Health policy implications of corporate social responsibility provisions in international investment agreements.

Objective: To analyse and classify inclusions of corporate social responsibility in international investment agreements, especially inclusions with reference to public health. Method: We extracted the text of international investment agreements containing corporate social responsibility inclusions from the Electronic Database of Investment Treaties. We conducted a documentary analysis of the corporate social responsibility inclusions, and we developed a typology categorizing inclusions based on level of detail and reference to international commitments. Findings: Of the 3816 agreements signed as of October 2023, 127 agreements contain corporate social responsibility inclusions. Since the first inclusion of corporate social responsibility in 2008, the percentage of agreements containing such inclusion signed each year has steadily increased from 4.6% (4/86) in 2008 to 42.8% (21/49) in 2018 and 33.3% (3/9) in 2023. Using the typology we developed, we categorized the level of detail as follows: nine were minimal, 27 were low, 35 were low-medium, 107 were medium, 11 were medium-high and seven were high. Health is mentioned in 36 of these inclusions. Conclusion: This analysis indicates that international investment agreements increasingly incorporate a high level of detail on expectations regarding investors' corporate social responsibility. Such provisions offer a potential tool to increase government guidance and accountability of global corporations, including with respect to governments' public health objectives.

Adverse Metabolic Phenotypes in Parenterally Fed Neonatal Pigs Do Not Persist into Adolescence.

BACKGROUND: Nutrition during fetal and neonatal life is an important determinant for the risk of adult-onset diseases, especially type 2 diabetes and obesity. OBJECTIVES: We aimed to determine whether total parenteral nutrition (TPN) compared with enteral formula feeding [enteral nutrition (EN)] in term piglets during the first 2 wk after birth would increase the long-term (5-mo) development of metabolic syndrome phenotypes with adverse glucose homeostasis, fatty liver disease, and obesity. METHODS: Neonatal female pigs were administered TPN (n = 12) or fed enterally with a liquid enteral milk-replacer formula (EN, n = 12) for 14 d. After transitioning TPN pigs to enteral feeding of liquid formula (days 15-26), both groups were adapted to a solid high-fat diet (30% of the total diet) and sucrose (20% of the total diet) diet (days 27-33), which was fed until the end of the study (140 d). Body composition was measured by dual-energy X-ray absorptiometry at 14, 45, and 140 d. Serum biochemistry and glucose-insulin values (after a fasting intravenous glucose tolerance test) were obtained at 140 d. Liver and muscle were analyzed for insulin receptor signaling and triglycerides. RESULTS: Body weight was similar, but percent fat was higher, whereas percent lean and bone mineral density were lower in TPN than in EN pigs (P < 0.01) at 45 d of age but not at 140 d. At 140 d, there were no differences in serum markers of liver injury or lipidemia. Intravenous glucose tolerance test at 140 d showed a lower (P < 0.05) AUC for both glucose and insulin in TPN than in EN pigs, but the ratio of AUCs of insulin and glucose was not different between groups. CONCLUSIONS: Administration of TPN during the neonatal period increased adipose deposition that transiently persisted in early adolescence when challenged with a high-fat diet but was not sustained or manifested as glucose intolerance.

Pulsatile Leucine Administration during Continuous Enteral Feeding Enhances Skeletal Muscle Mechanistic Target of Rapamycin Complex 1 Signaling and Protein Synthesis in a Preterm Piglet Model.

BACKGROUND: Continuous feeding does not elicit an optimal anabolic response in skeletal muscle but is required for some preterm infants. We reported previously that intermittent intravenous pulses of leucine (Leu; 800 µmol Leu·kg-1·h-1 every 4 h) to continuously fed pigs born at term promoted mechanistic target of rapamycin complex 1 (mTORC1) activation and protein synthesis in skeletal muscle. OBJECTIVES: The aim was to determine the extent to which intravenous Leu pulses activate mTORC1 and enhance protein synthesis in the skeletal muscle of continuously fed pigs born preterm. METHODS: Pigs delivered 10 d preterm was advanced to full oral feeding >4 d and then assigned to 1 of the following 4 treatments for 28 h: 1) ALA (continuous feeding; pulsed with 800 µmol alanine·kg-1·h-1 every 4 h; n = 8); 2) L1× (continuous feeding; pulsed with 800 µmol Leu·kg-1·h-1 every 4 h; n = 7); 3) L2× (continuous feeding; pulsed with 1600 µmol Leu·kg-1·h-1 every 4 h; n = 8); and 4) INT (intermittent feeding every 4 h; supplied with 800 µmol alanine·kg-1 per feeding; n = 7). Muscle protein synthesis rates were determined with L-[2H5-ring]Phenylalanine. The activation of insulin, amino acid, and translation initiation signaling pathways were assessed by Western blot. RESULTS: Peak plasma Leu concentrations were 134% and 420% greater in the L2× compared to the L1× and ALA groups, respectively (P < 0.01). Protein synthesis was greater in the L2× than in the ALA and L1× groups in both the longissimus dorsi and gastrocnemius muscles (P < 0.05) but not different from the INT group (P > 0.10). Amino acid signaling upstream and translation initiation signaling downstream of mTORC1 largely corresponded to the differences in protein synthesis. CONCLUSIONS: Intravenous Leu pulses potentiate mTORC1 activity and protein synthesis in the skeletal muscles of continuously fed preterm pigs, but the amount required is greater than in pigs born at term.

Prematurity blunts protein synthesis in skeletal muscle independently of body weight in neonatal pigs.

BACKGROUND: Postnatal growth failure in premature infants is associated with reduced lean mass accretion. Prematurity impairs the feeding-induced stimulation of translation initiation and protein synthesis in the skeletal muscle of neonatal pigs. The objective was to determine whether body weight independently contributes to the blunted postprandial protein synthesis. METHODS: Preterm and term pigs that were either fasted or fed were stratified into quartiles according to birth weight to yield preterm and term groups of similar body weight; first and second quartiles of preterm pigs and third and fourth quartiles of term pigs were compared (preterm-fasted, n = 23; preterm-fed, n = 25; term-fasted, n = 21; term-fed, n = 21). Protein synthesis rates and mechanistic target of rapamycin complex 1 (mTORC1) activation in skeletal muscle were determined. RESULTS: Relative body weight gain was lower in preterm compared to term pigs. Prematurity attenuated the feeding-induced increase in mTORC1 activation in longissimus dorsi and gastrocnemius muscles (P < 0.05). Protein synthesis in gastrocnemius (P < 0.01), but not in longissimus dorsi muscle, was blunted by preterm birth. CONCLUSION: A lower capacity of skeletal muscle to respond adequately to feeding may contribute to reduced body weight gain and lean mass accretion in preterm infants. IMPACT: This study has shown that the feeding-induced increase in protein synthesis of skeletal and cardiac muscle is blunted in neonatal pigs born preterm compared to pigs born at term independently of birth weight. These findings support the notion that preterm birth, and not low birth weight, impairs the capacity of skeletal and cardiac muscle to upregulate mechanistic target of rapamycin-dependent anabolic signaling pathways and protein synthesis in response to the postprandial increase in insulin and amino acids. These observations suggest that a blunted anabolic response to feeding contributes to reduced lean mass accretion and altered body composition in preterm infants.

Preterm birth alters the feeding-induced activation of Akt signaling in the muscle of neonatal piglets.

BACKGROUND: Postnatal lean mass accretion is commonly reduced in preterm infants. This study investigated mechanisms involved in the blunted feeding-induced activation of Akt in the skeletal muscle of preterm pigs that contributes to lower protein synthesis rates. METHODS: On day 3 following cesarean section, preterm and term piglets were fasted or fed an enteral meal. Activation of Akt signaling pathways in skeletal muscle was determined. RESULTS: Akt1 and Akt2, but not Akt3, phosphorylation were lower in the skeletal muscle of preterm than in term pigs (P < 0.05). Activation of Akt-positive regulators, PDK1 and mTORC2, but not FAK, were lower in preterm than in term (P < 0.05). The formation of Akt complexes with GAPDH and Hsp90 and the abundance of Ubl4A were lower in preterm than in term (P < 0.05). The abundance of Akt inhibitors, PHLPP and SHIP2, but not PTEN and IP6K1, were higher in preterm than in term pigs (P < 0.05). PP2A activation was inhibited by feeding in term but not in preterm pigs (P < 0.05). CONCLUSIONS: Our results suggest that preterm birth impairs regulatory components involved in Akt activation, thereby limiting the anabolic response to feeding. This anabolic resistance likely contributes to the reduced lean accretion following preterm birth. IMPACT: The Akt-mTORC1 pathway plays an important role in the regulation of skeletal muscle protein synthesis in neonates. This is the first evidence to demonstrate that, following preterm birth, the postprandial activation of positive regulators of Akt in the skeletal muscle is reduced, whereas the activation of negative regulators of Akt is enhanced. This anabolic resistance of Akt signaling in response to feeding likely contributes to the reduced accretion of lean mass in premature infants. These results may provide potential novel molecular targets for intervention to enhance lean growth in preterm neonates.

Regulation of skeletal muscle protein synthesis in the preterm pig by intermittent leucine pulses during continuous parenteral feeding.

BACKGROUND: Extrauterine growth restriction is a common complication of preterm birth. Leucine (Leu) is an agonist for the mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) signaling pathway that regulates translation initiation and protein synthesis in skeletal muscle. Previously, we showed that intermittent intravenous pulses of Leu to neonatal pigs born at term receiving continuous enteral nutrition increases muscle protein synthesis and lean mass accretion. Our objective was to determine the impact of intermittent intravenous pulses of Leu on muscle protein anabolism in preterm neonatal pigs administered continuous parenteral nutrition. METHODS: Following preterm delivery (on day 105 of 115 gestation), pigs were fitted with umbilical artery and jugular vein catheters and provided continuous parenteral nutrition. Four days after birth, pigs were assigned to receive intermittent Leu (1600 µmol kg-1 h-1 ; n = 8) or alanine (1600 µmol kg-1 h-1 ; n = 8) parenteral pulses every 4 h for 28 h. Anabolic signaling and fractional protein synthesis were determined in skeletal muscle. RESULTS: Leu concentration in the longissimus dorsi and gastrocnemius muscles increased in the leucine (LEU) group compared with the alanine (ALA) group (P < 0.0001). Despite the Leu-induced disruption of the Sestrin2·GATOR2 complex, which inhibits mTORC1 activation, in these muscles (P < 0.01), the abundance of mTOR·RagA and mTOR·RagC was not different. Accordingly, mTORC1-dependent activation of 4EBP1, S6K1, eIF4E·eIF4G, and protein synthesis were not different in any muscle between the LEU and ALA groups. CONCLUSION: Intermittent pulses of Leu do not enhance muscle protein anabolism in preterm pigs supplied continuous parenteral nutrition.

Educating the educators: Implementing cultural safety in the nursing and midwifery curriculum.

BACKGROUND: The Australian Nursing and Midwifery Accreditation Council mandates the teaching of cultural safety in Bachelor of Nursing and Midwifery programs in Australia. However nursing and midwifery academics may lack the awareness and knowledge required to share and develop cultural safety practices with their students. Specific cultural safety professional development for academics may be needed. OBJECTIVES: This research explores how nursing and midwifery academics at an Australian university understand cultural safety and whether they are equipped to embed it in the curriculum. It also examines whether professional development workshops can support academics to prepare for cultural safety. METHODS: An intervention involving three cultural safety professional development workshops was offered to nursing academics at an Australian university. The authors used qualitative surveys to consider whether the workshops deepened participants' understanding of cultural safety and developed the self-reflection required to embed cultural safety in teaching. RESULTS: The workshops contributed to participants' improved understandings of culture, colonisation, white privilege and the need for self-reflection, but not all participants developed a working knowledge of cultural safety practice. CONCLUSION: Professional development workshops can assist nursing and midwifery academics to develop their knowledge of cultural safety, but detailed, contextual understanding is likely to need more than three sessions. Academics' motivations to include cultural safety in their teaching may be linked to their desire for patient-driven and equitable services and a desire to meet accreditation requirements.

Future of biomedical, agricultural, and biological systems research using domesticated animals.

Increased knowledge of reproduction and health of domesticated animals is integral to sustain and improve global competitiveness of U.S. animal agriculture, understand and resolve complex animal and human diseases, and advance fundamental research in sciences that are critical to understanding mechanisms of action and identifying future targets for interventions. Historically, federal and state budgets have dwindled and funding for the United States Department of Agriculture (USDA) National Institute of Food and Agriculture (NIFA) competitive grants programs remained relatively stagnant from 1985 through 2010. This shortage in critical financial support for basic and applied research, coupled with the underappreciated knowledge of the utility of non-rodent species for biomedical research, hindered funding opportunities for research involving livestock and limited improvements in both animal agriculture and animal and human health. In 2010, the National Institutes of Health and USDA NIFA established an interagency partnership to promote the use of agriculturally important animal species in basic and translational research relevant to both biomedicine and agriculture. This interagency program supported 61 grants totaling over $107 million with 23 awards to new or early-stage investigators. This article will review the success of the 9-year Dual Purpose effort and highlight opportunities for utilizing domesticated agricultural animals in research.

Dietary and Complementary Feeding Practices of US Infants, 6 to 12 Months: A Narrative Review of the Federal Nutrition Monitoring Data.

Complementary foods and beverages (CFBs) are key components of an infant's diet in the second 6 months of life. This article summarizes nutrition and feeding practices examined by the 2020 Dietary Guidelines Advisory Committees during the CFB life stage. Breastfeeding initiation is high (84%), but exclusive breastfeeding at 6 months (26%) is below the Healthy People 2030 goal (42%). Most infants (51%) are introduced to CFBs sometime before 6 months. The primary mode of feeding (ie, human milk fed [HMF]; infant formula or mixed formula and human milk fed [FMF]) at the initiation of CFBs is associated with the timing of introduction and types of CFBs reported. FMF infants (42%) are more likely to be introduced to CFBs before 4 months compared with HMF infants (19%). Different dietary patterns, such as higher prevalence of consumption and mean amounts, were observed, including fruit, grains, dairy, proteins, and solid fats. Compared with HMF infants of the same age, FMF infants consume more total energy (845 vs 631 kcal) and protein (22 vs 12 g) from all sources, and more energy (345 vs 204 kcal) and protein (11 vs 6 g) from CFBs alone. HMF infants have a higher prevalence of risk of inadequate intakes of iron (77% vs 7%), zinc (54% vs <3%), and protein (27% vs <3%). FMF infants are more likely to have an early introduction (<12 months) to fruit juice (45% vs 20%) and cow's milk (36% vs 24%). Registered dietitian nutritionists and nutritional professionals should consider tailoring their advice to caregivers on dietary and complementary feeding practices, taking into account the primary mode of milk feeding during this life stage to support infants' nutrient adequacy. National studies that address the limitations of this analysis, including small sample sizes and imputed breast milk volume, could refine findings from this analysis.

Intermittent bolus feeding does not enhance protein synthesis, myonuclear accretion, or lean growth more than continuous feeding in a premature piglet model.

Optimizing enteral nutrition for premature infants may help mitigate extrauterine growth restriction and adverse chronic health outcomes. Previously, we showed in neonatal pigs born at term that lean growth is enhanced by intermittent bolus compared with continuous feeding. The objective was to determine if prematurity impacts how body composition, muscle protein synthesis, and myonuclear accretion respond to feeding modality. Following preterm delivery, pigs were fed equivalent amounts of formula delivered either as intermittent boluses (INT; n = 30) or continuously (CONT; n = 14) for 21 days. Body composition was measured by dual-energy X-ray absorptiometry (DXA) and muscle growth was assessed by morphometry, myonuclear accretion, and satellite cell abundance. Tissue anabolic signaling and fractional protein synthesis rates were determined in INT pigs in postabsorptive (INT-PA) and postprandial (INT-PP) states and in CONT pigs. Body weight gain and composition did not differ between INT and CONT pigs. Longissimus dorsi (LD) protein synthesis was 34% greater in INT-PP than INT-PA pigs (P < 0.05) but was not different between INT-PP and CONT pigs. Phosphorylation of 4EBP1 and S6K1 and eIF4E·eIF4G abundance in LD paralleled changes in LD protein synthesis. Satellite cell abundance, myonuclear accretion, and fiber cross-sectional area in LD did not differ between groups. These results suggest that, unlike pigs born at term, intermittent bolus feeding does not enhance lean growth more than continuous feeding in pigs born preterm. Premature birth attenuates the capacity of skeletal muscle to respond to cyclical surges in insulin and amino acids with intermittent feeding in early postnatal life.NEW & NOTEWORTHY Extrauterine growth restriction often occurs in premature infants but may be mitigated by optimizing enteral feeding strategies. We show that intermittent bolus feeding does not increase skeletal muscle protein synthesis, myonuclear accretion, or lean growth more than continuous feeding in preterm pigs. This attenuated anabolic response of muscle to intermittent bolus feeding, compared with previous observations in pigs born at term, may contribute to deficits in lean mass that many premature infants exhibit into adulthood.

Development of Food Pattern Recommendations for Infants and Toddlers 6-24 Months of Age to Support the Dietary Guidelines for Americans, 2020-2025.

BACKGROUND: Developing food-based dietary guidelines (FBDGs) for infants and toddlers is a complex task that few countries have attempted. OBJECTIVES: Our objectives are to describe the process of food pattern modeling (FPM) conducted to develop FBDGs for the Dietary Guidelines for Americans, 2020-2025 for infants 6 to <12 mo and toddlers 12 to <24 mo of age, as well as the implications of the results and areas needing further work. METHODS: The US 2020 Dietary Guidelines Advisory Committee, with the support of federal staff, conducted FPM analyses using 5 steps: 1) identified energy intake targets; 2) established nutritional goals; 3) identified food groupings and expected amounts, using 3 options for the amount of energy from human milk in each age interval; 4) estimated expected nutrient intakes for each scenario, based on nutrient-dense representative foods; and 5) evaluated expected nutrient intakes against nutritional goals. RESULTS: For human milk-fed infants (and toddlers), example combinations of complementary foods and beverages were developed that come close to meeting almost all nutrient recommendations if iron-fortified infant cereals are included at 6 to <12 mo of age. These combinations would also be suitable for formula-fed infants. For toddlers not fed human milk, 2 patterns were developed: the Healthy US-Style Pattern and the Healthy Vegetarian Pattern (a lacto-ovo vegetarian pattern). Achieving nutrient recommendations left virtually no remaining energy for added sugars. CONCLUSIONS: It is challenging to meet all nutrient needs during these age intervals. Added sugars should be avoided for infants and toddlers <2 y of age. Further work is needed to 1) establish a reference human milk composition profile, 2) update and strengthen the DRI values for these age groups, and 3) use optimization modeling, in combination with FPM, to identify combinations of foods that meet all nutritional goals.

Breastfeeding and risk of overweight in childhood and beyond: a systematic review with emphasis on sibling-pair and intervention studies.

BACKGROUND: Breastfeeding is associated with a lower risk of subsequent overweight or obesity, but it is uncertain whether this is a causal relation because most studies have not adequately reduced risk of bias due to confounding. OBJECTIVES: The aim of this review was to examine whether 1) ever compared with never consuming human milk and 2) different durations of human milk consumption among infants fed human milk are related to later risk of overweight or obesity, with emphasis on sibling-pair and intervention studies. METHODS: The 2020 Dietary Guidelines Advisory Committee, together with the Nutrition Evidence Systematic Review team, conducted a systematic review of articles relevant to healthy full-term infants in countries with a high or very high level of human development. We searched PubMed, Embase, Cochrane, and CINAHL; dual-screened the results using predetermined criteria; extracted data from and assessed the risk of bias for each included study; qualitatively synthesized the evidence; developed conclusion statements; and graded the strength of the evidence. RESULTS: The review included 42 articles, including 6 cohorts with sibling-pair analyses and 1 randomized controlled trial of a breastfeeding promotion intervention. Moderate evidence suggested that ever, compared with never, consuming human milk is associated with a lower risk of overweight and obesity at ages 2 y and older, particularly if the duration of human milk consumption is >6 mo. However, residual confounding cannot be ruled out. Evidence was insufficient to determine the relation between the duration of any human milk consumption, among infants fed human milk, and overweight and/or obesity at age 2 y and older. CONCLUSIONS: Further research, using strong study designs, is needed to disentangle the complex relation between infant feeding practices and the risk of subsequent overweight or obesity, as well as the biological and behavioral mechanisms if the relation is causal.

A guide for authors and readers of the American Society for Nutrition Journals on the proper use of P values and strategies that promote transparency and improve research reproducibility.

Two questions regarding the scientific literature have become grist for public discussion: 1) what place should P values have in reporting the results of studies? 2) How should the perceived difficulty in replicating the results reported in published studies be addressed? We consider these questions to be 2 sides of the same coin; failing to address them can lead to an incomplete or incorrect message being sent to the reader. If P values (which are derived from the estimate of the effect size and a measure of the precision of the estimate of the effect) are used improperly, for example reporting only significant findings, or reporting P values without account for multiple comparisons, or failing to indicate the number of tests performed, the scientific record can be biased. Moreover, if there is a lack of transparency in the conduct of a study and reporting of study results, it will not be possible to repeat a study in a manner that allows inferences from the original study to be reproduced or to design and conduct a different experiment whose aim is to confirm the original study's findings. The goal of this article is to discuss how P values can be used in a manner that is consistent with the scientific method, and to increase transparency and reproducibility in the conduct and analysis of nutrition research.

Intermittent Bolus Compared With Continuous Feeding Enhances Insulin and Amino Acid Signaling to Translation Initiation in Skeletal Muscle of Neonatal Pigs.

BACKGROUND: Nutrition administered as intermittent bolus feeds rather than continuously promotes greater protein synthesis rates in skeletal muscle and enhances lean growth in a neonatal piglet model. The molecular mechanisms responsible remain unclear. OBJECTIVES: We aimed to identify the insulin- and/or amino acid-signaling components involved in the enhanced stimulation of skeletal muscle by intermittent bolus compared to continuous feeding in neonatal pigs born at term. METHODS: Term piglets (2-3 days old) were fed equal amounts of sow milk replacer [12.8 g protein and 155 kcal/(kg body weight · d)] by orogastric tube as intermittent bolus meals every 4 hours (INT) or by continuous infusion (CTS). After 21 days, gastrocnemius muscle samples were collected from CTS, INT-0 (before a meal), and INT-60 (60 minutes after a meal) groups (n = 6/group). Insulin- and amino acid-signaling components relevant to mechanistic target of rapamycin complex (mTORC) 1 activation and protein translation were measured. RESULTS: Phosphorylation of the insulin receptor, IRS-1, PDK1, mTORC2, pan-Akt, Akt1, Akt2, and TSC2 was 106% to 273% higher in the skeletal muscle of INT-60 piglets than in INT-0 and CTS piglets (P  < 0.05), but phosphorylation of PTEN, PP2A, Akt3, ERK1/2, and AMPK did not differ among groups, nor did abundances of PHLPP, SHIP2, and Ubl4A. The association of GATOR2 with Sestrin1/2, but not CASTOR1, was 51% to 52% lower in INT-60 piglets than in INT-0 and CTS piglets (P  < 0.05), but the abundances of SLC7A5/LAT1, SLC38A2/SNAT2, SLC38A9, Lamtor1/2, and V-ATPase did not differ. Associations of mTOR with RagA, RagC, and Rheb and phosphorylation of S6K1 and 4EBP1, but not eIF2α and eEF2, were 101% to 176% higher in INT-60 piglets than in INT-0 and CTS piglets (P < 0.05). CONCLUSIONS: The enhanced rates of muscle protein synthesis and growth with intermittent bolus compared to continuous feeding in a neonatal piglet model can be explained by enhanced activation of both the insulin- and amino acid-signaling pathways that regulate translation initiation.