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Progressive collapsing foot deformity (PCFD) is frequently associated with a gastrocnemius contracture. Surgical treatment of PCFD often includes a gastrocnemius recession in addition to other corrective procedures, which typically requires a period of restricted weight bearing postoperatively. Isolated gastrocnemius recession may allow passive correction of the deformity, improve orthotic fit, and obviate the need for full reconstruction and restricted weight bearing. The goal of this study was to evaluate patient-reported outcomes after an isolated gastrocnemius recession for flexible PCFD in patients anticipated to have difficulty with postoperative restricted weight bearing.A total of 47 patients met the inclusion criteria: isolated gastrocnemius recession for flexible PCFD, no previous ipsilateral surgery, and more than 6 months of follow-up. Of 47 eligible patients, 29 (31 feet) participated. Available preoperative and postoperative patient-reported outcomes were gathered, including the Foot and Ankle Ability Measure Activities of Daily Living, visual analog scale, and the Patient-Reported Outcome Measurement Information System Physical Function Short Form 10a. In addition, patients were asked about satisfaction, willingness to undergo the procedure again, and whether orthotics provided better relief.At a mean of 5.1 (range, 0.6 to 9.0) years postoperatively, median Foot and Ankle Ability Measure Activities of Daily Living was 82.1, mean Patient-Reported Outcome Measurement Information System Physical Function Short Form 10a was 44.2, and median visual analog scale was 10 (of 100). Sixty-nine percent of patients were either satisfied or very satisfied, 69% would undergo the procedure again, and 62% reported improved relief with use of orthotics postoperatively. Among the 47 eligible patients, there were 5 (11%) subsequent flatfoot reconstructions.Isolated gastrocnemius recession for the management of flexible PCFD can be effective as this procedure demonstrated good outcomes scores with high procedural satisfaction and 11% of patients proceeding to subsequent flatfoot reconstruction. This alternative approach may be of particular value for patients anticipated to have difficulty with postoperative weight-bearing restrictions.:IV.

Electrically charged particles can be created by the decay of strong enough electric fields, a phenomenon known as the Schwinger mechanism1. By electromagnetic duality, a sufficiently strong magnetic field would similarly produce magnetic monopoles, if they exist2. Magnetic monopoles are hypothetical fundamental particles that are predicted by several theories beyond the standard model3-7 but have never been experimentally detected. Searching for the existence of magnetic monopoles via the Schwinger mechanism has not yet been attempted, but it is advantageous, owing to the possibility of calculating its rate through semi-classical techniques without perturbation theory, as well as that the production of the magnetic monopoles should be enhanced by their finite size8,9 and strong coupling to photons2,10. Here we present a search for magnetic monopole production by the Schwinger mechanism in Pb-Pb heavy ion collisions at the Large Hadron Collider, producing the strongest known magnetic fields in the current Universe11. It was conducted by the MoEDAL experiment, whose trapping detectors were exposed to 0.235 per nanobarn, or approximately 1.8 × 109, of Pb-Pb collisions with 5.02-teraelectronvolt center-of-mass energy per collision in November 2018. A superconducting quantum interference device (SQUID) magnetometer scanned the trapping detectors of MoEDAL for the presence of magnetic charge, which would induce a persistent current in the SQUID. Magnetic monopoles with integer Dirac charges of 1, 2 and 3 and masses up to 75 gigaelectronvolts per speed of light squared were excluded by the analysis at the 95% confidence level. This provides a lower mass limit for finite-size magnetic monopoles from a collider search and greatly extends previous mass bounds.

Our objective was to determine the effects of dietary quality and protein supplementation of a low-quality warm-season hay on energy metabolism and methane emissions of beef steers.Eight cross-bred steers were used in a respiration calorimetry study with a replicated 4 × 4 Latin square design. Experimental diets were (1) a low-quality forage-based diet (7.4% CP, 66.6% NDF); (2) a low-quality forage with supplemental cottonseed meal (10.0% CP, 66.3% NDF); (3) a medium-quality forage-based diet (10.5% CP, 65.0% NDF); and 4) a high-quality forage-based diet (13.0% CP, 58.4% NDF). Diets were based on bluestem (Bothriochloa ischaemum) hay cut at 2 stages of maturity.Organic matter, fiber, energy, and protein digestibility and energy retention increased (P < 0.05) as the quality of the forage-based diets increased. Total methane production was not affected by diet, but methane production per unit of digested OM or energy retention decreased (P < 0.05) with increased diet quality. Protein supplementation of the low-quality grass hay increased (P < 0.05) DM, fiber, energy, and protein digestion but did not affect methane production. Methane production per unit of energy and protein retention decreased (P < 0.05) with protein supplementation. Enteric nitrous oxide emissions were minor and not affected by diet. An automated head chamber system gave average emission results similar to respiration chambers.Results demonstrate that protein supplementation of low-quality forage or increasing the quality of forage-based diets will potentially decrease the carbon-footprint of beef production.

Background In the majority of cases, the cause of stillbirth remains unknown despite detailed clinical and laboratory evaluation. Approximately 10 to 20% of stillbirths are attributed to c...

Methane gas from livestock production activities is a significant source of greenhouse gas (GHG) emissions which have been shown to influence climate change. New technologies offer a potential to manipulate the rumen biome through genetic selection reducing CH4 production. Methane production may also be mitigated to varying degrees by various dietary intervention strategies. Strategies to reduce GHG emissions need to be developed which increase ruminant production efficiency whereas reducing production of CH4 from cattle, sheep, and goats. Methane emissions may be efficiently mitigated by manipulation of natural ruminal microbiota with various dietary interventions and animal production efficiency improved. Although some CH4 abatement strategies have shown efficacy in vivo, more research is required to make any of these approaches pertinent to modern animal production systems. The objective of this review is to explain how anti-methanogenic compounds (e.g., plant tannins) affect ruminal microbiota, reduce CH4 emission, and the effects on host responses. Thus, this review provides information relevant to understanding the impact of tannins on methanogenesis, which may provide a cost-effective means to reduce enteric CH4 production and the influence of ruminant animals on global GHG emissions.

Objective This study aimed to determine if delayed cord clamping (DCC) affected brain myelin water volume fraction (VFm) and neurodevelopment in term infants. Study Design This was a single-blinded randomized controlled trial of healthy pregnant women with term singleton fetuses randomized at birth to either immediate cord clamping (ICC) (≤ 20 seconds) or DCC (≥ 5 minutes). Follow-up at 12 months of age consisted of blood work for serum iron indices and lead levels, a nonsedated magnetic resonance imaging (MRI), followed within the week by neurodevelopmental testing. Results At birth, 73 women were randomized into one of two groups: ICC (the usual practice) or DCC (the intervention). At 12 months, among 58 active participants, 41 (80%) had usable MRIs. There were no differences between the two groups on maternal or infant demographic variables. At 12 months, infants who had DCC had increased white matter brain growth in regions localized within the right and left internal capsules, the right parietal, occipital, and prefrontal cortex. Gender exerted no difference on any variables. Developmental testing (Mullen Scales of Early Learning, nonverbal, and verbal composite scores) was not significantly different between the two groups. Conclusion At 12 months of age, infants who received DCC had greater myelin content in important brain regions involved in motor function, visual/spatial, and sensory processing. A placental transfusion at birth appeared to increase myelin content in the early developing brain. Key Points

Electroporation has been evaluated as a potential backend wastewater treatment for deactivation of Ascaris suum eggs in buffer solution. Initial results indicate that eggshell permeability is affected by the pulse train electric field strength and duration. Coupling electroporation with chemical exposure, using low concentrations of commercially available disinfectants, allows oxidizing agents to pass through the complex strata of the A. suum eggshell, specifically reaching the innermost embryonic environment, which leads to successful deactivation compared to either method used separately. The aim of this work is to identify and develop an alternative technique that efficiently inactivates helminth eggs present in wastewater.

Gene duplication and fusion events in protein evolution are postulated to be responsible for the common protein folds exhibiting internal rotational symmetry. Such evolutionary processes can also potentially yield regions of repetitive primary structure. Repetitive primary structure offers the potential for alternative definitions of critical regions, such as the folding nucleus (FN). In principle, more than one instance of the FN potentially enables an alternative folding pathway in the face of a subsequent deleterious mutation. We describe the targeted mutation of the carboxyl-terminal region of the (internally located) FN of the de novo designed purely-symmetric β-trefoil protein Symfoil-4P. This mutation involves wholesale replacement of a repeating trefoil-fold motif with a "blade" motif from a β-propeller protein, and postulated to trap that region of the Symfoil-4P FN in a nonproductive folding intermediate. The resulting protein (termed "Bladefoil") is shown to be cooperatively folding, but as a trimeric oligomer. The results illustrate how symmetric protein architectures have potentially diverse folding alternatives available to them, including oligomerization, when preferred pathways are perturbed.

Stretchable supercapacitors based on vertically aligned nanotubes or nanowires have attracted considerable attention because of their improved robustness and electrochemical performance under large and repeated deformations. However, it is still challenging to maintain the low electric resistance of stretchable electrodes of such a stretchable supercapacitor under extremely large strains due to the variation of the contacts between individual nanotubes/wires. Here, we develop and demonstrate a robust and high-performance stretchable electrode based on crumpled Au coated CNT forest (Au-CNT-forest), which significantly increases the conductivity of the original CNT-forest electrode while maintaining its unique crumpled hierarchical structures. Experimental measurements show that the resistance of the Au-CNT- forest electrode is around one order magnitude lower than that of a pure CNT-forest electrode and is comparable to that of a conventional thin film electrode. The biaxially crumpled Au-CNT-forest electrode demonstrates nearly identical electrochemical performance at all the measured charge/discharge rates (i.e., from 0.5 to 80 mA cm-2) under different strain conditions (i.e., from 0% to 800%), which can not be achieved by a pure CNT-forest electrode. The as-prepared symmetric supercapacitor with crumpled Au-CNT forest electrodes demonstrates a maximum specific capacitance of ~ 6 mF cm-2 at the scan rate of 40 mA cm-2 under different strains, exhibiting superior mechanical and electrochemical stability. This research demonstrates a facile process to fabricate highly stretchable supercapacitors based on vertically aligned nanotubes or nanowires for achieving exceptional and robust electrochemical performance.

The development of stretchable electronics requires the invention of compatible high-performance power sources, such as stretchable supercapacitors and batteries. In this work, two-dimensional (2D) titanium carbide (Ti3C2Tx) MXene is being explored for flexible and printed energy storage devices by fabrication of a robust, stretchable high-performance supercapacitor with reduced graphene oxide (RGO) to create a composite electrode. The Ti3C2Tx/RGO composite electrode combines the superior electrochemical and mechanical properties of Ti3C2Tx and the mechanical robustness of RGO resulting from strong nanosheet interactions, larger nanoflake size, and mechanical flexibility. It is found that the Ti3C2Tx/RGO composite electrodes with 50 wt % RGO incorporated prove to mitigate cracks generated under large strains. The composite electrodes exhibit a large capacitance of 49 mF/cm2 (∼490 F/cm3 and ∼140 F/g) and good electrochemical and mechanical stability when subjected to cyclic uniaxial (300%) or biaxial (200% × 200%) strains. The as-assembled symmetric supercapacitor demonstrates a specific capacitance of 18.6 mF/cm2 (∼90 F/cm3 and ∼29 F/g) and a stretchability of up to 300%. The developed approach offers an alternative strategy to fabricate stretchable MXene-based energy storage devices and can be extended to other members of the large MXene family.

HighlightsNitrous oxide is a greenhouse gas emitted from feedyard pen surfaces.Experiments were conducted to quantify nitrous oxide emissions from precipitation, urine, and feces.Nitrous oxide emissions from urine were about 30% of those from equal amounts of precipitation.Regression equations were developed for empirical modeling of emissions.Abstract. The amount of moisture deposited annually as urine (~320 mm) and feces (~95 mm) on typical semi-arid Texas beef cattle feedyard pens is considerable compared to the regional 470 mm mean annual precipitation. Precipitation is a primary factor affecting nitrous oxide (N2O) emissions from manure, but specific effects of urine and feces deposition are unknown. The objectives of this research were to (1) quantify N2O emissions following precipitation, urine, and feces deposition on a dry feedyard manure surface, and (2) develop equations for future empirical modeling of these emissions. Four experiments (Exp.) were conducted using recirculating flux chambers to quantify N2O emissions. Exp. 1 had treatments (TRT) of water (W), artificial urine (AU), and two urines collected from beef cattle fed high-quality forage (FU) or corn-based concentrate (CU). Exp. 2 had TRT of W, AU, and two feces levels (Fx1 and Fx2). In Exp. 3, N2O emissions were quantified from fresh feces pats. In Exp. 4, the effect of rainfall pH on N2O emissions was evaluated. Results from Exp. 1 showed that the W TRT had the highest mean cumulative N2O emission, while AU, FU, and CU ranged from 31.0% to 70.0% of W on an equal volume-applied basis. There was little correlation between N2O emissions and urine or water nitrogen (N) content. In Exp. 2, W again had the highest cumulative N2O. Cumulative N2O emissions expressed per unit of water added were 29.0, 3.8, 4.5, and 5.1 mg N kg-1 water added for W, AU, Fx1, and Fx2, respectively. In Exp. 3, fresh feces pats emitted no direct N2O, but N2O originated from the dry manure beneath the feces pat due to wetting. In Exp. 4, the highest N2O emissions occurred at pH 5 and pH 8, with lower emissions at pH 6 and pH 7. This research has shown that the addition of moisture to the pen surface from urine and feces contributes considerably to N2O emissions as compared to precipitation alone. The following recommendations were developed for future empirical modeling purposes: (1) N2O emissions from urine should be calculated as 32.7% of those emissions from the equivalent mass deposition of water, and (2) N2O emissions resulting from the mass of water in feces should be calculated as 15.6% of those emissions from the equivalent mass deposition of water. Keywords: Beef cattle, Greenhouse gas, Manure, Nitrous oxide, Urine, Precipitation.

The National Institutes of Health's Environmental influences on Child Health Outcomes (ECHO) Program was designed to address solution-oriented research questions about the links between children's early life environment and their risks of pre-, peri-, and post-natal complications, asthma, obesity, neurodevelopmental disorders, and positive health. Children born very preterm are at increased risk for many of the outcomes on which ECHO focuses, but the contributions of environmental factors to this risk are not well characterized. Three ECHO cohorts consist almost exclusively of individuals born very preterm. Data provided to ECHO from cohorts can be used to address hypotheses about (1) differential risks of chronic health and developmental conditions between individuals born very preterm and those born at term; (2) health disparities across social determinants of health; and (3) mechanisms linking early-life exposures and later-life outcomes among individuals born very preterm. IMPACT: The National Institutes of Health's Environmental Influences on Child Health Outcomes Program is conducting solution-oriented research on the links between children's environment and health. Three ECHO cohorts comprise study participants born very preterm; these cohorts have enrolled, to date, 1751 individuals born in 14 states in the U.S. in between April 2002 and March 2020. Extensive data are available on early-life environmental exposures and child outcomes related to neurodevelopment, asthma, obesity, and positive health. Data from ECHO preterm cohorts can be used to address questions about the combined effects of preterm birth and environmental exposures on child health outcomes.

Slower mobility is associated with mild cognitive impairment (MCI) and dementia. We examined the interaction of endurance with gait speed on prevalent MCI and dementia.Cross-sectional multinomial regression in the ARIC cohort (n = 2844 participants; 71 to 94 years; 44% men; 18% Black persons) with cognitive status (normal/MCI/dementia), 4 m gait speed, and endurance (2 minute walk [2MW]).Faster gait speed (up to but not above 1 m/s) and better 2MW were separately associated with lower dementia risk. Good performance in both (2MW = 200 m, gait speed = 1.2 m/s) was associated with 99% lower dementia (Relative Prevalence Ratio [RPR] = 0.01 [95% CI: 0.0 to 0.06]) and 73% lower MCI, RPR = 0.27 (0.15 to 0.48) compared to poor performance in both (2MW = 100 m, gait speed = 0.8 m/s). Models incorporating a gait speed-by-2MW interaction term outperformed gait speed-only models (Gait speed relationships with dementia diminish at faster gait speeds. Combining endurance with gait speed may yield more sensitive markers of MCI and dementia than gait speed alone.

Solving environmental odor issues can be confounded by many analytical, technological, and socioeconomic factors. Considerable know-how and technologies can fail to properly identify odorants responsible for the downwind nuisance odor and, thereby, focus on odor mitigation strategies. We propose enabling solutions to environmental odor issues utilizing troubleshooting techniques developed for the food, beverage, and consumer products industries. Our research has shown that the odorant impact-priority ranking process can be definable and relatively simple. The initial challenge is the prioritization of environmental odor character from the perspective of the impacted citizenry downwind. In this research, we utilize a natural model from the animal world to illustrate the rolling unmasking effect (RUE) and discuss it more systematically in the context of the proposed environmental odorant prioritization process. Regardless of the size and reach of an odor source, a simplification of odor character and composition typically develops with increasing dilution downwind. An extreme odor simplification-upon-dilution was demonstrated for the prehensile-tailed porcupine (P.T. porcupine); its downwind odor frontal boundary was dominated by a pair of extremely potent character-defining odorants: (1) ‘onion’/‘body odor’ and (2) ‘onion’/‘grilled’ odorants. In contrast with the outer-boundary simplicity, the near-source assessment presented considerable compositional complexity and composite odor character difference. The ultimate significance of the proposed RUE approach is the illustration of naturally occurring phenomena that explain why some environmental odors and their sources can be challenging to identify and mitigate using an analytical-only approach (focused on compound identities and concentrations). These approaches rarely move beyond comprehensive lists of volatile compounds emitted by the source. The novelty proposed herein lies in identification of those few compounds responsible for the downwind odor impacts and requiring mitigation focus.

DNA methyltransferase 1 (DNMT1) is an enzyme that functions as a maintenance methyltransferase during DNA replication, and depletion of this enzyme from cells is considered to be a rational goal in DNA methylation dependent disorders. Two DNMT1 depleting agents aza-dCyd (5-aza-29-deoxycytidine, decitabine) and aza-Cyd (5-aza-cytidine, azacitidine) are currently used for the treatment of myelodysplastic syndromes and acute myeloid leukemia, and have also been investigated for non-oncology indications such as sickle cell disease. However, these agents have several off-target activities leading to significant toxicities that limit dosing and duration of treatment. Development of more selective inhibitors of DNMT1 could therefore afford treatment for long durations at effective doses. We have discovered that 5-aza-49-thio-29-deoxycytidine (aza-T-dCyd) is as effective as aza-dCyd in depleting DNMT1 in mouse tumor models, but with markedly low toxicity. In this review we describe the preclinical studies that led to the development of aza-T-dCyd as a superior DNMT1 depleting agent with respect to aza-dCyd, and will describe its pharmacology, metabolism, and mechanism of action. In an effort to understand why aza-T-dCyd is a more selective DNMT1 depleting agent than aza-dCyd, we will also compare and contrast the activities of these two agents. Significance Statement Aza-T-dCyd is a potent DNMT1 depleting agent. Although similar in structure to decitabine (aza-dCyd) its metabolism and mechanism of action is different than that of aza-dCyd, resulting in less off target activity and less toxicity. The larger therapeutic index of aza-T-dCyd (DNMT1 depletion vs toxicity) in mice suggests that it would be a better clinical candidate to selectively deplete DNMT1 from target cells and determine whether or not depletion of DNMT1 is an effective target for various diseases.

Dabigatran etexilate (DABE), an oral anticoagulant prodrug, is nearly completely metabolized to the dabigatran (DAB) active metabolite by carboxylesterase-1 (CES1) and carboxylesterase-2 (CES2). The high interpatient variation in DAB plasma concentrations, coupled with its low therapeutic index, emphasizes the need to understand how CES1 and CES2 impact active metabolite formation. Previous work focused on CES1 enzyme activity but the contributions of CES2 remain unclear. The purpose of this study was to determine how CES2 activity influences DAB active metabolite formation. We compared the efficiency of DAB formation from DABE when exposed sequentially to human intestinal and then human hepatic microsomes (mimicking the normal metabolic sequence) with the reverse metabolic sequence in which DABE is exposed to hepatic and then intestinal microsomes. The poor efficiency of DAB formation with reverse sequential hydrolysis indicates that CES2 activity is crucial for active metabolite formation. Thus, the decrease in DAB formation with normal sequential hydrolysis was more sensitive to CES2 inhibition by verapamil (CES2 IC50 = 3.4 μM) than CES1 inhibition by diltiazem (CES2 IC50 = 9.1 μM). These results show CES2 activity plays a crucial role in DAB formation and that variability in its activity is an important determinant of therapeutic response.

Purpose To evaluate the clinical, radiographic, and prosthetic outcomes of a single custom CAD/CAM abutment system on implants from four manufacturers, with a mean clinical service of 4 years in a retrospective, multicenter case series study. Materials and methods Adult subjects (n = 142) previously restored with titanium or gold-shaded titanium nitride custom CAD/CAM abutments (Atlantis, Dentsply Sirona; n = 259) connected to implants from four different manufacturers (Dentsply Sirona Implants [AT], Biomet 3i [BM], Nobel Biocare [NB], Straumann [ST]), irrespective of implant-abutment interface, and replacing one or more teeth in any position were recalled for a single-visit examination by calibrated investigators at six university clinics. The primary outcomes evaluated included abutment success and survival; secondary outcomes included assessment of papillae fill, probing pocket depth (PD), bleeding on probing (BOP), marginal bone levels (MBLs), and patient-reported outcome measures (PROMs). Results Two-hundred fifty-five (98.5%) abutments supported cement-retained restorations, and four (1.5%) abutments supported screw-retained restorations. Forty-two patients had 64 AT implants (25%), 31 patients had 61 BM implants (24%), 26 patients had 50 NB implants (19%), and 43 patients had 84 ST implants (32%). The overall implant-CAD/CAM abutment success rate was 92.66% (95% CI: 88.78%, 95.53%) for all implants examined, and the survival rate was 98.84% (95% CI: 96.65%, 99.76%) for all implants evaluated. The Jemt papillae index demonstrated a minimum of at least 50% to complete fill of the interproximal papillae in 65.0% of sites. PDs had a median value of 3.0 mm, and BOP was present on 19% of abutment surfaces. Mean MBL changes from the time of placement to exam were -0.24 ± 0.99 mm (-4.9 to 2.3; P = .058) for mesial sites and -0.32 ± 0.96 mm (-4.9 to 2.1; P = .000) for distal sites. PROMs expressed 93% of patients reporting good to very good masticatory function, 97% of patients reporting being satisfied or very satisfied with their esthetic outcomes, and 94% of patients indicating that they were satisfied or very satisfied with their overall implant-restorative outcomes. Conclusion This retrospective, multicenter clinical study of FDA 510k-approved titanium CAD/CAM abutments of a single manufacturer on multiple implant systems demonstrated high levels of success and survival as well as stable peri-implant tissue outcomes, reflected by overwhelmingly positive PROMs.