The use of oral antibiotics and mechanical bowel preparation in elective colorectal resection for the reduction of surgical site infection.

Surgical site infection (SSI) is a major cause of morbidity following elective colorectal resection worldwide. Reduction in SSI rates can be achieved with the use of SSI reduction bundles. Debate about the role of mechanical bowel preparation and oral antibiotics (MOAB) in reducing SSI has persisted over decades with considerable variation in international practice. This article summarises the arguments for and against the routine use of MOAB in the elective setting, highlighting the areas of controversy and evidence gaps and provides pragmatic suggestions for colorectal practice.This topical debate paper was commissioned by the President and Executive of the Association of Coloproctology of Great Britain and Ireland. ACPGBI also funded the open access publication fee. The authors would like to thank Ms J Pipe for her comments from the patient perspective and Miss N Fearnhead for her support in developing this debate article

The method of educational assessment affects children’s neural processing and performance: behavioural and fMRI Evidence.

Standardised educational assessments are now widespread, yet their development has given comparatively more consideration to what to assess than how to optimally assess students’ competencies. Existing evidence from behavioural studies with children and neuroscience studies with adults suggest that the method of assessment may affect neural processing and performance, but current evidence remains limited. To investigate the impact of assessment methods on neural processing and performance in young children, we used functional magnetic resonance imaging to identify and quantify the neural correlates during performance across a range of current approaches to standardised spelling assessment. Results indicated that children’s test performance declined as the cognitive load of assessment method increased. Activation of neural nodes associated with working memory further suggests that this performance decline may be a consequence of a higher cognitive load, rather than the complexity of the content. These findings provide insights into principles of assessment (re)design, to ensure assessment results are an accurate reflection of students’ true levels of competency

Screening Patients with a Family History of Colorectal Cancer

OBJECTIVES: To compare screening practices and beliefs in patients with and without a clinically important family history. DESIGN: We mailed a brief questionnaire asking about family history and a second, longer survey asking about knowledge of and beliefs about colorectal cancer to all respondents with a family history and a random sample of respondents without a family history of colorectal cancer. We reviewed electronic medical records for screening examinations and recording of family history. PARTICIPANTS: One thousand eight hundred seventy of 6,807 randomly selected patients ages 35–55 years who had been continuously enrolled in a large multispecialty group practice for at least 5 years. MEASUREMENTS: Recognition of increased risk, screening practices, and beliefs—all according to strength of family history and patient’s age. RESULTS: Nineteen percent of respondents reported a family history of colorectal cancer. In 11%, this history was strong enough to warrant screening before age 50 years. However, only 39% (95% CI 36, 42) of respondents under the age of 50 years said they had been asked about family history and only 45% of those with a strong family history of colorectal cancer had been screened appropriately. Forty-six percent of patients with a strong family history did not know that they should be screened at a younger age than average risk people. Medical records mentioned family history of colorectal cancer in 59% of patients reporting a family history. CONCLUSIONS: More efforts are needed to translate information about family history of colorectal cancer into the care of patients

"We're not short of people telling us what the problems are. We're short of people telling us what to do": An appraisal of public policy and mental health

Background: There is sustained interest in public health circles in assessing the effects of policies on health and health inequalities. We report on the theory, methods and findings of a project which involved an appraisal of current Scottish policy with respect to its potential impacts on mental health and wellbeing. Methods: We developed a method of assessing the degree of alignment between Government policies and the 'evidence base', involving: reviewing theoretical frameworks; analysis of policy documents, and nineteen in-depth interviews with policymakers which explored influences on, and barriers to cross-cutting policymaking and the use of research evidence in decisionmaking. Results: Most policy documents did not refer to mental health; however most referred indirectly to the determinants of mental health and well-being. Unsurprisingly research evidence was rarely cited; this was more common in health policy documents. The interviews highlighted the barriers to intersectoral policy making, and pointed to the relative value of qualitative and quantitative research, as well as to the imbalance of evidence between "what is known" and "what is to be done". Conclusion: Healthy public policy depends on effective intersectoral working between government departments, along with better use of research evidence to identify policy impacts. This study identified barriers to both these. We also demonstrated an approach to rapidly appraising the mental health effects of mainly non-health sector policies, drawing on theoretical understandings of mental health and its determinants, research evidence and policy documents. In the case of the social determinants of health, we conclude that an evidence-based approach to policymaking and to policy appraisal requires drawing strongly upon existing theoretical frameworks, as well as upon research evidence, but that there are significant practical barriers and disincentives

DNA-Free Recombinant SV40 Capsids Protect Mice from Acute Renal Failure by Inducing Stress Response, Survival Pathway and Apoptotic Arrest

Viruses induce signaling and host defense during infection. Employing these natural trigger mechanisms to combat organ or tissue failure is hampered by harmful effects of most viruses. Here we demonstrate that SV40 empty capsids (Virus Like Particles-VLPs), with no DNA, induce host Hsp/c70 and Akt-1 survival pathways, key players in cellular survival mechanisms. We postulated that this signaling might protect against organ damage in vivo. Acute kidney injury (AKI) was chosen as target. AKI is critical, prevalent disorder in humans, caused by nephrotoxic agents, sepsis or ischemia, via apoptosis/necrosis of renal tubular cells, with high morbidity and mortality. Systemic administration of VLPs activated Akt-1 and upregulated Hsp/c70 in vivo. Experiments in mercury-induced AKI mouse model demonstrated that apoptosis, oxidative stress and toxic renal failure were significantly attenuated by pretreatment with capsids prior to the mercury insult. Survival rate increased from 12% to >60%, with wide dose response. This study demonstrates that SV40 VLPs, devoid of DNA, may potentially be used as prophylactic agent for AKI. We anticipate that these finding may be projected to a wide range of organ failure, using empty capsids of SV40 as well as other viruses

Utility of In Vivo Transcription Profiling for Identifying Pseudomonas aeruginosa Genes Needed for Gastrointestinal Colonization and Dissemination

Microarray analysis of Pseudomonas aeruginosa mRNA transcripts expressed in vivo during animal infection has not been previously used to investigate potential virulence factors needed in this setting. We compared mRNA expression in bacterial cells recovered from the gastrointestinal (GI) tracts of P. aeruginosa-colonized mice to that of P. aeruginosa in the drinking water used to colonize the mice. Genes associated with biofilm formation and type III secretion (T3SS) had markedly increased expression in the GI tract. A non-redundant transposon library in P. aeruginosa strain PA14 was used to test mutants in genes identified as having increased transcription during in vivo colonization. All of the Tn-library mutants in biofilm-associated genes had an attenuated ability to form biofilms in vitro, but there were no significant differences in GI colonization and dissemination between these mutants and WT P. aeruginosa PA14. To evaluate T3SS factors, we tested GI colonization and neutropenia-induced dissemination of both deletional (PAO1 and PAK) and insertional (PA14) mutants in four genes in the P. aeruginosa T3SS, exoS or exoU, exoT, and popB. There were no significant differences in GI colonization among these mutant strains and their WT counterparts, whereas rates of survival following dissemination were significantly decreased in mice infected by the T3SS mutant strains. However, there was a variable, strain-dependent effect on overall survival between parental and T3SS mutants. Thus, increased transcription of genes during in vivo murine GI colonization is not predictive of an essential role for the gene product in either colonization or overall survival following induction of neutropenia

Enhanced Hippocampal Long-Term Potentiation and Fear Memory in Btbd9 Mutant Mice

Polymorphisms in BTBD9 have recently been associated with higher risk of restless legs syndrome (RLS), a neurological disorder characterized by uncomfortable sensations in the legs at rest that are relieved by movement. The BTBD9 protein contains a BTB/POZ domain and a BACK domain, but its function is unknown. To elucidate its function and potential role in the pathophysiology of RLS, we generated a line of mutant Btbd9 mice derived from a commercial gene-trap embryonic stem cell clone. Btbd9 is the mouse homolog of the human BTBD9. Proteins that contain a BTB/POZ domain have been reported to be associated with synaptic transmission and plasticity. We found that Btbd9 is naturally expressed in the hippocampus of our mutant mice, a region critical for learning and memory. As electrophysiological characteristics of CA3-CA1 synapses of the hippocampus are well characterized, we performed electrophysiological recordings in this region. The mutant mice showed normal input-output relationship, a significant impairment in pre-synaptic activity, and an enhanced long-term potentiation. We further performed an analysis of fear memory and found the mutant mice had an enhanced cued and contextual fear memory. To elucidate a possible molecular basis for these enhancements, we analyzed proteins that have been associated with synaptic plasticity. We found an elevated level of dynamin 1, an enzyme associated with endocytosis, in the mutant mice. These results suggest the first identified function of Btbd9 as being involved in regulating synaptic plasticity and memory. Recent studies have suggested that enhanced synaptic plasticity, analogous to what we have observed, in other regions of the brain could enhance sensory perception similar to what is seen in RLS patients. Further analyses of the mutant mice will help shine light on the function of BTBD9 and its role in RLS

Neurolysosomal pathology in human prosaposin deficiency suggests essential neurotrophic function of prosaposin

A neuropathologic study of three cases of prosaposin (pSap) deficiency (ages at death 27, 89 and 119 days), carried out in the standard autopsy tissues, revealed a neurolysosomal pathology different from that in the non-neuronal cells. Non-neuronal storage is represented by massive lysosomal accumulation of glycosphingolipids (glucosyl-, galactosyl-, lactosyl-, globotriaosylceramides, sulphatide, and ceramide). The lysosomes in the central and peripheral neurons were distended by pleomorphic non-lipid aggregates lacking specific staining and autofluorescence. Lipid storage was borderline in case 1, and at a low level in the other cases. Neurolysosomal storage was associated with massive ubiquitination, which was absent in the non-neuronal cells and which did not display any immunohistochemical aggresomal properties. Confocal microscopy and cross-correlation function analyses revealed a positive correlation between the ubiquitin signal and the late endosomal/lysosomal markers. We suppose that the neuropathology most probably reflects excessive influx of non-lipid material (either in bulk or as individual molecules) into the neurolysosomes. The cortical neurons appeared to be uniquely vulnerable to pSap deficiency. Whereas in case 1 they populated the cortex, in cases 2 and 3 they had been replaced by dense populations of both phagocytic microglia and astrocytes. We suggest that this massive neuronal loss reflects a cortical neuronal survival crisis precipitated by the lack of pSap. The results of our study may extend the knowledge of the neurotrophic function of pSap, which should be considered essential for the survival and maintenance of human cortical neurons

Can we prevent or treat multiple sclerosis by individualised vitamin D supply?

Apart from its principal role in bone metabolism and calcium homeostasis, vitamin D has been attributed additional effects including an immunomodulatory, anti-inflammatory, and possibly even neuroprotective capacity which implicates a possible role of vitamin D in autoimmune diseases like multiple sclerosis (MS). Indeed, several lines of evidence including epidemiologic, preclinical, and clinical data suggest that reduced vitamin D levels and/or dysregulation of vitamin D homeostasis is a risk factor for the development of multiple sclerosis on the one hand, and that vitamin D serum levels are inversely associated with disease activity and progression on the other hand. However, these data are not undisputable, and many questions regarding the preventive and therapeutic capacity of vitamin D in multiple sclerosis remain to be answered. In particular, available clinical data derived from interventional trials using vitamin D supplementation as a therapeutic approach in MS are inconclusive and partly contradictory. In this review, we summarise and critically evaluate the existing data on the possible link between vitamin D and multiple sclerosis in light of the crucial question whether optimization of vitamin D status may impact the risk and/or the course of multiple sclerosis

Sensing the fuels: glucose and lipid signaling in the CNS controlling energy homeostasis

The central nervous system (CNS) is capable of gathering information on the body’s nutritional state and it implements appropriate behavioral and metabolic responses to changes in fuel availability. This feedback signaling of peripheral tissues ensures the maintenance of energy homeostasis. The hypothalamus is a primary site of convergence and integration for these nutrient-related feedback signals, which include central and peripheral neuronal inputs as well as hormonal signals. Increasing evidence indicates that glucose and lipids are detected by specialized fuel-sensing neurons that are integrated in these hypothalamic neuronal circuits. The purpose of this review is to outline the current understanding of fuel-sensing mechanisms in the hypothalamus, to integrate the recent findings in this field, and to address the potential role of dysregulation in these pathways in the development of obesity and type 2 diabetes mellitus