[Treatment of severe spinal deformity with 3D printing models]. / Tratamiento de deformidad severa de la columna vertebral con modelos de impresión 3D.

INTRODUCTION: Scoliosis is a complex deformity that affects all three planes of the axis of the spine. The association between neuromuscular pathology and vertebral alignment was initially described in 1960. Neuromuscular pathology is progressive and results in postural abnormalities. Surgical goals in patients with neuromuscular deformity include anatomical correction for sedation and ambulation, as well as functional improvement. The gold standard of treatment is by posterior approach with transpedicular screws. The "hands-free" technique saves surgical time, decreases radiation by reducing the use of fluoroscopy. The advent of 3D printing technology allows precise study of the anatomical area and detail of the deformity in its three planes. This model can be sterilized for transoperative guidance. A 13-year-old female patient who develops thoracolumbar neuromuscular scoliosis secondary to spastic cerebral palsy (CP), with previous instrumentation T11-L3 of which he develops severe proximal curve. After the segmentation of the three-dimensional model, pedicle violation greater than 2 mm towards bilateral medullary canal was detected in the pedicles of L1 and L2 of previous instrumentation, pedicle dysplasia and the morphological characteristics of the pedicles were observed. Three-dimensional planning and the use of surgical guides represent a tool for surgical planning, especially in severe cases and with pedicle dysplasia. It helps as a surgical guide for the placement of hands-free transpedicular screws with possible reduction of radiation and anesthetic time.

INTRODUCCIÓN: La escoliosis es una deformidad compleja que afecta los tres planos del eje de la columna vertebral. La asociación entre patología neuromuscular y la alineación vertebral fue descrita inicialmente en 1960. La patología neuromuscular es progresiva y resulta en anormalidades posturales. Las metas quirúrgicas en pacientes con deformidad neuromuscular engloban la corrección anatómica para la sedestación y deambulación, así como mejoría funcional. El estándar de oro de tratamiento es por vía posterior con tornillos transpediculares. La técnica de "manos libres" ahorra tiempo quirúrgico, disminuye la radiación al reducir el uso de fluoroscopía. El advenimiento de la tecnología de impresión 3D permite estudio preciso del área anatómica y detalle de la deformidad en sus tres planos. Este modelo puede ser esterilizado para guía transoperatoria. Paciente femenino de 13 años de edad que desarrolla escoliosis neuromuscular toracolumbar secundario a parálisis cerebral infantil (PCI) espástica, con instrumentación previa T11-L3 de la cual desarrolla curva severa proximal. Finalizada la segmentación del modelo tridimensional se detectó violación pedicular mayor a 2 mm hacia canal medular bilateral en los pedículos de L1 y L2 de instrumentación previa, displasia pedicular y se observaron las características morfológicas de los pedículos. La planeación tridimensional y el uso de guías quirúrgicas representan una herramienta para la planeación quirúrgica, sobre todo en casos severos y con displasia pedicular. Ayuda como guía quirúrgica para la colocación de tornillos transpediculares a manos libres con posible reducción de radiación y tiempo anestésico.

Laparoscopic pediatric pyeloplasty using the Flexdex® articulating needle driver: step-by-step video.

Ureteropelvic junction (UPJ) stenosis is the most common cause of pathological neonatal hydronephrosis. UPJ obstruction may be treated conservatively in some cases, but surgery is indicated if symptoms occur or renal function deteriorates. Pyeloplasty is the procedure of choice for UPJ stenosis. Pyeloplasty can be performed by open laparoscopic or robotic technique. The laparoscopic technique is safe and may be associated with shorter length of hospital stay and reduced complications. Lately, robotic pyeloplasty has been performed with similar results, adding the benefits of easier suturing maneuverability, but with increased costs. Flexdex® is a laparoscopic articulating needle driver that improves maneuverability and ergonomics. In this video, a laparoscopic pyeloplasty with the Flexdex® needle drive is described. The case was treated without any intraoperative complications and with no significant blood loss, and the patient was discharged the day after the procedure. After 90 days of follow-up, there were no complications reported.

Bone marrow mononuclear cells versus mesenchymal stem cells from adipose tissue on bone healing in an Old World primate: can this be extrapolated to humans? / Células mononucleares de medula óssea versus células-tronco mesenquimais de tecido adiposo em cicatrização de lesão óssea em primata: pode ser extrapolado para humanos?

In veterinary medicine, the cell therapy is still unexplored and there are many unanswered questions that researchers tend to extrapolate to humans in an attempt to treat certain injuries. Investigating this subject in nonhuman primates turns out to be an unparalleled opportunity to better understand the dynamics of stem cells against some diseases. Thus, we aimed to compare the efficiency of bone marrow mononuclear cells (BMMCs) and mesenchymal stem cells (MSCs) from adipose tissue of Chlorocebus aethiops in induced bone injury. Ten animals were used, male adults subjected, to bone injury the iliac crests. The MSCs were isolated by and cultured. In an autologous manner, the BMMCs were infused in the right iliac crest, and MSCs from adipose tissue in the left iliac crest. After 4.8 months, the right iliac crests fully reconstructed, while left iliac crest continued to have obvious bone defects for up to 5.8 months after cell infusion. The best option for treatment of injuries with bone tissue loss in old world primates is to use autologous MSCs from adipose tissue, suggesting we can extrapolate the results to humans, since there is phylogenetic proximity between species.(AU)

Na medicina veterinária, a terapia celular ainda é inexplorada e há muitas perguntas não respondidas, o que leva os pesquisadores a uma tendência a estender a terapia para os seres humanos, na tentativa de tratar certas lesões. Investigar esse assunto em primatas não humanos revela-se uma oportunidade sem precedentes para compreender melhor a dinâmica das células-tronco contra algumas doenças. Assim, objetivou-se comparar a eficiência das células mononucleares de medula óssea (BMMCs) e das células-tronco mesenquimais (MSCs) do tecido adiposo de Chlorocebus aetiops na lesão óssea induzida. Foram utilizados 10 animais, adultos do sexo masculino, submetidos à lesão óssea nas cristas ilíacas. As MSCs foram isoladas e cultivadas; de forma autóloga, as BMMCs foram infundidas na crista ilíaca direita e as MSCs de tecido adiposo na crista ilíaca esquerda. Após 4,8 meses, a crista ilíaca direita foi totalmente reconstruída, enquanto a crista ilíaca esquerda continuou apresentando defeito ósseo evidente por até 5,8 meses após a infusão. A melhor opção para o tratamento de lesões com perda de tecido ósseo em primatas do Velho Mundo é a utilização de MSCs autólogas de tecido adiposo, sugerindo que se podem estender os resultados para seres humanos, uma vez que há proximidade filogenética entre as espécies.(AU)

Adenoid cystic carcinoma with myoepithelial predominance affecting maxilla and maxillary sinus.

Adenoid cystic carcinoma (ACC) represents less than 10% of all salivary gland tumors, rarely occurring centrally in the jaws. Herein we describe the case of a 36-year-old female patient presenting a painless swelling in the right maxilla, resulting in marked facial asymmetry. Intra-orally it was observed a swelling covered by an erythematous and irregular-surfaced mucosa, affecting the gingiva and crossing the midline of the hard palate. Imaging studies showed a mixed radiolucent-radiopaque lesion with ill-defined borders, involving the right side of the maxilla and the maxillary sinus. Incisional biopsy revealed basophilic cribriform tumoral islands and solid sheets of neoplastic cells invading bone trabeculae. Most of the tumoral cells presented myoepithelial characteristics, while few true luminal/epithelial cells were observed. To illustrate the epithelial-myoepithelial pattern, immunohistochemical reactions were performed, as well as double immunohistochemical staining. The diagnosis was intraosseous ACC, which features were discussed as well as the potential differential diagnosis.

Carnitine partially improves oxidative stress, acrosome integrity, and reproductive competence in doxorubicin-treated rats.

Doxorubicin has been largely used in anticancer therapy in adults, adolescents, and children. The efficacy of l-carnitine as an antioxidant substance has been confirmed both in humans and rats. Carnitine, present in testis and epididymis, is involved in sperm maturation. It is also effective in infertility treatment. As a continuation of a previous study, we evaluated whether some spermatic qualitative parameters, DNA integrity, chromatin structure, and fertility status, could be ameliorated by the carnitine treatment in adult rats, which were subsequently exposed to doxorubicin at pre-puberty. Pre-pubertal male rats were distributed into four groups: Sham Control; Doxorubicin; l-carnitine; l-carnitine + Doxorubicin (l-carnitine injected 1 h before doxorubicin). At 100 days of age, all groups were reassigned into two sets: One set was submitted to the evaluation of sperm motility, acrosome integrity, mitochondrial activity, sperm chromatin structure analysis (SCSA), and evaluation of the oxidative stress. The other set of rats was destined to the evaluation of reproductive competence. The percentage of spermatozoa with intact acrosome integrity was higher in the Carnitine+Doxorubicin group when compared with the Doxorubicin group. However, sperm motility and mitochondrial activity were not improved by carnitine pre-treatment. Both values of malondialdehyde and nitrite (indirect measurement of nitric oxide) concentrations were statistically higher in the only doxorubicin-treated group when compared to the Carnitine + Doxorubicin group. Fertility index and implantation rate were lower in Doxorubicin group, when compared to Carnitine + Doxorubicin group. Moreover, the percentage of spermatozoa with damaged DNA was higher in the Doxorubicin-treated group when compared to the Carnitine+Doxorubicin group. l-carnitine, when administered before doxorubicin, partially preserved the acrosome integrity, an important feature related to sperm fertilization ability that positively correlated with the reproductive competence and sperm DNA integrity at adulthood. In conclusion, l-carnitine attenuated the long-term alterations caused by doxorubicin in the germ cells and improved male reproductive capacity in adulthood.

Using artificial neural networks to select the parameters for the prognostic of mild cognitive impairment and dementia in elderly individuals.

BACKGROUND AND OBJECTIVES: A huge number of solutions based on computational systems have been recently developed for the classification of cognitive abnormalities in older people, so that individuals at high risk of developing neurodegenerative diseases, such as Cognitive Impairment and Alzheimer?s disease, can be identified before the manifestation of the diseases. Several factors are related to these pathologies, making the diagnostic process a hard problem to solve. This paper proposes a computational model based on the artificial neural network to classify data patterns of older adults. METHODS: The proposal takes into account the several parameters as diagnostic factors as gender, age, the level of education, study time, and scores from cognitive tests (Mini-Mental State Examination, Semantic Verbal Fluency Test, Clinical Dementia Rating and Ascertaining Dementia). This non-linear regression model is designed to classify healthy and pathological aging with machine learning techniques such as neural networks, random forest, SVM, and stochastic gradient boosting. We deployed a simple linear regression model for the sake of comparison. The primary objective is to use a regression model to analyze the data set aiming to check which parameters are necessary to achieve high accuracy in the diagnosis of neurodegenerative disorders. RESULTS: The analysis demonstrated that the usage of cognitive tests produces median values for the accuracy greater than 90%. The ROC analysis shows that the best sensitivity performance is above 98% and specificity of 96% when the configurations have only cognitive tests. CONCLUSIONS: The presented approach is a valuable tool for identifying patients with dementia or MCI and for supporting the clinician in the diagnostic process, by providing an outstanding support decision tool in the diagnostics of neurodegenerative diseases.

Progressive lesions of central nervous system in microcephalic fetuses with suspected congenital Zika virus syndrome.

OBJECTIVE: To describe the pattern and progression of central nervous system (CNS) lesions in microcephalic fetuses with suspected Zika virus (ZIKV) infection. METHODS: In this prospective study in Salvador, Brazil, we analyzed fetuses diagnosed with microcephaly and suspected ZIKV infection after a routine primary care ultrasound scan between July 2015 and February 2016 raised suspicion of fetal microcephaly. The pregnancies were followed with serial ultrasound scans until delivery at one of the three main referral centers for fetal abnormalities in Salvador, Brazil. Microcephaly was diagnosed when the head circumference was two or more SDs below the mean for gestational age and its relationship with ZIKV infection was defined according to the World Health Organization's criteria. All women were interviewed, to assess potential factors associated with fetal microcephaly. Serology test results for toxoplasmosis, cytomegalovirus, rubella, syphilis and human immunodeficiency virus (HIV) were recorded, as were previous routine ultrasound results. Signs/symptoms of infection during the pregnancy were noted. RESULTS: Of 60 cases of suspected ZIKV-related fetal microcephaly seen during the study period, eight were excluded due to serological evidence of other congenital infections or major ultrasound chromosomal markers. In the remaining 52 fetuses, microcephaly was diagnosed between 19 and 40 (median, 27.7; interquartile range, 23.4-32.0) weeks of gestation. The main ultrasound findings were: ventriculomegaly (65.4% of cases), cerebral calcifications (44.2%) and posterior fossa abnormalities (32.7%). 9.6% presented with arthrogryposis as an associated finding. Microcephaly was an isolated finding in four cases (7.7%). While ventriculomegaly was progressive in 41.2% of cases with this finding, the velocity of head circumference increase decreased progressively in almost all cases. Exanthematic disease was present in the majority (86.5%) of the women, 67.3% presenting in the first trimester of pregnancy. Additional lesions were detected after birth in 71.4% of the 35 cases with neonatal follow-up. CONCLUSIONS: The majority of cases of congenital ZIKV syndrome have other ultrasonographic findings in addition to microcephaly. ZIKV-related CNS anomalies present mainly as progressive CNS lesions and slowing rate of growth of the fetal head, and this seems to be evident only in the late second trimester, even when maternal infection occurs in the first trimester. Other ultrasound findings, such as ventriculomegaly, brain calcifications and posterior fossa destruction lesions, are also common in this congenital syndrome. Posterior fossa destruction lesions and arthrogryposis are an uncommon finding in other congenital infections, perhaps suggesting a novel severe congenital syndrome associated with fetal ZIKV. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Predicting colostrum quality from performance in the previous lactation and environmental changes.

Nine New Hampshire Holstein dairies contributed to a study to investigate if colostrum quality could be predicted by cow performance in the previous lactation and by environmental factors during the 21-d prepartum period. The numbers of days below 5°C (D<), days above 23°C (D>), and days between 5 and 23°C (D) were used in the development of the regression equation. Between 2011 and 2014, 111 colostrum samples were obtained and analyzed for IgG. Producers recorded cow identification number, calf date of birth, sex of the calf, colostrum yield, hours from parturition to colostrum harvest, and weeks on pasture during the dry period (if any). Dairy Herd Improvement data from each cow and weather data were compiled for analysis. Information accessed was predicted transmitting abilities for milk, fat (PTAF), protein (PTAP), and dollars; previous lactation: milk yield, fat yield, fat percent, protein percent, protein yield, somatic cell score, days open, days dry, days in milk, and previous parity (PAR). Colostrum yield was negatively correlated with IgG concentration (r=-0.42) and D (r=-0.2). It was positively correlated with D> (r=0.30), predicted transmitting ability for milk (r=0.26), PTAF (r=0.21), and PTAP (r=0.22). Immunoglobulin G concentration (g/L) was positively correlated with days in milk (r=0.21), milk yield (r=0.30), fat yield (r=0.34), protein yield (r=0.26), days open (r=0.21), PAR (r=0.22), and tended to be positively correlated with DD (r=0.17). Immunoglobulin G concentration (g/L) was negatively correlated with D> (r=-0.24) and PTAF (r=-0.21) and tended to be negatively correlated with PTAP (r=-0.18). To determine the best fit, values >0 were transformed to natural logarithm. All nontransformed variables were also used to develop the model. A variance inflation factor analysis was conducted, followed by a backward elimination procedure. The resulting regression model indicated that changes in Ln fat yield (ß=2.29), Ln fat percent (ß=2.15), Ln protein yield (ß=-2.25), and Ln protein percent (ß=2.1) had largest effect on LnIgG. This model was validated using 27 colostrum samples from 9 different farms not used in the model. The difference between means for actual and predicted colostrum quality (IgG, g/L) was 13.6g/L. Previous lactation DHI data and weather data can be used to predict the IgG concentration of colostrum.

Short communication: Cinnamaldehyde taste preferences of weaned dairy heifers.

Within a dairy enterprise, one major cost is raising young calves. Optimizing the feeding programs of dairy calves is imperative for the sustainability and profitability of dairy operations. Essential oils appear to be natural alternatives to antibiotics and function similarly to ionophores. Supplemental antibiotic ionophores have been very successful in improving feed efficiency and rate of gain in calves, as well as decreasing disease incidences; however, calves may be developing resistance to ionophores and the use of antibiotics in animal feeds has been a major concern for consumers. No current research has examined the value or palatability of supplementing essential oils to dairy heifers. The purpose of this sequential elimination experiment was to evaluate the taste preferences of 6 weaned dairy heifers [approximately 3mo old; 95±10.8kg of body weight (BW)] provided with 0 (control), 1, 2, 3, or 4mg/kg of BW of cinnamaldehyde daily. Heifers had 2 d of adaptation to the new feeding regimen before the experiment started and were then offered the 5 experimental diets for 5 d. The most preferred diet was removed and the study continued with the 4 remaining diets. The most preferred diets were again eliminated sequentially, so that only 2 diets remained on d 13 and 14. Each diet was ranked based on the weight of feed refused at the end of each feeding segment. Overall ranking of the 5 treatments were control, 2, 1, 3, and 4mg/kg of BW of cinnamaldehyde. Results indicated that heifers preferred diets without cinnamaldehyde; however, when only cinnamaldehyde diets remained, dry matter intake was not negatively affected regardless of the concentration of cinnamaldehyde provided.

Prepartum supplementation of nicotinic acid: Effects on health of the dam, colostrum quality, and acquisition of immunity in the calf.

Nicotinic acid (NA) has been shown to reduce lipolysis, alter milk components and the ruminal environment, and increase blood flow. Increased blood flow to the mammary gland during colostrogenesis might increase nutrients and immunoglobulin concentration of colostrum. Twenty-six multiparous Holstein cows were housed in a tiestall barn. Cows were blocked by expected calving date and randomly assigned to 1 of 2 treatments 4 wk prepartum: (1) 0g/d of NA (control, CON) or (2) 48g/d of NA (NA). Total mixed ration amounts fed and refused were measured daily to determine dry matter intake. Blood samples were collected from dams every Monday, Wednesday, and Friday from the coccygeal vein or artery and were analyzed for glucose, nonesterified fatty acids (NEFA), and ß-hydroxybutyrate (BHB). Colostrum was collected and weighed within 90 min of parturition. Colostral immunoglobulin G (IgG) concentration was analyzed using radial immunodiffusion assay. Calves were removed from their dams before suckling and weighed within 30 min after birth. Calves received 3 L of a lacteal-based colostrum replacer that provided a total of 225.8g of IgG within 2h of birth. Calf blood samples were collected via jugular venipuncture at 0 and 24h of age and analyzed for IgG concentration and determination of apparent efficiency of absorption. Colostrum yield, dry matter intake, IgG yield, and fat and solids percentage of colostrum did not differ between treatments. Serum concentrations of glucose and BHB were not affected by treatment. We detected an effect of week on serum glucose concentrations at calving and on serum BHB concentrations at 1 wk postpartum. There was a treatment by week effect for serum NEFA concentrations at 1 wk postpartum, where cows that received NA prepartum had higher serum NEFA concentration than CON cows, indicating that a NEFA rebound occurred. No differences were observed for calf body weight, 0- or 24-h serum IgG concentration, or apparent efficiency of absorption. Supplementation of NA increased IgG concentration in colostrum from 73.8 to 86.8g/L. Results indicate that 48g/d of supplemental NA during the prepartum period improved colostrum quality.

Effects of human visitation on calf growth and performance of calves fed different milk replacer feeding levels.

Twenty-eight newborn Holstein heifer calves from the university herd and 8 newborn Holstein heifer calves from a commercial herd were blocked by birth and herd into 1 of 4 treatments: conventional [20% crude protein (CP), 20% fat] milk replacer (MR; treatment C) with (1) or without (0) human visitation, or a higher plane of MR nutrition (28% CP, 20% fat) regimen (treatment A) with (1) or (0) without human visitation. Calves on C MR treatments received 454g of MR from d 2 to 41. Calves on A MR received 916g of MR from d 2 to 8 and 1134g of MR from d 9 to 41. Visitation with calves occurred at 1030 and 1430h daily from d 1 to 56 and comprised verbal stimulation and stirring of starter grain. An opaque curtain divided the calf nursery, with calves in the front half assigned to visitation treatments and those in the rear half not assigned to visitation treatments. Calves were fed their MR treatment until d 43 (preweaning), after which all calves received half of their allotment of MR until d 49 (weaning). Calves were tracked for the next week until d 56 (postweaning). Starter grain and MR intakes were measured daily along with weekly body weight and skeletal measurements. One half of the calves on each treatment had blood samples taken via jugular venipuncture on d 41 (preweaning), 43, 45, 47, 49, and 51 (postweaning) to evaluate blood glucose, urea, nonesterified fatty acids, and cortisol concentrations. During the preweaning and weaning phases, calves on A0 and A1 treatments consumed more MR, less starter, and weighed more than the C0 and C1 calves. Calves on A0 and A1 had greater average daily gain (ADG), hip and withers gain, were taller at the hip, and had larger girths during the preweaning phase. Overall, body weight, withers and hip heights, and heart girths were greater in A0 andA1 calves during the weaning week. Efficiency of utilization of estimated metabolizable energy (ME) intake (ADG/ME) were similar. Glucose and nonesterified fatty acids concentrations were greater in visited calves preweaning. An interaction for glucose was observed during weaning, with A1 calves having the highest concentration and A0 calves having the lowest concentrations during weaning. Cortisol tended to be higher in visited calves during weaning. Postweaning, calves formerly fed A0 and A1 treatments had lower blood glucose and tended to have higher urea and cortisol concentrations than C0 and C1 treatments. The higher plane of nutrition fed calves tended to have higher cortisol concentrations indicating that they experienced more stress due to the removal of MR more than calves fed conventionally. Calves fed the higher plane of MR nutrition consumed more dry matter, ME, and water weighed more, had a greater ADG, and were taller than calves fed the conventional MR. These calves were more efficient (ADG/dry matter intake) when expressed on a dry matter basis, but had similar efficiency when expressed on an ME basis (ADG/ME). Visiting calves did little to reduce the stress of weaning when calves are fed the higher plane of nutrition MR feeding regimen.

Carnitine partially protects the rat testis against the late damage produced by doxorubicin administered during pre-puberty.

Doxorubicin, an anticancer drug, is widely included in chemotherapy protocols to combat childhood cancer. Carnitine, an important quaternary amine, is present in testis and epididymis and is involved in sperm maturation; it has been used in infertility treatment. In a previous study, our group observed that L-carnitine given before etoposide, another chemotherapeutic drug, reduces the spermatogenic damage and protects germ cells against apoptosis. This study aimed to evaluate the antiapoptotic and cytoprotective actions of L-carnitine in long- and mid-term basis, on the seminiferous epithelium of doxorubicin-treated pre-pubertal rats. Forty-eight 30-day-old male Wistar rats were distributed into four groups: sham-control; doxorubicin; carnitine; carnitine/doxorubicin (L-carnitine injected 1 h before doxorubicin). The rats were submitted to euthanasia at 64 and 100 days of age and their testes were collected for biometric, morphometric, and histopathological analyses. The numerical density of apoptotic germ cells was obtained (TUNEL method). In adult phase (100 days), the following spermatic parameters were analyzed: mature spermatid (19 step) count and sperm daily production per testis; sperm number and transit time through the epididymal caput/corpus and cauda; frequency of morphologically abnormal spermatozoa (from epididymal fluid), as well as sperm DNA integrity (Comet assay). The testicular and spermatic parameters at both ages were improved in rats treated with carnitine before doxorubicin. At 64 days, the TUNEL-positive germ cell frequency was lower in the carnitine/doxorubicin-treated rats comparatively to the doxorubicin-treated rats. At 100 days of age, the sperm DNA fragmentation was also lower in the previously carnitine-treated rats, as evidenced by the analysis of three parameters. Carnitine reduced the late testicular and spermatic damages caused by doxorubicin, probably providing a partial cytoprotection against the deleterious action of doxorubicin administration to pre-pubertal rats. However, further studies shall be undertaken to investigate the protective mechanisms involved in such germ cell preservation.

Multiple nevoid basal cell carcinoma syndrome associated with congenital orbital teratoma, caused by a PTCH1 frameshift mutation.

Gorlin-Goltz syndrome, or nevoid basal cell carcinoma syndrome (NBCCS), is a rare autosomal dominant disorder caused by mutations in the PTCH1 gene and shows a high level of penetrance and variable expressivity. The syndrome is characterized by developmental abnormalities or neoplasms and is diagnosed with 2 major criteria, or with 1 major and 2 minor criteria. Here, we report a new clinical manifestation associated with this syndrome in a boy affected by NBCCS who had congenital orbital teratoma at birth. Later, at the age of 15 years, he presented with 4 major and 4 minor criteria of NBCCS, including multiple basal cell carcinoma and 2 odontogenic keratocysts of the jaw, both confirmed by histology, more than 5 palmar pits, calcification of the cerebral falx, extensive meningeal calcifications, macrocephaly, hypertelorism, frontal bosses, and kyphoscoliosis. PTCH1 mutation analysis revealed the heterozygous germline mutation c.290dupA. This mutation generated a frameshift within exon 2 and an early premature stop codon (p.Asn97LysfsX43), predicting a truncated protein with complete loss of function. Identification of this mutation is useful for genetic counseling. Although the clinical symptoms are well-known, our case contributes to the understanding of phenotypic variability in NBCCS, highlighting that PTCH1 mutations cannot be used for predicting disease burden and reinforces the need of a multidisciplinary team in the diagnosis, treatment, and follow-up of NBCCS patients.

The Rst-Neph family of cell adhesion molecules in Gallus gallus.

The Rst-Neph family comprises an evolutionarily conserved group of single-pass transmembrane glycoproteins that belong to the immunoglobulin superfamily and participate in a wide range of cell adhesion and recognition events in both vertebrates and invertebrates. In mammals and fish, three Rst-Neph members, named Neph1-3, are present. Besides being widely expressed in the embryo, particularly in the developing nervous system, they also contribute to the formation and integrity of the urine filtration apparatus in the slit diaphragm of kidney glomerular podocytes, where they form homodimers, as well as heterodimers with Nephrin, another immunoglobulin-like cell adhesion molecule. In mice, absence of Neph1 causes severe proteinuria, podocyte effacement and perinatal death, while in humans, a mutated form of Nephrin leads to congenital nephrotic syndrome of the Finnish type. Intriguingly, neither Nephrin nor Neph3 are present in birds, which nevertheless have typical vertebrate kidneys with mammalian-like slit diaphragms. These characteristics make, in principle, avian systems very helpful for understanding the evolution and functional significance of the complex interactions displayed by Rst-Neph proteins. To this end we have started a systematic study of chicken Neph embryonic and post-embryonic expression, both at mRNA and protein level. RT-qPCR mRNA quantification of the two Neph paralogues in adult tissues showed that both are expressed in heart, brain, and retina. Neph1 is additionally present in kidney, liver, pancreas, lungs, and testicles, while Neph2 mRNA is barely detected in kidney, testicles, pancreas and absent in liver and lungs. In embryos, mRNA from both genes can already be detected at as early as stage HH14, and remain expressed until at least HH28. Finally, we used a specific antibody to examine the spatial dynamics and subcellular distribution of ggNeph2 between stages HH20-28, particularly in the mesonephros, dermomyotomes, developing heart, and retina.

Novel compound heterozygous mutations in the desmoplakin gene cause hair shaft abnormalities and culminate in lethal cardiomyopathy.

A 2-month-old white girl born to nonconsanguineous parents presented to the dermatology department with hair loss that had commenced a few months after birth. Although her hair loss later stabilized, it remained sparse. By the age of 2 years, she was noted to have developed focal keratoderma over pressure points of the soles. Aged 5 years, she was admitted to hospital with a chest infection, and investigations at that point revealed that she had a dilated cardiomyopathy. Subsequent genetic investigations identified compound heterozygous mutations in the 3' end of the desmoplakin (DSP) gene (7567delAAGA and 6577G>A), explaining the cardiocutaneous phenotype.

Colostrum replacer feeding regimen, addition of sodium bicarbonate, and milk replacer: the combined effects on absorptive efficiency of immunoglobulin G in neonatal calves.

Eighty Holstein and Holstein cross dairy calves were blocked by birth date and randomly assigned to 1 of 8 treatments within each block to examine the effect of a colostrum replacer (CR) feeding regimen, supplementation of CR with sodium bicarbonate (NaHCO3), and provision of a milk replacer (MR) feeding on IgG absorption. Calves were offered a CR containing 184.5g/L of IgG in either 1 feeding at 0h (within 30 min of birth), with or without 30g of NaHCO3, with or without a feeding of MR at 6h of age, or 2 feedings of CR (123g of IgG at 0h with or without 20g of NaHCO3 and 61.5g of IgG at 6h with or without 10g of NaHCO3), with or without a MR feeding at 12h. Therefore, treatments were (1) 1 feeding of CR; (2) 2 feedings of CR; (3) 1 feeding of CR + 30g of NaHCO3; (4) 2 feedings of CR + 30g of NaHCO3; (5) 1 feeding of CR + MR feeding; (6) 2 feedings of CR + MR feeding; (7) 1 feeding of CR + 30g NaHCO3 + MR feeding; and (8) 2 feedings of CR + 30g NaHCO3 + MR feeding. Blood samples were obtained at 0, 6, 12, 18, and 24h after birth and were analyzed for IgG via radial immunoassay. Results indicated that CR feeding schedule, MR feeding, and the interactions CR × Na, CR × MR, and CR × Na × MR were similar for 24-h serum IgG, apparent efficiency of absorption, or area under the curve. Serum IgG at 24h, apparent efficiency of absorption, and area under the curve were decreased with addition of NaHCO3 compared with calves not supplemented with NaHCO3. These data indicate that supplementation of CR with NaHCO3 is not beneficial to IgG absorption and feeding MR within 6h of CR feeding does not affect IgG absorption.

Effects of lasalocid and intermittent feeding of chlortetracycline on the growth of prepubertal dairy heifers.

Forty Holstein heifers entered the 12-wk study at approximately 12 wk of age. At enrollment, heifers were blocked by birth date and assigned to 1 of 4 treatments: (1) carrier (30 g; control); (2) lasalocid + carrier (1 mg/kg of body weight; L); (3) chlortetracycline + carrier (22 mg/kg of body weight; CTC); (4) L + CTC + carrier (CTCL). Heifers on CTC and CTCL were provided treatment Monday through Friday and carrier only on Saturday and Sunday. These heifers were provided their respective treatment during wk 1 to 4, 6, and 10; wk 5, 7 to 9, and 11 to 12 heifers were provided the nonmedicated carrier. Heifers were individually fed a total mixed ration with treatments top-dressed at 1200 h daily. Dry matter intake was monitored for each heifer and feed provided was adjusted according to individual intakes. Skeletal measurements were taken weekly and blood samples were obtained every Monday, Wednesday, and Friday. Blood samples were analyzed for thyroxine concentration via radial immunoassay. Heifers supplemented with L had lower average daily gain , overall body weight gain, and trends for lower daily body length gain and overall girth gain compared with CTC heifers, but similar to control and CTCL heifers. Heifers fed L had lower hip height gain and overall hip height gain compared with CTCL heifers, but similar to control and CTC heifers. Heifers fed L had lower overall withers height gain compared with control heifers, but similar to CTC and CTCL heifers. No treatment effect on thyroxine concentrations was observed. These data indicate that L did not increase growth. Results from this experiment indicate that supplementing heifers with L was not beneficial and no benefits to supplementing heifers with CTC or the combination of CTC and L were evident compared with control heifers. Heifers in this study experienced minimal health problems and were regarded to be under low stress levels. Supplementing CTC and L may be beneficial to growing heifers under conditions where disease exposure and stressors are greater.

Submandibular glands and the regulation of gastric proliferation and TGFα distribution during rat postnatal development

Rodent gastric mucosa grows and differentiates during suckling-weaning transition. Among the molecules in rat milk, EGF and TGFβ are important peptides in the control of cell proliferation, and together with TGFα, they are also produced by submandibular glands. We aimed to determine the effect of saliva and milk on epithelial cell proliferation in the stomach of rat pups. We also examined the distribution of TGFα in the gastric mucosa after sialoadenectomy (SIALO) and fasting in order to determine whether this growth factor is affected by the deprivation of molecules derived from saliva and milk. SIALO was performed at 14 days and fasting was induced 3 days later. Cell proliferation was evaluated through metaphasic index and TGFα was detected by immunohistochemistry. We observed that whereas SIALO did not alter cell division, since the metaphasic index (MI) was unchanged, fasting stimulated cell proliferation (P < 0.05). After SIALO and fasting, MI was reduced when compared to the fasted group (P < 0.05). We found that TGFα is distributed along gastric gland and SIALO did not interfere in the localization and number of immunolabeled cells, but fasting increased their density when compared to the control (P < 0.05). The association of SIALO and fasting reduced TGFα immunostaining (P < 0.05). Therefore, during fasting, high MI was parallel to increased TGFα in gastric epithelium, but interestingly, this effect was found only in the presence of submandibular glands. We suggest that during suckling, peptides derived from saliva and milk are important to regulate gastric growth.