Temperature triggers immune evasion by Neisseria meningitidis.

Neisseria meningitidis has multiple strategies to evade complement-mediated killing, which contribute to its ability to cause septicaemic disease and meningitis. However, the meningococcus is primarily an obligate commensal of the human nasopharynx, and it is unclear why the bacterium has evolved exquisite mechanisms to avoid host immunity. Here we demonstrate that mechanisms of meningococcal immune evasion and resistance against complement increase in response to an elevation in ambient temperature. We have identified three independent RNA thermosensors located in the 5′-UTRs of genes necessary for capsule biosynthesis, the expression of factor H binding protein, and sialylation of lipopolysaccharide, which are essential for meningococcal resistance against immune killing(1,2). Therefore increased temperature (which occurs during inflammation) acts as a ‘danger signal’ for the meningococcus which enhances defence against human immune killing. Infection with viral pathogens, such as influenza, leads to inflammation in the nasopharynx with an elevated temperature and recruitment of immune effectors(3,4). Thermoregulation of immune defence could offer an adaptive advantage to the meningococcus during co-infection with other pathogens, and promote the emergence of virulence in an otherwise commensal bacterium

Which quality of life score is best for glaucoma patients and why?

<p>Abstract</p> <p>Background</p> <p>The glaucomas are generally asymptomatic diseases until they are very advanced. They affect 2% of the population over 40 years of age and therefore represent a significant public health issue. There have been a number of attempts to develop quality of life scales for the disease. This review discusses the pros and cons of these scales and suggests the best of the current ones for use in a clinical setting.</p> <p>Methods</p> <p>Medline, Embase and Google Scholar were searched for relevant articles. No time period was defined and all types of article were included.</p> <p>Results</p> <p>11 Quality of Life scores were identified that have been used with glaucoma patients.</p> <p>Conclusion</p> <p>There is no generally accepted 'best' Quality of Life instrument for use in glaucoma. Many of the scales are biased towards physical symptoms and do little to address the personal or social factors of the disease. Further work is needed to produce scales that address all these areas as well as being simple to administer in a clinical setting.</p

Evaluation of Xpert® MTB/RIF and ustar easyNAT™ TB IAD for diagnosis of tuberculous lymphadenitis of children in Tanzania : a prospective descriptive study

Fine needle aspiration biopsy has become a standard approach for diagnosis of peripheral tuberculous lymphadenitis. The aim of this study was to compare the performance of Xpert MTB/RIF and Ustar EasyNAT TB IAD nucleic acid amplification assays, against acid-fast bacilli microscopy, cytology and mycobacterial culture for the diagnosis of TB lymphadenitis in children from a TB-endemic setting in Tanzania.; Children of 8 weeks to 16 years of age, suspected of having TB lymphadenitis, were recruited at a district hospital in Tanzania. Fine needle aspirates of lymph nodes were analysed using acid-fast bacilli microscopy, liquid TB culture, cytology, Xpert MTB/RIF and EasyNAT. Latent class analysis and comparison against a composite reference standard comprising "culture and/or cytology" was done, to assess the performance of Xpert MTB/RIF and EasyNAT for the diagnosis of TB lymphadenitis.; Seventy-nine children were recruited; 4 were excluded from analysis. Against a composite reference standard of culture and/or cytology, Xpert MTB/RIF and EasyNAT had a sensitivity and specificity of 58 % and 93 %; and 19 % and 100 % respectively. Relative to latent class definitions, cytology had a sensitivity of 100 % and specificity of 94.7 %.; Combining clinical assessment, cytology and Xpert MTB/RIF may allow for a rapid and accurate diagnosis of childhood TB lymphadenitis. Larger diagnostic evaluation studies are recommended to validate these findings and on Xpert MTB/RIF to assess its use as a solitary initial test for TB lymphadenitis in children

Canadian survey on pandemic flu preparations

<p>Abstract</p> <p>Background</p> <p>The management of pandemic influenza creates public health challenges.</p> <p>An ethical framework, 'Stand on Guard for Thee: ethical considerations in pandemic influenza preparedness' that served as a template for the World Health Organization's global consultation on pandemic planning, was transformed into a survey administered to a random sample of 500 Canadians to obtain opinions on key ethical issues in pandemic preparedness planning.</p> <p>Methods</p> <p>All framework authors and additional investigators created items that were pilot-tested with volunteers of both sexes and all socioeconomic strata. Surveys were telephone administered with random sampling achieved via random digit dialing (RDD). Eligible participants were adults, 18 years or older, with per province stratification equaling provincial percent of national population. Descriptive results were tabulated and logistic regression analyses were used to assess whether demographic factors were significantly associated with outcomes.</p> <p>Results</p> <p>5464 calls identified 559 eligible participants of whom 88.5% completed surveys. Over 90% of subjects agreed the most important goal of pandemic influenza preparations was saving lives, with 41% endorsing saving lives solely in Canada and 50% endorsing saving lives globally as the highest priority. Older age (OR = 8.51, p < 0.05) and current employment (OR = 9.48, p < 0.05) were associated with an endorsement of saving lives globally as highest priority. About 90% of respondents supported the obligation of health care workers to report to work and face influenza pandemic risks excepting those with a serious health condition that increased risks. Over 84% supported the government's provision of disability insurance and death benefits for health care workers facing elevated risk. Strong majorities favored stocking adequate protective antiviral dosages for all Canadians (92%) and, if effective, influenza vaccinations (95%). Over 70% agreed Canada should provide international assistance to poorer countries for pandemic preparation, even if resources for Canadians were reduced. While 92% of this group, believed provision should be 7 to 10% of all resources generated, 43% believed the provision should be greater than 10%.</p> <p>Conclusions</p> <p>Results suggest trust in public health officials to make difficult decisions, providing emphasis on reciprocity and respect for individual rights.</p

Public perceptions of quarantine: community-based telephone survey following an infectious disease outbreak

<p>Abstract</p> <p>Background</p> <p>The use of restrictive measures such as quarantine draws into sharp relief the dynamic interplay between the individual rights of the citizen on the one hand and the collective rights of the community on the other. Concerns regarding infectious disease outbreaks (SARS, pandemic influenza) have intensified the need to understand public perceptions of quarantine and other social distancing measures.</p> <p>Methods</p> <p>We conducted a telephone survey of the general population in the Greater Toronto Area in Ontario, Canada. Computer-assisted telephone interviewing (CATI) technology was used. A final sample of 500 individuals was achieved through standard random-digit dialing.</p> <p>Results</p> <p>Our data indicate strong public support for the use of quarantine when required and for serious legal sanctions against those who fail to comply. This support is contingent both on the implementation of legal safeguards to protect against inappropriate use and on the provision of psychosocial supports for those affected.</p> <p>Conclusion</p> <p>To engender strong public support for quarantine and other restrictive measures, government officials and public health policy-makers would do well to implement a comprehensive system of supports and safeguards, to educate and inform frontline public health workers, and to engage the public at large in an open dialogue on the ethical use of restrictive measures during infectious disease outbreaks.</p

Direction and magnitude of nicotine effects on the fMRI BOLD response are related to nicotine effects on behavioral performance

Considerable variability across individuals has been reported in both the behavioral and fMRI blood oxygen level-dependent (BOLD) response to nicotine. We aimed to investigate (1) whether there is a heterogeneous effect of nicotine on behavioral and BOLD responses across participants and (2) if heterogeneous BOLD responses are associated with behavioral performance measures. In this double-blind, placebo-controlled, cross-over study, 41 healthy participants (19 smokers)—drawn from a larger population-based sample—performed a visual oddball task after acute challenge with 1 mg nasal nicotine. fMRI data and reaction time were recorded during performance of the task. Across the entire group of subjects, we found increased activation in the anterior cingulate cortex, middle frontal gyrus, superior temporal gyrus, post-central gyrus, planum temporal and frontal pole in the nicotine condition compared with the placebo condition. However, follow-up analyses of this difference in activation between the placebo and nicotine conditions revealed that some participants showed an increase in activation while others showed a decrease in BOLD activation from the placebo to the nicotine condition. A reduction of BOLD activation from placebo to nicotine was associated with a decrease in reaction time and reaction time variability and vice versa, suggesting that it is the direction of BOLD response to nicotine which is related to task performance. We conclude that the BOLD response to nicotine is heterogeneous and that the direction of response to nicotine should be taken into account in future pharmaco-fMRI research on the central action of nicotine

Trends in health services utilization, medication use, and health conditions among older adults: a 2-year retrospective chart review in a primary care practice

<p>Abstract</p> <p>Background</p> <p>Population aging poses significant challenges to primary care providers and healthcare policy makers. Primary care reform can alleviate the pressures, but these initiatives require clinical benchmarks and evidence regarding utilization patterns. The objectives of this study is to measure older patients' use of health services, number of health conditions, and use of medications at the level of a primary care practice, and to investigate age- and gender-related utilization trends.</p> <p>Methods</p> <p>A cross-sectional chart audit over a 2-year study period was conducted in the academic family practice clinic of Sunnybrook Health Sciences Centre in Toronto, Ontario, Canada. All patients 65 years and older (n = 2450) were included. Main outcome measures included the number of family physician visits, specialist visits, emergency room visits, surgical admissions, diagnostic test days, inpatient hospital admissions, health conditions, and medications.</p> <p>Results</p> <p>Older patients (80-84 and 85+ age-group) had significantly more family physician visits (average of 4.4 visits per person per year), emergency room visits (average of 0.22 ER visits per year per patient), diagnostic days (average of 5.1 test days per person per year), health conditions (average of 7.7 per patient), and medications average of 8.2 medications per person). Gender differences were also observed: females had significantly more family physician visits and number of medications, while men had more specialist visits, emergency room visits, and surgical admissions. There were no gender differences for inpatient hospital admissions and number of health conditions. With the exception of the 85+ age group, we found greater intra-group variability with advancing age.</p> <p>Conclusion</p> <p>The data present a map of greater interaction with and dependency on the health care system with advancing age. The magnitudes are substantial and indicate high demands on patients and families, on professional health care providers, and on the health care system itself. There is the need to create and evaluate innovative models of care of multiple chronic conditions in the late life course.</p

A qualitative study of health care professionals' views and experiences of paediatric advance care planning

Background Good end-of-life care planning is vital to ensure optimal care is provided for patients and their families. Two key factors are open and honest advance care planning conversations between the patient (where possible), family, and health care professionals, focusing on exploring what their future wishes are; and the development of an advance care plan document. However, in paediatric and neonatal settings, there has been little research to demonstrate how advance care planning conversations take place. This study explored health care professionals’ views and experiences of paediatric advance care planning in hospitals, community settings and hospices. MethodsA qualitative methodology was employed using purposive sampling of health care professionals involved in the end-of-life care for children aged 0–18 years known to the hospital palliative care team, and had died at least three months before, but less than 18 months prior to the study. Ethics committee approval was obtained for the study. Located in the North of England, the study involved three hospitals, a children’s hospice, and community services. Data were collected using semi-structured, digitally recorded, telephone interviews. All interviews were transcribed verbatim and subjected to thematic analysis. ResultsTwenty-one health care professionals participated, including generalist paediatric staff as well as specialist palliative care staff.Two themes were generated from the study: The timing of planning conversations, including waiting for the relationship with the family to form; the introduction of parallel planning; avoiding a crisis situation. Secondly, supporting effective conversations around advance care planning, including where to have the conversation; introducing the conversation; and how to approach the topic encompassing the value of advance care planning and documentation for families. Conclusion The timing of when to start the advance care planning conversations remains an issue for health care professionals. The value of doing it in stages and considering the environment where the conversations are held was noted. Timely planning was seen as vital to avoid difficult conversations at a crisis point and for co-ordination of care. Good advance care planning is to provide the best person-centred care for the child and experience for the family

Lonely but avoidant—the unfortunate juxtaposition of loneliness and self-disgust

Loneliness is prevalent worldwide and is a known risk factor for numerous physical and mental health outcomes. The health consequences of chronic loneliness coupled with the cost on public health care has necessitated the development of interventions and campaigns to end loneliness globally. According to a recent meta-analysis, such interventions focus on improving social skills, increasing opportunities for social contact/support (i.e., reducing social isolation) or addressing maladaptive cognition (e.g., irrational thoughts, self-defeating, and self-blame thoughts). The results showed that changing maladaptive thoughts offer “the best chance” for alleviating feelings of loneliness. In accordance with the latter approach, this paper proposes a new paradigm in understanding and treating loneliness that takes into account self-disgust, an aversive self-conscious affective state that reflects disgust directed towards the self. Based on findings from published and unpublished data, it is argued that interventions against loneliness that focus exclusively on improving social skills and increasing opportunities for social contact may be ineffective because lonelier people experience more self-disgust, which makes them more socially inhibited and reluctant to connect with other people. Future interventions should consider self-disgust in the treatment of loneliness and explore ways to counter feelings of self-disgust

Essential versus accessory aspects of cell death: recommendations of the NCCD 2015

Cells exposed to extreme physicochemical or mechanical stimuli die in an uncontrollable manner, as a result of their immediate structural breakdown. Such an unavoidable variant of cellular demise is generally referred to as ‘accidental cell death’ (ACD). In most settings, however, cell death is initiated by a genetically encoded apparatus, correlating with the fact that its course can be altered by pharmacologic or genetic interventions. ‘Regulated cell death’ (RCD) can occur as part of physiologic programs or can be activated once adaptive responses to perturbations of the extracellular or intracellular microenvironment fail. The biochemical phenomena that accompany RCD may be harnessed to classify it into a few subtypes, which often (but not always) exhibit stereotyped morphologic features. Nonetheless, efficiently inhibiting the processes that are commonly thought to cause RCD, such as the activation of executioner caspases in the course of apoptosis, does not exert true cytoprotective effects in the mammalian system, but simply alters the kinetics of cellular demise as it shifts its morphologic and biochemical correlates. Conversely, bona fide cytoprotection can be achieved by inhibiting the transduction of lethal signals in the early phases of the process, when adaptive responses are still operational. Thus, the mechanisms that truly execute RCD may be less understood, less inhibitable and perhaps more homogeneous than previously thought. Here, the Nomenclature Committee on Cell Death formulates a set of recommendations to help scientists and researchers to discriminate between essential and accessory aspects of cell death