[Adaptation and military professional training].
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Adaptation, Physiological↗
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Results for “Trained Immunity”
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Pathomics-based machine learning models for predicting METTL5 expression and prognosis in lung adenocarcinoma.
BACKGROUND: METTL5, an N6-methyladenosine (m6A) RNA methyltransferase, has been implicated in tumor progression, but its prognostic value and non-invasive prediction in lung adenocarcinoma (LUAD) remain unclear. This study aimed to develop a pathomics-based machine learning model to predict METTL5 expression from histopathological images and evaluate its prognostic significance in LUAD. METHODS: A total of 327 LUAD patients from The Cancer Genome Atlas (TCGA) with matched hematoxylin and eosin (H&E) slides, transcriptomic, and clinical data were included and randomly divided into training and validation sets (7:3). Quantitative histopathological features were extracted using PyRadiomics. Feature selection was performed via maximum relevance minimum redundancy (mRMR) and recursive feature elimination (RFE), followed by construction of a Gradient Boosting Machine (GBM) model. A pathomics score (PS) was generated to assess prognostic relevance. Survival analyses, gene set variation analysis (GSVA), tumor mutational burden (TMB), immune infiltration analysis, and in vitro functional assays were conducted. RESULTS: METTL5 overexpression was independently associated with poor overall survival [hazard ratio (HR) =1.637, P=0.007]. The model achieved good predictive performance [area under the curve (AUC) =0.847 in the training set and 0.752 in the validation set]. High PS was significantly associated with worse survival and remained an independent prognostic factor (HR =1.563, P=0.03). Elevated PS correlated with altered metabolic pathways, increased TMB, and immune microenvironment changes. METTL5 knockdown reduced proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) in A549 cells. CONCLUSIONS: The pathomics-based model accurately predicts METTL5 expression and provides prognostic stratification in LUAD, supporting its potential as a practical imaging-derived biomarker.
Methyltransferase-like 5↗
Evaluation of anti-cocaine antibodies and a cocaine vaccine in a rat self-administration model.
RATIONALE: Previous pre-clinical studies with an anti-cocaine monoclonal antibody left open several issues critical to assessing the effectiveness of a vaccine for altering cocaine self-administration behavior. OBJECTIVES: The objectives of this study were to determine, first, whether changes in self-administration behavior would be systematically related to antibody level and, second, how the antibody affected the self-administration of different doses of cocaine. METHODS: Two experiments were conducted using a second-order schedule of drug delivery in rats. The first was a passive-administration study using the anti-cocaine monoclonal antibody MO240 to examine the relationship between antibody level and cocaine self-administration behavior, and the second was an active-immunization study to examine the efficacy of the cocaine vaccine IPC-1010 for blocking various doses of self-administered cocaine. RESULTS: The passive-administration experiment with control and 4-mg or 12-mg MO240 treatments showed that antagonism of the 1 mg/kg cocaine training dose was dependent on antibody level. In animals whose serum antibody levels were sustained above 0.05 mg/ml, there was a sufficient amount of antibody to reduce drug-seeking behavior and drug intake. In the active-immunization experiment, the cocaine vaccine IPC-1010 induced average serum antibody levels of 0.08 mg/ml and reduced the reacquisition of behavior by 1 mg/kg cocaine. Antagonism of cocaine self-administration after immunization was evident across a range of doses of cocaine and was only apparent in animals whose serum antibody levels exceeded 0.05 mg/ml. Furthermore, there was no evidence that the antagonism was surmountable within the dose range examined (up to 5.6 mg/kg). CONCLUSIONS: Antagonism of cocaine self-administration across a range of doses is feasible after immunization with a cocaine vaccine as long as antibody levels are of a sufficient concentration.
Animals↗
Transcriptome-wide analysis reveals potential roles of CFD and ANGPTL4 in fibroblasts regulating B cell lineage for extracellular matrix-driven clustering and novel avenues for immunotherapy in breast cancer.
BACKGROUND: The remodeling of the extracellular matrix (ECM) plays a pivotal role in tumor progression and drug resistance. However, the compositional patterns of ECM in breast cancer and their underlying biological functions remain elusive. METHODS: Transcriptome and genome data of breast cancer patients from TCGA database was downloaded. Patients were classified into different clusters by using non-negative matrix factorization (NMF) based on signatures of ECM components and regulators. Weighted Gene Co-expression Network Analysis (WGCNA) was used to identify core genes related to ECM clusters. Additional 10 independent public cohorts including Metabric, SCAN_B, GSE12276, GSE16446, GSE19615, GSE20685, GSE21653, GSE58644, GSE58812, and GSE88770 were collected to construct Training or Testing cohort, following machine learning calculating ECM correlated index (ECI) for survival analysis. Pathway enrichment and correlation analysis were used to explore the relationship among ECM clusters, ECI and TME. Single-cell transcriptome data from GSE161529 was processed for uncovering the differences among ECM clusters. RESULTS: Using NMF, we identified three ECM clusters in the TCGA database: C1 (Neuron), C2 (ECM), and C3 (Immune). Subsequently, WGCNA was employed to pinpoint cluster-specific genes and develop a prognostic model. This model demonstrated robust predictive power for breast cancer patient survival in both the Training cohort (n = 5,392, AUC = 0.861) and the Testing cohort (n = 1,344, AUC = 0.711). Upon analyzing the tumor microenvironment (TME), we discovered that fibroblasts and B cell lineage were the core cell types associated with the ECM cluster phenotypes. Single-cell RNA sequencing data further revealed that angiopoietin like 4 (ANGPTL4)+ fibroblasts were specifically linked to the C2 phenotype, while complement factor D (CFD)+ fibroblasts characterized the other ECM clusters. CellChat analysis indicated that ANGPTL4+ and CFD+ fibroblasts regulate B cell lineage via distinct signaling pathways. Additionally, analysis using the Kaplan-Meier Plotter website showed that CFD was favorable for immunotherapy response, whereas ANGPTL4 negatively impacted the outcomes of cancer patients receiving immunotherapy. CONCLUSION: We identified distinct ECM clusters in breast cancer patients, irrespective of molecular subtypes. Additionally, we constructed an effective prognostic model based on these ECM clusters and recognized ANGPTL4+ and CFD+ fibroblasts as potential biomarkers for immunotherapy in breast cancer.
Humans↗
Exercise, immunity and aging.
In general population, many protective immune responses are impaired in old age, leading to an increased risk of infection. However, recent studies in SENIEUR subjects (healthy centenarians who are examples of successful aging) suggest that complex remodeling and reshaping of the immune system occurs with aging. An appropriate regular regimen of endurance exercise might help elderly to lead a quality of life by preserving immune function. However, very little is known regarding the interaction between exercise, aging and the immune system. Given that a number of age-related changes occur in many physiological systems which are known to alter the immune function both at rest and during exercise, it would be of value to learn the extent to which both acute and chronic exercise influence immune function in the elderly. The immune system response to exercise is multifaceted, depending on the nature of exercise. Significant interaction between the neuroendocrine and immune systems, and the role of lifestyle factors in immune function are known to occur. In theory, moderate exercise should help to reverse the adverse effects of aging upon the immune system by increasing the production of endocrine hormones which may contribute to less accumulation of autoreactive immune cells by enhancing the programmed cell death. Active elderly subjects demonstrated a significantly greater proliferative response to phytohemagglutinins (PHA) and to pokeweed mitogen (PWM), and higher rates of interleukin-2 (IL-2), interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) production. A moderate training program can enhance the resting natural killer (NK) cell function of healthy elderly people, potentially increasing resistance to both viral infections and preventing the formation of malignant cells. Recent studies have suggested that endurance training in later life is associated with a lesser age-related decline in certain aspects of circulating T cell function and related cytokine production. It is important that the dose of physical activity needed to optimize immune function be defined more clearly at various points during the aging process both in females and males in order to optimize the immune function and to prevent any rise in adverse effects of exercise on the elderly population.
Aged↗
Malnutrition, cell-mediated immune deficiency and acute upper respiratory infections in rural Bangladeshi children.
A community-based longitudinal study conducted in rural Bangladesh investigated the association between nutritional status, cell-mediated immune status and acute upper respiratory infections (URI). A total of 696 children aged 0-59 months was followed prospectively for 1 y yielding 183,865 child-days' observation. Trained field workers visited each child every 4th d and collected morbidity data on symptoms suggesting URI (cough, fever, nasal discharge) for the preceding 3 d by recall. On the day of visit they examined each child reporting cough and/or fever to record the temperature, presence of nasal discharge, rate of respiration and presence of chest indrawing. Anthropometry for all children was conducted monthly. Cell-mediated immune competence was assessed by a multiple antigen skin test at baseline and thereafter every 3 months. The incidence of URI was 5.3 episodes per child-year observed. Approximately three-quarters of the study children were below -2 Z-score weight for age and height for age, and a quarter below -2 Z-score weight for height. During different test periods 9-21% of the study children did not respond to any of the test antigens. In a regression model children < -2 Z-score for weight for height had 16% [odds ratio (OR) 1.16, 95% confidence interval (CI) 1.03-1.31, p = 0.01] higher risk of developing URI. Anergic children had 20% higher risk (OR 1.20, CI 1.05-1.38, p = 0.009) of URI than immunocompetent children. The study demonstrated that wasting and depressed cell-mediated immunity (CMI), but not stunting, were associated with the incidence of URI among rural Bangladeshi children.
Anthropometry↗
Report of validation study of assessment of direct immunotoxicity in the rat. The ICICIS Group Investigators. International Collaborative Immunotoxicity Study.
The International Collaborative Immunotoxicity Study (ICICIS) was established in 1986 as a joint activity of the International Programme on Chemical Safety (a cooperative programme of the United Nations Environment Programme, the International Labour Office and the World Health Organization), the Commission of the European Union and the United Kingdom Department of Health. The objectives were to examine whether various experimental techniques could be used in the rat to indicate toxic effects on the immune system, and so to suggest their possible value as general indicators of immunotoxicity. For this purpose scientists in a number of laboratories in different countries agreed to do joint studies, first of azathioprine (AZA) and then of cyclosporin A (CYA), as potent immunosuppressive compounds. The general experimental procedures and the detailed techniques employed were selected to explore whether the limited pathological investigations in the conventional 28-day subacute toxicity test in the rat (OECD, 1995), or 'Enhanced Pathology' tests (weight determination and examination of additional lymphoid organs and application of structured assessment and semiquantitative grading of changes in the principal compartments of lymphoid tissues) would suffice to indicate ('flag') the occurrence of immunotoxicity due to a chemical, or whether specific tests of immune function would be required. When the second chemical, CYA, was studied, standardisation of the protocol for the test, and of all the investigations, and prior training of the toxicological pathologists in the structured assessment scheme, were shown to greatly reduce interlaboratory variation in the results. The initial investigation of AZA had shown that the indicative power of the experiments had been diminished by the use of diverse experimental procedures. The studies were done as toxicity tests, in which three dose levels, including the maximum tolerated dose, and a vehicle control group were employed. The prime objective was to detect any immunotoxic effect of the test compound. It was shown that the limited, basic 'Pathology' investigations specified in Guideline 407 (OECD, 1981) were not able to reveal the effects on the immune system of AZA and CYA, but that several of the additional 'Enhanced Pathology' investigations did so. Of the immune function assays, the most reliable and useful was the 'Antibody Forming Cell' technique. Other immunological evaluations, such as examination of proliferation induced by selected mitogens and NK cell assay, showed promise. The methods employed have the potential to reveal an 'immunotoxic' effect, without necessarily indicating its mechanism, although the changes in different lymphoid compartments can afford a valuable guide to the detailed nature of the toxic action on the immune system. Function tests, being inherently quantitative in nature may well suggest the nature or mechanism of any effect seen, in addition to indicating the occurrence of the effect. However, they may be less convenient to do as part of a routine toxicity test. Overall, the work in ICICIS has shown that the immunotoxic actions of two chemicals were detectable within a 28-day subacute oral toxicity test in the rat, provided that the conventional laboratory procedures were extended to include extra investigations. Both additional selected pathology investigations and immune function tests 'flagged' the immunotoxicity.
Animals↗
Spatial memory in rats: electroconvulsive shock selectively disrupts working memory but spares reference memory.
In two experiments rats were trained until they displayed highly accurate spatial memories when a 4-h delay was imposed between the to-be-remembered event (TBRE) and the retention test in a 12-arm radial maze. If the procedure tested only working memory (WM) electronvulsive shock (ECS) 2 h after the TBRE produced amnesia but ECS immediately after the TBRE was ineffective. If the testing procedure also involved a reference memory (RM) component, ECS degraded WM regardless of whether it was given 0 or 2 h after the TBRE. RM was not affected. With either training procedure administering ECS 2 h before the TBRE was ineffective. Thus, in the radial maze truly old spatial RM was immune to disruption by ECS while more recent WM was vulnerable. Possible explanations of the data are presented.
Animals↗
Sarcopenia: causes, consequences, and preventions.
With the onset of advancing age, muscle tissue is gradually lost, resulting in diminished mass and strength, a condition referred to as sarcopenia. The sequela of sarcopenia often contributes to frailty, decreased independence, and subsequently increased health care costs. The following was adapted from an introduction to the conference "Sarcopenia, Age-Related Muscle Loss-Causes, Consequences, and Prevention," sponsored by the Kronos Longevity Research Institute in June 2002. This brief review will introduce potential mechanisms that may contribute to sarcopenia, although no one mechanism has yet, and may not completely, define this process. The only agreed-upon intervention from these proceedings was regular physical exercise, stressing weight-training for elderly men and women. However, even those individuals who maintain their fitness through exercise do not appear to be immune to sarcopenia.
Aging↗
Pediatric emergency physicians and communicable diseases: can we be trusted to take care of ourselves?
OBJECTIVE: To determine if pediatric emergency physicians (PEP) are following Centers for Disease Control and Prevention (CDC) recommendations that all health care workers receive routine vaccines and annual tuberculosis screens. DESIGN: A two-page mail survey with one follow-up mailing. PARTICIPANTS: All active members of the American Academy of Pediatrics (AAP), Section on Emergency Medicine. Additional inclusion criteria were completion of training and employment in an emergency setting. RESULTS: Of 407 surveys, 286 (60%) were returned; 209 met inclusion criteria. Proof of immunization was not required of 43% of PEP; 42% were not required to have an annual tuberculosis (TB) screen. PEP reported immunity to the following: polio (95%), measles (94%), hepatitis B (91%), rubella (90%), mumps (90%), varicella (90%), and diphtheria-tetanus (86%). However, only 72% received a TB screen, and 60% received an influenza vaccine within the past year. Proof of vaccination for employment was required by 57/85 hospitals, 47/79 universities, and 6/32 self-employed/group practices (chi 2, P < 0.001). Proof of an annual TB screen was required by 64/87 hospitals, 44/82 universities, and 8/32 self-employed/group practices (chi 2, P < 0.001). PEP were more likely to have had a recent annual TB screen if required by their employer (104/117) than if left to their own initiative (42/87) (chi 2, P < 0.001). CONCLUSIONS: Although PEP are well protected against most vaccine-preventable diseases, many are not receiving annual TB screens nor influenza vaccines. The CDC guidelines are not being routinely followed by PEP.
Adult↗
[Professional profiles of physicians certified in epidemiology in the view of hospital managers in the Silesian Voivodeship of Poland].
In Poland, the target profile of a new medical specialty--epidemiology--is subject to discussion. The objective of this paper was to review opinions concerning the tasks and areas of responsibilities of a physician-epidemiologist, expressed by 55 managers (out of 120 invited) of hospitals located in Silesian Voivodship. The results revealed that the preferable areas of professional activity of a physician-epidemiologist include: (a) control of infectious diseases, (b) design and control of vaccination programmes, (c) provision of health care in case of disasters/catastrophies, including assessment of potential health effects of emergency events, (d) prevention, diagnostics and evaluation of hospital-based infections, (e) planning and conducting population-based health monitoring programmes, (f) planning, designing, supervision and evaluation of population-based preventive measures, (g) design and conduct of investigations of diagnostic and therapeutic procedures and preventive strategies; (i) involvement in planning of local health policies, and (j) assessment of the health impact of new technologies. The findings could be addressed while drafting the curriculum of postgraduate medical training in epidemiology.
Biotechnology↗
Influence of conditioned psychological stress on immunological recovery in mice exposed to low-dose X irradiation.
A study was initiated to determine the effects of psychological stress on the immune response in BALB/c mice recovering from exposure to a low dose of ionizing radiation. Mice were first subjected to conditioning training for 12 days, then exposed to 200 R, subjected to psychological stress for 14 days, and assessed for peak anti-sheep RBC response. The seven treatment groups included two unirradiated groups and five irradiated groups. Mice exposed to 200 R and then subjected to conditioned psychological stress responded less vigorously to antigenic stimulation than those of the other irradiated groups. The psychological stress imposed upon these mice did not influence the antibody-forming capacity of unirradiated mice. These results indicate that a psychological stress which did not affect the immunological activity of unirradiated mice can curtail the immunological recovery of mice exposed to low doses of ionizing radiation.
Animals↗
An evaluation of the knowledge and practices of trained traditional birth attendants in Bodinga, Sokoto State, Nigeria.
To improve Maternal and Child Health services especially in the rural areas, a programme to train traditional birth attendants (Ungo Zoma) was established by the Sokoto State government of Nigeria in 1975. The impact of the training programme on the knowledge and practices of traditional birth attendants (TBAs) in a rural community in the state was studied. Seventy-four TBAs, consisting of 43 trained and 31 untrained attendants, were interviewed. Statistically significant differences were observed in the proportion of both groups of TBAs able to recognize high risk pregnancies and deliveries for referral to health institutions. In contrast to the trained attendants, none of the untrained TBAs offered any of the following Maternal and Child Health services: antenatal care, advice on immunization of children or their mothers during pregnancy, and family planning. Suggestions for improving the knowledge and practices of the TBAs in Sokoto as well as in other communities wishing to embark on similar programmes are offered.
Adolescent↗
[Comparative evaluation of studies of the action of different levels of hypoxia on the human immunobiological status].
The effect of hypoxic hypoxia on the specific factors of immunity of 16 test subjects was studied during their 30-day exposure to an altitude of 2100-4200 m above the sea level in the area of the Elbrus mountain. In order to differentiate the effect of hypoxia per se from that of other factors typical of highlands, five runs of altitude chamber experiments were carried out. In each run the test subjects were 10 times lifted to altitudes of 3200 m, 4200 m and 5200 m. The chamber experiments were performed on 28 test subjects, aged 26-46. During an exposure to an altitude the test subjects did two or three times exercises of 450-900 kgm/min on a bicycle ergometer. The experimental findings show that hypoxic hypoxia brings about consistent changes in the immunobiological status of man that are directly correlated with the level of hypoxia. These changes include a decline in the acquired antiviral and antitoxic immunity activation of the autoimmune process and an increase in the phagocytic activity of neutrophils. Our results suggest optimal profiles of the hypoxic effect to which test subjects should be exposed during mountain training for a specific occupational activity.
Acclimatization↗
Exercise immunology: neuroendocrine regulation of NK-cells.
Natural immunity, including that of the natural killer (NK) cells, is strongly influenced by physical exercise, but the physiological significance of the reported changes in NK cells after exercise training is as yet unclear. The exercise effect is likely mediated by interactions between the central nervous and endocrine systems. Chronic activation of endogenous opioid systems augments natural cytotoxicity. We have investigated the possible involvement of opioids in the exercise-induced enhancement of NK cell function. The pathways by which the central nervous system may communicate with the periphery include neuroendocrine outflow via the hypothalamic-pituitary-adrenal axis and the autonomic nervous system (ANS) through direct nerve fiber connections with cells or the organs of the immune system. This review will discuss the role of various neuroendocrine factors such as growth hormone, catecholamines and glucocorticoids and the role of the ANS, in particular the sympathetic division, in modulating NK cell function in response to exercise.
Afferent Pathways↗
Future role of micronutrients on immune functions.
The future is bright in the field of micronutrients and immunity. New advances in technology now permit the design of many new research studies, and an increased application of the findings to clinical and public health practices. More investigators will need to be trained in the fundamentals of both nutritional and immunological sciences. More basic information will be needed in both fields, but the scientific and clinical values of merging these two fields are already well established. The development of additional animal models will be needed to dissect out the role of each essential micronutrient and its potential importance in each step of the immune response. Based on future studies, new RDAs must be formulated and applied widely in medical and public health practices and in public education.
Animals↗
Association between nutritional status, cell-mediated immune status and acute lower respiratory infections in Bangladeshi children.
OBJECTIVE: To investigate the association between nutritional status, cell-mediated immune status and the incidence of acute lower respiratory infections (ALRI). DESIGN: Community-based longitudinal study. SETTING: Three villages in rural Bangladesh at Matlab. SUBJECT: 696 children aged 0-59 months were followed up for a year. METHODS: Trained field workers visited all children every fourth day and collected morbidity data for the preceding three days by recall. To determine the type and severity of respiratory infections, the field workers physically examined each child reporting a cough. Anthropometric status was determined monthly and cell-mediated immune status by skin tests was assessed at the beginning of the study and thereafter every 3 months. RESULTS: The incidence of ALRI was 23 episodes per 100 child-years. A total of 73-78% of the children were below -2 z score weight for age, 15-30% were below - 2 z score weight for height, and 68-76% were below -2 z score height for age. In logistic regression models, malnutrition as assessed by weight-for-height status [odds ratio (OR) 0.66, 95% confidence interval (CI) 0.45-0.96, P = 0.03] or weight-for-age status (OR 0.64, 95% CI 0.45-0.92, P = 0.02) was significant predictor of ALRI. Anergic children had a higher risk of ALRI which approached to be statistically significant (OR 1.81, 95% CI 0.92-3.55, P = 0.08). CONCLUSIONS: Improvement of nutritional and cell-mediated immune status in rural Bangladeshi children should reduce the incidence of ALRI.
Acute Disease↗
Health professionals' attitudes to MMR vaccine. More interactive training and updates on immunisation should be provided.
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Clinical Competence↗