Abnormalities In Organs Research Articles

Evaluation of Toxicity and Efficacy of Inotodiol as an Anti-Inflammatory Agent Using Animal Model.

Chaga mushroom (Inonotus obliquus) comprises polyphenolic compounds, triterpenoids, polysaccharides, and sterols. Among the triterpenoid components, inotodiol has been broadly examined because of its various biological activities. The purpose of this study is to examine inotodiol from a safety point of view and to present the potential possibilities of inotodiol for medical usage. From chaga mushroom extract, crude inotodiol (INO20) and pure inotodiol (INO95) were produced. Mice were treated with either INO20 or INO95 once daily using oral administration for repeated dose toxicity evaluation. Serum biochemistry parameters were analyzed, and the level of pro-inflammatory cytokines in the serum was quantified. In parallel, the effect of inotodiol on food allergic symptoms was investigated. Repeated administration of inotodiol did not show any mortality or abnormalities in organs. In food allergy studies, the symptoms of diarrhea were ameliorated by administration with INO95 and INO20. Furthermore, the level of MCPT-1 decreased by treatment with inotodiol. In this study, we demonstrated for the first time that inotodiol does not cause any detrimental effect by showing anti-allergic activities in vivo by inhibiting mast cell function. Our data highlight the potential to use inotodiol as an immune modulator for diseases related to inflammation.

MYL9 deficiency is neonatal lethal in mice due to abnormalities in the lung and the muscularis propria of the bladder and intestine.

Class II myosin complexes are responsible for muscle contraction as well as other non-sarcomeric contractile functions in cells. Myosin heavy chain molecules form the core of these structures, while light chain molecules regulate their stability and function. MYL9 is a light chain isoform that is thought to regulate non-sarcomeric myosin. However, whether this in only in specific cell types or in all cells remains unclear. To address this, we generated MYL9 deficient mice. These mice die soon after birth with abnormalities in multiple organs. All mice exhibited a distended bladder, shortening of the small intestine and alveolar overdistension in the lung. The Myl9 allele in these mice included a LacZ reporter knockin that allowed for mapping of Myl9 gene expression. Using this reporter, we show that MYL9 expression is restricted to the muscularis propria of the small intestine and bladder, as well as in the smooth muscle layer of the bronchi in the lung and major bladder vessels in all organs. This suggests that MYL9 is important for the function of smooth muscle cells in these organs. Smooth muscle dysfunction is therefore likely to be the cause of the abnormalities observed in the intestine, bladder and lung of MYL9 deficient mice and the resulting neonatal lethality.

Early Gonadal Development and Sex Determination in Mammal.

Sex determination is crucial for the transmission of genetic information through generations. In mammal, this process is primarily regulated by an antagonistic network of sex-related genes beginning in embryonic development and continuing throughout life. Nonetheless, abnormal expression of these sex-related genes will lead to reproductive organ and germline abnormalities, resulting in disorders of sex development (DSD) and infertility. On the other hand, it is possible to predetermine the sex of animal offspring by artificially regulating sex-related gene expression, a recent research hotspot. In this paper, we reviewed recent research that has improved our understanding of the mechanisms underlying the development of the gonad and primordial germ cells (PGCs), progenitors of the germline, to provide new directions for the treatment of DSD and infertility, both of which involve manipulating the sex ratio of livestock offspring.

Efficacy and toxicity of the DPCPX nanoconjugate drug study for the treatment of spinal cord injury in rats.

Effects of the Adenosine A1 blockade using 8-cyclopentyl-1,3-diprophyxanthine (DPCPX) nanoconjugate on inducing recovery of the hemidiaphragm paralyzed by hemisection have been thoroughly examined previously; however, the toxicology of DPCPX nanoconjugate remains unknown. This research study investigates the therapeutic efficacy and toxicology of the nanoconjugate DPCPX in the cervical spinal cord injury (SCI) rat model. We hypothesized that a single injection of nanoconjugate DPCPX in the paralyzed left hemidiaphragm (LDH) of hemisected rats at the 2nd cervical segment (C2Hx) would lead to the long-term recovery of LDH while showing minimal toxicity. Adult male rats underwent left C2Hx surgery and the diaphragms' baseline electromyography (EMG). Subsequently, rats were randomized into a control group and four treated subgroups. Three subgroups received a single intradiaphragmatic dose of either 0.09, 0.15, or 0.27 µg/kg, and one subgroup received 0.1 mg/kg of native DPCPX two times per day intravenously (i.v.) for 3 days (total 0.6 mg/kg). Rats were monitored for a total of 56 days. Compared with control, the treatment with nanoconjugate DPCPX at 0.09 µg/kg, 0.15 µg/kg, and 0.27 µg/kg doses elicited significant recovery of paralyzed LDH (i.e., 67% recovery at 8 wk) (P < 0.05). DPCPX nanoconjugate-treated rats had significant weight loss for first 2 wk but recovered significantly by day 56 (P < 0.05). The levels of gold in the blood and body tissues were below the recommended levels. No sign of weakness, histology of tissue damage, or organ abnormality was observed. A dose of DPCPX nanoconjugate can induce long-term diaphragm recovery after SCI without observed toxicity.NEW & NOTEWORTHY The intradiaphragmatic administration of nanoconjugate is safe and has the promise to significantly reduce the therapeutic dosage for the treatment and achieve long-term and possibly permanent recovery in respiratory muscle dysfunction after SCI. No toxicity of nanoconjugate was found in any of the experimental animals.

Earlier Detection of Brain Tumor by Pre-Processing Based on Histogram Equalization with Neural Network.

MRI is an influential diagnostic imaging technology specifically worn to detect pathological changes in tissues with organs early. It is also a non-invasive imaging method. Medical image segmentation is a complex and challenging process due to the intrinsic nature of images. The most consequential imaging analytical approach is MRI, which has been in use to detect abnormalities in tissues and human organs. The portrait was actualized for CAD (computer-assisted diagnosis) utilizing image processing techniques with deep learning, initially to perceive a brain tumor in a person with early signs of brain tumor. Using AHCN-LNQ (adaptive histogram contrast normalization with learning-based neural quantization), the first image is preprocessed. When compared to extant techniques, the simulation outcome shows that this proposed method achieves an accuracy of 93%, precision of 92%, and 94% of specificity.

Composition optimization and safety assessment of lactic-acid-bacteria-loaded composite film

ABSTRACT In this experiment, response surface methodology–central composite rotatable design was used to optimize the ratio of hydroxypropyl cellulose, konjac flour, and glycerol to obtain optimal composite film. Taking into account the importance of tensile strength, elongation at break and lactobacillus survivability, to the overall properties of composite film, a comprehensive index was proposed to evaluate comprehensive property by fuzzy comprehensive evaluation method. Optimization experiments showed that the optimal composition of the biocomposite membrane that maximized the combined response value was 0.586% HPC, 0.858% KF, and 1.620% GL. In vitro toxicology experiments were used for the safety evaluation of the membranes. In the 14-day feeding test, the mice in each experimental group grew well, and there were no obvious abnormalities in gross anatomical organs and related blood biochemical indicators. A 14-day mouse feeding experiment showed that the biocomposite film had no short-term toxicity, so the biocomposite film could be considered food-safe.

A CLINICAL CASE OF SECONDARY HYPERTENSION IN A 20-YEAR-OLD FEMALE WITH COARCTATION OF THE AORTA

Objective: Coarctation of the aorta (CoA) is a curable cause of secondary hypertension. Patients with CoA and associated heart disease typically are diagnosed in childhood, while isolated CoA may not be recognized until adulthood. Design and method: We report a case of diagnosis and treatment of CoA in a young female, previously observed with a diagnosis of essential hypertension. Results: A 20 years old female, diagnosed with hypertension at the age of 18, with difficult control of blood pressure (BP) values under treatment with angiotensin-converting enzyme inhibitors, beta-blockers and diuretics. The patient was referred to our clinic for evaluation. The clinical examination showed normal body development. BP on the left arm was 203/115 mm Hg, on the right arm - 206/115 mm Hg, normal heart sounds, 76 bpm. A systolic murmur was audible at the parasternal left area. BP on both legs was 140/90 mm Hg. There were no clinically significant abnormalities in other organs and systems. At transthoracic echocardiography we found the signs of a CoA, with a gradient of 80/32 mm Hg, and post-stenotic blood flow in the abdominal aorta. According to the computed tomography angiography signs of CoA in a typical place were confirmed as well as collateral blood flow through the dilated intercostal and mammary arteries. A week after admission to the hospital an operation of resecting the CoA, prosthetics of the arch and descending aorta, and transection of the aortopulmonary ligament was performed. The postoperative period was uneventful, the patient was discharged 10 days after the intervention with the recommendations of continuous administration of metoprolol 100 mg, torasemide 5 mg. At the 3–month follow–up visit the BP was stabilized at 130/80 mm Hg. Conclusions: This clinical case presented a rare isolated type of CoA and demonstrates the importance of qualitative examination of young patients with hypertension, including BP measurement on the lower extremities and transthoracic echocardiography with a compulsory examination of the aorta.

60-OR: High Prevalence of Multiorgan Steatosis and Fibroinflammation, Identified by Multiparametric Magnetic Resonance Imaging, in People with Type 2 Diabetes

Type 2 diabetes (T2D) is a multi-system disease characterised by a high prevalence of co-morbidities and micro- and macro-vascular complications. The aim of this study was to provide --comprehensive assessment of multi-organ health and pre-clinical detection of diabetes-related organ damage with a single, non-contrast MRI scan. We recruited 138 adults with T2D (median 62 yrs, 60 % male; BMI 31 kg/m2, 92 % on metformin [NCT04114682]) . MRI data were acquired to derive organ-specific measures of size, fat deposition, fibroinflammation, body composition and aortic distensibility (CoverScan®, Perspectum Ltd.) . Reference values of MRI metrics were based on 92 healthy volunteers and published literature. Statistical significance of co-prevalence was assessed by simulation assuming that values were independently binomially distributed. There was a high prevalence of abnormality in individual organs (Figure, left) . Prevalence of low skeletal muscle index and elevated pancreatic fat were associated with T2D duration. There was further evidence of co-prevalence of organ abnormalities (Figure right; 86 % with at least 2 organs affected) . Aortic stiffness was frequently associated with organ steatosis. MRI assessment can enrich the current blunt assessment of multi-organ abnormalities in T2D to inform earlier intervention and treatments. Disclosure N.Eichert: Employee; Perspectum Ltd. S.Ali: Other Relationship; NICE committee for diabetes. G.Thanabalasingham: Speaker's Bureau; Boehringer Ingelheim International GmbH. D.Cuthbertson: Other Relationship; AstraZeneca, Novo Nordisk. K.Gibbons: None. A.Hamid: None. R.Ramkhelawon: Other Relationship; NICE committee. V.E.Woolgar: None. R.Suriano: None. H.B.Thomaides-brears: Employee; Perspectum Ltd, Stock/Shareholder; Perspectum Ltd. R.Banerjee: Employee; Perspectum Ltd., Other Relationship; Perspectum Ltd., Stock/Shareholder; Perspectum Ltd. G.Kemp: None. Funding Innovate UK (Digital Health Technology Catalyst scheme) ; Perspectum Ltd.

1166-P: Distinct Phenotypes of Multiorgan Abnormalities in Long COVID and Type 2 Diabetes Identified by Multiparametric Magnetic Resonance Imaging

Introduction: Both long COVID and Type 2 Diabetes (T2D) are multi-system conditions requiring multi-organ assessment to monitor organ health and detect co-morbidities earlier. Here, we defined multi-organ abnormalities in both patient groups with a rapid, non-contrast MRI scan. Methods: We recruited 135 long COVID patients (NCT04369807) and 135 T2D patients (NCT04114682) . MRI data were acquired for organ-specific measures of size, fat deposition and fibroinflammation (CoverScan®, Perspectum Ltd.) . Reference values were based on 92 controls and published literature. Results: There was a high prevalence of organ abnormality in both patient groups (Figure, left) , including increased fat deposition (steatosis) in liver, pancreas, and kidney (Figure, right) . 35% of T2D patients had clustering of abnormalities involving at least 2 organs, compared to 23% in long COVID. Abnormalities affecting the liver and renomegaly were more common in T2D than in long COVID. Considering only obese patients, liver fibroinflammation, hepatomegaly, and renomegaly remained significantly more prevalent in T2D than in long COVID. Conclusion: Multi-organ MRI assessment can enrich the current blunt assessment of multi-system abnormalities in diverse disease states to inform earlier intervention and treatments. Disclosure N.Eichert: Employee; Perspectum Ltd. G.Kemp: None. D.Cuthbertson: Other Relationship; AstraZeneca, Novo Nordisk. A.Banerjee: Research Support; AstraZeneca. A.Telford: Employee; Perspectum Ltd. A.Roca-fernandez: Employee; Perspectum Ltd. A.Hamid: None. H.B.Thomaides-brears: Employee; Perspectum Ltd, Stock/Shareholder; Perspectum Ltd. A.Dennis: Employee; Perspectum Ltd. R.Banerjee: Employee; Perspectum Ltd., Other Relationship; Perspectum Ltd., Stock/Shareholder; Perspectum Ltd. S.Ali: Other Relationship; NICE committee for diabetes. G.Thanabalasingham: Speaker's Bureau; Boehringer Ingelheim International GmbH. Funding EU RADIcAL grant, Innovate UK

Molecular characterization of CTNSmutations in Tunisian patients with ocular cystinosis.

BackgroundOcular cystinosis is a rare autosomal recessive disorder characterized by intralysosomal cystine accumulation in renal, ophthalmic (cornea, conjunctiva), and other organ abnormalities. Patients with ocular cystinosis are mostly asymptomatic and typically experience mild photophobia due to cystine crystals in the cornea observed accidently during a routine ocular examination. The ocular cystinosis is associated with different mutations in CTNS gene. Cysteamine therapy mostly corrects the organ abnormalities.MethodsThis study was performed in collaboration with the department of ophthalmology of Farhat Hached Hospital. The Optical Coherence Tomography (OCT) of the cornea and retinal photography were used to search cystine crystals within the corneas and conjunctiva in eight Tunisian patients. Screening for the common 57-kb deletion was performed by standard multiplex PCR, followed by direct sequencing of the entire CTNS gene.ResultsThe studied patients were found to have cystine crystal limited anterior corneal stroma and the conjunctiva associated with retinal crystals accumulation. CTNS gene sequencing disclosed 7 mutations: three missense mutations (G308R, p.Q88K, and p.S139Y); one duplication (C.829dup), one framshift mutation (p.G258f), one splice site mutation (c.681 + 7delC) and a large deletion (20,327-bp deletion). Crystallographic structure analysis suggests that the novel mutation p.S139Y is buried in a first transmembrane helix closed to the lipid bilayer polar region, introducing a difference in hydrophobicity which could affect the hydrophobic interactions with the membrane lipids. The second novel mutation p.Q88K which is located in the lysosomal lumen close to the lipid membrane polar head region, introduced a basic amino acid in a region which tolerate only uncharged residue. The third missense mutation introduces a positive change in nonpolar tail region of the phospholipid bilayer membrane affecting the folding and stability of the protein in the lipid bilayer.ConclusionsOur data demonstrate that impaired transport of cystine out of lysosomes is the most common, which is obviously associated with the mutations of transmembrane domains of cystinosine resulting from a total loss of its activity.

Diagnostic hysterolaparoscopy: An important tool in evaluation of female infertility, in beneficiaries of ESI scheme in Eastern India

Background: The WHO estimates that 60–80 million couples worldwide suffer from infertility and the overall prevalence of the primary infertility in India is 3.9–16.8%. As usual tests and examinations are unable to appreciate majority of pelvic pathology in infertile women, diagnostic laparoscopy has become an essential part of infertility evaluation. Diagnostic laparohysteroscopy (DHL) gives the opportunity to directly visualize and manipulate pelvic organs which allow accurate diagnosis and give an option to treat at the samesitting. Aims and Objectives: The aims of this study were to detect pelvic organ abnormalities by diagnostic hysteroscopy and laparoscopy in the evaluation of female infertility in a tertiary care hospital. Materials and Methods: This cross-sectional observational study recruited 50 patients who attended the infertility clinic during 1 year period as per inclusion and exclusion criteria. Those with male factor and endocrine abnormality were excluded from the study. The patients having abnormal hystero-salpingography (HSG) findings and those who in spite of having normal HSG finding, did not conceive even after three cycles of ovulation induction, underwent DHL. Results: Out of the 50 patients, 35 (70%) suffering from the primary and 15 (30%) suffering from the secondary infertility. The mean age of the study population was 29.5±5.3 years. Most of the cases presented with 3–6 years of infertility. The most common reported laparoscopic abnormality was ovarian in 58% cases, followed by 56% of pelvic and peritoneal abnormalities, 44% tubal factor abnormality, 36% having endometriosis at different stages, and 30% having uterine abnormality. Conclusions: Hystero -laparoscopy has good diagnostic accuracy in evaluating pelvic pathologies. The combination of hysteroscopy with laparoscopy done in a single setting improves the detection rate of abnormalities of uterus, fallopian tubes, ovaries, and pelvic peritoneum.

A review of intravaginal ejaculatory dysfunction and unconsummated marriage cases in the outpatient clinic for male infertility at the University of Tsukuba Hospital

ABSTRACT Introduction Male infertility can be classified into three categories of causes: testicular factors, seminal tract obstruction, and sexual disorders. Sexual disorders, in particular, have been increasing in recent years, as people now marry later in life, and lifestyles have become more diverse. This study focused on erectile dysfunction (ED) and ejaculation dysfunction (EjD) because they are direct causes of sexual disorders and infertility. The most serious sexual disorders are intravaginal ejaculation dysfunction (IVEjD), which indicates a lack of ability to ejaculate during sexual intercourse, and unconsummated marriage (UM), which means no experience of sexual intercourse after marriage. In this study, we reviewed the actual statuses of IVEjD and UM in male infertility patients who were consulted at our clinic. Objective To examine the characteristics of IVEjD and UM by comparing them with other male infertility patients. Methods This study was approved by the relevant ethical review board. We obtained data on 83 male infertility patients diagnosed from 2018–2020 at our clinic. We extracted information on IVEjD and UM patients, which were defined as serious sexual disorders (SSD). We analyzed the factors of SSD cases related to infertility. Results Of 83 male infertility cases, 26 cases had either ED or EjD. We found nine SSD cases; seven cases had IVEjD, and two cases had UM. The mean age was 38.8 years (IQR: 30–50), and the mean age of the wives was 33.6 years (IQR: 2–43). All SSD cases had never had ejaculatory intercourse with a woman including their wives. Seven cases possibly had ED or EjD, but all SSDs were able to ejaculate by masturbation. One case had premature ejaculation, and six cases had delayed ejaculation during masturbation. Three cases had poor semen findings (oligozoospermia or asthenozoospermia), one case had an organic abnormality (after phimosis surgery), and one case had active depression, but there were no abnormalities in the testicular volume or endocrine findings. The causes of SSDs were inappropriate methods of masturbation in three cases (push method in two cases, strong grip in one case), a lack of sexual experience in two cases, and sexual aversion in one case. In three cases, the wives were able to conceive, but all had undergone fertility treatments without sexual intercourse. Conclusion In this study, 31.3% of male infertility patients had sexual disorders, which is higher than the figure in the national survey. In addition, 10.8% of men had never had sexual intercourse with ejaculation in their lives, and even if we consider the fact that these are patients who visit specialized outpatient clinics, it is clear that there are more patients suffering from SSD than expected. Although sexual disorders can be caused by physical abnormalities such as neurological disorders, vascular disorders, and endocrine disorders, all nine cases examined in this study were able to ejaculate by masturbation, suggesting that lifestyle and psychological problems are the major factors of infertility. Given the difficulty in providing medical interventions for these factors, only a small percentage of cases with severe sexual dysfunction resulted in pregnancy, suggesting the difficulty involved in treating sexual dysfunctions. Disclosure Work supported by industry: no.

Synthesis, Characterization, and In V ivo Toxicological Evaluation of Copper (II) Oxide Containing Herbometallic Siddha Nanocomplex "Thamira Parpam".

“Thamira parpam” (TP), a copper-based herbometallic oxide (copper (II) oxide) nanodrug has been used in Siddha medicine for centuries because of its anti-ulcerogenic property. However, the physicochemical properties and in vivo toxicity of TP still remain elusive. Rigorous clinical translation requires deciphering these vital properties. We have synthesized TP following a gold standard protocol in the traditional Siddha methodology. We assessed the size, phase, elemental constituents, and thermal stability of TP by SEM and TEM, XRD, EPR, and EDAX analyses, respectively. The results depicted the conversion of metallic copper into copper (II) oxide in the final stages of TP preparation and exhibited nanodimensions ranging between 10 and 50 nm. The XPS spectra revealed the presence of oxygen-deficient state and a carbonaceous coating was found on the surface of TP using TEM analysis. In vivo safety was studied in rat toxicity models by adopting OECD guidelines. Body weight changes, feed, and water intake were unaltered upon TP administration. Hematological, biochemical profiling, and histopathological findings also suggested its nontoxic nature with no abnormalities in major organs and its functions. Interestingly, we found that the metal toxicity could have been subdued because of the carbonaceous coating around the nanoparticle copper (II) oxide, confirming that the drug is safe at a low dose. Overall, our study has enlightened the safety of TP supporting the use of Siddha formulations.

Effect of Rosmarinus officinalis L inhalation on reducing primary dysmenorrhoea in female students of the Bali International University

Background: Primary dysmenorrhea is a symptom that occurs in the absence of genital organ abnormalities. Non-steroidal anti-inflammatory drugs (NSAIDs) can be used but may cause adverse reactions if used repeatedly without doctor supervision. This study aims to analyse the effect of rosemary aromatherapy inhalation on reducing primary dysmenorrhoea in female students of the Bali International University. Method: This experimental research with a pretest and posttest control group design was conducted in March 2021 among 56 female students of the Bali International University. Pain intensity was measured by the Numerical Rating Scale (NRS) scale. Result: The Mann Whitney test revealed a p-value = 0.0001, indicating that rosemary aromatherapy (-3.250) has a significant effect on reducing the intensity of menstrual pain compared to jojoba oil used as a placebo (0,928). Conclusion: This research could demonstrate that rosemary aromatherapy inhalation can reduce pain levels and be a non-pharmacological therapy option for primary dysmenorrhoea.

Evaluation of supramolecular complex of fenbendazole effect on embryonic development

The purpose of the research is to study the embryotropic effect of supramolecular complex of fenbendazole (SMСF).Materials and methods. The experiment to assess the embryotropic properties of SMCF was carried out on 40 white female and 20 male rats in accordance with the Guidelines for the experimental (preclinical) study of new pharmacological substances. Pregnant female rats were divided into 3 experimental and one control groups. SMCF was administered intragastrically on the 1–6 days of embryogenesis (group 1); on the 7–14 days (group 2) and on the 15–19 days (group 3) in three times therapeutic dose – 6,0 mg/kg of active substance. The animals of the control group received saline from the first to the 19th days of pregnancy. Rats were euthanized on the 20th day of pregnancy. The uterus with fetuses was removed after laparotomy, the number of corpora lutea, implantation sites, the number of living, dead and resorbed fetuses were recorded, the weight and diameter of the placenta were determined. The embryos were examined, weighed, the craniocaudal sizes were determined, the levels of total embryonic, preimplantation and postimplantation embryo death were calculated. The fetuses were examined for abnormalities of internal organs and changes in the skeletal system according to the methods of J. G. Wilson (1965) and A. B. Dawson (1926), modified in the department of embryology of the IEM of the USSR Academy of Medical Sciences.Results and discussion. As a result, SMCF does not induce toxic effects on the fetus: mortality rates, size and weight of embryos were at the level of the control group in a threefold therapeutic dose 6,0 mg/kg at intragastric administration on the 1–6; 7–14 and 15–19 days of pregnancy. SMCF did not cause external and internal malformations.

A Personalized Multidisciplinary Approach to Evaluating and Treating Autism Spectrum Disorder

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder without a known cure. Current standard-of-care treatments focus on addressing core symptoms directly but have provided limited benefits. In many cases, individuals with ASD have abnormalities in multiple organs, including the brain, immune and gastrointestinal system, and multiple physiological systems including redox and metabolic systems. Additionally, multiple aspects of the environment can adversely affect children with ASD including the sensory environment, psychosocial stress, dietary limitations and exposures to allergens and toxicants. Although it is not clear whether these medical abnormalities and environmental factors are related to the etiology of ASD, there is evidence that many of these factors can modulate ASD symptoms, making them a potential treatment target for improving core and associated ASD-related symptoms and improving functional limitation. Additionally, addressing underlying biological disturbances that drive pathophysiology has the potential to be disease modifying. This article describes a systematic approach using clinical history and biomarkers to personalize medical treatment for children with ASD. This approach is medically comprehensive, making it attractive for a multidisciplinary approach. By concentrating on treatable conditions in ASD, it is possible to improve functional ability and quality of life, thus providing optimal outcomes.

Abstract P033: Higher Ambulatory Sbp Is Associated With Increasing Number Of Target Organ Abnormalities In Youth: The Ship Ahoy Study

Hypertension is associated with elevated left ventricular mass index (LVMI), cardiac dysfunction and increased arterial stiffness in adults which predict cardiovascular (CV) events. The extent to which elevated BP in youth is associated with subclinical CV target organ damage (TOD) is not known. We explored the relation between BP level and number of TOD abnormalities (nTOD). We measured clinic and ambulatory BP (ABP), anthropometrics, and nTOD in 244 adolescents (mean 15.5 + 1.8 years, 67% white, 60% male). Subjects were recruited as low-risk (L=98, SBP%&lt;80 th %), mid-risk (Mid=60, SBP% 80-&lt;90 th %); and high-risk (H=86, SBP% &gt;=90 th %) based on mean of 6 aneroid clinic BPs by age-, sex- and height-specific cut-points. 24-hour ABP was measured with an oscillometric device per pediatric guidelines. Four measures of TOD were: LVMI &gt; 38.6 g/m 2.7 ; LV systolic strain (Strain %) &gt; -18; LV diastolic function (E/e’) &gt; 8; pulse wave velocity (PWV) &gt; 5.8 m/sec. ANOVA was used to evaluate differences in CV risk factors and chi square for differences in nTOD across groups. Logistic regression models were used to determine if clinic and/or ABP was an independent predictor of nTOD after adjustment for age, sex, race, and BMI z-score. BP groups did not differ in BMI z-score. Clinic and ABP systolic and diastolic BP increased across BP groups. The distribution of nTOD was shifted towards higher BP group with most nTOD= 0 (47%) in the L and all (100%) nTOD = 4 in the H group (X 2 = 0.08) and became significant when L (clinic SBP&lt;75 th %) was compared to M+H (clinic SBP &gt; 80 th %; X 2 =0.04). Daytime ABP index (subject daytime systolic ABP/95 th % for daytime systolic ABP) and BMI z-score (both p &lt; 0.003) were significantly associated with nTOD in a model containing clinic SBP, age, sex and race (other covariates NS; full model p &lt; 0.0001, R 2 =0.22). We conclude that higher ABP is associated with a greater number of cardiac and vascular abnormalities in youth. ABP should be applied in youth with elevated BP to evaluate need for intensification of therapy to prevent CV TOD.

Pediatric patient with oculocutaneous albinism

Oculocutaneous albinism (OCA) is a heterogeneous autosomal recessive disorder characterized by a reduced or absent melanin synthesis. OCA causes a complete or partial absence of pigment in the skin, hair, and eyes. Reduction of melanin in the eyes results in reduced visual acuity, photophobia, and nystagmus. A 6-year-old boy, the first child of a related couple, was born following a normal gestation and delivery. At term, he weighed 3800 g, and his length was 50 cm. OCA was noted at birth; there was total depigmentation of the skin, hair, and iris. He presented with photophobia and bilateral strabismus. The patient had white hair, eyebrows, eyelashes, and depigmented skin (A). Ophthalmologic examination revealed characteristic iris depigmentation and translucency (B), retinal depigmentation (C), misrouting of the optic nerve fibers and reduced visual acuity (5/10). He had a normal mental development with no other congenital deformities. He did not have any abnormalities of the internal organs. The diagnosis of OCA is based on clinical findings of hypopigmentation of the skin and hair, in addition to the characteristic ocular symptoms. However, due to the clinical overlap between the OCA subtypes, molecular diagnosis is necessary in order to establish the gene defect and thus the OCA subtype. Reduced visual acuity can be helped in various ways. Glasses, possibly bifocals, may often be of sufficient help. Oculocutaneous albinism is an autosomal recessive disorder that presents with heterogeneous expressivity.

A clinical review of enuresis and its associated psychiatric comorbidities

Enuresis is a common childhood condition treated by pediatricians and psychiatrists. Enuresis is also commonly referred as bedwetting. It is more prevalent among boys than girls. Enuresis is an involuntary voiding of urine continuing after an anticipated age of control in the absence of any organic abnormality. This review summarizes the current knowledge about epidemiology, diagnosis, etiological factors, psychiatric comorbidities, and behavioral (enuresis alarm and star charts) as well as pharmacological (desmopressin and imipramine) management of enuresis. It is important to understand the epidemiology, etiology, behavioral as well as pharmacological management, and screening for psychiatric comorbidities for the better outcome among the children with enuresis. Enuresis can be stressful physically as well as mentally for both child and parents. Many times, parents of children with enuresis either do not show willingness or hesitate to report the bedwetting behavior of their children due to perceived stigma related to enuresis. Hence, there is a paucity of data in this field that the detailed evaluation of the prevalence, causative factors, and risk factors is needed and of great value to understand the psychiatric comorbidities associated with enuresis for the better outcome. Psychological support and motivation are needed for both children and their parents for improving their treatment-seeking behavior and for an effective management of enuresis.

Deep phenotyping and association with diagnostic yield of prenatal exome sequencing for fetal brain abnormalities

To evaluate whether deep prenatal phenotyping of fetal brain abnormalities (FBA) increases diagnostic yield of trio-exome sequencing (ES) compared to standard phenotyping. Prospective prenatal ES study recruiting from multiple sites. Participants were eligible if a fetal anomaly was diagnosed and subsequently found to have a normal microarray. Deep phenotyping was defined as phenotype based on targeted ultrasound plus pre or postnatal MRI, autopsy, and/or known phenotypes of other affected family members. Standard phenotyping was defined as phenotype based on targeted ultrasound alone. Fetal brain abnormalities were categorized by major brain findings on prenatal ultrasound, with some cases having more than one FBA finding. Cases with diagnostic ES results were compared to those with non-diagnostic results by available phenotyping as well as diagnosed FBA. Data were analyzed using t-test, chi-square, and pairwise comparisons as appropriate. A total of 153 trios were sequenced, of which 62 (41%) had an FBA diagnosed on prenatal ultrasound. Of the 62 trios with FBA, 21 (34%) cases had a diagnostic ES result and 41 (66%) had a non-diagnostic result. There was no difference in the number of cases with multisystem organ abnormalities between groups (90% vs 72%, p=0.12). Individual modalities of deep phenotyping were not associated with diagnostic ES results (Table 1). Anomalies of the posterior fossa and corpus callosum were the most common FBA identified (Table 2). Those with deep phenotyping available were not more likely to receive a diagnostic ES result (unadjusted OR 1.5, [0.5, 4.3] p=0.4). Neural tube defect was significantly associated with receipt of a non-diagnostic ES result (0% vs 17%, p=0.04). Deep phenotyping was not associated with increased diagnostic yield of ES for FBA in this small cohort. Of the FBA identified, neural tube defects were associated with non-diagnostic ES results. Further study is needed to identify specific prenatal and postnatal phenotypic variables that may increase diagnostic yield in the context of sequencing efforts.View Large Image Figure ViewerDownload Hi-res image Download (PPT)