Aldosterone-progesterone relationship in sexually intact Chihuahua bitches.

BACKGROUND: Aldosterone represents an important target of heart failure therapy and may be a valuable indicator of the renin-angiotensin-aldosterone system activity. However, its assessment might be challenging because of the effect of individual factors. In a recent study, intact female dogs showed the highest value of urinary aldosterone-to-creatinine ratio (UAldo:C) compared to other sex categories. In humans and rodents, an influence of progesterone has been reported by several studies. To our knowledge, the relationship between aldosterone and progesterone has not yet been investigated in dogs. The aim of this prospective study was to investigate this relationship in sexually intact Chihuahua females, measuring both hormones twice in the same bitch, that is in anoestrus when progesterone concentrations are baseline and in dioestrus when they are high. RESULTS: The study population consisted of 14 sexually intact Chihuahua bitches. Serum progesterone (34.06 (21.17-44.90) vs. 0.19 [0.13-0.38] ng/ml; P < 0.001) and urinary aldosterone (9886.98 ± 5735.22 vs. 5005.72 ± 2127.73 pg/ml; P = 0.01) were significantly higher in dioestrus compared to anoestrous. Urinary aldosterone-to-creatinine ratio was higher in dioestrus compared to anoestrus (4.16 [3.17-6.80] vs. 3.39 ± 1.64 µg/g), but it did not reach the statistical significance (P = 0.056). Serum progesterone showed a moderate positive correlation with urinary aldosterone (ρ = 0.638, P < 0.001) and UAldo:C (ρ = 0.516, P = 0.005). CONCLUSIONS: The results of the present study suggest the existence of a progesterone-aldosterone relationship in canine species, indicating that sex and phase of reproductive cycle should be taken into account when interpreting aldosterone concentrations. Further studies are needed to confirm these results on a larger canine population and to identify the underlying mechanisms in this species.

Effects of animal position on M-mode, two-dimensional, and Doppler echocardiographic measurements in healthy French bulldogs.

Echocardiography is the most widely accepted diagnostic tool for assessment of cardiac function and morphology in dogs and is usually performed in lateral recumbency. However, in some situations or in stressed patients, it is necessary to perform it in a standing position. Only one study evaluated the effects of animal position on selected two-dimensional and M-mode echocardiographic variables in four healthy dogs of different breeds, but not in brachycephalic breeds. In these breeds echocardiographic evaluation is sometimes needed in standing position due to the severity of brachycephalic obstructive airway syndrome and the impossibility of managing them in lateral recumbency without causing stress and choking danger. The objectives of this prospective, observational study were to (a) evaluate the effects of lateral recumbency versus standing positions on echocardiographic M-mode, two-dimensional, Doppler flow measurements, and Tissue Doppler imaging in healthy French bulldogs (FBs); (b) assess the intra- and interoperator variability of the standing echocardiographic examination; and (c) compare the obtained results with the available data from the literature. Forty healthy FBs (20 females/20 males) were sampled. The median age and weight were 2.45 years (IQR25-75 , 1.18-4.16) and 12.7 kg (IQR25-75 , 10.88-13.46). There were no differences between lateral recumbency and standing position measurements (P > 0.05). Intraoperator coefficients of variation (CVs) ranged from 0.5% to 10.1%, whereas interoperator CVs ranged from 1% to 14.2%. Only E wave peak velocity, aortic, and pulmonary flows were consistent with the previously published reference ranges in lateral recumbency. In conclusion, echocardiography in a standing position could be a useful tool in FBs.

The transcriptome profile of human trisomy 21 blood cells.

BACKGROUND: Trisomy 21 (T21) is a genetic alteration characterised by the presence of an extra full or partial human chromosome 21 (Hsa21) leading to Down syndrome (DS), the most common form of intellectual disability (ID). It is broadly agreed that the presence of extra genetic material in T21 gives origin to an altered expression of genes located on Hsa21 leading to DS phenotype. The aim of this study was to analyse T21 and normal control blood cell gene expression profiles obtained by total RNA sequencing (RNA-Seq). RESULTS: The results were elaborated by the TRAM (Transcriptome Mapper) software which generated a differential transcriptome map between human T21 and normal control blood cells providing the gene expression ratios for 17,867 loci. The obtained gene expression profiles were validated through real-time reverse transcription polymerase chain reaction (RT-PCR) assay and compared with previously published data. A post-analysis through transcriptome mapping allowed the identification of the segmental (regional) variation of the expression level across the whole genome (segment-based analysis of expression). Interestingly, the most over-expressed genes encode for interferon-induced proteins, two of them (MX1 and MX2 genes) mapping on Hsa21 (21q22.3). The altered expression of genes involved in mitochondrial translation and energy production also emerged, followed by the altered expression of genes encoding for the folate cycle enzyme, GART, and the folate transporter, SLC19A1. CONCLUSIONS: The alteration of these pathways might be linked and involved in the manifestation of ID in DS.

Breed-specific vertebral heart score, vertebral left atrial size, and radiographic left atrial dimension in Cavalier King Charles Spaniels: Reference interval study.

Cavalier King Charles Spaniels (CKCS) are predisposed to developing myxomatous mitral valve disease (MMVD), with radiographs frequently used to screen for evidence of left-sided cardiomegaly secondary to MMVD. Vertebral heart size (VHS), vertebral left atrial size (VLAS), modified VLAS (M-VLAS), and radiographic left atrial dimension (RLAD) are reported as objective measurements of global heart size and left atrial size. Normal VHS in CKCS (10.6 ± 0.5) is reportedly higher than the non-breed-specific value (9.7±0.5). Breed-specific VLAS, M-VLAS, and RLAD cut-offs have not been reported in CKCS. The aim of this prospective reference interval study was to describe the VHS, VLAS, M-VLAS, and RLAD values for 30 clinically healthy adult CKCS. Inclusion criteria were unremarkable physical examination, normal echocardiography, and thoracic radiographs without malposition/abnormalities. There were 22 female and eight male dogs. Ages ranged from 1 to 6 years. The VHS mean value in our sample was 10.08 ± 0.56 (95% range, 9.87-10.29). This was significantly greater than a previously published general canine reference value of 9.7 ± 0.5 and significantly less than a previously published CKCS breed-specific value of 10.6 ± 0.5 (P < 0.01). Mean VLAS, M-VLAS, and the RLAD values in our study were 1.79 ± 0.3 (95% range, 1.68-1.9), 2.23 ± 0.44 (95% range, 2.06-2.39), and 1.2 ± 0.34 (95% range, 1.07-1.33), respectively. These were significantly less than previously published reference interval values (P < 0.001). The VHS, M-VLAS, and the RLAD were not affected by sex, body weight, or BCS; whereas the VLAS was moderately affected by body weight. Findings from this study can be used as background for future thoracic radiographic assessments in CKCS.

Factors affecting the urinary aldosterone-to-creatinine ratio in healthy dogs and dogs with naturally occurring myxomatous mitral valve disease.

BACKGROUND: Chronic renin-angiotensin-aldosterone system (RAAS) activation in course of heart diseases contributes to cardiac remodeling and heart failure. Myxomatous mitral valve disease (MMVD) is characterized by different stages of severity and trend of RAAS activity during the course of the disease is still uncertain. The urinary aldosterone-to-creatinine ratio (UAldo:C) has been proven to reflect RAAS activation in dogs and might be a useful marker in monitoring therapy and disease progression, but data about this parameter need to be expanded. The objective of this study was to evaluate the UAldo:C in healthy dogs and dogs with naturally occurring MMVD, and to investigate the relationships between this parameter and clinical, echocardiographic and laboratory variables. RESULTS: The study population consisted of 149 dogs: 49 healthy and 100 MMVD dogs (45 stage B1, 13 stage B2 and 42 stage C). Urinary aldosterone-to-creatinine ratio was not significantly different among healthy and MMVD dogs of any stages. Breed, sex and age showed a significant impact on UAldo:C. In particular, Chihuahua and Cavalier King Charles spaniel showed significantly higher UAldo:C than other breeds, as well as intact females than other genders. In stage C dogs, UAldo:C appeared to be increased by spironolactone and was positively associated with furosemide dose (P = 0.024). Aldosterone breakthrough (ABT) appeared to occur in 36% (8/22) of stage C dogs not receiving spironolactone. A significant positive association between UAldo:C and left atrium-to-aortic root ratio (LA/Ao) was found. CONCLUSIONS: Individual factors such as breed, sex and age appeared to influence UAldo:C, and therapy seemed to add further variability. In the light of these results, comparing the UAldo:C of a single patient with a population-based reference value might lead to wrong interpretations and an individual monitoring should be considered. The prevalence of ABT in the present study (36%) was in line with those previously reported. However, due to the high individual variability of UAldo:C found in the study, even this result should be re-evaluated in the setting of an individual longitudinal approach. The positive association between UAldo:C and LA/Ao supports the mutual relationship between RAAS and cardiac remodeling.

Interobserver variability of radiographic methods for the evaluation of left atrial size in dogs.

The objectives of this retrospective, observer agreement study were to (a) test variability of radiographic left atrial dimension (RLAD) and vertebral left atrial size (VLAS) measurements among observers with different levels of expertise in thoracic radiology and cardiology, (b) assess whether one method is better than the other in detecting left atrial enlargement (LAE), and (c) assess the agreement among RLAD, VLAS, and American College of Veterinary Internal Medicine (ACVIM) classes. Seventy-four dogs (eight healthy and 66 with mitral valve disease) with thoracic radiographs and echocardiography performed on the same day were reviewed. Thirty showed echocardiographic LAE. Left atrial dimension was quantified using RLAD and VLAS by six different operators with three levels of clinical experience in veterinary cardiology/radiology. Vertebral heart score and fourth thoracic vertebra (T4) were also measured. Differences in T4, vertebral heart score (VHS), RLAD, and VLAS measurements were found among six operators and among the three levels of clinical expertise as well as between veterinary cardiology readers and veterinary radiology readers (P < .05). The area under the receiver operating characteristic (AUC) curve for VHS showed good performances for all observers and level and type of expertise; the AUC for RLAD and VLAS was suboptimal only for the radiology student. Our RLAD and VLAS cutoffs (1.9 and 2.43 v, respectively) were better related to qualitative radiographic than quantitative echocardiographic LAE evaluation. Radiographic LA dimension and VLAS showed an increase proportional to the worsening of the ACVIM class. In conclusion, these results allow us to affirm that RLAD and VLAS are reproducible measurements for detecting LAE. Better performances are associated with clinical expertise and background.

Human trisomy 21 fibroblasts rescue methotrexate toxic effect after treatment with 5-methyl-tetrahydrofolate and 5-formyl-tetrahydrofolate.

Trisomy 21 causes Down syndrome (DS), the most common human genetic disorder and the leading genetic cause of intellectual disability. The alteration of one-carbon metabolism was described as the possible metabolic cause of the intellectual disability development in subjects with DS. One of the biochemical pathways involved in the one-carbon group transfer is the folate cycle. The cytotoxic drug methotrexate (MTX) is a folic acid (FA) analogue which inhibits the activity of dihydrofolate reductase enzyme involved in the one-carbon metabolic cycle. Trisomy 21 cells are more sensitive to the MTX effect than euploid cells, and in 1986 Jérôme Lejeune and Coll. demonstrated that MTX was twice as toxic in trisomy 21 lymphocytes than in control cells. In the present work, the rescue effect on MTX toxicity mediated by FA and some of its derivatives, tetrahydrofolate (THF), 5-formyl-THF, and 5-methyl-THF, in both normal and trisomy 21 skin fibroblast cells, was evaluated. A statistically significant rescue effect was obtained by 5-formyl-THF, 5-methyl-THF, and their combination, administered together with MTX. In conclusion, trisomy 21 fibroblast cell lines showed a good response to the rescue effects of 5-formyl-THF and 5-methyl-THF on the MTX toxicity almost as normal cell lines.

Systematic reanalysis of partial trisomy 21 cases with or without Down syndrome suggests a small region on 21q22.13 as critical to the phenotype.

A 'Down Syndrome critical region' (DSCR) sufficient to induce the most constant phenotypes of Down syndrome (DS) had been identified by studying partial (segmental) trisomy 21 (PT21) as an interval of 0.6-8.3 Mb within human chromosome 21 (Hsa21), although its existence was later questioned. We propose an innovative, systematic reanalysis of all described PT21 cases (from 1973 to 2015). In particular, we built an integrated, comparative map from 125 cases with or without DS fulfilling stringent cytogenetic and clinical criteria. The map allowed to define or exclude as candidates for DS fine Hsa21 sequence intervals, also integrating duplication copy number variants (CNVs) data. A highly restricted DSCR (HR-DSCR) of only 34 kb on distal 21q22.13 has been identified as the minimal region whose duplication is shared by all DS subjects and is absent in all non-DS subjects. Also being spared by any duplication CNV in healthy subjects, HR-DSCR is proposed as a candidate for the typical DS features, the intellectual disability and some facial phenotypes. HR-DSCR contains no known gene and has relevant homology only to the chimpanzee genome. Searching for HR-DSCR functional loci might become a priority for understanding the fundamental genotype-phenotype relationships in DS.

Genotype-phenotype correlation for congenital heart disease in Down syndrome through analysis of partial trisomy 21 cases.

Among Down syndrome (DS) children, 40-50% have congenital heart disease (CHD). Although trisomy 21 is not sufficient to cause CHD, three copies of at least part of chromosome 21 (Hsa21) increases the risk for CHD. In order to establish a genotype-phenotype correlation for CHD in DS, we built an integrated Hsa21 map of all described partial trisomy 21 (PT21) cases with sufficient indications regarding presence or absence of CHD (n=107), focusing on DS PT21 cases. We suggest a DS CHD candidate region on 21q22.2 (0.96Mb), being shared by most PT21 cases with CHD and containing three known protein-coding genes (DSCAM, BACE2, PLAC4) and four known non-coding RNAs (DSCAM-AS1, DSCAM-IT1, LINC00323, MIR3197). The characterization of a DS CHD candidate region provides a useful approach to identify specific genes contributing to the pathology and to orient further investigations and possibly more effective therapy in relation to the multifactorial pathogenesis of CHD.

Serum proteomic profiles in CKCS with Mitral valve disease.

BACKGROUND: Myxomatous mitral valve disease (MVD) is the most common acquired heart disease in dogs, and the Cavalier King Charles Spaniel (CKCS) is the most studied breed because of the high prevalence, early onset and hereditary component evidenced in the breed. MVD has different severity levels, and there are many practical limitations in identifying its asymptomatic stages. Proteomic techniques are valuable for studying the proteins and peptides involved in cardiovascular diseases, including the period prior to the clinical onset of the disease. The aim of this study was to identify the serum proteins that were differentially expressed in healthy CKCS and those affected by MVD in mild to severe stages. Proteomics analysis was performed using two-dimensional gel electrophoresis separation and a bioinformatics analysis for the detection of differentially expressed spots. In a comparative analysis, protein spots with a p < 0.05 (ANOVA) were considered statistically significant and were excised from the gels for analysis by MALDI-TOF-MS for protein identification. RESULTS: Eight proteins resulted differentially expressed among the groups and significantly related to the progression of the disease. In mild affected group versus healthy dogs complement factor H isoform 2, inhibitor of carbonic anhydrase, hemopexin, dystrobrevin beta isoform X7 and CD5 molecule-like resulted to be down-regulated, whereas fibronectin type-III domain-containing protein 3A isoform X4 was up-regulated. In severe affected dogs versus healthy group complement factor H isoform 2, calpain-3 isoform X2, dystrobrevin beta isoform X7, CD5 molecule-like and l-2-hydroxyglutarate dehydrogenase resulted to be down-regulated. Complement factor H isoform 2, calpain-3 isoform X2, dystrobrevin beta isoform X7, CD5 molecule-like and hydroxyglutarate dehydrogenase were found to be down-regulated in mild affected group versus healthy dogs. All of these proteins except complement factor H followed a decreasing trend according to the progression of the pathology. CONCLUSION: The differential expression of serum proteins demonstrates the possibility these might be valuable for the detection and monitoring of the disease. Further longitudinal studies are required to determine whether differential protein expression occurs sufficiently early in the progression of the disease and with sufficient predictive value to allow proteomics analysis to be used as an early detection and on-line diagnostic tool.

Is urinary neutrophil gelatinase-associated lipocalin able to predict acute kidney injury episodes in very low birth weight infants in clinical settings?

BACKGROUND: We evaluated the potential utility of elevated urinary neutrophil gelatinase-associated lipocalin (UNGAL) concentration as a screening test for early identification of acute kidney injury (AKI) in very low birth weight (VLBW) newborns. METHODS: Urine for UNGAL analysis was collected prospectively daily until 32 wk postmenstrual age in 91 VLBW newborns, yielding 2,899 specimens. UNGAL values > 50 ng/ml were considered elevated. AKI was defined as two or more consecutive elevations in s[Cr] above the 95th percentile adjusted for gestational age and chronological age within a 48 h period. We compared UNGAL values taken during the 5 d prior to AKI onset (pre-AKI) to values taken during non-AKI days. RESULTS: Overall, 15 episodes of AKI were identified in 13 infants. UNGAL was available in 44 pre-AKI days and 969 non-AKI days. UNGAL > 50 ng/ml occurred more often in pre-AKI days than in non-AKI days (risk ratio 3.48 (1.89, 6.40)). Positive and negative likelihood ratios were 1.92 (1.52, 2.41) and 0.52 (0.34, 0.78), respectively. CONCLUSION: Although UNGAL elevation > 50 ng/ml discriminates between pre-AKI and non-AKI days, high false positive and false negative rates limit utility as a screening test in VLBW newborns.

Serum creatinine concentration in very-low-birth-weight infants from birth to 34-36 wk postmenstrual age.

BACKGROUND: Serum creatinine (s[Cr]) reference ranges for very-low-birth-weight (VLBW) infants must account for physiologic changes in the first months of life. METHODS: We retrospectively identified a sample of 218 appropriate-for-gestational age (GA) VLBW infants without risk factors for renal impairment, and classified into one of three GA groups: 25-27, 28-29, and 30-33 wk. We observed three phases of s[Cr] change (initial, decline, and equilibrium), whose characteristics varied by GA group. We used mixed-effects regression models to estimate mean and upper 95th prediction interval of s[Cr] for each GA group from birth to 34-36 wk post menstrual age (PMA). RESULTS: In phase I, s[Cr] increased after birth, then returned slowly to baseline. The duration of phase I and the magnitude of s[Cr] rise decreased with increasing GA. In phase II, s[Cr] declined abruptly at a rate that increased with GA. A gradual transition to phase III, a steady-state equilibrium with similar s[Cr] among GA groups, began at approximately 34-36 wk PMA. We constructed GA group-specific nomograms depicting s[Cr] behaviour across the three phases. CONCLUSION: The reference ranges derived from a sample of infants without risk factors for renal impairment provide a context for quantitative interpretation of s[Cr] trends in VLBW infants.

First clinical evidence that trimethylsulfonium can serve as a biomarker for the production of the signaling molecule hydrogen sulfide.

BACKGROUND: Hydrogen sulfide (H2S) is established as the third gaseous signaling molecule and is known to be overproduced in down syndrome (DS) due to the extra copy of the CBS gene on chromosome 21, which has been suggested to contribute to the clinical manifestation of this condition. We recently discovered trimethylsulfonium (TMS) in human urine and highlighted its potential as a selective methylation metabolite of endogenously produced H2S, but the clinical utility of this novel metabolite has not been previously investigated. We hypothesize that the elevation of H2S production in DS would be reflected by an elevation in the methylation product TMS. METHODS: To test this hypothesis, a case-control study was performed and the urinary levels of TMS were found to be higher in the DS group (geo. mean 4.5 nM, 95 % CI 2.4-3.9) than in the control (N) group (3.1 nM, 3.5-6.0), p-value 0.01, whereas the commonly used biomarker of hydrogen sulfide, thiosulfate, failed to reflect this alteration in H2S production (15 µM (N) vs. 13 µM (DS), p-value 0.24. RESULTS: The observed association is in line with the proposed hypothesis and provides first clinical evidence of the utility of TMS as a novel and more sensitive biomarker for the endogenous production of the third gaseous signaling molecule than the conventionally used biomarker thiosulfate, which is heavily dependent on bacterial hydrogen sulfide production. CONCLUSION: This work shows that TMS must be explored in clinical conditions where altered metabolism of hydrogen sulfide is implicated.

Cross-sectional developmental trajectories in the adaptive functioning of children and adolescents with Down syndrome.

BACKGROUND: Persons with Down syndrome (DS) reveal adaptive functioning (AF) difficulties. Studies on AF in DS have focused mainly on describing the profile (i.e., strengths in socialization, and weaknesses in communication), while less is known about age-related differences. This study aimed to elucidate how AF changes with age in children and adolescents with DS, taking a cross-sectional developmental trajectory approach. Moreover, the contribution of both chronological age (CA) and mental age (MA) on AF development was explored. METHOD: This study involved 115 children and adolescents (between 3 and 16 years old) with DS. Parents were interviewed about their children's AF on communication, daily living and socialization skills. Children and adolescents with DS were assessed on their developmental level. RESULTS: While participants' standard scores on AF decreased linearly over time, their age-equivalent scores increased with linear or segmented patterns, depending on the skill considered. CA and MA were related to daily living skills and socialization to much the same degree, while MA correlated more strongly than CA with communication. CONCLUSION: This study contributes to the understanding of how AF develops in children and adolescents with DS, showing that CA and MA both contribute to shaping the skills involved.

Study of correlations between serum taurine, thyroid hormones and echocardiographic parameters of systolic function in clinically healthy Golden retrievers fed with commercial diet.

Taurine deficiency predisposes to the development of nutritional dilated cardiomyopathy and is widespread in dogs fed with non-traditional diets. However, Golden retrievers show lower plasma taurine concentration and an impaired systolic function compared to breeds of the same size and morphotype. For these reasons, it can be difficult to classify a subject from a cardiological point of view, with the risk of considering as pathological characteristics that can be completely normal in this breed. This is a cross-sectional multicenter study. The aims were 1) to identify breed-specific range of serum taurine concentration, 2) to describe a correlation between serum taurine concentration and echocardiographic parameters of systolic function in clinically healthy Golden retrievers fed with traditional diet, 3) to identify a correlation between thyroid hormones, serum taurine concentration and echocardiographic indices. Sixty clinically healthy Golden retrievers (33% males, 67% females) were included. Fifty-three dogs were fed with traditional diets and their range of serum taurine concentration was 398.2 (31.8-430) nmol/ml. Serum taurine concentration was found to be negatively correlated to systolic internal diameter of the left ventricle and systolic and diastolic left ventricular indices and volumes obtained with different methods, whereas was positively correlated to the left ventricle ejection and shortening fractions but difference was not statistically significative. A weak but significant correlation between serum taurine and T4 was demonstrated. Serum taurine median values in dogs with normal systolic function were higher than in dogs with impaired systolic function. A cut-off of serum taurine concentration of 140.6 nmol/ml had a moderate sensitivity and specificity in the identification of an impaired left ventricular systolic function (AUC 0.6, Se 78%, Sp 44%). This study showed that the median serum taurine concentration was significantly lower in dogs with impaired systolic function. Therefore, echocardiographic monitoring is recommended in all dogs with serum taurine concentration lower than 140.6 nmol/ml.

The functional roles of S-adenosyl-methionine and S-adenosyl-homocysteine and their involvement in trisomy 21.

The one-carbon metabolism pathway is involved in critical human cellular functions such as cell proliferation, mitochondrial respiration, and epigenetic regulation. In the homocysteine-methionine cycle S-adenosyl-methionine (SAM) and S-adenosyl-homocysteine (SAH) are synthetized, and their levels are finely regulated to ensure proper functioning of key enzymes which control cellular growth and differentiation. Here we review the main biological mechanisms involving SAM and SAH and the known related human diseases. It was recently demonstrated that SAM and SAH levels are altered in plasma of subjects with trisomy 21 (T21) but how this metabolic dysregulation influences the clinical manifestation of T21 phenotype has not been previously described. This review aims at providing an overview of the biological mechanisms which are altered in response to changes in the levels of SAM and SAH observed in DS.

Corrigendum: One-carbon pathway metabolites are altered in the plasma of subjects with Down syndrome: relation to chromosomal dosage.

[This corrects the article DOI: 10.3389/fmed.2022.1006891.].

Zinc metabolism and its role in immunity status in subjects with trisomy 21: chromosomal dosage effect.

Introduction: Trisomy 21 (T21), which causes Down syndrome (DS), is the most common chromosomal aneuploidy in humankind and includes different clinical comorbidities, among which the alteration of the immune system has a heavy impact on patient's lives. A molecule with an important role in immune response is zinc and it is known that its concentration is significantly lower in children with T21. Different hypotheses were made about this metabolic alteration and one of the reasons might be the overexpression of superoxide dismutase 1 (SOD1) gene, as zinc is part of the SOD1 active enzymatic center. Methods: The aim of our work is to explore if there is a linear correlation between zinc level and immune cell levels measured in a total of 217 blood samples from subjects with T21. Furthermore, transcriptome map analyses were performed using Transcriptome Mapper (TRAM) software to investigate whether a difference in gene expression is detectable between subjects with T21 and euploid control group in tissues and cells involved in the immune response such as lymphoblastoid cells, thymus and white blood cells. Results: Our results have confirmed the literature data stating that the blood zinc level in subjects with T21 is lower compared to the general population; in addition, we report that the T21/control zinc concentration ratio is 2:3, consistent with a chromosomal dosage effect due to the presence of three copies of chromosome 21. The transcriptome map analyses showed an alteration of some gene's expression which might explain low levels of zinc in the blood. Discussion: Our data suggest that zinc level is not associated with the levels of immunity cells or proteins analyzed themselves and rather the main role of this ion might be played in altering immune cell function.

Structural brain abnormalities in Pallister-Killian syndrome: a neuroimaging study of 31 children.

BACKGROUND: Pallister-Killian syndrome (PKS) is a rare genetic disorder caused by mosaic tetrasomy of 12p with wide neurological involvement. Intellectual disability, developmental delay, behavioral problems, epilepsy, sleep disturbances, and brain malformations have been described in most individuals, with a broad phenotypic spectrum. This observational study, conducted through brain MRI scan analysis on a cohort of patients with genetically confirmed PKS, aims to systematically investigate the neuroradiological features of this syndrome and identify the possible existence of a typical pattern. Moreover, a literature review differentiating the different types of neuroimaging data was conducted for comparison with our population. RESULTS: Thirty-one individuals were enrolled (17 females/14 males; age range 0.1-17.5 years old at first MRI). An experienced pediatric neuroradiologist reviewed brain MRIs, blindly to clinical data. Brain abnormalities were observed in all but one individual (compared to the 34% frequency found in the literature review). Corpus callosum abnormalities were found in 20/30 (67%) patients: 6 had callosal hypoplasia; 8 had global hypoplasia with hypoplastic splenium; 4 had only hypoplastic splenium; and 2 had a thin corpus callosum. Cerebral hypoplasia/atrophy was found in 23/31 (74%) and ventriculomegaly in 20/31 (65%). Other frequent features were the enlargement of the cisterna magna in 15/30 (50%) and polymicrogyria in 14/29 (48%). Conversely, the frequency of the latter was found to be 4% from the literature review. Notably, in our population, polymicrogyria was in the perisylvian area in all 14 cases, and it was bilateral in 10/14. CONCLUSIONS: Brain abnormalities are very common in PKS and occur much more frequently than previously reported. Bilateral perisylvian polymicrogyria was a main aspect of our population. Our findings provide an additional tool for early diagnosis.Further studies to investigate the possible correlations with both genotype and phenotype may help to define the etiopathogenesis of the neurologic phenotype of this syndrome.

Does the Cambridge classification alone predict the possibility to perform echocardiographic examination in lateral recumbency in dogs affected by brachycephalic obstructive airways syndrome?

OBJECTIVES: To evaluate if the functional grading system (Cambridge classification) of brachycephalic obstructive airways syndrome (BOAS) and the temperament score can be useful tools in predicting the feasibility of echocardiographic examination in lateral recumbency. The hypothesis is that the temperament of the dog, rather than the severity of BOAS alone, can exacerbate respiratory symptoms (dyspnea, stertor, stridor and/or cyanosis) during lateral containment. METHODS: Prospective cross-sectional study. Twenty-nine French Bulldogs were included and classified according to the Cambridge classification for the BOAS and to the Maddern score for the temperament. Receiver operating characteristic analysis was used to evaluate the sensitivity (Se) and specificity (Sp) of the Cambridge classification, of the temperament score and their sum to predict the feasibility of the echocardiography in lateral recumbency without dyspnea/cyanosis. RESULTS: 8 females (27.59%) and 21 (72.41%) males French Bulldogs of 3 years (IQR25-75 1-4), and 12.45 kg (IQR25-7511.5-13.25) were included. The Cambridge classification alone was not predictive for the possibility of performing the echocardiography in lateral recumbency, unlike temperament score and the sum of the two classification indices. The diagnostic accuracy of Cambridge classification (AUC 0.81, Se 50%, Sp 100%), temperament score (AUC 0.73, Se 75%, Sp 69%), and their sum (AUC 0.83, Se 75%, Sp 85%) cut-offs was moderate for each score. CLINICAL SIGNIFICANCE: The dog's temperament, and therefore its susceptibility to stress, rather than the severity of BOAS (Cambridge classification) alone, is a good predictor of the possibility of performing the echocardiographic examination in standing instead of lateral recumbency.