Post-weaning social isolation of rats leads to long-term disruption of the gut microbiota-immune-brain axis.

PMID: 

Brain Behav Immun. 2018 02 ;68:261-273. Epub 2017 Nov 6. PMID: 29104061

Abstract Title: 

Post-weaning social isolation of rats leads to long-term disruption of the gut microbiota-immune-brain axis.

Abstract: 

Early-life stress is an established risk for the development of psychiatric disorders. Post-weaning isolation rearing of rats produces lasting developmental changes in behavior and brain function that may have translational pathophysiological relevance to alterations seen in schizophrenia, but the underlying mechanisms are unclear. Accumulating evidence supports the premise that gut microbiota influence brain development and function by affecting inflammatory mediators, the hypothalamic-pituitaryadrenal axis and neurotransmission, but there is little knowledge of whether the microbiota-gut-brain axis might contribute to the development of schizophrenia-related behaviors. To this end the effects of social isolation (SI; a well-validated animal model for schizophrenia)-induced changes in rat behavior were correlated with alterations in gut microbiota, hippocampal neurogenesis and brain cytokine levels. Twenty-four male Lister hooded rats were housed in social groups (group-housed, GH, 3 littermates per cage) or alone (SI) from weaning (post-natal day 24) for four weeks before recording open field exploration, locomotor activity/novel object discrimination (NOD), elevated plus maze, conditioned freezing response (CFR) and restraint stress at one week intervals. Post-mortem caecal microbiota composition, cortical and hippocampal cytokines and neurogenesis were correlated to indices of behavioral changes. SI rats were hyperactive in the open field and locomotor activity chambers traveling further than GH controls in the less aversive peripheral zone. While SI rats showed few alterations in plus maze or NOD they froze for significantly less time than GH following conditioning in the CFR paradigm, consistent with impaired associative learning and memory. SI rats had significantly fewer BrdU/NeuN positive cells in the dentate gyrus than GH controls. SI rats had altered microbiota composition with increases in Actinobacteria and decreases in the class Clostridia compared to GH controls. Differences were also noted at genus level. Positive correlations were seen between microbiota, hippocampal IL-6 and IL-10, conditioned freezing and open field exploration. Adverse early-life stress resulting from continuous SI increased several indices of 'anxiety-like' behavior and impaired associative learning and memory accompanied by changes to gut microbiota, reduced hippocampal IL-6, IL-10 and neurogenesis. This study suggests that early-life stress may produce long-lasting changes in gut microbiota contributing to development of abnormal neuronal and endocrine function and behavior which could play a pivotal role in the aetiology of psychiatric illness.

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These findings suggest that the perception of loneliness is more closely linked to self-reported illness symptoms than objectively measured social isolation.

PMID: 

Health Psychol. 2017 05 ;36(5):512-520. Epub 2017 Mar 30. PMID: 28358524

Abstract Title: 

Loneliness predicts self-reported cold symptoms after a viral challenge.

Abstract: 

OBJECTIVE: Loneliness is a well-established risk factor for poor physical health. Much less is known about how loneliness affects patient-reported outcomes (PROs), such as somatic symptoms, which are increasingly important for guiding symptom management and assessing quality of patient care. The current study investigates whether (a) loneliness and social isolation predict cold symptoms independent of each other, and (b) whether loneliness is a more robust risk factor than objective social isolation for experiencing cold symptoms.METHOD: As part of a larger parent study, 213 healthy participants completed the Short Loneliness Scale (LON) and the Social Network Index (SNI) at baseline. They were given nasal drops containing rhinovirus 39 (RV39; i.e., a common cold virus), then quarantined for 5 days during which they reported on subjective cold symptoms in addition to being monitored for objective indicators of infection. Data from 160 of the participants (who were infected with the virus) were used in the present analyses.RESULTS: A hierarchical multiple regression revealed that baseline loneliness predicted self-reported cold symptoms over time (assessed via area under the curve), over and above demographic variables, season of participation, and depressive affect. Interestingly, social network size and diversity did not predict cold symptoms.CONCLUSIONS: These findings suggest that the perception of loneliness is more closely linked to self-reported illness symptoms than objectively measured social isolation. Assessing psychosocial factors such as loneliness when treating and evaluating the common cold could contribute to health care practitioners' understanding of their patients' experiences with acute illness. (PsycINFO Database Record

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Adverse social experiences and social isolation may induce inflammatory responses while suppressing antiviral immunity.

PMID: 

Psychosom Med. 2019 10 ;81(8):711-719. PMID: 31600173

Abstract Title: 

Two Distinct Immune Pathways Linking Social Relationships With Health: Inflammatory and Antiviral Processes.

Abstract: 

OBJECTIVE: Social relationships can both influence and be influenced by immune processes. Past work implicates two distinct pathways along which this interaction may occur: inflammatory processes and antiviral processes. This article reviews how social behavior is modulated by these two immune processes and how such processes may in turn regulate social behavior.METHODS: This narrative review outlines existing work on social behavior and both inflammatory and antiviral processes. We propose an evolutionary framework that aims to integrate these findings. Specifically, social isolation has evolutionarily increased the likelihood of wounding and therefore increased the need for inflammation, which works to promote healing. Conversely, broader social networks provide protection from physical threats but also lead to increased pathogen exposure, necessitating a more robust antiviral response.RESULTS: This review highlights that social adversity, such as social exclusion or loneliness, is associated with increased inflammation, whereas social contact is associated with increased antiviral immunity. Furthermore, increased inflammation leads to sensitivity to social stimuli, presumably to avoid hostile conspecifics and approach allies who may provide care while vulnerable. Individuals with inadequate antiviral immunity engage in behaviors that minimize pathogen exposure, such as reduced affiliative behavior.CONCLUSIONS: This review suggests that adverse social experiences (social isolation, perceived social threat) may induce inflammatory responses while suppressing antiviral immunity, whereas positive experiences of social connection may reduce inflammation and bolster antiviral responses. Although acutely elevated inflammation would be adaptive under conditions where wounding is likely, chronic inflammation related to continued social adversity may have detrimental health consequences.

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Loneliness in healthy young adults predicts inflammatory responsiveness to a mild immune challenge in vivo.

PMID: 

Brain Behav Immun. 2019 Nov ;82:298-301. Epub 2019 Aug 30. PMID: 31476413

Abstract Title: 

Loneliness in healthy young adults predicts inflammatory responsiveness to a mild immune challenge in vivo.

Abstract: 

The established link between loneliness and poor health outcomes may stem from aberrant inflammatory regulation. The present study tested whether loneliness predicted the inflammatory response to a standardised in vivo immune challenge. Using a within-subjects double blind placebo-controlled design, 40 healthy men (mean age = 25, SD = 5) received a Salmonella Typhi vaccination (0.025 mg; Typhim Vi, Sanofi Pasteur, UK) and placebo (saline) on two separate occasions. Loneliness was assessed using the R-UCLA loneliness scale. Regression analyses showed that those that reported feeling more lonely exhibited an elevated interleukin-6 response (β = 0.564, 95% confidence interval [0.003, 0.042], p 

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Aerobic exercise can improve the homeostasis of immune environment.

PMID: 

Sheng Li Xue Bao. 2019 Oct 25 ;71(5):769-782. PMID: 31646331

Abstract Title: 

[Advance in effect of aerobic exercise on immune system and autoimmune diseases].

Abstract: 

Autoimmune diseases are a kind of chronic diseases with unclear etiology, which has the characteristics of repetition and difficulty to cure completely. Aerobic exercise, as an effective intervention method for chronic diseases, has also received extensive attention in the field of the prevention and treatment of autoimmune diseases. In this paper, the effects of aerobic exercise on immune system and autoimmune diseases in recent years are reviewed, and the related mechanisms are discussed. It is pointed out that aerobic exercise can improve the homeostasis of immune environment by affecting the number and function of immune cells, inhibit the systemic inflammatory response of the body, and then delay the occurrence and development of autoimmune diseases.

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Effects of exercise on the tumour microenvironment.

PMID: 

Adv Exp Med Biol. 2020 ;1225:31-51. PMID: 32030646

Abstract Title: 

Effects of Exercise on the Tumour Microenvironment.

Abstract: 

Epidemiological evidence suggests that exercise improves survival in cancer patients. However, much is still unknown regarding the mechanisms of this positive survival effect and there are indications that exercise may not be universally beneficial for cancer patients. The key to understanding in which situations exercise is beneficial may lie in understanding its influence on the tumour microenvironment (TME)-and conversely, the influence of the tumour on physical functioning. The TME consists of a vast multitude of different cell types, mechanical and chemical stressors and humoral factors. The interplay of these different components greatly influences tumour cell characteristics and, subsequently, tumour growth rate and aggression. Exercise exerts whole-body physiological effects and can directly and indirectly affect the TME. In this chapter, we first discuss the possible role of exercise capacity ('fitness') and exercise adaptability on tumour responsiveness to exercise. We summarise how exercise affects aspects of the TME such as tumour perfusion, vascularity, hypoxia (reduced oxygenation) and immunity. Additionally, we discuss the role of myokines and other circulating factors in eliciting these changes in the TME. Finally, we highlight unanswered questions and key areas for future research in exercise oncology and the TME.

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The role of physical exercise on gut microbiota modulation in older people with osteoarthritis.

PMID: 

Nutrients. 2020 Feb 22 ;12(2). Epub 2020 Feb 22. PMID: 32098380

Abstract Title: 

Gut-Joint Axis: The Role of Physical Exercise on Gut Microbiota Modulation in Older People with Osteoarthritis.

Abstract: 

Osteoarthritis (OA) is considered one of the most common joint disorders worldwide and its prevalence is constantly increasing due to the global longevity and changes in eating habits and lifestyle. In this context, the role of gut microbiota (GM) in the pathogenesis of OA is still unclear. Perturbation of GM biodiversity and function, defined as 'gut dysbiosis', might be involved in the development of inflammaging, one of the main risk factors of OA development. It is well known that physical exercise could play a key role in the prevention and treatment of several chronic diseases including OA, and it is recommended by several guidelines as a first line intervention. Several studies have shown that physical exercise could modulate GM composition, boosting intestinal mucosal immunity, increasing the Bacteroidetes-Firmicutes ratio, modifying the bile acid profile, and improving the production of short chain fatty acids. Moreover, it has been shown that low intensity exercise might reduce the risk of gastrointestinal diseases, confirming the hypothesis of a strict correlation between skeletal muscle and GM. However, up to date, there is still a lack of clinical trials focusing on this research field. Therefore, in this narrative, we aimed to summarize the state-of-the-art of the literature regarding the correlation between these conditions, supporting the hypothesis of a 'gut-joint axis' and highlighting the role of physical exercise combined with adequate diet and probiotic supplements in rebalancing microbial dysbiosis.

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Exercise reduced the severity of acute respiratory infections symptoms.

PMID: 

Cochrane Database Syst Rev. 2020 Apr 4 ;4:CD010596. Epub 2020 Apr 4. PMID: 32246780

Abstract Title: 

Exercise versus no exercise for the occurrence, severity, and duration of acute respiratory infections.

Abstract: 

BACKGROUND: Acute respiratory infections (ARIs) last for less than 30 days and are the most common acute diseases affecting people. Exercise has been shown to improve health generally, but it is uncertain whether exercise may be effective in reducing the occurrence, severity, and duration of ARIs. This is an update of our review published in 2015.OBJECTIVES: To evaluate the effectiveness of exercise for altering the occurrence, severity, or duration of acute respiratory infections.SEARCH METHODS: We searched CENTRAL (2020, Issue 2), MEDLINE (1948 to March week 1, 2020), Embase (1974 to 05 March 2020), CINAHL (1981 to 05 March 2020), LILACS (1982 to 05 March 2020), SPORTDiscus (1985 to 05 March 2020), PEDro (searched 05 March 2020), OTseeker (searched 05 March 2020), and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) and ClinicalTrials.gov (searched 05 March 2020).SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs (method of allocation that is not truly random, e.g. based on date of birth, medical record number) of exercise for ARIs in the general population.DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data from the included trials using a standard form. One review author entered data, which a second review author checked. We contacted trial authors to request missing data. There were sufficient differences in the populations trialed and in the nature of the interventions to use the random-effects model (which makes fewer assumptions than the fixed-effect model) in the analysis.MAIN RESULTS: We included three new trials for this update (473 participants) for a total of 14 trials involving 1377 adults, published between 1990 and 2018. Nine trials were conducted in the USA, and one each in Brazil, Canada, Portugal, Spain, and Turkey. Sample sizes ranged from 16 to 419 participants, aged from 18 to 85 years. The proportion of female participants ranged from 52% to 100%. Follow-up duration ranged from 1 to 36 weeks (median = 12 weeks). Moderate-intensity aerobic exercise (walking, bicycling, treadmill, or a combination) was evaluated in 11 trials, and was most commonly prescribed at least three times a week for 30 to 45 minutes. There was no difference between exercise and no exercise in the number of ARI episodes per person per year (risk ratio (RR) 1.00, 95% confidence interval (CI) 0.77 to 1.30; 4 trials; 514 participants; low-certainty evidence); proportion of participants who experienced at least one ARI over the study period (RR 0.88, 95% CI 0.72 to 1.08; 5 trials; 520 participants; low-certainty evidence); and the number of symptom days per episode of illness (mean difference (MD) -0.44 day, 95% CI -2.33 to 1.46; 6 trials; 557 participants; low-certainty evidence). Exercise reduced the severity of ARI symptoms measured on the Wisconsin Upper Respiratory Symptom Survey (WURSS-24) (MD -103.57, 95% CI -198.28 to -8.87; 2 trials; 373 participants; moderate-certainty evidence) and the number of symptom days during follow-up period (MD -2.24 days, 95% CI -3.50 to -0.98; 4 trials; 483 participants; low-certainty evidence). Excercise did not have a significant effect on laboratory parameters (blood lymphocytes, salivary secretory immunoglobulin, and neutrophils), quality of life outcomes, cost-effectiveness, and exercise-related injuries. There was no difference in participant dropout between the intervention and control groups. Overall, the certainty of the evidence was low, downgraded mainly due to limitations in study design and implementation, imprecision, and inconsistency. Seven trials were funded by public agencies; five trials did not report funding; and two trials were funded by private companies.AUTHORS' CONCLUSIONS: Exercise did not reduce the number of ARI episodes, proportion of participants experiencing at least one ARI during the study, or the number of symptom days per episode of illness. However, exercise reduced the severity of ARI symptoms (two studies) and the number of symptom days during the study follow-up period (four studies). Small study size, risk of bias, and heterogeneity in the populations studied contributed to the uncertainty of the findings. Larger trials that are designed to avoid risk of bias associated with participant selection, blinding of outcomes assessors, and with adequate reporting of all outcomes proposed for measurement in trials, would help to provide more robust evidence.

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Characterization of synergistic antibacterial effect of silver nanoparticles and ebselen.

PMID: 

Artif Cells Nanomed Biotechnol. 2019 Dec ;47(1):3338-3349. PMID: 31387398

Abstract Title: 

Characterization of synergistic antibacterial effect of silver nanoparticles and ebselen.

Abstract: 

The emerging and spreading of multi-drug resistant (MDR) bacteria have been becoming one of the most severe threats to human health. Enhancing oxidative stress as mimicking immune system was considered as a potential strategy to fight against infection of MDR bacteria. In this study, we investigated the antibacterial efficiency of such a strategy which combines silver nanoparticles (AgNPs) with ebselen. The results showed that AgNPs and ebselen combination had significant synergistic killing effects both on() and(), including model strains of China Veterinary Culture Collection and MDR clinical isolates, which is similar as the combination of silver ion and ebselen. AgNPs exhibited to be a strong inhibitor of bacterial thioredoxin reductase, same as a free silver ion. Ebselen mitigated the cytotoxicity of AgNPs to HeLa cells. However, in a bacteria-cell coexistence condition, the synergistic bactericidal effect was only observed on(

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The WHO Announces “Suspected” Cases of COVID-19 Should Be Written As COVID-19 Deaths (No Virus Test Required)

In a stunning disregard for medical and scientific integrity, the WHO posted its new guidelines for determining official deaths from COVID-19 which do not require cases be positively confirmed through virus testing, but only that it is suspected to be a cause of death.  

Emergency use ICD codes for COVID-19 disease outbreak

The COVID-19 disease outbreak has been declared a public health emergency of international concern.

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