Benefits and challenges of transitioning preterm infants to at-breast feedings

Upon hospital discharge it is not unusual for mothers of preterm infants to continue to meet all or most of their infants' nutritional needs through bottle feedings of expressed breast milk (EBM) because of infants' physiological immaturity and maternal concerns with an inadequacy of milk supply. Although for some mothers the challenge of transitioning the infant to feeding at the breast may be beyond their ability and resources, for others it appears to be based on a conscious choice. Mothers are often unaware of the advantages of breastfeeding at the breast. The purpose of this article is to examine some of the factors that may contribute to the inability and resistance of mothers to transition their preterm infants, and to report on the potential short and long-term advantages associated with feeding at the breast as opposed to feeding bottles of EBM

Milk production of Holstein-Friesian cows of divergent Economic Breeding Index evaluated under seasonal pasture-based management

peer-reviewedThe objective of this study was to validate the effect of genetic improvement using the Irish genetic merit index, the Economic Breeding Index (EBI), on total lactation performance and lactation profiles for milk yield, milk solids yield (fat plus protein; kg), and milk fat, protein, and lactose content within 3 pasture-based feeding treatments (FT) and to investigate whether an interaction exists between genetic group (GG) of Holstein-Friesian and pasture-based FT. The 2 GG were (1) extremely high EBI representative of the top 5% nationally (referred to as the elite group) and (2) representative of the national average EBI (referred to as the NA group). Cows from each GG were randomly allocated each year to 1 of 3 pasture-based FT: control, lower grass allowance, and high concentrate. The effects of GG, FT, year, parity, and the interaction between GG and FT adjusted for calving day of year on milk and milk solids (fat plus protein; kg) production across lactation were studied using mixed models. Cow was nested within GG to account for repeated cow records across years. The overall and stage of lactation-specific responses to concentrate supplementation (high concentrate vs. control) and reduced pasture allowance (lower grass allowance vs. control) were tested. Profiles of daily milk yield, milk solids yield, and milk fat, protein, and lactose content for each week of lactation for the elite and NA groups within each FT and for each parity group within the elite and NA groups were generated. Phenotypic performance was regressed against individual cow genetic potential based on predicted transmitting ability. The NA cows produced the highest milk yield. Milk fat and protein content was higher for the elite group and consequently yield of solids-corrected milk was similar, whereas yield of milk solids tended to be higher for the elite group compared with the NA group. Milk lactose content did not differ between GG. Responses to concentrate supplementation or reduced pasture allowance did not differ between GG. Milk production profiles illustrated that elite cows maintained higher production but with lower persistency than NA cows. Regression of phenotypic performance against predicted transmitting ability illustrated that performance was broadly in line with expectation. The results illustrate that the superiority of high-EBI cattle is consistent across diverse pasture-based FT. The results also highlight the success of the EBI to deliver production performance in line with the national breeding objective: lower milk volume with higher fat and protein content

Acute Renal Responses to Moderate-Intensity Aerobic Exercise with Non-traditional markers of Renal Health and Function in Healthy Individuals: A Pilot Study

Aerobic exercise elicits a multitude of physiological improvements in both healthy and diseased populations. However, acute changes in renal function with aerobic exercise remain difficult to quantify by traditional marker serum creatinine (sCr) to estimate glomerular filtration rate (eGFR). Recently, novel biomarkers cystatin C (CyC) and urine epidermal growth factor (uEGF) have been introduced as more reliable markers of renal health and function to be used in conjunction with sCr to assess changes in renal health and function in mid-spectrum CKD. Potentially, greater changes in novel markers of renal health and function similar to mid-spectrum CKD can be observed in healthy individuals. PURPOSE: To determine if an acute bout of moderate-intensity aerobic exercise can transiently alter novel markers of renal health and function in healthy individuals. METHODS: Thirty-nine participants (n = 18 men; n = 21 women; age 32.5 + 12.6 yr; height 171.1 + 11.4 cm; weight 78.7 + 15.6 kg; BMI 27.1 + 5.8) completed a single acute bout of moderate-intensity (50-65% HRR) aerobic exercise. Blood and urine samples were collected pre-exercise and 15 minutes post-exercise by the same technician under standardized conditions and stored at -60 ºC until project completion. Serum creatinine (sCR), urine creatinine (uCr), urine epidermal growth factor (uEGF), uEGF/uCr ratio (uEGFR), cystatin C (CyC) and eGFR - modification of diet in renal disease (MDRD) and the CKD-EPI- responses were analyzed using a paired sample t-test. RESULTS: Relative to pre-exercise measures: sCR (p = 0.38), uEGF (p = 0.35), and uEGFR (p = 0.09) remained unchanged, whereas, uCr (p = 0.045) and CyC (p = 0.00) significantly changed post-exercise. There was a difference in uEGF pre- to post-exercise, but the standard deviation was large, likely preventing this from being significant. In contrasts MDRD (p = 0.04) significantly increased while CKD-EPI (p = 0.22) had no significant changes. CONCLUSION: Acute changes in traditional and novel biomarkers of renal health and function in healthy individuals remain unclear after an acute bout of moderate-intensity aerobic exercise. Further investigation focused on sampling time and exercise intensity is needed to solidify the current understanding of renal health and function

Is Age an Independent Factor in Assessing Renal Health and Function in Healthy Individuals? A Pilot Study

Estimated glomerular filtration rate (eGFR) is a measure of renal filtration and clearance of serum creatinine and is conventionally used to characterize the progressive decline in renal function. Assessment of renal function and health is traditionally believed to be age-dependent. However, in the absence of cardiometabolic diseases (hypertension, diabetes, hyperlipemia, etc.), this may not be the case. Recently, novel markers of renal health and function support the notion that age is a secondary factor influencing renal decline. PURPOSE: To determine the magnitude of age as an influencing factor involved in the decline of renal function with novel markers of renal health and function in the absence of cardiometabolic risk factors. METHODS: Thirty-nine participants (n = 18 men; n = 21 women; age 32.5 + 12.6 yr; height 171.1 + 11.4 cm; weight 78.7 + 15.6 kg; BMI 27.1 + 5.8; SBP 120 + 11.2; DBP 78 + 6.6; CHOL 173 + 30; and GLU 96 + 7) completed a single health assessment to quantify renal health and function. Blood and urine samples were collected by the same technician under standardized conditions and stored at -60 ºC until project completion. Serum creatinine (sCR), urine creatinine (uCr), urine epidermal growth factor (uEGF), uEGF/uCr ratio (uEGFR), cystatin C (CyC) and eGFR - modification of diet in renal disease (MDRD) and the CKD-EPI - responses were analyzed and compared in age groups (20s, 30s, 40s, 50s) using 4 (group) by 1 (sample) ANOVAs. RESULTS: There were no significant differences in markers of renal health and function between any age group. sCR (p = 0.90), uCr (p = 0.17), uEGF (p = 0.15), CyC (p = 0.32), uEGFR (p = 0.28), MDRD (p = 0.17), and CKD-EPI (p = 0.83). CONCLUSION: In healthy individuals, changes in renal health and function appear to be independent of age in the absence of cardiometabolic diseases. Indicating renal health and function could potentially be maintained throughout adulthood, middle age, and possibly attenuated in the senior years with the continued absence of cardiometabolic diseases

Cellular levels of p120 catenin function as a set point for cadherin expression levels in microvascular endothelial cells

The mechanisms by which catenins regulate cadherin function are not fully understood, and the precise function of p120 catenin (p120ctn) has remained particularly elusive. In microvascular endothelial cells, p120ctn colocalized extensively with cell surface VE-cadherin, but failed to colocalize with VE-cadherin that had entered intracellular degradative compartments. To test the possibility that p120ctn binding to VE-cadherin regulates VE-cadherin internalization, a series of approaches were undertaken to manipulate p120ctn availability to endogenous VE-cadherin. Expression of VE-cadherin mutants that competed for p120ctn binding triggered the degradation of endogenous VE-cadherin. Similarly, reducing levels of p120ctn using siRNA caused a dramatic and dose-related reduction in cellular levels of VE-cadherin. In contrast, overexpression of p120ctn increased VE-cadherin cell surface levels and inhibited entry of cell surface VE-cadherin into degradative compartments. These results demonstrate that cellular levels of p120ctn function as a set point mechanism that regulates cadherin expression levels, and that a major function of p120ctn is to control cadherin internalization and degradation

Incidental findings from cancer next generation sequencing panels

Next-generation sequencing (NGS) technologies have facilitated multi-gene panel (MGP) testing to detect germline DNA variants in hereditary cancer patients. This sensitive technique can uncover unexpected, non-germline incidental findings indicative of mosaicism, clonal hematopoiesis (CH), or hematologic malignancies. A retrospective chart review was conducted to identify cases of incidental findings from NGS-MGP testing. Inclusion criteria included: 1) multiple pathogenic variants in the same patient; 2) pathogenic variants at a low allele fraction; and/or 3) the presence of pathogenic variants not consistent with family history. Secondary tissue analysis, complete blood count (CBC) and medical record review were conducted to further delineate the etiology of the pathogenic variants. Of 6060 NGS-MGP tests, 24 cases fulfilling our inclusion criteria were identified. Pathogenic variants were detected in TP53, ATM, CHEK2, BRCA1 and APC. 18/24 (75.0%) patients were classified as CH, 3/24 (12.5%) as mosaic, 2/24 (8.3%) related to a hematologic malignancy, and 1/24 (4.2%) as true germline. We describe a case-specific workflow to identify and interpret the nature of incidental findings on NGS-MGP. This workflow will provide oncology and genetic clinics a practical guide for the management and counselling of patients with unexpected NGS-MGP findings

Macrosystems ecology: Understanding ecological patterns and processes at continental scales

Macrosystems ecology is the study of diverse ecological phenomena at the scale of regions to continents and their interactions with phenomena at other scales. This emerging subdiscipline addresses ecological questions and environmental problems at these broad scales. Here, we describe this new field, show how it relates to modern ecological study, and highlight opportunities that stem from taking a macrosystems perspective. We present a hierarchical framework for investigating macrosystems at any level of ecological organization and in relation to broader and finer scales. Building on well-established theory and concepts from other subdisciplines of ecology, we identify feedbacks, linkages among distant regions, and interactions that cross scales of space and time as the most likely sources of unexpected and novel behaviors in macrosystems. We present three examples that highlight the importance of this multiscaled systems perspective for understanding the ecology of regions to continents

Understanding Evolutionary Impacts of Seasonality: An Introduction to the Symposium

Seasonality is a critically important aspect of environmental variability, and strongly shapes all aspects of life for organisms living in highly seasonal environments. Seasonality has played a key role in generating biodiversity, and has driven the evolution of extreme physiological adaptations and behaviors such as migration and hibernation. Fluctuating selection pressures on survival and fecundity between summer and winter provide a complex selective landscape, which can be met by a combination of three outcomes of adaptive evolution: genetic polymorphism, phenotypic plasticity, and bet-hedging. Here, we have identified four important research questions with the goal of advancing our understanding of evolutionary impacts of seasonality. First, we ask how characteristics of environments and species will determine which adaptive response occurs. Relevant characteristics include costs and limits of plasticity, predictability, and reliability of cues, and grain of environmental variation relative to generation time. A second important question is how phenological shifts will amplify or ameliorate selection on physiological hardiness. Shifts in phenology can preserve the thermal niche despite shifts in climate, but may fail to completely conserve the niche or may even expose life stages to conditions that cause mortality. Considering distinct environmental sensitivities of life history stages will be key to refining models that forecast susceptibility to climate change. Third, we must identify critical physiological phenotypes that underlie seasonal adaptation and work toward understanding the genetic architectures of these responses. These architectures are key for predicting evolutionary responses. Pleiotropic genes that regulate multiple responses to changing seasons may facilitate coordination among functionally related traits, or conversely may constrain the expression of optimal phenotypes. Finally, we must advance our understanding of how changes in seasonal fluctuations are impacting ecological interaction networks. We should move beyond simple dyadic interactions, such as predator prey dynamics, and understand how these interactions scale up to affect ecological interaction networks. As global climate change alters many aspects of seasonal variability, including extreme events and changes in mean conditions, organisms must respond appropriately or go extinct. The outcome of adaptation to seasonality will determine responses to climate change

Hematopoietic Cell Transplantation in Patients With Primary Immune Regulatory Disorders (PIRD): A Primary Immune Deficiency Treatment Consortium (PIDTC) Survey.

Primary Immune Regulatory Disorders (PIRD) are an expanding group of diseases caused by gene defects in several different immune pathways, such as regulatory T cell function. Patients with PIRD develop clinical manifestations associated with diminished and exaggerated immune responses. Management of these patients is complicated; oftentimes immunosuppressive therapies are insufficient, and patients may require hematopoietic cell transplant (HCT) for treatment. Analysis of HCT data in PIRD patients have previously focused on a single gene defect. This study surveyed transplanted patients with a phenotypic clinical picture consistent with PIRD treated in 33 Primary Immune Deficiency Treatment Consortium centers and European centers. Our data showed that PIRD patients often had immunodeficient and autoimmune features affecting multiple organ systems. Transplantation resulted in resolution of disease manifestations in more than half of the patients with an overall 5-years survival of 67%. This study, the first to encompass disorders across the PIRD spectrum, highlights the need for further research in PIRD management