Macroscopic colony morphology is an indicator of underlying biofilm architecture and fungal physiology. A hypoxia-locked colony morphotype of
has abundant colony furrows that coincide with a reduction in vertically oriented hyphae within biofilms and increased low oxygen growth and virulence. Investigation of this morphotype has led to the identification of the causative gene,
(
), a small cryptic open reading frame within a subtelomeric gene cluster. BafA is sufficient to induce the hypoxia-locked colony morphology and biofilm architecture in
Analysis across a large population of
isolates identified a larger family of
genes, all of which have the capacity to modulate hyphal architecture, biofilm development, and hypoxic growth. Furthermore, introduction of
into
is sufficient to generate the hypoxia-locked colony morphology, biofilm architecture, and increased hypoxic growth. Together, these data indicate the potential broad impacts of this previously uncharacterized family of small genes to modulate biofilm architecture and function in clinical and industrial settings.
The manipulation of microbial biofilms in industrial and clinical applications remains a difficult task. The problem is particularly acute with regard to filamentous fungal biofilms for which molecular mechanisms of biofilm formation, maintenance, and function are only just being elucidated. Here, we describe a family of small genes heterogeneously expressed across
strains that are capable of modifying colony biofilm morphology and microscopic hyphal architecture. Specifically, these genes are implicated in the formation of a hypoxia-locked colony morphotype that is associated with increased virulence of
Synthetic introduction of these gene family members, here referred to as biofilm architecture factors, in both
and
additionally modulates low oxygen growth and surface adherence. Thus, these genes are candidates for genetic manipulation of biofilm development in aspergilli.
Chemical stabilization of microbial-derived products such as extracellular enzymes (EE) onto mineral surfaces has gained attention as a possibly important mechanism leading to the persistence of soil ...organic carbon (SOC). While the controls on EE activities and their stabilization in the surface soil are reasonably well-understood, how these activities change with soil depth and possibly diverge from those at the soil surface due to distinct physical, chemical, and biotic conditions remains unclear. We assessed EE activity to a depth of 1 m (10 cm increments) in 19 soil profiles across the Critical Zone Observatory Network, which represents a wide range of climates, soil orders, and vegetation types. For all EEs, activities per mass of soil correlated positively with microbial biomass (MB) and SOC, and all three of these variables decreased logarithmically with depth (p < 0.05). Across all sites, over half of the potential EE activities per mass soil consistently occurred below 20 cm for all measured EEs. Activities per unit MB or SOC were substantially higher at depth (soils below 20 cm accounted for 80% of whole-profile EE activity), suggesting an accumulation of stabilized (i.e. mineral sorbed) EEs in subsoil horizons. The pronounced enzyme stabilization in subsurface horizons was corroborated by mixed-effects models that showed a significant, positive relationship between clay concentration and MB-normalized EE activities in the subsoil. Furthermore, the negative relationships between soil C, N, and P and C-, N-, and P-acquiring EEs found in the surface soil decoupled below 20 cm, which could have also been caused by EE stabilization. This finding suggests that EEs may not reflect soil nutrient availabilities deeper in the soil profile. Taken together, our results suggest that deeper soil horizons hold a significant reservoir of EEs, and that the controls of subsoil EEs differ from their surface soil counterparts.
To understand therapeutic priorities, a secondary data analysis on a retrospective cohort was conducted to classify rehabilitation goals according to the International Classification of Functioning, ...Disability, and Health (ICF).PURPOSETo understand therapeutic priorities, a secondary data analysis on a retrospective cohort was conducted to classify rehabilitation goals according to the International Classification of Functioning, Disability, and Health (ICF).Therapeutic goals from an initial outpatient physical or occupational therapy evaluation for patients post-stroke or with Parkinson disease, were classified into Level 1 of the ICF. Goals in the Activity and Participation component were further sub-classified as activity capacity or activity performance (self-report or direct) in daily life.MATERIALS AND METHODSTherapeutic goals from an initial outpatient physical or occupational therapy evaluation for patients post-stroke or with Parkinson disease, were classified into Level 1 of the ICF. Goals in the Activity and Participation component were further sub-classified as activity capacity or activity performance (self-report or direct) in daily life.776 goals across 104 participants were classified into Level 1 of the ICF. The majority, 73% (563/776) were classified as Activity and Participation, 20% (155/776) as Body Function and 2% (17/776) as Environmental Factors. Fifty-two percent (400/776) of all goals were classified as activity capacity and 21% (163/776) as activity performance in daily life, with 21% (160/776) of goals measuring self-report activity performance in daily life and less than 1% (3/776) of goals measuring direct activity performance in daily life.RESULTS776 goals across 104 participants were classified into Level 1 of the ICF. The majority, 73% (563/776) were classified as Activity and Participation, 20% (155/776) as Body Function and 2% (17/776) as Environmental Factors. Fifty-two percent (400/776) of all goals were classified as activity capacity and 21% (163/776) as activity performance in daily life, with 21% (160/776) of goals measuring self-report activity performance in daily life and less than 1% (3/776) of goals measuring direct activity performance in daily life.While the majority of therapeutic goals were classified into the Activity and Participation component, less than 1% of goals measured direct activity performance in daily life. If people seek outpatient rehabilitation to improve functioning in their real-world environment, therapeutic goal setting should reflect this.CONCLUSIONSWhile the majority of therapeutic goals were classified into the Activity and Participation component, less than 1% of goals measured direct activity performance in daily life. If people seek outpatient rehabilitation to improve functioning in their real-world environment, therapeutic goal setting should reflect this.
Objective
To evaluate 8‐year weight losses achieved with intensive lifestyle intervention (ILI) in the Look AHEAD (Action for Health in Diabetes) study.
Design and Methods
Look AHEAD assessed the ...effects of intentional weight loss on cardiovascular morbidity and mortality in 5,145 overweight/obese adults with type 2 diabetes, randomly assigned to ILI or usual care (i.e., diabetes support and education DSE). The ILI provided comprehensive behavioral weight loss counseling over 8 years; DSE participants received periodic group education only.
Results
All participants had the opportunity to complete 8 years of intervention before Look AHEAD was halted in September 2012; ≥88% of both groups completed the 8‐year outcomes assessment. ILI and DSE participants lost (mean ± SE) 4.7% ± 0.2% and 2.1 ± 0.2% of initial weight, respectively (P < 0.001) at year 8; 50.3% and 35.7%, respectively, lost ≥5% (P < 0.001), and 26.9% and 17.2%, respectively, lost ≥10% (P < 0.001). Across the 8 years ILI participants, compared with DSE, reported greater practice of several key weight‐control behaviors. These behaviors also distinguished ILI participants who lost ≥10% and kept it off from those who lost but regained.
Conclusions
Look AHEAD's ILI produced clinically meaningful weight loss (≥5%) at year 8 in 50% of patients with type 2 diabetes and can be used to manage other obesity‐related co‐morbid conditions.
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