A novel inhibitory BAK antibody enables assessment of non-activated BAK in cancer cells.

BAX and BAK are pro-apoptotic members of the BCL2 family that are required to permeabilize the mitochondrial outer membrane. The proteins can adopt a non-activated monomeric conformation, or an activated conformation in which the exposed BH3 domain facilitates binding either to a prosurvival protein or to another activated BAK or BAX protein to promote pore formation. Certain cancer cells are proposed to have high levels of activated BAK sequestered by MCL1 or BCLXL, thus priming these cells to undergo apoptosis in response to BH3 mimetic compounds that target MCL1 or BCLXL. Here we report the first antibody, 14G6, that is specific for the non-activated BAK conformer. A crystal structure of 14G6 Fab bound to BAK revealed a binding site encompassing both the α1 helix and α5-α6 hinge regions of BAK, two sites involved in the unfolding of BAK during its activation. In mitochondrial experiments, 14G6 inhibited BAK unfolding triggered by three diverse BAK activators, supporting crucial roles for both α1 dissociation and separation of the core (α2-α5) and latch (α6-α9) regions in BAK activation. 14G6 bound the majority of BAK in several leukaemia cell lines, and binding decreased following treatment with BH3 mimetics, indicating only minor levels of constitutively activated BAK in those cells. In summary, 14G6 provides a new means of assessing BAK status in response to anti-cancer treatments.

Postpartum care needs assessment: women's understanding of postpartum care, practices, barriers, and educational needs.

BACKGROUND: Complications in the postpartum period pose substantial risks to women and can result in significant maternal morbidity and mortality. However, there is much less attention on postpartum care compared to pregnancy and childbirth. The goal of this study was to gather information on women's knowledge of postpartum care and complications, recovery practices after childbirth, perceived barriers to receiving care during the postpartum period, and educational needs in four health centers. The findings can inform the development of appropriate curriculum and interventions for postnatal care education in similar settings. METHODS: A descriptive qualitative study design was employed. Eight focus group discussions were conducted among 54 postpartum women who delivered in four health centers in Sagnarigu District in Tamale, Ghana. Audio recordings of focus group data were transcribed and translated, and thematic analysis was conducted. RESULTS: There were six main themes that emerged from the focus group discussions: 1) baby focused postpartum care; 2) postpartum practices; 3) inadequate knowledge ofpostpartum danger signs; 4) barriers to accessing postpartum care 5) experiences of poor mental health; and 6) need for postpartum education. CONCLUSIONS: Postpartum care for women in this study was primarily perceived as care of the baby post-delivery and missing key information on physical and mental health care for the mother. This can result in poor adjustment postpartum and critically, a lack of knowledge on danger signs for common causes of morbidity and mortality in the postpartum period. Future research needs to understand how to communicate important information on postpartum mental and physical health to better protect mothers in the region.

Faculty Time Expenditure Across Research, Teaching, and Service: Do Gender Differences Persist?

Faculty members are continually confronted with a multitude of activities among which they must divide their time. Prior research suggests that while men and women academics spend the same number of weekly hours working, women tend to expend more time on teaching and service relative to men while men expend more time on research relative to women. Based on cross-sectional survey data from a sample of 783 tenured or tenure-track faculty members from multiple universities, we examine gender differences in time spent in research, teaching, and university service. Regression analyses show that gender differences in time allocation continue to persist after controlling for work and family factors. More specifically, women report more time on teaching and university service than do men, while men report more time spent on research than do women. Results provide evidence that gendered differences in faculty time allocation are robust across time. Potential implications for policy are discussed.

EMBRACE: One Small Story in Lupus-One Giant Challenge in Clinical Trials.

Clinical trials of novel therapeutics in the United States have not been adequately representative of diverse populations, particularly racial and ethnic minorities. The challenges and consequences of underrepresentation in clinical trial recruitment are exemplified by the case of belimumab, a biologic treatment for systemic lupus erythematosus (SLE), a disease that is more prevalent in patients of Black African ancestry and of Hispanic/Latino ethnicity than in other patient populations. Although belimumab was found to be effective in phase 2 and 3 clinical trials in the general population, post hoc analyses of efficacy data in patients of Black African ancestry showed inconsistent results. Consequently, a cautionary statement regarding belimumab use in this population was added to the product label. To alleviate concerns that belimumab may not be safe and effective for patients of Black African ancestry, the Efficacy and Safety of Belimumab in Black Race Patients with SLE (EMBRACE) study was conducted in a post-marketing commitment to the Food and Drug Administration. The study recruited only patients who self-identified as being of Black race; its findings led to the removal of the cautionary labeling of belimumab use in patients of Black African ancestry. Our manuscript highlights the critical lessons learned from the successes and failures of the EMBRACE study. It also provides suggestions for overcoming health disparities, highlighting strategies for conducting well-designed clinical trials to overcome systematic barriers to diversity in recruitment, with a focus on enacting long-term support to ensure equity in the process, products, and benefits from drug development and clinical trials.

In Patients Admitted to a Home Rehabilitation Service, Is Remote Completion of the Patient-Generated Subjective Global Assessment Physical Examination Using Still Images Captured by Allied Health Assistants a Valid Alternative to an In-Person Physical Examination?

BACKGROUND: There is increasing provision of telehealth services, including nutrition services. However, remote nutrition assessments are challenging due to difficulties in conducting physical assessments remotely, a crucial component of assessing nutritional status. OBJECTIVE: The aim of this study was to evaluate whether remote completion of the Patient-Generated Subjective Global Assessment physical examination using still images captured by allied health assistants (AHAs) is a valid alternative to an in-person physical examination in patients admitted to a home rehabilitation service. DESIGN: This study was cross-sectional in design. PARTICIPANTS/SETTING: This study involved 104 adults admitted to the home rehabilitation service at Southern Adelaide Local Health Network, Adelaide, Australia, over 2 sampling periods in 2019 and 2020 who were receiving home visits by an AHA and were engaged in rehabilitation activities. MAIN OUTCOME MEASURES: Validity of the still image-based physical assessment was determined using still images collected by an AHA and an in-person physical assessment completed by a dietitian from each participant. A dietitian blinded to the in-person results later assessed the de-identified still images to determine the presence and extent of deficit at each anatomical site and overall physical examination component of the Patient-Generated Subjective Global Assessment. STATISTICAL ANALYSES PERFORMED: Percentage agreement, weighted κ, sensitivity, and specificity between the still image based and in-person physical examinations were determined to assess agreement between the 2 methods of assessment. RESULTS: The still image based physical examination achieved a percentage agreement of 75% against the in-person examination, with a weighted κ of 0.662 (95% confidence interval 0.516-0.808) and a sensitivity-specificity pair of 76.6% and 89.1%. CONCLUSIONS: Physical examination using still images collected by AHAs achieved percentage agreement, κ, and sensitivity and specificity compared with an in-person physical examination that is consistent with or superior to commonly adopted nutrition screening and assessment tools. There is potential for implementation of this method to facilitate remote nutritional assessments by dietitians; however, further work is needed to ensure dietitians are able to assess still images reliably.

Selective border permeability: Governing complex environmental issues through and beyond COVID-19.

COVID-19 has changed the permeability of borders in transboundary environmental governance regimes. While borders have always been selectively permeable, the pandemic has reconfigured the nature of cross-border flows of people, natural resources, finances and technologies. This has altered the availability of spaces for enacting sustainability initiatives within and between countries. In Southeast Asia, national governments and businesses seeking to expedite economic recovery from the pandemic-induced recession have selectively re-opened borders by accelerating production and revitalizing agro-export growth. Widening regional inequities have also contributed to increased cross-border flows of illicit commodities, such as trafficked wildlife. At the same time, border restrictions under the exigencies of controlling the pandemic have led to a rolling back and scaling down of transboundary environmental agreements, regulations and programs, with important implications for environmental democracy, socio-ecological justice and sustainability. Drawing on evidence from Southeast Asia, the article assesses the policy challenges and opportunities posed by the shifting permeability of borders for organising and operationalising environmental activities at different scales of transboundary governance.

Performance-based assessment of social skills in a large sample of participants with schizophrenia, bipolar disorder and healthy controls: Correlates of social competence and social appropriateness.

INTRODUCTION: Performance-based assessments of social skills have detected impairments in people with severe mental illness and are correlated with functional outcomes in people with schizophrenia and bipolar disorder. The most common of these assessments, the Social Skills Performance Assessment (SSPA), has two communication scenarios and items measuring both social competence and appropriateness. As real-world competence and appropriateness appear to have different correlates, we hypothesized that SSPA Items measuring competence and appropriateness would be distinct and have different correlations with other outcomes. METHODS: We aggregated data from 557 people with schizophrenia, 106 with bipolar disorder, and 378 well controls from 4 separate research studies. All participants were assessed with both SSPA scenarios and other performance based and clinician-rated measures. A single expert rated the SSPA interactions for competence and appropriateness while blind to participant diagnoses. RESULTS: Participants with bipolar disorder and schizophrenia performed more poorly on every item of the SSPA than healthy controls. Items measuring social competence and appropriateness in communication were intercorrelated across scenarios, as were elements of socially competent communication, although the items measuring competence did not correlate substantially with appropriateness. Items assessing social competence, but not social appropriateness, correlated with better cognitive and functional performance and residential and financial independence. DISCUSSION: Social competence and social appropriateness were distinct elements of performance-based social skills with potential differences in their functional correlates. As both social competence and appropriateness impact functional outcomes, improvement in the measurement and treatment of appropriate communication seems to be an important goal.

Real world sedentary behavior and activity levels in patients with schizophrenia and controls: An ecological momentary assessment study.

BACKGROUND: People with schizophrenia often experience poor health, leading to shortened lifespans. The health of people with schizophrenia may be further exacerbated by increased sedentary behavior, which independently predicts health risk in the general population. However, the prevalence and patterns of objectively measured sedentary behavior in schizophrenia have not been studied extensively on a momentary basis. METHODS: Activity of 100 patients with schizophrenia was compared to that of healthy controls (HC; n=71) using ecological momentary assessment (EMA). EMA provides real-time, real-world monitoring of behavior. We sampled behavior seven times per day for seven days, quantifying active versus inactive behaviors and four different movement patterns (recumbent, seated, standing, and moving). Due to different employment rates between samples, we focused on surveys completed at home. RESULTS: Four of the five most commonly reported activities for participants with schizophrenia involved sitting or lying down. When considering activity during the last hour, participants with schizophrenia were more likely to be sitting or pacing and less likely to be standing than HC. If participants with schizophrenia only did one thing in the last hour, it was more likely to involve sitting and less likely to involve standing compared to HC. DISCUSSION: People with schizophrenia were significantly more likely to be seated and less likely to be standing or active during the past hour than HC, despite high frequencies of seated behaviors in the HC as well. The adverse health consequences of sitting for extended periods may be especially relevant for people with schizophrenia and likely contribute to premature mortality in this population.

Capturing Clinical Symptoms with Ecological Momentary Assessment: Convergence of Momentary Reports of Psychotic and Mood Symptoms with Diagnoses and Standard Clinical Assessments.

Objective: The development and deployment of technology-based assessments of clinical symptoms are increasing. This study used ecological momentary assessment (EMA) to examine clinical symptoms and relates these sampling results to structured clinical ratings. Methods: Three times a day for 30 days, participants with bipolar disorder (n=71; BPI) or schizophrenia (n=102; SCZ) completed surveys assessing five psychosis-related and five mood symptoms, in addition to reporting their location and who they were with at the time of survey completion. Participants also completed Positive and Negative Syndrome Scale (PANSS) interviews with trained raters. Mixed-model repeated-measures (MMRM) analyses examined diagnostic effects and the convergence between clinical ratings and EMA sampling. Results: In total, 12,406 EMA samples were collected, with 80-percent adherence to prompts. EMA-reported psychotic symptoms manifested substantial convergence with equivalent endpoint PANSS items. Patients with SCZ had more severe PANSS and EMA psychotic symptoms. There were no changes in symptom severity scores as a function of the number of previous assessments. Conclusions: EMA surveyed clinical symptoms converged substantially with commonly used clinical rating scales in a large sample, with high adherence. This suggested that remote assessment of clinical symptoms is valid and practical and was not associated with alterations in symptoms as a function of reassessment, with additional benefits of "in the moment" sampling, such as eliminating recall bias and the need for informant reports.

Evidence for avolition in bipolar disorder? A 30-day ecological momentary assessment comparison of daily activities in bipolar disorder and schizophrenia.

OBJECTIVES: Disability is common in bipolar disorder (BD) and predicted by persistent sadness. We used ecological momentary assessment (EMA) to examine daily activities in people with BD and schizophrenia. We classified activities as productive, unproductive, or passive recreation, relating them to momentary sadness, location, and social context. METHODS: 71 people with BD and 102 people with schizophrenia were sampled 3 times/day for 30 days with an EMA survey. Each survey asked where they were, with whom, what they were doing, and if they were sad. RESULTS: People with BD were home more than 50% of the time. There were no differences in prevalence of activity types across diagnoses. People with BD were less likely to report only one activity since the prior survey, but the most surveys still reported only one. For both groups, sadness and being home and alone since the last survey was associated with less productive activity and more passive recreation. CONCLUSIONS: Participants with BD and schizophrenia manifested high levels of unproductive and passive activities, predicted by momentary sadness. These activity patterns are consistent with descriptions of avolition and they minimally differentiated people with BD and schizophrenia. Previous reports of negative symptoms in BD may have been identifying these behaviors.

Flow cytometry-based assessment of direct-targeting anti-cancer antibody immune effector functions.

Monoclonal antibody-based therapies are increasingly being used to treat cancer. Some mediate their therapeutic effects through modifying the function of immune cells globally, while others bind directly to tumor cells and can recruit immune effector cells through their Fc regions. As new direct-binding agents are developed, having the ability to test their Fc-mediated functions in a high-throughput manner is important for selecting antibodies with immune effector properties. Here, using monoclonal anti-CD20 antibody (rituximab) as an example and the CD20+ Raji cell line as tumor target, we describe flow cytometry-based assays for determining an antibody's capacity for mediating antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP) and complement-dependent cytotoxicity (CDC). These assays are sensitive, reliable, affordable and avoid the use of radioactivity.

Incorporating LGBTQ health into the curriculum: Assessment of student pharmacists' knowledge and comfort level in caring for transgender patients.

BACKGROUND AND PURPOSE: This study aimed to measure the effects of instruction regarding transgender health in second-year student pharmacists and provide qualitative insight regarding their impressions of the educational experience. EDUCATIONAL ACTIVITY AND SETTING: Students completed a pre- and post-survey assessing knowledge regarding transgender therapeutics, the pharmacist's role, level of comfort providing care, and impression of exposure to the topic. McNemar's test and paired t-tests compared respondent data before and after the activity. The post-survey evaluated the learning activity, with an opportunity to leave open comments that were then analyzed using content analysis. FINDINGS: Eighty-five of 107 (79.4%) students completed both surveys and were included in the analysis. Transgender therapeutics knowledge, participant understanding of pharmacist's role, comfort level, and assessment of adequateness of exposure improved significantly (p < 0.001). A majority (82.4%) affirmed that more than one exposure to issues regarding care of transgender patients is needed in the curriculum. Fifty-five open comments offered by 23 students were coded and categorized into two overall themes with four and two subthemes, respectively. Strengths of the activity were topic importance, exposure appreciation, presentation style, and knowledge foundation. Opportunities for improvement included providing more information and different types of information. SUMMARY: The activity increased student pharmacists' knowledge regarding transgender therapeutics, the pharmacist's role, and comfort level in caring for this patient population. Respondents found the content valuable and desired more. Colleges of pharmacy should consider increasing exposure to specific patient populations, such as transgender patients, to prepare students for practice.

An evaluation of the validity of nutrition screening and assessment tools in patients admitted to a vascular surgery unit.

Vascular surgery patients are nutritionally vulnerable. Various malnutrition screening and assessment tools are available; however, none has been developed or validated in vascular patients. The present study aimed to: (1) investigate the validity of four commonly administered malnutrition screening tools (Malnutrition Screening Tool (MST), Malnutrition Universal Screening Tool (MUST), Nutrition Risk Screen-2002 (NRS-2002) and the Mini-Nutritional Assessment - Short Form (MNA-SF) and an assessment tool (the Patient-Generated Subjective Global Assessment (PG-SGA)) compared against a comprehensive dietitian's assessment and (2) evaluate the ability of the instruments to predict outcomes. Vascular inpatients were screened using the four malnutrition screening tools and assessed using the PG-SGA. Each was assessed by a dietitian incorporating nutritional biochemistry, anthropometry and changes in dietary intake. Diagnostic accuracy, consistency and predictive ability were determined. A total of 322 (69·3 % male) patients participated, with 75 % having at least one parameter indicating nutritional deficits. No instrument achieved the a priori levels for sensitivity (14·9-52·5 %). Neither tool predicted EuroQoL 5-dimension 5-level score. All tools except the MNA-SF were associated with length of stay (LOS); however, the direction varied with increased risk of malnutrition on the MUST and NRS-2002 being associated with shorter LOS (P=0·029 and 0·045) and the reverse with the MST and PG-SGA (P=0·005 and <0·001). The NRS-2002 was associated with increased risk of complications (P=0·039). The MST, NRS-2002 and PG-SGA were predictive of discharge to an institution (P=0·004, 0·005 and 0·003). The tools studied were unable to identify the high prevalence of undernutrition; hence, vascular disease-specific screening and/or assessment tools are warranted.

Developing an Inclusive and Welcoming LGBTQ Clinic.

People who identify as lesbian, gay, bisexual, transgender, queer, and questioning (LGBTQ) are underserved and face barriers to knowledgeable health care. Most health systems are ill prepared to provide care that addresses the needs of the LGBTQ community. Basic steps to developing an LGBTQ welcoming health care program are presented. It can be adapted to diverse health care models, from obstetrics and gynecology and other primary care services whether public or private and to hospitals and specialty clinics. This LGBTQ inclusive health care model was developed in collaboration with the LGBTQ community, a multidisciplinary team of health care providers, and professionals of Law and Information Technology.

Evaluating Photographs as a Replacement for the In-Person Physical Examination of the Scored Patient-Generated Subjective Global Assessment in Elderly Hospital Patients.

BACKGROUND: Undernourished patients discharged from the hospital require follow-up; however, attendance at return visits is low. Teleconsultations may allow remote follow-up of undernourished patients; however, no valid method to remotely perform physical examination, a critical component of assessing nutritional status, exists. OBJECTIVE: This study aims to compare agreement between photographs taken by trained dietitians and in-person physical examinations conducted by trained dietitians to rate the overall physical examination section of the scored Patient Generated Subjective Global Assessment (PG-SGA). DESIGN: Nested cross-sectional study. PARTICIPANTS/SETTING: Adults aged ≥60 years, admitted to the general medicine unit at Flinders Medical Centre between March 2015 and March 2016, were eligible. All components of the PG-SGA and photographs of muscle and fat sites were collected from 192 participants either in the hospital or at their place of residence after discharge. MAIN OUTCOME MEASURES: Validity of photograph-based physical examination was determined by collecting photographic and PG-SGA data from each participant at one encounter by trained dietitians. A dietitian blinded to data collection later assessed de-identified photographs on a computer. STATISTICAL ANALYSES PERFORMED: Percentage agreement, weighted kappa agreement, sensitivity, and specificity between the photographs and in-person physical examinations were calculated. All data collected were included in the analysis. RESULTS: Overall, the photograph-based physical examination rating achieved a percentage agreement of 75.8% against the in-person assessment, with a weighted kappa agreement of 0.526 (95% CI: 0.416, 0.637; P<0.05) and a sensitivity-specificity pair of 66.9% (95% CI: 57.8%, 75.0%) and 92.4% (95% CI: 82.5%, 97.2%). CONCLUSIONS: Photograph-based physical examination by trained dietitians achieved a nearly acceptable percentage agreement, moderate weighted kappa, and fair sensitivity-specificity pair. Methodological refinement before field testing with other personnel may improve the agreement and accuracy of photograph-based physical examination.

Economic evaluation of an extended nutritional intervention in older Australian hospitalized patients: a randomized controlled trial.

BACKGROUND: Prevalence of malnutrition in older hospitalized patients is 30%. Malnutrition is associated with poor clinical outcomes in terms of high morbidity and mortality and is costly for hospitals. Extended nutrition interventions improve clinical outcomes but limited studies have investigated whether these interventions are cost-effective. METHODS: In this randomized controlled trial, 148 malnourished general medical patients ≥60 years were recruited and randomized to receive either an extended nutritional intervention or usual care. Nutrition intervention was individualized and started with 24 h of admission and was continued for 3 months post-discharge with a monthly telephone call whereas control patients received usual care. Nutrition status was confirmed by Patient generated subjective global assessment (PG-SGA) and health-related quality of life (HRQoL) was measured using EuroQoL 5D (EQ-5D-5 L) questionnaire at admission and at 3-months follow-up. A cost-effectiveness analysis was conducted for the primary outcome (incremental costs per unit improvement in PG-SGA) while a cost-utility analysis (CUA) was undertaken for the secondary outcome (incremental costs per quality adjusted life year (QALY) gained). RESULTS: Nutrition status and HRQoL improved in intervention patients. Mean per included patient Australian Medicare costs were lower in intervention group compared to control arm (by $907) but these differences were not statistically significant (95% CI: -$2956 to $4854). The main drivers of higher costs in the control group were higher inpatient ($13,882 versus $13,134) and drug ($838 versus $601) costs. After adjusting outcomes for baseline differences and repeated measures, the intervention was more effective than the control with patients in this arm reporting QALYs gained that were higher by 0.0050 QALYs gained per patient (95% CI: -0.0079 to 0.0199). The probability of the intervention being cost-effective at willingness to pay values as low as $1000 per unit improvement in PG-SGA was > 98% while it was 78% at a willingness to pay $50,000 per QALY gained. CONCLUSION: This health economic analysis suggests that the use of extended nutritional intervention in older general medical patients is likely to be cost-effective in the Australian health care setting in terms of both primary and secondary outcomes. TRIAL REGISTRATION: ACTRN No. 12614000833662 . Registered 6 August 2014.

Cost-effectiveness of food, supplement and environmental interventions to address malnutrition in residential aged care: a systematic review.

Background: observational studies have shown that nutritional strategies to manage malnutrition may be cost-effective in aged care; but more robust economic data is needed to support and encourage translation to practice. Therefore, the aim of this systematic review is to compare the cost-effectiveness of implementing nutrition interventions targeting malnutrition in aged care homes versus usual care. Setting: residential aged care homes. Methods: systematic literature review of studies published between January 2000 and August 2017 across 10 electronic databases. Cochrane Risk of Bias tool and GRADE were used to evaluate the quality of the studies. Results: eight included studies (3,098 studies initially screened) reported on 11 intervention groups, evaluating the effect of modifications to dining environment (n = 1), supplements (n = 5) and food-based interventions (n = 5). Interventions had a low cost of implementation (<£2.30/resident/day) and provided clinical improvement for a range of outcomes including weight, nutritional status and dietary intake. Supplements and food-based interventions further demonstrated a low cost per quality adjusted life year or unit of physical function improvement. GRADE assessment revealed the quality of the body of evidence that introducing malnutrition interventions, whether they be environmental, supplements or food-based, are cost-effective in aged care homes was low. Conclusion: this review suggests supplements and food-based nutrition interventions in the aged care setting are clinically effective, have a low cost of implementation and may be cost-effective at improving clinical outcomes associated with malnutrition. More studies using well-defined frameworks for economic analysis, stronger study designs with improved quality, along with validated malnutrition measures are needed to confirm and increase confidence with these findings.

Graduation Day: Healthcare Transition From Pediatric to Adult.

Because more patients with pediatric-onset chronic conditions are surviving into adulthood, they are graduating from pediatric healthcare to self-management and adult healthcare. This transfer of care needs to be a process of transitioning medical and nutrition care. Despite having position statements from professional organizations and several proposed models, issues in the transition process have been well described, and gaps in transition care persist. Healthcare providers need to be aware of special needs of emerging adults related to education on chronic condition and self-management skills, emotional support before and after transition, and legal rights for both the patient and the parent if the emerging adult is not developmentally appropriate to make his or her own healthcare decisions. Both pediatric and adult providers need to be in active communication with each other and the patient to develop trusting relationships and actively support the transition of care. This review of literature describes several models for transitioning, measureable outcomes, insurance provider issues, and legal issues pertaining to healthcare transition.

Agreement between the Malnutrition Universal Screening Tool and the Patient-Generated Subjective Global Assessment for Cancer Outpatients Receiving Chemotherapy: A Cross-Sectional Study.

Malnutrition is a common occurrence in cancer. Early detection of malnutrition is imperative but often overlooked in busy clinical routine. This study aimed to assess the agreement between malnutrition universal screening tool (MUST) and the patient-generated subjective global assessment (PG-SGA) to detect risk of malnutrition in a medical oncology outpatient setting. A cross-sectional study was conducted with 100 adult patients with cancer receiving chemotherapy. Nutrition screening and assessment were performed using MUST and PG-SGA, respectively. Sensitivity, specificity, predictive values, kappa agreement, and receiver operating characteristics (ROC) curve were used to compare MUST with PG-SGA. Prevalence of malnutrition or risk of malnutrition among subjects was 45% according to the MUST. Body mass index (BMI) against PG-SGA indicated a low capacity to detect malnutrition with 28.9% sensitivity and 96.4% specificity. Unintentional weight loss in the last 3-6 mo against PG-SGA resulted in 55.6% sensitivity and 98.2% specificity. MUST against PG-SGA resulted in 86.7% sensitivity and 94.5% specificity. MUST indicated a perfect agreement with PG-SGA (Kappa = 0.81; P < 0.05) and highest area under the ROC curve (AUC ROC = 0.91). MUST has high level of agreement with PG-SGA to detect chemotherapy outpatients at risk of malnutrition.

Multiple receptors shape the estrogen response pathway and are critical considerations for the future of in vitro-based risk assessment efforts.

Current in life toxicity testing paradigms are being challenged as the future of risk assessment moves towards more comprehensive mode of action/adverse outcome pathway based approaches. In particular, endocrine disruption screening is now a global activity and key initiatives in the United States focus on the use of high throughput in vitro assays to prioritize compounds for further testing of estrogen, androgen or thyroid disruption. Of these pathways, much of the emphasis to date has been on high-throughput methods for estrogenic activity primarily using ligand binding and trans-activation assays. However, as the knowledge regarding estrogen receptor signaling pathways continues to evolve, it is clear that the assumption of a simple one-receptor pathway underlying current in vitro screening assays is out of date. To develop more accurate models for estrogen-initiated pathways useful for quantitative safety assessments, we must design assays that account for the key signaling processes driving cellular dose response based on up-to-date understanding of the biological network. In this review, we summarize the state of the science for the estrogen receptor signaling network, particularly with regard to proliferative effects, and highlight gaps in current high throughput approaches. From the sum of this literature, we propose a model for the estrogen-signaling pathway that should serve as a starting point for development of new in vitro methods fit for the purpose of predicting dose response for estrogenic chemicals in the human.