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.

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Clinical Outcomes of a Zika Virus Mother–Child Pair Cohort in Spain

Pathogens ◽

10.3390/pathogens9050352 ◽

2020 ◽

Vol 9 (5) ◽

pp. 352 ◽

Cited By ~ 1

Author(s):

Antoni Soriano-Arandes ◽

Marie Antoinette Frick ◽

Milagros García López-Hortelano ◽

Elena Sulleiro ◽

Carlota Rodó ◽

...

Keyword(s):

Zika Virus ◽

Adverse Outcomes ◽

Zikv Infection ◽

Child Pair ◽

Referral Hospitals ◽

Congenital Zika Syndrome ◽

Endemic Areas ◽

Neurodevelopmental Abnormalities ◽

Congenital Microcephaly

Background: Zika virus (ZIKV) infection has been associated with congenital microcephaly and other neurodevelopmental abnormalities. There is little published research on the effect of maternal ZIKV infection in a non-endemic European region. We aimed to describe the outcomes of pregnant travelers diagnosed as ZIKV-infected in Spain, and their exposed children. Methods: This prospective observational cohort study of nine referral hospitals enrolled pregnant women (PW) who travelled to endemic areas during their pregnancy or the two previous months, or those whose sexual partners visited endemic areas in the previous 6 months. Infants of ZIKV-infected mothers were followed for about two years. Results: ZIKV infection was diagnosed in 163 PW; 112 (70%) were asymptomatic and 24 (14.7%) were confirmed cases. Among 143 infants, 14 (9.8%) had adverse outcomes during follow-up; three had a congenital Zika syndrome (CZS), and 11 other potential Zika-related outcomes. The overall incidence of CZS was 2.1% (95%CI: 0.4–6.0%), but among infants born to ZIKV-confirmed mothers, this increased to 15.8% (95%CI: 3.4–39.6%). Conclusions: A nearly 10% overall risk of neurologic and hearing adverse outcomes was found in ZIKV-exposed children born to a ZIKV-infected traveler PW. Longer-term follow-up of these children is needed to assess whether there are any later-onset manifestations.

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Three-Year Clinical Follow-Up of Children Intrauterine Exposed to Zika Virus

Viruses ◽

10.3390/v13030523 ◽

2021 ◽

Vol 13 (3) ◽

pp. 523

Author(s):

Rosa Estela Gazeta ◽

Ana Paula Antunes Pascalicchio Bertozzi ◽

Rita de Cássia de Aguirre Bernardes Dezena ◽

Andrea Cristina Botelho Silva ◽

Thamirys Cosmo Gillo Fajardo ◽

...

Keyword(s):

Zika Virus ◽

Clinical Manifestations ◽

Laboratory Diagnosis ◽

Autism Spectrum ◽

First Year ◽

Cognitive Delay ◽

Long Term Follow Up ◽

Simplex Virus ◽

First Year Of Life

Congenital Zika virus (ZIKV) infection may present with a broad spectrum of clinical manifestations. Some sequelae, particularly neurodevelopmental problems, may have a later onset. We conducted a prospective cohort study of 799 high-risk pregnant women who were followed up until delivery. Eighty-three women and/or newborns were considered ZIKV exposed and/or infected. Laboratory diagnosis was made by polymerase chain reaction in the pregnant mothers and their respective newborns, as well as Dengue virus, Chikungunya virus, and ZIKV serology. Serology for toxoplasmosis, rubella, cytomegalovirus, herpes simplex virus, and syphilis infections were also performed in microcephalic newborns. The newborns included in the study were followed up until their third birthday. Developmental delay was observed in nine patients (13.2%): mild cognitive delay in three patients, speech delay in three patients, autism spectrum disorder in two patients, and severe neurological abnormalities in one microcephalic patient; sensorineural hearing loss, three patients and dysphagia, six patients. Microcephaly due to ZIKV occurred in three patients (3.6%). Clinical manifestations can appear after the first year of life in children infected/exposed to ZIKV, emphasizing the need for long-term follow-up.

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Wide spectrum of clinical manifestations in children with tuberous sclerosis complex – Follow-up of 20 children

Brain and Development ◽

10.1016/j.braindev.2013.05.006 ◽

2014 ◽

Vol 36 (4) ◽

pp. 306-314 ◽

Cited By ~ 11

Author(s):

Roland R. Mettin ◽

Andreas Merkenschlager ◽

Matthias K. Bernhard ◽

Heidrun Elix ◽

Wolfgang Hirsch ◽

...

Keyword(s):

Tuberous Sclerosis ◽

Tuberous Sclerosis Complex ◽

Wide Spectrum ◽

Clinical Manifestations

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Circulating Very-Long-Chain SFA Concentrations Are Inversely Associated with Incident Type 2 Diabetes in US Men and Women

Journal of Nutrition ◽

10.1093/jn/nxz240 ◽

2019 ◽

Vol 150 (2) ◽

pp. 340-349 ◽

Cited By ~ 4

Author(s):

Andres V Ardisson Korat ◽

Vasanti S Malik ◽

Jeremy D Furtado ◽

Frank Sacks ◽

Bernard Rosner ◽

...

Keyword(s):

Type 2 Diabetes ◽

Fatty Acids ◽

Fatty Acid ◽

Arachidic Acid ◽

Plasma Concentrations ◽

Behenic Acid ◽

Men And Women ◽

Long Chain

ABSTRACT Background Very-long-chain SFAs (VLCSFAs), such as arachidic acid (20:0), behenic acid (22:0), and lignoceric acid (24:0), have demonstrated inverse associations with cardiometabolic conditions, although more evidence is needed to characterize their relation with risk of type 2 diabetes (T2D). In addition, little is known regarding their potential dietary and lifestyle predictors. Objective We aimed to examine the association of plasma and erythrocyte concentrations of VLCSFAs with incident T2D risk. Methods We used existing measurements of fatty acid concentrations in plasma and erythrocytes among 2854 and 2831 participants in the Nurses’ Health Study (NHS) and Health Professionals Follow-Up Study (HPFS), respectively. VLCSFAs were measured using GLC, and individual fatty acid concentrations were expressed as a percentage of total fatty acids. Incident T2D cases were identified by self-reports and confirmed by a validated supplementary questionnaire. Cox proportional hazards regression was used to evaluate the association between VLCSFAs and T2D, adjusting for demographic, lifestyle, and dietary variables. Results During 39,941 person-years of follow-up, we documented 243 cases of T2D. Intakes of peanuts, peanut butter, vegetable fat, dairy fat, and palmitic/stearic (16:0–18:0) fatty acids were significantly, albeit weakly, correlated with plasma and erythrocyte VLCSFA concentrations (|rs| ≤ 0.19). Comparing the highest with the lowest quartiles of plasma concentrations, pooled HRs (95% CIs) were 0.51 (0.35, 0.75) for arachidic acid, 0.43 (0.28, 0.64) for behenic acid, 0.40 (0.27, 0.61) for lignoceric acid, and 0.41 (0.27, 0.61) for the sum of VLCSFAs, after multivariate adjustments for demographic, lifestyle, and dietary factors. For erythrocyte VLCSFAs, only arachidic acid and behenic acid concentrations were inversely associated with T2D risk. Conclusions Our findings suggest that, in US men and women, higher plasma concentrations of VLCSFAs are associated with lower risk of T2D. More research is needed to understand the mechanistic pathways underlying these associations.

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Safety_and_Pharmacokinetics_of_Dapivirine_Delivery.7

10.31234/osf.io/t4j95 ◽

2020 ◽

Author(s):

Lungwani Muungo

Keyword(s):

Adverse Events ◽

Hiv Transmission ◽

Plasma Concentrations ◽

Vaginal Fluid ◽

Time Curve ◽

Vaginal Microbicides ◽

Intravaginal Rings ◽

Lower Genital Tract ◽

The Matrix

Vaginal microbicides for the prevention of HIV transmission maybe an important option for protecting women from infection.Incorporation of dapivirine, a lead candidate nonnucleoside reversetranscriptase inhibitor, into intravaginal rings (IVRs) for sustainedmucosal delivery may increase microbicide product adherence andefficacy compared with conventional vaginal formulations. Twentyfourhealthy HIV-negative women 18–35 years of age were randomlyassigned (1:1:1) to dapivirine matrix IVR, dapivirine reservoir IVR,or placebo IVR. Dapivirine concentrations were measured in plasmaand vaginal fluid samples collected at sequential time points over the33-day study period (28 days of IVR use, 5 days of follow-up). Safetywas assessed by pelvic/colposcopic examinations, clinical laboratorytests, and adverse events. Both IVR types were safe and well toleratedwith similar adverse events observed in the placebo and dapivirinegroups. Dapivirine from both IVR types was successfully distributedthroughout the lower genital tract at concentrations over 4 logs greaterthan the EC50 against wild-type HIV-1 (LAI) in MT4 cells. Maximumconcentration (Cmax) and area under the concentration–time curve(AUC) values were significantly higher with the matrix than reservoirIVR. Mean plasma concentrations of dapivirine were ,2 ng/mL.These findings suggest that IVR delivery of microbicides is a viableoption meriting further study.Key Words: dapivirine, HIV, intravaginal ring, microbicide,pharmacokinetics, prevention

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Monogenic Diabetes: Genetics and Relevance on Diabetes Mellitus Personalized Medicine

Current Diabetes Reviews ◽

10.2174/1573399816666191230114352 ◽

2020 ◽

Vol 16 (8) ◽

pp. 807-819 ◽

Cited By ~ 1

Author(s):

Madalena Sousa ◽

Jácome Bruges-Armas

Keyword(s):

Diabetes Mellitus ◽

Complex Disease ◽

Clinical Manifestations ◽

Neonatal Diabetes ◽

Monogenic Diabetes ◽

Diabetes Genetics ◽

Individualize Treatment

Background: Diabetes mellitus (DM) is a complex disease with significant impression in today's world. Aside from the most common types recognized over the years, such as type 1 diabetes (T1DM) and type 2 diabetes (T2DM), recent studies have emphasized the crucial role of genetics in DM, allowing the distinction of monogenic diabetes. Methods: Authors did a literature search with the purpose of highlighting and clarifying the subtypes of monogenic diabetes, as well as the accredited genetic entities responsible for such phenotypes. Results: The following subtypes were included in this literature review: maturity-onset diabetes of the young (MODY), neonatal diabetes mellitus (NDM) and maternally inherited diabetes and deafness (MIDD). So far, 14 subtypes of MODY have been identified, while three subtypes have been identified in NDM - transient, permanent, and syndromic. Discussion: Despite being estimated to affect approximately 2% of all the T2DM patients in Europe, the exact prevalence of MODY is still unknown, accentuating the need for research focused on biomarkers. Consequently, due to its impact in the course of treatment, follow-up of associated complications, and genetic implications for siblings and offspring of affected individuals, it is imperative to diagnose the monogenic forms of DM accurately. Conclusion: Currently, advances in the genetics field allowed the recognition of new DM subtypes, which until now, were considered slight variations of the typical forms. Thus, it is imperative to act in the close interaction between genetics and clinical manifestations, to facilitate diagnosis and individualize treatment.

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Cerebellotrigeminal Dermal Dysplasia (Gómez-López-Hernández Syndrome)

Journal of Pediatric Neurology ◽

10.1055/s-0038-1667021 ◽

2018 ◽

Vol 16 (05) ◽

pp. 362-368 ◽

Cited By ~ 1

Author(s):

Federica Sullo ◽

Agata Polizzi ◽

Stefano Catanzaro ◽

Selene Mantegna ◽

Francesco Lacarrubba ◽

...

Keyword(s):

De Novo ◽

Chromosomal Rearrangements ◽

Number Of Patients ◽

Wide Range ◽

Visual Problems ◽

Neurodevelopmental Abnormalities ◽

Clinical Triad ◽

High Degree ◽

Motor Handicap

Cerebellotrigeminal dermal (CTD) dysplasia is a rare neurocutaneous disorder characterized by a triad of symptoms: bilateral parieto-occipital alopecia, facial anesthesia in the trigeminal area, and rhombencephalosynapsis (RES), confirmed by cranial magnetic resonance imaging. CTD dysplasia is also known as Gómez-López-Hernández syndrome. So far, only 35 cases have been described with varying symptomatology. The etiology remains unknown. Either spontaneous dominant mutations or de novo chromosomal rearrangements have been proposed as possible explanations. In addition to its clinical triad of RES, parietal alopecia, and trigeminal anesthesia, CTD dysplasia is associated with a wide range of phenotypic and neurodevelopmental abnormalities.Treatment is symptomatic and includes physical rehabilitation, special education, dental care, and ocular protection against self-induced corneal trauma that causes ulcers and, later, corneal opacification. The prognosis is correlated to the mental development, motor handicap, corneal–facial anesthesia, and visual problems. Follow-up on a large number of patients with CTD dysplasia has never been reported and experience is limited to few cases to date. High degree of suspicion in a child presenting with characteristic alopecia and RES has a great importance in diagnosis of this syndrome.

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Adult systemic lupus erythematosus in Egypt: The nation-wide spectrum of 3661 patients and world-wide standpoint

Lupus ◽

10.1177/09612033211014253 ◽

2021 ◽

pp. 096120332110142

Author(s):

Tamer A Gheita ◽

Rasha Abdel Noor ◽

Esam Abualfadl ◽

Osama S Abousehly ◽

Iman I El-Gazzar ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Lupus Erythematosus ◽

Age Of Onset ◽

Wide Spectrum ◽

Age At Onset ◽

Disease Onset ◽

Clinical Manifestations ◽

Population Based ◽

Systemic Lupus ◽

Cross Sectional

Objective The aim of this study was to present the epidemiology, clinical manifestations and treatment pattern of systemic lupus erythematosus (SLE) in Egyptian patients over the country and compare the findings to large cohorts worldwide. Objectives were extended to focus on the age at onset and gender driven influence on the disease characteristics. Patients and method This population-based, multicenter, cross-sectional study included 3661 adult SLE patients from Egyptian rheumatology departments across the nation. Demographic, clinical, and therapeutic data were assessed for all patients. Results The study included 3661 patients; 3296 females and 365 males (9.03:1) and the median age was 30 years (17–79 years), disease duration 4 years (0–75 years) while the median age at disease onset was 25 years (4–75 years). The overall estimated prevalence of adult SLE in Egypt was 6.1/100,000 population (1.2/100,000 males and 11.3/100,000 females).There were 316 (8.6%) juvenile-onset (Jo-SLE) and 3345 adult-onset (Ao-SLE). Age at onset was highest in South and lowest in Cairo (p < 0.0001). Conclusion SLE in Egypt had a wide variety of clinical and immunological manifestations, with some similarities with that in other nations and differences within the same country. The clinical characteristics, autoantibodies and comorbidities are comparable between Ao-SLE and Jo-SLE. The frequency of various clinical and immunological manifestations varied between gender. Additional studies are needed to determine the underlying factors contributing to gender and age of onset differences.

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A New Multiplatform Model for Outpatient Prenatal and Postpartum Care in a Cohort of COVID-19-Affected Obstetric Patients

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18105144 ◽

2021 ◽

Vol 18 (10) ◽

pp. 5144

Author(s):

Mar Muñoz-Chápuli Gutiérrez ◽

Ana Durán-Vila ◽

Javier Ruiz-Labarta ◽

Pilar Payá-Martínez ◽

Pilar Pintado Recarte ◽

...

Keyword(s):

Clinical Manifestations ◽

Specific Treatment ◽

Rt Pcr ◽

Good Adherence ◽

Major Morbidity ◽

Reference Hospital ◽

The Mean ◽

Discharge From Hospital ◽

Over Time

Spain was one of the epicenters of the first wave of the COVID-19 pandemic. We describe in this article the design and results of a new telephone-and-telematic multiplatform model of systematic prenatal and postpartum follow-up for COVID-19-affected women implemented in a tertiary reference hospital in Madrid. We included patients with RT-PCR-confirmed COVID-19 during pregnancy or delivery from 10 March 2020 to 15 December 2020. We had a total of 211 obstetric patients: 148 (70.1%) were tested at the onset of suspicious clinical manifestations and 62 (29.4%) were tested in the context of routine screening. Of all the patients, 60 women (28.4%) were asymptomatic and 97 (46%) presented mild symptoms. Fifty-one women (24.2%) were admitted to our hospital for specific treatment because of moderate or severe symptoms. We had no missed cases and a good adherence. The mean number of calls per patient was 2.3. We performed 55 in-person visits. We analyzed the complexity of our program over time, showing a two-wave-like pattern. One patient was identified as needing hospitalization and we did not record major morbidity. Telemedicine programs are a strong and reproducible tool to reach to pregnant population affected by COVID-19, to assess its symptoms and severity, and to record for pregnancy-related symptoms both in an outpatient regime and after discharge from hospital.

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Clinical presentations and long term prognosis of childhood onset polyarteritis nodosa in single centre of Korea

Scientific Reports ◽

10.1038/s41598-021-87718-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Jeong-Seon Lee ◽

Joong-Gon Kim ◽

Soyoung Lee

Keyword(s):

Polyarteritis Nodosa ◽

Clinical Manifestations ◽

Long Term Outcomes ◽

Childhood Onset ◽

Laboratory Findings ◽

Clinical Presentations ◽

Long Term Prognosis ◽

Digital Amputation

AbstractChildhood-onset polyarteritis nodosa (PAN) is a rare and systemic necrotising vasculitis in children affecting small- to medium-sized arteries. To date, there have been only a few reports because of its rarity. Thus, we aimed to investigate the clinical manifestations, laboratory findings, treatment, and long-term outcomes in patients with childhood-onset PAN and to evaluate the usefulness of the paediatric vasculitis activity score (PVAS). We retrospectively analysed the data of nine patients with childhood-onset PAN from March 2003 to February 2020. The median ages at symptom onset, diagnosis, and follow-up duration were 7.6 (3–17.5), 7.7 (3.5–17.6), and 7.0 (1.6–16.3) years, respectively. All patients had constitutional symptoms and skin manifestations, while five exhibited Raynaud’s phenomenon. Organ involvement was observed in one patient. The median PVAS at diagnosis was 7 (range: 2–32). Prednisolone was initially used for induction in all patients, and other drugs were added in cases refractory to prednisolone. All patients survived, but three patients with high PVAS at diagnosis experienced irreversible sequelae, including intracranial haemorrhage and digital amputation. In conclusion, early diagnosis and treatment may minimise sequelae in patients with childhood-onset PAN. This study suggests that high PVAS score at diagnosis may be associated with poor prognosis.

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