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PubMed2002

The use of a carbon fiber plate for periprosthetic supracondylar femoral fractures.

Operative management of periprosthetic supracondylar femoral fractures in poor-quality bone presents a challenging task for the orthopaedic surgeon. We report our experience with the use of a semirigid carbon fiber-reinforced plate in the treatment of 5 patients, all of whom were elderly women with severe osteoporosis and highly restricted mobility. All 5 of the fractures were sustained after low-energy trauma at least 2 years after primary knee arthroplasty. Except for 1 patient who died of pulmonary embolism, all 4 surviving patients progressed uneventfully to fracture union with good mobility and no residual pain. The use of this method for the treatment of periprosthetic femoral fractures has not been reported previously, and we believe it provides a successful and technically undemanding solution to this difficult problem.

Aged↗

PubMed1994

A review of probes and robots: implementing new technologies in meat evaluation.

Changes in function from fat-depth measurement to meat quality measurement, and vice versa, have occurred in the history of electrical and optical meat probes. In the future, robotic systems might use ultrasonics to measure subcutaneous fat depth while at the same time positioning a fiber-optic probe relative to the skeleton to measure meat quality. There is a major distinction between probes that make a measurement at a single site within the carcass and those that produce a vector of measurements as they move through the carcass. Vector measurements were introduced to find subcutaneous fat thickness, but they may be used for meat quality measurements to deal with intra- and intermuscular variation. Replacement of hand-held probes by robots is in progress and could change meat distribution and marketing, perhaps replacing conventional meat grading by lowering the unit cost of grading and improving reliability for consumers. The feasibility of using ultrasonics to find probe measuring sites in the thoraco-lumbar region of pork carcasses has been proven. This requires new types of carcass morphometry data, such as rib angles and curvatures, and intercostal dimensions.

Abattoirs↗

PubMed2004

Saturable absorbers incorporating carbon nanotubes directly synthesized onto substrates and fibers and their application to mode-locked fiber lasers.

We present novel carbon-nanotube-based saturable absorbers. Using the low-temperature alcohol catalytic chemical-vapor deposition method, high-quality single-walled carbon nanotubes (SWNTs) were directly synthesized on quartz substrates and fiber ends. We successfully applied the SWNTs to mode lock a fiber laser producing subpicosecond pulses at a 50-MHz repetition rate.

Journal Article↗

PubMed2003

Use of hollow fiber membrane filtration for the removal of DMSO from platelet concentrates.

It has been hypothesized that, in addition to freezing injury, some damage to platelets may result from the cell packing that occurs during removal of the cryoprotectant. This study examined DMSO removal by fluid exchange across hollow-fiber (HF) filters as an alternative to centrifugation. The DMSO solution with or without cell suspension was passed once through the filter. The optimum exchange during unloading of DMSO was determined by varying the flow rates in the external and internal compartments of the HF filter. Initially, buffered solutions of a 5% DMSO solution in the absence of platelets were pumped into the fibers and exchanged against PBS. The residual DMSO was determined by osmometry. The exchange of DMSO across the membrane was flow dependent and also influenced by the chemical nature of the HF fibers. No protocol using a reasonable rate flow through the fibers removed more than 95% of the DMSO in a single pass. The optimum protocol was achieved with polysynthane fibers with an internal flow rate of approximately 20 mi/min and an external flow rate of 100 ml/min. Subsequently, frozen/thawed platelet concentrates in DMSO were washed using centrifugation and compared to the HF filtration method. Platelet quality was assayed by flow cytometry, cell count, morphology and osmotic stress test. Both filtration and centrifugal washing techniques resulted in comparable morphological scores and numbers of discoid cells. When agents reducing platelet activation were added, platelet quality was improved after washing by either technique. The lower platelet osmotic response with HF filtration than with centrifugation while using activation inhibitors was attributed to the remaining amount of the inhibitors. All other parameters tested were similar. The expression of CD62P was equivalent with both techniques, and centrifugation did not activate platelets more than filtration contrary to what was originally anticipated. In conclusion, platelet quality was comparable after washing by either technique but hollow fiber filtration does remove cryoprotectant more rapidly than does centrifugation.

Blood Platelets↗

PubMed2005

Dynamic hollow fiber-supported headspace liquid-phase microextraction.

With the increasing concern over deteriorating environmental quality, the analysis of organic pollutants in air, water, and soil has become critically important. The development of simple, efficient, and inexpensive analytical sample pretreatment is crucial for monitoring and evaluating the environment. In this work, a dynamic hollow-fiber supported headspace liquid-phase microextraction (DHF-HS-LPME) approach was developed. In dynamic LPME, the extracting solvent is held within a hollow fiber, affixed to a syringe needle and immersed in the sample solution, and is moved to-and-fro by using a programmable syringe pump. The movement facilitates mass transfer from the sample to the solvent. Here, a similar approach was adopted, except that extraction was from the headspace rather than by direct immersion. Analysis of the extract was carried out by gas chromatography-mass spectrometry. The effect of sampling temperature, water, salt, dwelling time were investigated. Results indicated that this novel headspace microextraction method gave good analyte-enrichment factors, linear range, limits of detection and repeatability, all of which were evaluated by extracting PAHs from soil samples. This technique represents an inexpensive, convenient, fast and simple sample preparation of this class of semi-volatile organic compounds.

Chromatography, Liquid↗

PubMed1993

Selectivity of lingual nerve fibers to chemical stimuli.

The cell bodies of the lingual branch of the trigeminal nerve were localized in the trigeminal ganglion using extracellular recordings together with horseradish peroxidase labeling from the tongue. Individual lingual nerve fibers were characterized with regard to their conduction velocities, receptive fields, and response to thermal, mechanical, and chemical stimuli. Fibers were classified as C, A delta, A beta, cold, and warm. The chemical stimuli included NaCl, KCl, NH4Cl, CaCl2, menthol, nicotine, hexanol, and capsaicin. With increasing salt concentration the latency of the response decreased and the activity increased. The responses elicited by salts (to 2.5 M), but not nonpolar stimuli such as menthol, were reversibly inhibited by 3.5 mM of the tight junction blocker, LaCl3. These data suggest that salts diffuse into stratified squamous epithelia through tight junctions in the stratum corneum and stratum granulosum, whereupon they enter the extracellular space. 11 C fibers were identified and 5 were characterized as polymodal nociceptors. All of the C fibers were activated by one or more of the salts NaCl, KCl, or NH4Cl. Three C fibers were activated by nicotine (1 mM), but none were affected by CaCl2 (1 M), menthol (1 mM), or hexanol (50 mM). However, not all C fibers or even the subpopulation of polymodals were activated by the same salts or by nicotine. Thus, it appears that C fibers display differential responsiveness to chemical stimuli. A delta fibers also showed differential sensitivity to chemicals. Of the 35 characterized A delta mechanoreceptors, 8 responded to NaCl, 9 to KCl, 9 to NH4Cl, 0 to CaCl2, menthol, or hexanol, and 2 to nicotine. 8 of 9 of the cold fibers (characterized as A delta's) responded to menthol, none responded to nicotine, 8 of 16 were inhibited by hexanol, 9 of 19 responded to 2.5 M NH4Cl, 5 of 19 responded to 2.5 M KCl, and 1 of 19 responded to 2.5 M NaCl. In summary, lingual nerve fibers exhibit responsiveness to chemicals introduced onto the tongue. The differential responses of these fibers are potentially capable of transmitting information regarding the quality and quantity of chemical stimuli from the tongue to the central nervous system.

Ammonium Chloride↗

PubMed1996

Application of sweet potato fiber to skin wound in rat.

In order to introduce a suitable drug mixing base or covering for burns or decubital wounds, the usefulness of fiber extracted from the sweet potato was investigated. The healing effect of the fiber was evaluated by examining the extent of reduction in the size of wounds and changes in the quality of wounds in rats. In contrast to the control, the use of the fiber alone as a wound covering material reduced wounded areas by 21.0% at postoperative day 9, 19.5% at day 11, and 18.7% at day 13, and resulted in an obvious increase in the rats' weight. The number of days required for healing in all treated rats was 19 for the fiber groups and over 21 d for the control. In vitro, the fiber indicated excellent absorptive ability for serum and good adhesive ability for a number of proteins. This result suggested that the fiber has favorable properties for healing wounds which contain large amounts of exudate. Our macroscopic findings also indicated that the fiber protected wounds from dryness. These results suggested that sweet potato fiber could be use as a covering material in combination with drugs in skin wound therapy.

Absorption↗

PubMed1998

Meat quality variation in the robotic sorting of pork loins.

A robot was used to make fiber-optic reflectance measurements from 400 to 700 nm in 10-nm increments at six sites, 10 cm apart, along the length of 48 pork loins. Meat quality was assessed in the longissimus dorsi near the thoracolumbar junction using 1) a bag-drip method for fluid loss, 2) a subjective evaluation of wetness, 3) a colorimeter measurement of paleness (CIE L), and 4) a subjective evaluation for Japanese pork color scores (JPCS). Sorting of the loins in the commercial plant from which they originated was correlated (P < .01) with fluid loss (r=.57), with wetness scores (r=-.57), with CIE L* (r=.71), and with JPCS (r=-.64). Laboratory measurements of pH at the site of meat quality assessment were correlated (P < .01) with fluid loss (r=-.61), with wetness scores (r=.65), with CIE L* (r=-.74), and with JPCS (r=.77). Average spectra obtained robotically were correlated (P < .01) with fluid loss (r=.56 at 670 nm, and R=.76 adding 560 and 540 nm), with wetness score (r=-.65 at 480 nm, and R=.75 adding 530 and 570 nm), with CIE L* (r=.76 at 480 nm, and R=.82 adding 690 and 520 nm), and with JPCS (r=-.70). In sorting loins that were all categorized as normal at the plant, mean reflectance data collected robotically were correlated with fluid loss, r=.42 (P > .05) at 700 nm and R=.58 (P > .05) adding 430 nm; with wetness score, r=.25 (P > .05); with CIE L*, r=.58 (P < .025) at 700 nm; and with JPCS, r=-.71 (P < .01) at 700 nm. Thus, as well as detecting obvious PSE loins, the robotic probe also had a limited capability to sort loins all categorized as normal at the plant.

Animals↗

PubMed2004

Optimal degradation rate for collagen chambers used for regeneration of peripheral nerves over long gaps.

The experimental study of peripheral nerve regeneration has depended heavily on the use of a nerve chamber in which the stumps of the transected nerve are inserted. A large variety of chamber fillings and chamber types have been used in an effort to induce a higher quality of regeneration across the gap initially separating the two stumps. In this study we studied the morphology of nerves regenerated across a 15 mm gap following implantation of a series of five chambers. The chambers were fabricated from type I collagen and possessed identical pore volume fractions as well as average pore diameters, but differed in cross-link density continuously along the series. The residual mass of the implanted chambers at 9 weeks was observed to increase continuously with increasing cross-link density along the series, indicating a continuous decrease in degradation rate. The quality of regenerated nerves, determined by the number of large diameter fibers (A-fibers) per nerve, the average diameter of all axons and the ratio of area occupied by axons (N-Ratio), was superior at an intermediate level of chamber degradation rate. The maximal quality of peripheral nerve regeneration corresponded to an optimal degradation rate with an estimated chamber half-life of approximately 2-3 weeks following implantation. A speculative mechanistic explanation of the observed optimum focuses on the hypothetical role of cell and cytokine traffic that may take place through holes in the chamber generated by the degradation process. The data show the presence of a hitherto unreported optimal chamber degradation rate that leads to regenerated nerves of maximum quality.

Absorbable Implants↗

PubMed1990

Preproenkephalin upregulation in nucleus caudalis: high and low intensity afferent stimulation differentially modulate early and late responses.

Nucleus caudalis expression of preproenkephalin mRNA changes following lesions depleting small-caliber primary afferent fibers and after stimulation of trigeminal afferents at different intensities. Animals treated neonatally with capsaicin display reduced preproenkephalin gene expression in nucleus caudalis neurons. Stimulation of normal animals at low intensities enhances preproenkephalin expression in a bimodal temporal pattern. High intensity stimulation is effective only at later time points in normal animals, but it causes both early and late effects on preproenkephalin expression when applied to animals neonatally lesioned with capsaicin. Transsynaptic regulation of preproenkephalin expression in pain-modulating areas of the nucleus caudalis of the trigeminal nerve thus depends on the specific type of primary afferent input. The rapid responses noted after selective large fiber stimulation appear to be suppressed by coactivation of small caliber fibers. Later responses appear less influenced by the quality of the eliciting afferent stimulus.

Afferent Pathways↗

PubMed1998

Why is transurethral microwave thermotherapy (TUMT) positively effective?

Between 1992 and 1994, 157 patients with benign prostatic hyperplasia were treated with transurethral microwave thermotherapy (TUMT). In evaluating the efficacy of TUMT with the International PrOstate Symptom Score (I-PSS) in 121 patients, 18 (15%) showed excellent and 42 (35%) showed good response. In evaluation of QOL, the result was 43 patients (33%) excellent and 42 patients (35%) good response. In objective evaluation of uroflow in 93 patients, 12 (13%) showed excellent and 13 (14%) showed good response. The prostatic volume did not show a significant decrease after treatment. In terms of overall improvement, according to the criteria proposed at the 2nd International Consultation on BPH, the treatment was considered effective in 53 of 108 patients (48%). Histological examination of the prostate enucleated from a patient 7 months after TUMT revealed degenerative changes of nerve fibres on S-100 protein immunohistochemical staining, which were more extensive than those in smooth muscle cells on HE staining. In in vitro tests the isometric contraction force of the rabbit prostatic tissue was measured after exposure to different temperatures, ranging from 37 to 50 degrees C. No significant change was observed up to 45 degrees C vs. 37 degrees C. After exposure to 48 degrees C, the nerve mediated contractions became completely depressed, although phenylephrine or KCl induced contractions were only partially suppressed. After exposure to 50 degrees C, no contraction was induced by any type of stimuli. In conclusion, it is suggested that good symptomatic improvement after TUMT results from both neural and muscular damage to the prostate. As TUMT is not aiming at a relief of anatomical obstruction, 50 degrees C is thought to be a sufficient thermal condition to cause an irreversible damage to prostatic tissue, which will provide a relief from functional obstruction and urethral instability.

Aged↗

PubMed2025

Lysine-rich rice enhanced muscle growth and development in young rats.

Rice is the staple food for half of the world's population but is low in lysine content. We previously developed transgenic lysine-rich rice with enhanced free lysine content in rice seeds and demonstrated that it could improve skeletal growth and development in rats. However, the effects of lysine-rich rice on muscle remain to be studied. We hypothesized that lysine-rich rice was able to improve muscle growth in weaning rats via its anabolic effects on muscle metabolism. Male weaning Sprague-Dawley rats received lysine-rich rice (HFL) diet, wild-type rice (WT) diet, or wild-type rice with various doses of lysine supplementation (WT + Lys) diet (+ 0%, + 10%, + 20%, and + 40% lysine) for 70 days. Muscle strength and quality were analyzed by biomechanical test and muscle fiber typing of the extensor digitorum longus (EDL) muscles. Molecular mechanisms of lysine on muscle growth were also explored by rat serum biochemistry and cell culture systems. Results indicated that the HFL diet improved rats' muscle growth, strength, and physiological cross-sectional area (CSA) over the WT diet group. The CSAs of fast-twitch muscle fibers (Type IIb and IIx) were also increased. In addition, the HFL increased serum insulin-like growth factor 1 (IGF-1) and decreased serum myostatin (MSTN) concentrations. The cell culture model showed that lysine deficiency reduced IGF-1 expression and inhibited myoblast differentiation associated with muscle growth. Our findings showed that lysine-rich rice improved muscle growth and development in weaning rats. Higher dietary lysine possibly inhibited MSTN and activated of IGF-1 signaling pathway for muscle growth and development.

Animals↗

PubMed2006

Hyperspectral NIR imaging for calibration and prediction: a comparison between image and spectrometer data for studying organic and biological samples.

A hyperspectral image in the near infrared contains thousands of position-referenced spectra. After imaging reference materials of known composition it is possible to build Partial Least Squares (PLS) regression models for predicting unknown compositions from new images or spectra. In this paper a comparison is made between spectra from a hyperspectral image and spectra from two spectrometers: a scanning grating instrument with rotating sample holders and an FT-NIR instrument utilizing a fiber-optic probe. The raw spectra and the quality of the PLS calibration models and predictions are compared. Two sample datasets consist of a set of 13 designed artificial mixtures of pure constituents and a selection of 13 sampled cheeses. The prediction error from the hyperspectral image spectra is between that of the two spectrometers. For a typical food sample, the average bias [and replicate standard deviation] was -0.6% [0.5%] for protein and -0.2% [1.3%] for fat. Comparable values for the best spectrometer were -0.2% bias for protein and -0.5% for fat. Some of the advantages of working with hyperspectral images are highlighted: the simultaneous exploration of representations of both spectral and spatial data, and the analysis of concentration profiles and concentration maps all contribute to better characterization of organic and biological materials.

Calibration↗

PubMed2003

Optimization of dextran production by Leuconostoc mesenteroides NRRL B-512 using cheap and local sources of carbohydrate and nitrogen.

Using pure components for the fermentation medium in dextran production imposes high costs on the industry. In the present study, the economic production of dextran using local and cheap sources of carbohydrate and nitrogen was investigated. Different concentrations of molasses and wheat-bran extract, after filtration, steam sterilization and pH adjustment, were inoculated with a fresh suspension of Leuconostoc mesenteroides. Cultures were incubated, and then diluted with an equal volume of ethanol. The bacteria were pelleted, and an aliquot of the supernatant was diluted with ethanol and dextran was precipitated. The supernatant was removed and the precipitate was dissolved in a minimal volume of water. Activated charcoal was added and the solution was boiled. The solution was filtered and protein impurities removed by 2-methylbutan-2-ol/chloroform extraction. Dextran was again precipitated with cold ethanol as described above, and the precipitate was dried in a desiccator. Optimum conditions and composition of culture media for dextran production using sugar-beet molasses and wheat bran were determined. The best results were obtained when 20% (w/v) molasses and 15% (w/v) wheat bran were used. The optimal initial pH for dextran production was 7.5.

Bioreactors↗

PubMed2004

Morphoanatomical studies of Uncaria tomentosa and Uncaria guianensis bark and leaves.

The genus Uncaria Schreber (Rubiaceae) includes species that are widely distributed in tropical areas. The inner bark of the stems and leaves of two native species of South America, Uncaria tomentosa (Willd. ex Roemer & Schultes) DC., and Uncaria guianensis (Aublet) J. F. Gmelin, "cat's claw" are used in either folk medicine or in procuring phytotherapeutic drugs. These species contain about sixty active substances which are being tested widely for possible medicinal value. The following applications are considered: peptic ulcer, rheumatism, tumours, antiinflammatory effect, inflammation, diabetes and as general tonic. Currently, Uncaria tomentosa is in demand as tea, tablets or capsules in more than 30 countries outside Perú, as well as inside the country. Pharmacognosy studies are required to determine the comparative morphoanatomical and micrographic features for identification and quality control purposes. Several microscopic parameters, including phloem fibers, calcium oxalate crystals, starch granules, trichomes, and foliar architecture should be considered. The aim of our work is to analyse comparative morphoanatomical and micrographic features which might provide assistance in the identification, analysis and standardization of Uncaria tomentosa (Willd. ex Roemer & Schultes) DC. and Uncaria guianensis (Aublet) J. F. Gmelin stem bark and leaves in order to obtain phytotherapeutic drugs, and of the crude drug as well.

Cat's Claw↗

PubMed2005

Decreasing inflammatory response of injured patellar tendons results in increased collagen fibril diameters.

Tissue inflammation is essential in the healing process, but its effect on the quality of the healing tissue is not clear. This study determines the effect of decreasing early inflammation during wound healing in genetic deficient mice on collagen fibril diameter. Two strains of mice were used: three C3H/HeJ mice and three C3H/HeN mice for each of two time points (7 and 14 days postinjury). C3H/HeJ mice have a genetic deficiency in the production of tumor necrosis factor by macrophages and other cytokines in response to endotoxin, and C3H/HeN mice have no genetic deficiency. The right patellar tendon of both mouse strains was transversely transected, whereas the left patellar tendon was left intact for control. After 7 and 14 days, both right and left patellar tendons were harvested, and tendon samples were examined with transmission electron microscopy. We found that at 7 days, transected tendons of C3H/HeJ mice exhibited on average 1.6 times larger collagen fibril diameters than transected C3H/HeN tendons, whereas at 14 days, collagen fibril diameters of the C3H/HeJ mice were 1.3 times that of C3H/HeN mice. Also, at both 7 days and 14 days, collagen fibrils in C3H/HeJ mice appeared more organized than C3H/HeN mice. In addition, control tendons in both mouse strains showed no significant differences in collagen fibril diameter and organization. Therefore, these results suggest that decreasing the inflammatory response in the early stages of tendon wound healing enhances the quality of the healing tendon through increased collagen fiber diameter and better organization.

Animals↗

PubMedDate not supplied

Aging of the rotator cuff.

The many years of challenge in treating athletes disabled by tendinitis stimulated a study of the aging of tendons. Autopsy specimens, representing tendons from 20-, 50-, and 70-year-old subjects, were obtained. Each specimen, consisting of a wedge of the greater tuberosity with the attached supraspinatus tendon, was examined roentgenographically to study the morphologic features of the greater tuberosity and was decalcified and stained with Safranin O to evaluate the amount of fibro-cartilage, with van Gieson to identify Sharpey's fibers, and with hematoxylin and eosin to determine cellularity, fiber integrity, and vascularity of the tendon. The comparison related to chronological age documented a morphologic change of the greater tuberosity and progressive degeneration of all elements of the tendinous structures with progressive (1) osteitis of the greater tuberosity, cystic degeneration, and irregularity of the cortical margin; (2) degenerative sulcus between the greater tuberosity and the articular surface; (3) disruption of the integrity of the attachment of the tendon to the bone by Sharpey's fibers; (4) loss of cellularity, loss of staining quality, and fragmentation of the tendon; (5) diminution of the vascularity of the tendon; and (6) diminution of fibrocartilage.

Adult↗

PubMed2004

Value of sunflower seed in finishing diets of feedlot cattle.

The value of sunflower seed (SS) in finishing diets was assessed in two feeding trials. In Exp. 1, 60 yearling steers (479 +/- 45 kg) were fed five diets (n = 12). A basal diet (DM basis) of 84.5% steam-rolled barley, 9% barley silage, and 6.5% supplement was fed as is (control), with all the silage replaced (DM basis) with rolled SS, or with grain:silage mix replaced with 9% whole SS, 14% whole SS, or 14% rolled SS. Liver, diaphragm, and brisket samples were obtained from each carcass. In Exp. 2, 120 yearling steers (354 +/- 25 kg) were fed corn- or barley-based diets containing no SS, high-linoleic acid SS, or high-oleic acid SS (a 2 x 3 factorial arrangement, n = 20). Whole SS was included at 10.8% in the corn-based and 14% in the barley-based diets (DM basis). In Exp. 1, feeding whole SS linearly increased DMI (P = 0.02), ADG (P = 0.01), and G:F (P = 0.01). Regression of ME against level of whole SS indicated that SS contained 4.4 to 5.9 Mcal ME/kg. Substituting whole for rolled SS did not significantly alter DMI, ADG, or G:F (8.55 vs. 8.30 kg/d; 1.36 vs. 1.31 kg; and 0.157 vs. 0.158, respectively). Replacing the silage with rolled SS had no effect on DMI (P = 0.91) but marginally enhanced ADG (P = 0.10) and improved G:F (P = 0.01). Dressing percent increased linearly (P = 0.08) with level of SS in the diet. Feeding SS decreased (P < 0.05) levels of 16:0 and 18:3 in both diaphragm and subcutaneous fats, and increased (P = 0.05) the prevalence of 18:1, 18:2, cis-9,trans-11-CLA and trans-10,cis-12-CLA in subcutaneous fat. In Exp. 2, barley diets supplemented with high-linoleic SS decreased DMI (P = 0.02) and ADG (P = 0.007) by steers throughout the trial, whereas no decrease was noted with corn (interaction P = 0.06 for DMI and P = 0.01 for ADG). With barley, high-linoleic SS decreased final live weight (554 vs. 592 kg; P = 0.01), carcass weight (329 vs. 346 kg; P = 0.06), and dressing percent (58.5 vs. 59.4%; P = 0.04). Steers fed high-linoleic SS plus barley had less (P < 0.05) backfat than those fed other SS diets. No adverse effects of SS on liver abscess incidence or meat quality were detected. Although they provide protein and fiber useful in formulating finishing diets for cattle, and did improve performance in Exp. 1, no benefit from substituting SS for grain and roughage was detected in Exp. 2. Because of unexplained inconsistencies between the two experiments, additional research is warranted to confirm the feeding value of SS in diets for feedlot cattle.

Adipose Tissue↗