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This study was undertaken to evaluate the cardiac dimensions and various indices of myocardial function, determined by echocardiography, in a group of 12 infants with congenital hypothyroidism. Left ventricular systolic and diastolic dimensions, posterior wall thickness, enddiastolic and systolic volumes were all significantly lower in the hypothyroid infants compared with 25 normal infants of the same age. No pericardial effusion was found. Hypothyroid infant had a lower heart rate with a reduced cardiac output. The mean velocity of circumferential fibre shortening and the shortening fraction of the left ventricle were normal. The pre-ejection period of the left ventricle (PEP), however, was abnormally prolonged as well as the ratio PEP over left ventricular ejection time (PEP/ET). This ratio correlated inversely with the end-diastolic volume, suggesting that the increased PEP/ET could be partly the result of decreased preload. [ABSTRACT FROM PUBLISHER]

Recently it has been shown that in patients with transposition of the great arteries the isometric relaxation time of the left ventricle could be negative in the presence of normal pulmonary artery pressure. In order to find an explanation for this apparently paradoxical situation, it was decided to evaluate the importance of the delay of closure of the pulmonary valve in 15 patients with transposition of the great arteries. This delay is called the hang-out time. The hang-out time was found to correlate inversely with the isometric relaxation time as well as with the pulmonary artery systolic (r = -0 . 70) and mean pressures. A weaker correlation was found between the isometric relaxation time and the time of mitral valve opening. These results show that in transposition of the great arteries with normal pulmonary artery pressure, the pulmonary valve has a prolonged hang-out time, to the extent that it frequently closes after the opening of the mitral valve, explaining the negative isometric relaxation time found in these cases. This finding may help in the non-invasive assessment of the pulmonary vascular resistance of patients with transposition of the great arteries. [ABSTRACT FROM PUBLISHER]

The pre-ejection period of the right ventricle in d-transposition of the great arteries is known to be prolonged, compared with the same interval of the left ventricle of normal subjects. In the present study, the echocardiographic measurement of the components of the pre-ejection period of the right ventricle of 14 patients with d-transposition of the great arteries shows that the isometric contraction time of the right ventricle in d-transposition of the great arteries is similar to the same interval calculated on the left ventricle of 76 normal children of comparable age. On the other hand, the electromechanical delay was significantly greater for the right ventricle of d-transposition of the great arteries than for the left ventricle of the normal subjects. It is concluded that the prolonged pre-ejection period of the right ventricle in d-transposition of the great arteries is not the result of right ventricular dysfunction but solely of a longer electromechanical delay. [ABSTRACT FROM PUBLISHER]

The study aimed to identify the best echocardiographic time interval (systolic or diastolic) for assessing pulmonary artery pressure in children with d-transposition of the great arteries. Echocardiograms were performed in 21 children with d-transposition of the great arteries within 48 hours of cardiac catheterisation. None of the children had had a Mustard procedure. Twenty-four recordings were obtained, three patients having been catheterised twice. Highest correlations were found for the ratio of the isovolumic relaxation time over the ejection time of the left ventricle (IRT/LVET) to the systolic pressure in the pulmonary artery and also between IRT/LVET and the difference between mean pulmonary artery pressure and mean left atrial pressure. All patients with a negative IRT/LVET ratio had a pulmonary systolic pressure lower than 35 mmHg and a mean pulmonary pressure lower than 25 mmHg. In patients with d-transposition, a negative IRT/LVET ratio appears to be a reliable indication of normal pressure in the pulmonary circulation. Serial echocardiographic studies for the follow-up of patients with d-transposition should include measurement of the time of relaxation of the left ventricle. [ABSTRACT FROM PUBLISHER]

Five multiparous, ruminally and duodenally cannulated Holstein cows were assigned to 5 x 5 Latin squares at wk 2 (experiment 1), wk 11 to 13 (experiment 2), and wk 17 to 19 postpartum (experiment 3) to determine extent of Met limitation. Treatments were duodenally infused and consisted of 10 g/d of L-Lys plus 0, 3.5, 7.0, 10.5, or 16.0 g/d of DL-Met in experiments 1 and 2 and 8 g/d of L-Lys plus 0, 5, 10, 15, or 20 g/d of DL-Met in experiment 3. Calculated Lys contributions to total AA (TAA) in duodenal digesta for control treatments were 8.6, 7.5, and 9.0% for experiments 1, 2, and 3, respectively. Methionine contributions to TAA for the 5 infusion treatments were 1.9, 2.1, 2.2, 2.4, and 2.7% for experiment 1; 2.1, 2.3, 2.4, 2.5, and 2.7% for experiment 2; and 1.8, 2.0, 2.2, 2.4, and 2.5% for experiment 3, respectively. Milk protein yield increased linearly in experiments 1 and 2, indicating that Met contribution to TAA in duodenal digesta for maximal milk protein synthesis exceeded 2.7 for early-lactation cows. In experiment 2, a quadratic relationship was found between level of infused Met and milk protein content, with the response reaching a plateau when 12.2 g of Met was infused, corresponding with a Met contribution to TAA in duodenal digesta of 2.4%. In experiment 3, milk protein content increased quadratically, but milk yield declined linearly with increasing levels of infused Met; hence, milk protein yield was unaffected by treatment. The calculated plateau point of the milk protein content response curve was determined to be 12.4 g of infused Met, which corresponds to a Met contribution to TAA in duodenal digesta of 2.3%. Experiment 3 results indicate that the required level of Met in duodenal digesta for maximizing milk protein yield is lower than that required for maximizing milk protein content. [ABSTRACT FROM AUTHOR]

Eighty-four Holstein cows were assigned to a randomized block experiment to determine effects of supplementing pre- and postpartum diets containing high-Lys protein supplements with rumen-protected Met and Lys. Before parturition, cows received a basal diet with 1) no rumen-protected amino acids (AA), 2) 10.5 g/d of Met from rumen-protected Met, or 3) 10.2 g/d of Met and 16.0 g/d of Lys from rumen-protected Met plus Lys. After parturition, cows continued to receive AA treatments but switched to diets balanced for 16.0 or 18.5% crude protein (CP). Diets were corn-based; supplemental protein was provided by soybean products and blood meal. Cows received treatments through d 105 of lactation. Compared with basal and Met-supplemented diets, Met + Lys supplementation increased yield of energy-corrected milk, fat, and protein, and tended to increase production of 3.5% fat-corrected milk. Significant CP x AA interactions were observed only for milk protein and fat content. Supplementation of the 16% CP diet with Met and Met + Lys had no effect on milk true protein and fat content. However, Met and Met + Lys supplementation of the 18.5% CP diet increased milk protein content by 0.21 and 0.14 percentage units, respectively, and Met supplementation increased fat content by 0.26 percentage units. Results of this study indicate that early-lactation cows fed corn-based diets are responsive to increased intestinal supplies of Lys and Met and that the responses depend on dietary CP concentration, supply of metabolizable protein, and intestinal digestibility of the rumen-undegradable fraction of supplemental proteins. [ABSTRACT FROM AUTHOR]

The objective of this study was to evaluate the effects of methionine supplementation prior to and during a lipopolysaccharide (LPS) challenge on the performance and inflammatory biomarkers of receiving beef steers. Steers ( n  = 65; 295.8 ± 46.5 kg) were randomly assigned to 3 treatment groups: L0 = Control, receiving no supplement; L1 = 10 g/hd/d rumen-protected methionine (MetaSmart, Adisseo USA Inc., Alpharetta, GA); and L2 = 20 g/hd/d rumen-protected methionine and fed for 40 d at the West Texas A&M University Research Feedlot. On day 40, a subset of steers ( n  = 32; L0 = 10; L1 = 11; L2 = 11) were transported to the USDA Livestock Issues Research Unit, and on day 41 steers were weighed and fitted with indwelling rectal thermometers and jugular catheters. On day 42, steers were challenged i.v. with LPS (0.25 µg/kg BW). Blood samples were collected at -2, 0, 2, 4, 6, 8, 10, 12, 18, 24, 36, and 48 h relative to the LPS administration at 0 h. Serum was isolated to determine serum chemistry and inflammatory marker concentrations. Whole blood was used for hematology analysis. There were no differences in DMI or ADG ( P  ≥ 0.75) during 35 d of supplementation. A treatment × time interaction ( P  = 0.01) occurred for rectal temperature, where L2 steers had the greatest temperature following the challenge ( P  ≤ 0.05) compared to L1 and L0 steers. There was a treatment × time interaction ( P  = 0.03) for the change in white blood cells where L0 steers had the greatest change compared to L1 and L2 steers at various timepoints. There was a treatment × time interaction ( P  = 0.02) for the change in tumor necrosis factor-α concentration, where there was a greater increase in concentration in L0 compared to L1 and L2 steers. Additionally, there was a treatment × time interaction ( P  < 0.01) for Macrophage Inflammatory Protein-1β (MIP-1β) concentrations, where concentrations were greater in L0 compared with L1 and L2 steers from 2 to 4 h post-challenge. There was a treatment × time interaction for plasma total protein concentration ( P  < 0.01) where L0 steers had less plasma total protein compared with L1 and L2 steers, while L1 steers had less plasma total protein than L2 steers at -2 h prior to LPS challenge. These data suggest that methionine supplementation may have an immunomodulatory effect in beef steers that may improve response to pathogens., (Published by Oxford University Press for the American Society of Animal Science 2024.)

The hippocampus (HP) receives neurochemically diverse inputs from the raphe nuclei, including glutamatergic axons characterized by the expression of the vesicular glutamate transporter type 3 (VGLUT3). These raphe-HP VGLUT3 projections have been suggested to play a critical role in HP functions, yet a complete anatomical overview of raphe VGLUT3 projections to the forebrain, and in particular to the HP, is lacking. Using anterograde viral tracing, we describe largely nonoverlapping VGLUT3-positive projections from the dorsal raphe (DR) and median raphe (MnR) to the forebrain, with the HP receiving inputs from the MnR. A limited subset of forebrain regions such as the amygdaloid complex, claustrum, and hypothalamus receives projections from both the DR and MnR that remain largely segregated. This highly complementary anatomical pattern suggests contrasting roles for DR and MnR VGLUT3 neurons. To further analyze the topography of VGLUT3 raphe projections to the HP, we used retrograde tracing and found that HP-projecting VGLUT3-positive neurons (VGLUT3 HP ) distribute over several raphe subregions (including the MnR, paramedian raphe, and B9 cell group) and lack co-expression of serotonergic markers. Strikingly, double retrograde tracing experiments unraveled two parallel streams of VGLUT3-positive projections targeting the dorsal and ventral poles of the HP. These results demonstrate highly organized and segregated VGLUT3-positive projections to the HP, suggesting independent modulation of HP functions such as spatial memory and emotion-related behavior., (© 2023 Wiley Periodicals LLC.)

Conducting polymer coatings on metal electrodes are an efficient solution to improve neural signal recording and stimulation, due to their mixed electronic-ionic conduction and biocompatibility. To date, only a few studies have been reported on conducting polymer coatings on metallic wire electrodes for muscle signal recording. Chronic muscle signal recording of freely moving animals can be challenging to acquire with coated electrodes, due to muscle movement around the electrode that can increase instances of coating delamination and device failure. The poor adhesion of conducting polymers to some inorganic substrates and the possible degradation of their electrochemical properties after harsh treatments, such as sterilization, or during implantation limits their use for biomedical applications. Here, we demonstrate the mechanical and electrochemical stability of the conducting polymer, poly(3,4-ethylenedioxythiophene) (PEDOT) doped with LiClO 4 , deposited on stainless steel multistranded wire electrodes for invasive muscle signal recording in mice. The mechanical and electrochemical stability was achieved by tuning the electropolymerization conditions. PEDOT-coated and bare stainless steel electrodes were implanted in the neck muscle of five mice for electromyographic (EMG) activity recording over a period of 6 weeks. The PEDOT coating improved the electrochemical properties of the stainless steel electrodes, lowering the impedance, resulting in an enhanced signal-to-noise ratio during in vivo EMG recording compared to bare electrodes.

Hippocampal theta rhythm arises from a combination of recently described intrinsic theta oscillators and inputs from multiple brain areas. Interneurons expressing the markers parvalbumin (PV) and somatostatin (SOM) are leading candidates to participate in intrinsic rhythm generation and principal cell (PC) coordination in distal CA1 and subiculum. We tested their involvement by optogenetically activating and silencing PV or SOM interneurons in an intact hippocampus preparation that preserves intrinsic connections and oscillates spontaneously at theta frequencies. Despite evidence suggesting that SOM interneurons are crucial for theta, optogenetic manipulation of these interneurons modestly influenced theta rhythm. However, SOM interneurons were able to strongly modulate temporoammonic inputs. In contrast, activation of PV interneurons powerfully controlled PC network and rhythm generation optimally at 8 Hz, while continuously silencing them disrupted theta. Our results thus demonstrate a pivotal role of PV but not SOM interneurons for PC synchronization and the emergence of intrinsic hippocampal theta., (Copyright © 2015 Elsevier Inc. All rights reserved.)

FATP1 is involved in lipid transport into cells and in intracellular lipid metabolism. We showed previously that this protein interacts with and inhibits the limiting-step isomerase of the visual cycle RPE65. Here, we aimed to analyze the effect of Fatp1-deficiency in vivo on the visual cycle, structure and function, and on retinal aging. Among the Fatp family members, we observed that only Fatp1 and 4 are expressed in the control retina, in both the neuroretina and the retinal pigment epithelium. In the neuroretina, Fatp1 is mostly expressed in photoreceptors. In young adult Fatp1(-/-) mice, Fatp4 expression was unchanged in retinal pigment epithelium and reduced two-fold in the neuroretina as compared to Fatp1(+/+) mice. The Fatp1(-/-) mice had a preserved retinal structure but a decreased electroretinogram response to light. These mice also displayed a delayed recovery of the b-wave amplitude after bleaching, however, visual cycle speed was unchanged, and both retinal pigment epithelium and photoreceptors presented the same fatty acid pattern compared to controls. In 2 year-old Fatp1(-/-) mice, transmission electron microscopy studies showed specific abnormalities in the retinas comprising choroid vascularization anomalies and thickening of the Bruch membrane with material deposits, and sometimes local disorganization of the photoreceptor outer segments. These anomalies lead us to speculate that the absence of FATP1 accelerates the aging process.

Post-mortem studies suggest that GABAergic neurotransmission is impaired in schizophrenia. However, it remains unclear if these changes occur early during development and how they impact overall network activity. To investigate this, we used a mouse model of prenatal infection with the viral mimic, polyriboinosinic-polyribocytidilic acid (poly I:C), a model based on epidemiological evidence that an immune challenge during pregnancy increases the prevalence of schizophrenia in the offspring. We found that prenatal infection reduced the density of parvalbumin- but not somatostatin-positive interneurons in the CA1 area of the hippocampus and strongly reduced the strength of inhibition early during postnatal development. Furthermore, using an intact hippocampal preparation in vitro, we found reduced theta oscillation generated in the CA1 area. Taken together, these results suggest that redistribution in excitatory and inhibitory transmission locally in the CA1 is associated with a significant alteration in network function. Furthermore, given the role of theta rhythm in memory, our results demonstrate how a risk factor for schizophrenia can affect network function early in development that could contribute to cognitive deficits observed later in the disease.

The shape and volume of microglia (brain immune cells) change when they activate during brain inflammation and become migratory and phagocytic. Swollen rat microglia express a large Cl(-) current (I(Clswell)), whose biophysical properties and functional roles are poorly understood and whose molecular identity is unknown. We constructed a fingerprint of useful biophysical properties for comparison with I(Clswell) in other cell types and with cloned Cl(-) channels. The microglial I(Clswell) was rapidly activated by cell swelling but not by voltage, and showed no time-dependence during voltage-clamp steps. Like I(Clswell) in many cell types, the halide selectivity sequence was I(-) > Br(-) > Cl(-) > F(-). However, it differed in lacking inactivation, even at +100 mV with high extracellular Mg(2+), and in having a much lower single-channel conductance: 1-3 pS. Based on these fundamental differences, the microglia channel is apparently a different gene product than the more common intermediate-conductance I(Clswell). Microglia express several candidate genes, with relative mRNA expression levels of: CLIC1 > ClC3 > I(Cln) > or = ClC2 > Best2 > Best1 > or = Best3 > Best4. Using a pharmacological toolbox, we show that all drugs that reduced the microglia current (NPPB, IAA-94, flufenamic acid and DIOA) increased the resting cell volume in isotonic solution and inhibited the regulatory volume decrease that followed cell swelling in hypotonic solution. Both channel blockers tested (NPPB and flufenamic acid) dose-dependently inhibited microglia phagocytosis of E. coli bacteria. Because I(Clswell) is involved in microglia functions that involve shape and volume changes, it is potentially important for controlling their ability to migrate to damage sites and phagocytose dead cells and debris.

Objectives: To determine, in North American children, reference values for respiratory resistance measurements by the forced oscillation (Rfo) technique and to examine whether sitting height, as index of truncal length, is a better determinant of resistance, less influenced by race and gender, than standing height., Design/setting: A prospective cross-sectional study of healthy nonobese children, carefully selected for absence of atopy, exposure to tobacco smoke, and recent upper respiratory tract infection., Measurements: Three measurements of respiratory resistance by forced oscillation were obtained at the fixed frequencies of 8 Hz (Rfo8), 12 Hz (Rfo12), and at 16 Hz (Rfo16) using the Custo Vit R (Custo Med GMBH; Munich, Germany). In cooperative children, routine spirometry (FEV1, FVC, and peak expiratory flow rate [PEFR]) was also performed., Results: We recruited 217 healthy children aged 3 to 17 years. Reproducible measurements of Rfo8 were obtained for 206 children, Rfo12 for 197 children, and Rfo16 for 209 children. Normal FEV1, FVC, and PEFR values were documented in all 69 subjects who were able to reproducibly cooperate with spirometry. Multiple linear regression identified measurements of either sitting or standing height as the best, and equally strong, determinants of respiratory resistance at all three frequencies. Gender and race were not important factors once either sitting or standing height measurement was considered. Our regression equations at 8 Hz are comparable to published reference values obtained at fixed frequencies of 6, 8, and 10 Hz using other instruments. However, in comparison to our results, prior values tended to underestimate resistance in the shortest children or to overestimate it in the tallest ones. Our regression equation for Rfo12 is similar to the only previously published one, while no reference values at 16 Hz were available for comparison., Conclusions: Height is the best predictor for total respiratory resistance at 8, 12, and 16 Hz in children aged > or = 3 years. Use of sitting height does not appear to be a stronger determinant of resistance than standing height.

Lactation diets based on wilted alfalfa silage and heated whole soybeans are common in the midwestern US. We examined the milk production response of multiparous Holstein cows to the addition of ruminally protected methionine at two percentages to a basal total mixed ration. An additional total mixed ration included both methionine and lysine supplementation. Sixteen Holstein cows in early lactation were used in a replicated 4 x 4 Latin square design with 21-d periods. Milk production, milk composition, and dry matter intake were determined for the last 5 d of each period. Milk production (41.5 kg/d), dry matter intake (25.9 kg/d), and milk fat concentration (3.26%) were unaffected by the supplementation of amino acids. The addition of methionine increased milk protein concentration and yield linearly. Each gram of methionine increased milk protein yield by 4 g, and milk protein concentration increased from 2.89 to 2.99% with the addition of 10.5 g/d of methionine. The proportion of casein N in total milk N was unaffected by treatment. The addition of lysine did not elicit a response. Total mixed rations based on alfalfa haylage, heated soybeans, and animal proteins were clearly limited by their methionine content but were adequate in their lysine content.

In this paper, we study the problem of estimating non-parametrically a quantile regression curve as it applies to computing reference values. We propose an automatic procedure that uses a symmetrized nearest-neighbor kernel estimator of conditional distributions. We also discuss ways of measuring the dispersion of quantile regression estimator. One is based on the asymptotic distribution of such quantiles, while the other relies on the bootstrap method. The results of a small simulation study show that the methods of the paper perform rather well even in a situation where a good parametric solution is available. As an example, we analyze a small part of a data set that was collected to establish reference values for blood velocity in different parts of the umbilical cord of human fetuse as they grow toward birth.

Sixty multiparous Holsteins were used in a 200-d continuous lactation trial designed to measure the response to a mixture of ruminally protected Met and Lys. Response to AA was determined at two dietary concentrations of degraded protein designed to provide 85 and 100% of NRC recommended amounts. This difference in degraded protein content was achieved by addition of urea. Diets without urea supported lactation as well as diets with added urea in early lactation. In midlactation, urea addition was detrimental to yields of milk and milk protein; addition of AA prevented this negative effect. In early lactation, AA addition raised milk protein concentration and yield by 1 g/kg of milk of 37 g/d and did not interact with urea. Increases in protein concentration in response to AA addition were similar in early and late lactation and corresponded to changes in the casein fraction of milk. These results support previous work showing the importance of adequate absorbable Lys and Met to maximize the protein content of milk. The results suggest that interactions may occur between ruminal ammonia production and AA supply.