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An abstract of the conference paper "First-in-human phase 1 trial of the safety and immunogenicity of a recombinant adenovirus serotype 5 HVR48 (rAd5HVR48) HIV-1 vaccine" by S. R. Walsh and colleagues is presented.

Background: The intimate association between parasitic plants and their hosts favours the exchange of genetic material, potentially leading to horizontal gene transfer (HGT) between plants. With the recent publication of several parasitic plant nuclear genomes, there has been considerable focus on such non-sexual exchange of genes. To enhance the picture on HGT events in a widely distributed parasitic genus, Cuscuta (dodders), we assembled and analyzed the organellar genomes of two recently sequenced species, C. australis and C. campestris, making this the first account of complete mitochondrial genomes (mitogenomes) for this genus., Results: The mitogenomes are 265,696 and 275,898 bp in length and contain a typical set of mitochondrial genes, with 10 missing or pseudogenized genes often lost from angiosperm mitogenomes. Each mitogenome also possesses a structurally unusual ccmF C gene, which exhibits splitting of one exon and a shift to trans-splicing of its intron. Based on phylogenetic analysis of mitochondrial genes from across angiosperms and similarity-based searches, there is little to no indication of HGT into the Cuscuta mitogenomes. A few candidate regions for plastome-to-mitogenome transfer were identified, with one suggestive of possible HGT., Conclusions: The lack of HGT is surprising given examples from the nuclear genomes, and may be due in part to the relatively small size of the Cuscuta mitogenomes, limiting the capacity to integrate foreign sequences., (© 2021. The Author(s).)

Background: The Patient Health Questionnaire-8 (PHQ-8) is a screening questionnaire of depressive symptoms. However, it is unknown whether it is equivalent across time and between groups of individuals. The aim of our paper was to test whether the PHQ-8 has the same meaning in two groups of individuals over time., Methods: Primary care patients were proactively recruited from three German cities. PHQ-8 data from a baseline assessment (n = 588), two assessments during the intervention (n = 246/225), and a six (n = 437) and 12 months (n = 447) follow-up assessment were first used to examine the factor structure of the PHQ-8 by confirmatory factor analysis (CFA). The best fitting factor solution was then used to test longitudinal invariance across time and between intervention and control group by Multiple Group CFA., Results: A two-factor structure consistently showed the best model fit. Only configural longitudinal invariance was evidenced when the baseline assessment was included in the analysis. Without the baseline assessment, strict longitudinal invariance was shown across the intervention and the follow-up assessments. Scalar invariance was established between the intervention and control group for the baseline assessment and strict invariance between groups and across the 6- and 12-month follow-up assessments., Conclusions: The lack of longitudinal invariance might be attributed to various differences between the baseline assessments and all following assessments, e.g., assessment mode (iPad vs telephone), potential changes in symptom perception, and setting., Trial Registration: DRKS0001163 5, date of trial registration: 20.01.2017; DRKS00011637 , date of trial registration: 25.01.2017., (© 2021. The Author(s).)

Background: Predischarge home assessments (PDHA) aim to support safe discharge from hospital or rehabilitation. There is insufficient evidence on the effectiveness of PDHA. For adults with any diagnosis, we aimed to determine (1) the effects of PDHA on outcomes associated with the successful return to community living (e.g., Activities of Daily Living, falls) and (2) the associated barriers and facilitators in order to derive recommendations for clinical practice., Methods: We searched Medline, EMBASE, CINAHL, five additional databases and other sources. We included individual and cluster randomized (RCT/cRCT) and controlled clinical trials comparing PDHA versus usual care/other intervention, as well as qualitative/mixed methods studies dealing with PDHA. Critical appraisal was performed according to the Cochrane risk-of-bias tool in quantitative studies and the Critical Appraisal Skills Programme (CASP) as well as the McMaster University Guidelines for Critical Review Form for qualitative studies and data extraction. Meta-analysis, thematic synthesis and integrative synthesis were performed., Results: Eight RCTs (n = 1072) and ten qualitative studies (n = 336) met the inclusion criteria. RCTs reported a variety of outcomes (n = 17). We are uncertain if PDHA has any effect on patient outcomes in Activities of Daily Living, quality of life, mobility and fear of falling, falls and hospital readmissions (with moderate to very low quality of the evidence). The qualitative studies revealed facilitators and barriers which should be considered by therapists when conducting PDHA. These were related to the following topics: patient safety education, patient information, patients' acceptance of modifications and aids, functional assessment, standardization of procedures as well as the consideration of relevant patient conditions and contextual factors in PDHA., Conclusion: There is no evidence from the meta-analysis for the effectiveness of PDHA. Further robust studies are needed to adapt and evaluate PDHA interventions, taking the identified stakeholders' views on PDHA into account and following the current recommendations for the development and evaluation of complex interventions., Trial Registration: The review was registered and methods were reported on PROSPERO on 18th July 2018 ( CRD42018100636 ).

Background: Motor and cognitive deficits and consequently mobility problems are common in geriatric patients. The currently available methods for diagnosis and for the evaluation of treatment in this vulnerable cohort are limited. The aims of the ComOn (COgnitive and Motor interactions in the Older populatioN) study are (i) to define quantitative markers with clinical relevance for motor and cognitive deficits, (ii) to investigate the interaction between both motor and cognitive deficits and (iii) to assess health status as well as treatment outcome of 1000 geriatric inpatients in hospitals of Kiel (Germany), Brescia (Italy), Porto (Portugal), Curitiba (Brazil) and Bochum (Germany)., Methods: This is a prospective, explorative observational multi-center study. In addition to the comprehensive geriatric assessment, quantitative measures of reduced mobility and motor and cognitive deficits are performed before and after a two week's inpatient stay. Components of the assessment are mobile technology-based assessments of gait, balance and transfer performance, neuropsychological tests, frailty, sarcopenia, autonomic dysfunction and sensation, and questionnaires to assess behavioral deficits, activities of daily living, quality of life, fear of falling and dysphagia. Structural MRI and an unsupervised 24/7 home assessment of mobility are performed in a subgroup of participants. The study will also investigate the minimal clinically relevant change of the investigated parameters., Discussion: This study will help form a better understanding of symptoms and their complex interactions and treatment effects in a large geriatric cohort.

Background: Gene expression changes that govern essential biological processes can occur at the cell-specific level. To gain insight into such events, laser microdissection is applied to cut out specific cells or tissues from which RNA for gene expression analysis is isolated. However, the preparation of plant tissue sections for laser microdissection and subsequent RNA isolation usually involves fixation and embedding, processes that are often time-consuming and can lower the yield and quality of isolated RNA., Results: Infection sites of the parasitic plant Cuscuta reflexa growing on its compatible host plant Pelargonium zonale were sectioned using a vibratome and dried on glass slides at 4 °C before laser microdissection. High quality RNA (RQI > 7) was isolated from 1 mm 2 , 3 mm 2 and 6 mm 2 total surface areas of laser microdissection-harvested C. reflexa tissue, with the yield of RNA correlating to the amount of collected material (on average 7 ng total RNA/mm 2 ). The expression levels of two parasite genes previously found to be highly expressed during host plant infection were shown to differ individually between specific regions of the infection site. By drying plant sections under low pressure to reduce the dehydration time, the induced expression of two wound-related genes during preparation was avoided., Conclusions: Plants can be prepared quickly and easily for laser microdissection by direct sectioning of fresh tissue followed by dehydration on glass slides. We show that RNA isolated from material treated in this manner maintains high quality and enables the investigation of differential gene expression at a high morphological resolution., Competing Interests: Competing interestsThe authors declare that they have no competing interests.

Background: The complex process of development of the pituitary gland is regulated by a number of signalling molecules and transcription factors. Mutations in these factors have been identified in rare cases of congenital hypopituitarism but for most subjects with combined pituitary hormone deficiency (CPHD) genetic causes are unknown. Bone morphogenetic proteins (BMPs) affect induction and growth of the pituitary primordium and thus represent plausible candidates for mutational screening of patients with CPHD., Methods: We sequenced BMP2, 4 and 7 in 19 subjects with CPHD. For validation purposes, novel genetic variants were genotyped in 1046 healthy subjects. Additionally, potential functional relevance for most promising variants has been assessed by phylogenetic analyses and prediction of effects on protein structure., Results: Sequencing revealed two novel variants and confirmed 30 previously known polymorphisms and mutations in BMP2, 4 and 7. Although phylogenetic analyses indicated that these variants map within strongly conserved gene regions, there was no direct support for their impact on protein structure when applying predictive bioinformatics tools., Conclusions: A mutation in the BMP4 coding region resulting in an amino acid exchange (p.Arg300Pro) appeared most interesting among the identified variants. Further functional analyses are required to ultimately map the relevance of these novel variants in CPHD.

Introduction: Maternal body mass index has an impact on maternal and fetal pregnancy outcome. An increased maternal BMI is known to be associated with admission of the newborn to a neonatal care unit. The reasons and impact of this admission on fetal outcome, however, are unknown so far., Objective: The aim of our study was to investigate the impact of maternal BMI on maternal and fetal pregnancy outcome with special focus on the children admitted to a neonatal care unit., Methods: A cohort of 2049 non-diabetic mothers giving birth in the Charite university hospital was prospectively studied. The impact of maternal BMI on maternal and fetal outcome parameters was tested using multivariate regression analysis. Outcome of children admitted to a neonatal ward (n = 505) was analysed., Results: Increased maternal BMI was associated with an increased risk for hypertensive complications, peripheral edema, caesarean section, fetal macrosomia and admission of the newborn to a neonatal care unit, whereas decreased BMI was associated with preterm birth and lower birthweight. In the neonatal ward children from obese mothers are characterized by hypoglycaemia. They need less oxygen, and exhibit a shorter stay on the neonatal ward compared to children from normal weight mothers, whereas children from underweight mothers are characterized by lower umbilical blood pH and increased incidence of death corresponding to increased prevalence of preterm birth., Conclusion: Pregnancy outcome is worst in babies from mothers with low body mass index as compared to healthy weight mothers with respect to increased incidence of preterm birth, lower birth weight and increased neonate mortality on the neonatal ward. We demonstrate that the increased risk for neonatal admission in children from obese mothers does not necessarily indicate severe fetal impairment.

Background: The holoparasitic plant genus Cuscuta comprises species with photosynthetic capacity and functional chloroplasts as well as achlorophyllous and intermediate forms with restricted photosynthetic activity and degenerated chloroplasts. Previous data indicated significant differences with respect to the plastid genome coding capacity in different Cuscuta species that could correlate with their photosynthetic activity. In order to shed light on the molecular changes accompanying the parasitic lifestyle, we sequenced the plastid chromosomes of the two species Cuscuta reflexa and Cuscuta gronovii. Both species are capable of performing photosynthesis, albeit with varying efficiencies. Together with the plastid genome of Epifagus virginiana, an achlorophyllous parasitic plant whose plastid genome has been sequenced, these species represent a series of progression towards total dependency on the host plant, ranging from reduced levels of photosynthesis in C. reflexa to a restricted photosynthetic activity and degenerated chloroplasts in C. gronovii to an achlorophyllous state in E. virginiana., Results: The newly sequenced plastid genomes of C. reflexa and C. gronovii reveal that the chromosome structures are generally very similar to that of non-parasitic plants, although a number of species-specific insertions, deletions (indels) and sequence inversions were identified. However, we observed a gradual adaptation of the plastid genome to the different degrees of parasitism. The changes are particularly evident in C. gronovii and include (a) the parallel losses of genes for the subunits of the plastid-encoded RNA polymerase and the corresponding promoters from the plastid genome, (b) the first documented loss of the gene for a putative splicing factor, MatK, from the plastid genome and (c) a significant reduction of RNA editing., Conclusion: Overall, the comparative genomic analysis of plastid DNA from parasitic plants indicates a bias towards a simplification of the plastid gene expression machinery as a consequence of an increasing dependency on the host plant. A tentative assignment of the successive events in the adaptation of the plastid genomes to parasitism can be inferred from the current data set. This includes (1) a loss of non-coding regions in photosynthetic Cuscuta species that has resulted in a condensation of the plastid genome, (2) the simplification of plastid gene expression in species with largely impaired photosynthetic capacity and (3) the deletion of a significant part of the genetic information, including the information for the photosynthetic apparatus, in non-photosynthetic parasitic plants.