Lower extremity and trunk sagittal plane coordination strategies and kinetic distribution during landing in males and females.

Force attenuation during landing requires coordinated motion of the ankle, knee, hip, and trunk, and strategies may differ between sexes. Sagittal plane coordination of the ankle/knee, knee/hip, and knee/trunk, and lower extremity and trunk kinematics and kinetics was compared throughout landing between 28 males and 28 females. Coordination was assessed with a modified vector coding technique and binning analysis. Total support moments (TSM), each joint's percent contribution, and timing of the TSM were compared. Females landed with less isolated knee flexion in the ankle/knee, knee/hip, and knee/trunk couplings, but more simultaneous ankle/knee flexion, less simultaneous knee flexion/hip extension, and more simultaneous trunk/knee flexion. Females landed with larger plantarflexion angles from 0-16% and smaller trunk flexion angles from 0-78%. In females, absolute TSM were larger from 0-6% and smaller from 42-100%, and normalized TSM were larger from 0-8% and 26-42%. Females had greater ankle contribution to the TSM from 14-15% and 29-35%, smaller absolute peak TSM, and the peak TSM occurred earlier. Females compensated for less isolated knee flexion with greater simultaneous ankle/knee flexion early in landing and knee/trunk flexion later in landing. Coordination and TSM differences may influence force attenuation strategies and have implications for knee injury disparity between sexes.

Rapid adaptation of primate LGN neurons to drifting grating stimulation.

The visual system needs to dynamically adapt to changing environments. Much is known about the adaptive effects of constant stimulation over prolonged periods. However, there are open questions regarding adaptation to stimuli that are changing over time, interrupted, or repeated. Feature-specific adaptation to repeating stimuli has been shown to occur as early as primary visual cortex (V1), but there is also evidence for more generalized, fatigue-like adaptation that might occur at an earlier stage of processing. Here, we show adaptation in the lateral geniculate nucleus (LGN) of awake, fixating monkeys following brief (1 s) exposure to repeated cycles of a 4-Hz drifting grating. We examined the relative change of each neuron's response across successive (repeated) grating cycles. We found that neurons from all cell classes (parvocellular, magnocellular, and koniocellular) showed significant adaptation. However, only magnocellular neurons showed adaptation when responses were averaged to a population response. In contrast to firing rates, response variability was largely unaffected. Finally, adaptation was comparable between monocular and binocular stimulation, suggesting that rapid LGN adaptation is monocular in nature.NEW & NOTEWORTHY Neural adaptation can be defined as reduction of spiking responses following repeated or prolonged stimulation. Adaptation helps adjust neural responsiveness to avoid saturation and has been suggested to improve perceptual selectivity, information transmission, and predictive coding. Here, we report rapid adaptation to repeated cycles of gratings drifting over the receptive field of neurons at the earliest site of postretinal processing, the lateral geniculate nucleus of the thalamus.

The impact of male factor infertility on early and late morphokinetic parameters: a retrospective analysis of 4126 time-lapse monitored embryos.

STUDY QUESTION: Is there an effect of male factor infertility (MFI) on either early or late morphokinetic parameters obtained during embryonic culture to blastocyst stage in a time-lapse imaging (TLI) incubator? SUMMARY ANSWER: Neither mild nor severe MFI had an impact on overall time to blastocyst or duration of individual cleavage stages in the total embryo population. WHAT IS KNOWN ALREADY: Prior studies have suggested that paternal DNA and sperm quality affect embryo morphokinetic parameters, but the impact of MFI is not fully understood. STUDY DESIGN, SIZE, DURATION: This retrospective cohort study, at a major academic fertility centre, included 536 couples (women, ≤44 years of age) undergoing IVF between September 2013 and September 2016. PARTICIPANTS/MATERIALS, SETTING, METHODS: Data from 4126 embryos cultured to the blastocyst stage in a TLI-monitored incubator were retrospectively reviewed. Embryos derived from the sperm of men with MFI were compared with those derived from patients with other infertility diagnoses. Generalized fixed and random effects models, t-test and χ2 were used as appropriate. MAIN RESULTS AND THE ROLE OF CHANCE: Couples with MFI had a higher rate of ICSI utilization and fewer usable embryos on average, and the men were older compared with couples with other diagnoses. Additionally, the women in MFI couples were younger and had higher antral follicle counts (AFCs) and higher anti-Müllerian hormone (AMH) levels compared with the other women undergoing IVF. When controlling for maternal and paternal ages, AMH and fertilization method (conventional IVF versus ICSI), neither mild nor severe MFI affected duration of individual cleavage stages or overall time to the blastocyst stage, when all or only usable embryos were examined (coefficient 0.44 hours in all embryos, P = 0.57; coefficient 0.39 hours in usable embryos, P = 0.60). Whether the sperm was surgically extracted similarly had no significant effect on embryo morphokinetic parameters. When the fertilization method was assessed independently, ICSI lengthened the overall time to blastocyst stage by 1.66 hours (P = 0.03) on average, primarily due to an increase in duration of the time from 5-cell embryo stage to early blastulation (P5SB). LIMITATIONS, REASONS FOR CAUTION: This large cohort study avoided embryo selection bias due to random assignment of embryos to the TLI incubators. However, our findings may not be generalizable to groups under-represented in our clinic population. Future studies should also evaluate the impact of male hormonal status and detailed sperm morphology, such as head versus flagellum defects, on embryo morphokinetic development. WIDER IMPLICATIONS OF THE FINDINGS: Our findings suggest that the fertilization method rather than MFI per se impacts time to early blastulation. The clinical implications of this effect on embryo development warrant further investigation. STUDY FUNDING/COMPETING INTEREST(S): There were no sources of funding for this study. There are no competing interests. TRIAL REGISTRATION NUMBER: N/A.

Allocation to male vs female floral function varies by currency and responds differentially to density and moisture stress.

Allocation of finite resources to separate reproductive functions is predicted to vary across environments and affect fitness. Biomass is the most commonly measured allocation currency; however, in comparison with nutrients it may be less limited and express different environmental and evolutionary responses. Here, we measured carbon, nitrogen, phosphorus, and biomass allocation among floral whorls in recombinant inbred lines of Brassica rapa in multiple environments to characterize the genetic architecture of floral allocation, including its sensitivity to environmental heterogeneity and to choice of currency. Mass, carbon, and nitrogen allocation to female whorls (pistils and sepals) decreased under high density, whereas nitrogen allocation to male organs (stamens) decreased under drought. Phosphorus allocation decreased by half in pistils under drought, while stamen phosphorus was unaffected by environment. While the contents of each currency were positively correlated among whorls, selection to improve fitness through female (or male) function typically favored increased allocation to pistils (or stamens) but decreased allocation to other whorls. Finally, genomic regions underlying correlations among allocation metrics were mapped, and loci related to nitrogen uptake and floral organ development were located within mapped quantitative trait loci. Our candidate gene identification suggests that nutrient uptake may be a limiting step in maintaining male allocation. Taken together, allocation to male vs female function is sensitive to distinct environmental stresses, and the choice of currency affects the interpretation of floral allocation responses to the environment. Further, genetic correlations may counter the evolution of allocation patterns that optimize fitness through female or male function.

More than a corridor: use of a main stem stream as supplemental foraging habitat by a brook trout metapopulation.

Coldwater fishes in streams, such as brook trout (Salvelinus fontinalis), typically are headwater specialists that occasionally expand distributions downstream to larger water bodies. It is unclear, however, whether larger streams function simply as dispersal corridors connecting headwater subpopulations, or as critical foraging habitat needed to sustain large mobile brook trout. Stable isotopes (δ(13)C and δ(15)N) and a hierarchical Bayesian mixing model analysis was used to identify brook trout that foraged in main stem versus headwater streams of the Shavers Fork watershed, West Virginia. Headwater subpopulations were composed of headwater and to a lesser extent main stem foraging individuals. However, there was a strong relationship between brook trout size and main stem prey contributions. The average brook trout foraging on headwater prey were limited to 126 mm standard length. This size was identified by mixing models as a point where productivity support switched from headwater to main stem dependency. These results, similar to other studies conducted in this watershed, support the hypothesis that productive main stem habitat maintain large brook trout and potentially facilitates dispersal among headwater subpopulations. Consequently, loss of supplementary main stem foraging habitats may explain loss of large, mobile fish and subsequent isolation of headwater subpopulations in other central Appalachian watersheds.

Customized recommendations for production management clusters of North American automatic milking systems.

Automatic milking systems (AMS) are implemented in a variety of situations and environments. Consequently, there is a need to characterize individual farming practices and regional challenges to streamline management advice and objectives for producers. Benchmarking is often used in the dairy industry to compare farms by computing percentile ranks of the production values of groups of farms. Grouping for conventional benchmarking is commonly limited to the use of a few factors such as farms' geographic region or breed of cattle. We hypothesized that herds' production data and management information could be clustered in a meaningful way using cluster analysis and that this clustering approach would yield better peer groups of farms than benchmarking methods based on criteria such as country, region, breed, or breed and region. By applying mixed latent-class model-based cluster analysis to 529 North American AMS dairy farms with respect to 18 significant risk factors, 6 clusters were identified. Each cluster (i.e., peer group) represented unique management styles, challenges, and production patterns. When compared with peer groups based on criteria similar to the conventional benchmarking standards, the 6 clusters better predicted milk produced (kilograms) per robot per day. Each cluster represented a unique management and production pattern that requires specialized advice. For example, cluster 1 farms were those that recently installed AMS robots, whereas cluster 3 farms (the most northern farms) fed high amounts of concentrates through the robot to compensate for low-energy feed in the bunk. In addition to general recommendations for farms within a cluster, individual farms can generate their own specific goals by comparing themselves to farms within their cluster. This is very comparable to benchmarking but adds the specific characteristics of the peer group, resulting in better farm management advice. The improvement that cluster analysis allows for is characterized by the multivariable approach and the fact that comparisons between production units can be accomplished within a cluster and between clusters as a choice.

Factors associated with increased milk production for automatic milking systems.

Automatic milking systems (AMS) are increasingly popular throughout the world. Our objective was to analyze 635 North American dairy farms with AMS for (risk) factors associated with increased milk production per cow per day and milk production per robot per day. We used multivariable generalized mixed linear regressions, which identified several significant risk factors and interactions of risk factors associated with milk production. Free traffic was associated with increased production per cow and per robot per day compared with forced systems, and the presence of a single robot per pen was associated with decreased production per robot per day compared with pens using 2 robots. Retrofitted farms had significantly less production in the first 4 yr since installation compared with production after 4 yr of installation. In contrast, newly built farms did not see a significant change in production over time since installation. Overall, retrofitted farms did not produce significantly more or less milk than newly constructed farms. Detailed knowledge of factors associated with increased production of AMS will help guide future recommendations to producers looking to transition to an AMS and maximize their production.

Does neoadjuvant therapy for esophageal cancer increase postoperative morbidity or mortality?

Neoadjuvant therapy has proven to be effective in the reduction of locoregional recurrence and mortality for esophageal cancer. However, induction treatment has been reported to be associated with increased risk of postoperative complications. We therefore compared outcomes after esophagectomy for esophageal cancer for patients who underwent neoadjuvant therapy and patients treated with surgery alone. Using the American College of Surgeons National Surgical Quality Improvement Program database (2005-2011), we identified 1939 patients who underwent esophagectomy for esophageal cancer. Seven hundred and eight (36.5%) received neoadjuvant therapy, while 1231 (63.5%) received no neoadjuvant therapy within 90 days prior to surgery. Primary outcome was 30-day mortality, and secondary outcomes included overall and serious morbidity, length of stay, and operative time. Patients who underwent neoadjuvant treatment were younger (62.3 vs. 64.7, P < 0.001), were more likely to have experienced recent weight loss (29.4% vs. 15.9%, P < 0.001), and had worse preoperative hematological cell counts (white blood cells <4.5 or >11 × 10(9) /L: 29.3% vs. 15.0%, P < 0.001; hematocrit <36%: 49.7% vs. 30.0%, P < 0.001). On unadjusted analysis, 30-day mortality, overall, and serious morbidity were comparable between the two groups, with the exception of the individual complications of venous thromboembolic events and bleeding transfusion, which were significantly lower in the surgery-only patients (5.71% vs. 8.27%, P = 0.027; 6.89% vs. 10.57%, P = 0.004; respectively). Multivariable and matched analysis confirmed that 30-day mortality, overall, and serious morbidity, as well as prolonged length of stay, were comparable between the two groups of patients. An increasing trend of preoperative neoadjuvant therapy for esophageal cancer was observed through the study years (from 29.0% in 2005-2006 to 44.0% in 2011, P < 0.001). According to our analysis, preoperative neoadjuvant therapy for esophageal cancer does not increase 30-day mortality or the overall risk of postoperative complications after esophagectomy.

Fusion of Magnetic Resonance Imaging and Real-Time Elastography to Visualize Prostate Cancer: A Prospective Analysis using Whole Mount Sections after Radical Prostatectomy.

PURPOSE: To determine whether the fusion of multiparametric magnetic resonance imaging (MRI) with transrectal real-time elastography (RTE) improves the visualization of PCa lesions compared to MRI alone. MATERIALS AND METHODS: In a prospective setting, 45 patients with biopsy-proven PCa received prostate MRI prior to radical prostatectomy (RP). T2 and diffusion-weighted imaging (T2WI/DW-MRI) and, if applicable, dynamic contrast-enhanced sequences (T2WI/DW/DCE-MRI) were used to perform MRI/RTE fusion. The probability of PCa on MRI was graded according to the PI-RADS score for 12 different prostate sectors per patient. MRI images were fused with RTE to stratify suspicious from non-suspicious sectors. Imaging results were compared to whole mount sections using nonparametrical receiver operating characteristic curves and the area under these curves (AUC). RESULTS: 41 of 45 patients were eligible for final analyses. Histopathology confirmed PCa in 261 (53%) of 492 prostate sectors. MRI alone provided an AUC of 0.62 (T2WI/DW-MRI) and 0.65 (T2WI/DW/DCE-MRI) to predict PCa and was meaningfully enhanced to 0.75 (T2WI/DW-MRI) and 0.74 (T2WI/DW/DCE-MRI) using MRI/RTE fusion. Sole MRI showed a sensitivity and specificity of 57.9% and 61% with the best results for ventral prostate sectors whereas RTE was superior in dorsal and apical sectors. MRI/RTE fusion improved sensitivity and specificity to 65.9% and 75.3%, respectively. Additional use of DCE sequences showed a sensitivity and specificity of 65% and 55.7% for MRI and 72.1% and 66% for MRI/RTE fusion. CONCLUSION: MRI/RTE fusion provides improved PCa visualization by combining the strength of both imaging techniques in regard to prostate zonal anatomy and thereby might improve future biopsy-guided PCa detection.

Quantitative food web analysis supports the energy-limitation hypothesis in cave stream ecosystems.

Energy limitation has long been the primary assumption underlying conceptual models of evolutionary and ecological processes in cave ecosystems. However, the prediction that cave communities are actually energy-limited in the sense that constituent populations are consuming all or most of their resource supply is untested. We assessed the energy-limitation hypothesis in three cave streams in northeastern Alabama (USA) by combining measurements of animal production, demand, and resource supplies (detritus, primarily decomposing wood particles). Comparisons of animal consumption and detritus supply rates in each cave showed that all, or nearly all, available detritus was required to support macroinvertebrate production. Furthermore, only a small amount of macroinvertebrate prey production remained to support other predatory taxa (i.e., cave fish and salamanders) after accounting for crayfish consumption. Placing the energy demands of a cave community within the context of resource supply rates provided quantitative support for the energy-limitation hypothesis, confirming the mechanism (limited energy surpluses) that likely influences the evolutionary processes and population dynamics that shape cave communities. Detritus-based surface ecosystems often have large detrital surpluses. Thus, cave ecosystems, which show minimal surpluses, occupy the extreme oligotrophic end of the spectrum of detritus-based food webs.

Age and sex differences in the incidence of esophageal adenocarcinoma: results from the Surveillance, Epidemiology, and End Results (SEER) Registry (1973-2008).

Risk factors driving sex disparity in esophageal cancer are unclear. Recent molecular evidence suggests hormonal factors. We conducted a national descriptive epidemiological study to assess the hypothesis that estrogen exposure could explain the male predominance in observed esophageal adenocarcinoma incidence. We analyzed the esophageal cancer incidence trends by histology and sex from 1973 to 2008 in nine population-based cancer registries of the Surveillance, Epidemiology, and End Results (SEER) 9 Registry Database. We used age as a proxy for estrogen exposure in females. The collective age groups annual percentage change in esophageal adenocarcinoma for females is positive (0.03%; 95% confidence interval: 0.02, 0.03%) during the study period. Interestingly, the esophageal adenocarcinoma annual percentage change in incidence rates for females during the same time period is significantly negative from ages 50-54 to ages 60-64. Even though the incidence of esophageal adenocarcinoma rises in both males and females, the male-to-female ratio across age peaks in the 50-54 years then decreases. Furthermore, the esophageal adenocarcinoma age-adjusted incidence rate in postmenopausal females age 80 and above increases with age unlike their male counterparts. Taken together, these data support the hypothesis that the endocrine milieu in pre- and perimenopausal females serves as a protective factor against esophageal adenocarcinoma, and with loss of estrogen or because of the increasing time period away from estrogen exposure, the rate of esophageal adenocarcinoma incidence increases in the older postmenopausal female. Because females comprise the largest portion of the elderly population with esophageal adenocarcinoma, these findings are significant.

[Pulmonary hypertension: microRNAs in pathogenesis, diagnosis and therapy]. / Pulmonale Hypertonie: mikroRNAs in Pathogenese, Diagnostik und Therapie.

Whereas pulmonary arterial hypertension is an orphan disease, the term pulmonary hypertension includes several common entities and is of major clinical significance. The pathophysiological triad of vasoconstriction, microthrombosis and vascular remodeling is found in most forms of pulmonary hypertension, independently of the underlying etiology. In this review, novel aspects in the pathogenesis of the remodeling, in particular microRNAs, will be discussed. MicroRNAs are small RNA fragments which bind specifically to the mRNA of a target gene thus decreasing its stability or inhibiting further translation ("gene silencing"). Of major interest is the association between microRNAs and the expression of bone morphogenetic protein receptor type II which has been found to be dysregulated on pulmonary endothelial and vascular smooth muscle cells in several forms of pulmonary hypertension. The specific inhibition of microRNAs by antagomiRs makes microRNAs a potential therapeutic target. Moreover, microRNAs are being validated in serum as biomarkers for diagnosis, severity and prognosis of pulmonary hypertension.

COVID-19 Hospitalization in Hawai'i and Patterns of Insurance Coverage, Race and Ethnicity, and Vaccination.

Importance: The people of Hawai'i have both high rates of health insurance and high levels of racial and ethnic diversity, but the degree to which insurance status and race and ethnicity contribute to health outcomes in COVID-19 remains unknown. Objective: To evaluate the associations of insurance coverage, race and ethnicity (using disaggregated race and ethnicity data), and vaccination with outcomes for COVID-19 hospitalization. Design, Setting, and Participants: This retrospective cohort study included hospitalized patients at a tertiary care medical center between March 2020 and March 2022. All patients hospitalized for acute COVID-19, identified based on diagnosis code or positive results on polymerase chain reaction-based assay for SARS-CoV-2, were included in analysis. Data were analyzed from May 2022 to May 2023. Exposure: COVID-19 requiring hospitalization. Main Outcome and Measures: Electronic medical record data were collected for all patients. Associations among race and ethnicity, insurance coverage, receipt of at least 1 COVID-19 vaccine, intensive care unit (ICU) transfer, in-hospital mortality, and COVID-19 variant wave (pre-Delta vs Delta and Omicron) were assessed using adjusted multivariable logistic regression. Results: A total of 1176 patients (median [IQR] age of 58 [41-71] years; 630 [54%] male) were hospitalized with COVID-19, with a median (IQR) body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) of 30 (25-36) and Sequential Organ Failure Assessment score of 1 (0-2). The sample included 16 American Indian or Alaska Native patients, 439 Asian (not otherwise specified) patients, 15 Black patients, 66 Chinese patients, 246 Filipino patients, 76 Hispanic patients, 107 Japanese patients, 10 Korean patients, 299 Native Hawaiian patients, 523 Pacific Islander (not otherwise specified) patients, 156 Samoan patients, 5 Vietnamese patients, and 311 White patients (patients were able to identify as >1 race or ethnicity). When adjusting for age, BMI, sex, medical comorbidities, and socioeconomic neighborhood status, there were no differences in either ICU transfer (eg, Medicare vs commercial insurance: odds ratio [OR], 0.84; 95% CI, 0.43-1.64) or in-hospital mortality (eg, Medicare vs commercial insurance: OR, 0.85; 95% CI, 0.36-2.03) as a function of insurance type. Disaggregation of race and ethnicity revealed that Filipino patients were more likely to die in the hospital (OR, 1.79; 95% CI, 1.04-3.03; P = .03). When considering variant waves, mortality among Filipino patients was highest during the pre-Delta time period (OR, 2.72; 95% CI, 1.02-7.14; P = .04), when mortality among Japanese patients was lowest (OR, 0.19; 95% CI, 0.03-0.78; P = .04); mortality among Native Hawaiian patients was lowest during the Delta and Omicron period (OR, 0.35; 95% CI, 0.13-0.79; P = .02). Patients with Medicare, compared with those with commercial insurance, were more likely to have received at least 1 COVID-19 vaccine (OR, 1.85; 95% CI, 1.07-3.21; P = .03), but all patients, regardless of insurance type, who received at least 1 COVID-19 vaccine had reduced ICU admission (OR, 0.40; 95% CI, 0.21-0.70; P = .002) and in-hospital mortality (OR, 0.42; 95% CI, 0.21-0.79; P = .01). Conclusions and Relevance: In this cohort study of hospitalized patients with COVID-19, those with government-funded insurance coverage (Medicare or Medicaid) had similar outcomes compared with patients with commercial insurance, regardless of race or ethnicity. Disaggregation of race and ethnicity analysis revealed substantial outcome disparities and suggests opportunities for further study of the drivers underlying such disparities. Additionally, these findings illustrate that vaccination remains a critical tool to protect patients from COVID-19 mortality.

Enzyme-Polymer Conjugates with Photocleavable Linkers for Control Over Protein Activity.

Reversible conjugation of polymers to proteins is important for a variety of applications, for example to control protein activity. Light is often employed as an external trigger to allow for spatio and temporal control over release of a payload. In this report, we demonstrate preparation of photocleavable poly(polyethylene glycol) acrylate)-lysozyme (pPEGA-Lys) conjugates via ortho-nitrobenzyl linkages. The conjugates were made by both grafting-to and grafting-from in order to compare and contrast the two synthetic approaches. First, a lysine-reactive ortho-nitrobenzyl atom transfer radical polymerization (ATRP) initiator was synthesized. For the grafting-to strategy, the initiator was employed in the ATRP of PEGA, and the subsequent polymer was conjugated to the lysine residues of lysozyme. For the grafting-from strategy, lysozyme was modified first with the photocleavable initiator, and the purified macroinitiator was then subjected to polymerization conditions to synthesize the protein-polymer conjugate. The polymer was cleaved from the protein via UV light, and activity before and after polymer removal was evaluated, showing 83% recovery. This work provides evidence that reversing conjugation is successful for activity modulation for ortho-nitrobenzyl linked protein-polymer conjugates.

Controlling rates and reversibilities of elimination reactions of hydroxybenzylammoniums by tuning dearomatization energies.

Hydroxybenzylammonium compounds can undergo a reversible 1,4- or 1,6-elimination to afford quinone methide intermediates after release of the amine. These molecules are useful for the reversible conjugation of payloads to amines. We hypothesized that aromaticity could be used to alter the rate of reversibility as a distinct thermodynamic driving force. We describe the use of density functional theory (DFT) calculations to determine the effect of aromaticity on the rate of release of the amine from hydroxybenzylammonium compounds. Namely, the aromatic scaffold affects the dearomatization reaction to reduce the kinetic barrier and prevent the reversibility of the amine elimination. We consequently synthesized a small library of polycyclic hydroxybenzylammoniums, which resulted in a range of release half-lives from 18 minutes to 350 hours. The novel mechanistic insight provided herein significantly expands the range of release rates amenable to hydroxybenzylammonium-containing compounds. This work provides another way to affect the rate of payload release in hydroxybenzylammoniums.

The influence of steroidal implants and manganese sulfate supplementation on growth performance, trace mineral status, hepatic gene expression, hepatic enzyme activity, and circulating metabolites in feedlot steers.

Angus-cross steers (n = 144; 359 kg ±â€…13.4) were used to assess the effect of dietary Mn and steroidal implants on performance, trace minerals (TM) status, hepatic enzyme activity, hepatic gene expression, and serum metabolites. Steers (n = 6/pen) were stratified by BW in a 3 × 2 factorial. GrowSafe bunks recorded individual feed intake (experimental unit = steer; n = 24/treatment). Dietary treatments included (MANG; 8 pens/treatment; Mn as MnSO4): (1) no supplemental Mn (analyzed 14 mg Mn/kg DM; Mn0); (2) 20 mg supplemental Mn/kg DM (Mn20); (3) 50 mg supplemental Mn/kg DM (Mn50). Within MANG, steers received a steroidal implant treatment (IMP) on day 0: (1) no implant; NO; or (2) combination implant (Revalor-200; REV). Liver biopsies for TM analysis and qPCR, and blood for serum glucose, insulin, non-esterified fatty acids, and urea-N (SUN) analysis were collected on days 0, 20, 40, and 77. Data were analyzed as a randomized complete block with a factorial arrangement of treatments including fixed effects of Mn treatment (MANG) and implant (IMP) using PROC MIXED of SAS 9.4 using initial BW as a covariate. Liver TM, serum metabolite, enzyme activity, and gene expression data were analyzed as repeated measures. No MANG × IMP effects were noted (P ≥ 0.12) for growth performance or carcass characteristic measures. Dietary Mn did not influence final body weight, overall ADG, or overall G:F (P ≥ 0.14). Liver Mn concentration increased with supplemental Mn concentration (MANG; P = 0.01). An IMP × DAY effect was noted for liver Mn (P = 0.01) where NO and REV were similar on day 0 but NO cattle increased liver Mn from days 0 to 20 while REV liver Mn decreased. Relative expression of MnSOD in the liver was greater in REV (P = 0.02) compared to NO and within a MANG × IMP effect (P = 0.01) REV increased liver MnSOD activity. These data indicate current NASEM Mn recommendations are adequate to meet the demands of finishing beef cattle given a steroidal implant. Despite the roles of Mn in metabolic pathways and antioxidant defense, a basal diet containing 14 mg Mn/kg DM was sufficient for the normal growth of finishing steers. This study also provided novel insight into how implants and supplemental Mn influence genes related to arginine metabolism, urea synthesis, antioxidant capacity, and TM homeostasis as well as arginase and MnSOD activity in hepatic tissue of beef steers.

Steroidal implants improve cattle growth and efficiency partially through increased net protein synthesis resulting in increased skeletal muscle hypertrophy. Necessary to support this increased growth are trace minerals (TM). Manganese (Mn) is essential, serving as a cofactor and activator of various enzymes. Manganese plays a crucial role in ruminant animals by supporting nitrogen recycling while also being essential for mitochondrial antioxidant defense. Consulting nutritionists routinely supplement Mn, amongst other TM, at concentrations greater than current recommendations. However, there is limited research on the impact of supplemental Mn in implanted finishing cattle. Our prior work suggests steroidal implants decrease liver Mn concentration. This is of interest as liver Mn concentration is tightly regulated. Therefore, this study evaluated the effects of steroidal implants and manganese sulfate supplementation on cattle growth performance, trace mineral status, expression of relevant hepatic genes, hepatic enzyme activity, and circulating metabolites in feedlot steers. In this study, supplementing Mn at the recommended concentration did not influence the growth of both implanted and non-implanted cattle.

Assessing the arrhythmogenic propensity of fibrotic substrate using digital twins to inform a mechanisms-based atrial fibrillation ablation strategy.

Atrial fibrillation (AF), the most common heart rhythm disorder, may cause stroke and heart failure. For patients with persistent AF with fibrosis proliferation, the standard AF treatment-pulmonary vein isolation-has poor outcomes, necessitating redo procedures, owing to insufficient understanding of what constitutes good targets in fibrotic substrates. Here we present a prospective clinical and personalized digital twin study that characterizes the arrhythmogenic properties of persistent AF substrates and uncovers locations possessing rotor-attracting capabilities. Among these, a portion needs to be ablated to render the substrate not inducible for rotors, but the rest (37%) lose rotor-attracting capabilities when another location is ablated. Leveraging digital twin mechanistic insights, we suggest ablation targets that eliminate arrhythmia propensity with minimum lesions while also minimizing the risk of iatrogenic tachycardia and AF recurrence. Our findings provide further evidence regarding the appropriate substrate ablation targets in persistent AF, opening the door for effective strategies to mitigate patients' AF burden.

Does V1 response suppression initiate binocular rivalry?

During binocular rivalry (BR) only one eye's view is perceived. Neural underpinnings of BR are debated. Recent studies suggest that primary visual cortex (V1) initiates BR. One trigger might be response suppression across most V1 neurons at the onset of BR. Here, we utilize a variant of BR called binocular rivalry flash suppression (BRFS) to test this hypothesis. BRFS is identical to BR, except stimuli are shown with a ∼1s delay. If V1 response suppression was required to initiate BR, it should occur during BRFS as well. To test this, we compared V1 spiking in two macaques observing BRFS. We found that BRFS resulted in response facilitation rather than response suppression across V1 neurons. However, BRFS still reduces responses in a subset of V1 neurons due to the adaptive effects of asynchronous stimulus presentation. We argue that this selective response suppression could serve as an alternate initiator of BR.

A role for ocular dominance in binocular integration.

Neurons in the primate primary visual cortex (V1) combine left- and right-eye information to form a binocular output. Controversy surrounds whether ocular dominance, the preference of these neurons for one eye over the other, is functionally relevant. Here, we demonstrate that ocular dominance impacts gain control during binocular combination. We recorded V1 spiking activity while monkeys passively viewed grating stimuli. Gratings were either presented to one eye (monocular), both eyes with the same contrasts (binocular balanced), or both eyes with different contrasts (binocular imbalanced). We found that contrast placed in a neuron's dominant eye was weighted more strongly than contrast placed in a neuron's non-dominant eye. This asymmetry covaried with neurons' ocular dominance. We then tested whether accounting for ocular dominance within divisive normalization improves the fit to neural data. We found that ocular dominance significantly improved model performance, with interocular normalization providing the best fits. These findings suggest that V1 ocular dominance is relevant for response normalization during binocular stimulation.

Lower extremity coordination strategies to mitigate dynamic knee valgus during landing in males and females.

Frontal and sagittal plane landing biomechanics differ between sexes but reported values don't account for simultaneous segment or joint motion necessary for a coordinated landing. Frontal and sagittal plane coordination patterns, angles, and moments were compared between 28 males and 28 females throughout the landing phase of a drop vertical jump. Females landed with less isolated thigh abduction (p = 0.018), more in-phase motion (p < 0.001), and more isolated shank adduction (p = 0.028) between the thigh and shank in the frontal plane compared with males. Females landed with less in-phase (p = 0.012) and more anti-phase motion (p = 0.019) between the thigh and shank in the sagittal plane compared with males. Females landed with less isolated knee flexion (p = 0.001) and more anti-phase motion (p < 0.001) between the sagittal and frontal plane knee coupling compared with males. Waveform and discrete metric analyses revealed females land with less thigh abduction from 20 % to 100 % and more shank abduction from 0 to 100 % of landing, smaller knee adduction at initial contact (p = 0.002), greater peak knee abduction angles (p = 0.015), smaller knee flexion angles at initial contact (p = 0.035) and peak (p = 0.034), greater peak knee abduction moments (p = 0.024), greater knee abduction angles from 0 to 13 % and 19 to 30 %, greater knee abduction moments from 19 to 25 %, and smaller knee flexion moments from 3 to 5 % of landing compared with males. Females utilize greater frontal plane motion compared with males, which may be due to different inter-segmental joint coordination and smaller sagittal plane angles. Larger knee abduction angles and greater knee adduction motion in females are due to aberrant shank abduction rather than thigh adduction.