Impaired Response to Polysaccharide Vaccine in Selective IgE Deficiency.

PURPOSE: Immunoglobulin E deficiency (IgED) (defined as IgE < 2 IU/mL) is enriched in patients with primary antibody deficiency (PAD). We hypothesized that selective IgED (sIgED) is a more sensitive predictor of the development of PAD than declining IgG, as IgE production typically requires two class switch recombination (CSR) events in contrast to IgG. Thus, the inability of patients with sIgED to mount an appropriate antibody response to a T-cell independent antigen or evidence of aberrant induction of ɛ germ line (ɛGL) or IgE heavy chain (IgEHC) transcripts in vitro would support the concept that sIgED is a biomarker for emerging PAD. METHODS: We compared pre- and post-polysaccharide vaccination titers in healthy patients with sIgED without a history of recurrent infections or autoimmunity (n = 20) and in healthy controls (HCs) (n = 17). Subsequently, we assessed in vitro induction of εGL and IgEHC transcripts in patients with sIgED and HC (n = 6) in response to IL-4 + CD40L stimulation. RESULTS: Thirty percent of patients with sIgED did not have a robust vaccine response compared to 0% of HCs (p = 0.017). Individuals with sIgED with an abnormal vaccine response demonstrated persistent germline mRNA expression in their B-cells at day 5, with lower levels of IgEHC, compared to both HCs and sIgED participants with a normal vaccine response. CONCLUSION: Patients with sIgED are more likely to have abnormal antibody responses to a T cell-independent antigen and may have dysregulated CSR machinery. Following individuals with sIgED longitudinally may be beneficial in the early identification of PAD.

Macrophage Phenotypes and Gene Expression Patterns Are Unique in Naturally Occurring Metabolically Healthy Obesity.

Obesity impacts 650 million individuals globally, often co-occurring with metabolic syndrome. Though many obese individuals experience metabolic abnormalities (metabolically unhealthy obese [MUO]), ~30% do not (metabolically healthy obese [MHO]). Conversely, >10% of lean individuals are metabolically unhealthy (MUL). To evaluate the physiologic drivers of these phenotypes, a 44-animal African green monkey cohort was selected using metabolic syndrome risk criteria to represent these four clinically defined health groups. Body composition imaging and subcutaneous adipose tissue (SQ AT) biopsies were collected. Differences in adipocyte size, macrophage subtype distribution, gene expression, vascularity and fibrosis were analyzed using digital immunohistopathology, unbiased RNA-seq, endothelial CD31, and Masson's trichrome staining, respectively. MHO AT demonstrated significant increases in M2 macrophages (p = 0.02) and upregulation of fatty acid oxidation-related terms and transcripts, including FABP7 (p = 0.01). MUO AT demonstrated downregulation of these factors and co-occurring upregulation of immune responses. These changes occurred without differences in AT distributions, adipocyte size, AT endothelial cells, collagen I deposition, or circulating cytokine levels. Without unhealthy diet consumption, healthy obesity is defined by an increased SQ AT M2/M1 macrophage ratio and lipid handling gene expression. We highlight M2 macrophages and fatty acid oxidation as targets for improving metabolic health with obesity.

TSPEAR variants are primarily associated with ectodermal dysplasia and tooth agenesis but not hearing loss: A novel cohort study.

Biallelic loss-of-function variants in the thrombospondin-type laminin G domain and epilepsy-associated repeats (TSPEAR) gene have recently been associated with ectodermal dysplasia and hearing loss. The first reports describing a TSPEAR disease association identified this gene is a cause of nonsyndromic hearing loss, but subsequent reports involving additional affected families have questioned this evidence and suggested a stronger association with ectodermal dysplasia. To clarify genotype-phenotype associations for TSPEAR variants, we characterized 13 individuals with biallelic TSPEAR variants. Individuals underwent either exome sequencing or panel-based genetic testing. Nearly all of these newly reported individuals (11/13) have phenotypes that include tooth agenesis or ectodermal dysplasia, while three newly reported individuals have hearing loss. Of the individuals displaying hearing loss, all have additional variants in other hearing-loss-associated genes, specifically TMPRSS3, GJB2, and GJB6, that present competing candidates for their hearing loss phenotype. When presented alongside previous reports, the overall evidence supports the association of TSPEAR variants with ectodermal dysplasia and tooth agenesis features but creates significant doubt as to whether TSPEAR variants are a monogenic cause of hearing loss. Further functional evidence is needed to evaluate this phenotypic association.

Potential regional declines in species richness of tomato pollinators in North America under climate change.

About 70% of the world's main crops depend on insect pollination. Climate change is already affecting the abundance and distribution of insects, which could cause geographical mismatches between crops and their pollinators. Crops that rely primarily on wild pollinators (e.g., crops that cannot be effectively pollinated by commercial colonies of honey bees) could be particularly in jeopardy. However, limited information on plant-pollinator associations and pollinator distributions complicate the assessment of climate change impacts on specific crops. To study the potential impacts of climate change on pollination of a specific crop in North America, we use the case of open-field tomato crops, which rely on buzz pollinators (species that use vibration to release pollen, such as bumble bees) to increase their production. We aimed to (1) assess potential changes in buzz pollinator distribution and richness, and (2) evaluate the overlap between areas with high densities of tomato crops and high potential decrease in richness. We used baseline (1961-1990) climate and future (2050s and 2080s) climatic projections in ecological niche models fitted with occurrences of wild bees, documented in the literature as pollinators of tomatoes, to estimate the baseline and future potential distribution of suitable climatic conditions of targeted species and to create maps of richness change across North America. We obtained reliable models for 15 species and found important potential decreases in the distribution of some pollinators (e.g., Lasioglossum pectorale and Augochlorella aurata). We observed geographical discrepancies in the projected change in species richness across North America, detecting important declines in the eastern United States (up to 11 species decrease for 2050s). After overlapping the maps of species richness change with a tomato crop map for the United States, we found spatial correspondence between richness declines and areas with high concentration of tomato crops. Disparities in the effects of climate change on the potential future distribution of different wild pollinators and geographical variation in richness highlight the importance of crop-specific studies. Our study also emphasizes the challenges of compiling and modeling crop-specific pollinator data and the need to improve our understanding of current distribution of pollinators and their community dynamics under climate change.

Violence against children in Latin America and the Caribbean: What do available data reveal about prevalence and perpetrators?

OBJECTIVE: To describe the prevalence of recent physical, sexual, and emotional violence against children 0 - 19 years of age in Latin America and the Caribbean (LAC) by age, sex, and perpetrator. METHODS: A systematic review and analysis of published literature and large international datasets was conducted. Eligible sources from first record to December 2015 contained age-, sex-, and perpetrator-specific data from LAC. Random effects meta-regressions were performed, adjusting for relevant quality covariates and differences in violence definitions. RESULTS: Seventy-two surveys (2 publications and 70 datasets) met inclusion criteria, representing 1 449 estimates from 34 countries. Prevalence of physical and emotional violence by caregivers ranged from 30% - 60%, and decreased with increasing age. Prevalence of physical violence by students (17% - 61%) declined with age, while emotional violence remained constant (60% - 92%). Prevalence of physical intimate partner violence (IPV) ranged from 13% - 18% for girls aged 15 - 19 years. Few or no eligible past-year estimates were available for any violence against children less than 9 years and boys 16 - 19 years of age; sexual violence against boys (any age) and girls (under 15 years); IPV except for girls aged 15 - 19 years; and violence by authority figures (e.g., teachers) or via gangs/organized crime. CONCLUSION: Past-year physical and emotional violence by caregivers and students is widespread in LAC across all ages in childhood, as is IPV against girls aged 15 - 19 years. Data collection must be expanded in LAC to monitor progress towards the sustainable development goals, develop effective prevention and response strategies, and shed light on violence relating to organized crime/gangs.

The implementation road: engaging community partnerships in evidence-based cancer control interventions.

Southern rural and underserved counties have high proportions of individuals with increased mortality for cervical and breast cancers. To improve the integration of behavioral research into practice, the dissemination and implementation of efficacious interventions to encourage the use of screening have increased in recent years. This study addressed gaps in the dissemination and implementation of evidence-based interventions with a pilot called Team Up. Qualitative interviews with 24 key individuals in six state-level partnerships explored partnership characteristics that influenced selection and use of evidence-based interventions among low-income, rarely or never screened women. Guided by diffusion of innovations theory and the Lasker and Weiss partnership functioning model, interviews about the intervention centered on (a) knowledge surrounding evidence base; (b) identification, selection, and adoption; (c) planning and adaptation; (d) implementation; and (e) partnership reflections and impact. Using grounded theory and content analysis, data revealed that lack of communication and high partner turnover hindered adoption and adaptation, whereas failure of partnership leaders to engage local stakeholders and lack of sufficient funds hampered implementation. Delivery of evidence-based interventions was more effective when partnerships included local partners in early decision making and when coaches were introduced to facilitate strategic thinking about translating evidence-based interventions into practice. A challenge for public health partnerships was the translation of interventions into successful programs, such that underserved communities benefited from early detection intervention research.

Seeking an Integrated Approach to Trauma and Problematic Sexual Behaviors in Adolescents: Learning from Practitioners.

More than a third of all sexual crimes are committed by adolescents. In addition, many adolescents struggle with problematic sexual behaviors (PSB) that may not rise to a criminal offense, but cause harm to themselves and those around them. A significant number of these adolescents also have histories of their own trauma; yet there are no treatment models that integrate both PSB and trauma into one comprehensive treatment for this population. This qualitative study's aim was to use the expertise of clinicians who work with adolescents with PSB as well as clients and their caregivers who had completed PSB treatment to understand what they believe are the necessary components and elements needed for an integrated model that seeks to simultaneously address both PSB and the consequences of traumatic experiences. Twenty-six mental health professionals and one former client and his caregiver participated in focus groups (three with clinicians and one with the caregiver and former client) to share their experiences and expertise regarding an integrated model. The thematic analysis procedure yielded six major themes: family, external systems, treatment structure, therapeutic themes, specialized PSB targets, and trauma and PSB integration. Each of these major themes was comprised of subthemes that are presented as well. Implications for practice and future research are discussed, including that clinicians could benefit from guidance and structure to assist them in structuring their interventions to address the multiple needs of their clients that seek to reduce their risk of reoffending while simultaneously enhancing the quality of their lives.

Exploring the Impact of Amyotrophic Lateral Sclerosis on Otolaryngological Functions.

IMPORTANCE: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive degeneration of upper and lower motor neurons at the spinal or bulbar level. OBJECTIVE: We aim to describe the most frequent otolaryngology (ORL) complaints and voice disturbances in patients with bulbar onset ALS. DESIGN: Retrospective cohort study. SETTING: Single-center study with combined ORL and ALS clinic evaluation. PARTICIPANTS: Patients with a confirmed diagnosis of ALS following an ORL visit and who underwent comprehensive voice assessments between January 2021 and January 2023. EXPOSURE: Objective voice assessments. MAIN OUTCOMES AND MEASURES: Glottal functional index (GFI), voice handicap index (VHI), reflux system index (RSI), and voice quality characteristics such as shimmer, jitter, maximum phonation time (MPT), and other essential parameters were assessed. RESULTS: One hundred and thirty-three patients (age 62.17 ± 10.79, 54.48% female) were included. Three patients were referred from the ORL department to the ALS clinic. The most frequent symptoms were; dysphagia, dysarthria, facial weakness, pseudobulbar affect, and sialorrhea. The mean of forced vital capacity was 59.85%, EAT-10 15.91 ± 11.66, RSI 25.84 ± 9.03, GFI 14.12 ± 5.58, VHI-10 42.81 ± 34.94, MPT 15.22 s ± 8.06. Many patients reported voice impairments mainly related to spastic dysarthria and the combination of lower and upper motor neuron dysarthria, hypernasality, reduced verbal expression, and articulatory accuracy. Shimmer was increased to 8.46% ± 7.20, and jitter to 2.26% ± 1.39. CONCLUSIONS AND RELEVANCE: Based on our cohort, this population with bulbar onset ALS has a higher frequency of voice disturbance characterized by hypernasality, spastic dysarthria, and reduced verbal expression. LEVEL OF EVIDENCE: Level 3.

Aquaponics in schools: Hands-on learning about healthy eating and a healthy planet.

Our food system is giving rise to a growing social, health and environmental crisis. Much of the food consumed in the United Kingdom is cheap, nutrient-poor and highly processed, leading to under-consumption of essential foods such as grains, beans, vegetables and fruit. This has contributed to a rise in diet-related diseases, with approximately 22% of primary school leavers being overweight or obese. Food production is unsustainable with agriculture responsible for 10% of the UK's greenhouse gas emissions and intensive farming practices have led to a significant loss of soil carbon and a decline in biodiversity. COVID-19 increased inequalities in our food system. Therefore, there is an urgent need for interventions to counteract these adverse social, health and environmental impacts. Education can play a crucial role as an intervention to address challenges in the food system. We tested an innovative school initiative using portable aquaponic pods and aligned to the national curriculum, to engage pupils in food production and foster learning about sustainability, climate change and healthy eating. The evaluation, based on teacher surveys, aquapod chart data, student blogs and postcards and feedback from the development team, revealed positive impacts on students' environmental awareness, as well as sustainability and practical food production knowledge. However, the programme encountered logistical challenges and we therefore highlight future improvements to produce a curriculum programme that can be delivered at scale to enhance food education and empower pupils to drive the agenda on tackling food sustainability and climate change.

Laryngeal chondromas: Current knowledge and future directions.

Objective: Cartilaginous tumors of the larynx are rare, representing less than 1% of all laryngeal tumors. Chondromas are benign mesenchymal tumors characterized by a slow-paced growth, primarily originated in the cricoid cartilage, followed by the thyroid, arytenoid, and epiglottic cartilages. This scoping review aims to understand the extent of evidence on the epidemiology, clinical characteristics, morbidity, and recurrence of the laryngeal chondroma (LC). Data sources: MEDLINE (Ovid), Embase (Elsevier), Web of Science (Clarivate), Cochrane Central Register of Controlled Trials and Systematic Reviews, Lilacs, Scopus, and Google Scholar databases. Review methods: The scoping review was conducted from 1816 to 2023, for observational studies describing LC. Titles and abstracts were screened for relevance, followed by an evaluation of the full text for eligibility. The data were collected from the qualifying articles, and a narrative summary of the outcomes was prepared. Results: One hundred and nineteen studies met the inclusion criteria. Ninety-four case reports, 22 case series, and 3 cohorts. Two hundred and four participants with a diagnosis of LC were described. Male:female ratio was 2.8:1. The most common localization was the cricoid (113; 47.08%), followed by the thyroid (45; 18.75%), and the arytenoid cartilage (27; 11.25%). Dyspnea (78.85%) and hoarseness (74.28%) were the most reported symptoms. The recurrence rate was 11.25%, and complications were uncommon following the resection. Conclusion: This scoping review found a low-frequency rate over all the cartilaginous laryngeal tumors. Most patients were treated with resection, with a low rate of malignancy conversion. This population has low attributable mortality, morbidity, and recurrence according to the current literature.

Effects of late gestational nutrient restriction on uterine artery blood flow, placental size, and cotyledonary mRNA expression in primiparous beef females.

Fall-calving primiparous beef females [body weight (BW): 451 ±â€…28 (SD) kg; body condition score (BCS): 5.4 ±â€…0.7] were individually-fed either 100% (control; CON; n = 13) or 70% (nutrient restricted; NR; n = 13) of metabolizable energy and metabolizable protein requirements for maintenance, pregnancy, and growth from day 160 of gestation to parturition. Doppler ultrasonography of both uterine arteries was conducted pre-treatment and every 21 d from days 181 to 265 of gestation. Expelled placentas were collected, and ipsilateral cotyledonary tissue was sampled to assess relative messenger ribonucleic acid (mRNA) expression. Placentas were separated into ipsilateral and contralateral sides, dissected (cotyledonary vs. intercotyledonary), and dried. Data were analyzed with nutritional plane, treatment initiation date, and calf sex (when P < 0.25) as fixed effects. Uterine blood flow included day and nutritional plane × day as repeated measures. We previously reported that post-calving, NR dams weighed 64 kg less and were 2.0 BCS lower than CON, but calf birth weight was not affected. Maternal heart rate was less (P < 0.001) for NR dams than CON after nutritional planes began. Nutritional plane did not affect (P ≥ 0.20) uterine artery hemodynamics, but all variables were affected (P ≤ 0.04) by day. Contralateral cotyledonary and placental weight were less (P ≤ 0.04) and contralateral intercotyledonary weight and number of cotyledons tended to be less (P ≤ 0.10) for NR dams than CON, but ipsilateral and whole placental weights were not affected (P ≥ 0.13). Ipsilateral placental weight as a percentage of total placental weight was greater (P = 0.03) for NR dams than CON. Whole placental cotyledonary: intercotyledonary weight was less (P = 0.01) for NR dams than CON. Placental efficiency was not affected (P = 0.89) by nutritional plane. Cotyledonary relative mRNA expression of GLUT3 and SNAT2 was greater (P ≤ 0.05) and relative expression of GLUT1, GLUT4, and NOS3 tended to be greater (P ≤ 0.07) for NR dams than CON. Nutritional plane did not affect (P ≥ 0.13) relative mRNA expression of GLUT5, 4F2hc, CAT1, LAT1, LAT2, VEGFA, FLT1, KDR, GUCY1B3, and PAG2. Despite less contralateral placental growth, beef heifers experiencing late gestational nutrient restriction maintained uterine artery blood flow and total placental mass and had 4 nutrient transporters and 1 angiogenic factor upregulated in cotyledons, all of which likely contributed to conserving fetal growth.

Nutrient requirements increase substantially during late gestation in the beef female to support fetal, uteroplacental, and mammary growth, and in the still-growing heifer, nutrients are also needed for maternal tissue growth. During pregnancy, the placenta serves as the interface for the metabolism and transport of nutrients, gases, and wastes between maternal and fetal circulations. Inadequate gestational nutrition can result in placental insufficiency and intrauterine growth restriction of the offspring, resulting in postnatal consequences. How late gestational undernutrition in beef heifers impacts the factors involved in placental nutrient transport capacity is poorly understood. We observed that late gestational nutrient restriction in heifers decreased maternal heart rate, but total uterine artery blood flow was not affected. Additionally, total placental mass was maintained, while cotyledonary expression of 4 nutrient transporters and an angiogenic factor were upregulated in placentas of nutrient restricted dams, which collectively allowed for similar calf birth weights as adequately-fed dams.

Late gestational nutrient restriction in primiparous beef females: Performance and metabolic status of lactating dams and pre-weaning calves.

Fall-calving primiparous beef females [body weight (BW): 451 ±â€…28 (SD) kg; body condition score (BCS): 5.4 ±â€…0.7] were individually-fed 100% (control; CON; n = 13) or 70% (nutrient restricted; NR; n = 13) of estimated metabolizable energy and metabolizable protein requirements from day 160 of gestation to calving. Post-calving, all dams were individually-fed tall fescue hay supplemented to meet estimated nutrient requirements for maintenance, growth, and lactation in Calan gates until day 149 of lactation, which limited calves to milk only. From day 150 of lactation until weaning at day 243, dams and calves were group-fed in drylots. Dam BW and metabolic status were determined every 21 d, and BCS and backfat (BF) were determined every 42 d of lactation until weaning. Pre-weaning calf BW, size, and metabolic status were determined every 21 d. Data were analyzed with nutritional plane, calving date, and calf sex (when P < 0.25) as fixed effects. Circulating metabolites included day and nutritional plane × day as repeated measures. We previously reported that post-calving, NR dams were 64 kg and 2.0 BCS less than CON, but calf BW and size at birth were not affected. During the first 147 d of lactation, NR dams gained more (P < 0.01) BW than CON and increased (P < 0.01) BCS, while CON decreased (P ≤ 0.01) BCS and BF. Previously, NR dams had lower (P < 0.01) circulating triglycerides on day 1 of lactation, tended to have lower (P = 0.08) triglycerides on day 21, and had lower (P ≤ 0.04) non-esterified fatty acids (NEFA) on days 21 and 243 than CON. Maternal glucose and urea N were not affected (P ≥ 0.73). At weaning, NR dams weighed 17 kg less (P = 0.15), were 0.67 BCS lower (P < 0.01), and tended to have less (P = 0.06) BF. Calves born to NR dams weighed less (P = 0.02) than CON by day 42 of age and were 13% smaller (P < 0.01) at weaning. Calf girth measures diverged (P ≤ 0.05) by day 21 of age, and skeletal size measures were less (P ≤ 0.08) for calves born to NR dams at most timepoints after day 63 of age. Calves born to NR dams tended to have lower (P = 0.09) circulating urea N pre-weaning than CON, but glucose, triglycerides, and NEFA were not affected (P ≥ 0.16). In summary, first-parity beef females that were nutrient restricted during late gestation experienced compensatory growth and gained body condition during lactation but were still thinner at weaning. Nutrient restriction reduced pre-weaning calf growth, likely due to decreased milk production.

Nutrient requirements increase substantially during late gestation in the beef female; however, poor forage nutrient availability can result in undernutrition. For heifers, the added nutrient requirements needed to continue growing during their first pregnancy and lactation pose an even greater challenge. It is plausible that lingering effects of late gestational nutrient restriction may exist for the dam and calf pre-weaning. We report that first-parity beef females that were nutrient restricted during late gestation and then fed to meet estimated nutrient requirements during lactation recovered quickly metabolically and experienced compensatory growth, but still had less body condition at weaning than controls. Late gestational nutrient restriction did not affect calf size at birth but resulted in calf body weight and size measures diverging early in life. Ultimately, nutrient restriction resulted in a 13% decrease in weaning weight, which was likely due to decreased milk production (in a companion paper). Despite this, metabolic status of calves born to nutrient restricted dams was not greatly altered. In summary, first-parity beef females that were nutrient restricted during late gestation prioritized partitioning nutrients to maternal growth and energy reserves over milk production during lactation, but dams were thinner at weaning, and pre-weaning calf growth was slowed.

Nutrient restriction during late gestation reduces milk yield and mammary blood flow in lactating primiparous beef females.

Fall-calving primiparous beef females [body weight (BW): 451 ±â€…28 (SD) kg; body condition score (BCS): 5.4 ±â€…0.7] were individually-fed 100% (control; CON; n = 13) or 70% (nutrient restricted; NR; n = 13) of estimated metabolizable energy and metabolizable protein requirements from day 160 of gestation to calving. Post-calving, all dams were individually-fed tall fescue hay supplemented to meet estimated nutrient requirements for maintenance, growth, and lactation until day 149 of lactation. Four-hour milk yields were collected on days 21, 42, 63, 84, 105, and 147 of lactation, and milk nutrient composition was determined. Doppler ultrasonography of both pudendoepigastric arterial trunks was conducted every 21 d from days 24 to 108 of lactation. Total mammary blood flow was calculated, and hemodynamics from both sides were averaged. Data were analyzed as repeated measures with nutritional plane, day of lactation, their interaction, calving date, and calf sex (if P < 0.25) as fixed effects. We previously reported that post-calving, NR dams weighed 64 kg less and were 2.0 BCS lower than CON, but calf birth weight was not affected. Milk weight and volume were 15% less (P = 0.04) for NR dams than CON. Milk protein concentration was lower (P = 0.008) for NR dams than CON, but triglyceride and lactose concentrations were not affected (P ≥ 0.20) by nutritional plane. Milk urea N concentration of NR dams tended to be greater (P = 0.07) on day 42 but was lower (P = 0.01) on day 147 of lactation than CON. Total milk protein, triglyceride, and lactose yields were less (P ≤ 0.05) for NR dams than CON. Total milk urea N yield was less (P ≤ 0.03) for NR dams than CON on days 21, 63, and 147 of lactation. Maternal heart rate was greater (P = 0.008), but pudendoepigastric arterial trunk peak systolic velocity, resistance index, and cross-sectional area were less (P ≤ 0.04) and pulsatility index tended to be less (P = 0.06) for NR dams than CON. Mammary blood flow was 19% less (P = 0.004) for NR dams than CON, but mammary blood flow relative to milk weight or dam BW was not affected (P ≥ 0.14) by nutritional plane. Most milk yield, milk nutrient composition, and mammary blood flow variables were affected (P ≤ 0.04) by day of lactation. In summary, first-parity beef females that were nutrient restricted during late gestation and then fed to meet estimated nutrient requirements during lactation had decreased milk nutrient yield and a similar reduction in mammary blood flow.

Mammary development in preparation for lactation is largely complete at the time of calving, and final prepartum mammary growth and differentiation are occurring for the first time in heifers. Nutrient requirements increase substantially during late gestation, resulting in competition for nutrient use among maternal growth, fetal growth, and mammary growth in primiparous beef females. Undernutrition during late gestation can occur due to poor forage nutrient availability or drought, potentially impacting mammary gland development and subsequent milk production. We report that first-parity beef females that were nutrient restricted during late gestation and then fed to meet estimated nutrient requirements during lactation had 15% lower milk yield, reduced milk protein concentration, and less total milk protein, triglycerides, lactose, and urea N available for their calves than controls. Additionally, previously nutrient restricted dams had 19% less total mammary blood flow, and the major arteries supplying the mammary gland were smaller.

Genes involved in the cholecystokinin receptor signaling map were differentially expressed in the jejunum of steers with variation in residual feed intake.

The jejunum is a critical site for nutrient digestion and absorption, and variation in its ability to take up nutrients within the jejunum is likely to affect feed efficiency. The purpose of this study was to determine differences in gene expression in the jejunum of beef steers divergent for residual feed intake (RFI) in one cohort of steers (Year 1), and to validate those genes in animals from a second study (Year 2). Steers from Year 1 (n = 16) were selected for high and low RFI. Jejunum mucosal tissue was obtained for RNA-seq. Thirty-two genes were differentially expressed (PFDR≤0.15), and five were over-represented in pathways including inflammatory mediator, cholecystokinin receptor (CCKR) signaling, and p38 MAPK pathways. Several differentially expressed genes (ALOX12, ALPI, FABP6, FABP7, FLT1, GSTA2, MEF2B, PDK4, SPP1, and TTF2) have been previously associated with RFI in other studies. Real-time qPCR was used to validate nine differentially expressed genes in the Year 1 steers used for RNA-seq, and in the Year 2 validation cohort. Six genes were validated as differentially expressed (P < 0.1) using RT-qPCR in the Year 1 population. In the Year 2 population, five genes displayed the same direction of expression as the Year 1 population and 3 were differentially expressed (P < 0.1). The CCKR pathway is involved in digestion, appetite control, and regulation of body weight making it a compelling candidate for feed efficiency in cattle, and the validation of these genes in a second population of cattle is suggestive of a role in feed efficiency.

Association of glucose metabolism and insulin resistance with feed efficiency and production traits of finishing beef steers.

Increasing nutrient utilization efficiency is an important component of enhancing the sustainability of beef cattle production. The objective of this experiment was to determine the association of glucose metabolism and insulin resistance with dry matter intake (DMI), average daily gain (ADG), gain:feed ratio (G:F), and residual feed intake (RFI). Steers (n = 54; initial body weight = 518 ±â€…27.0 kg) were subjected to an intravenous glucose tolerance test (IVGTT) where glucose was dosed through a jugular catheter and serial blood samples were collected. Three days after the last group's IVGTT, steers began a 63-d DMI and ADG test. Body weight was measured on days 0, 1, 21, 42, 62, and 63, and DMI was measured using an Insentec Roughage Intake Control system (Hokofarm Group, Emmeloord, the Netherlands). To examine relationships between DMI, ADG, G:F, and RFI with IVGTT measurements, Pearson correlations were calculated using Proc Corr of SAS 9.4 (SAS Inst. Inc., Cary, NC). Additionally, cattle were classified based on DMI, ADG, RFI, and G:F, where the medium classification was set as mean ±â€…0.5 SD, the low classification was < 0.5 SD from the mean, and the high classification was > 0.5 SD from the mean. No associations between DMI and IVGTT parameters were observed, and no differences were detected when classifying cattle as having low, medium, or high DMI. Peak insulin concentration in response to the IVGTT tended to be correlated with ADG (r = 0.28; P = 0.07), indicating cattle with greater ADG tend to have a greater insulin release in response to glucose. Glucose nadir concentrations tended to be positively correlated with ADG (r = 0.26; P = 0.10). Additionally, the glucose nadir was greater in high-ADG steers (P = 0.003). The association of greater glucose nadir with high-ADG could indicate that high-ADG steers do not clear glucose as efficiently as low-ADG steers, potentially indicating increased insulin resistance. Further, RFI was not correlated with IVGTT measurements, but low RFI steers had a greater peak glucose concentration (P = 0.040) and tended to have a greater glucose area under the curve (P = 0.09). G:F was correlated with glucose area under the curve (r = 0.33; P = 0.050), glucose nadir (r = 0.35; P = 0.011), and insulin time to peak (r = 0.39; P = 0.010). These results indicate that glucose metabolism and insulin signaling are associated with growth and efficiency, but the molecular mechanisms that drive these effects need to be elucidated.

Feed efficiency is an important component of improving the sustainability of beef production. There is a need to understand how metabolism influences feed efficiency. This experiment aimed to explore the association of glucose metabolism and insulin resistance with feed intake, growth, and efficiency of finishing beef cattle. The results indicate that there is a relationship between insulin resistance and improved efficiency measured as the ratio of growth to feed intake. The findings of this experiment are novel as they show a relationship between insulin resistance and feed efficiency and indicate further research is needed to determine the mechanisms of insulin resistance in ruminants that contribute to improved feed efficiency.

Adolescent neglect, juvenile delinquency and the risk of recidivism.

Victims of child abuse and neglect are at an increased risk of involvement with the juvenile justice and adult correctional systems. Yet, little is known about the continuation and trajectories of offending beyond initial contact with law enforcement. Neglect likely plays a critical role in continued offending as parental monitoring, parental rejection and family relationships are instrumental in explaining juvenile conduct problems. This study sought to determine whether neglect is associated with recidivism for moderate and high risk juvenile offenders in Washington State. Statewide risk assessments and administrative records for child welfare, juvenile justice, and adult corrections were analyzed. The sample was diverse (24 % female, 13 % African American, 8 % Hispanic, 5 % Native American) and included all moderate and high risk juvenile offenders screened by juvenile probation between 2004 and 2007 (n = 19,833). Official records from child protection were used to identify juvenile offenders with a history of child neglect and to identify juvenile offenders with an ongoing case of neglect. Event history models were developed to estimate the risk of subsequent offending. Adolescents with an ongoing case neglect were significantly more likely to continue offending as compared with youth with no official history of neglect. These findings remain even after controlling for a wide range of family, peer, academic, mental health, and substance abuse covariates. Interrupting trajectories of offending is a primary focus of juvenile justice. The findings of the current study indicate that ongoing dependency issues play a critical role in explaining the outcomes achieved for adolescents in juvenile justice settings. The implications for improved collaboration between child welfare and juvenile justice are discussed.

Brief Communication: Histological Assessment of Nonhuman Primate Brown Adipose Tissue Highlights the Importance of Sympathetic Innervation.

Objective: The objective of this study was to functionally analyze the correlation of key histological features in brown adipose tissue (BAT) with clinical metabolic traits in nonhuman primates. Methods: Axillary adipose tissue biopsies were collected from a metabolically diverse nonhuman primate cohort with clinical metabolism-related data. Expression of tyrosine hydroxylase (TH), uncoupling protein 1 (UCP1), cluster of differentiation 31 (CD31), cytochrome c oxidase subunit 4 (COX IV), beta-3 adrenergic receptor (ß3-AR), and adipose cell size were quantified by immunohistochemical analysis. Computed tomography scans were performed to assess body composition. Results: Tyrosine hydroxylase was negatively correlated with whole body fat mass as a percentage of body weight (p = 0.004) and was positively correlated with the density of UCP1 (p = 0.02), COX IV (p = 0.006), CD31 (p = 0.007), and cell density (p = 0.02) of the BAT samples. Beta-3 adrenergic receptor abundance had a weak positive correlation with COX IV (p = 0.04) in BAT but did not significantly correlate to UCP1 or TH expression in BAT. Conclusions: Our findings highlight that there is a disparity in innervation provided to BAT based on body composition, as seen with the negative association between TH, a marker for innervation, and adiposity. These findings also support the importance of innervation in the functionality of BAT, as TH abundance not only supports leaner body composition but is also positively correlated with known structural elements in BAT (UCP1, COX IV, CD31, and cell density). Based on our observations, ß3-AR abundance does not strongly drive these structural elements or TH, all of which are known to be important in the function of brown adipose tissue. In effect, while the role of other receptors, such as ß2-AR, should be reviewed in BAT function, these results support the development of safe sympathetic nervous system stimulants to activate brown adipose tissue for obesity treatment.

Visceral adipose microbial and inflammatory signatures in metabolically healthy and unhealthy nonhuman primates.

OBJECTIVE: Obesity is a key risk factor for metabolic syndrome (MetS); however, >10% of lean individuals meet MetS criteria. Visceral adipose tissue (VAT) disproportionately contributes to inflammation and insulin resistance compared with subcutaneous fat depots. The primary aim of this study was to profile tissue microbiome components in VAT over a wide range of metabolic statuses in a highly clinically relevant model. METHODS: VAT was profiled from nonhuman primates that naturally demonstrate four distinct health phenotypes despite consuming a healthy diet, namely metabolically healthy lean and obese and metabolically unhealthy lean and obese. RESULTS: VAT biopsied from unhealthy lean and obese nonhuman primates demonstrated upregulation of immune signaling pathways, a tissue microbiome enriched in gram-negative bacteria including Pseudomonas, and deficiencies in anti-inflammatory adipose tissue M2 macrophages. VAT microbiomes were distinct from fecal microbiomes, and fecal microbiomes did not differ by metabolic health group, which was in contrast to the VAT bacterial communities. CONCLUSIONS: Immune activation with gram-negative VAT microbial communities is a consistent feature in elevated MetS risk in both lean and obesity states.

Technical note: colorimetric methods for accurate determination of nutrient composition in beef cow colostrum and milk.

Our objectives were to develop colorimetric methods to accurately measure nutrient concentrations of beef cow colostrum and milk, to determine if the yield of colostrum from a single rear quarter is representative of complete collection of colostrum in beef cows, and to compare data from our developed colorimetric methods with Fourier transform infrared spectroscopy (FTIR) analysis to determine the accuracy of FTIR for beef cow colostrum and milk. In Exp. 1, colostral weight and volume of the most full rear quarter were compared with complete collection of colostrum from post-calving, unsuckled beef heifers. Both volume and weight had r2 = 0.85 (P < 0.001) between single-quarter and 4 quarter yields. In Exp. 2, colostrum (n = 35) and milk at d 35 (n = 42) and d 60 (n = 38) of lactation were collected from multiparous, fall-calving, crossbred beef cows. Subsamples were submitted for FTIR analysis and frozen for colorimetric analysis. Colorimetric analyses were developed for lactose, triglycerides (measure of fat), protein, and urea N. To validate method accuracy, spike recoveries were determined for lactose (96.8% average) and milk protein (100.1% average), triglyceride concentration was compared with fat concentration determined by the Mojonnier method (r2 ≥ 0.91, P < 0.001), and colostral or milk urea N was compared with serum urea N from the same sampling day (r2 ≥ 0.72, P < 0.001). Coefficients of determination between colorimetric methods and FTIR were determined for colostrum, d 35 milk, and d 60 milk. Colostral lactose concentration from FTIR was positively associated (r2 = 0.24, P = 0.01) with colorimetric analysis, but there was no relationship (r2 ≤ 0.09, P ≥ 0.14) between methods for colostral fat, protein, or urea N. Milk nutrient composition was positively associated for all nutrients measured at d 35 (r2 = 0.28 to 0.58, P < 0.001), and coefficients of determination strengthened for all nutrients measured at d 60 (r2 = 0.38 to 0.82, P < 0.001). In conclusion, colostrum yield of a single rear quarter can be used to indicate complete collection of colostrum for beef cows, and colorimetric methods developed have adequate accuracy for beef cow colostral and milk nutrient analysis. Based on our analyses, nutrient composition of beef cow colostrum was not accurately analyzed by FTIR. Accuracy of FTIR for beef cow milk varies with component and may be affected by the day of lactation.

The purpose was to develop laboratory methods to measure lactose, fat, protein, and urea nitrogen in beef cow colostrum (first milk) and milk and to validate single-quarter colostrum yield as a predictor of total colostrum yield. Additionally, new methods were compared with Fourier transform infrared spectroscopy (FTIR), which is the primary method of dairy cow milk nutrient analysis. New laboratory methods were determined to be accurate for beef cow colostrum and milk analysis, and single-quarter colostrum yield was successful in predicting total colostrum yield. Overall, our data suggest that beef cow colostrum cannot be accurately analyzed by FTIR instruments, and accuracy of FTIR for beef cow milk analysis varies with nutrients and may be affected by the day of lactation.

Late gestational nutrient restriction in primiparous beef females: nutrient partitioning among the dam, fetus, and colostrum during gestation.

Fall-calving primiparous crossbred beef females [body weight (BW): 451 ±â€…28 (SD) kg; body condition score (BCS): 5.4 ±â€…0.7] were allocated by fetal sex and expected calving date to receive either 100% (control; CON; n = 13) or 70% (nutrient restricted; NR; n = 13) of metabolizable energy and metabolizable protein requirements for maintenance, pregnancy, and growth from day 160 of gestation to calving. Heifers were individually-fed chopped poor quality hay and supplemented to meet targeted nutritional planes based on estimated hay intakes. Dam BW, BCS, backfat, and metabolic status were determined pre-treatment, every 21 d (BW and metabolic status) or 42 d (BCS and backfat) during gestation, and post-calving. At birth, calf BW and size were measured, and total colostrum from the most full rear quarter was collected pre-suckling. Data were analyzed with nutritional plane, treatment initiation date, and calf sex (when P < 0.25) as fixed effects. Gestational metabolites included day and nutritional plane × day as repeated measures. During late gestation, CON dams gained (P < 0.01) maternal (non-gravid) BW and maintained (P ≥ 0.17) BCS and backfat, while NR dams lost (P < 0.01) maternal BW, BCS, and backfat. Circulating glucose, urea N, and triglycerides were less (P ≤ 0.05) in NR dams than CON at most late gestational timepoints after treatment initiation. Circulating non-esterified fatty acids were greater (P < 0.01) in NR dams than CON. Post-calving, NR dams weighed 63.6 kg less (P < 0.01) and were 2.0 BCS less (P < 0.01) than CON. At 1 h post-calving, NR dams had less (P = 0.01) plasma glucose and tended to have less (P = 0.08) plasma triglycerides than CON. Nutrient restriction did not affect (P ≥ 0.27) gestation length, calf birth weight, or calf size at birth. Colostrum yield was 40% less (P = 0.04) in NR dams than CON. Protein and immunoglobulin concentrations were greater (P ≤ 0.04), but free glucose and urea N concentrations were less (P ≤ 0.03), in colostrum of NR dams than CON. Colostrum total lactose, free glucose, and urea N were less (P ≤ 0.03) in NR dams than CON, but total protein, triglycerides, and immunoglobulins were not affected (P ≥ 0.55). In summary, beef heifers experiencing late gestational nutrient restriction prioritized partitioning nutrients to fetal growth and colostrum production over maternal growth. During undernutrition, fetal and colostral nutrient demands were largely compensated for by catabolism of maternal tissue stores.

Nutrient requirements increase substantially during late gestation in the beef female. Even in well-managed herds, it is possible for females to be nutrient restricted during this time due to challenges of poor forage quality or availability and environmental stress. For heifers, the added nutrient requirements needed to continue growing pose an even greater challenge during their first pregnancy. However, little is known about how late gestational undernutrition impacts nutrient partitioning between maternal growth, the developing offspring, and colostrum production in beef heifers. Our data show that late gestational nutrient restriction in heifers slowed the expected maternal growth and instead maternal tissue stores were catabolized. Less nutrients were available in the maternal circulation, yet calf weight and size at birth were not affected. Late gestational nutrient restriction resulted in less colostrum produced by the dam and less lactose available to the offspring, but the total protein, fat, and immunoglobulins available in colostrum were not altered. In summary, beef heifers experiencing late gestational nutrient restriction prioritized partitioning nutrients to fetal growth and colostrum production over maternal growth and maintenance of body condition.