The complete genome sequence of the Tanzanian strain of Cassava brown streak virus and comparison with the Ugandan strain sequence

The complete genome sequence for an isolate of the Ugandan and Tanzanian strain types of Cassava brown streak virus have been determined using the novel approach of non-directed next generation sequencing. Comparison of the genome sequences revealed that CBSV is highly heterogeneous at the isolate level as well as the strain level. The isolate of the Ugandan strain was found to have a genome 9,070 nucleotides long coding for a polypeptide with 2,902 amino acid residues. The isolate of the Tanzanian strain was 9,008 nucleotides long and coded for a polypeptide with 2,916 amino acid residues. Nucleotide identity between the isolates across the genome was 76%, with protein encoding regions 57–77% and individual proteins had 65–91% amino acid similarity. In addition between the two strains four protein products (PIPO, CI, NIa-Vpg and coat protein) varied in size and an unusual HAM1-like protein, whilst of identical nucleotide length, was found to have the lowest homology. The implication of diversity of CBSV is discussed in the context of speciation, evolution, development of diagnostics, and breeding for resistance.     

Adolescent depressive symptoms and subsequent pregnancy, pregnancy completion and pregnancy termination in young adulthood: findings from the victorian adolescent health cohort study

Study ObjectiveTo examine relationships between depressive symptoms in adolescence (14-18 years of age) and becoming pregnant, completing a pregnancy (live birth) and terminating a pregnancy in young adulthood (21-24 years of age).Participants and DesignData from 1000 females were drawn from a larger sample of 1943 young Australians participating in a longitudinal study of adolescent health and development, followed across 8 waves from adolescence (waves 1-6) to young adulthood (waves 7 and 8).SettingVictoria, Australia.Main Outcome MeasuresPregnancy, pregnancy completion and pregnancy termination between 21-24 years of age.ResultsWe observed a twofold increase in the odds of becoming pregnant in those reporting persisting patterns of depressive symptoms during adolescence (2+ waves); however, after staged adjustment for adolescent antisocial behaviour, drug use and socioeconomic disadvantage, there was no evidence of association. Of particular note, and consistent with previous research, adolescent antisocial and drug use behavior were strongly associated with becoming pregnant and pregnancy termination in young adulthood.ConclusionsAdolescent antisocial and drug use behavior, not depressive symptoms, independently predict pregnancy outcomes in young adulthood.     

A prospective study of effects of psychological factors and sleep on obstetric interventions, mode of birth, and neonatal outcomes among low-risk British Columbian women

ABSTRACT: BACKGROUND: Obstetrical interventions, including caesarean sections, are increasing in Canada. Canadian women's psychological states, fatigue, and sleep have not been examined prospectively for contributions to obstetric interventions and adverse neonatal outcomes. Context and purpose of the study: The prospective study was conducted in British Columbia (BC), Canada with 650 low-risk pregnant women. Of those women, 624 were included in this study. Women were recruited through providers' offices, media, posters, and pregnancy fairs. We examined associations between pregnant women's fatigue, sleep deprivation, and psychological states (anxiety and childbirth fear) and women's exposure to obstetrical interventions and adverse neonatal outcomes (preterm, admission to NICU, low APGARS, and low birth weight). METHODS: Data from our cross-sectional survey were linked, using women's personal health numbers, to birth outcomes from the Perinatal Services BC database. After stratifying for parity, we used Pearson's Chi-square to examine associations between psychological states, fatigue, sleep deprivation and maternal characteristics. We used hierarchical logistic regression modeling to test 9 hypotheses comparing women with high and low childbirth fear and anxiety on likelihood of having epidural anaesthetic, a caesarean section (stratified for parity), assisted vaginal delivery, and adverse neonatal outcomes and women with and without sleep deprivation and high levels of fatigue on likelihood of giving birth by caesarean section, while controlling for maternal, obstetrical (e.g., infant macrosomia), and psychological variables. RESULTS: Significantly higher proportions of multiparas, reporting difficult and upsetting labours and births, expectations of childbirth interventions, and health stressors, reported high levels of childbirth fear. Women who reported antenatal relationship, housing, financial, and health stressors and multiparas reporting low family incomes were significantly more likely to report high anxiety levels. The hypothesis that high childbirth fear significantly increased the risk of using epidural anaesthesia was supported. CONCLUSIONS: Controlling for some psychological states and sleep quality while examining other contributors to outcomes decreases the likelihood of linking anxiety, sleep deprivation, and fatigue to increased odds of caesarean section. Ameliorating women's childbirth fear to reduce their exposure to epidural anaesthesia can occur through developing effective interventions. These include helping multiparous women process previous experiences of difficult and upsetting labour and birth.     

Childhood cancer survivors exposed to total body irradiation are at significant risk for slipped capital femoral epiphysis during recombinant growth hormone therapy

Background

Childhood cancer survivors treated with cranial or total body irradiation (TBI) are at risk for growth hormone deficiency (GHD). Recombinant growth hormone (rhGH) therapy is associated with slipped capital femoral epiphysis (SCFE). We compared the incidence of SCFE after TBI versus cranial irradiation (CI) in childhood cancer survivors treated with rhGH.

Procedure

Retrospective cohort study (1980–2010) of 119 survivors treated with rhGH for irradiation‐induced GHD (56 TBI; 63 CI). SCFE incidence rates were compared in CI and TBI recipients, and compared with national registry SCFE rates in children treated with rhGH for idiopathic GHD.

Results

Median survivor follow‐up since rhGH initiation was 4.8 (range 0.2–18.3) years. SCFE was diagnosed in 10 subjects post‐TBI and none after CI (P < 0.001). All 10 subjects had atypical valgus SCFE, and 7 were bilateral at presentation. Within TBI recipients, age at cancer diagnosis, sex, race, underlying malignancy, age at radiation, and age at initiation of rhGH did not differ significantly between those with versus without SCFE. The mean (SD) age at SCFE diagnosis was 12.3 (2.7) years and median duration of rhGH therapy to SCFE was 1.8 years. The SCFE incidence rate after TBI exposure was 35.9 per 1,000 person years, representing a 211‐fold greater rate than reported in children treated with rhGH for idiopathic GH deficiency.

Conclusions

The markedly greater SCFE incidence rate in childhood cancer survivors with TBI‐associated GHD, compared with rates in children with idiopathic GHD, suggests that cancer treatment effects to the proximal femoral physis may contribute to SCFE. Pediatr Blood Cancer 2013;60:1766–1771. © 2013 Wiley Periodicals, Inc.     

Increased yield of full GBA sequencing in Ashkenazi Jews with Parkinson's disease

Background

Variants in GBA are the most common genetic risk factor for Parkinson's disease (PD), and are especially prevalent in the Ashkenazi Jewish (AJ) population. However, most studies on GBA in AJ genotype only seven selected Gaucher-associated pathogenic variants rather than sequencing the whole gene, which may leave carriers of PD-associated GBA variants undiscovered.

Exome sequencing identified a de novo mutation of PURA gene in a patient with familial Xp22.31 microduplication

The clinical significance of Xp22.31 microduplication is controversial as it is reported in subjects with developmental delay (DD), their unaffected relatives and unrelated controls. We performed multifaceted studies in a family of a boy with hypotonia, dysmorphic features and DD who carried a 600?Kb Xp22.31 microduplication (7515787-8123310bp, hg19) containing two genes, VCX and PNPLA4. The duplication was transmitted from his cognitively normal maternal grandfather.We found no evidence of the duplication causing the proband's DD and congenital anomalies based on unaltered expression of PNPLA4 in the proband and his mother in comparison to controls and preferential activation of the paternal chromosome X with Xp22.31 duplication in proband's mother. However, a de novo, previously reported deleterious, missense mutation in Pur-alpha gene (PURA) (5q31.2), with a role in neuronal differentiation was detected in the proband by exome sequencing.We propose that the variability in the phenotype in carriers of Xp22.31 microduplication can be due to a second and more deleterious genetic mutation in more severely affected carriers. Widespread use of whole genome next generation sequencing in families with Xp22.31 CNV could help identify such cases.     

Racial/ethnic differences in prognosis communication during initial inpatient palliative care consultations among people with advanced cancer

ObjectiveWe examined whether conversations involving Black or Latino patients with advanced cancer differ in the presence or characteristics of prognosis communication.MethodsWe audio-recorded initial consultations between 54 palliative care clinicians and 231 hospitalized people with advanced cancer. We coded for the presence and characteristics of prognosis communication. We examined whether the presence or characteristics of prognosis communication differed by patients' self-reported race/ethnicity.ResultsIn 231 consultations, 75.7% contained prognosis communication. Prognosis communication was less than half as likely to occur during conversations with Black or Latino patients (N = 48) compared to others. Among consultations in which prognosis was addressed, those involving Black or Latino patients were more than 8 times less likely to contain optimistically cued prognoses compared to others.ConclusionPrognosis communication occurred less frequently for Black and Latino patients and included fewer optimistic cues than conversations with other patients. More work is needed to better understand these observed patterns of prognosis communication that vary by race and ethnicity.Practice implicationsGrowing evidence supports prognosis communication being important for end-of-life decision-making and disproportionately rare among non-White populations. Therefore, our findings identify a potentially salient target for clinical interventions that are focused on ameliorating disparities in end-of-life care.     

Thymic stroma is required for the development of human T cell lineages in vitro

Development of the T cell lineage is characterized by the homingof hematopoietic precursors to thymus, followed by their acquisitionof receptors for antigen. T cell receptors are ß or heterodimers associated with CD3 (TCR-CD3). Very early T cellprecursors in humans have been characterized as CD7+45+ cellswhich lack the T cell differentiation antigens CD1, CD2, CD3,CD4, and CD8. A phenotypically equivalent early thymocyte populationalso occurs in postnatal life, and we have previously shownthat interleukin 2 (IL2) promotes the development in vitro ofboth the ß and the T cells from these early thymocytes.Here we have analyzed the requirements of the induction of theIL2 pathway in early thymocytes, and their developmental potential.We show that: (I) thymic stromal cells, which are present inthymocyte suspensions, are necessary to induce the IL2 pathwayand the development of ß or T cell lineages fromearly thymocytes in vitro; and (II) when removed from the invivo environment, early thymocytes can develop in vitro intoTCR-CD3^– cells of the natural killer (NK) lineage. Weconclude that CD7+45+, CD1–2–3–4–8–early thymocytes are multipotential progenitors that, at least,have the capacity to develop into ß or T cell andNK lineages. The analysis of the mechanisms of generation andselection of human T and NK cell diversity, not feasible inbone marrow cultures, is now possible.