Bioscaffold Valve with and without Mechanically Conditioned Stem Cells for the Treatment of Critical Mitral Valve Diseases in the Young

Congenital heart disease, which includes heart valve defects, are the most common type of birth abnormality in the US. Infants with critical congenital valve disease have no established treatment-measure other than compassionate care options, owing to an absence of prosthetic valves in small sizes and their inability to support somatic growth. A regenerable valve would be appealing since these barriers could be overcome; it can potentially provide for growth, self-repair, infection resistance and be a permanent approach for replacing defective heart valves. Porcine small intestinal submucosa (PSIS) bioscaffold was used to create valvular constructs with the possibility to grow overtime. PSIS bio-scaffolds consisting of two different yarn-twist configurations (2ply and 4ply) were assessed for mechanical properties to determine which scaffold would withstand fatigue loading in a similar manner to the native heart valves. It was found that fatigued 2ply PSIS exhibited higher yield stress (p Next, a pilot study was investigated for implanting 2ply hand-made PSIS mitral valves into juvenile baboons (n=3) to assess their functionality and somatic growth longitudinally. Bioscaffold mitral heart valve function was assessed via echocardiography, while somatic growth was evaluated with a novel parameter, normalized aspect growth ratio (NAGR), where ideal growth is 1, and via histological analysis after the valves were explanted. Our results showed trivial to mild regurgitation up to 17-months post-implantation demonstrating proper functionality of the PSIS mitral valves. The NAGR was found to be roughly 1 within the first 2-4 months, showing ideal growth. The PSIS mitral valve explants were found to develop extracellular matrix (ECM) proteins of collagen, elastin, proteoglycans and fibrin at all explant time points (3-, 11- and 20- months). Overall, the PSIS mitral valves functioned well and regenerated the proper ECM components over their implantation durations. However, sudden valve failure (at 3-, 11- and 20-months post-bioscaffold mitral valve implantation) occurred in all 3 subjects. As a possible means to circumvent valve failure, PSIS tubular mitral bioscaffold valves were subsequently seeded in vitro with bone marrow stem cells and exposed to fluid-induced shear stress patterns in a perfusion bioreactor. The cells secreted a thin layer of ECM, which potentially could help mitigate chronic inflammatory responses, an underlying reason for the valve failure that was observed with the raw PSIS bioscaffolds. It was found that our flow-conditioned valve could produce ECM proteins significantly higher (pde novo ECM that was secreted and the valvular phenotype that resulted from the flow-based mechanical conditioning of allogeneic stem cells-seeded, bioscaffold mitral valves have the potential to accelerate in vivo valve tissue formation. We thus expect these flow-conditioned valves to have longer-term function post-implantation compared to what was possible with the bioscaffold valves-alone

De novo valve tissue morphology following bioscaffold mitral valve replacement in a juvenile non-human primate model

The utility of implanting a bioscaffold mitral valve consisting of porcine small intestinal submucosa (PSIS) in a juvenile baboon model (12 to 14 months old at the time of implant; n = 3) to assess their in vivo tissue remodeling responses was investigated. Our findings demonstrated that the PSIS mitral valve exhibited the robust presence of de novo extracellular matrix (ECM) at all explantation time points (at 3-, 11-, and 20-months). Apart from a significantly lower level of proteoglycans in the implanted valve’s annulus region (p \u3c 0.05) at 3 months compared to the 11-and 20-month explants, there were no other significant differences (p \u3e 0.05) found between any of the other principal valve ECM components (collagen and elastin) at the leaflet, annulus, or chordae tendinea locations, across these time points. In particular, neochordae tissue had formed, which seamlessly integrated with the native papillary muscles. However, additional processing will be required to trigger accelerated, uniform and complete valve ECM formation in the recipient. Regardless of the specific processing done to the bioscaffold valve, in this proof-of-concept study, we estimate that a 3-month window following bioscaffold valve replacement is the timeline in which complete regeneration of the valve and integration with the host needs to occur

Evaluation of Beef Top Sirloin Steaks of Four Quality Grades Cooked to Three Degrees of Doneness

The objective of this study was to evaluate the impact of USDA quality grade on beef eating quality of top sirloin steaks when cooked to multiple degrees of doneness (DOD). Beef top sirloin butts (N = 60; 15/quality grade) were collected to equally represent 4 quality grades [Prime, Top Choice (modest00 to moderate100), Low Choice, and Select]. Steaks were assigned to 1 of 3 DOD: rare (60°C), medium (71°C), and well-done (77°C). Steaks were allocated to either consumer sensory analysis, trained sensory analysis, fat and moisture analysis, or Warner-Bratzler shear force (WBSF). There were no interactions (P > 0.05) for all consumer ratings of palatability traits, indicating increases in DOD had the same impact across all quality grades. Prime steaks had greater (P medium > well-done). There was a quality grade × DOD interaction (P medium > well-done). Lastly, there was no quality grade by DOD interaction (P > 0.05) for Warner-Bratzler shear force. These results indicate that regardless of the DOD top sirloin steaks are cooked to, quality grade had minimal impact on palatability. Therefore, it is unnecessary for consumers, retailers, and foodservice to pay premium prices for higher quality top sirloin steaks, as the same eating experience will be provided

Pork Quality Attributes and Eating Characteristics Among Different Premium and Commodity Pork Loin Programs

Pork branding is a common tool used to differentiate products based on quality to assist consumers in making purchasing decisions. Most pork processers have premium pork programs with different parameters related to color, mar-bling, and other quality factors, though many differences in specific criteria exist among programs. The objective of this study was to assess differences in pork quality and the associated eating experience of different premium and commodity pork loin programs available in the retail market. Loins (n=30/brand) from 7 branded (PRE A, B, C, D, and E) and commodity (COM A and B) programs were acquired and fabricated at 14–15 d post-box date into 2.54-cm chops for visual color, marbling, pH, intramuscular fat, drip loss, purge loss, shear force, and trained sensory panels. Overall, few differences were found among products for most of the quality traits evaluated. One commodity brand, COM B, had higher (P<0.05) loin L* values and chop L* values and had lower chop a* values, visual color scores, pH, and drip loss than other treatments, but it did not differ (P>0.05) in initial juiciness, sustained juiciness, or any tenderness measurement. The only quality measurement that was associated with changes in eating experience was shear force value, with the PRE C product having the highest (P<0.05) Warner-Brazler shear force and slice shear force values and the associated lowest (P<0.05) myofibrillar tenderness and overall tenderness ratings in the sensory panels. There were no differences (P>0.05) among any treatment for initial juiciness, sustained juiciness, and pork flavor intensity. The results from this study indicate that the range of pork quality differences sold domestically among the evaluated premium and commodity programs is minimal and does not result in associated differences in eating experience

Do Published Cooking Temperatures Correspond with Consumer and Chef Perceptions of Steak Degrees of Doneness?

The objective of this study was to assess consumer and chef perceptions and knowledge of beef degrees of doneness (DOD) as well as to measure the changes in cooked color over time related to DOD. Steaks from strip loins (M. longissimus lumborum) from each of 5 quality treatments were used for this study. Steaks were cooked to an endpoint temperature of either very-rare (54°C), rare (60°C), medium-rare (63°C), medium (71°C), well-done (77°C), or very well-done (82°C). L*, a*, and b* were evaluated at 0, 1, 2, 3, 6, 9, and 12 min post-cutting and digital pictures were taken immediately on an internal surface of the steak. Digital surveys for the evaluation of the images of the cooked steaks were created for consumers and chefs. There were time × DOD interactions (P 0.05) for DOD responses for steak pictures evaluated by consumers or chefs. Consumers identified the DOD of cooked steaks as the DOD that corresponds to published end-point temperatures 27 to 35% of the time. Chefs typically identified the DOD as 1 DOD higher than which the steaks were cooked for steaks cooked to medium or less and 1 DOD lower for steaks cooked to well-done and higher. This indicates differences exist in the perceptions of DOD between culinary professionals and consumers, and may contribute to decreased consumer satisfaction when ordering steaks in a restaurant

Biodiversity on the Rocks : Macrofauna Inhabiting Authigenic Carbonate at Costa Rica Methane Seeps

Carbonate communities:The activity of anaerobic methane oxidizing microbes facilitates precipitation of vast quantities of authigenic carbonate at methane seeps. Here we demonstrate the significant role of carbonate rocks in promoting diversity by providing unique habitat and food resources for macrofaunal assemblages at seeps on the Costa Rica margin (400–1850 m). The attendant fauna is surprisingly similar to that in rocky intertidal shores, with numerous grazing gastropods (limpets and snails) as dominant taxa. However, the community feeds upon seep-associated microbes. Macrofaunal density, composition, and diversity on carbonates vary as a function of seepage activity, biogenic habitat and location. The macrofaunal community of carbonates at non-seeping (inactive) sites is strongly related to the hydrography (depth, temperature, O2) of overlying water, whereas the fauna at sites of active seepage is not. Densities are highest on active rocks from tubeworm bushes and mussel beds, particularly at the Mound 12 location (1000 m). Species diversity is higher on rocks exposed to active seepage, with multiple species of gastropods and polychaetes dominant, while crustaceans, cnidarians, and ophiuroids were better represented on rocks at inactive sites. Macro-infauna (larger than 0.3 mm) from tube cores taken in nearby seep sediments at comparable depths exhibited densities similar to those on carbonate rocks, but had lower diversity and different taxonomic composition. Seep sediments had higher densities of ampharetid, dorvilleid, hesionid, cirratulid and lacydoniid polychaetes, whereas carbonates had more gastropods, as well as syllid, chrysopetalid and polynoid polychaetes. Stable isotope signatures and metrics: The stable isotope signatures of carbonates were heterogeneous, as were the food sources and nutrition used by the animals. Carbonate δ13Cinorg values (mean = -26.98‰) ranged from -53.3‰to +10.0‰, and were significantly heavier than carbonate δ13Corg (mean = -33.83‰), which ranged from -74.4‰to -20.6‰. Invertebrates on carbonates had average δ13C (per rock) = -31.0‰ (range -18.5‰to -46.5‰) and δ15N = 5.7‰(range -4.5‰to +13.4‰). Average δ13C values did not differ between active and inactive sites; carbonate fauna from both settings depend on chemosynthesis-based nutrition. Community metrics reflecting trophic diversity (SEAc, total Hull Area, ranges of δ13C and δ15N) and species packing (mean distance to centroid, nearest neighbor distance) also did not vary as a function of seepage activity or site. However, distinct isotopic signatures were observed among related, co-occurring species of gastropods and polychaetes, reflecting intense microbial resource partitioning. Overall, the substrate and nutritional heterogeneity introduced by authigenic seep carbonates act to promote diverse, uniquely adapted assemblages, even after seepage ceases. The macrofauna in these ecosystems remain largely overlooked in most surveys, but are major contributors to biodiversity of chemosynthetic ecosystems and the deep sea in general

Visual Degree of Doneness Impacts Beef Palatability for Consumers with Different Degree of Doneness Preferences

The objective of this study was to determine the impact on beef palatability perceptions when consumers with varying degree of doneness (DOD) preferences are served steaks cooked to multiple DOD. Paired Low Choice strip loin steaks were randomly assigned to a DOD of either rare (60°C), medium-rare (63°C), medium (71°C), medium-well (74°C), or well-done (77°C). Consumer panelists were prescreened for DOD preference (rare, medium, or well-done) prior to sensory panels and were assigned to panels based on their DOD preference. In the first round of testing, consumers were served 1 sample from each of the 5 DOD under low-intensity red incandescent light to mask any DOD differences among samples. In round 2 of testing, consumers were fed the paired samples cooked to the same DOD under white incandescent lights. There were no (P > 0.05) consumer DOD preference × steak DOD interactions or consumer DOD preference effects for tenderness, juiciness, and flavor ratings when steaks were evaluated under both lighting types. Within the white-lighting testing, there was a consumer DOD preference × steak DOD interaction (P 0.05) in overall palatability among DOD under white-lighting, whereas consumers who preferred steaks cooked to rare and medium rated steaks lower (P < 0.05) for overall palatability as DOD increased. Regardless of DOD preference, consumer sensory ratings decreased (P < 0.05) when steaks were cooked above the consumer’s preferred DOD; whereas sensory ratings improved (P < 0.05) when steaks were served below the consumers’ preferences. These results indicate that overcooking steaks has the greatest negative impact on beef palatability perception and thus, foodservice should err on the side of undercooking steaks to preserve, and potentially improve, eating satisfaction

Management of Pediatric Appendicitis During the COVID-19 Pandemic: A Nationwide Multicenter Cohort Study

BACKGROUND: The COVID-19 pandemic has impacted timely access to care for children, including patients with appendicitis. This study aimed to evaluate the effect of the COVID-19 pandemic on management of appendicitis and patient outcomes. METHODS: A multicenter retrospective study was performed including 19 children\u27s hospitals from April 2019-October 2020 of children (age≤18 years) diagnosed with appendicitis. Groups were defined by each hospital\u27s city/state stay-at-home orders (SAHO), designating patients as Pre-COVID (Pre-SAHO) or COVID (Post-SAHO). Demographic, treatment, and outcome data were obtained, and univariate and multivariable analysis was performed. RESULTS: Of 6,014 patients, 2,413 (40.1%) presented during the COVID-19 pandemic. More patients were managed non-operatively during the COVID-19 pandemic compared to before the pandemic (147 (6.1%) vs 144 (4.0%), p \u3c 0.001). Despite this change, there was no difference in the proportion of complicated appendicitis between groups (1,247 (34.6%) vs 849 (35.2%), p = 0.12). COVID era non-operative patients received fewer additional procedures, including interventional radiology (IR) drain placements, compared to pre-COVID non-operative patients (29 (19.7%) vs 69 (47.9%), p \u3c 0.001). On adjusted analysis, factors associated with increased odds of receiving non-operative management included: increasing duration of symptoms (OR=1.01, 95% CI: 1.01-1.012), African American race (OR=2.4, 95% CI: 1.3-4.6), and testing positive for COVID-19 (OR=10.8, 95% CI: 5.4-21.6). CONCLUSION: Non-operative management of appendicitis increased during the COVID-19 pandemic. Additionally, fewer COVID era cases required IR procedures. These changes in the management of pediatric appendicitis during the COVID pandemic demonstrates the potential for future utilization of non-operative management

Diagnosis and management in Rubinstein-Taybi syndrome:first international consensus statement

Rubinstein-Taybi syndrome (RTS) is an archetypical genetic syndrome that is characterised by intellectual disability, well-defined facial features, distal limb anomalies and atypical growth, among numerous other signs and symptoms. It is caused by variants in either of two genes (CREBBP, EP300) which encode for the proteins CBP and p300, which both have a function in transcription regulation and histone acetylation. As a group of international experts and national support groups dedicated to the syndrome, we realised that marked heterogeneity currently exists in clinical and molecular diagnostic approaches and care practices in various parts of the world. Here, we outline a series of recommendations that document the consensus of a group of international experts on clinical diagnostic criteria for types of RTS (RTS1: CREBBP; RTS2: EP300), molecular investigations, long-term management of various particular physical and behavioural issues and care planning. The recommendations as presented here will need to be evaluated for improvements to allow for continued optimisation of diagnostics and care.</p