- Monozygotic multiple pregnancies after transfer of single in vitro produced equine embryos. [Case Reports]
- EVEquine Vet J 2019 Jun 24
- CONCLUSIONS: In vitro embryo production resulted in a higher incidence of multiple monozygotic pregnancy, which could only be diagnosed after development of the embryo proper and is likely to result in pregnancy loss later in gestation if left untreated. This article is protected by copyright. All rights reserved.
- Neuropsychological and socioeconomic outcomes in adult survivors of pediatric low-grade glioma. [Journal Article]
- CCancer 2019 Jun 24
- CONCLUSIONS: Decades after treatment, survivors treated with radiotherapy and at younger ages had poorer neuropsychological and SES outcomes. Lifelong surveillance of survivors of pediatric low-grade gliomas may be warranted as life events, stages, and transitions (employment, family, and aging) present new challenges and risks.
- Measles Virus Infection Fosters Dendritic Cell Motility in a 3D Environment to Enhance Transmission to Target Cells in the Respiratory Epithelium. [Journal Article]
- FIFront Immunol 2019; 10:1294
- Transmission of measles virus (MV) from dendritic to airway epithelial cells is considered as crucial to viral spread late in infection. Therefore, pathways and effectors governing this process are p…
Transmission of measles virus (MV) from dendritic to airway epithelial cells is considered as crucial to viral spread late in infection. Therefore, pathways and effectors governing this process are promising targets for intervention. To identify these, we established a 3D respiratory tract model where MV transmission by infected dendritic cells (DCs) relied on the presence of nectin-4 on H358 lung epithelial cells. Access to recipient cells is an important prerequisite for transmission, and we therefore analyzed migration of MV-exposed DC cultures within the model. Surprisingly, enhanced motility toward the epithelial layer was observed for MV-infected DCs as compared to their uninfected siblings. This occurred independently of factors released from H358 cells indicating that MV infection triggered cytoskeletal remodeling associated with DC polarization enforced velocity. Accordingly, the latter was also observed for MV-infected DCs in collagen matrices and was particularly sensitive to ROCK inhibition indicating infected DCs preferentially employed the amoeboid migration mode. This was also implicated by loss of podosomes and reduced filopodial activity both of which were retained in MV-exposed uninfected DCs. Evidently, sphingosine kinase (SphK) and sphingosine-1-phosphate (S1P) as produced in response to virus-infection in DCs contributed to enhanced velocity because this was abrogated upon inhibition of sphingosine kinase activity. These findings indicate that MV infection promotes a push-and-squeeze fast amoeboid migration mode via the SphK/S1P system characterized by loss of filopodia and podosome dissolution. Consequently, this enables rapid trafficking of virus toward epithelial cells during viral exit.
- A Novel CAPN1 Mutation Causes a Pure Hereditary Spastic Paraplegia in an Italian Family. [Case Reports]
- FNFront Neurol 2019; 10:580
- CAPN1 encodes calpain-1, a large subunit of μ-calpain, a calcium-activated cysteine protease widely present in the central nervous system. Mutations in CAPN1 have recently been identified in a compli…
CAPN1 encodes calpain-1, a large subunit of μ-calpain, a calcium-activated cysteine protease widely present in the central nervous system. Mutations in CAPN1 have recently been identified in a complicated form of Hereditary Spastic Paraplegia (HSP) with a combination of cerebellar ataxia and corticomotor tract disorder (SPG76). Therefore, CAPN1 is now considered one of those genes that clinically manifest with a spectrum of disorders ranging from spasticity to cerebellar ataxia and represent a link between Spinocerebellar Ataxia and HSP, two groups of diseases previously considered separate but sharing pathophysiological pathways. We here describe clinical and molecular findings of two Italian adult siblings affected with a pure form of HSP and harboring the novel homozygote c.959delA variant (p.Tyr320Leufs*73) in the CAPN1 gene. Although the reason why mutations in CAPN1 may cause heterogeneous clinical pictures remains speculative, our findings confirm that the spectrum of the CAPN1-linked phenotypes includes pure HSP with onset during the third decade of life. Further studies are warrantied in order to clarify the mechanism underlying the differences in CAPN1 mutation clinical expression.
- Adolescent betel nut use in Guam: beliefs, attitudes and social norms. [Journal Article]
- ARAddict Res Theory 2019; 27(5):394-404
- Betel (areca) nut is an addictive substance chewed with or without tobacco widely in Asia and the Pacific, including the U.S.-affiliated Pacific Islands (USPI). Betel nut use has been found to cause …
Betel (areca) nut is an addictive substance chewed with or without tobacco widely in Asia and the Pacific, including the U.S.-affiliated Pacific Islands (USPI). Betel nut use has been found to cause oral cancer. Research suggests that most betel nut use initiation occurs in adolescence. However, very little is currently known about the etiology of adolescent betel nut use. The present study reports findings of a formative, qualitative research conducted to understand the attitudinal and social factors associated with adolescent betel nut use in USAPI. The objective was to develop a theoretical framework of adolescent betel nut etiology that would guide the development of a prevention program. Semi-structured interviews were conducted with 20 adolescent betel nut users (M age = 14.5; SD = 2.2) from Guam. Findings suggested a framework of adolescent betel nut etiology in which intrapersonal, social, and environmental factors influence betel nut use behavior. The framework is consistent with ecological frameworks of adolescent substance use in which proximal personal and social influences on adolescent substance use occur within the context of a wider socio-cultural context conducive to adolescent substance use. Specifically, we found that beliefs such as betel nut tastes good and induces relaxation represent some of the betel nut use motives; parental permissiveness and peer and sibling use encourage betel nut use; and cultural acceptance and easy accessibility to betel nuts provide an environmental context conducive to betel nut use. Findings are discussed in the context of developing an adolescent betel nut use prevention program.
- A Sibling Suicide: One Sister's Ethical Dilemma. [Journal Article]
- JSJ Soc Work End Life Palliat Care 2019 Jun 22; :1-4
- COL4A1 mutations as a potential novel cause of autosomal dominant CAKUT in humans. [Journal Article]
- HGHum Genet 2019 Jun 22
- Congenital anomalies of the kidney and urinary tract (CAKUT) are the most common cause of chronic kidney disease (~ 45%) that manifests before 30 years of age. The genetic locus containing COL4A1 (13…
Congenital anomalies of the kidney and urinary tract (CAKUT) are the most common cause of chronic kidney disease (~ 45%) that manifests before 30 years of age. The genetic locus containing COL4A1 (13q33-34) has been implicated in vesicoureteral reflux (VUR), but mutations in COL4A1 have not been reported in CAKUT. We hypothesized that COL4A1 mutations cause CAKUT in humans. We performed whole exome sequencing (WES) in 550 families with CAKUT. As negative control cohorts we used WES sequencing data from patients with nephronophthisis (NPHP) with no genetic cause identified (n = 257) and with nephrotic syndrome (NS) due to monogenic causes (n = 100). We identified a not previously reported heterozygous missense variant in COL4A1 in three siblings with isolated VUR. When examining 549 families with CAKUT, we identified nine additional different heterozygous missense mutations in COL4A1 in 11 individuals from 11 unrelated families with CAKUT, while no COL4A1 mutations were identified in a control cohort with NPHP and only one in the cohort with NS. Most individuals (12/14) had isolated CAKUT with no extrarenal features. The predominant phenotype was VUR (9/14). There were no clinical features of the COL4A1-related disorders (e.g., HANAC syndrome, porencephaly, tortuosity of retinal arteries). Whereas COL4A1-related disorders are typically caused by glycine substitutions in the collagenous domain (84.4% of variants), only one variant in our cohort is a glycine substitution within the collagenous domain (1/10). We identified heterozygous COL4A1 mutations as a potential novel autosomal dominant cause of CAKUT that is allelic to the established COL4A1-related disorders and predominantly caused by non-glycine substitutions.
- Identification and characterization of hematopoietic stem cell transplant candidates in a sickle cell disease cohort. [Journal Article]
- BBBiol Blood Marrow Transplant 2019 Jun 20
- Sickle cell disease (SCD) is associated with significant morbidity and allogeneic hematopoietic stem cell transplantation (HSCT) remains the primary curative treatment. Recently, the Brazilian Minist…
Sickle cell disease (SCD) is associated with significant morbidity and allogeneic hematopoietic stem cell transplantation (HSCT) remains the primary curative treatment. Recently, the Brazilian Ministry of Health released a regulation to require the publically funded healthcare system pay for HSCT for SCD patients with defined indications. We used an existing 2794-member SCD cohort established during the period 2013-2015 to characterize candidates for HSCT and estimate number of possible donors. Of 2064 patients with SC anemia (SCA), 152 of 974 children (16%) and 279 of 1090 adults (26%) had at least 1 HSCT indication. The most common indication for transplant was stroke (n=239) followed by avascular necrosis (n=96), priapism (n=82), cerebrovascular disease (n=55), >2 vasocclusive episodes (n=38), alloantibodies and chronic transfusion therapy (n=18) and >2 acute chest syndrome episodes (n=11). Increasing age, number of transfusions, abnormal transcranial Doppler, retinopathy, dactilytis and use of hydroxyurea were more frequent in the 152 children with an indication for HSCT compared to 822 without (p<0.001). Of 152 children and 279 adults meeting the eligibility definition, 77 (50%) and 204 (73%), respectively, had at least 1 non-SCD full sibling who could potentially serve as a donor. In conclusion, in a large cohort of SCA patients, 16% of children and 26% of adults have at least 1 indication for HSCT; these indications are associated with the severity of the disease. This study provides clinical data necessary for estimating the costs and infrastructure that would be required to implement HSCT in a public healthcare system.
- Neonatal social isolation increases the proportion of the immature spines in the layer 2/3 pyramidal neurons of the somatosensory cortex. [Journal Article]
- NRNeurosci Res 2019 Jun 18
- Social isolation during the juvenile period is postulated to leave specific sequelae, such as attention deficits and emotion recognition. Miswiring of the cortical neuronal circuit during postnatal d…
Social isolation during the juvenile period is postulated to leave specific sequelae, such as attention deficits and emotion recognition. Miswiring of the cortical neuronal circuit during postnatal development may underlie such behavioral impairments, but the details of the circuit-level impairment associated with social isolation have not yet been clarified. In this study, we evaluated the possibility that environmental factors may induce alternation in spine characteristics and dynamics. We isolated mice from the mother and siblings from postnatal day 7 to 11 for 6 hours per day. Both dynamics and structural properties of spines in the layer 2/3 pyramidal neurons of the somatosensory cortex were measured at postnatal 3 weeks by in vivo two-photon microscopy. We found decrease in the ratio of PSD-95-positive dendritic spines in the mice after social isolation. These mice did not show alteration in spine dynamics. Those results suggest that the neonatal social isolation results in less mature spines, with normal rate of their turnover, which is distinct from spine phenotype seen in multiple models of autism spectrum disorders.
New Search Next
- Increased facial asymmetry in autism spectrum conditions is associated with symptom presentation. [Journal Article]
- ARAutism Res 2019 Jun 21
- A key research priority in the study of autism spectrum conditions (ASC) is the discovery of biological markers that may help to identify and elucidate etiologically distinct subgroups. One physical …
A key research priority in the study of autism spectrum conditions (ASC) is the discovery of biological markers that may help to identify and elucidate etiologically distinct subgroups. One physical marker that has received increasing research attention is facial structure. Although there remains little consensus in the field, findings relating to greater facial asymmetry (FA) in ASC exhibit some consistency. As there is growing recognition of the importance of replicatory studies in ASC research, the aim of this study was to investigate the replicability of increased FA in autistic children compared to nonautistic peers. Using three-dimensional photogrammetry, this study examined FA in 84 autistic children, 110 typically developing children with no family history of the condition, and 49 full siblings of autistic children. In support of previous literature, significantly greater depth-wise FA was identified in autistic children relative to the two comparison groups. As a further investigation, increased lateral FA in autistic children was found to be associated with greater severity of ASC symptoms on the Autism Diagnostic Observation Schedule, second edition, specifically related to repetitive and restrictive behaviors. These outcomes provide an important and independent replication of increased FA in ASC, as well as a novel contribution to the field. Having confirmed the direction and areas of increased FA in ASC, these findings could motivate a search for potential underlying brain dysmorphogenesis. Autism Res 2019. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: This study looked at the amount of facial asymmetry (FA) in autistic children compared to typically developing children and children who have siblings with autism. The study found that autistic children, compared to the other two groups, had greater FA, and that increased FA was related to greater severity of autistic symptoms. The face and brain grow together during the earliest stages of development, and so findings of facial differences in autism might inform future studies of early brain differences associated with the condition.