Abstract The gut microbiota interacts with the host via neuroimmune, neuroendocrine and neural pathways. These pathways are components of the brain-gut-microbiota axis and preclinical evidence ...suggests that the microbiota can recruit this bidirectional communication system to modulate brain development, function and behaviour. The pathophysiology of depression involves neuroimmune-neuroendocrine dysregulation. However, the extent to which changes in gut microbiota composition and function mediate the dysregulation of these pathways is unknown. Thirty four patients with major depression and 33 matched healthy controls were recruited. Cytokines, CRP, Salivary Cortisol and plasma Lipopolysaccharide binding protein were determined by ELISA. Plasma tryptophan and kynurenine were determined by HPLC. Fecal samples were collected for 16s rRNA sequencing. A Fecal Microbiota transplantation was prepared from a sub group of depressed patients and controls and transferred by oral gavage to a microbiota-deficient rat model. We demonstrate that depression is associated with decreased gut microbiota richness and diversity. Fecal microbiota transplantation from depressed patients to microbiota-depleted rats can induce behavioural and physiological features characteristic of depression in the recipient animals, including anhedonia and anxiety-like behaviours, as well as alterations in tryptophan metabolism. This suggests that the gut microbiota may play a causal role in the development of features of depression and may provide a tractable target in the treatment and prevention of this disorder.
High-throughput sequencing has enabled detailed insights into complex microbial environments, including the human gut microbiota. The accuracy of the sequencing data however, is reliant upon ...appropriate storage of the samples prior to DNA extraction. The aim of this study was to conduct the first MiSeq sequencing investigation into the effects of faecal storage on the microbiota, compared to fresh samples. Culture-based analysis was also completed.
Seven faecal samples were collected from healthy adults. Samples were separated into fresh (DNA extracted immediately), snap frozen on dry ice and frozen for 7 days at -80°C prior to DNA extraction or samples frozen at -80°C for 7 days before DNA extraction. Sequencing was completed on the Illumina MiSeq platform. Culturing of total aerobes, anaerobes and bifidobacteria was also completed.
No significant differences at phylum or family levels between the treatment groups occurred. At genus level only Faecalibacterium and Leuconostoc were significantly different in the fresh samples compared to the snap frozen group (p = 0.0298; p = 0.0330 respectively). Diversity analysis indicated that samples clustered based on the individual donor, rather than by storage group. No significant differences occurred in the culture-based analysis between the fresh, snap or -80°C frozen samples.
Using the MiSeq platform coupled with culture-based analysis, this study highlighted that limited significant changes in microbiota occur following rapid freezing of faecal samples prior to DNA extraction. Thus, rapid freezing of samples prior to DNA extraction and culturing, preserves the integrity of the microbiota.
ObjectivesOver two million people in the UK are living with and beyond cancer. A third report diminished quality of life.DesignA review of published systematic reviews to identify effective ...non-pharmacological interventions to improve the quality of life of cancer survivors.Data sourcesDatabases searched until May 2017 included PubMed, Cochrane Central, EMBASE, MEDLINE, Web of Science, the Cumulative Index to Nursing and Allied Health Literature, and PsycINFO.Study selectionPublished systematic reviews of randomised trials of non-pharmacological interventions for people living with and beyond cancer were included; included reviews targeted patients aged over 18. All participants had already received a cancer diagnosis. Interventions located in any healthcare setting, home or online were included. Reviews of alternative therapies or those non-English reports were excluded. Two researchers independently assessed titles, abstracts and the full text of papers, and independently extracted the data.OutcomesThe primary outcome of interest was any measure of global (overall) quality of life.Analytical methodsQuality assessment assessing methdological quality of systematic reviews (AMSTAR) and narrative synthesis, evaluating effectiveness of non-pharmacological interventions and their components.ResultsOf 14 430 unique titles, 21 were included in the review of reviews. There was little overlap in the primary papers across these reviews. Thirteen reviews covered mixed tumour groups, seven focused on breast cancer and one focused on prostate cancer. Face-to-face interventions were often combined with online, telephone and paper-based reading materials. Interventions included physical, psychological or behavioural, multidimensional rehabilitation and online approaches. Yoga specifically, physical exercise more generally, cognitive behavioural therapy (CBT) and mindfulness-based stress reduction (MBSR) programmes showed benefit in terms of quality of life.ConclusionsExercise-based interventions were effective in the short (less than 3–8 months) and long term. CBT and MBSR also showed benefits, especially in the short term. The evidence for multidisciplinary, online and educational interventions was equivocal.
Between Orders and Heresy foregrounds the dynamic, creative, and diverse late medieval religious landscapes that flourished within the spaces of social and ecclesiastical structures.
This collection ...reconsiders the arguments put forward in Herbert Grundmann’s monumental book, Religious Movements in the Middle Ages, and challenges his traditional interpretive binary, recognized as the shared origins of many medieval religious movements. The contributors explore the social relationships fostered between secular clergy members, including parish priests, local canons, and aristocratic confessors, and examine the ways in which laypeople inspired and engaged in devotion beyond religious orders.
Each essay in the volume considers a major theme in medieval religious history, such as the implementation of apostolic ideals, pastoral relationships, crusade connections, vernacular traditions, and reform. Organized to historicize and challenge the deeply embedded historiographical tendencies that have long distorted the complex dynamics of the late medieval world, Between Orders and Heresy is a major assessment of medieval religious belief and activity beyond and between the binary of orders and heresies
Rural cancer inequalities are evident internationally, with rural cancer patients 5% less likely to survive than their urban counterparts. There is evidence to suggest that diagnostic delays prior to ...entry into secondary care may be contributing to these poorer rural cancer outcomes. This study explores the symptom appraisal and help-seeking decision-making of people experiencing symptoms of colorectal cancer in rural areas of England. Patients were randomly invited from 4 rural practices, serving diverse communities. Semi-structured interviews were undertaken with 40 people who had experienced symptoms of colorectal cancer in the preceding 8 weeks. Four key themes were identified as influential in participants' willingness and timeliness of consultation: a desire to rule out cancer (facilitator of help-seeking); stoicism and self-reliance (barrier to help-seeking); time scarcity (barrier to help-seeking); and GP/patient relationship (barrier or facilitator, depending on perceived strength of the relationship). Self-employed, and "native" rural residents most commonly reported experiencing time scarcity and poor GP/patient relationships as a barrier to (re-)consultation. Targeted, active safety-netting approaches, and increased continuity of care, may be particularly beneficial to expedite timely diagnoses and minimise cancer inequalities for rural populations.
Introduction
Head and neck cancer (HNC) diagnosis and treatment can be a significant life trauma. Some HNC survivors experience post-traumatic growth (PTG), which has been linked with better ...health-related quality-of-life. Empirical research on PTG, and theoretical models, point to the importance of being able to purposely make sense of the traumatic experience. Intrusive rumination, by contrast, is linked to poorer outcomes. This study explored HNC survivors’ experiences of rumination.
Methods
Twenty HNC survivors between 9 months and 5 years post-diagnosis were recruited (11 male, 9 female, age range 46–83). They had a range of HNC sub-types and cancer treatments. Participants underwent a semi-structured interview about their cancer diagnosis and treatment. Reflexive thematic analysis identified themes and sub-themes around rumination.
Results
Four themes with linked subthemes on the content and process of rumination were identified. Theme 1 was
rumination and worry related to diagnosis
. Here, survivors discussed how the HNC diagnosis and plans for treatment had dominated their initial thoughts. Theme 2 was
processing the trauma of HNC
. This theme reflected rumination on the traumatic experience of diagnosis and treatment and how the participant was reacting to it. Theme 3 was
considering the impact
. This theme encompassed retrospective thinking (e.g., on treatment decisions made) and comparisons between the participant now versus the early days after diagnosis. Theme 4 was
continued rumination
. This theme included ongoing intrusive and distressing rumination about the trauma and impact of cancer. Those who expressed ongoing rumination revisited fears (e.g., concerns about their future) or returned to negative experiences (e.g., distressing exchanges with healthcare professionals or what they perceived as poor care).
Conclusion
This study uniquely describes the nature and content of rumination following HNC. Early intrusive rumination is common and may reflect perceptions of cancer as an existential threat. Over time, rumination can become more reflective and move towards deliberate meaning-making. Some HNC survivors may benefit from interventions to reduce barriers to this transition. The content of distressing and difficult to control rumination (commonly focused on ongoing fears or inability to resolve difficult experiences) helps to identify those who may benefit from more directed psychological support.
Abstract The in vitro activity and spectrum of tedizolid and comparators were analyzed against 6884 Gram-positive clinical isolates collected from multiple US and European sites as part of the ...Surveillance of Tedizolid Activity and Resistance Program in 2011 and 2012. Organisms included 4499 Staphylococcus aureus , 537 coagulase-negative staphylococci (CoNS), 873 enterococci, and 975 β-hemolytic streptococci. The MIC values that inhibited 90% of the isolates within each group (MIC90 ) were 0.25 μg/mL for Staphylococcus epidermidis and β-hemolytic streptococci and 0.5 μg/mL for S. aureus , other CoNS, and enterococci. Of 16 isolates with elevated tedizolid or linezolid MIC values (intermediate or resistant isolates), 10 had mutations in the genes encoding 23S rRNA (primarily G2576T), 5 had mutations in the genes encoding ribosomal proteins L3 or L4, and 5 carried the cfr multidrug resistance gene. Overall, tedizolid showed excellent activity against Gram-positive bacteria and was at least 4-fold more potent than linezolid against wild-type and linezolid-resistant isolates. Given the low overall frequency of isolates that would be resistant to tedizolid at the proposed break point of 0.5 μg/mL (0.19%) and potent activity against contemporary US and European isolates, tedizolid has the potential to serve as a valuable therapeutic option in the treatment of infections caused by Gram-positive pathogens.
IntroductionApproximately 10 300 people are diagnosed with pancreatic cancer each year in the UK. The cancer and its treatment inflict a significant physical, functional and emotional burden on ...patients. Research suggests that patients have many ongoing needs for support and care, but that these needs are not met by existing services. Family members often step in to fill this gap and provide support and care during and after treatment. Research in other cancers shows that this informal caregiving can place a very heavy burden on carers. However, there are few studies in the international literature that have focused on informal carers in pancreatic cancer; none have been conducted in the UK.Methods and analysisTwo complementary research methods will be utilised. First, a longitudinal quantitative study of 300 carers investigating, using validated questionnaires to assess the impact of caregiving (Caregiver Reaction Assessment), the unmet needs of carers (Supportive Care Needs Survey) and the quality-of-life (Short Form 12-item health survey), will be conducted. Second, qualitative interviews will be conducted with up to 30 carers to explore their experiences in more depth. Mixed-effects regression models will be applied to survey results to determine how impact, needs and quality-of-life vary over time, compare outcomes between carers of patients with operable and inoperable disease and identify social factors which affect outcomes. Interview data will undergo reflexive thematic analysis.Ethics and disseminationThe protocol has been approved by the Health Research Authority of the UK (Ethical approval IRAS ID 309503). Findings will be published in peer-reviewed journals and presented at national and international conferences.
Cell envelope–active agents, particularly β‐lactams, play a pivotal role in the treatment of bacterial infections and the extent to which their activity is affected by the emergence of ...multidrug‐resistant organisms is of concern. We analyzed the Surveillance Network (TSN) database to evaluate resistant trends for key cell envelope–active drugs among ESKAPE pathogens. Analysis demonstrated that the activity of these drugs has been notably influenced by the emergence of multidrug resistance; this was especially evident for the β‐lactam drugs. For example, Acinetobacter baumannii resistance to imipenem increased from 23.9% to 34.3%, and resistance to piperacillin–tazobactam increased from 37.0% to 49.7% between 2007 and 2011. During the same time period Klebsiella pneumoniae resistance to imipenem increased from 0.8% to 3.8%. As β‐lactams are a cornerstone of anti‐infective therapy, it is important to closely monitor the activity of the agents being used today and to aggressively pursue new strategies that can augment current drugs and thwart ever‐emerging β‐lactam resistance mechanisms that are continuously encountered.
Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder that may be triggered by enteric pathogens and has also been linked to alterations in the microbiota and the host ...immune response. The authors performed a detailed analysis of the faecal microbiota in IBS and control subjects and correlated the findings with key clinical and physiological parameters.
The authors used pyrosequencing to determine faecal microbiota composition in 37 IBS patients (mean age 37 years; 26 female subjects; 15 diarrhoea-predominant IBS, 10 constipation-predominant IBS and 12 alternating-type IBS) and 20 age- and gender-matched controls. Gastrointestinal and psychological symptom severity and quality of life were evaluated with validated questionnaires and colonic transit time and rectal sensitivity were measured.
Associations detected between microbiota composition and clinical or physiological phenotypes included microbial signatures associated with colonic transit and levels of clinically significant depression in the disease. Clustering by microbiota composition revealed subgroups of IBS patients, one of which (n=15) showed normal-like microbiota composition compared with healthy controls. The other IBS samples (n=22) were defined by large microbiota-wide changes characterised by an increase of Firmicutes-associated taxa and a depletion of Bacteroidetes-related taxa.
Detailed microbiota analysis of a well-characterised cohort of IBS patients identified several clear associations with clinical data and a distinct subset of IBS patients with alterations in their microbiota that did not correspond to IBS subtypes, as defined by the Rome II criteria.
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