271 research outputs found

    Mastitomics, the integrated omics of bovine milk in an experimental model of Streptococcus uberis mastitis: 2. Label-free relative quantitative proteomics

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    Mastitis, inflammation of the mammary gland, is the most common and costly disease of dairy cattle in the western world. It is primarily caused by bacteria, with Streptococcus uberis as one of the most prevalent causative agents. To characterize the proteome during Streptococcus uberis mastitis, an experimentally induced model of intramammary infection was used. Milk whey samples obtained from 6 cows at 6 time points were processed using label-free relative quantitative proteomics. This proteomic analysis complements clinical, bacteriological and immunological studies as well as peptidomic and metabolomic analysis of the same challenge model. A total of 2552 non-redundant bovine peptides were identified, and from these, 570 bovine proteins were quantified. Hierarchical cluster analysis and principal component analysis showed clear clustering of results by stage of infection, with similarities between pre-infection and resolution stages (0 and 312 h post challenge), early infection stages (36 and 42 h post challenge) and late infection stages (57 and 81 h post challenge). Ingenuity pathway analysis identified upregulation of acute phase protein pathways over the course of infection, with dominance of different acute phase proteins at different time points based on differential expression analysis. Antimicrobial peptides, notably cathelicidins and peptidoglycan recognition protein, were upregulated at all time points post challenge and peaked at 57 h, which coincided with 10 000-fold decrease in average bacterial counts. The integration of clinical, bacteriological, immunological and quantitative proteomics and other-omic data provides a more detailed systems level view of the host response to mastitis than has been achieved previously

    Epidemiology of adult overweight recording and management by UK GPs:a systematic review

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    Supplementary Table: Key components of included studies. A table detailing key components of included studies. (PDF 99 kb

    Epidemiology of adult overweight recording and management by UK GPs:a systematic review

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    BackgroundPrimary care guidelines for managing adult overweight/obesity recommend routine measurement of body mass index (BMI) and the offer of weight management interventions. Many studies state that this is rarely done, but the extent to which overweight/obesity is recognised, considered, and documented in routine care has not been determined.AimTo identify the epidemiology of adult overweight documentation and management by UK GPs.Design and settingA systematic review of studies since 2006 from eight electronic databases and grey literature.MethodIncluded studies measured the proportion of adult patients with documented BMI or weight loss intervention offers in routine primary care in the UK. A narrative synthesis reports the prevalence and pattern of the outcomes.ResultsIn total, 2845 articles were identified, and seven were included; four with UK-wide data and three with regional-level data. The proportion of patients with a documented BMI was 58–79% (28–37% within a year). For overweight/obese patients alone, 43–52% had a recent BMI record, and 15–42% had a documented intervention offer. BMI documentation was positively associated with older age, female sex, higher BMI, coexistent chronic disease, and higher deprivation.ConclusionBMI is under-recorded and weight loss interventions are under-referred for primary care adult patients in the UK despite the obesity register in the Quality and Outcomes Framework (QOF). The review identified likely underserved groups such as younger males and otherwise healthy overweight/obese individuals to whom attention should now be directed. The proposed amendment to the obesity register QOF could prompt improvements but has not been adopted for 2017.</jats:sec

    What effect have NHS commissioners’ policies for body mass index had on access to knee replacement surgery in England?:An interrupted time series analysis from the National Joint Registry

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    ObjectiveTo assess the impact of local commissioners' policies for body mass index on access to knee replacement surgery in England.MethodsA Natural Experimental Study using interrupted time series and difference-in-differences analysis. We used National Joint Registry for England data linked to the 2015 Index of Multiple Deprivation for 481,555 patients who had primary knee replacement surgery in England between January 2009 and December 2019. Clinical Commissioning Group policies introduced before June 2018 to alter access to knee replacement for patients who were overweight or obese were considered the intervention. The main outcome measures were rate per 100,000 of primary knee replacement surgery and patient demographics (body mass index, Index of Multiple Deprivation, independently-funded surgery) over time.ResultsRates of surgery had a sustained fall after the introduction of a policy (trend change of -0.98 operations per 100,000 population aged 40+, 95% confidence interval -1.22 to -0.74, PConclusionsBody mass index policy introduction was associated with decreases in the rates of knee replacement surgery across localities that introduced policies. This affected all patient groups, not just obese patients at whom the policies were targeted. Changes in patient demographics seen after policy introduction suggest these policies may increase health inequalities and further qualitative research is needed to understand their implementation and impact

    Context-specific economic evaluation for molecular pathology tests: An application in colorectal cancer in the West of Scotland.

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    The cost-effectiveness of molecular pathology testing is highly context dependent. The field is fast-moving, and national health technology assessment may not be relevant or timely for local decision makers. This study illustrates a method of context-specific economic evaluation that can be carried out in a limited timescale without extensive resources. We established a multi-disciplinary group including an oncologist, pathologists and a health economist. We set out diagnostic and treatment pathways and costs using registry data, health technology assessments, guidelines, audit data, and estimates from the group. Sensitivity analysis varied input parameters across plausible ranges. The evaluation setting was the West of Scotland and UK NHS perspective was adopted. The evaluation was assessed against the AdHopHTA checklist for hospital-based health technology assessment. A context-specific economic evaluation could be carried out on a timely basis using limited resources. The evaluation met all relevant criteria in the AdHopHTA checklist. Health outcomes were expected to be at least equal to the current strategy. Annual cost savings of £637,000 were estimated resulting primarily from a reduction in the proportion of patients receiving intravenous infusional chemotherapy regimens. The result was not sensitive to any parameter. The data driving the main cost saving came from a small clinical audit. We recommended this finding was confirmed in a larger population. The method could be used to evaluate testing changes elsewhere. The results of the case study may be transferable to other jurisdictions where the organization of cancer services is fragmented

    Neural stem cells restore myelin in a demyelinating model of Pelizaeus-Merzbacher disease

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    Pelizaeus-Merzbacher disease is a fatal X-linked leukodystrophy caused by mutations in the PLP1 gene, which is expressed in the CNS by oligodendrocytes. Disease onset, symptoms and mortality span a broad spectrum depending on the nature of the mutation and thus the degree of CNS hypomyelination. In the absence of an effective treatment, direct cell transplantation into the CNS to restore myelin has been tested in animal models of severe forms of the disease with failure of developmental myelination, and more recently, in severely affected patients with early disease onset due to point mutations in the PLP1 gene, and absence of myelin by MRI. In patients with a PLP1 duplication mutation, the most common cause of Pelizaeus-Merzbacher disease, the pathology is poorly defined because of a paucity of autopsy material. To address this, we examined two elderly patients with duplication of PLP1 in whom the overall syndrome, including end-stage pathology, indicated a complex disease involving dysmyelination, demyelination and axonal degeneration. Using the corresponding Plp1 transgenic mouse model, we then tested the capacity of transplanted neural stem cells to restore myelin in the context of PLP overexpression. Although developmental myelination and axonal coverage by endogenous oligodendrocytes was extensive, as assessed using electron microscopy (n = 3 at each of four end points) and immunostaining (n = 3 at each of four end points), wild-type neural precursors, transplanted into the brains of the newborn mutants, were able to effectively compete and replace the defective myelin (n = 2 at each of four end points). These data demonstrate the potential of neural stem cell therapies to restore normal myelination and protect axons in patients with PLP1 gene duplication mutation and further, provide proof of principle for the benefits of stem cell transplantation for other fatal leukodystrophies with ‘normal’ developmental myelination

    Conceptual Analysis: A Social Neuroscience Approach to Interpersonal Interaction in the Context of Disruption and Disorganization of Attachment (NAMDA)

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    Humans are strongly dependent upon social resources for allostasis and emotion regulation. This applies especially to early childhood because humans – as an altricial species – have a prolonged period of dependency on support and input from caregivers who typically act as sources of co-regulation. Accordingly, attachment theory proposes that the history and quality of early interactions with primary caregivers shape children’s internal working models of attachment. In turn, these attachment models guide behavior, initially with the set goal of maintaining proximity to caregivers, but eventually paving the way to more generalized mental representations of self and others. Mounting evidence in nonclinical populations suggests that these mental representations coincide with differential patterns of neural structure, function, and connectivity in a range of brain regions previously associated with emotional and cognitive capacities. What is currently lacking, however, is an evidence-based account of how early adverse attachment-related experiences and/or the emergence of attachment disorganization impact the developing brain. While work on early childhood adversities offers important insights, we propose that how these events become biologically embedded crucially hinges on the context of the child-caregiver attachment relationships in which the events take place. Our selective review distinguishes between direct social neuroscience research on disorganized attachment and indirect maltreatment-related research, converging on aberrant functioning in neurobiological systems subserving aversion, approach, emotion regulation, and mental state processing in the wake of severe attachment disruption. To account for heterogeneity of findings, we propose two distinct neurobiological phenotypes characterized by hyper- and hypo-arousal primarily deriving from the caregiver serving either as a threatening or as an insufficient source of co-regulation, respectively
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