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Autosomal dominant polycystic kidney disease (ADKPD) is the most frequent type of polycystic kidney disease. It is inherited through family members, with an incidence of approximately 1:400 to1:1000.Typically, individuals with ADKPD are identified between their fourth and fifth decade of life. ADKPD occurs as a results of mutation in one of the two genes, PDK1 and PDK2.Patients with PKD1 experience renal failure at an earlier onset than those with PKD2. We report on a 2 year-old-boy with hepatosplenomegaly and signs of portal hypertension. Both kidneys appeared normal until the age of 8, when multiple cysts developed, this being typical of ADKPD. Suspecting ADKPD, we performed whole exome sequencing, thereby confirming a mutation of c.6730 673del p.(Ser 2244Hisfs*17). The investigations of all family members found other individuals affected by ADKPD.

Introduction: In this study estimated genetic and phenotypic correlations between fifteen complete blood count (CBC) traits and thirty-three heritable plasma metabolites in young healthy nursery pigs. In addition, it provided an opportunity to identify candidate genes associated with variation in metabolite concentration and their potential association with immune response, disease resilience, and production traits.Methods: The blood samples were collected from healthy young pigs and Nuclear Magnetic Resonance (NMR) was used to quantify plasma metabolites. CBC was determined using the ADVIA® 2120i Hematology System. Genetic correlations of metabolite with CBC traits and single step genome-wide association study (ssGWAS) were estimated using the BLUPF90 programs.Results: Results showed low phenotypic correlation estimates between plasma metabolites and CBC traits. The highest phenotypic correlation was observed between lactic acid and plasma basophil concentration (0.36 ± 0.04; p < 0.05). Several significant genetic correlations were found between metabolites and CBC traits. The plasma concentration of proline was genetically positively correlated with hemoglobin concentration (0.94 ± 0.03; p < 0.05) and L-tyrosine was negatively correlated with mean corpuscular hemoglobin (MCH; −0.92 ± 0.74; p < 0.05). The genomic regions identified in this study only explained a small percentage of the genetic variance of metabolites levels that were genetically correlated with CBC, resilience, and production traits.Discussion: The results of this systems approach suggest that several plasma metabolite phenotypes are phenotypically and genetically correlated with CBC traits, suggesting that they may be potential genetic indicators of immune response following disease challenge. Genomic analysis revealed genes and pathways that might interact to modulate CBC, resilience, and production traits.

Accelerated growth programs during prepubertal periods have been promoted to advance the first calving of beef heifers. The objectives of the present study were to evaluate nutrition-induced changes on first lactation milk yield and composition and on gene expression of the mammary gland in Parda de Montaña primiparous cows. Female calves ( = 16) were involved in a 2 × 2 factorial experiment. In the preweaning period (PRE-W; 0-6 mo), female calves were either fed a creep feed supplement (Creep) or fed only their dam's milk (Control). In the postweaning period (POST-W; 6-15 mo), heifers received either a high-energy diet (91.7 MJ/d) or a moderate-energy diet (79.3 MJ/d). All the heifers were managed together from breeding (15 mo) to the end of their first lactation (32 mo). Animal performance; milk production and quantity during the first lactation; plasma glucose, IGF-I, and leptin concentrations; and RNA samples from the mammary gland at the end of the first lactation of the primiparous cows (32 mo) were analyzed. The BW and ADG of the primiparous cow during its first lactation were not different among treatments; however, creep feeding during PRE-W reduced milk production (0.01), milk CP, crude fat, lactose, nonfat solids, and casein content throughout lactation and increased somatic cell count in the third (0.05) and fourth month of lactation (0.10). The energy level during the POST-W had no effect on milk production and quality. Gene expression in the mammary gland was affected by the diet in the PRE-W and POST-W, with the PRE-W diet having the greatest impact. During the PRE-W, creep feeding resulted in upregulation of genes related to immune response and chemokine activity, suggesting that these animals might be in a compromised immune status. Therefore, this strategy would not be recommendable; meanwhile, increasing the energy level in the diet during the POST-W would be recommendable, because it had no deleterious effects on milk yield and composition.

High Intensity Focused Ultrasound (HIFU) therapy is an innovative approach for tissue ablation, based on high intensity focused ultrasound beams. At the focus, HIFU induces a temperature elevation and the tissue can be thermally destroyed. In fact, this approach has been tested in a number of clinical studies for the treatment of several tumors, primarily the prostate, uterine, breast, bone, liver, kidney and pancreas. For transcranial brain therapy, the skull bone is a major limitation, however, new adaptive techniques of phase correction for focusing ultrasound through the skull have recently been implemented by research systems, paving the way for HIFU therapy to become an interesting alternative to brain surgery and radiotherapy.

Transcranial high intensity focused ultrasound (HIFU) therapy guided by magnetic resonance imaging (MRI) is a promising approach for the treatment of brain tumours. Our objective is to validate a dedicated therapy monitoring system for rodents for transcranial HIFU therapy under MRI guidance in an in vivo brain tumour model.A dedicated MR-compatible ultrasound therapy system and positioning frame was developed. Three MR-compatible prefocused ultrasonic monoelement transducers were designed, operating at 1.5 MHz and 2.5 MHz with different geometries. A full protocol of transcranial HIFU brain therapy under MRI guidance was applied in n = 19 rats without and n = 6 rats with transplanted tumours (RG2). Different heating strategies were tested. After treatment, histological study of the brain was performed in order to confirm thermal lesions.Relying on a larger aperture and a higher frequency, the 2.5 MHz transducer was found to give better results than other ones. This single element transducer optimised the ratio of the temperature elevation at the focus to the one at the skull surface. Using optimised transducer and heating strategies enabled thermal necrosis both in normal and tumour tissues as verified by histology while limiting overheating in the tissues in contact with the skull.In this study, a system for transcranial HIFU therapy guided by MRI was developed and tested in an in vivo rat brain tumour model. The feasibility of this therapy set-up to induce thermal lesions within brain tumours was demonstrated.

The aim of this study was to investigate the effects of vitamin E (VE) supplementation and alfalfa grazing during fattening on fatty acid composition and mRNA expression of genes related to lipid metabolism in the LM of Rasa Aragonesa light lambs. After weaning, 48 lambs were kept indoors and fed a commercial concentrate and a VE supplemented concentrate (480 mg DL-α-tocopheryl acetate/kg DM) for 0 (control [CON]), 10 (VE10d), 20 (VE20d), and 30 d (VE30d) before slaughtering at 22 to 24 kg. Simultaneously, 8 unweaned lambs grazed in alfalfa (154 mg α-tocopherol/kg DM) paddocks with their dams and supplemented with the commercial concentrate (ALF). Immediately after slaughter, LM was sampled to determine gene expression. After 24 h of cooling at 4°C, LM was extracted to determine intramuscular fat (IMF) content and fatty acid composition. The IMF content did not differ with the dietary treatment ( = 0.212). Unweaned grazing alfalfa lambs had greater concentration of rumenic acid (C18:2 c9,t11; P0.001) and lower oleic acid (C18:1 c9; = 0.001) content and PUFA n-6:n-3 ratio (P0.001) but similar expression of genes implicated in lipid metabolism compared to the concentrate-fed lambs. Vitamin E supplementation did not modify muscle fatty acid composition; however, it increased the expression of FADS2 and ELOVL6, which are involved in desaturation of long-chain fatty acid and the elongation of SFA and MUFA. The results showed that a short period of VE supplementation, especially 10 (VE10d) and 20 d (VE20d), modified gene expression. Overall, the results showed that VE may be acting as a regulatory factor for transcriptional control of genes related to lipid metabolism in the muscle of Rasa Aragonesa light lambs (22-24 kg live weight and younger than 90 d old).

Aim: Gaucher disease is a multisystemic disorder characterized by glucocerebrosidase enzyme deficiency. The aim of this study was to present clinical aspects and diagnostic data of 19 patients (17 type 1, 2 type 3) in our service. Methods: Clinical findings, genetic analysis, laboratory work up, liver and spleen volumes were analyzed for 19 patients. Results: Mean age was 17 years (5-32 years); mean age at diagnosis was 11, 4 years (5-31 years). Most common presenting symptom was splenomegaly (all patients). Most frequent mutation was heterozygous N370S. One patient had severe anemia before the treatment. 16 patients had thrombocytopenia. All patients had high level of chitotriosidase before the treatment (240 times higher than normal value). Conclusion: There is a large variety of clinical signs in Gaucher disease. In our experience a proper investigation of patient followed by further expensive examinations is the cornerstone of diagnostic.

High Intensity Focused Ultrasound (HIFU) therapy is an innovative approach for tissue ablation, based on high intensity focused ultrasound beams. At the focus, HIFU induces a temperature elevation and the tissue can be thermally destroyed. In fact, this approach has been tested in a number of clinical studies for the treatment of several tumors, primarily the prostate, uterine, breast, bone, liver, kidney and pancreas. For transcranial brain therapy, the skull bone is a major limitation, however, new adaptive techniques of phase correction for focusing ultrasound through the skull have recently been implemented by research systems, paving the way for HIFU therapy to become an interesting alternative to brain surgery and radiotherapy.

Meat intramuscular fat (IMF) contributes to meat quality and consumer acceptance. Molecular events that occur during IMF deposition and the identification of genes that are differentially expressed during this process are important to the design of an optimal nutrition plan for animals. In the present study, we examined the effect of the forage type (grazing vs. hay pasture) fed to ewes and the effect of lamb sex on the LM fatty acid (FA) profile and gene expression of suckling lambs (10 to 12 kg of BW at slaughter); ewes received pasture hay (PH) or grazed pasture (GRE). Forage type had a significant effect on IMF FA profile. Ewes grazing green forage (GRE) promoted the formation and deposition of vaccenic acid (C18:1n-7), CLA, and PUFA n-3 in LM from their suckling lambs (P0.05). We found that forage type affected the expression of the sterol regulatory element binding transcription factor 1 (SREBF1) gene in females. However, in males, it modulated stearoyl CoA desaturase (SCD) gene expression (P0.05). Moreover, our results showed that females, independent of the diet of the ewes (PH or GRE), are predisposed to develop fat and to upregulate the expression of key genes of transcriptional factors PPARA, CEBPB, SREBF1, and lipoprotein lipase (LPL) and SCD (P0.05). The data suggest that SREBF1, SCD, and most likely CEBPB gene expression in young suckling lambs is modulated by both lamb sex and forage type fed to ewes. Fatty acid indicators PUFA, n-6/n-3, CLA, and SFA are closely related to LPL, SCD, PPARA, and CEBPB gene expression depending on animal sex or the diet of ewes. This study suggests that grazing pasture affects FA composition promoting greater vaccenic, CLA, and total PUFA n-3 FA in female and male suckling lambs, and it is mediated through the regulation of lipogenic enzyme expression.

In the framework of HIFU transcranial brain therapy, it is mandatory to develop techniques capable of assessing the focusing quality and location before the treatment. Monitoring heat deposition in real time and verifying the extension of the treated area are also important steps. In this study, an imaging protocol is proposed to:1/ locate the US radiation force induced displacement in tissues and quantify the acoustic pressure at focus prior to HIFU; 2/ monitor the temperature rise during HIFU; and 3/ assess the changes in elasticity in the treated area. A 7T MRI scanner was equipped with a home‐made stereotactic frame for rats and a US focused transducer working at 1.5 MHz. Such a tool is key for the evaluation of the biological effects of HIFU on brain tissue and tumors. The proposed protocol was successfully tested on 12 rats with and without injected tumors. The accurate localization of the focal point prior to HIFU was demonstrated in vivo. Furthermore, the pressure estimation in situ allowed to acc...

International audience; Recent studies have demonstrated the feasibility of transcranial high-intensity focused ultrasound (HIFU) therapy in the brain using adaptive focusing techniques. However, the complexity of the procedures imposes provision of accurate targeting, monitoring and control of this emerging therapeutic modality in order to ensure the safety of the treatment and avoid potential damaging effects of ultrasound on healthy tissues. For these purposes, a complete workflow and setup for HIFU treatment under magnetic resonance (MR) guidance is proposed and implemented in rats. For the first time, tissue displacements induced by the acoustic radiation force are detected in vivo in brain tissues and measured quantitatively using motion-sensitive MR sequences. Such a valuable target control prior to treatment assesses the quality of the focusing pattern in situ and enables us to estimate the acoustic intensity at focus. This MR-acoustic radiation force imaging is then correlated with conventional MR-thermometry sequences which are used to follow the temperature changes during the HIFU therapeutic session. Last, pre- and post-treatment magnetic resonance elastography (MRE) datasets are acquired and evaluated as a new potential way to non-invasively control the stiffness changes due to the presence of thermal necrosis. As a proof of concept, MR-guided HIFU is performed in vitro in turkey breast samples and in vivo in transcranial rat brain experiments. The experiments are conducted using a dedicated MR-compatible HIFU setup in a high-field MRI scanner (7 T). Results obtained on rats confirmed that both the MR localization of the US focal point and the pre- and post-HIFU measurement of the tissue stiffness, together with temperature control during HIFU are feasible and valuable techniques for efficient monitoring of HIFU in the brain. Brain elasticity appears to be more sensitive to the presence of oedema than to tissue necrosis.

Objective The aim of the study is to evaluate the effectiveness of mental health screening to identify co morbidities in different pediatric population at risk. Methods The SDQ is a brief screening questionnaire that investigates the presence of emotional and behavioral problems in children and adolescents. We have analyzed 416 questionnaires completed by children and parents referred to Child Neurology, Pediatric Endocrinology and Gastroenterology Units. Results Results indicate a higher presence of psychopathological disorders in entire population which means high needs for therapeutic intervention. The main psychiatric diagnoses more frequent in entire pediatric population in study result: ADHD 2.9%, Anxiety Disorders 13.2%, Somatization Disorder 12%, Obsessive-compulsive disorder 5.7% and Behavioral Disorder 2.9%. Conclusion The SDQ could be used by clinicians to detect early psychopathological disorders in children with different kind of chronic organic disease. These findings draw attention to the important role of screening for urgent needs related to self-harm, depression and violent behaviors to children in emergency unit (4) or screening for mood disorders to other pediatric units as hematology or cardiology.

The paper proposes a switched-capacitor approach to generate a high voltage sinusoid at a frequency of few hundred Hertz for driving a highly capacitive load. The need for such a driver stemmed from an ITS (intelligent transportation systems) project that requires efficient inverters for driving electroluminescent (EL) displays. The EL devices are for outdoor use, to be powered by batteries, and low power consumption is a design requirement. The proposed inverter circuit employs the EL device as the hold capacitor and multiple dc levels are switched in to develop a 'stepped' sinusoid around the capacitor. The large time constant of the load necessitates that switching be done in smaller voltage steps. It also reduces stress on the switches and ordinary low voltage transistors can be used in the circuit implementation. The circuitry takes advantage of the floating nature of the load to employ switching at a frequency higher than the desired signal frequency. This leads to simpler filtering to remove the unwanted noise in the 'stepped' signal. The advantages of the proposed inverter are: power efficiency, no use of bulky inductors and capacitors, digital frequency tuning, and a cost effective low profile design. The circuit operations, configurations, and basic experimental results is presented in the paper.