Plasma lipidome profiling of newborns with antenatal exposure to Zika virus.

The 2015-2016 Zika virus (ZIKV) outbreak in Brazil was remarkably linked to the incidence of microcephaly and other deleterious clinical manifestations, including eye abnormalities, in newborns. It is known that ZIKV targets the placenta, triggering an inflammatory profile that may cause placental insufficiency. Transplacental lipid transport is delicately regulated during pregnancy and deficiency on the delivery of lipids such as arachidonic and docosahexaenoic acids may lead to deficits in both brain and retina during fetal development. Here, plasma lipidome profiles of ZIKV exposed microcephalic and normocephalic newborns were compared to non-infected controls. Our results reveal major alterations in circulating lipids from both ZIKV exposed newborns with and without microcephaly relative to controls. In newborns with microcephaly, the plasma concentrations of hydroxyoctadecadienoic acid (HODE), primarily as 13-HODE isomer, derived from linoleic acid were higher as compared to normocephalic ZIKV exposed newborns and controls. Total HODE concentrations were also positively associated with levels of other oxidized lipids and several circulating free fatty acids in newborns, indicating a possible plasma lipidome signature of microcephaly. Moreover, higher concentrations of lysophosphatidylcholine in ZIKV exposed normocephalic newborns relative to controls suggest a potential disruption of polyunsaturated fatty acids transport across the blood-brain barrier of fetuses. The latter data is particularly important given the neurocognitive and neurodevelopmental abnormalities observed in follow-up studies involving children with antenatal ZIKV exposure, but normocephalic at birth. Taken together, our data reveal that plasma lipidome alterations associated with antenatal exposure to ZIKV could contribute to identification and monitoring of the wide spectrum of clinical phenotypes at birth and further, during childhood.

Hospital based surveillance of congenital rubella syndrome cases in the pre-vaccine era in Amhara Regional State, Ethiopia: A base line information for the country.

BACKGROUND: Rubella virus infection in early pregnancy lead to serious multi-organ birth defects known as congenital rubella syndrome (CRS). The incidence of CRS varies in different populations and the highest burden is found in developing countries in which rubella vaccination is not included in their national immunization programs. In Ethiopia, there is scarcity of data about congenital rubella syndrome. Therefore, the aim of this study was to determine the burden of CRS-related birth defects and its incidence in the pre-vaccine era in Amhara Regional State, Ethiopia. MATERIALS AND METHODS: A cross sectional study was conducted in Dessie, Felege-Hiwot and University of Gondar Referral Hospitals, from December 2015 to August 2017. After getting informed assent from each parent/guardian, blood was collected from infants < 1 year of age for laboratory determination of anti-rubella virus antibodies. Their socio-demographic data and clinical information compatible with congenital rubella syndrome were collected using WHO guideline. RESULTS: During the study period, a total of 50 infants suspected for congenital rubella syndrome were included in the study. All infants suspected for CRS were tested against rubella specific IgM and IgG [for infants ≥ 6 months of age] antibodies using ELISA method. Of these, 9/50 (18%) and 4/14 (28.6%) of them were laboratory confirmed and potential CRS cases, respectively. In the present study, the most common laboratory confirmed defect was ocular manifestations 6 (66.7%) followed by heart related problems 5 (55.6%). In the present study, most of the laboratory confirmed cases (66.7%) were reported among 1-5 months of age infants. In addition, 5 (55.6%) of the infants with laboratory confirmed CRS cases were male and 6 (66.7%) of them were from urban settings. In this study, the incidence of CRS was 0.4 per 1000 live births. CONCLUSION: In this study, nearly one fifth of the infants had laboratory confirmed congenital rubella syndrome and most of them had multiple rubella associated congenital defects at a time. Most of these congenital anomalies were reported among infants ≥ 1 month of age. Based on our result, the incidence of the CRS was line with the global incidence of the CRS in the pre-vaccine era. Therefore, establishing strong rubella/CRS surveillance system as well as introducing the rubella containing vaccine in the national immunization program might be important to reduce the burden of rubella and CRS in the country.

NGAL as an early biomarker of kidney disease in Joubert syndrome: three brothers compared.

Joubert syndrome (JBTS) is a rare autosomal recessive disorder with an underestimated prevalence due to lack of recognition of clinical signs or failure to diagnose this pathology. JBTS is clinically heterogeneous, and it is characterized by a multiple organ involvement predominantly due to the requirement for Joubert gene function in several tissues. Renal disease affects approximately 30% of patients with JBTS, presenting itself in most cases as nephronophthisis (NPHP), a structural tubulo-interstitial disorder characterized by thickened basal membrane of the tubular epithelium and progressive interstitial fibrosis, associated with cysts at the cortico-medullary junction. We propose three cases concerning three patients with JBTS having different years of illness and degrees of renal impairment, evaluating the parameters of renal function at the time of genetic diagnosis and seen after a follow-up of 7 years. We measured neutrophil gelatinase-associated lipocalin (NGAL), considered as an excellent predictor of kidney injury, to evaluate whether this biomarker might be an early biomarker for JBTS-related kidney disease. NGAL was high in all three cases, but with different levels, indicating a tubular suffering typical of this syndrome, with dissimilar severity in the analyzed subjects. NGAL could represent an early indicator of renal damage useful to start an intensive nephrologic follow-up.

A novel rapid genotyping technique for Collie eye anomaly: SYBR Green-based real-time polymerase chain reaction method applicable to blood and saliva specimens on Flinders Technology Associates filter paper.

Collie eye anomaly (CEA) is a canine inherited ocular disease that shows a wide variety of manifestations and severity of clinical lesions. Recently, a CEA-associated mutation was reported, and a DNA test that uses conventional polymerase chain reaction (PCR) has now become available. The objective of the current study was to develop a novel rapid genotyping technique by using SYBR Green-based real-time PCR for future large-scale surveys as a key part in the strategy to eradicate CEA by selective breeding. First, a SYBR Green-based real-time PCR assay for genotyping of CEA was developed and evaluated by using purified DNA samples from normal, carrier, and affected Border Collies in which genotypes had previously been determined by conventional PCR. This real-time PCR assay demonstrated appropriate amplifications in all genotypes, and the results were consistent with those of conventional PCR. Second, the availability of Flinders Technology Associates filter paper (FTA card) as DNA templates for the real-time PCR assay was evaluated by using blood and saliva specimens to determine suitability for CEA screening. DNA-containing solution prepared from a disc of blood- or saliva-spotted FTA cards was available directly as templates for the real-time PCR assay when the volume of solution was 2.5% of the PCR mixture. In conclusion, SYBR Green-based real-time PCR combined with FTA cards is a rapid genotyping technique for CEA that can markedly shorten the overall time required for genotyping as well as simplify the sample preparation. Therefore, this newly developed technique suits large-scale screening in breeding populations of Collie-related breeds.

The Arf tumor suppressor gene promotes hyaloid vascular regression during mouse eye development.

A key tumor suppressor mechanism that is disrupted frequently in human cancer involves the ARF and p53 genes. In mouse fibroblasts, the Arf gene product responds to abnormal mitogenic signals to activate p53 and trigger either cell cycle arrest or apoptosis. Recent evidence indicates that Arf also has p53-independent functions that may contribute to its tumor suppressor activity. Using Arf(-/-) and p53(-/-) mice, we have discovered a p53-independent requirement for Arf in the developmental regression of the hyaloid vascular system (HVS) in the mouse eye. Arf is expressed in the vitreous of the eye and is induced before HVS regression in the first postnatal week. In the absence of Arf, failed HVS regression causes a pathological process that resembles persistent hyperplastic primary vitreous, a developmental human eye disease thought to have a genetic basis. These findings demonstrate an essential and unexpected role for Arf during mouse eye development, provide insights into the potential genetic basis for persistent hyperplastic primary vitreous, and indicate that Arf regulates vascular regression in a p53-independent manner. The latter finding raises the possibility that Arf may function as a tumor suppressor at least in part by regulating tumor angiogenesis.

Ocular abnormalities in Alagille syndrome.

OBJECTIVE: To assess the type and frequency of ocular abnormalities occurring in Alagille syndrome (AS) in a large group of affected patients and their parents and the potential pathogenetic role of fat-soluble vitamin deficiency. DESIGN: Observational case series. PARTICIPANTS: Twenty-two children with AS and 23 of their parents participated. MAIN OUTCOME MEASURES: Participants underwent full ophthalmic examination, including refraction, orthoptic examination, keratometry, slit-lamp examination, and funduscopy. Corneal diameter measurement was performed in a subset of nine and fluorescein angiography in a subset of six. Serum levels of vitamins A and E and cholesterol were measured. RESULTS: The most common ocular abnormalities in patients with AS were posterior embryotoxon (95%), iris abnormalities (45%), diffuse fundus hypopigmentation (57%, a previously unreported finding), speckling of the retinal pigment epithelium (33%), and optic disc anomalies (76%). Microcornea was not associated with large refractive errors, and visual acuity was not significantly affected by these ocular changes. Vitamin levels were normal. Ocular abnormalities including posterior embryotoxon, iris abnormalities, and optic disc or fundus pigmentary changes were detected in one parent in 36% of cases. CONCLUSIONS: Alagille syndrome is associated with a characteristic group of ocular findings without apparent serious functional significance and probably unrelated to fat-soluble vitamin deficiency. Simple ophthalmic examination of children with neonatal cholestatic jaundice and their parents should allow early diagnosis of AS, eliminating the need for extensive and invasive investigations.