Social history and exposure to pathogen signals modulate social status effects on gene regulation in rhesus macaques.

Social experience is an important predictor of disease susceptibility and survival in humans and other social mammals. Chronic social stress is thought to generate a proinflammatory state characterized by elevated antibacterial defenses and reduced investment in antiviral defense. Here we manipulated long-term social status in female rhesus macaques to show that social subordination alters the gene expression response to ex vivo bacterial and viral challenge. As predicted by current models, bacterial lipopolysaccharide polarizes the immune response such that low status corresponds to higher expression of genes in NF-κB-dependent proinflammatory pathways and lower expression of genes involved in the antiviral response and type I IFN signaling. Counter to predictions, however, low status drives more exaggerated expression of both NF-κB- and IFN-associated genes after cells are exposed to the viral mimic Gardiquimod. Status-driven gene expression patterns are linked not only to social status at the time of sampling, but also to social history (i.e., past social status), especially in unstimulated cells. However, for a subset of genes, we observed interaction effects in which females who fell in rank were more strongly affected by current social status than those who climbed the social hierarchy. Taken together, our results indicate that the effects of social status on immune cell gene expression depend on pathogen exposure, pathogen type, and social history-in support of social experience-mediated biological embedding in adulthood, even in the conventionally memory-less innate immune system.

Common bacterial infections and risk of incident cognitive decline or dementia: a systematic review protocol.

INTRODUCTION: The global burden of dementia is rising, emphasising the urgent need to develop effective approaches to risk reduction. Recent evidence suggests that common bacterial infections may increase the risk of dementia, however the magnitude and timing of the association as well as the patient groups affected remains unclear. We will review existing evidence of the association between common bacterial infections and incident cognitive decline or dementia. METHODS AND ANALYSIS: We will conduct a comprehensive search of published and grey literature from inception to 18 March 2019. The following electronic databases will be searched; MEDLINE, EMBASE, Global health, PsycINFO, Web of Science, Scopus, Cochrane Library, the Cumulative Index to Nursing and Allied Health Literature, Open Grey and the British Library of Electronic Theses databases. There will be no restrictions on the date, language or geographical location of the studies. We will include longitudinal studies with a common clinically symptomatic bacterial infection as an exposure and incident cognitive decline or dementia as an outcome. Study selection, data extraction and risk of bias will be performed independently by two researchers. We will assess the risk of bias using the Cochrane collaboration approach. The overall quality of the studies will be assessed using the Grading of Recommendations, Assessment, Development and Evaluations criteria. We will explore the heterogeneity of relevant studies and, if feasible, a meta-analysis will be performed, otherwise we will present a narrative synthesis. We will group the results by exposure and outcome definitions and differences will be described by subgroups and outcomes. ETHICS AND DISSEMINATION: Ethical approval will not be required as this is a systematic review of existing research in the public domain. Results will be disseminated in a peer-reviewed journal and presented at national and international meetings and conferences. PROSPERO REGISTRATION NUMBER: CRD42018119294.

Value of parental concern and clinician's gut feeling in recognition of serious bacterial infections: a prospective observational study.

BACKGROUND: Serious bacterial infections (SBI) are a significant cause of mortality worldwide. Parental concern and clinician's gut feeling that there is something wrong has been associated with increased likelihood of developing SBI in primary care studies. The aim of this study is to assess the diagnostic value of parental concern and gut feeling at the emergency department of a tertiary hospital. METHODS: This prospective observational study included children with fever attending the emergency department of Children's Clinical University hospital in Riga between October 2017 and July 2018. Data were collected via parental and clinician questionnaires. "Gut feeling" was defined as intuitive feeling that the child may have a serious illness, and "Sense of reassurance" as a feeling that the child has a self-limiting illness. "Parental concern" was defined as impression that this illness is different from previous illnesses. SBI included bacterial meningitis, sepsis, bacteraemia, pneumonia, urinary tract infection, appendicitis, bacterial gastroenteritis, and osteomyelitis. Pearson's Chi-Squared test or Fisher's exact test were used to compare the variables between children with and without SBI. Positive likelihood ratio was calculated for "gut feeling", "sense of reassurance", and parental concern. RESULTS: The study included 162 patients aged 2 months to 17.8 years. Forty-six patients were diagnosed with SBI. "Sense of reassurance" expressed by all clinicians was associated with lower likelihood of SBI (positive likelihood ratio 8.8, 95% confidence interval 2.2-34.8). "Gut feeling" was not significantly predictive of the patient being diagnosed with SBI (positive likelihood ratio 3.1, 95% confidence interval 1.9-5.1), The prognostic rule-in value of parental concern was insignificant (positive likelihood ratio 1.4, 95% confidence interval 1.1-1.7). CONCLUSION: Sense of reassurance was useful in ruling out SBI. Parental concern was not significantly predictive of SBI.

Incomplete childhood vaccination and associated factors among children aged 12-23 months in Gondar city administration, Northwest, Ethiopia 2018.

OBJECTIVE: Despite the fact that immunization services are offered free of charge in Ethiopia but the coverage of complete vaccination is still low. The aim of the study is to determine incomplete vaccination and associated factors among children aged 12-23 months in Gondar city administration, Northwest Ethiopia, 2018. RESULT: The proportion of incomplete vaccination among children aged 12-23 months in Gondar city adminstration was 24.3% (95% CI 19.3, 29.2). Knowledge about the benefits of vaccination (AOR = 6.1 (95% CI 1.3, 28.9), the age at which the child begins vaccination (AOR = 2.4 (95% CI 1.09, 8.4) time taken to reach nearby health facility and means of transportation to nearby health facility (AOR = 0.22 95% CI 0.06, 0.9) have statistically significant association with incomplete vaccination. In the current study the proportion of incomplete vaccination was found to be high. Increasing the awareness about vaccination for child care givers and further improve caregiver's knowledge towards the benefit of vaccination is important.

Evaluation in general practice of the patient's feelings about a recent hospitalization and isolation for a multidrug-resistant infection.

BACKGROUND: Isolation precautions used against multidrug-resistant (MDR) organisms are responsible for many emotional side effects. We evaluated patient's feeling after a hospitalization for an MDR infection. METHODS: We conducted a qualitative study that included 11 interviews from August 2017 to June 2018. We used phenomenology and verbatim transcription analysis was performed using NVivo software. Patients reported mainly negative feelings. Among them, 4 main themes were expressed: a desire to "be free from carriage," self-questioning regarding its nosocomial origin, the reduction of the therapeutic arsenal, and the expression of many fears especially relapse. RESULTS: For most of the participants (n = 6/11), the type of bacteria that colonized their digestive tract was precisely known including the MDR characteristics of the infection. Participants were convinced that the infection was strongly linked to the hospital and considered it as nosocomial that led to anxiety, especially regarding the origin of the infection and the absence of formal source of infection. CONCLUSIONS: MDR infections are negatively impacting patient's lived experience even after hospital discharge, partly owing to prior implementation of isolation precautions. We need to improve communication between specialists and general practitioners to reassure the patient and his surroundings regarding the anxiety resulting from such hospitalization.

The socio-economic impact of multidrug-resistant nosocomial infections: a qualitative study.

The burden of healthcare-associated infections (HCAIs) has traditionally been measured using clinical and economic outcomes. We conducted semi-structured interviews with 18 patients or their caregivers affected by HCAI caused by multidrug-resistant organisms to better understand the human impact of HCAI. Most patients had misconceptions about HCAI and antimicrobial resistance, leading to strong negative feelings towards HCAIs despite positive views of their healthcare providers. Communication issues across power imbalances need to be addressed to help deal with trauma of HCAIs. A holistic approach to HCAIs incorporating patient perspectives will likely help guide policymakers developing solutions to improve patient outcomes.

Synergistic Effects of Psychosocial Stress and Mild Peripheral Infection on Inducing Microglial Activation in the Hippocampal Dentate Gyrus and Long-Lasting Deficits in Hippocampus-Related Memory.

Lipopolysaccharide (LPS) treatment and stress may cause immune activation in the brain, an event which has been thought to play a role in mediating stress-induced cognitive dysfunction. However, the enduring impact of psychosocial stress on brain immune activation or cognitive deficits has not been well investigated. Likewise, it remains unexplored whether there exist synergistic effects of psychosocial stress and a weak systemic LPS treatment on brain immune activation and/or cognitive function. In this work, a 10-day social defeat regimen was used to model psychosocial stress and the number and density of ionized calcium-binding adaptor molecule 1 (Iba1)-stained microglia was used to reveal brain immune activation in male Balb/C mice. The social defeat regimen did not cause observable microglial activation in dentate gyrus (DG) 24 h after the conclusion of the regimen. Microglial activation peaked in DG 24 h following a single 1 mg/kg intra-peritoneal LPS injection. At this time point, DG microglial activation was not evident providing 0.125 mg/kg or lower of LPS was used, this dose of LPS was, thus, regarded as the "sub-threshold" in this study. Twenty-four h after the conclusion of the defeat regimen, mice received a social interaction test to determine their defeat stress susceptibility and a "sub-threshold" LPS injection. DG microglial activation was observed in the defeat-stress susceptible, but not in the resilient, mice. Furthermore, the stress-susceptible mice showed impairment in object location and Y maze tasks 24 and 72 h after the "sub-threshold" LPS injection. These results suggest that psychosocial stress, when combined with a negligible peripheral infection, may induce long-lasting hippocampus-related memory deficits exclusively in subjects susceptible to psychosocial stresses.

Campaign Preparation for Complex Initiatives: A Person-Centered Approach to Audience Segmentation of Parents' Antibiotic Stewardship.

The evolution of antibiotic resistance is outpacing the speed at which new antibiotics will reach the marketplace. To slow the rate of resistance, people need to engage in antibiotic stewardship, which includes acts to prevent the spread of bacteria and judicious use of antibiotics to treat infections. This study identified the patterns and predictors of antibiotic stewardship behaviors of parents (N = 516) related to their children. The latent class analysis revealed three profiles of parental stewardship, labeled Stewards, Requesters, and Non-Stewards. The findings implied different campaign goals: to encourage Stewards to follow through on their intentions, to encourage Requesters to stop asking providers for antibiotics when their children have ear infections, and to influence Non-Stewards to accept medical advice when an antibiotic is not indicated and to dispose of leftover antibiotics. The covariate analysis provided theoretical insight into the strategies to pursue in campaigns targeting these three groups. For example, parents who perceived antibiotic-resistant infections as less serious health conditions, felt less worry when thinking about their child getting an antibiotic-resistant infection, and had stronger misattributions of antibiotics' efficacy to treat multiple symptoms were more likely to be Requesters and Non-Stewards, instead of Stewards.

Resilience to stress and risk of gastrointestinal infections.

Background: Exposure to psychological stress can elicit a physiological response that may influence characteristics of the gastrointestinal mucosa, including increased intestinal permeability, in turn possibly increasing susceptibility to gastrointestinal infections. We investigated whether low stress resilience in adolescence is associated with an 'increased' risk of gastrointestinal infections in subsequent adulthood. Methods: Data were provided by Swedish registers for a cohort of 237 577 men who underwent military conscription assessment in late adolescence (1969-76). As part of the assessment procedure, certified psychologists evaluated stress resilience through semi-structured interviews. The cohort was followed from conscription assessment until 31 December 2009 (up to age 57 years). Cox regression assessed the association of stress resilience with gastrointestinal infections (n = 5532), with adjustment for family background measures in childhood and characteristics in adolescence. Peptic ulcer disease (PUD) in adulthood was modelled as a time-dependent covariate. Results: Compared with high stress resilience, lower stress resilience was associated with a 'reduced' risk of gastrointestinal infections after adjustment for family background in childhood, characteristics in adolescence and PUD in adulthood, with hazard ratios (and 95% confidence intervals) of 0.88 (0.81-0.97) and 0.83 (0.77-0.88) for low and moderate stress resilience, respectively. Conclusion: Lower stress resilience in adolescence is associated with reduced risk of gastrointestinal infections in adulthood, rather than the hypothesized increased risk.

Preliminary investigation of the STBBI Stigma Scale: Description and pilot results.

OBJECTIVES: Sexually transmitted and blood-borne infections (STBBIs) are associated with stigmatizing attitudes and beliefs, which can affect the quality of and access to health care, as well as mental health and quality of life. The current study describes the adaptation from an HIV-related stigma scale and pilot testing of a new STBBI Stigma Scale, assessing the stigmatizing attitudes and beliefs of health and social service providers in Canada. METHODS: 144 health and social service providers from across Canada completed the newly adapted scale assessing stigma associated with HIV, hepatitis C, other viral STBBIs and bacterial STBBIs, as well as demographic information, a scale of social desirability and measures of convergent and divergent validity. Participants were recruited through listservs and completed the scale online. RESULTS: The new scale, consisting of 21 items for each category, demonstrated excellent internal consistency, reliability, and convergent and divergent validity. The factor structure of the scale supports a tripartite model of stigma consisting of stereotyping, prejudice and discrimination. Stereotyping had the highest relative scores on the subscales, and attitudes regarding other viral STBBIs differed significantly from the other STBBI categories. CONCLUSION: The new scale provides a contextually relevant and applicable psychometrically valid tool to assess STBBI-related stigma among health and social service providers in Canada. The tool can be used to assess attitudes and beliefs, as well as guide self-assessment and possible trainings for providers.

Patient engagement with infection management in secondary care: a qualitative investigation of current experiences.

OBJECTIVE: To understand patient engagement with decision-making for infection management in secondary care and the consequences associated with current practices. DESIGN: A qualitative investigation using in-depth focus groups. PARTICIPANTS: Fourteen members of the public who had received antimicrobials from secondary care in the preceding 12 months in the UK were identified for recruitment. Ten agreed to participate. All participants had experience of infection management in secondary care pathways across a variety of South-East England healthcare institutes. Study findings were subsequently tested through follow-up focus groups with 20 newly recruited citizens. RESULTS: Participants reported feelings of disempowerment during episodes of infection in secondary care. Information is communicated in a unilateral manner with individuals 'told' that they have an infection and will receive an antimicrobial (often unnamed), leading to loss of ownership, frustration, anxiety and ultimately distancing them from engaging with decision-making. This poor communication drives individuals to seek information from alternative sources, including online, which is associated with concerns over reliability and individualisation. Failures in communication and information provision by clinicians in secondary care influence individuals' future ideas about infections and their management. This alters their future actions towards antimicrobials and can drive prescription non-adherence and loss to follow-up. CONCLUSIONS: Current infection management and antimicrobial prescribing practices in secondary care fail to engage patients with the decision-making process. Secondary care physicians must not view infection management episodes as discrete events, but as cumulative experiences which have the potential to shape future patient behaviour and understanding of antimicrobial use.

Using antibiotics responsibly: are we there yet?

Problems of antibiotic access and excess coexist in the world today and are compounded by rising rates of antibiotic resistance. We introduce two dimensions of responsibility to this context: responsible individual practices and a broad societal obligation centered on sustainability. Acting on these responsibilities requires recognizing the potential tensions between an individual optimum for antibiotic use and the societal optimum. We relate the tragedy of the commons metaphor to this situation to illustrate the complexity involved, and we draw on real-world experiences in Uganda, India, China and France. We conclude that we must form a global stewardship of antibiotics that can link access, innovation and conservation efforts across countries to ensure sustainable access to effective antibiotics for all who need them.

[Topical preparations for therapy of tonsillar pathology].

This paper highlights clinical and diagnostic aspects of tonsillar pathology with special reference to modern methods for the treatment of pharyngeal diseases of different etiology. A detailed characteristic of local symptomatic therapy is presented including the use of NSAIDs (non-steroidal anti-inflammatory drugs). These agents have advantages over other medications for local therapy due to high anti-inflammatory and analgesic activities. Also, they significantly improve the patients' quality of life. The use of a local anti-inflammatory drug is a major component of the treatment of inflammatory pharyngeal pathology. Regardless of the nature of the disease, either bacterial or viral.

The Association between Infections and General Cognitive Ability in Young Men - A Nationwide Study.

BACKGROUND: Infections and activated immune responses can affect the brain through several pathways that might also affect cognition. However, no large-scale study has previously investigated the effect of infections on the general cognitive ability in the general population. METHODS: Danish nationwide registers were linked to establish a cohort of all 161,696 male conscripts during the years 2006-2012 who were tested for cognitive ability, which was based on logical, verbal, numerical and spatial reasoning at a mean age of 19.4 years. Test scores were converted to a mean of 100.00 and with a standard deviation (SD) of 15. Data were analyzed as a cohort study with severe infections requiring hospitalization as exposure using linear regression. RESULTS: Adjusted effect sizes were calculated with non-exposure to severe infections as reference, ranging from 0.12 SD to 0.63 SD on general cognitive ability. A prior infection was associated with significantly lower cognitive ability by a mean of 1.76 (95%CI: -1.92 to -1.61; corresponding to 0.12 SD). The cognitive ability was affected the most by the temporal proximity of the last infection (P<0.001) and by the severity of infection measured by days of admission (P<0.001). The number of infections were associated with decreased cognitive ability in a dose-response relationship, and highest mean differences were found for ≥10 hospital contacts for infections (Mean: -5.54; 95%CI: -7.20 to -3.89; corresponding to 0.37 SD), and for ≥5 different types of infections (Mean: -9.44; 95%CI: -13.2 to -5.69; corresponding to 0.63 SD). Hospital contacts with infections had occurred in 35% of the individuals prior to conscription. CONCLUSIONS: Independent of a wide range of possible confounders, significant associations between infections and cognitive ability were observed. Infections or related immune responses might directly affect the cognitive ability; however, associated heritable and environmental factors might also account for the lowered cognitive ability.

Repeated exposure of male mice to low doses of lipopolysaccharide: dose and time dependent development of behavioral sensitization and tolerance in an automated light-dark anxiety test.

Although lipopolysaccharide (LPS) is widely used to examine immune behavior relationships there has been little consideration of the effects of low doses and the roles of sensitization and, or tolerance. Here low doses of LPS (1.0, 5.0 and 25.0 µg/kg) were peripherally administered to male mice on Days 1, 4, 28 and 32 after a baseline recording of anxiety-like behaviors in an automated light-dark apparatus (total time in the light chamber, number of light-dark transitions, nose pokes into the light chamber). LPS at 1.0 µg/kg, while having no significant effects on anxiety-like behaviors in the light-dark test on Days 1 and 4, displayed sensitization with the mice exhibiting significantly enhanced anxiety-like responses on Days 28 and 32. LPS at 5.0 µg/kg had no consistent significant effects on anxiety-like behavior on Days 1 and 4, with sensitization and enhanced anxiety-like behaviors on Day 28 followed by tolerance on Day 32. LPS at 25 µg/kg significantly enhanced anxiety-like behaviors on Day 1, followed by tolerance on Day 4, which was not evident by Day 28 and re-emerged on Day 32. There was a similar overall pattern of sensitization and tolerance for LPS-induced decreases in locomotor activity in the safe dark chamber, without, however, any significant effects on activity in the riskier light chamber. This shows that low doses of LPS induce anxiety-like behavior and these effects are subject to sensitization and tolerance in a dose, context, and time related manner.

Sexual dimorphism in oxytocin responses to health perception and disgust, with implications for theories on pathogen detection.

In response to a recent hypothesis that the neuropeptide oxytocin might be involved in human pathogen avoidance mechanisms, we report the results of a study in which we investigate the effect of intranasal oxytocin on two behaviors serving as proxies for pathogen detection. Participants received either oxytocin or a placebo and were asked to evaluate (1) the health of Caucasian male computer-generated pictures that varied in facial redness (an indicator of hemoglobin perfusion) and (2) a series of pictures depicting disgusting scenarios. Men, but not women, evaluated all faces, regardless of color, as less healthy when given oxytocin compared to a placebo. Women, on the other hand, expressed decreased disgust when given oxytocin compared to a placebo. These results suggest that intranasal oxytocin administration does not facilitate pathogen detection based on visual cues, but instead reveal clear sex differences in the perception of health and sickness cues.

Cysticlean® a highly pac standardized content in the prevention of recurrent urinary tract infections: an observational, prospective cohort study.

BACKGROUND: The present study was aimed at determining the prophylactic efficacy of American cranberry (AC) extract (Cysticlean®) in women with recurrent symptomatic postcoital urinary tract infections (PCUTI), non-consumer of AC extract in the past 3 months before inclusion, and to determine changes in their quality of life (QoL). METHODS: This was a single center, observational, prospective study in a total of 20 women (mean age 35.2 years; 50.0% were married). Patients were followed up for 3 and 6 months during treatment. RESULTS: The number of PCUTIs in the previous 3 months prior to start the treatment with Cysticlean® was 2.8±1.3 and it was reduced to 0.2±0.5 at Month 6 (P<0.0001), which represent a 93% improvement. At baseline, the mean score on the VAS scale (range from 0 to 100) for assessing the QoL was 62.4±19.1, increasing to 78.2±12.4 at Month 6 (P=0.0002), which represents a 20% improvement. All patients had an infection with positive urine culture at baseline, after 6 months there were only 3 symptomatic infections (P<0.001). The most common bacterium was Escherichia coli. CONCLUSIONS: Prophylaxis with American cranberry extract (Cysticlean®) could be an alternative to classical therapies with antibiotics. Further studies are needed to confirm results obtained in this pilot study.

Increased risk of cognitive impairment in cirrhotic patients with bacterial infections.

BACKGROUND & AIMS: A causal relationship between infection, systemic inflammation, and hepatic encephalopathy (HE) has been suggested in cirrhosis. No study, however, has specifically examined, in cirrhotic patients with infection, the complete pattern of clinical and subclinical cognitive alterations and its reversibility after resolution. Our investigation was aimed at describing the characteristics of cognitive impairment in hospitalized cirrhotic patients, in comparison with patients without liver disease, with and without infection. METHODS: One hundred and fifty cirrhotic patients were prospectively enrolled. Eighty-one patients without liver disease constituted the control group. Bacterial infections and sepsis were actively searched in all patients independently of their clinical evidence at entry. Neurological and psychometric assessment was performed at admission and in case of nosocomial infection. The patients were re-evaluated after the resolution of the infection and 3months later. RESULTS: Cognitive impairment (overt or subclinical) was recorded in 42% of cirrhotics without infection, in 79% with infection without SIRS and in 90% with sepsis. The impairment was only subclinical in controls and occurred only in patients with sepsis (42%). Multivariate analysis selected infection as the only independent predictor of cognitive impairment (OR 9.5; 95% CI 3.5-26.2; p=0.00001) in cirrhosis. The subclinical alterations detected by psychometric tests were also strongly related to the infectious episode and reversible after its resolution. CONCLUSIONS: Infections are associated with a worse cognitive impairment in cirrhotics compared to patients without liver disease. The search and treatment of infections are crucial to ameliorate both clinical and subclinical cognitive impairment of cirrhotic patients.

Guns, germs, and stealing: exploring the link between infectious disease and crime.

Can variation in crime rates be traced to the threat of infectious disease? Pathogens pose an ongoing challenge to survival, leading humans to adapt defenses to manage this threat. In addition to the biological immune system, humans have psychological and behavioral responses designed to protect against disease. Under persistent disease threat, xenophobia increases and people constrict social interactions to known in-group members. Though these responses reduce disease transmission, they can generate favorable crime conditions in two ways. First, xenophobia reduces inhibitions against harming and exploiting out-group members. Second, segregation into in-group factions erodes people's concern for the welfare of their community and weakens the collective ability to prevent crime. The present study examined the effects of infection incidence on crime rates across the United States. Infection rates predicted violent and property crime more strongly than other crime covariates. Infections also predicted homicides against strangers but not family or acquaintances, supporting the hypothesis that in-group-out-group discrimination was responsible for the infections-crime link. Overall, the results add to evidence that disease threat shapes interpersonal behavior and structural characteristics of groups.