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Pigs are valuable large animal models for biomedical and genetic research, but insights into the tissue- and cell-type-specific transcriptome and heterogeneity remain limited. By leveraging single-cell RNA sequencing, we generate a multiple-organ single-cell transcriptomic map containing over 200,000 pig cells from 20 tissues/organs. We comprehensively characterize the heterogeneity of cells in tissues and identify 234 cell clusters, representing 58 major cell types. In-depth integrative analysis of endothelial cells reveals a high degree of heterogeneity. We identify several functionally distinct endothelial cell phenotypes, including an endothelial to mesenchymal transition subtype in adipose tissues. Intercellular communication analysis predicts tissue- and cell type-specific crosstalk between endothelial cells and other cell types through the VEGF, PDGF, TGF-β, and BMP pathways. Regulon analysis of single-cell transcriptome of microglia in pig and 12 other species further identifies MEF2C as an evolutionally conserved regulon in the microglia. Our work describes the landscape of single-cell transcriptomes within diverse pig organs and identifies the heterogeneity of endothelial cells and evolutionally conserved regulon in microglia., (© 2022. The Author(s).)

Background: Differing results regarding articulation skills in young children with cleft palate (CP) have been reported and often interpreted as a consequence of different surgical protocols., Aims: To assess the influence of different timing of hard palate closure in a two-stage procedure on articulation skills in 3-year-olds born with unilateral cleft lip and palate (UCLP). Secondary aims were to compare results with peers without CP, and to investigate if there are gender differences in articulation skills. Furthermore, burden of treatment was to be estimated in terms of secondary surgery, hearing and speech therapy., Methods & Procedures: A randomized controlled trial (RCT). Early hard palate closure (EHPC) at 12 months versus late hard palate closure (LHPC) at 36 months in a two-stage procedure was tested in a cohort of 126 Danish-speaking children born with non-syndromic UCLP. All participants had the lip and soft palate closed around 4 months of age. Audio and video recordings of a naming test were available from 113 children (32 girls and 81 boys) and were transcribed phonetically. Recordings were obtained prior to hard palate closure in the LHPC group. The main outcome measures were percentage consonants correct adjusted (PCC-A) and consonant errors from blinded assessments. Results from 36 Danish-speaking children without CP obtained previously by Willadsen in 2012 were used for comparison., Outcomes & Results: Children with EHPC produced significantly more target consonants correctly (83%) than children with LHPC (48%; p < .001). In addition, children with LHPC produced significantly more active cleft speech characteristics than children with EHPC (p < .001). Boys achieved significantly lower PCC-A scores than girls (p = .04) and produced significantly more consonant errors than girls (p = .02). No significant differences were found between groups regarding burden of treatment. The control group performed significantly better than the EHPC and LHPC groups on all compared variables., (© 2017 Royal College of Speech and Language Therapists.)

Background: Longstanding uncertainty surrounds the selection of surgical protocols for unilateral cleft lip and palate, and randomised trials have only rarely been performed. The Scandcleft Project consists of three trials commenced in 1997 involving ten centres in Denmark, Finland, Norway, Sweden, and the UK. Three groups of centres tested a newly-defined common technique for palatal repair (Arm A) against their local protocols (Arms B, C, D). Arm A was familiar to most of the surgeons in Trial 1, but not to the surgeons in the other Trials., Aim: To evaluate surgical events and complications of the 448 (293 boys, 155 girls) patients with complete unilateral cleft lip and palate (UCLP) enrolled in the three trials., Method: The three trials were carried out in parallel in adherence with a fully developed, ethically approved protocol. Operative time, bleeding, complications, and major dehiscence during and after both primary surgeries were recorded by the surgeon. Rates of fistula and surgery for velopharyngeal incompetence (VPI) were assessed until the youngest patient of the study had reached the age of 9 years. Pearson Chi-square statistical analysis was used to compare the outcomes., Results: No significant differences in bleeding, infection, anaesthetic complications or length of hospital stay between the different arms were found for Trial 1. However, in Trials 2 and 3 there were more airway problems in Arm A than with the traditional local protocols (Arms C or D). In Trial 3 fistula and VPI surgery rates were also higher in Arm A., Conclusions: The results do not provide statistical evidence that any technique is better than others, but indicate that surgery was more problematic for surgeons who were still gaining experience with an unfamiliar surgical protocol., Trial Registration: ISRCTN29932826.

Background and Aims: Longstanding uncertainty surrounds the selection of surgical protocols for the closure of unilateral cleft lip and palate, and randomised trials have only rarely been performed. This paper is an introduction to three randomised trials of primary surgery for children born with complete unilateral cleft lip and palate (UCLP). It presents the protocol developed for the trials in CONSORT format, and describes the management structure that was developed to achieve the long-term engagement and commitment required to complete the project., Method: Ten established national or regional cleft centres participated. Lip and soft palate closure at 3-4 months, and hard palate closure at 12 months served as a common method in each trial. Trial 1 compared this with hard palate closure at 36 months. Trial 2 compared it with lip closure at 3-4 months and hard and soft palate closure at 12 months. Trial 3 compared it with lip and hard palate closure at 3-4 months and soft palate closure at 12 months. The primary outcomes were speech and dentofacial development, with a series of perioperative and longer-term secondary outcomes., Results: Recruitment of 448 infants took place over a 9-year period, with 99.8% subsequent retention at 5 years., Conclusion: The series of reports that follow this introductory paper include comparisons at age 5 of surgical outcomes, speech outcomes, measures of dentofacial development and appearance, and parental satisfaction. The outcomes recorded and the numbers analysed for each outcome and time point are described in the series., Trial Registration: ISRCTN29932826.

Objective: The objective of the study was to analyze the craniofacial morphology in infants with unilateral complete cleft lip and palate (UCCLP) in which the lip and the anterior part of the palate had been surgically closed at 2 months of age and to compare the morphology with that of a control group with unilateral incomplete cleft lip (UICL) in which the lip had also been surgically closed at 2 months of age., Design: The sample consisted of a total of 108 cleft children all fulfilling the entry criteria, besides diagnosis, as follows: The child was of Danish origin; the age of the child was between 650 and 750 days (approximately 22 months) at the time of examination; the child was healthy except for its single cleft malformation; the surgical procedure in each group had been performed at about 2 months of age by the same surgeon. The surgical methods used were a Tennison procedure (UICL group) and a Tennison procedure supplemented by palatovomer plasty (UCCLP group)., Methods: The method of investigation was infant cephalometry in the lateral, frontal, and axial projections. Linear, angular, and area variables describing the craniofacial morphology were calculated and supplemented by mean plots from the cephalometric projections in the two groups., Results and Conclusions: Statistical analysis based on Student's t test showed that the facial morphology in the 22-month-old UCCLP group differed significantly from that of the UICL group. The most pronounced differences were found in the maxillary complex and the mandible. The deviations observed in the UCCLP group at 22 months of age were similar to those previously observed at 2 months of age. However, several of the dysmorphic traits had become less pronounced; some had remained the same; and a few had become worse with time.

This paper reports a longitudinal quantitative cephalometric analysis of the craniofacial growth in subjects with unilateral complete cleft lip and palate (UCCLP), and unilateral incomplete cleft lip (UICL), from 2 to 22 months of age. The purpose of the study was to determine the amount and direction of growth in UCCLP compared to UICL (control group) from 2 months of age (just prior to lip repair) to 22 months of age, 20 months later. The sample comprised of 49 subjects with UCCLP (37 males and 11 females) and 45 with UICL (29 males and 16 females). The cephalometric analysis of the craniofacial morphology included lateral, frontal, and axial projections. The data were presented as mean plots of the craniofacial region including the calvaria, cranial base, orbits, nasal bone, maxilla, mandible, cervical column, pharynx, and soft-tissue profile. A valid common coordinate system (registration according to the n-s line in the lateral projection, latero-orbitale line in the frontal projection, and meatus acusticus externus line in the axial projection for the landmark positions at examination 1 and 2) was ascertained. The growth at a specific anatomical location in a patient was defined as the displacement vector from the coordinate of the corresponding landmark in the X-ray at examination 1 to its coordinate at examination 2, corrected for X-ray magnification. The growth of an anatomical region in a patient was assessed by investigating the growth pattern formed by a collection of individual growth vectors in that region. The amount of growth in the UCCLP and UICL group was very similar. The general craniofacial growth pattern, in terms of the direction of growth, was also fairly similar in the UCCLP group and the control group. However, the maxilla and mandible showed a more vertical growth pattern than that observed in the control group. This study confirms that UCCLP is a localized deviation, and not a craniofacial anomaly, due to the fact that a normal growth potential has been observed in all craniofacial regions, except where the growth had been directly influenced by surgical intervention. Furthermore, the vertical growth pattern of the maxilla and mandible supports the hypothesis of a special facial type in cleft lip and palate individuals, and the facial type as a liability factor increasing the probability of cleft lip and palate.

This paper reports a cephalometric analysis of the craniofacial morphology in infants with unoperated unilateral complete cleft lip and palate (UCCLP) and unoperated unilateral incomplete cleft lip (UICL). The purpose of the study was to determine the nature and extent of the craniofacial deviations in UCCLP as compared to the morphology in UICL, which has previously been shown to be close to normal. The samples comprised 82 infants with UCCLP (58 males and 24 females) and 75 with UICL (48 males and 27 females). The mean age was about 2 months in both groups. The cephalometric analysis of craniofacial morphology included the lateral, frontal, and axial projections. The data were presented as mean plots of the craniofacial region including the calvaria, cranial base, orbits, nasal bone, maxilla, mandible, cervical column, pharynx, and soft-tissue profile. The most pronounced deviations in the UCCLP group were observed in the maxillary complex and the mandible. The most striking findings were: markedly increased width of the maxilla, a short mandible, and bimaxillary retrognathia except for the premaxillary area, which was relatively protruding and asymmetric. The study did not support the hypothesis previously suggested in the literature that cleft lip and palate is a craniofacial anomaly as size and shape of the calvaria and cranial base were found to be normal. The etiology of cleft lip and palate is still incompletely understood. Based on the present study, we suggest that facial type may be a liability factor that could represent a developmental threshold increasing the probability of cleft lip and palate.

Aarhus Cleft Palate Institute receives approximately 75 new cleft patients a year. Due to statuary notification of all newborn cleft patients to the Institute, the treatment protocol can be offered to the family from right after birth, and a coordinated team approach can be established. The individually planned primary surgery, speech and growth of the maxillo-facial skeleton is followed by regular team examinations. Speech development is followed from the child is one year old in order to be able to provide speech assessment as soon as problems of hypernasality and articulation disorders or language delay is evident. One of the goals of speech assessment is to achieve acceptable speech as early as possible and at best before school start. Orthodontic treatment is usually started at 8 years of age, in UCLP and BCLP patients in combination with bonegrafting at 9-11 years of age. In patients with impaired growth of the maxilla, attention is paid to identify candidates for orthognathic surgical treatment as early as possible. All secondary surgical treatment on jaws, lips and nose are coordinated and usually the treatment can be finished by the late teens. The described team approach towards the parameters of care for cleft lip and palate patients has basically been used for more than 50 years. A systematic follow-up and data collection on all patients provide a scientific base for evaluation of treatment results. Based on long-term investigations the protocol has gradually been modified during time to improve the quality of patient care.

Sixty patients with unilateral cleft lip and palate were compared for lip and nose appearance. All patients were photographed from an anteroposterior and a basal view at 7-10 years of age. The photographic registration method was tested for validity and accuracy. Although the four groups of 15 patients each were treated according to different protocols, many similarities were found with shorter lip heights at the cleft side and inclination of the rima oris. Asymmetry of nose and retropositioning at the cleft side naris were generally seen. Significantly straighter noses were demonstrated in the group treated with a two-stage lip nose operation combined with nose plugs, and the two groups where vomer flaps were used showed the greatest deviation of the nose.

Craniofacial morphology and dental occlusion were studied at early school age in 15 consecutive patients with unilateral cleft lip and palate from each of four Scandinavian cleft centres. Treatment differed mainly in the techniques of palatal repair. Push-back closure of the palate particularly impaired maxillary development, which resulted in an increased incidence of crossbite and reduced intercanine distance when compared with patients who had been operated on by the von Langenbeck method or in whom the anterior palate had not yet been closed.

Fifty-seven consecutive complete unilateral cleft lip and palate patients were followed longitudinally from birth to 21 years of age. All patients were operated with the same primary surgical procedures. Reevaluation at age 21 with respect to speech, dental condition, need for secondary surgery, and skeletal and soft tissue facial growth was completed. Speech results indicated that 13 patients (23 percent) had required a pharyngeal flap, and that at age 21 only one patient still had unacceptable speech. The majority of patients had slight speech disturbances related to articulation and voice quality. Fifty-one patients had acceptable occlusion following orthodontic treatment, twenty-two patients (39 percent) without need for prosthodontic treatment of the cleft area. Secondary surgery for correction of nasal deformities was required for fifty-two patients. Growth analysis demonstrated deficiency in growth; however, normal and acceptable profiles were obtained in 50/57 of the patients.

Experimental skin flaps in rats were treated with an active/non-active Diapulse unit in a double-blind trial to clarify whether or not pulsed electromagnetic energy had any effect on the surviving length of flaps. The observed differences in surviving flap areas between the Diapulse treated group and the untreated group as compared to the predicted survival by fluoresceine and/or vital capillary television microscopy were not statistically significant (p less than 0.10) in a set up, that on a significance level of 5%, would have detected an enhancement of flap survival of greater than or equal to 10% in 98% of trials.