Timing of Primary Surgery for Cleft Palate.

BACKGROUND: Among infants with isolated cleft palate, whether primary surgery at 6 months of age is more beneficial than surgery at 12 months of age with respect to speech outcomes, hearing outcomes, dentofacial development, and safety is unknown. METHODS: We randomly assigned infants with nonsyndromic isolated cleft palate, in a 1:1 ratio, to undergo standardized primary surgery at 6 months of age (6-month group) or at 12 months of age (12-month group) for closure of the cleft. Standardized assessments of quality-checked video and audio recordings at 1, 3, and 5 years of age were performed independently by speech and language therapists who were unaware of the trial-group assignments. The primary outcome was velopharyngeal insufficiency at 5 years of age, defined as a velopharyngeal composite summary score of at least 4 (scores range from 0 to 6, with higher scores indicating greater severity). Secondary outcomes included speech development, postoperative complications, hearing sensitivity, dentofacial development, and growth. RESULTS: We randomly assigned 558 infants at 23 centers across Europe and South America to undergo surgery at 6 months of age (281 infants) or at 12 months of age (277 infants). Speech recordings from 235 infants (83.6%) in the 6-month group and 226 (81.6%) in the 12-month group were analyzable. Insufficient velopharyngeal function at 5 years of age was observed in 21 of 235 infants (8.9%) in the 6-month group as compared with 34 of 226 (15.0%) in the 12-month group (risk ratio, 0.59; 95% confidence interval, 0.36 to 0.99; P = 0.04). Postoperative complications were infrequent and similar in the 6-month and 12-month groups. Four serious adverse events were reported (three in the 6-month group and one in the 12-month group) and had resolved at follow-up. CONCLUSIONS: Medically fit infants who underwent primary surgery for isolated cleft palate in adequately resourced settings at 6 months of age were less likely to have velopharyngeal insufficiency at the age of 5 years than those who had surgery at 12 months of age. (Funded by the National Institute of Dental and Craniofacial Research; TOPS ClinicalTrials.gov number, NCT00993551.).

Selenium Speciation Analysis Reveals Improved Antioxidant Status in Finisher Pigs Fed L-Selenomethionine, Alone or Combined with Sodium Selenite, and Vitamin E.

Conditions associated with selenium (Se) and/or vitamin E (VitE) deficiency are still being reported in high-yielding pigs fed the recommended amounts. Here, the dietary effects of Se source (sodium selenite, NaSe, 0.40 or 0.65 mg Se/kg; L-selenomethionine, SeMet, 0.19 or 0.44 mg Se/kg; a NaSe-SeMet mixture, SeMix, 0.44-0.46 mg Se/kg) and VitE concentration (27, 50-53 or 101 mg/kg) on the antioxidant status of finisher pigs were compared with those in pigs fed non-Se-supplemented diets (0.08-0.09 mg Se/kg). Compared to NaSe-enriched diets, SeMet-supplemented diets resulted in significantly (p < 0.0018) higher plasma concentrations of total Se (14-27%) and selenospecies (GPx3, SelP, SeAlb; 7-83%), significantly increased the total Se accumulation in skeletal muscles, myocardium, liver and brain (10-650%), and enhanced the VitE levels in plasma (15-74%) and tissues (8-33%) by the end of the 80-day trial, proving better Se distribution and retention in pigs fed organic Se. Injecting lipopolysaccharide (LPS) intravenously half-way into the trial provoked a pyrogenic response in the pigs followed by a rapid increase of inorganic Se after 5-12 h, a drastic drop of SeMet levels between 12 and 24 h that recovered by 48 h, and a small increase of SeCys by 24-48 h, together with a gradual rise of GPx3, SelP and SeAlb in plasma up to 48 h. These changes in Se speciation in plasma were particularly significant (0.0024 > p > 0.00007) in pigs receiving SeMet- (0.44 mg Se/kg, above EU-legislated limits) or SeMix-supplemented (SeMet and NaSe both at 0.2 mg Se/kg, within EU-legislated limits) diets, which demonstrates Se metabolism upregulation to counteract the LPS-induced oxidative stress and a strengthened antioxidant capacity in these pigs. Overall, a Se source combination (without exceeding EU-legislated limits) and sufficient VitE supplementation (≥ 50 mg/kg) improved the pigs' antioxidant status, while doubling the allowed dietary organic Se increased the Se in tissues up to sixfold without compromising the animal's health due to toxicity. This study renders valuable results for revising the current dietary SeMet limits in swine rations.

A wearable microwave instrument can detect and monitor traumatic abdominal injuries in a porcine model.

Abdominal injury is a frequent cause of death for trauma patients, and early recognition is essential to limit fatalities. There is a need for a wearable sensor system for prehospital settings that can detect and monitor bleeding in the abdomen (hemoperitoneum). This study evaluates the potential for microwave technology to fill that gap. A simple prototype of a wearable microwave sensor was constructed using eight antennas. A realistic porcine model of hemoperitoneum was developed using anesthetized pigs. Ten animals were measured at healthy state and at two sizes of bleeding. Statistical tests and a machine learning method were used to evaluate blood detection sensitivity. All subjects presented similar changes due to accumulation of blood, which dampened the microwave signal ([Formula: see text]). The machine learning analysis yielded an area under the receiver operating characteristic (ROC) curve (AUC) of 0.93, showing 100% sensitivity at 90% specificity. Large inter-individual variability of the healthy state signal complicated differentiation of bleedings from healthy state. A wearable microwave instrument has potential for accurate detection and monitoring of hemoperitoneum, with automated analysis making the instrument easy-to-use. Future hardware development is necessary to suppress measurement system variability and enable detection of smaller bleedings.

Federation of European Laboratory Animal Science Associations recommendations of best practices for the health management of ruminants and pigs used for scientific and educational purposes.

Most ruminants and pigs used for scientific and educational aims are bred not for these purposes but in a farm environment. Given the wide range of diseases that these species might have, ensuring that the animals' health status is appropriate can be complex and challenging. The Federation of European Laboratory Animal Science Associations has previously published recommendations for the health monitoring of experimental colonies of pigs (1998) and, respectively, calves, sheep and goats (2000). Unfortunately, the uptake of those recommendations was poor and insufficiently reported in scientific publications. These new recommendations for best practice focus on the main species of ruminants (cattle, sheep and goats) and pigs. They provide general and specific information helpful for designing a health management programme for the suppliers and for the user establishments, as well as guidance on animal procurement. Critical thinking based on the fields of use of the animals is promoted, aiming to help in taking informed decisions rather than establishing an exhaustive exclusion list for pathogens. Implementing the best health and welfare management practices should be done under the guidance of a competent attending veterinarian, with expertise and sufficient authority to take the appropriate action, doubled by excellent communication skills. It is strongly recommended that the user establishment's veterinarian works in close collaboration with the supplier's veterinarian.

Beneficial antioxidant status of piglets from sows fed selenomethionine compared with piglets from sows fed sodium selenite.

BACKGROUND: Studies in mammals proved dietary organic selenium (Se) being superior to inorganic Se regarding effects on growth performance, antioxidative status, immune response, and Se homeostasis. However, the picture of possible effects of different Se sources and - levels can be expanded. The present field study evaluated the effects on weight gain, hematological and selected biochemical variables as well as plasma concentrations of vitamin E (vitE), total Se and selenobiomolecules in piglets throughout the suckling period. METHODS: Piglets were monitored from birth to 38 days of age (d). The mother sows' diets were enriched with l-selenomethionine (SeMet-0.26 and -0.43 mg Se/kg feed) or sodium selenite (NaSe-0.40 and -0.60 mg Se/kg feed) from 1 month prior to farrowing until the end of lactation period. Piglets received pelleted feed supplemented with Se similarly to the sows' diets from one week of age. Selenite at 0.40 mg Se/kg (NaSe-0.40) represents a common Se source and -level in pig feed and served as control diet. RESULTS: From 24d, piglets in SeMet-groups had higher mean body weight (BW) compared with piglets from sows fed NaSe-0.40. Furthermore, from five-d and above, piglets from sows fed NaSe-0.60 had significantly higher BW than offspring from sows fed NaSe-0.40. Neonatal piglets in group SeMet-0.43 had significantly lower red blood cell counts (RBC), hemoglobin (Hgb) and hematocrit (Hct) concentrations compared with piglets from sows fed with NaSe-0.40. Neonatal and 5d-old piglets in group SeMet-0.26 showed higher gamma-glutamyl transferase activity than piglets in group NaSe-0.40. From five d and above, group NaSe-0.60 excelled with increased specific hematological variables culminating at age 38d with increased Hct, mean corpuscular volume (MCV), and MC hemoglobin (MCH) as well as increased activities of aspartate transaminase and lactate dehydrogenase compared with the other groups. Generally, offspring in the SeMet groups had higher total Se-concentrations in plasma than those from sows fed selenite, and showed a dose-response effect on plasma Se-concentrations. Furthermore, SeMet-fed piglets had higher plasma levels of the selenoproteins (Sel) glutathione peroxidase 3 (GPx3) and SelP as well as selenoalbumin. Plasma vitE levels were significantly negatively correlated with RBC throughout trial period. CONCLUSIONS: Maternal supplementation with SeMet during gestation influenced hematology and clinical biochemistry in neonatal piglets in a different way than in offspring from sows receiving selenite enriched diets. Growth performance was positively influenced by both dietary Se source and Se level. Higher plasma levels of GPx3 observed in piglets receiving SeMet probably improved the protection against birth or growth related oxidative stress. These might prime the piglets for demanding situations as indicated by higher weight gain in offspring from sows fed with SeMet-supplemented diets. Our results on some enzyme activities might indicate that piglets fed NaSe-0.60 had to cope with increased levels of oxidative stress compared with those originating from sows fed SeMet or lower dietary levels of selenite. We assume that combining inorganic and organic Se sources in complete feed for breeding sows might be beneficial fro reproduction and the offspring's performance.

A descriptive report of the selenium distribution in tissues from pigs with mulberry heart disease (MHD).

BACKGROUND: Mulberry Heart Disease (MHD) is a condition affecting mainly young pigs in excellent body condition. Feed efficient pigs showing high average daily gains are more likely to be affected. MHD has been described as a challenge in Norwegian pig production over the last decade despite abundant supplies of vitamin E, and selenium (Se) close to the upper limits set by the EU. From 2015 to 2017, samples from documented MHD field cases were collected and compared with controls regarding post mortem findings and Se concentrations in numerous internal and external organs were determined in order to characterize the Se distribution, and to identify any differences between MHD cases and controls. CASE PRESENTATION: Eight MHD cases from commercial farms and a pet pig producer located in the South West and East of Norway, and three control animals originating from these farms were included in this study. MHD cases and controls were weaned pigs with an average bodyweight (BW) of 17 kg (range 9 to 46 kg BW), with the exception of one pet piglet (Mangalica, 6 kg BW) that had only received sow milk. Selenium was determined in samples from the cardiovascular, digestive, immune, endocrine, integumentary, muscular, respiratory and urinary systems using inductively coupled plasma mass spectrometry (QQQ ICP-MS). All pigs with MHD suffered sudden deaths. Control animals were euthanized without being bled prior to necropsy and sampling. Significantly different mean Se concentrations between MHD cases and controls were found in cardiac samples as well as almost all skeletal muscles (P < 0.05). Based on the samples from ten different muscles (except the cardiac samples), mean Se concentrations in MHD cases were 0.34 (0.01) mg/ kg DM compared with 0.65 (0.02) mg/ kg DM in control pigs (P < 0.0001). In cardiac samples, mean Se concentrations from MHD cases were 0.87 (0.02) mg/ kg DM vs. 1.12 (0.04) mg/ kg DM (P < 0.0001). Additionally, significantly lower Se concentrations compared with controls were found in the liver as well as the caecum, duodenum, gastric ventricle, jejunum, kidney, skin and thymus samples. CONCLUSIONS: Based on the present work, the current common practice regarding tissue analyses in MHD cases could be refined to include other organs than liver and heart. The evident differences in mean Se concentrations in 9 out of 10 samples from the muscular system, could make such samples relevant for complementary measurements of Se concentrations to help confirm the MHD diagnosis. We find it interesting that although our limited number of sampled pigs are different in terms of genetics, size and feeding regimes, the variation of Se concentrations in a given organ was low between MHD cases. Since this report includes a limited number of MHD cases and controls, our results should be corroborated by a controlled, larger study.

Effects of sodium selenite and L-selenomethionine on feed intake, clinically relevant blood parameters and selenium species in plasma, colostrum and milk from high-yielding sows.

A field study in periparturient sows fed different dietary concentrations of either sodium selenite or L-selenomethionine (SeMet) was conducted to evaluate feed intake, haematological and biochemical parameters as well as to describe some key selenium (Se) species, namely selenoprotein P (SelP), selenoalbumin (SeAlb) and selenomethionine (SeMet) as well as total Se in plasma, colostrum and milk. Thirty-two sows were allotted to four treatments from 30 days (d) prepartum throughout on average a 32 d lactation period. Sodium selenite supplemented diets contained 0.40 and 0.60 mg Se/kg feed, while SeMet supplemented feed contained 0.26 and 0.43 mg Se/kg feed. Concentrations of sodium selenite and SeMet in complete feed exceeded the upper limits for total dietary Se and added organic Se, respectively, according to the European Union legislation. Blood samples were collected at initiation of the study, at farrowing and at weaning. Colostrum samples were collected at farrowing and milk samples at weaning. Se species were subjected to liquid chromatography, and total Se and Se species were determined using inductively coupled plasma mass spectrometry. The SeMet supplemented diets resulted in higher feed intake and in higher levels of total Se, SelP, SeAlb and SeMet in colostrum compared with sows fed sodium selenite. Similar results were obtained for levels of total Se and SeMet in milk at weaning. The higher dietary sodium selenite concentration in sows' feed did not increase the Se transfer into colostrum or milk when compared with those receiving the lower level of sodium selenite. However, the increase in serum-Zn from initiation until farrowing, observed in sows fed SeMet as well as the higher glutamate dehydrogenase activity in sodium selenite supplemented sows in this period might indicate a higher requirement of antioxidant defence in sodium selenite-supplemented sows. To our knowledge, the present data on Se species in plasma, colostrum and milk of sows represent the most complete investigation of Se in sows conducted to date. A higher amount of the above-mentioned Se species in the colostrum of sows supplemented with SeMet might strengthen the piglets' antioxidative system and passive immunity as well as improve their average daily weight gain. The higher feed intake in sows fed diets supplemented with SeMet is an interesting finding that warrants further investigation.

Developments of reproductive management and biotechnology in the pig.

This review aims to describe changes in production environment, management tools and technology to alleviate problems seen with the present hyperprolific sow model. Successful parturition in the pig includes the possibility to express adequate maternal behaviour, rapid expulsion of piglets, complete expulsion of placenta, elimination of uterine contamination and debris, neonatal activity and colostrum intake. We focus on management of large litters, including maternal behaviour, ease of parturition, colostrum production, piglet quality parameters and intermittent suckling. There are also some interesting developments in technology to assess colostrum and immune state of the piglet. These developments may be utilized to improve the success rate of reproductive management around farrowing, lactation and after weaning. We also discuss new insights in how to examine the health of the mammary gland, uterus and ovaries of hyperprolific sows. Finally, we assess the latest developments on breeding and technology of hyperprolific sows, including artificial insemination (AI), real-time ultrasound of the genital tract and embryo transfer (ET). We conclude that 1) for the sow to produce sufficient colostrum, both the behavioural and physiological needs of the sow need to be met before and after parturition. Furthermore, 2) new ultrasound and biopsy technology can be effectively applied for accurate diagnosis of inflammatory processes of the udder and uterus and timing of AI regarding ovulation to improve insemination efficiency. Finally, 3) developments in cryopreservation of germ cells and embryos appear promising but lack of valid oocyte collection techniques and nonsurgical ET techniques are a bottleneck to commercial ET. These latest developments in management of parturition and reproductive technology are necessary to cope with the increasing challenges associated with very large litter sizes.

Effects of dietary sodium selenite and organic selenium sources on immune and inflammatory responses and selenium deposition in growing pigs.

The study was conducted to compare effects of different dietary Se sources (sodium selenite [NaSe], Se-enriched yeast [Se yeast] or L-selenomethionine [SeMet]) and one Se-deficient control diet on the expression of selected genes, hematological and clinical biochemical parameters, and muscle morphology in two parallel trials with finisher pigs. Se concentrations in blood plasma and tissues were also monitored. From the pigs in one of the parallel groups, muscle samples obtained from Musculus longissimus dorsi (LD) before and during the trial were examined. The pigs in the other parallel group were challenged once with lipopolysaccharide (LPS) intravenously. Transcriptional analyses of LD showed that selenogenes SelenoW and H were higher expressed in pigs fed Se-supplemented diets compared with control. Furthermore, the expression of interferon gamma and cyclooxygenase 2 was lower in the Se-supplemented pigs versus control. In whole blood samples prior to LPS, SelenoN, SelenoS and thioredoxin reductase 1 were higher expressed in pigs fed NaSe supplemented feed compared with the other groups, possibly indicating a higher level of oxidative stress. After LPS exposure glutathione peroxidase 1 and SelenoN were more reduced in pigs fed NaSe compared with pigs fed organic Se. Products of most above-mentioned genes are intertwined with the oxidant-antioxidant system. No significant effects of Se-source were found on hematologic parameters or microscopic anatomy. The Se-concentrations in various skeletal muscles and heart muscle were significantly different between the groups, with highest concentrations in pigs fed SeMet, followed by those fed Se yeast, NaSe, and control diet. Consistent with previous reports our results indicate that dietary Se at adequate levels can support the body's antioxidant system. Our results indicate that muscle fibers of pigs fed organic Se are less vulnerable to oxidative stress compared with the other groups.

Selenium deficiency associated porcine and human cardiomyopathies.

Selenium (Se) is a trace element playing an important role in animal and human physiological homeostasis. It is a key component in selenoproteins (SeP) exerting multiple actions on endocrine, immune, inflammatory and reproductive processes. The SeP family of glutathione peroxidases (GSH-Px) inactivates peroxides and thereby maintains physiological muscle function in humans and animals. Animals with high feed conversion efficiency and substantial muscle mass have shown susceptibility to Se deficiency related diseases since nutritional requirements of the organism may not be covered. Mulberry Heart Disease (MHD) in pigs is an important manifestation of Se deficiency often implicating acute heart failure and sudden death without prior clinical signs. Post-mortem findings include hemorrhagic and pale myocardial areas accompanied by fluid accumulation in the pericardial sac and pleural cavity. Challenges in MHD are emerging in various parts of the world. Se is of fundamental importance also to human health. In the 1930s the Se deficiency associated cardiomyopathy named Keshan Disease (KD) was described for the first time in China. Various manifestations, such as cardiogenic shock, enlarged heart, congestive heart failure, and cardiac arrhythmias are common. Multifocal necrosis and fibrous replacement of myocardium are characteristic findings. Pathological findings in MD and KD show striking similarities.

Bile enhances glucose uptake, reduces permeability, and modulates effects of lectins, trypsin inhibitors and saponins on intestinal tissue.

Antinutritional factors (ANFs) can disrupt digestive and other intestinal functions. ANFs in soybean meal (SBM) are implicated in proliferative and inflammatory responses in the intestine of various (functionally) monogastric animals, including Atlantic salmon (Salmo salar L.). The goal of the current study was to investigate the effect of ex vivo exposure of mid and distal intestinal tissue of salmon to soybean saponins (SAP), lectin (LEC) and Kunitz' trypsin inhibitor (KTI), singly and in combination, on epithelial function, as assessed by measuring in vitro glucose uptake pathways along a glucose concentration gradient. As solubilization of SAP in the calcium-containing Ringer's solution was problematic but resolved with the addition of a physiological concentration of bile collected from the gall bladder of salmon, an evaluation of bile effects became an added element. Results indicated that bile increased baseline glucose absorption and possibly transport, and also had a protective effect on the epithelial barrier, at least partially due to taurocholate. Compared to controls, tissues exposed to LEC+bile, KTI+bile and LEC+KTI+bile exhibited increased glucose uptake at the higher glucose concentrations, apparently due to markedly increased tissue permeability. Addition of SAP, however, attenuated the response, possibly by binding bile components. SAP+bile, also in combination with LEC and/or KTI, as well as LEC, KTI and LEC+KTI without bile often reduced transcellular glucose uptake pathways, while maintaining low tissue permeability. SAP+LEC+KTI+bile, LEC and KTI caused the most marked reductions. The distal intestine was more affected, reflecting the restriction of in vivo SBM-induced inflammatory changes to this region.

Superiorly based pharyngeal flap for treatment of velopharyngeal insufficiency in patients with 22q11.2 deletion syndrome.

BACKGROUND: There are no previous blinded studies for comparison of preoperative versus postoperative perceptual speech assessments when using a pharyngeal flap for treating velopharyngeal insufficiency (VPI) in patients diagnosed with 22q11.2 deletion syndrome. The aim of the study was to evaluate the effect of superiorly based pharyngeal flap surgery on speech in these patients using blinded judgments of experienced speech therapists. METHODS: A retrospective study of 12 consecutive patients who had undergone pharyngeal flap surgery for treatment of VPI between 2002 and 2009 was conducted. Seven girls and 5 boys between 4 and 15 (median, 6) years old at the time of surgery were included in the study. Six patients were born with a submucous cleft palate (including 2 occult), and 1 patient, with an overt cleft palate. The remaining 5 patients had no signs of a palatal pathology. All palatal clefts had been repaired before pharyngeal flap surgery except in 2 patients with occult submucous cleft palate. Preoperative and postoperative audio recordings were blinded for scoring independently by 3 senior speech therapists. RESULTS: There was a significant improvement in hypernasality (P = 0.002), audible nasal emission (P = 0.033), weak pressure consonants (P = 0.008), and speech intelligibility (P = 0.021) after pharyngeal flap surgery. Hyponasality did not develop significantly with surgery. One patient was diagnosed with obstructive sleep apnea. CONCLUSIONS: Superiorly based pharyngeal flap resulted in a significant speech improvement in 12 consecutive patients with 22q11.2 deletion syndrome having VPI.