Faecal virome of the Australian grey-headed flying fox from urban/ suburban environments contains novel coronaviruses, retroviruses and sapoviruses

Bats are important reservoirs for viruses of public health and veterinary concern. Virus studies in Australian bats usually target the families Paramyxoviridae, Coronaviridae and Rhabdoviridae, with little known about their overall virome composition. We used metatranscriptomic sequencing to characterise the faecal virome of greyheaded flying foxes from three colonies in urban/suburban locations from two Australian states. We identified viruses from three mammalian-infecting (Coronaviridae, Caliciviridae, Retroviridae) and one possible mammalianinfecting (Birnaviridae) family. Of particular interest were a novel bat betacoronavirus (subgenus Nobecovirus) and a novel bat sapovirus (Caliciviridae), the first identified in Australian bats, as well as a potentially exogenous retrovirus. The novel betacoronavirus was detected in two sampling locations 1375 km apart and falls in a viral lineage likely with a long association with bats. This study highlights the utility of unbiased sequencing of faecal samples for identifying novel viruses and revealing broad-scale patterns of virus ecology and evolution

A New Twist: The Combination of Sulbactam/Avibactam Enhances Sulbactam Activity against Carbapenem-Resistant

An increasing number of untreatable infections are recorded every year. Many studies have focused their efforts on developing new β-lactamase inhibitors to treat multi-drug resistant (MDR) isolates. In the present study, sulbactam/avibactam and sulbactam/relebactam combination were tested against 187 multi-drug resistant (MDR) Acinetobacter clinical isolates; both sulbactam/avibactam and sulbactam/relebactam restored sulbactam activity. A decrease ≥2 dilutions in sulbactam MICs was observed in 89% of the isolates when tested in combination with avibactam. Sulbactam/relebactam was able to restore sulbactam susceptibility in 40% of the isolates. In addition, the susceptibility testing using twenty-three A. baumannii AB5075 knockout strains revealed potential sulbactam and/or sulbactam/avibactam target genes. We observed that diazabicyclooctanes (DBOs) β-lactamase inhibitors combined with sulbactam restore sulbactam susceptibility against carbapenem-resistant Acinetobacter clinical isolates. However, relebactam was not as effective as avibactam when combined with sulbactam. Exploring novel combinations may offer new options to treat Acinetobacter spp. infections, especially for widespread oxacillinases and metallo-β-lactamases (MBLs) producers

The Role of Neutrophils during Mild and Severe Influenza Virus Infections of Mice

Neutrophils have been implicated in both protective and pathological responses following influenza virus infections. We have used mAb 1A8 (anti-Ly6G) to specifically deplete LyG6high neutrophils and induce neutropenia in mice infected with virus strains known to differ in virulence. Mice were also treated with mAb RB6-8C5 (anti-Ly6C/G or anti-Gr-1), a mAb widely used to investigate the role of neutrophils in mice that has been shown to bind and deplete additional leukocyte subsets. Using mAb 1A8, we confirm the beneficial role of neutrophils in mice infected with virus strains of intermediate (HKx31; H3N2) or high (PR8; H1N1) virulence whereas treatment of mice infected with an avirulent strain (BJx109; H3N2) did not affect disease or virus replication. Treatment of BJx109-infected mice with mAb RB6-8C5 was, however, associated with significant weight loss and enhanced virus replication indicating that other Gr-1+ cells, not neutrophils, limit disease severity during mild influenza infections

Persistent frequent attenders in primary care: costs, reasons for attendance, organisation of care and potential for cognitive behavioural therapeutic intervention

<p><b>Abstract</b></p> <p>Background</p> <p>The top 3% of frequent attendance in primary care is associated with 15% of all appointments in primary care, a fivefold increase in hospital expenditure, and more mental disorder and functional somatic symptoms compared to normal attendance. Although often temporary if these rates of attendance last more than two years, they may become persistent (persistent frequent or regular attendance). However, there is no long-term study of the economic impact or clinical characteristics of regular attendance in primary care. Cognitive behaviour formulation and treatment (CBT) for regular attendance as a motivated behaviour may offer an understanding of the development, maintenance and treatment of regular attendance in the context of their health problems, cognitive processes and social context.</p> <p>Methods/design</p> <p>A case control design will compare the clinical characteristics, patterns of health care use and economic costs over the last 10 years of 100 regular attenders (≥30 appointments with general practitioner [GP] over 2 years) with 100 normal attenders (6–22 appointments with GP over 2 years), from purposefully selected primary care practices with differing organisation of care and patient demographics. Qualitative interviews with regular attending patients and practice staff will explore patient barriers, drivers and experiences of consultation, and organisation of care by practices with its challenges. Cognitive behaviour formulation analysed thematically will explore the development, maintenance and therapeutic opportunities for management in regular attenders. The feasibility, acceptability and utility of CBT for regular attendance will be examined.</p> <p>Discussion</p> <p>The health care costs, clinical needs, patient motivation for consultation and organisation of care for persistent frequent or regular attendance in primary care will be explored to develop training and policies for service providers. CBT for regular attendance will be piloted with a view to developing this approach as part of a multifaceted intervention.</p

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Impact of age at onset on the phenomenology of depression in treatment-seeking adults in the STARD trial

- Adolescence is characterized by biological, emotional, and behavioral changes. The onset of depression during this vulnerable time may confer specific risks. This study examined whether symptoms of depression were associated with age at onset (AAO), and whether AAO impacted depression symptom networks in adulthood. - Data were from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial. 3,184 depressed participants were included in analyses. A series of multiple regressions examined whether pretreatment differences in depression item-level symptom severity varied by AAO. Participants were divided into four groups based on AAO; GLASSO networks of depressive symptoms were estimated in each group and tests of differences between networks were performed. - Earlier AAO was associated with more severe symptom levels, with the exception of sleep-which increased with AAO, and loss of libido, psychomotor disturbance, and appetite-weight disturbance, which were invariant with AAO. In network analyses, the adolescent AAO symptom network significantly differed from the young adult and middle age AAO networks in structure and strength. In contrast, the child AAO network differed from the middle age AAO network in strength only. - Age at onset was recalled retrospectively and may be subject to bias. Future prospective studies should be conducted to address this limitation. - Adolescence stands out as a time when onset of depression is associated with specific network characteristics. The unique severity of symptoms and network strength and structure caused by onset of depression during adolescence highlights the long-lasting impact of depression on the developing brain

The severity and role of somatic depressive symptoms in psychological networks in a longitudinal sample of peripartum women

The inclusion of somatic symptoms in assessing peripartum depression (PPD), which encompasses depression during pregnancy and the postpartum period, has remained controversial, as there is substantial overlap between somatic depression symptoms and normal features of pregnancy/postpartum. This study examined whether trajectories differed by PPD symptom subscale and whether PPD symptom networks changed as a function of the peripartum phase. 418 women with a history of neuropsychiatric illness participated in a longitudinal observational study, completing symptom questionnaires assessing affective, cognitive, and somatic symptoms throughout pregnancy and the first year postpartum. Assessments were grouped into five peripartum phases: three trimesters of pregnancy and early/late postpartum. Two analyses were performed. First, a series of multilevel spline regression models examined depression subscale trajectories over peripartum phase. Second, symptom networks and related metrics were estimated for each peripartum phase and compared. Somatic symptoms were most severe and had the most variable peripartum trajectory. The role of somatic symptoms within the networks also changed as a function of peripartum phase. Our results suggest that somatic symptoms can be severe and may play a crucial role in the maintenance of PPD. Thus, somatic symptoms should not be disregarded when assessing for PPD in obstetrical, psychiatric, and pediatric clinics, and clinical research. •Somatic depression symptoms were most severe across peripartum time.•The trajectory of somatic depression symptoms varied most over peripartum time.•Somatic symptoms are critical in the maintenance of peripartum depression.•Somatic symptoms should be included when assessing peripartum depression in the lab and clinic

Characterisation and comparative genomics of three new Varanus-associated Borrelia spp. from Indonesia and Australia

Abstract Background Borrelia are important disease-causing tick- and louse-borne spirochaetes than can infect a wide variety of vertebrates, including humans and reptiles. Reptile-associated (REP) Borrelia, once considered a peculiarity, are now recognised as a distinct and important evolutionary lineage, and are increasingly being discovered worldwide in association with novel hosts. Numerous novel Borrelia spp. associated with monitor lizards (Varanus spp.) have been recently identified throughout the Indo-Pacific region; however, there is a lack of genomic data on these Borrelia. Methods We used metagenomic techniques to sequence almost complete genomes of novel Borrelia spp. from Varanus varius and Varanus giganteus from Australia, and used long- and short-read technologies to sequence the complete genomes of two strains of a novel Borrelia sp. previously isolated from ticks infesting Varanus salvator from Indonesia. We investigated intra- and interspecies genomic diversity, including plasmid diversity and relatedness, among Varanus-associated Borrelia and other available REP Borrelia and, based on 712 whole genome orthologues, produced the most complete phylogenetic analysis, to the best of our knowledge, of REP Borrelia to date. Results The genomic architecture of Varanus-associated Borrelia spp. is similar to that of Borrelia spp. that cause relapsing fever (RF), and includes a highly conserved megaplasmid and numerous smaller linear and circular plasmids that lack structural consistency between species. Analysis of PF32 and PF57/62 plasmid partitioning genes indicated that REP Borrelia plasmids fall into at least six distinct plasmid families, some of which are related to previously defined Borrelia plasmid families, whereas the others appear to be unique. REP Borrelia contain immunogenic variable major proteins that are homologous to those found in Borrelia spp. that cause RF, although they are limited in copy number and variability and have low sequence identities to RF variable major proteins. Phylogenetic analyses based on single marker genes and 712 single copy orthologs also definitively demonstrated the monophyly of REP Borrelia as a unique lineage. Conclusions In this work we present four new genomes from three novel Borrelia, and thus double the number of REP Borrelia genomes publicly available. The genomic characterisation of these Borrelia clearly demonstrates their distinctiveness as species, and we propose the names Borrelia salvatorii, ‘Candidatus Borrelia undatumii’, and ‘Candidatus Borrelia rubricentralis’ for them. Graphical Abstrac

Cierre de la etapa de clasificación y filtrado del catálogo

El siguiente reporte muestra el trabajo realizado de los equipos de diseño y producción audiovisual del Proyecto de Aplicación Profesional Alter CÓDIGO, el cual se desarrolló bajo los lineamientos del manual de producción, manual de uso redes, manual de identidad gráfica, filtro conceptual y filtro técnico para la buena elaboración de los productos entregados. El objetivo del proyecto fue dignificar la imagen de grupos socialmente desfavorecidos, en este caso los adultos mayores en el Área Metropolitana de Guadalajara. Se generaron contenidos audiovisuales y gráficos en torno a la diversidad de la vejez, el envejecimiento activo y la inversión de la pirámide poblacional