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BACKGROUND: The Parenting Sense of Competence (PSOC) is a self-report measure of parenting efficacy and satisfaction that is widely used by researchers and clinicians in many countries. Despite its popularity, there have been some criticisms of the instrument. The aims of the current study were to identify and address shortcomings of the PSOC and to produce a revised measure that reflected the original constructs and that demonstrated robust psychometric properties. METHODS: The researchers examined the original PSOC and proposed changes to overcome identified issues. A sample of 3056 Australian mothers provided data for the revised instrument's factor structure and psychometric analyses. RESULTS: We identified a number of problems with the original instrument, including factorial inconsistency, and multipart or potentially ambiguous questions. Of particular concern was the fact that all negatively worded items load onto one subscale and all positively worded questions load onto the other subscale. In addressing these issues, we produced a 16-item instrument (the Parenting Sense of Competence-Revised; PSOC-R) with strong internal consistency, excellent test-retest reliability and good evidence of construct validity including factorial validity and criterion-related validity. CONCLUSIONS: The PSOC-R maintains the intent of the original measure in assessing parenting Efficacy (10 items) and Satisfaction (6 items). It represents improvements in item construction including reductions in complexity, with no multipart items and a lower reading level requirement than previously. Data across four child age groups enhance the instrument's clinical utility.

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BACKGROUND: Cancer cachexia is a syndrome of unintentional weight loss resulting in progressive functional impairment. Knowledge of radiation therapy utilization in patients with cancer cachexia is limited. We evaluated the use of curative and palliative-intent radiation for the management of patients with non-small cell lung cancer (NSCLC) with cachexia to determine whether tumor-directed therapy affected cachexia-associated outcomes. METHODS: Using an Institutional Tumor Registry, we evaluated all patients with stages of NSCLC treated at a tertiary care system from 2006 to 2013. We adopted the international consensus definition for cachexia, with staging designated by the registry and positron emission tomography. Radiotherapy delivery and intent were retrospectively assessed. RESULTS: In total, 1330 patients with NSCLC were analyzed. Curative-intent radiotherapy was utilized equally between patients with cachexia and non-cachexia with stages I to III NSCLC. Conversely, significantly more patients with stage IV disease and cachexia received palliative radiotherapy versus those without (74% vs 63%, P = 0.006). Cachexia-associated survival was unchanged irrespective of tumor-directed radiation therapy with curative or palliative intent. In fact, pretreatment cachexia was associated with reduced survival for patients with stage III NSCLC receiving curative-intent radiotherapy (median survival = 23.9 vs 15.0 mo, P = 0.009). Finally, multivariate analysis identified pretreatment cachexia as an independent variable associated with worsened survival (hazard ratio = 1.31, CI: 1.14,1.52). CONCLUSION: Patients with advanced NSCLC with cachexia received more palliative-intent radiation than those without weight loss. Tumor-directed therapy in either a curative or palliative approach failed to alter cachexia patient survival across all stages of the disease. These findings offer critical information on the appropriate utilization of radiation in the management of patients with NSCLC with cachexia.

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BACKGROUND: Siblings represent an important influence on children's development. It is possible that sibling influence on developmental outcomes differs in sibling pairs when one of the children has a disability. Previous research has tended to focus on outcomes for typically developing siblings when they have a brother/sister with a disability. AIMS: The purpose of this scoping review was to explore empirical studies reporting on the impact of siblings on the developmental outcomes of children with disability to better understand the areas that are influenced by siblings and the factors that contribute to this influence. METHOD: To identify relevant studies, the electronic databases of EBSCO, ERIC, Informit, Ovid, ProQuest and Scopus were searched. These searches were supplemented by direction from the authors on relevant literature and citation searches of papers identified for inclusion. Descriptive details were extracted, followed by details related to research design and findings of the studies. OUTCOMES AND RESULTS: Twenty-two papers were determined to meet inclusion criteria. Investigations of sibling influence have concentrated on children with ASD; other groups are not well represented. There is some evidence that having older siblings may be protective for children with ASD; however, this was not an invariable finding. There is too little consistency across studies to determine whether and how siblings influence development of children with disability. CONCLUSIONS AND IMPLICATIONS: Further work is required to understand the potentially crucial influence that siblings may have on developmental outcomes of children with disability.

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PURPOSE: Cachexia is a paraneoplastic syndrome of unintentional adipose and muscle tissue wasting with severe impacts to functionality and quality of life. Although health inequities across minority and socioeconomically disadvantaged groups are known, the role of these factors in cachexia progression is poorly characterized. This study aims to evaluate the relationship between these determinants and cachexia incidence and survival in patients with gastrointestinal tract cancer. METHODS: Through retrospective chart review from a prospective tumor registry, we established a cohort of 882 patients with gastroesophageal or colorectal cancer diagnosed between 2006 and 2013. Patient race, ethnicity, private insurance coverage, and baseline characteristics were evaluated through multivariate, Kaplan-Meier, and Cox regression analyses to determine associations with cachexia incidence and survival outcomes. RESULTS: When controlling for potentially confounding covariates (age, sex, alcohol and tobacco history, comorbidity score, tumor site, histology, and stage), Black (odds ratio [OR], 2.447; P < .0001) and Hispanic (OR, 3.039; P < .0001) patients are at an approximately 150% and 200%, respectively, greater risk of presenting with cachexia than non-Hispanic White patients. Absence of private insurance coverage was associated with elevated cachexia risk (OR, 1.439; P = .0427) compared to privately insured patients. Cox regression analyses with previously described covariates and treatment factors found Black race (hazard ratio [HR], 1.304; P = .0354) to predict survival detriments, while cachexia status did not reach significance (P = .6996). CONCLUSION: Our findings suggest that race, ethnicity, and insurance play significant roles in cachexia progression and related outcomes that are not accounted for by conventional predictors of health. Disproportionate financial burdens, chronic stress, and limitations of transportation and health literacy represent targetable factors for mitigating these health inequities.

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Introduction: Cancer cachexia, found in more than a third of patients with NSCLC, directly leads to functional and survival detriments. As screening and interventions for cachexia and NSCLC improve, deficits in health care access and quality among patients disadvantaged by racial-ethnic and socioeconomic factors must be addressed. Methods: We retrospectively evaluated 957 patients diagnosed with having stage IV NSCLC between 2014 and 2020 in Dallas, Texas. Cachexia was retrospectively assessed by applying criteria for substantial unintentional weight loss in the time leading up to cancer diagnosis. Nonparametric, parametric, multivariate logistic regression, and Kaplan-Meier analyses were conducted to evaluate for variables potentially associated with cachexia incidence and survival. Results: In multivariate analysis including age, sex, comorbidities, body mass index, risk behaviors, and tumor characteristics, Black race and Hispanic ethnicity were independently associated with more than a 70% increased risk of presenting with cachexia at the time of NSCLC diagnosis (p < 0.05). When private insurance status was included as a covariate, this association was diminished for Hispanic patients only. Black patients presented with stage IV disease at an average of approximately 3 years younger than White patients (Kruskal-Wallis p = 0.0012; t test p = 0.0002). Cachexia status at diagnosis consistently predicted for survival detriments, further highlighting the importance of addressing differential cachexia risk across racial-ethnic groups. Conclusions: Fundamentally, our findings reveal elevated cachexia risk in Black and Hispanic patients with stage IV NSCLC with associated survival detriments. These differences are not fully accounted for by traditional determinants of health and suggest novel avenues for addressing oncologic health inequities.

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BACKGROUND: Cancer cachexia is frequently documented by self-reported, single time-point weight histories. This approach lacks the granularity needed to fully elucidate the progression of cachexia syndrome. This study aimed to longitudinally assess body weight changes pre- and post-cancer diagnosis in gastrointestinal (GI) cancer patients. METHODS: Body weights and relevant clinical data recorded in the electronic health record 12 months pre- and post-GI cancer (colorectal, gastroesophageal, hepatobiliary and pancreatic) diagnosis were extracted. Weight loss was categorized by the International Consensus Definition for cachexia. RESULTS: A total of 879 patients were included in the final cohort including patients diagnosed with colorectal (n = 317), hepatocellular (n = 185), biliary (n = 72), pancreatic (n = 186) or gastroesophageal (n = 119) cancer. Stage of disease was equally distributed. Patients without cachexia at diagnosis (n = 608) remained weight stable during the 12 months pre-diagnosis (+0.5 ± 0.5% body weight; P = 0.99). Patients with cachexia at diagnosis (n = 271) remained weight stable 6 to 12 months prior to diagnosis (+0.4 ± 0.8%; P > 0.9999) and lost 8.7 ± 0.6% (P < 0.0001) within the 6 months pre-diagnosis. Patients without cachexia at diagnosis lost more weight post-diagnosis (6.3 ± 0.6%) than patients with cachexia at diagnosis (4.7 ± 1.0%; P = 0.01). Pre-diagnosis weight trajectories did not differ between primary malignancies or stage of disease in patients without or with cachexia at diagnosis (all P ≥ 0.05). Post-diagnosis weight trajectories did differ by primary malignancy (P ≤ 0.0002) and stage (P < 0.0001). In both patients without and with cachexia at diagnosis, colorectal patients lost the least amount of weight post-diagnosis and gastroesophageal patients lost the most amount of weight post-diagnosis. Stage 4 patients without or with cachexia at diagnosis lost the most weight post-diagnosis (P ≤ 0.0003). Regardless of cachexia status at diagnosis, patients lost more weight when treated with systemic therapy (7.1 ± 0.7%; P < 0.0001; n = 419) or radiation therapy (8.4 ± 1.4%; P = 0.02; n = 116) compared to those who did not. Patients who did not have surgery lost more weight post-diagnosis (7.6 ± 1.1%; P < 0.0001; n = 355) compared to those who did have surgery. By 12 months post-diagnosis, 83% of the surviving GI cancer patients in this cohort had transitioned into cachexia syndrome. CONCLUSIONS: Significant weight loss in patients with GI cancer cachexia at diagnosis initiates at least 6 months prior to diagnosis, and most patients will transition into cachexia syndrome post-diagnosis, regardless of pre-diagnosis weight change and stage of disease. These findings punctuate the importance of weight surveillance in cancer detection and earlier palliative interventions post-diagnosis in the GI cancer patient population.

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Triple negative breast cancer (TNBC) is an aggressive and highly metastatic breast cancer subtype with limited treatment options. Obesity and insulin resistance are associated with a worse prognosis in those with TNBC. Moringa oleifera (moringa) is a tropical edible plant used for both food and medicinal purposes and found to have anti-obesity and anti-cancer effects in vitro and in preclinical models. The anti-cancer effects of moringa seed extract alone and in combination with chemotherapy were evaluated in immunocompromised female mice with diet-induced obesity bearing MDA-MB-231-derived xenograft tumors. Moringa supplementation protected against high-fat diet- and chemotherapy-induced increases in fasting glucose and improved insulin sensitivity. Moringa supplementation alone did not attenuate tumor growth relative to chemotherapy alone, and in combination worsened tumor progression. Moringa supplementation alone reduced angiogenesis, but this effect was abrogated in combination with chemotherapy. Moringa supplementation may be an effective strategy to improve metabolic health in mice with obesity and TNBC and reduce angiogenesis in tumors, but may have a negative interaction when used as a concurrent complementary therapy. Caution should be taken when considering the consumption of moringa seed extracts while receiving chemotherapy for breast cancer treatment. Further investigations of alternative timings of moringa therapy are warranted.

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Obesity is a risk factor for developing several cancers. The dysfunctional metabolism and chronic activation of inflammatory pathways in obesity create a milieu that supports tumor initiation, progression, and metastasis. Obesity-associated metabolic, endocrine, and inflammatory mediators, besides interacting with cells leading to a malignant transformation, also modify the intrinsic metabolic and functional characteristics of immune myeloid cells. Here, the evidence supporting the hypothesis that obesity metabolically primes and promotes the expansion of myeloid cells with immunosuppressive and pro-oncogenic properties is discussed. In consequence, the accumulation of these cells, such as myeloid-derived suppressor cells and some subtypes of adipose-tissue macrophages, creates a microenvironment conducive to tumor development. In this review, the role of lipids, insulin, and leptin, which are dysregulated in obesity, is emphasized, as well as dietary nutrients in metabolic reprogramming of these myeloid cells. Moreover, emerging evidence indicating that obesity enhances immunotherapy response and hypothesized mechanisms are summarized. Priorities in deeper exploration involving the mechanisms of cross talk between metabolic disorders and myeloid cells related to cancer risk in patients with obesity are highlighted.

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BACKGROUND: Community perceptions of schizophrenia potentially influence the wellbeing and quality of life of individuals with the disorder. There is some evidence of improved community knowledge of schizophrenia in recent years; however, misconceptions still remain. AIMS: The aims were to investigate community perceptions of schizophrenia at two points in time. METHOD: Two cross-sectional surveys were used to assess perceptions of schizophrenia. Using personal contacts and a snowball approach, members of the Australian community were recruited in 2005 (n = 1214) and in 2017 (n = 985). Participants were asked "What is the first thing that comes to mind when you think about schizophrenia?" RESULTS: Analyses revealed that community knowledge of schizophrenia was more accurate at the second time point and prosocial tendencies were more evident. Perceptions of dangerousness, aggressiveness and unpredictability did not differ at the two time points. Despite there being fewer responses that confused schizophrenia with dissociative identity disorder, this misconception was still evident. CONCLUSIONS: Although community knowledge about schizophrenia appears to have become more accurate and empathic, the endurance of negative stereotypes and misunderstandings highlights the need for community education programmes to combat stigma and discrimination.

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Previous research has shown that the quality of mother-child interactions between pre-term children and their mothers tends to be poorer than that of full-term children and their mothers (Forcada-Guex, Pierrehumbert, Borghini, Moessinger & Muller-Nix, 2006). Mothers of pre-term children are less responsive and more intrusive in interactions with their children than mothers of full-term children (Forcada-Guex et al., 2006; Ionio, Lista, Mascheroni, Olivari, Confalonieri, Mastrangelo, Brazzoduro, Balestriero, Banfi, Bonanomi, Bova, Castoldi, Colombo, Introvini & Scelsa, 2017; Laing, McMahon, Ungerer, Taylor, Badawi & Spence, 2010). The current research explored differences between mothers of pre-term and full-term children in terms of interactive beliefs and style, and the potential for language development to be differentially predicted by maternal interactive beliefs and styles in pre-term versus full-term children. Independent t-tests were conducted to compare pre-term and full-term groups in relation to the measures of maternal interactive beliefs and styles. A series of multiple regression analyses were then performed separately for each group to examine the shared and unique contributions of maternal interactive beliefs and styles on full-term versus pre-term children's language development. The results showed that mothers of pre-term children were more intrusive-directive than mothers of full-term children; in contrast, mothers of full-term children were more responsive and supportive-directive in interactions with their children. Moreover, predictors of language development were different in full-term versus pre-term children; in full-term children, maternal supportive beliefs and responsiveness were significant predictors of language development evaluated by both the Bayley Scales of Infant and Toddler Development and the MacArthur Communicative Development Inventory; in the pre-term group, maternal supportive and directive beliefs, as well as supportive and intrusive directiveness, were significant predictors, with the latter being negatively associated with language development indicators. This research can shed light on how to prevent language delay in children and improve mother-child interactions that contribute to language development, which may in turn improve language development in vulnerable children, children born pre-term in particular.

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BACKGROUND: It is not well understood whether qualified teachers believe neuromyths, and whether this affects their practice and learner outcomes. METHOD: A standardised survey was administered to practising teachers (N = 228) to determine whether or not they believe fictional (neuromyth) or factual statements about the brain, the confidence in those beliefs, and their application. RESULTS: Although factual knowledge was high, seven neuromyths were believed by >50% of the sample. Participants who endorsed neuromyths were generally more confident in their answers than those who identified the myths. Key neuromyths appear to be incorporated into classrooms. CONCLUSION: Australian teachers, like their overseas counterparts, have some neuroscience awareness but are susceptible to neuromyths. A stronger partnership with neuroscientists would addresss the complex problem of disentangling brain facts from fictions, and provide better support for teachers. This study uncovered psychometric weaknesses in the commonly used neuromyth measure that future research should address.

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During its intra-erythrocytic growth phase, the malaria parasite Plasmodium falciparum relies heavily on glycolysis for its energy requirements. Pyruvate kinase (PYK) is essential for regulating glycolytic flux and for ATP production, yet the allosteric mechanism of P. falciparum PYK (PfPYK) remains poorly understood. Here we report the first crystal structure of PfPYK in complex with substrate analogues oxalate and the ATP product. Comparisons of PfPYK structures in the active R-state and inactive T-state reveal a 'rock-and-lock' allosteric mechanism regulated by rigid-body rotations of each subunit in the tetramer. Kinetic data and structural analysis indicate glucose 6-phosphate is an activator by increasing the apparent maximal velocity of the enzyme. Intriguingly, the trypanosome drug suramin inhibits PfPYK, which points to glycolysis as a set of potential therapeutic targets against malaria.

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Readability of infant formula preparation instructions is universally poor, which may result in inaccurate infant feeding. Given that inaccurate formula dispensing can lead to altered infant growth and increased adiposity, there is an increased need for easy to follow instructions for formula preparation. We hypothesize that altering infant formula instruction labels using feedback from iterative focus groups will improve the preparation accuracy of powdered infant formula in a randomized controlled trial. Participants were recruited from the community, 18 years of age or older, willing to disclose demographic information for focus group matching, and willing to participate freely in the first (n = 21) or second (n = 150) phase of the study. In the second phase, participants were randomized to use the standard manufacturer instructions or to use the modified instructions created in the first phase. Accuracy was defined as the percent error between manufacturer-intended powder formula quantity and the amount dispensed by the participant. Participants who were assigned to the modified instructions were able to dispense the powdered formula more accurately than participants who used the standard manufacturer instructions (-0.67 ± 0.76 vs. -4.66 ± 0.74% error; p < 0.0001). Accuracy in powdered formula dispensing was influenced by bottle size (p = 0.02) but not by body mass index (p = 0.17), education level (p = 0.75), income (p = 0.7), age (p = 0.89) or caregiver status (p = 0.18). Percent error of water measurement was not different between the groups (standard: -1.4 ± 0.6 vs. modified: 0.7 ± 0.6%; p = 0.38). Thus, caloric density was more accurate in the modified instructions group compared to the standard manufacturer instructions group (-0.3 ± 0.6 vs.-2.9 ± 0.9%; p = 0.03). Infant formula label modifications using focus group feedback increased infant formula preparation accuracy.

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AIM: To assess outcomes in adolescence after surgery for congenital heart disease (CHD) in infancy. Domains analysed included cognition and executive function, social and emotional well-being, adaptive behaviour, academic achievement, and health-related quality of life (HRQoL). METHOD: Twenty-one participants (10 males, 11 females) ranged in age from 14 to 17 years (mean 15y 4.8mo, SD 8.4mo). Twenty had biventricular repairs. All were classified as New York Heart Association class I. Measures included: Wechsler Intelligence and Achievement scales; Wide Range Assessment of Memory and Learning, Second Edition; California Verbal Learning Test - Children's Version; Behaviour Rating Inventory of Executive Function; Conners, Third Edition; Adaptive Behavior Assessment System, Second Edition; Behavior Assessment System for Children, Second Edition; Rey-Osterrieth Complex Figure; and Pediatric Quality of Life Inventory. RESULTS: Outcomes were significantly lower (p≤0.01) than population norms for processing speed, mathematical achievement, attention, and visual-spatial ability. Participants reported more frequent learning problems but more positive family relations. HRQoL was significantly lower across most domains by self- and parent-proxy report. INTERPRETATION: Individuals with CHD may experience difficulties across a range of domains. These findings emphasize the importance of comprehensive screening, early intervention, and long-term follow-up, as deficits may extend into young adulthood. WHAT THIS PAPER ADDS: Identified cognitive, learning, and attentional impairments in adolescents after congenital heart disease surgery in infancy. Combined self-report, caregiver report, and laboratory tasks in a comprehensive neurodevelopmental assessment protocol. Health-related quality of life was lower across most domains.

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Background: The sex- and gender-specific health (SGSH) multimedia case-based learning modules (MCBLMs) were developed to address the absence of validated or peer-reviewed material that incorporates topics of sex and gender differences into medical curricula. This article provides the methodology for development of the modules and reports the results of a field test of the modules in different medical educational settings. Methods: MCBLMs were created by a multidisciplinary committee of scientists, health profession educators, and students. Two modules, osteoporosis and diabetes, were tested in various settings based on the curricular needs at each of the five accredited institutions. Each module consisted of a pretest and three interactive, multimedia stand-alone sections with post-tests. Scores on the tests were compared using a paired-samples t-test. A postmodule survey was used to evaluate the format. Results: Four hundred eighteen students participated in the field testing. For the 194 who completed the osteoporosis module, the post-test scores (M = 13.71, standard deviation [SD] = 2.09) were significantly higher than the pretest scores (M = 10.54, SD = 2.41), p < 0.001. Post-test scores for the 285 who completed the diabetes module (M = 16.55, SD = 2.46) were also significantly higher than the pretest scores (M = 13.71, SD = 2.09), p < 0.001. The postmodule survey showed positive acceptance of the format with an average score of 3.54/4 for osteoporosis and 3.45/4 for diabetes. Conclusion: The SGSH MCBLM field testing results show that the modules have a positive effect on content knowledge in multiple settings and are well accepted by learners.

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In response to the stress of infection, Mycobacterium tuberculosis (Mtb) reprograms its metabolism to accommodate nutrient and energetic demands in a changing environment. Pyruvate kinase (PYK) is an essential glycolytic enzyme in the phosphoenolpyruvate-pyruvate-oxaloacetate node that is a central switch point for carbon flux distribution. Here we show that the competitive binding of pentose monophosphate inhibitors or the activator glucose 6-phosphate (G6P) to MtbPYK tightly regulates the metabolic flux. Intriguingly, pentose monophosphates were found to share the same binding site with G6P. The determination of a crystal structure of MtbPYK with bound ribose 5-phosphate (R5P), combined with biochemical analyses and molecular dynamic simulations, revealed that the allosteric inhibitor pentose monophosphate increases PYK structural dynamics, weakens the structural network communication, and impairs substrate binding. G6P, on the other hand, primes and activates the tetramer by decreasing protein flexibility and strengthening allosteric coupling. Therefore, we propose that MtbPYK uses these differences in conformational dynamics to up- and down-regulate enzymic activity. Importantly, metabolome profiling in mycobacteria reveals a significant increase in the levels of pentose monophosphate during hypoxia, which provides insights into how PYK uses dynamics of the tetramer as a competitive allosteric mechanism to retard glycolysis and facilitate metabolic reprogramming toward the pentose-phosphate pathway for achieving redox balance and an anticipatory metabolic response in Mtb.

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We have tested the effect of all 20 proteinogenic amino acids on the activity of the M2 isoenzyme of pyruvate kinase (M2PYK) and show that, within physiologically relevant concentrations, phenylalanine, alanine, tryptophan, methionine, valine, and proline act as inhibitors, while histidine and serine act as activators. Size exclusion chromatography has been used to show that all amino acids, whether activators or inhibitors, stabilise the tetrameric form of M2PYK. In the absence of amino-acid ligands an apparent tetramer-monomer dissociation Kd is estimated to be ∼0.9 µM with a slow dissociation rate (t1/2 ∼ 15 min). X-ray structures of M2PYK complexes with alanine, phenylalanine, and tryptophan show the M2PYK locked in an inactive T-state conformation, while activators lock the M2PYK tetramer in the active R-state conformation. Amino-acid binding in the allosteric pocket triggers rigid body rotations (11°) stabilising either T or R states. The opposing inhibitory and activating effects of the non-essential amino acids serine and alanine suggest that M2PYK could act as a rapid-response nutrient sensor to rebalance cellular metabolism. This competition at a single allosteric site between activators and inhibitors provides a novel regulatory mechanism by which M2PYK activity is finely tuned by the relative (but not absolute) concentrations of activator and inhibitor amino acids. Such 'allostatic' regulation may be important in metabolic reprogramming and influencing cell fate.

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Background: To improve weight management in pregnant women, there is a need to deliver specific, data-based recommendations on energy intake. Objective: This cross-sectional study evaluated the accuracy of an electronic reporting method to measure daily energy intake in pregnant women compared with total daily energy expenditure (TDEE). Methods: Twenty-three obese [mean ± SEM body mass index (kg/m2): 36.9 ± 1.3] pregnant women (aged 28.3 ±1.1 y) used a smartphone application to capture images of their food selection and plate waste in free-living conditions for ≥6 d in early (13-16 wk) and late (35-37 wk) pregnancy. Energy intake was evaluated by the smartphone application SmartIntake and compared with simultaneous assessment of TDEE obtained by doubly labeled water. Accuracy was defined as reported energy intake compared with TDEE (percentage of TDEE). Ecological momentary assessment prompts were used to enhance data reporting. Two-one-sided t tests for the 2 methods were used to assess equivalency, which was considered significant when accuracy was >80%. Results: Energy intake reported by the SmartIntake application was 63.4% ± 2.3% of TDEE measured by doubly labeled water (P = 1.00). Energy intake reported as snacks accounted for 17% ± 2% of reported energy intake. Participants who used their own phones compared with participants who used borrowed phones captured more images (P = 0.04) and had higher accuracy (73% ± 3% compared with 60% ± 3% of TDEE; P = 0.01). Reported energy intake as snacks was significantly associated with the accuracy of SmartIntake (P = 0.03). To improve data quality, excluding erroneous days of likely underreporting (<60% TDEE) improved the accuracy of SmartIntake, yet this was not equivalent to TDEE (-22% ± 1% of TDEE; P = 1.00). Conclusions: Energy intake in obese, pregnant women obtained with the use of an electronic reporting method (SmartIntake) does not accurately estimate energy intake compared with doubly labeled water. However, accuracy improves by applying criteria to eliminate erroneous data. Further evaluation of electronic reporting in this population is needed to improve compliance, specifically for reporting frequent intake of small meals. This trial was registered at www.clinicaltrials.gov as NCT01954342.

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Pyruvate kinase (PYK) is an essential glycolytic enzyme that controls glycolytic flux and is critical for ATP production in all organisms, with tight regulation by multiple metabolites. Yet the allosteric mechanisms governing PYK activity in bacterial pathogens are poorly understood. Here we report biochemical, structural and metabolomic evidence that Mycobacterium tuberculosis (Mtb) PYK uses AMP and glucose-6-phosphate (G6P) as synergistic allosteric activators that function as a molecular "OR logic gate" to tightly regulate energy and glucose metabolism. G6P was found to bind to a previously unknown site adjacent to the canonical site for AMP. Kinetic data and structural network analysis further show that AMP and G6P work synergistically as allosteric activators. Importantly, metabolome profiling in the Mtb surrogate, Mycobacterium bovis BCG, reveals significant changes in AMP and G6P levels during nutrient deprivation, which provides insights into how a PYK OR gate would function during the stress of Mtb infection.

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