Small intestinal volvulus in 47 cows.

Objective: To describe the findings, treatment, and outcome of small intestinal volvulus (SIV) in 47 cows. Animals and procedure: Retrospective analysis of medical records. Comparison of the findings for 18 surviving and 29 non-surviving cows. Results: The most common abnormal vital signs were tachycardia (68.0%), tachypnea (59.6%), and decreased rectal temperature (51.1%). Signs of colic occurred in 66.0% of cows in the study. Rumen motility was reduced or absent in 93.6% of cows, and intestinal motility in 76.6%. Clinical signs on ballottement and/or percussion and simultaneous auscultation were positive on the right side in 78.7% of cows. Transrectal examination showed dilated small intestines in 48.9% of cows. The rectum contained little or no feces in 93.6% of cows. The principal laboratory abnormalities were hypocalcemia (74.1%), hypokalemia (73.8%), azotemia (62.8%), hypermagnesemia (61.6%), and hemoconcentration (60.0%). The principal ultrasonographic findings were dilated small intestines (87.1%) and reduced or absent small intestinal motility (85.2%). Forty-one of the 47 cows underwent right flank laparotomy and the SIV was reduced in 21 cows. When comparing the clinical and laboratory findings of 18 surviving and 29 non-surviving cows, the groups differed significantly with respect to severely abnormal general condition (16.7 versus 37.9%), rumen stasis (22.2 versus 79.3%), intestinal atony (16.7 versus 48.3%), serum urea concentration (6.5 versus 9.8 mmol/L), and serum magnesium concentration (0.98 versus 1.30 mmol/L). In summary, 38.3% of the cows were discharged and 61.7% were euthanized before, during, or after surgery. Conclusion and clinical relevance: An acute course of disease, little or no feces in the rectum, and dilated small intestines were characteristic of SIV in this study population.

Volvulus de l'intestin grêle chez 47 vaches. Objectif: Décrire les données, le traitement et les résultats du volvulus de l'intestin grêle (SIV) chez 47 vaches. Animaux et procédure: Analyse rétrospective des dossiers médicaux. Comparaison des résultats pour 18 vaches survivantes et 29 vaches non survivantes. Résultats: Les signes vitaux anormaux les plus courants étaient la tachycardie (68,0 %), la tachypnée (59,6 %) et la diminution de la température rectale (51,1 %). Des signes de coliques sont apparus chez 66,0 % des vaches étudiées. La motilité du rumen était réduite ou absente chez 93,6 % des vaches et la motilité intestinale chez 76,6 %. Les signes cliniques de ballottement et/ou percussion et auscultation simultanée étaient positifs du côté droit chez 78,7 % des vaches. L'examen transrectal a montré une dilatation de l'intestin grêle chez 48,9 % des vaches. Le rectum contenait peu ou pas de matières fécales chez 93,6 % des vaches. Les principales anomalies des analyses de laboratoire étaient l'hypocalcémie (74,1 %), l'hypokaliémie (73,8 %), l'azotémie (62,8 %), l'hypermagnésémie (61,6 %) et l'hémoconcentration (60,0 %). Les principaux résultats échographiques étaient une dilatation de l'intestin grêle (87,1 %) et une motilité intestinale réduite ou absente (85,2 %). Quarante et une des 47 vaches ont subi une laparotomie du flanc droit et le SIV a été corrigé chez 21 vaches. En comparant les résultats cliniques et biologiques de 18 vaches survivantes et de 29 vaches non survivantes, les groupes différaient significativement en ce qui concerne l'état général sévèrement anormal (16,7 contre 37,9 %), la stase du rumen (22,2 contre 79,3 %), l'atonie intestinale (16,7 contre 48,3 %), la concentration sérique d'urée (6,5 contre 9,8 mmol/L) et la concentration sérique de magnésium (0,98 contre 1,30 mmol/L). En résumé, 38,3 % des vaches ont reçu leur congé et 61,7 % ont été euthanasiées avant, pendant ou après l'intervention chirurgicale. Conclusion et pertinence clinique: Une évolution aiguë de la maladie, peu ou pas de selles dans le rectum et un intestin grêle dilaté étaient caractéristiques du SIV dans cette population étudiée.(Traduit par Dr Serge Messier).

Small intestinal strangulation in 60 cattle - clinical, laboratory and ultrasonographic findings, treatment and outcome.

BACKGROUND: Intestinal strangulation is constriction of the intestine by a band of tissue, ligament or blood vessel causing partial or complete intestinal obstruction. This retrospective study describes the clinical, laboratory and ultrasonographic findings, treatment and outcome of 60 cows with intestinal strangulation. RESULTS: The general condition was abnormal in all cows (60/60), 23.3% (14/60) had nonspecific signs of pain, 40.0% (24/60) had signs of colic and 48.3% (29/60) had signs of somatic (parietal) pain. The most common digestive tract abnormalities were, in decreasing frequency, reduced or absent intestinal motility (100%, 60/60), reduced or absent faecal output (98.3%, 59/60), reduced or absent rumen motility (93.4%, 56/60), dilated small intestines on transrectal palpation (63.3%, 38/60), positive ballottement and swinging auscultation (BSA) and/or percussion and simultaneous auscultation (PSA) on the right side of the abdomen (58.3%, 35/60) and at least one positive foreign body test, most commonly the back grip, in 33.9% (20/59) of the cows. Other common findings were reduced skin surface temperature (67.8%, 40/59), reduced skin turgor (51.7%, 31/60), prolonged capillary refill time (49.2%, 29/59), enophthalmus (48.3%, 29/60) and moderate to severe scleral injection (46.6%, 27/58). The most common laboratory findings were hypokalaemia (58.3%, 35/60), haemoconcentration (57.6%, 34/59), base excess (51.1%, 24/47), hyperproteinaemia (45.8%, 27/59), hyperbilirubinaemia (43.3%, 26/60), acidosis (42.6%, 20/47) and azotaemia (38.3%, 23/60). The principal ultrasonographic findings were subjectively reduced or absent small intestinal motility and dilated small intestines, but the strangulation could not be visualised by ultrasonography. With one exception, all cows underwent a right flank laparotomy to resolve the strangulation by transection or resection of the impinging tissue. Forty-nine (81.7%) cows were discharged and 11 (18.3%) were euthanized before, during or after surgery. CONCLUSIONS: Without laparotomy, intestinal strangulation could be clinically (transrectally) diagnosed in only 10% of the cows. A laparotomy is therefore essential for the correct diagnosis. The prognosis is good with prompt surgical treatment.

Exudative glomerulonephritis associated with acute leptospirosis in dogs.

In the past 20 years in Switzerland, dogs with suspect acute leptospirosis frequently showed severe glomerular changes that had not been previously reported. These features were characterized by abundant extravasated erythrocytes and fewer neutrophils accompanied by marked fibrin exudation into the urinary space that was interpreted as an exudative glomerulonephritis (GN). This retrospective study describes this significant glomerular pathological change and investigates the association with leptospirosis. Tissues from 50 dogs with exudative GN, retrieved from 2 pathology archives in Switzerland were reviewed using hematoxylin and eosin, periodic acid-Schiff, phosphotungstic acid-hematoxylin, and Warthin and Starry stains. Clinical and postmortem data were collected for each case. Immunohistochemistry (IHC) and/or polymerase chain reactions were used as confirmatory tests for leptospirosis. While all 50 cases had clinical and pathological features supporting a diagnosis of leptospirosis, 37 cases were confirmed for the disease. Using a LipL32 antibody in addition to the OMV2177 antibody raised against the lipopolysaccharide of Leptospira interrogans serovar Copenhageni increased the detection rate of Leptospira by IHC in exudative GN from 24% to 62%. Signalment, seasonality, clinical signs, blood results, and pathological changes in dogs with exudative GN were similar to those reported for dogs without GN and confirmed infection by Leptospira spp.. Exudative GN was common among Swiss dogs with leptospirosis where it caused acute severe disease. Leptospirosis should be considered as a cause of this new pathologic feature by the pathologist. The pathogenesis remains unclear, but involvement of a geographic-specific serovar with unique virulence factors is suspected and warrants further investigation.

Efficacy and safety of P11-4 for the treatment of periodontal defects in dogs.

OBJECTIVES: This study's aim was to investigate the safety and performance of a self-assembling peptide matrix (SAPM) P11-4 for the treatment of periodontal disease in a controlled pre-clinical study. MATERIALS AND METHODS: Acute buccal bony dehiscence defects (LxW: 5 × 3 mm) were surgically created on the distal root of four teeth on one mandible side of 7 beagle dogs followed by another identical surgery 8 weeks later on the contralateral side. SAPM P11-4 (with and without root conditioning with 24% EDTA (T1, T2)), Emdogain® (C) and a sham intervention (S) were randomly applied on the four defects at each time point. Four weeks after the second surgery and treatment, the animals were sacrificed, the mandibles measured by micro-computed tomography (µ-CT) and sections of the tissue were stained and evaluated histologically. RESULTS: Clinically and histologically, no safety concerns or pathological issues due to the treatments were observed in any of the study groups at any time point. All groups showed overall similar results after 4 and 12 weeks of healing regarding new cementum, functionality of newly formed periodontal ligament and recovery of height and volume of the new alveolar bone and mineral density. CONCLUSION: A controlled clinical study in humans should be performed in a next step as no adverse effects or safety issues, which might affect clinical usage of the product, were observed. CLINICAL RELEVANCE: The synthetic SAPM P11-4 may offer an alternative to the animal-derived product Emdogain® in the future.

Clinical and histological comparison of the soft tissue morphology between zirconia and titanium dental implants under healthy and experimental mucositis conditions-A randomized controlled clinical trial.

OBJECTIVES: To analyse the soft tissue morphology under healthy and experimental mucositis conditions comparing zirconia and titanium implants. METHODS: Forty-two patients with two adjacent missing teeth received one zirconia (Zr) and one titanium (Ti) implant, with the mesial and distal position randomized. At 3 months, half of the patients were instructed to continue (healthy; h) and the other half to omit (experimental mucositis; m) oral hygiene around the implants for 3 weeks. Clinical parameters were evaluated before and after the experimental phase, and a soft tissue biopsy was harvested. Mixed model analyses were performed to analyse the data. RESULTS: The plaque control record increased significantly for the two mucositis groups, reaching 68.3 ± 31.9% (mean ± SD) for Zr-m and 75.0 ± 29.4% for Ti-m (p < .0001), being also significantly lower for Zr-m than for Ti-m. Bleeding on probing remained stable in group Zr-m and amounted to 21.7 ± 23.6%, but increased significantly in group Ti-m (p = .040), measuring 32.5 ± 27.8%. The number of inflammatory cells and the length of the junctional epithelium did not significantly differ between the groups. CONCLUSION: Both implants rendered similar outcomes under healthy conditions. Lower plaque and bleeding scores were detected for zirconia implants under experimental mucositis conditions. Histologically, only minimal differences were observed.

Chlamydia pecorum-Induced Arthritis in Experimentally and Naturally Infected Sheep.

Chlamydia pecorum is an obligate intracellular pathogen with a wide host range including livestock such as sheep, cattle, goats, and pigs as well as wildlife species such as koalas. Chlamydial polyarthritis is an economically important disease resulting in swollen joints, lameness, stiffness, and weight loss in young sheep. In the present study, tissues from sheep experimentally or naturally infected with Chlamydia pecorum were assessed by histopathology and immunohistochemistry. Carpal, hock, and stifle joints as well as spleen, liver, kidney, lymph nodes, lung, and brain of 35 sheep from different inoculation groups were available. Two different C. pecorum strains (IPA and E58), different routes of administration (intraarticular or intravenous), UVA-irradiated IPA strain, and corresponding noninfected control groups were investigated. Similar investigations on tissues from 5 naturally infected sheep were performed. The most obvious inflammatory lesions were observed in synovial tissues and, notably, in the renal pelvis from the experimentally infected group and naturally infected animals. This resulted in chronic or chronic-active arthritis and pyelitis. Intralesional chlamydial inclusions could be demonstrated by immunohistochemistry in both tissues. Immunohistochemical evaluation of the presence and distribution of macrophages, T and B cells in synovial tissues revealed macrophages as the most prevalent inflammatory cell population. Previous observations indicated that C. pecorum isolates can infect circulating monocytes. Together with the finding of the histological lesions in synovial tissues and internal organs alongside the presence of C. pecorum DNA, these observations suggest chlamydial arthritis in lambs is the result of hematogeneous spread of C. pecorum.

Cellular self-assembly into 3D microtissues enhances the angiogenic activity and functional neovascularization capacity of human cardiopoietic stem cells.

While cell therapy has been proposed as next-generation therapy to treat the diseased heart, current strategies display only limited clinical efficacy. Besides the ongoing quest for the ideal cell type, in particular the very low retention rate of single-cell (SC) suspensions after delivery remains a major problem. To improve cellular retention, cellular self-assembly into 3D microtissues (MTs) prior to transplantation has emerged as an encouraging alternative. Importantly, 3D-MTs have also been reported to enhance the angiogenic activity and neovascularization potential of stem cells. Therefore, here using the chorioallantoic membrane (CAM) assay we comprehensively evaluate the impact of cell format (SCs versus 3D-MTs) on the angiogenic potential of human cardiopoietic stem cells, a promising second-generation cell type for cardiac repair. Biodegradable collagen scaffolds were seeded with human cardiopoietic stem cells, either as SCs or as 3D-MTs generated by using a modified hanging drop method. Thereafter, seeded scaffolds were placed on the CAM of living chicken embryos and analyzed for their perfusion capacity in vivo using magnetic resonance imaging assessment which was then linked to a longitudinal histomorphometric ex vivo analysis comprising blood vessel density and characteristics such as shape and size. Cellular self-assembly into 3D-MTs led to a significant increase of vessel density mainly driven by a higher number of neo-capillary formation. In contrast, SC-seeded scaffolds displayed a higher frequency of larger neo-vessels resulting in an overall 1.76-fold higher total vessel area (TVA). Importantly, despite that larger TVA in SC-seeded group, the mean perfusion capacity (MPC) was comparable between groups, therefore suggesting functional superiority together with an enhanced perfusion efficacy of the neo-vessels in 3D-MT-seeded scaffolds. This was further underlined by a 1.64-fold higher perfusion ratio when relating MPC to TVA. Our study shows that cellular self-assembly of human cardiopoietic stem cells into 3D-MTs substantially enhances their overall angiogenic potential and their functional neovascularization capacity. Hence, the concept of 3D-MTs may be considered to increase the therapeutic efficacy of future cell therapy concepts.

Clinical, laboratory and ultrasonographic findings in 87 cows with type-4 abomasal ulcer.

BACKGROUND: This study evaluated the clinical, laboratory, ultrasonographic and pathological findings in 87 cows aged 2 to 10 years (4.5 ± 1.5 years) with type-4 abomasal ulcer. RESULTS: The most common clinical findings were in decreasing order compromised health status accompanied by partial or complete anorexia (100%), abdominal guarding (81%), congested scleral vessels (77%), ruminal atony (73%), tachycardia (68%), tachypnoea (65%), positive foreign body tests (58%), decreased skin surface temperature (53%), fever (49%), reduction in negative intraabdominal pressure assessed transrectally (39%), poorly subdivided plant fragments in faeces (35%) and arched back (28%). The principal haematological abnormalities were hypokalaemia (72%), haemoconcentration (69%), azotaemia (56%), metabolic acidosis (49%), hyperfibrinogenaemia (45%), leukopenia (35%) and hypoproteinaemia (29%). Other abnormalities were aciduria (56%), haematuria (44%), increased chloride concentration in rumen fluid (34%) and abnormal peritoneal fluid (98%). Of 75 examined cows, 65 (87%) had ultrasonographic evidence of local or generalised peritonitis. On postmortem examination all cows had a type-4 abomasal ulcer and generalised peritonitis. In addition, 36 cows had type-1 ulcers, 6 had type-2 ulcers and one cow had a type-3 ulcer. DISCUSSION: The clinical signs in cows with type-4 abomasal ulcer are associated with generalised peritonitis. An increased haematocrit, indicating shock-induced haemoconcentration is characteristic in contrast to cows with traumatic reticuloperitonitis. Ultrasonography is useful for visualising and assessing generalised peritonitis. CONCLUSIONS: The diagnosis of type-4 abomasal ulcer based on clinical signs alone is difficult and therefore requires additional diagnostic procedures including the determination of the haematocrit and plasma protein concentration, abdominal ultrasonography and analysis of peritoneal fluid. In most cases, these steps lead to a correct diagnosis and allow timely euthanasia of the cow to prevent further suffering and unnecessary treatment costs. METHODS: The cows underwent a clinical, laboratory, ultrasonographic and postmortem examination.

Bovine Fetal Placenta During Pregnancy and the Postpartum Period.

Bovine abortion is a worldwide problem, but despite extensive histopathologic and molecular investigations, the cause of abortion remains unclear in about 70% of cases. Cellular debris is a commonly observed histopathologic finding in the fetal placenta and is often interpreted as necrosis. In this study, the nature of this cellular debris was characterized, and histologic changes in the normal fetal placenta during pregnancy and after delivery were assessed. In addition, the presence of the most common abortifacient pathogens in Switzerland ( Chlamydiaceae, Coxiella burnetii, Neospora caninum) was tested by polymerase chain reaction. We collected 51 placentomes and 235 cotyledons from 41 and from 50 cows, respectively. In total, cellular debris was present in 48 of 51 (94%) placentomes and in 225 of 235 (96%) cotyledons, inflammation occurred in 1 of 51 (2%) placentomes and in 46 of 235 (20%) cotyledons, vasculitis was seen in 1 of 51 (2%) placentomes and 46 of 235 (20%) cotyledons, and 18 of 51 (35%) placentomes and 181 of 235 (77%) cotyledons had mineralization. The amount of cellular debris correlated with areas of positive signals for cleaved caspase 3 and lamin A. Therefore, this finding was interpreted as an apoptotic process. In total, 10 of 50 cotyledons (20%) were positive for C. burnetii DNA, most likely representing subclinical infections. The results of our study indicate that histologic features in the fetal placenta such as cellular debris, inflammation, vasculitis, and mineralization must be considered physiological processes during pregnancy and after delivery. Therefore, their presence in placentae of aborted fetuses must be interpreted with caution and might not be necessarily linked to an infectious cause of abortion.

Oral Application of Recombinant Bacillus subtilis Spores to Dogs Results in a Humoral Response against Specific Echinococcus granulosus Paramyosin and Tropomyosin Antigens.

Bacillus subtilis is known as an endospore- and biofilm-forming bacterium with probiotic properties. We have recently developed a method for displaying heterologous proteins on the surface of B. subtilis biofilms by introducing the coding sequences of the protein of interest into the bacterial genome to generate a fusion protein linked to the C terminus of the biofilm matrix protein TasA. Although B. subtilis is a regular component of the gut microflora, we constructed a series of recombinant B. subtilis strains that were tested for their ability to be used to immunize dogs following oral application of the spores. Specifically, we tested recombinant spores of B. subtilis carrying either the fluorescent protein mCherry or else selected antigenic peptides (tropomyosin and paramyosin) from Echinococcus granulosus, a zoonotic intestinal tapeworm of dogs and other carnivores. The application of the recombinant B. subtilis spores led to the colonization of the gut with recombinant B. subtilis but did not cause any adverse effect on the health of the animals. As measured by enzyme-linked immunosorbent assay and immunoblotting, the dogs were able to develop a humoral immune response against mCherry as well as against E. granulosus antigenic peptides. Interestingly, the sera of dogs obtained after immunization with recombinant spores of E. granulosus peptides were able to recognize E. granulosus protoscoleces, which represent the infective form of the head of the tapeworms. These results represent an essential step toward the establishment of B. subtilis as an enteric vaccine agent.

Mouse intestinal microbiota reduction favors local intestinal immunity triggered by antigens displayed in Bacillus subtilis biofilm.

BACKGROUND: We previously engineered Bacillus subtilis to express an antigen of interest fused to TasA in a biofilm. B. subtilis has several properties such as sporulation, biofilm formation and probiotic ability that were used for the oral application of recombinant spores harboring Echinococcus granulosus paramyosin and tropomyosin immunogenic peptides that resulted in the elicitation of a specific humoral immune response in a dog model. RESULTS: In order to advance our understanding of the research in oral immunization practices using recombinant B. subtilis spores, we describe here an affordable animal model. In this study, we show clear evidence indicating that a niche is required for B. subtilis recombinant spores to colonize the densely populated mice intestinal microbiota. The reduction of intestinal microbiota with an antibiotic treatment resulted in a positive elicitation of local humoral immune response in BALB/c mice after oral application of recombinant B. subtilis spores harboring TasA fused to E. granulosus (102-207) EgTrp immunogenic peptide. Our results were supported by a lasting prevalence of spores in mice feces up to 50 days after immunization and by the presence of specific secretory IgA, isolated from feces, against E. granulosus tropomyosin. CONCLUSIONS: The reduction of mouse intestinal microbiota allowed the elicitation of a local humoral immune response in mice after oral application with spores of B. subtilis harboring immunogenic peptides against E. granulosus.

Correction to: Insemination with border disease virus-infected semen results in seroconversion in cows but not persistent infection in fetuses.

The original article [1] contained an error whereby a co-author, Sarah Züblin had their name displayed incorrectly. This error has now been corrected.

Insemination with border disease virus-infected semen results in seroconversion in cows but not persistent infection in fetuses.

BACKGROUND: This study examined various health variables in cows after artificial insemination with Border disease virus (BDV)-infected semen and the occurrence of persistent infection in ensuing fetuses. Five cows were inseminated (day 0) with BDV-infected semen as well as with semen from a fertile Eringer bull. One cow, inseminated with virus-free semen only, served as a control. Clinical examination, assessment of eating and rumination activities, measurement of intraruminal temperature and leukocyte count were used to monitor the health of the cows. Blood samples were collected at regular intervals for the detection of viral RNA and antibodies against BDV, and the cows were slaughtered on day 56. The uteri, placentae and fetuses were examined macroscopically, histologically, immunohistochemically and by means of molecular methods for the presence of pestiviruses. RESULTS: The demeanour, eating and rumination activities and intraruminal temperature were not affected by insemination with BDV-infected semen, whereas the total leukocyte and lymphocyte counts dropped transiently and were significantly lower on day 6 than on day 0. Seroconversion occurred by day 28 in the five infected cows but not in the control cow. The uteri, placentae and fetuses had no macroscopic or histological lesions, and immunohistochemical examination and RT-PCR were negative for pestiviruses. CONCLUSIONS: The findings showed that cows inseminated with BDV-infected semen seroconverted and fetuses thus produced were not persistently infected. Transmission of BDV to cattle through infected semen, therefore, seems to be of minor importance.

Border Disease Virus Infection of Bovine Placentas.

Subsequent to a previous study of border disease virus (BDV) horizontal transmission from a persistently BDV-infected calf to 6 seronegative pregnant heifers, the heifers were slaughtered 60 days after exposure to the infected calf, and their fetuses and placentas were examined. Immunohistochemical examination of fetal organs and placenta showed positive labeling of moderate intensity for pestivirus antigen in 3 of 6 heifers. BDV infection in these 3 animals was confirmed by the detection of BDV RNA in different organs using reverse transcription quantitative polymerase chain reaction. In the placenta, the positive cells were visualized mostly on the fetal side. In those 3 heifers that harbored an infected fetus, the placental tissue in the placentome region showed a moderate to severe mononuclear and fibrosing placentitis and, in severe cases, necrotic areas. The inflammatory population was composed predominantly of T and B cells, a substantial number of macrophages, and, to a lesser extent, plasma cells. This is a novel report of placentitis in persistently BDV-infected fetuses from pregnant heifers that became acutely infected by cohousing with a calf persistently infected with BDV, which extends previous reports on bovine viral diarrhea virus-infected and BDV-infected cattle and sheep, respectively.

Chemical Composition, but Not Specific Surface Area, Affects Calcium Retention of Nanostructured Calcium Compounds in Growing Rats.

Background: Low dietary calcium intake and bioavailability may adversely affect bone health. Reducing the size of calcium compounds increases their specific surface area (SSA, expressed as m2/g) and may increase calcium dissolution and bioavailability.Objective: We investigated the influence of SSA and chemical composition on the bioavailability of calcium and compared in vitro calcium dissolution with in vivo absorption.Methods: Calcium dissolution was measured in 0.1 M phosphoric acid, whereas color and pH changes of foods were assessed as indicators for potential sensory performance. Calcium absorption, retention, and fractional retention were measured over a 5-d balance study in growing Sprague-Dawley male rats after 21 d of feeding. Femoral and vertebral bone mineral density (BMD) and extensive tissue histology were assessed at study end. The influence of SSA on calcium bioavailability was assessed by comparing the groups fed pure calcium carbonate (CaCO3) with increasing SSAs of 3, 36, and 64 m2/g (CaCO3_3, CaCO3_36 and CaCO3_64), whereas chemical composition was assessed by comparing the smallest CaCO3_64, a 50:50 wt:wt percent solution mixture of CaCO3 and hydroxyapatite_94, and pure hydroxyapatite_100.Results: In vivo, fractional calcium retention from hydroxyapatite_100 (mean ± SEM: 54.86% ± 0.95%/5 d) was significantly greater than from CaCO3_64 (49.66% ± 1.15%/5 d) (P = 0.044). Increasing SSA of the pure CaCO3 did not significantly improve calcium retention. Across all 5 groups, there were no significant differences in BMD or tissue calcification by histology. In vitro calcium dissolution did not correlate with SSA or calcium absorption. In selected food matrixes, hydroxyapatite_100 caused less color change and/or smaller pH increase than did the other calcium compounds.Conclusions: Our findings suggest that chemical composition rather than SSA is a predictor of nanostructured calcium bioavailability and that in vitro dissolution of nanostructured calcium does not predict in vivo absorption. Although its phosphorus content may limit use in some populations, nanostructured hydroxyapatite may be a promising calcium compound for food fortification.

A missense mutation in TUBD1 is associated with high juvenile mortality in Braunvieh and Fleckvieh cattle.

BACKGROUND: Haplotypes with reduced or missing homozygosity may harbor deleterious alleles that compromise juvenile survival. A scan for homozygous haplotype deficiency revealed a short segment on bovine chromosome 19 (Braunvieh haplotype 2, BH2) that was associated with high juvenile mortality in Braunvieh cattle. However, the molecular genetic underpinnings and the pathophysiology of BH2 remain to be elucidated. RESULTS: The frequency of BH2 was 6.5 % in 8,446 Braunvieh animals from the national bovine genome databases. Both perinatal and juvenile mortality of BH2 homozygous calves were higher than the average in Braunvieh cattle resulting in a depletion of BH2 homozygous adult animals (P = 9.3x10(-12)). The analysis of whole-genome sequence data from 54 Braunvieh animals uncovered a missense mutation in TUBD1 (rs383232842, p.H210R) that was compatible with recessive inheritance of BH2. The availability of sequence data of 236 animals from diverse bovine populations revealed that the missense mutation also segregated at a low frequency (1.7 %) in the Fleckvieh breed. A validation study in 37,314 Fleckvieh animals confirmed high juvenile mortality of homozygous calves (P = 2.2x10(-15)). Our findings show that the putative disease allele is located on an ancestral haplotype that segregates in Braunvieh and Fleckvieh cattle. To unravel the pathophysiology of BH2, six homozygous animals were examined at the animal clinic. Clinical and pathological findings revealed that homozygous calves suffered from chronic airway disease possibly resulting from defective cilia in the respiratory tract. CONCLUSIONS: A missense mutation in TUBD1 is associated with high perinatal and juvenile mortality in Braunvieh and Fleckvieh cattle. The mutation is located on a common haplotype likely originating from an ancient ancestor of Braunvieh and Fleckvieh cattle. Our findings demonstrate for the first time that deleterious alleles may segregate across closed cattle breeds without recent admixture. Homozygous calves suffer from chronic airway disease resulting in poor growth performance and high juvenile mortality. The respiratory manifestations resemble key features of diseases resulting from impaired function of airway cilia.

Randomized controlled clinical study evaluating effectiveness and safety of a volume-stable collagen matrix compared to autogenous connective tissue grafts for soft tissue augmentation at implant sites.

AIM: To test whether or not the use of a collagen matrix (VCMX) results in short-term soft tissue volume increase at implant sites non-inferior to an autogenous subepithelial connective tissue graft (SCTG), and to evaluate safety and tissue integration of VCMX and SCTG. METHODS: In 20 patients with a volume deficiency at single-tooth implant sites, soft tissue volume augmentation was performed randomly allocating VCMX or SCTG. Soft tissue thickness, patient-reported outcome measures (PROMs), and safety were assessed up to 90 days (FU-90). At FU-90 (abutment connection), tissue samples were obtained for histological analysis. Descriptive analysis was computed for both groups. Non-parametric tests were applied to test non-inferiority for the gain in soft tissue thickness at the occlusal site. RESULTS: Median soft tissue thickness increased between BL and FU-90 by 1.8 mm (Q1:0.5; Q3:2.0) (VCMX) (p = 0.018) and 0.5 mm (-1.0; 2.0) (SCTG) (p = 0.395) (occlusal) and by 1.0 mm (0.5; 2.0) (VCMX) (p = 0.074) and 1.5 mm (-2.0; 2.0) (SCTG) (p = 0.563) (buccal). Non-inferiority with a non-inferiority margin of 1 mm could be demonstrated (p = 0.020); the difference between the two group medians (1.3 mm) for occlusal sites indicated no relevant, but not significant superiority of VCMX versus SCTG (primary endpoint). Pain medication consumption and pain perceived were non-significantly higher in group SCTG up to day 3. Median physical pain (OHIP-14) at day 7 was 100% higher for SCTG than for VCMX. The histological analysis revealed well-integrated grafts. CONCLUSIONS: Soft tissue augmentation at implant sites resulted in a similar or higher soft tissue volume increase after 90 days for VCMX versus SCTG. PROMs did not reveal relevant differences between the two groups.

Palatal wound healing using a xenogeneic collagen matrix - histological outcomes of a randomized controlled clinical trial.

AIM: The aim of this study was to test whether or not a collagen matrix can improve early wound healing compared to spontaneous healing based on histological and immunohistologic analyses. METHODS: In 20 volunteers, 6 mm punch biopsies were harvested at the palate. A xenogeneic collagen matrix (XCM) was sutured in one site; the other one was left untreated (control). Biopsies with a diameter of 8 mm were subsequently obtained at 4, 8, 15 and 29 days and histological and immunohistologic analyses were performed. RESULTS: At day 4, wound bed keratinization amounted to 12.4 ± 7.5% (control) and 18.0 ± 10.2% (XCM). This increased up to day 8 (19.7 ± 25.5% control; 29.1 ± 8.0% XCM) and reached complete keratinization at day 15 in both groups. The quantitative analyses of the superficial compartment measured an increase in the amount of granulation tissue (32-88% control; 14-41% XCM) from day 4 to day 8. Angiogenesis was first detected at 8 days. At day 29, the amount of connective tissue in all compartments reached values similar to the native tissue at baseline. CONCLUSIONS: The application of a XCM as a wound dressing on palatal wounds might be beneficial in the early stages of wound healing. Further research with a larger sample size is needed to confirm these results.

Penetration depth of corneal cross-linking with riboflavin and UV-A (CXL) in horses and rabbits.

OBJECTIVE: CXL penetration depth is an important variable influencing clinical treatment effect and safety. The purposes of this study were to determine the penetration depth of CXL in rabbit and equine corneas in epithelium-on and epithelium-off procedures and to assess an ex vivo fluorescent biomarker staining assay for objective assessment of CXL penetration depth. PROCEDURES: CXL treatment was performed according to a standardized protocol on 21 and 17 rabbit eyes and on 12 and 10 equine eyes with and without debridement, respectively. Control corneas were treated similarly, but not exposed to CXL. Hemicorneas were stained with either phalloidin and DAPI to visualize intracellular F-actin and nuclei, or with hematoxylin and eosin. Loss of actin staining was measured and compared between groups. RESULTS: Epithelium-off CXL caused a median actin cytoskeleton loss with a demarcation at 274 µm in rabbits and 173 µm in horses. In non-CXL-treated controls, we observed a median actin cytoskeleton loss with a demarcation at 134 µm in rabbits and 149 µm in horses. No effect was detected in the epithelium-on procedure. CONCLUSIONS: CXL penetration depth, as determined by a novel ex vivo fluorescent assay, shows clear differences between species. A distinct effect was observed following epithelium-off CXL treatment in the anterior stroma of rabbits, but no different effect was observed in horses in comparison with nontreated controls. Different protocols need to be established to effectively treat equine patients with infectious corneal disease.