An evaluation of the Index4 tool for chemotherapy toxicity prediction in cancer patients older than 70 years old.

Chemotherapy, although beneficial for improving outcomes in both localized and metastatic cancers, may be associated with significant adverse effects, especially for patients with decreased functional reserves. Prediction of patients who will not tolerate well chemotherapy treatment may help in modifying treatment plans and in reallocating resources to vulnerable patients. One hundred seventeen consecutive cancer patients over the age of 70 scheduled for chemotherapy treatment in a single cancer center were included in the study. Prediction of adverse chemotherapy outcomes were calculated using a prediction tool proposed and validated from the Cancer and Aging Research Group (CARG) and a prediction tool proposed by us, called Index4. The 2 tools were compared for their ability to predict grade 3 and 4 toxicities, Emergency Department (ED) and hospital admissions and chemotherapy discontinuation. The accuracy of both predictive tools was suboptimal. A high CARG score had a sensitivity of 46.3% and a specificity of 82% and an Index4 of 1 or above had a sensitivity of 53.7% and a specificity of 60% in predicting grade 3-4 adverse effects. The performance of the 2 tools in predicting ED and hospital admissions and chemotherapy discontinuation was comparable. An Index4 score of 0 was superior in predicting absence of grade 3-4 toxicities than a low CARG score (p = 0.002, McNemar's test). The CARG tool for chemotherapy adverse effect prediction in geriatric cancer patients and the Index4 were able to predict adverse outcomes with moderate accuracy. Given its ease of calculation Index4 may be an alternative to CARG tool, suitable for a busy oncology practice.

Prognostic Role of Tumor Budding in Breast Cancer Patients Receiving Neo-Adjuvant Therapy.

BACKGROUND: Isolated tumor cells or small clusters of tumor cells observed in the vicinity of the main tumor mass in pathology sections, termed tumor budding, are common in cancers and have been associated with prognosis in some settings. This study examined the clinical associations and treatment efficacy implications of tumor budding in breast cancer patients receiving neo-adjuvant therapy. METHODS: Breast cancer patients that received neo-adjuvant therapy before definitive surgical treatment in a single cancer center over a 7-year period were included, and their records were reviewed. Data extracted included patient demographics, tumor characteristics and pathologic response to treatment at surgery. The initial breast cancer biopsy before any therapy was reviewed by two pathologists, and a hot spot area was evaluated for tumor budding (defined as 1 to 5 cancer cells observed detached from the main tumor mass). RESULTS: Seventy-five patients who received neo-adjuvant therapy (73 received chemotherapy and 2 received hormonal therapy) were included. Tumor budding was observed in two-thirds of the patients. There were no significant differences in patient (age and menopause status) and tumor (stage, histology and molecular sub-type equivalent) characteristics between the group that had tumor budding and the group that did not have tumor budding in the pre-treatment biopsy. Likewise, no statistically significant differences were observed in the frequency of complete or partial responses between the two groups. CONCLUSION: In this cohort of breast cancer patients receiving neo-adjuvant therapy, tumor budding was frequent, but it was not associated with tumor characteristics or pathologic responses to treatment. The value of tumor budding as a prognostic factor in the neo-adjuvant setting within the general breast cancer population could not be confirmed, but such a value in specific sub-groups deserves further investigation, given the pathophysiologic rationale and data from other settings.

Mechanistic Effect Modeling of Earthworms in the Context of Pesticide Risk Assessment: Synthesis of the FORESEE Workshop.

Earthworms are important ecosystem engineers, and assessment of the risk of plant protection products toward them is part of the European environmental risk assessment (ERA). In the current ERA scheme, exposure and effects are represented simplistically and are not well integrated, resulting in uncertainty when the results are applied to ecosystems. Modeling offers a powerful tool to integrate the effects observed in lower tier laboratory studies with the environmental conditions under which exposure is expected in the field. This paper provides a summary of the (In)Field Organism Risk modEling by coupling Soil Exposure and Effect (FORESEE) Workshop held 28-30 January 2020 in Düsseldorf, Germany. This workshop focused on toxicokinetic-toxicodynamic (TKTD) and population modeling of earthworms in the context of ERA. The goal was to bring together scientists from different stakeholder groups to discuss the current state of soil invertebrate modeling and to explore how earthworm modeling could be applied to risk assessments, in particular how the different model outputs can be used in the tiered ERA approach. In support of these goals, the workshop aimed at addressing the requirements and concerns of the different stakeholder groups to support further model development. The modeling approach included 4 submodules to cover the most relevant processes for earthworm risk assessment: environment, behavior (feeding, vertical movement), TKTD, and population. Four workgroups examined different aspects of the model with relevance for risk assessment, earthworm ecology, uptake routes, and cross-species extrapolation and model testing. Here, we present the perspectives of each workgroup and highlight how the collaborative effort of participants from multidisciplinary backgrounds helped to establish common ground. In addition, we provide a list of recommendations for how earthworm TKTD modeling could address some of the uncertainties in current risk assessments for plant protection products. Integr Environ Assess Manag 2021;17:352-363. © 2020 SETAC.

Application of General Unified Threshold Models of Survival Models for Regulatory Aquatic Pesticide Risk Assessment Illustrated with an Example for the Insecticide Chlorpyrifos.

Mathematical models within the General Unified Threshold models of Survival (GUTS) framework translate time-variable chemical exposure information into expected survival of animals. The GUTS models are species and compound specific and explicitly describe the internal exposure dynamics in an organism (toxicokinetics) and the related damage and effect dynamics (toxicodynamics), thereby connecting the external exposure concentration dynamics with the simulated mortality or immobility over time. In a recent scientific opinion on toxicokinetic-toxicodynamic (TKTD) models published by the European Food Safety Authority (EFSA), the GUTS modeling framework was considered ready for use in the aquatic risk assessment for pesticides and aquatic fauna. The GUTS models are suggested for use in risk assessment, if they are sufficiently validated for a specific substance-species combination. This paper aims to illustrate how they can be used in the regulatory environmental risk assessment for pesticides for a specific type of refinement, that is, when risks are triggered by lower tiers in acute as well as in chronic risk assessment and mortality or immobility is the critical endpoint. This approach involves the evaluation of time-variable exposure regimes in a so-called "Tier-2C" assessment. The insecticide chlorpyrifos was selected as an example compound because a large data set was available. The GUTS models for 13 different freshwater arthropods and 8 different theoretical aquatic exposure profiles were used to calculate a series of GUTS-based risk estimates, including exposure profile-specific multiplication factors leading to 50% mortality or immobility at the end of the tested profile (LP50/EP50) as "margins of safety." To put the use of GUTS models within the tiered aquatic risk assessment into perspective, GUTS models for the 13 aquatic arthropods were also used to predict the environmental risks of a measured chlorpyrifos exposure profile from an experimental ditch study (Tier-3 approach), and the results are discussed in the context of calibration of the tiered approach. Integr Environ Assess Manag 2021;17:243-258. © 2020 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

The challenge of timing: a qualitative study on clinician and patient perspectives about implementing exercise-based rehabilitation in an acute cancer treatment setting.

OBJECTIVE: Assess the barriers and facilitators to implementing an exercise-based rehabilitation program in an acute setting for cancer survivors receiving treatment. METHODS: A qualitative study using individual semi-structured interviews and focus groups was completed with 25 clinicians working in oncology and 9 patients receiving cancer treatment who were purposively sampled at a tertiary hospital. Interviews were audio-recorded and transcribed verbatim with coding completed independently by two reviewers and confirmed by a third reviewer, followed by thematic analysis. RESULTS: The main theme was finding the 'right time' for rehabilitation. Exercise-based rehabilitation was seen as important to deliver in the acute cancer treatment setting but challenging due to patient factors such as feeling overwhelmed and health service constraints. Barriers and facilitators to acute exercise-based rehabilitation were raised under four sub-themes: attitudes, knowledge, convenience and resources. There was agreement among both patients and clinicians around the main themes. CONCLUSION: Implementing exercise-based rehabilitation in the acute cancer treatment setting is viewed as necessary but challenging to implement. Positive attitudes towards exercise-based cancer rehabilitation services from staff and patients in this study are at odds with current levels of service delivery. This study provides evidence for why this might be the case, and can be used to inform the design of future models of rehabilitation in the acute treatment setting to meet the needs of this patient group.

Mosquito Community and West Nile Virus Risk on a National Guard Training Base in Oklahoma.

Military bases are important areas for mosquito surveillance to maintain active duty combat readiness and protect training exercises. The aim of this study was to assist Camp Gruber National Guard training facility personnel to assess their mosquito community and West Nile virus (WNV) risk using biweekly sampling of 50 sites. Between May and October 2018, 10,259 adult female mosquitoes consisting of 6 genera and 26 species were collected over 662 trap-nights using 2 trap types. The most commonly collected genus was Culex (72.2% of total), followed by Psorophora (13.3%) and Aedes (10.2%). Of note, most of the medically important species were collected in the area containing troop living quarters, including 1 WNV-positive pool of Culex tarsalis. Two specimens of Aedes aegypti were collected around a vehicle storage area. While smaller in land mass size than many other active military bases in Oklahoma, the diversity of species at Camp Gruber was comparable to collections from 4 larger bases in Oklahoma. These data demonstrate the need for regular season-long mosquito monitoring of training bases to protect the health of active duty and reserve military personnel.

Prediction of hospital admissions and grade 3-4 toxicities in cancer patients 70 years old and older receiving chemotherapy.

AIM: To predict chemotherapy toxicity and hospitalisations in elderly patients using clinical and laboratory parameters. METHODS: Records of cancer patients 70 years old or older who received adjuvant chemotherapy or first-line chemotherapy for a cancer in a single centre were reviewed. Factors associated with hospitalisations, grade 3-4 toxicities and dose reductions during treatment were evaluated. RESULTS: A total of 275 patients included in the study. Most patients (53.8%) were 70 to 75 years old. One hundred and five patients (38.2%) had a hospital admission during or within a month after their chemotherapy treatment. The only factor associated with admissions in the multivariate analysis was ECOG performance status (PS) >1 (p = .008, odds ratio 2.66, 95% CI: 1.28-5.53) and hypoalbuminaemia approached significance. Grade 3 and 4 toxicities were associated with a lower creatinine clearance in the multivariate analysis (p = .01, odds ratio 0.98, 95% CI: 0.97-1.0), and dose reductions were associated with metastatic stage (p = .03, odds ratio 1.88, 95% CI: 1.05-3.35). A combined index with all four parameters was associated with all three outcomes of interest. CONCLUSION: ECOG PS, stage, albumin and creatinine clearance may be predictive of hospital admissions, grade 3-4 toxicities and dose reduction rates in cancer patients 70 years old and older receiving chemotherapy.

Instrument-Assisted Soft Tissue Mobilization: A Systematic Review and Effect-Size Analysis.

OBJECTIVE: To determine the overall effectiveness of instrument-assisted soft tissue mobilization (IASTM) in improving range of motion (ROM), pain, strength, and patient-reported function in order to provide recommendations for use. We also sought to examine the influence of IASTM on injured and healthy participants, body part treated, and product used. DATA SOURCES: We searched the Academic Search Premier, Alt Healthwatch, CINAHL Complete, Cochrane Library, MEDLINE with full text, NLM PubMed, Physical Education Index, Physiotherapy Evidence Database (PEDro), SPORTDiscus with full text, and Web of Science databases for articles published from 1997 through 2016. The Boolean string advantEDGE OR astym OR graston OR iastm OR "instrument assist* soft tissue mobil*" OR "augment* soft tissue mobil*" OR "myofascial release" OR "instrument assist* massage" OR "augment* massage" OR "instrument assist* cross fiber massage" was used. STUDY SELECTION: Included articles were randomized controlled trials that measured ROM, pain, strength, or patient-reported function and compared IASTM treatment with at least 1 other group. DATA EXTRACTION: Thirteen articles met the inclusion criteria. Four independent reviewers assessed study quality using the PEDro and Centre for Evidence-Based Medicine scales. Twelve articles were included in the effect-size analysis. DATA SYNTHESIS: The average PEDro score for studies of uninjured participants was 5.83 (range = 5 to 7) and that for studies of injured participants was 5.86 (range = 3 to 7). Large effect sizes were found in outcomes for ROM (uninjured participants), pain (injured participants), and patient-reported function (injured participants). The different IASTM tools used in these studies revealed similar effect sizes in the various outcomes. CONCLUSIONS: The current literature provides support for IASTM in improving ROM in uninjured individuals as well as pain and patient-reported function (or both) in injured patients. More high-quality research involving a larger variety of patients and products is needed to further substantiate and allow for generalization of these findings.

Patient perceptions and interactions with their web portal-based laboratory results.

BACKGROUND: The movement to improve patient-centred care, combined with the development of user-friendly technology has led to the spread of electronic patient portals (EPP). Little research has examined the effects of providing patients with access to their laboratory results on their healthcare and health behaviours. OBJECTIVE: The purpose of this study was to gain insight into the use of EPPs, understand why patients use EPPs to access their laboratory results and explore its impact on their health. METHOD: Semistructured interviews were conducted with 21 patients who used the laboratory results section of an EPP. Interviews were analysed using a grounded theory approach. RESULTS: Participant interactions with their laboratory results varied based on their level of understanding of their results. Benefits of EPP-based access to test results included convenience, fewer appointments and decreased anxiety. Some participants described increased engagement in their healthcare and positive health changes. However, some were concerned about receiving alarming test results. CONCLUSION: Healthcare providers using EPPs to provide patients with their test results should try to ensure their patients understand their test results. Patient comprehension of test results may be improved by having providers comment on the meaning of test results and by encouraging patients to use specific websites and search options within EPPs.

The metabolic syndrome and its components as prognostic factors in metastatic colorectal cancer.

BACKGROUND: Components of the metabolic syndrome (MetS) are involved in colorectal cancer development and the incidence of the disease is higher in obese and diabetic patients. Nevertheless, the value of these diseases or the MetS as a whole as prognostic markers once colorectal cancer is diagnosed is controversial. METHODS: Patients with metastatic colorectal cancer treated in our center over a 6-year period were reviewed and data on baseline characteristics of the patients and their cancers were extracted. Data on the presence and pharmacologic treatments of the four components of the MetS (obesity, diabetes, hypertension, and dyslipidemia) were also recorded. Overall survival (OS) and progression-free survival (PFS), Kaplan-Meier curves of the various groups were constructed and compared with the log-rank test. RESULTS: One hundred and twenty-three patients were included in the analysis. The prevalence of the four MetS components was 66.1% for overweight/obesity, 25.2% for diabetes, 61% for hypertension, and 41.5% for dyslipidemia. Among the four components of the metabolic syndrome, none was associated with either PFS or OS. Diabetes tended to approach significance for PFS (p = 0.08). The MetS as a whole did not influence survival outcome. MetS was not prognostic even if the overweight category was not considered as a positive element of the syndrome. CONCLUSION: These data suggest that diabetes or other metabolic syndrome elements are not prognostic factors for PFS or OS in metastatic colorectal cancer. Further investigation may be warranted with a focus on refinement of the metabolic evaluation.

Diabetes, Obesity, and the Metabolic Syndrome as Prognostic Factors in Stages I to III Colorectal Cancer Patients.

BACKGROUND: Attempts to introduce prognostic factors for survival outcomes in localized colorectal cancer patients receiving surgical treatment with or without adjuvant therapies, beyond the classic staging parameters, have been met with limited success. Obesity and diabetes mellitus are among the conditions that predispose to colorectal cancer but their value as prognostic markers once the disease is diagnosed is controversial. PATIENTS AND METHODS: This study examines the prognostic value of the components of metabolic syndrome in a retrospective series of colorectal cancer patients with stages I to III disease followed in a single center. RESULTS: Among the four components of the metabolic syndrome, only diabetes was independently associated with progression-free survival (PFS) while obesity, hypertension, and dyslipidemia were not. No associations of the metabolic syndrome (MS) or its components with overall survival (OS) were observed in multivariate analysis. CONCLUSION: These data pinpoint to diabetes mellitus (DM) as a possible prognostic factor for PFS in localized colorectal cancer and further cast doubt for the value of obesity as measured by body mass index (BMI) on local stage colorectal cancer prognosis.

'A good stepping stone to normality': a qualitative study of cancer survivors' experiences of an exercise-based rehabilitation program.

PURPOSE: Exercise-based rehabilitation is not routinely offered to patients. We explored the experience of cancer survivors completing an exercise-based cancer rehabilitation program with and without motivational interviewing. METHOD: A qualitative study using semi-structured interviews and thematic analysis was completed with a purposive sample of 26 cancer survivors (n = 17 female, n = 18 post-treatment) participating in cancer rehabilitation at a tertiary hospital. Interviews were recorded and transcribed verbatim. Coding was completed by two reviewers independently and confirmed by a third reviewer. RESULTS: The main theme that emerged was exercise-based rehabilitation facilitated a return to normality after diagnosis which included positive changes in physical activity behaviour. Sub-themes were that rehabilitation is person-centred, challenges expectations, empowering and facilitated by expert staff. Common themes emerged whether participants received additional motivational interviewing or not. However, participants who received motivational interviewing were more likely to report feeling accountable for their physical activity levels. Transition to ongoing independent physical activity remained a challenge for some people who did not feel empowered or socially supported. CONCLUSION: Exercise-based cancer rehabilitation is important in facilitating 'return to normal' including increased participation in physical activity. To challenge expectations and to empower cancer survivors, rehabilitation programs should be person-centred and led by expert staff.

Quantifying pesticide deposits and spray patterns at micro-scales on apple (Malus domesticus) leaves with a view to arthropod exposure.

BACKGROUND: Pesticides used in commercial crop systems can adversely affect non-target arthropod populations. The spatial distribution of pesticide residues is rarely studied at scales relevant to these populations. Here, we combine two methods for assessing pesticide spray deposits at spatial scales relevant to non-target arthropods found in apple orchards. Pesticide residues were determined on individual apple leaves through conventional residue analysis; water-sensitive paper was used to investigate spatial distributions in deposits at the micro-scale. We also evaluated how accurately a digital image analysis program estimated pesticide residues. RESULTS: We found that mean pesticide spray coverage on water-sensitive paper varied by up to 6.1% (95% CI 9.4%, 2.7%) within an apple orchard, and leaf residues varied by up to 0.95 (95% CI 0.54, 1.36) mg kg-1 within a tree. Leaf residues based on analytical chemistry were six times lower than pesticide deposition estimated through image analysis of water-sensitive paper, although these correlated strongly. This correlation allowed estimation of actual residues by application of a correction factor. CONCLUSION: Our method demonstrates accurate estimation of pesticide deposits at the individual leaf scale through digital analysis of water-sensitive paper and is a low-cost, rapid alternative to conventional residue analysis techniques. © 2018 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Scientific Opinion on the state of the art of Toxicokinetic/Toxicodynamic (TKTD) effect models for regulatory risk assessment of pesticides for aquatic organisms.

Following a request from EFSA, the Panel on Plant Protection Products and their Residues (PPR) developed an opinion on the state of the art of Toxicokinetic/Toxicodynamic (TKTD) models and their use in prospective environmental risk assessment (ERA) for pesticides and aquatic organisms. TKTD models are species- and compound-specific and can be used to predict (sub)lethal effects of pesticides under untested (time-variable) exposure conditions. Three different types of TKTD models are described, viz., (i) the 'General Unified Threshold models of Survival' (GUTS), (ii) those based on the Dynamic Energy Budget theory (DEBtox models), and (iii) models for primary producers. All these TKTD models follow the principle that the processes influencing internal exposure of an organism, (TK), are separated from the processes that lead to damage and effects/mortality (TD). GUTS models can be used to predict survival rate under untested exposure conditions. DEBtox models explore the effects on growth and reproduction of toxicants over time, even over the entire life cycle. TKTD model for primary producers and pesticides have been developed for algae, Lemna and Myriophyllum. For all TKTD model calibration, both toxicity data on standard test species and/or additional species can be used. For validation, substance and species-specific data sets from independent refined-exposure experiments are required. Based on the current state of the art (e.g. lack of documented and evaluated examples), the DEBtox modelling approach is currently limited to research applications. However, its great potential for future use in prospective ERA for pesticides is recognised. The GUTS model and the Lemna model are considered ready to be used in risk assessment.

High Incomplete Skeletal Muscle Fatty Acid Oxidation Explains Low Muscle Insulin Sensitivity in Poorly Controlled T2D.

Context: Almost 50% of type 2 diabetic (T2D) patients are poorly controlled [glycated hemoglobin (HbA1c) ≥ 7%]; however, the mechanisms responsible for progressively worsening glycemic control are poorly understood. Lower skeletal muscle mitochondrial respiratory capacity is associated with low insulin sensitivity and the development of T2D. Objective: We investigated if skeletal muscle insulin sensitivity (SI) was different between well-controlled T2D (WCD) and poorly controlled T2D (PCD) and if the difference was associated with differences resulting from mitochondrial respiratory function. Design: Vastus lateralis muscle mitochondrial respiration, mitochondrial content, mitochondrial enzyme activity, and fatty acid oxidation (FAO) were measured. SI and the acute response to glucose (AIRg) were calculated by MINMOD analysis from glucose and insulin obtained during a modified, frequently sampled, intravenous glucose tolerance test. Results: SI and AIRg were lower in PCD than WCD. Muscle incomplete FAO was greater in PCD than WCD and greater incomplete FAO was associated with lower SI and higher HbA1c. Hydroxyacyl-coenzyme A dehydrogenase expression and activity were greater in PCD than WCD. There was no difference in maximal mitochondrial respiration or content between WCD and PCD. Conclusion: The current results suggest that greater skeletal muscle incomplete FAO in poorly controlled T2D is due to elevated ß oxidation and is associated with worsening muscle SI.

Results of a prospective randomized control trial comparing hydrophilic to uncoated catheters in children with neurogenic bladder.

INTRODUCTION: Children with neurogenic bladder (NGB) often require a lifetime of clean intermittent catheterization (CIC), typically using uncoated catheters (UCs). Hydrophilic catheters (HCs) have lower friction than UCs with reported less damage to the urethra. The purpose of this study is to compare outcomes between these catheters. METHODS: An investigator-initiated, prospective, randomized clinical trial was conducted to compare HCs versus UCs. Children aged 2-17 years with NGB on CIC were enrolled for 1 year. Block randomization was used. Dexterity scores were obtained in those who perform self-catheterization. Outcomes were UTI, difficulty passing the catheter, urethral injury, and patient satisfaction. RESULTS: Demographic data is presented in the Table. Seventy-eight patients were enrolled. Age and gender were similar between the groups. Fifteen patients in each group performed CIC via an abdominal wall stoma. Eight and 15 patients withdrew from the UC and HC groups, respectively. The HC group overall had more problems with the catheter, mainly difficulty with handling. There were no differences for passing the catheter, pain, hematuria, or urethral injuries. There were two urinary tract infections (UTIs) in two HC patients and 17 UTIs in seven UC patients (p = 0.003). Patients with UTIs in the HC group went from 16% in the previous year to 5% during the study. Three children in the HC group had three or more UTIs in the year before enrollment and none during the study. The patients that completed the study with HC were overall satisfied and many requested to continue with the HC. CONCLUSIONS: HCs may decrease the risk of UTI in children with NGB. Urethral complications were low in both groups. Most HC patients were pleased but some found the slippery coating difficult to handle.

A risk assessment example for soil invertebrates using spatially explicit agent-based models.

Current risk assessment methods for measuring the toxicity of plant protection products (PPPs) on soil invertebrates use standardized laboratory conditions to determine acute effects on mortality and sublethal effects on reproduction. If an unacceptable risk is identified at the lower tier, population-level effects are assessed using semifield and field trials at a higher tier because modeling methods for extrapolating available lower-tier information to population effects have not yet been implemented. Field trials are expensive, time consuming, and cannot be applied to variable landscape scenarios. Mechanistic modeling of the toxicological effects of PPPs on individuals and their responses combined with simulation of population-level response shows great potential in fulfilling such a need, aiding ecologically informed extrapolation. Here, we introduce and demonstrate the potential of 2 population models for ubiquitous soil invertebrates (collembolans and earthworms) as refinement options in current risk assessment. Both are spatially explicit agent-based models (ABMs), incorporating individual and landscape variability. The models were used to provide refined risk assessments for different application scenarios of a hypothetical pesticide applied to potato crops (full-field spray onto the soil surface [termed "overall"], in-furrow, and soil-incorporated pesticide applications). In the refined risk assessment, the population models suggest that soil invertebrate populations would likely recover within 1 year after pesticide application, regardless of application method. The population modeling for both soil organisms also illustrated that a lower predicted average environmental concentration in soil (PECsoil) could potentially lead to greater effects at the population level, depending on the spatial heterogeneity of the pesticide and the behavior of the soil organisms. Population-level effects of spatial-temporal variations in exposure were elucidated in the refined risk assessment, using ABMs and population-level endpoints while yielding outputs that directly address the protection goals. We recommend choosing model outputs that are closely related to specific protection goals, using available toxicity data and accepted fate models to the extent possible in parameterizing models to minimize additional data needs and testing, evaluating, and documenting models following recent guidance.

Insulin sensitivity is related to glycemic control in type 2 diabetes and diabetes remission after Roux-en Y gastric bypass.

BACKGROUND: After initial onset, adequate glycemic control in patients with type 2 diabetes (T2DM) presents a continuing challenge even with aggressive pharmacologic treatment, and longer disease duration is associated with poorer resolution in response to Roux-en Y gastric bypass (RYGB). Skeletal muscle insulin sensitivity is an important determinant of glycemic control. We investigated whether skeletal muscle insulin sensitivity is predictive of T2DM resolution with RYGB and is in general lower in patients with longer-duration T2DM. METHODS: Insulin sensitivity (SI) and the acute response to glucose (AIRg) were calculated by MINMOD analysis from glucose and insulin obtained during a modified frequently sampled intravenous glucose tolerance test. RESULTS: Pre-RYGB SI and duration but not AIRg were predictive of T2DM resolution by RYGB. In addition, HbA1c was greater and SI and AIRg lower in long- (8+ years) compared with short-duration (1- to 7-year) T2DM. Multiple linear regression analysis demonstrated that SI explained 32% and AIRg 21% of the variance in HbA1c, respectively. CONCLUSION: The current results suggest that pre-RYGB SI is predictive of T2DM resolution after RYGB, skeletal muscle insulin sensitivity and ß-cell function worsen after the onset of T2DM, and low skeletal muscle insulin sensitivity as well as low ß cell function contribute to poor glycemic control in T2DM.

Effect of short-term exercise training on intramyocellular lipid content.

The purpose of this study was to investigate the influence of exercise training on intramyocellular lipid (IMCL) content and test the hypothesis that the effect of endurance-oriented exercise training on IMCL is dependent on characteristics of the population studied. Lean (N = 11, body mass index (BMI) = 22.2 ± 0.7 kg·m⁻²), obese (N = 14, BMI = 38.8 ± 1.7 kg·m⁻²), and type 2 diabetic (N = 9, BMI = 35.5 ± 2.5 kg·m⁻²) participants were examined before and after 10 consecutive days of endurance-oriented (60 min·day⁻¹ at ~70% [Formula: see text]O(2peak)) exercise training. IMCL and muscle glycogen were measured by Oil-Red-O and periodic acid - Schiff staining, respectively. The results indicated that IMCL was elevated (p < 0.05) in the obese and diabetic groups compared with the lean subjects prior to training. After training, IMCL content decreased (-35%) in the participants with type 2 diabetes; there were no changes in IMCL in the lean or obese groups. Muscle glycogen content was lower in the diabetic subjects than in the lean subjects both before and after training. These data indicate that changes in IMCL with exercise training do not exhibit a universal response but rather depend on the metabolic status of the population studied.