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Context Heating of meat leads to structural changes reflected in the juiciness and the tenderness of the cooked meat. Aims This study aimed to characterise the effect of prolonged ageing and cooking on pork-quality traits. Methods Longissimus lumborum samples from 12 carcasses were aged 3 days (conventional ageing) or 15 days (prolonged ageing) and pork cuboids were cooked at 50–80°C for 30 min. Cooking loss, total water content (TWC), Warner–Bratzler shear force (WBSF) and shrinkage (longitudinal, transverse and estimated volume) of the pork loin cuboids were measured. Key results Prolonged ageing for 15 days reduced the WBSF of samples cooked at 50°C, and the cooking loss for samples cooked at 70°C and 80°C, relative to conventional ageing for 3 days. The WBSF of pork aged for 15 days was not different from that of pork aged for 3 days. Prolonged ageing reduced longitudinal shrinkage of cuboids, but TWC and transverse/volume shrinkage of cuboids were not affected by ageing. The diameter of cooked muscle fibre fragments was smaller in pork subjected to prolonged ageing. Conclusions Prolonged ageing was favourable for minimising cooking loss at higher cooking temperatures but was only favourable for tenderness at the lowest cooking temperature. Low pH of the samples is likely to have caused the lack of tenderisation with ageing.

Context Electrical stimulation is often used by meat processors to promote fast muscle pH decline and optimise meat quality. Meat colour can be made more acceptable by this process, but how this relates to the microstructure and light-scattering properties of muscle is still unknown. Aims To investigate the effect of electrical stimulation of beef carcasses on the meat colour at grading and the role of the muscle fibre microstructure and light scattering in determining colour differences. Methods Electrical stimulation inputs (electrical stimulation inputs (ES), n = 8; no electrical stimulation inputs (NS), n = 8) were applied to beef carcasses from female cattle of approximately 18–24 months of age. ES comprised electrical immobilisation, bleed rail electric simulation and hide puller rigidity probe, which have all been shown to increase pH fall post-mortem in beef carcasses. pH fall was monitored, the longissimus thoracis was graded at 20–22 h postmortem and measurements were made of colour, muscle-fibre structure and light scattering. Key results The decline of pH was increased in ES relative to NS, as indicated by lower pH at 2 h postmortem (5.83 vs 6.86 respectively, s.e. = 0.068; P

Identification of disordered platelet function is important to guide peri-operative bleeding management as well as long term treatment and prognostic strategies in individuals with platelet bleeding disorders. Light transmission aggregometry (LTA), the current gold standard diagnostic test of platelet function is a time consuming technique almost exclusively performed in specialised laboratories and almost universally unavailable in regional centres in Australia, where there is an unmet need for access to specialised platelet function diagnostic services. 96-well plate-based aggregometry (Optimul, UK), has been utilised in research laboratories as a novel platform to investigate platelet function. We evaluated the Optimul assay at two centres in Australia, one regional and one tertiary metropolitan, to assess its feasibility as a screening test applicable to remote regional centres. Concentration-response curves were established from 45 healthy volunteers at the participating regional hospital and from 31 healthy volunteers at the tertiary institution. Optimul successfully detected anti-platelet effects in individuals taking aspirin (n=4), NSAID (n=2), clopidogrel (n=2) and dual therapy with aspirin and clopidogrel (n=1). When tested in parallel to LTA in individuals referred for the evaluation of abnormal bleeding symptoms there was overall a very good level of agreement between Optimul and LTA [Cohen's kappa (k

Background A third dose of measles-mumps-rubella vaccine (MMR3) is recommended in mumps outbreak scenarios, but the immune response and the need for widespread use of MMR3 remain uncertain. Herein, we characterized measles-specific immune responses to MMR3 in a cohort of 232 healthy subjects. Methods Serum and peripheral blood mononuclear cells (PBMCs) were sampled at day 0 and day 28 after MMR3. Measles-specific binding and neutralizing antibodies were quantified in sera by enzyme-linked immunosorbent assay and a microneutralization assay, respectively. PBMCs were stimulated with inactivated measles virus, and the release of cytokines/chemokines was assessed by a multiplex assay. Demographic variables of subjects were examined for potential correlations with immune outcomes. Results Of the study participants, 95.69% and 100% were seropositive at day 0 and day 28, respectively. Antibody avidity significantly increased from 38.08% at day 0 to 42.8% at day 28 (P = .00026). Neutralizing antibodies were significantly enhanced, from 928.7 at day 0 to 1289.64 mIU/mL at day 28 (P = .0001). Meanwhile, cytokine/chemokine responses remained largely unchanged. Body mass index was significantly correlated with the levels of inflammatory cytokines/chemokines. Conclusions Measles-specific humoral immune responses, but not cellular responses, were enhanced after MMR3 receipt, extending current understanding of immune responses to MMR3 and supporting MMR3 administration to seronegative or high-risk individuals.

While Montesquieu’s The Spirit of Laws is recognized as one of the foundational philosophical works on the subject of liberty, much work still needs to be done to ferret out exactly what Montesquieu’s teaching is on the subject. This essay attempts to contribute to this endeavor by clarifying certain key elements of Books 11 and 12 of that book.

Violent victimization in adolescence spurs risk-taking behaviors (e.g., violent offending and substance use/abuse), undermines mental well-being, disrupts developmental transitions, and even has interpersonal and relational consequences. Adolescent victims initiate earlier and progress faster through sexual and romantic relationships. Because the reasons for the links between victimization and relationship behaviors remain unclear, we explored how violent victimization might shape how adolescents think and feel about intimate/romantic relationships. We focus specifically on interest in forming relationships and expectations about intimate/sexual activity occurring within relationships. Using data from the National Longitudinal Study of Adolescent to Adult Health (Add Health; n = 10,570 [54% girls; 56% non-Hispanic white; ages 11–18]), we found that adolescent victims of violence were more pessimistic about marriage and more favorable toward sexual activity, with patterns varying by age at victimization and gender. Late adolescent victims were marginally more interested in romantic relationships but were pessimistic about marriage. Early adolescent and girl victims were less favorable toward sexual activity in relationships, while later adolescent and boy victims were more permissive. Violent victimization may foster problematic attitudes toward intimate relationships, which may account for previously observed increased involvement in risky relational and sex behaviors.

This article summarizes the available evidence on pediatric cochlear implantation to provide current guidelines for clinical protocols and candidacy recommendations in the United States. Candidacy determination involves specification of audiologic and medical criteria per guidelines of the Food and Drug Administration. However, recommendations for a cochlear implant evaluation also should maintain flexibility and consider a child's skill progression (i.e., month-for-month progress in speech, language, and auditory development) and quality of life with appropriately fit hearing aids. Moreover, evidence supports medical and clinical decisions based on other factors, including (a) ear-specific performance, which affords inclusion of children with asymmetric hearing loss and single-sided deafness as implant candidates; (b) ear-specific residual hearing, which influences surgical technique and device selection to optimize hearing; and (c) early intervention to minimize negative long-term effects on communication and quality of life related to delayed identification of implant candidacy, later age at implantation, and/or limited commitment to an audiologic rehabilitation program. These evidence-based guidelines for current clinical protocols in determining pediatric cochlear implant candidacy encourage a team-based approach focused on the whole child and the family system.

Bile acids are present at high concentrations in breast cysts and in the plasma of postmenopausal women with breast cancer. The farnesoid X receptor (FXR) is a member of the nuclear receptor superfamily that regulates bile acid homeostasis. FXR was detected in normal and tumor breast tissue, with a high level of expression in ductal epithelial cells of normal breast and infiltrating ductal carcinoma cells. FXR was also present in the human breast carcinoma cells, MCF-7 and MDA-MB-468. Activation of FXR by high concentrations of ligands induced MCF-7 and MDA-MB-468 apoptosis. At lower concentrations that had no direct effect on viability, the FXR agonist GW4064 induced expression of mRNA for the FXR target genes, small heterodimer partner (SHP), intestinal bile acid binding protein, and multidrug resistance–associated protein 2 (MRP-2), and repressed the expression of the SHP target gene aromatase. In contrast to MRP-2, mRNA for the breast cancer target genes MDR-3, MRP-1, and solute carrier transporter 7A5 were decreased. Although multidrug resistance transporters were regulated and are known FXR target genes, GW4064 had no effect on the cell death induced by the anticancer drug paclitaxel. Our findings show for the first time that FXR is expressed in breast cancer tissue and has multiple properties that could be used for the treatment of breast cancer. (Cancer Res 2006; 66(20): 10120-6)

Supplementary Figures 1-4 from The Farnesoid X Receptor Is Expressed in Breast Cancer and Regulates Apoptosis and Aromatase Expression

Thrombosis of the lung microvasculature is a characteristic of COVID-19 disease, which is observed in large excess compared to other forms of acute respiratory distress syndrome and thus suggests a trigger for thrombosis that is endogenous to the lung. Our recent work has shown that the SARS-CoV-2 Spike protein activates the cellular TMEM16F chloride channel and scramblase. Through a screening on >3,000 FDA/EMA approved drugs, we identified Niclosamide and Clofazimine as the most effective molecules at inhibiting Spike-induced TMEM16 activation. As TMEM16F plays an important role in stimulating the procoagulant activity of platelets, we investigated whether Spike directly affects platelet activation and pro-thrombotic function and tested the effect of Niclosamide and Clofazimine on these processes. Here we show that Spike, present either on the virion envelope or on the cell plasma membrane, promotes platelet activation, adhesion and spreading. Spike was active as a sole agonist or, even more effectively, by enhancing the function of known platelet activators. In particular, Spike-induced a marked procoagulant phenotype in platelets, by enhancing Ca2+ flux, phosphatidylserine externalization on the platelet outer cell membrane, and thrombin generation. Eventually, this increased thrombin-induced clot formation and retraction. Both Niclosamide and Clofazimine blocked this Spike-induced procoagulant response. These findings provide a pathogenic mechanism to explain lung thrombosis-associated with severe COVID-19 infection. We propose that Spike, present in SARS-CoV-2 virions or exposed on the surface of infected cells in the lungs, enhances the effects of inflammation and leads to local platelet stimulation and subsequent activation of the coagulation cascade. As platelet TMEM16F is central in this process, these findings reinforce the rationale of repurposing Niclosamide for COVID-19 therapy.

The microbiome revolution brought the realization that diet, health, and safety for humans in reality means diet, health, and safety for the human holobiont/superorganism. Eating healthier means much more than just feeding human cells. Our diet must also nourish the combination of our microbiome and our connected physiological systems (e.g., the microimmunosome). For this reason, there has been an interest in returning to ancestral “complete” unprocessed foods enriched in microbes, including raw milks. To contribute to this inevitable “nourishing the holobiont” trend, we introduce a systematic risk–benefit analysis tool (evidence mapping), which facilitates transdisciplinary state-of-the-science decisions that transcend single scientific disciplines. Our prior paper developed an evidence map (a type of risk–benefit mind map) for raw vs. processed/pasteurized human breast milk. In the present paper, we follow with a comprehensive evidence map and narrative for raw/natural vs. processed/pasteurized cow’s milk. Importantly, the evidence maps incorporate clinical data for both infectious and non-communicable diseases and allow the impact of modern agricultural, food management, and medical and veterinary monitoring outcomes to be captured. Additionally, we focus on the impact of raw milks (as “complete” foods) on the microimmunosome, the microbiome-systems biology unit that significantly determines risk of the world’s number one cause of human death, non-communicable diseases.

Background Platelets circulate in the blood of healthy individuals for approximately 7-10 days regulated by finely balanced processes of production and destruction. As platelets are anucleate we reasoned that their protein composition would change as they age and that this change would be linked to alterations in structure and function. Objective To isolate platelets of different ages from healthy individuals to test the hypothesis that changes in protein content cause alterations in platelet structure and function. Methods Platelets were separated according to thiazole orange fluorescence intensity as a surrogate indicator of mRNA content and so a marker of platelet age and then subjected to proteomics, imaging, and functional assays to produce an in-depth analysis of platelet composition and function. Results Total protein content was 45±5% lower in old platelets compared to young platelets. Predictive proteomic pathway analysis identified associations with 28 biological processes, notably higher hemostasis in young platelets whilst apoptosis and senescence were higher in old platelets. Further studies confirmed platelet ageing was linked to a decrease in cytoskeletal protein and associated capability to spread and adhere, a reduction in mitochondria number, and lower calcium dynamics and granule secretion. Conclusions Our findings demonstrate changes in protein content are linked to alterations in function as platelets age. This work delineates physical and functional changes in platelets as they age and serves as a base to examine differences associated with altered mean age of platelet populations in conditions such as immune thrombocytopenia and diabetes.

Given notable recent spikes in gun purchases in the U.S., we revisit the ‘fear and loathing’ hypothesis of firearm demand by (1) establishing how crime/victimization fears are shaped by broader economic, cultural, and racial status anxieties (those emerging from group status threats [loathing]) and (2) illustrating how both fear and loathing matter for protective gun ownership and gun carry (among owners), and openness to future protective ownership among non-owners. Using data from a nationwide survey of adults in the U.S. (n = 2,262) collected in 2019, we find that fears of crime and victimization are often more strongly associated with status anxieties than with safety threats. Both status anxieties and victimization are associated with protective ownership and carry. Among non-owners, those higher in cultural anxiety are especially likely to be open toward future protective gun ownership. This study illustrates the multidimensional fear-guns link, wherein both status-related threats and victimization-related fears shape why individuals own guns, and how they use guns.

Context Different cereal grain sources may be used in beef production but little is known about their effects on beef quality. Aims This study evaluated fatty acid composition, α-tocopherol concentration and oxidative stability of beef from bulls fed barley or a combination of barley and either ground or toasted flaked maize. Methods Fatty acid composition, α-tocopherol concentration, lipid oxidation and colour stability were measured in beef from late maturing bulls finished on a barley-based concentrate (BC) or on the concentrate with barley partially replaced by either maize meal (MM) or flaked meal (FM). Samples of M. longissimus thoracis were subjected to simulated retail display (4°C) for 3, 7, 10 and 14 days in modified atmosphere packs (O2:CO2; 80:20). Muscle was analysed for fatty acid and α-tocopherol concentrations, colour stability and lipid oxidation. Key results There were differences in the fatty acid concentrations. Total fatty acids, monounsaturated fatty acids and saturated fatty acids were higher (P 0.05) in colour stability of muscle due to dietary treatment. Conclusions Partial replacement of barley with maize in the diet of bulls influences muscle fatty acid concentration and profile, leading to a marginal increase in lipid oxidation with no detrimental effect on colour stability. Implications Toasted-flaked or ground maize may partially substitute for rolled barley in a concentrate ration without affecting colour stability of meat under retail display conditions. The slight increase in lipid oxidation, after prolonged storage, in beef from bulls fed flaked toasted maize is unlikely to be of significance from a product acceptability perspective.

Platelet ageing is an area of research which has gained much interest in recent years. Newly formed platelets, often referred to as reticulated platelets, young platelets or immature platelets, are defined as RNA-enriched and have long been thought to be hyper-reactive. This latter view is largely rooted in associations and observations in patient groups with shortened platelet half-lives who often present with increased proportions of newly formed platelets. Evidence from such groups suggests that an increased proportion of newly formed platelets is associated with an increased risk of thrombotic events and a reduced effectiveness of standard anti-platelet therapies. Whilst research has highlighted the existence of platelet subpopulations based on function, size and age within patient groups, the common intrinsic changes which occur as platelets age within the circulation are only just being explored. By understanding the changes that occur during the natural ageing processes of platelets, we may be able to identify the triggers for alterations in platelet life span and platelet reactivity. Here we review research on platelet ageing in the context of health and disease, paying particular attention to the experimental approaches taken and the robustness of conclusions that can be drawn.

Pediatric cochlear implantation affects communication skills and quality of life, specifically how children interact with others and feel about themselves. Numerous studies worldwide examine well-being among pediatric cochlear implant users, but none to date compare condition-specific quality of life across countries. This retrospective study compares parent-reported cochlear implant-specific quality of life summary data across 14 published studies spanning 11 countries and 9 languages. Sample size ranged from 7 to 370 participants, and children across studies varied in mean chronologic age (3.1–12.2 years), implantation age (1.5–4.6 years), and cochlear implant experience (1.3–8.2 years). Parents completed the Children with Cochlear Implants: Parental Perspectives (CCIPP) questionnaire, an instrument assessing parent-reported cochlear implant-specific quality of life, in their home language. Analysis of variance tests were run for each CCIPP subscale across studies using summary data to determine significant differences between published manuscripts. Across countries, parents of children with cochlear implants appraise communication, social relations, and self-reliance most positively, and the effects of implantation and supporting the child least positively. Cross-country analyses revealed a significant effect of study (country) on quality of life ratings in each domain, with the largest differences in the communication domain. Limited access to implant-related accommodations, cultural awareness of hearing loss, and varying parent expectations may explain country differences in parental ratings of quality of life. Culturally sensitive psychoeducation for the entire family may foster improved life satisfaction for pediatric cochlear implant users and their families.

Background Antiplatelet therapy (APT) has improved cardiovascular outcomes, but some patients develop thrombosis despite APT. Adjusting APT to platelet reactivity with conventional platelet reactivity tests has proven unsuccessful. Many circulating noncoding RNAs (ncRNAs) are derived from platelets and could serve as novel platelet function markers. Material and methods Platelet reactivity was assessed using light transmission aggregometry (LTA) in the Bruneck 2015 study (N = 338), using the agonists arachidonic acid, adenosine diphosphate, collagen, TRAP-6 amide and U46619. LTA platelet releasates were then used for RT-qPCR of five platelet-enriched microRNAs, three circular RNAs and two long non-coding RNAs. Platelet-poor plasma (PPP) was used as negative control. Results and conclusions Platelet agonists induced aggregation and ncRNA release, with aspirin takers (N = 155) showing lower ncRNA release than individuals not on aspirin (N = 183). Agonist responsiveness differed among ncRNAs, with miR-150 being hyperresponsive to adenosine diphosphate and miR-21 being hyperresponsive to arachidonic acid, whereas other ncRNAs were most strongly released to collagen, suggesting a selective release mechanism. In individuals not on aspirin, the inflammation markers C-reactive protein and granulocyte counts correlated positively with platelet-derived ncRNAs in PPP, while they correlated inversely with platelet-derived ncRNAs in releasates. These correlations were not present in aspirin takers. Higher PPP levels and lower releasate levels of platelet-derived ncRNAs in inflammation suggest platelet exhaustion ex vivo due to platelet pre-activation in vivo. Funding sources British Heart Foundation, VASCage (Centre for Promoting Vascular Health in the Ageing Community) of the Austrian Research Promotion Agency FFG (COMET program - Competence Centers for Excellent Technologies).

Background and purpose P2Y12 receptor antagonists reduce platelet aggregation and the incidence of arterial thrombosis. Adenosine signalling in platelets directly affects cyclic nucleotide tone, which we have shown to have a synergistic relationship with P2Y12 inhibition. Several studies suggest that ticagrelor inhibits erythrocyte uptake of adenosine and that this could also contribute to its antiplatelet effects. We therefore examined the effects on platelet activation of adenosine signalling activators in combination with the P2Y12 receptor antagonists ticagrelor and prasugrel. Experimental approach Human washed platelets, platelet-rich plasma and whole blood were used to test the interactions between ticagrelor or prasugrel and adenosine or 5'-N-ethylcarboxamidoadenosine (NECA). Platelet reactivity to thrombin, protease-activated receptor 1 (PAR-1) activation or collagen was assessed by a combination of 96-well plate aggregometry, light transmission aggregometry, whole blood aggregometry, ATP release assay and levels of cAMP. Key results The inhibitory effects of ticagrelor and prasugrel on platelet aggregation and ATP release were enhanced in the presence of adenosine or NECA. Isobolographic analysis indicated a powerful synergy between P2Y12 receptor inhibition and adenosine signalling activators. Increased levels of cAMP in platelets were also observed. In all cases, ticagrelor showed similar synergistic effects on platelet inhibition as prasugrel in the presence of adenosine or NECA. Conclusion and implications These results indicate that P2Y12 antagonists have a synergistic relationship with adenosine signalling and that their efficacy may depend partly upon the presence of endogenous adenosine. This effect was common for prasugrel and ticagrelor despite reports of differences in their effects upon adenosine reuptake.

An evidence map is visualized as a starting point for deliberations by trans-disciplinary stakeholders, including microbiologists with interests in the evidence and its influence on health and safety. Available evidence for microbial benefits and risks of the breastmilk ecosystem was structured as an evidence map using established risk analysis methodology. The evidence map based on the published literature and reports included the evidence basis, pro- and contra-arguments with supporting and attenuating evidence, supplemental studies on mechanisms, overall conclusions, and remaining uncertainties. The evidence basis for raw breastmilk included one benefit–risk assessment, systematic review, and systematic review/meta-analysis, and two cohort studies. The evidence basis for benefits was clear, convincing, and conclusive, with supplemental studies on plausible mechanisms attributable to biologically active raw breastmilk. Limited evidence was available to assess microbial risks associated with raw breastmilk and pasteurized donor milk. The evidence map provides transparent communication of the ‘state-of-the-science’ and uncertainties for microbial benefits and risks associated with the breastmilk microbiota to assist in deeper deliberations of the evidence with decision makers and stakeholders. The long-term aims of the evidence map are to foster deliberation, motivate additional research and analysis, and inform future evidence-based policies about pasteurizing donor breastmilk.

This study conducted a retrospective analysis of historical Meat Standard Australia (MSA) carcass data in combination with Bureau of Meteorology (BOM) weather data, to evaluate the relationship between climatic conditions prior to feedlot departure on the incidence of dark cutting grain-fed beef. Data records for 2,795,754 carcasses from 17 commercial feedlots over a 6-year period were evaluated within this study. Carcasses were consigned to 16 abattoirs. Weather data from BOM were recorded at 30-min intervals and were obtained from weather stations with the closest proximity to each feedlot. These data were used to calculate the Temperature Humidity Index (THI). Climatic data were amalgamated into daily observations and a series of predictors including ambient temperature (TA, °C), relative humidity (RH, %), wind speed (WS, m/s), rainfall (mm) and THI. In addition, lag interactions from 24 h out to 28 days prior to exiting the feedlot were generated. The incidence of dark cutting was determined as percentage per cohort with an ultimate pH > 5.7. Data were analysed using three models: model 1 included feedlot, abattoir, hormone growth promotant status and sex as fixed effects. Model 2 incorporated the fixed effects within model 1 and minimum, maximum and standard deviation (SD) of TA and RH, daily range in TA, average WS and rainfall as random effects. Model 3 incorporated minimum, maximum, range and SD of THI, average WS and rainfall as random effects in addition to the fixed effects of model 1. The incidence of dark cutting within feedlot had a 10.1% range in estimated means with the lowest incidence was observed at feedlot 17 (0%) and highest incidence at feedlot 10 (10.1%). The inclusion of the climatic variables in model 2 and model 3 accounted for an additional 0.1 to 0.2% of the incidence of dark cutting carcasses. Higher maximum TA, RH and THI in the 3 to 28 days prior to consignment were all associated with an increased incidence of dark cutting (P 0.05). Low minimum TA and low THI were also associated with an increase the incidence of dark cutting across all lag periods (P

Purpose The sibling relationship teaches children to navigate social interactions with their peers. However, the presence of an exceptionality, such as hearing loss, in one child can affect the dynamic of this relationship. This article examines quantitative and qualitative effects of having a brother or sister with a cochlear implant (CI) on siblings with typical hearing (TH) to determine how children with TH perceive their sibling with a CI and how having a CI user in the family affects the sibling's activities, emotions, and parental attention. Method Participants include 36 siblings with TH ( M age = 11.6 years) of CI users ( M age = 11.9 years) who completed quantitative measures of their perspectives of their brother/sister with CIs and the effect of hearing loss on themselves. Siblings with TH also could express their opinions via open-ended prompts. Results Overall, siblings with TH express positive perspectives of their brother/sister with CIs and report having a CI user in the family does not affect them much, particularly if the CI user has adequate communication skills. Responses to both quantitative and qualitative items converge on the close relationship between siblings but diverge relative to differential attention from parents (i.e., open-ended responses suggest parents spend more time with the CI user than the sibling with TH). Additionally, siblings acknowledge the presence of social communication deficits of the CI user in real-world situations. Conclusion This nuanced look at relationships among the parent, CI user, and sibling with TH highlights the importance of understanding the family system when working with children with hearing loss.

Lameness is a persistent and underreported health and welfare problem in the dairy industry, resulting in reduced cow performance and profitability as well as early culling. The study objectives were (1) to quantify the impact of the first instance of lameness, at different stages of lactation, on production and economic performance, and (2) to further quantify the impacts of the first instance of lameness when only cows that remain in the herd for at least 100 d in milk (DIM) and those that remain for 305 DIM are included in the analysis. A retrospective longitudinal study was conducted using pre-existing data from animal health records and Dairy Herd Improvement Association records. Data were edited based on selected inclusion criteria, yielding a data set containing records from 15,159 first-lactation Holstein cows from 120 herds with year of first calving between 2003 and 2014. Lame cows were assigned to 1 of 4 groups based on when in the lactation the first event of lameness occurred: transition (1-21 DIM), early lactation (22-100 DIM), mid-lactation (101-200 DIM), or late lactation (201+ DIM). Mid- and late-lactation lame cows were also stratified by cumulative milk yield before the lameness event. Healthy cows (i.e., no recorded lameness event) were randomly assigned for each lactation stage, with mid-lactation healthy and late-lactation healthy cows similarly stratified. Production performance (cumulative milk, fat, and protein yield) and economic performance [milk value, margin over feed cost (MOFC), and gross profit] were analyzed using a mixed model with herd as a random effect. Cumulative milk yields were 811 to 1,290 kg lower for lame cows than for healthy cows, with milk component yields undergoing similar reductions. Reductions in milk yield contributed to losses in milk value (-Can$527 to -Can$1,083; -US$419 to -US$862) and MOFC (-Can$510 to -Can$774; -US$406 to -US$616). Higher losses were reported using gross profit (-Can$753 to -Can$1,052; -US$599 to -US$837), which includes all lameness-related costs. Production and performance losses were smaller when 100 DIM and 305 DIM thresholds were applied (i.e., exclusion of cows culled before 100 and 305 DIM, respectively), however, mid- and late-lactation lame cows maintained high levels of significant losses for all 6 variables analyzed. Lameness also led to higher levels of culling, masking losses for transition and early-lactation lame cows in the 305-DIM analysis. Increasing producer understanding of the costs associated with lameness not only serves to provide insight to producers for more informed culling decisions, but may also help producers weigh the costs of adopting new methods and technologies targeted at reducing on-farm lameness.

It is well established that percutaneous coronary intervention (PCI) is a life-saving procedure for acute myocardial infarction (AMI) in the general population and is guideline-recommended for both STEMI and NSTEMI. There is little literature regarding its use in patients with a pre-implanted Left Ventricular Assist Device (LVAD).We retrospectively analyzed data from the National Inpatient Sample (NIS) Database to select all US adult patients (18 years) with an LVAD diagnosed with an AMI divided into two groups; those who received PCI during the hospitalization and those who did not.A total of 3722 LVAD patients with AMI were identified, of these 17% of patients received PCI and 83% did not. After propensity matching of LVAD patients with AMI, there were 626 patients who received PCI and 623 who did not. Of patients receiving PCI, 37.5% had a STEMI while 29.7% of patients who did not receive PCI had STEMI. Rates of kidney injury (36.5% vs. 43.3%, OR 0.75, 95% CI 0.60-0.94, p = 0.016), sepsis (3.2% vs. 11.4%, OR 0.26, 95% CI 0.15-0.43, p 0.001), cardiogenic shock (44.1% vs. 50.4%, OR 0.78, 95% CI 0.62-0.97, p = 0.03) and mortality (17.4% vs. 28.9%, OR 0.52, 95% CI 0.40-0.68, p 0.001) were all better for patients receiving PCI. Vascular complications (1.4% vs. 0%, p = 0.008) and intracerebral hemorrhage (ICH) (1.6% vs. 0, p = 0.004) were both more common in the group receiving PCI.In this study, patients supported by LVAD with AMI had an elevated risk of mortality compared to generally accepted mortality rates of patients without LVAD. In this analysis PCI was associated with a decreased risk of mortality, cardiogenic shock, and kidney injury while increasing the risk for vascular complications and intracranial hemorrhage.

Connective tissue is considered to influence the toughness of pork, but most studies on connective tissue focus on the loin muscle. Cooking loss, Warner–Bratzler shear force (WBSF), texture profile analysis (hardness, springiness, chewiness, resilience, and cohesiveness), total and insoluble collagen content, the percentage of type III collagen relative to the total of type I and III collagen, proteoglycan content and intramuscular fat (IMF) content were measured for pork Biceps femoris (BF) and Longissimus thoracis et lumborum (LTL) and Pearson’s correlation was performed. The results showed that BF had higher WBSF, resilience, total, and insoluble collagen content than LTL (P < 0.05). When considering both muscles, total and insoluble collagen content were positively correlated (P < 0.05) with WBSF (r = 0.47 and 0.49, respectively), hardness (r = 0.49 and 0.50, respectively), cohesiveness (r = 0.50 and 0.50, respectively), chewiness (r = 0.58 and 0.59, respectively) and resilience (r = 0.63 and 0.63, respectively). The percentage of type III collagen content was negatively correlated (P < 0.05) with WBSF (r = −0.68) and hardness (r = −0.58). Collagen content was correlated (P < 0.05) with WBSF (r = 0.75) and hardness (r = 0.61) in LTL and with cohesiveness (r = 0.74) and resilience (r = 0.63) in BF. Collagen characteristics differ between muscles and contribute to pork texture in both LTL and BF.

Adverse Childhood Experiences (ACEs) are traumatic childhood events that can undermine youth development, and are linked to chronic health problems, mental illness, and risk-taking behaviors in adulthood. ACEs are preventable, yet effective response strategies require comprehensive conceptualization and measurement of adversity. Although typically measured as individual experiences in the family and home (e.g., abuse, neglect), adversity also exists outside the home, in the many contexts in which youth development unfolds (e.g., communities, neighborhoods). Yet, such contexts and experiences are often absent in ACEs research. Using data from a nationally representative youth sample, this study addresses that gap, advancing a measure that contextualizes individual-level ACEs within social and structural domains of community-level adversity. Among 13,267 youth (mean age = 15.25 [range 12-18]; 51% female; 71% White; 13% Black; 10% Hispanic; 3% Asian; 2% American Indian/Multiracial), 61% and 73% were exposed to at least one individual and community ACE, respectively, while 15% of youth reported severe individual ACE exposure (≥3 ACEs) and 20% were exposed to severe (≥3) community ACEs. All ACE exposures were associated with problem behaviors later in adolescence, but youth reporting both severe individual and community ACEs were especially at high risk for later violence, delinquency, and other health-risk behaviors. These findings highlight that community adversity exacerbates the damaging effects of individual/family adversity and thus should be addressed in efforts to prevent ACEs and reduce their long-term harm.

Connective tissue is considered to influence the toughness of pork, but most studies on connective tissue focus on the loin muscle. Cooking loss, Warner-Bratzler shear force (WBSF), texture profile analysis (hardness, springiness, chewiness, resilience, and cohesiveness), total and insoluble collagen content, the percentage of type III collagen relative to the total of type I and III collagen, proteoglycan content and intramuscular fat (IMF) content were measured for pork

The proportion of young platelets, also known as newly formed or reticulated, within the overall platelet population has been clinically correlated with adverse cardiovascular outcomes. However, our understanding of this is incomplete because of limitations in the technical approaches available to study platelets of different ages. In this study, we have developed and validated an in vivo temporal labeling approach using injectable fluorescent antiplatelet antibodies to subdivide platelets by age and assess differences in functional and molecular characteristics. With this approach, we found that young platelets (

Protection is now the modal motivation for gun ownership, and men continue to outnumber women among gun owners. While research has linked economic precarity (e.g., insecurity and anxiety) to gun ownership and attitudes, separating economic well-being from constructions of masculinity is challenging. In response to blocked economic opportunities, some gun owners prioritize armed protection, symbolically replacing the masculine role of “provider” with one associated with “protection.” Thus, understanding both persistently high rates of gun ownership in the United States (in spite of generally declining crime) alongside the gender gap in gun ownership requires deeper investigations into the meaning of guns in the United States and the role of guns in conceptualizations of American masculinity. We use recently collected crowdsourced survey data to test this provider-to-protector shift, exploring how economic precarity may operate as a cultural-level masculinity threat for some, and may intersect with marital/family status to shape gun attitudes and behaviors for both gun owners and nonowners. Results show that investments in stereotypical masculine ideals, rather than economic precarity, are linked to support for discourses associated with protective gun ownership and empowerment.

Guns are present in many households in the U.S., including those with children. Safe storage of guns at home can mitigate the increased risks of both the unintentional and intentional injury that in-home gun access presents; yet estimates suggest fewer than half of gun owners store their weapon(s) safely. Unsafe storage in homes with children is especially problematic given that gun-owning parents make incorrect assumptions about both children’s awareness of firearm storage locations, and their actions upon encountering an unsecured gun. There is limited identification and understanding of why some parents do not engage in safe storage practices. Using 2019 survey data from an internet-based sample of gun-owning adults with children at home, this study explores various potential correlates of unsafe storage. Findings suggest that unsafe storage occurs not in response to crime/victimization fears, but from broader, group- and status-based threats. Understanding the complex factors preventing gun-owning parents from implementing safe storage practices has important implications for both victimization scholarship and public health/injury prevention efforts.

Several instruments and outcomes measures have been reported in pediatric patients undergoing epilepsy surgery. The objective of this systematic review is to summarize, evaluate, and quantify outcome metrics for the surgical treatment of pediatric epilepsy that address seizure frequency, neuropsychological, and health-related quality of life (HRQL). We performed a systematic review according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to identify publications between 2010 and June 2021 from PubMed, Embase, and the Cochrane Database of Systematic Reviews that report clinical outcomes in pediatric epilepsy surgery. Eighty-one articles were included for review. Overall, rates of postoperative seizure frequency were the most common metric reported (n = 78 studies, 96%). Among the seizure frequency metrics, the Engel Epilepsy Surgery Outcome Scale (n = 48 studies, 59%) was most commonly reported. Neuropsychological outcomes, performed in 32 studies (40%) were assessed using 36 different named metrics. HRQL outcomes were performed in 16 studies (20%) using 13 different metrics. Forty-six studies (57%) reported postoperative changes in antiepileptic drug (AED) regimen, and time-to-event analysis was performed in 15 (19%) studies. Only 13 outcomes metrics (1/5 seizure frequency, 6/13 HRQL, 6/36 neuropsychological) have been validated for use in pediatric patients with epilepsy and only 13 have been assessed through reliability studies (4/5 seizure frequency, 6/13 HRQL, and 3/36 neuropsychological). Of the 81 included studies, 17 (21%) used at least one validated metric. Outcome variable metrics in pediatric epilepsy surgery are highly variable. Although nearly all studies report seizure frequency, there is considerable variation in reporting. HRQL and neuropsychological outcomes are less frequently and much more heterogeneously reported. Reliable and validated outcomes metrics should be used to increase standardization and accuracy of reporting outcomes in pediatric patients undergoing epilepsy surgery.

Vitamin D plays crucial roles in calcium absorption, bone metabolism, and immune, neurological and cardiovascular-related functions. In plants, it plays an important role in the form of D2 (ergocal...

Background: Currently, no authors of existing studies have attempted to classify the signal characteristics of disc herniation on magnetic resonance imaging (MRI) and their temporal relationship to symptoms of lumbar radiculopathy. The purpose of this study was to determine whether the MRI signal characteristics are predictive of acuity of symptoms in patients with lumbar disc herniation (LDH). Methods: A retrospective cohort study was conducted on patients treated at an academic center for LDH from 2015 to 2018. Patients were divided into 2 groups based on symptom duration (acute: ≤6 weeks; or chronic: >4 months). Two independent observers measured T1, T2 signal, and other MRI characteristics at the affected disc level. Univariate analysis was used to compare differences between groups. Multiple logistic regression was used to determine predictors of acuity. Results: Eighty-nine patients were included (33 acute, 56 chronic) with no significant baseline differences between groups. Rater 2 observed a higher proportion of disc bulges in the chronic group (P = .021) and a higher abnormal T1 herniation signal in the acute group (P = .048). Rater 1 found a higher Pfirrmann grade (P = .005) and a higher prevalence of vertebral body spurring (P = .007) in the chronic group. Interobserver agreement for T1 central and herniation signals demonstrated poor to fair agreement, whereas the remainder of the measurements showed moderate to substantial agreement (κ = 0.4–0.8). Multiple logistic regression showed that Pfirrmann Grade 5 (odds ratio = 0.12, 95% confidence interval [0.02, 0.74], P = .022) and anterior/posterior spurring (odds ratio = 0.053 [0.03, 0.85], P = .023) were not associated with acuity. Conclusions: Other than Pfirrmann grade or vertebral body spurring, no MRI characteristics could be reliably identified that correlate with acuity of symptoms. Level of Evidence: 3.

Parents of children with cochlear implants (CIs) face unique challenges in caring for their child, potentially fostering parental stress. Most studies of stress in parents of CI users do not examine stress specific to having a deaf and hard-of-hearing (DHH) child. This study compares general and condition-specific stress (via the Family Stress Scale) in 31 parents of CI users (8–16 years) to previously published samples of DHH children, and it examines child- and CI-related factors associated with parental stress. Parents of modern-day CI users reported significantly lower stress than parents of children using older-generation CI technology and similar levels of overall stress to parents of young children preimplantation. However, significant item-level differences emerged (e.g., communication, device management) pre- versus postimplant. Child temperament significantly predicted parental stress after controlling for other variables. Intervention strategies for children with CIs should engage a family systems approach to reduce parental stress and better support the child.

Background While administration of the measles-mumps-rubella (MMR-II®) vaccine has been effective at preventing rubella infection in the United States, the durability of humoral immunity to the rubella component of MMR vaccine has not been widely studied among older adolescents and adults. Methods In this longitudinal study, we sought to assess the durability of rubella virus (RV)-specific humoral immunity in a healthy population (n = 98) of adolescents and young adults at two timepoints: ~7 and ~17 years after two doses of MMR-II® vaccination. Levels of circulating antibodies specific to RV were measured by ELISA and an immune-colorimetric neutralization assay. RV-specific memory B cell responses were also measured by ELISpot. Results Rubella-specific IgG antibody titers, neutralizing antibody titers, and memory B cell responses declined with increasing time since vaccination; however, these decreases were relatively moderate. Memory B cell responses exhibited a greater decline in men compared to women. Conclusions Collectively, rubella-specific humoral immunity declines following vaccination, although subjects’ antibody titers remain well above the currently recognized threshold for protective immunity. Clinical correlates of protection based on neutralizing antibody titer and memory B cell ELISpot response should be defined.

Introduction Rubella virus (RV) was eliminated in the United States in 2004, although a small portion of the population fails to develop long-term immunity against RV even after two doses of the measles-mumps-rubella (MMR) vaccine. We hypothesized that inherent biological differences in cytokine and chemokine signaling likely govern an individual’s response to a third dose of the vaccine. Methods Healthy young women (n = 97) were selected as study participants if they had either low or high extremes of RV-specific antibody titer after two previous doses of MMR vaccine. We measured cytokine and chemokine secretion from RV-stimulated PBMCs before and 28 days after they received a third dose of MMR vaccine and assessed correlations with humoral immune response outcomes. Results High and low antibody vaccine responders exhibited a strong pro-inflammatory cellular response, with an underlying Th1-associated signature (IL-2, IFN-γ, MIP-1β, IP-10) and suppressed production of most Th2-associated cytokines (IL-4, IL-10, IL-13). IL-10 and IL-4 exhibited significant negative associations with neutralizing antibody titers and memory B cell ELISpot responses among low vaccine responders. Conclusion IL-4 and IL-10 signaling pathways may be potential targets for understanding and improving the immune response to rubella vaccination or for designing new vaccines that induce more durable immunity.

Study Design: Retrospective cohort study. Objective: The goal of this study was to determine whether the absolute size (mm2), relative size (% canal compromise), or location of a single-level, lumbar disc herniation (LDH) on axial and sagittal cuts of magnetic resonance imaging (MRI) were predictive of eventual surgical intervention. Methods: MRIs of 89 patients were reviewed, and patients were split into groups based on type of management received (34 nonoperative vs 55 microdiscectomy). Radiographic characteristics—including size of disc herniation (mm2), size of spinal canal (mm2), location of herniation on axial (central, paracentral, foraminal) and sagittal (disc level, suprapedicle, pedicle, infrapedicle) planes, and type of herniation (bulge, protrusion, extrusion, sequestration)—were measured by 2 independent, orthopedic spine fellows and compared between groups via univariate and multivariate analyses. Results: The operative group showed a significantly higher percentage of canal compromise (39.5% vs 31.1%, P = .001) compared to the nonoperative group. Multiple logistic regression analysis showed higher odds of eventual operative intervention for a disc protrusion (odds ratio [OR] 6.30 [1.99, 19.86], P = .002) or disc extrusion (OR 11.5 [1.63, 81.2], P = .014) for Rater 1 and a higher odds of eventual surgical management for a paracentral location for both Rater 1 and Rater 2 (OR = 3.39 [1.25, 9.22], P = .017, and OR = 5.46 [1.77, 16.8], P = .003, respectively). Conclusions: Disc herniations in a paracentral location were more likely to undergo operative treatment than those more centrally located, on axial MRI views.

International audience; Background: Implementation of proteomics over the last decade has been an important step toward a better understanding of the complex biological systems underlying the conversion of muscle to meat. These sophisticated analytical tools have helped to reveal the biochemical pathways involved in fresh meat colour and have identified key protein biomarkers.Scope and approach: Until recently, there have been no detailed or critical studies on the role of protein biomarkers in determining meat colour. This review presents an integromics of recent muscle proteomic studies to investigate pathways and mechanisms of beef colour. A database was created from 13 independent proteomic-based studies including data on five muscles and a list of 79 proteins which were significantly correlated with colour traits. The database was subjected to a multistep analysis including Gene Ontology annotations, pathway analysis and literature mining. This report discusses the key protein biomarkers and the biological pathways associated with fresh beef colour. Biomarkers were prioritised by the frequency of identification and the need for future validation experiments is discussed.Key findings and conclusions: This review identifies six pathways involved in beef colour including energy metabolism, heat shock and oxidative stress, myofibril structure, signalling, proteolysis and apoptosis. The data-mining of the list of the putative biomarkers showed that certain proteins, such as beta-enolase (ENO3), Peroxiredoxin 6 (PRDX6), HSP27 (HSPB1), Phosphoglucomutase 1 (PGM1), Superoxide Dismutase [Cu-Zn] (SOD1) and mu-calpain (CAPN1) were consistently reported by multiple studies as being differentially expressed and having a significant role in beef colour. This integromics work proposes a list of 27 putative biomarkers of beef colour for validation using adapted high-throughput methods.

Meat shrinks and assumes an irregular shape during heating due to the varying distribution of connective tissue and extracellular spaces. The terrestrial 3D laser scanning technology is proposed as an alternative method to manual measurements to estimate the volume of irregularly shaped meat cuboids and to predict the cooking loss based on the heating induced volume shrinkage. Cuboids from aged pork loins (longissimus lumborum, n = 12) were heated at 50, 60, 70 or 80 °C for 30 min. Two methods of 3D reconstruction and volume estimation of the pork cuboids by laser scanning were used; without a base scan (laser-B) and with inclusion of a base scan (laser+B), as well as two methods based on manual caliper measurements of all twelve edges (caliper-12) or of three edges in each direction (caliper-3). Both laser scanning methods (Laser+B and Laser-B) resulted in greater volume estimates for the raw samples than the caliper-12 and caliper-3 measurements (38.3, 39.4 compared to 33.9, 34.8 cm3, respectively). Cooking loss across the different temperatures could be best predicted by the caliper-based perimeter shrinkage (r = 0.94, P 0.05) with the cooking loss. 3D laser scanning technologies can be considered by the food industry for 3D reconstruction and volume estimation, however improvements are needed in the data processing to allow for better predictability of meat quality attributes.