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[Impact of chronic psychophysical stress on some neutrophil functions].

It is known, that psychophysical stress causes some changes in distribution and activity of many components of the immune system. The research was aimed at examination the influence of different military service conditions on some neutrophil functions. In this study granulocyte chemiluminescence both without stimulation and after stimulation with fMLP, PMA and zymosan was evaluated. In addition, the expression of surface adhesion molecules--CD11b on circulating granulocytes was examined. The studied group consisted of 20 soldiers from an assault unit (group A) and 20 soldiers from a support unit (group B), the age ranged from 18 to 23 years. The examinations were conducted at the beginning of the basic training and after the 8 weeks period. In group A the following results were obtained: a significant increase (p < 0.001) in granulocyte chemiluminescence without stimulation and after stimulation with fMLP, PMA and zymosan, as well as, a significant decrease (p < 0.05) in CD11b expression on granulocytes. And in group B: a significant increase (p < 0.05) in granulocyte chemiluminescence without stimulation but a significant decrease (p < 0.05) after cells stimulation with fMLP and PMA were observed. In this group CD11b expression on granulocytes was significantly (p < 0.001) decreased. The results of the present examination indicate, that military service conditions influence some parameters of the innate immunity.

Adult↗

The prognostic value and molecular mechanisms of Porphyromonas gingivalis infection-associated differentially expressed genes in oral squamous cell carcinoma.

BACKGROUND: Increasing evidence suggests that Porphyromonas gingivalis (Pg) is associated with oral squamous cell carcinoma (OSCC) development and progression. This study aimed to identify Pg-associated genes with prognostic relevance in OSCC through integrated bioinformatics analysis. METHODS: OSCC-related differentially expressed genes (DEGs) were identified from the The Cancer Genome Atlas (TCGA)-OSCC cohort and intersected with Pg supernatant-associated DEGs from GSE192887. Raw count data were analyzed with DESeq2, whereas transcripts per million (TPM)-transformed expression values were used for downstream visualization and model construction. Weighted gene co-expression network analysis (WGCNA), univariate Cox regression, least absolute shrinkage and selection operator (LASSO) regression, and multivariable Cox modeling were used to develop a seven-gene prognostic signature, which was externally evaluated in GSE41613. Additional analyses examined treatment-associated expression changes in the seven model genes, pairwise correlations among the model genes, and correlations between Pg supernatant-associated differentially expressed gene (PgSDEG)-derived module eigengenes and immune-cell fractions. Quantitative reverse-transcription polymerase chain reaction (qRT-PCR) was performed in eight paired OSCC and adjacent non-tumor tissues and in supplemented-brain heart infusion (BHI) vehicle-control and Pg culture-supernatant-treated HOK, HSC-3, and CAL-27 cells. RESULTS: A prognostic signature comprising CXCL8, GAST, HBQ1, PADI3, STC1, TEX19, and TMEM92 was established. The signature showed limited-to-moderate discrimination in the TCGA training cohort, with 1-, 3-, and 5-year areas under the curve (AUCs) of 0.68, 0.69, and 0.69, respectively, and limited discrimination in the GSE41613 external cohort (AUCs: 0.66, 0.67, and 0.61). Kaplan-Meier analysis showed poorer survival in the high-risk group in both cohorts. The GSE192887 analysis showed significant treatment-associated expression changes in all seven genes after Pg culture-supernatant exposure. In paired tissues, CXCL8 and TMEM92 were significantly higher in OSCC tissues, whereas STC1 was not significant after Holm correction. In CAL-27 cells, CXCL8, STC1, and TMEM92 increased significantly after culture-supernatant treatment, whereas the corresponding comparisons were not significant in HOK or HSC-3 cells after adjustment. CONCLUSIONS: This study developed a seven-gene Pg-associated prognostic signature for OSCC and provided complementary transcriptomic, immune-correlation, tissue, and cell-based evidence that placed the signature in biological context. The model showed limited-to-moderate discrimination and is not ready for clinical use. The enrichment, gene-correlation, and immune-correlation findings are hypothesis-generating rather than mechanistic evidence. Further independent validation and dedicated functional studies are required.

Oral squamous cell carcinoma (OSCC)↗

Prediction of binding to MHC class I molecules.

The binding of antigenic peptide sequences to major histocompatibility complex (MHC) molecules is a prerequisite for stimulation of cytotoxic T cell responses. Neural networks are here used to predict the binding capacity of polypeptides to MHC class I molecules encoded by the gene HLA-A*0201. Given a large database of 552 nonamers and 486 decamers and their known binding capacities, the neural networks achieve a predictive hit rate of 0.78 for classifying peptides which might induce an immune response (good or intermediate binders) vs. those which cannot (weak or non-binders). The neural nets also depict specific motifs for different binding capacities. This approach is in principle applicable to all MHC class I and II molecules, given a suitable set of known binding capacities. The trained networks can then be used to perform a systematic search through all pathogen or tumor antigen protein sequences for potential cytotoxic T lymphocyte epitopes.

HLA-A Antigens↗

Recall (versus recognition) of taste and immunization against aversive taste anticipations based on illness.

Two experiments show that, after taste-aversion conditioning, rats can use external retrieval cues to recall or anticipate the aversive taste solution and avoid its location without making contact with the flavor. They also show that the rat's avoidance of a conditioned aversive taste and its consumption of the aversive flavored solution can be attenuated by giving it prior runway training in which taste reward is given inconsistently on a partial reinforcement schedule.

Animals↗

Detection of circulating tumor cells from renal carcinoma patients: experiences of a two-center study.

Approximately 30-40% of primary and localized renal cell carcinoma (RCC) will eventually become metastatic disease. Therefore, the detection and molecular characterization of circulating tumor cells (CTC) in RCC may have important prognostic and therapeutic implications. Venous blood samples were obtained from a total of 214 RCC patients before and after nephrectomy or during adjuvant immune chemotherapy in two urological centers. After density gradient centrifugation, the CD45-negative cell population was isolated from peripheral blood samples (BS) by a semi-automated immunomagnetic depletion procedure using the MACS technology. Enriched cell populations potentially containing CTC were stained for cytokeratin and evaluated by a trained pathologist. CTC were found in 105 out of 363 BS (29%) originating from 80 out of 214 patients (37%). The median tumor cell number was five (range 1-51) per BS, i.e. approximately one CTC was detectable per 2-3 ml peripheral blood after tumor cell enrichment. For a subpopulation, follow-up data indicate that 62% of the patients with CTC detection in the blood developed progressive disease with single or multiple distant metastases or died because of RCC within two years. Here we show that the standardized immunomagnetic depletion protocol is a powerful tool for detecting and isolating intact RCC-derived CTC. The occurrence and the quantity of CTC in RCC patients is an early disease event. Furthermore, the occurrence of CTC is correlated with an advanced tumor stage and seems to be associated with a more aggressive tumor phenotype.

Biomarkers, Tumor↗

[Strategies to reduce morbidity and mortality caused by acute diarrhea in Latin America].

Following the World Health Organization guidelines, the Latin American Diarrheal Disease Control Programs have directed its efforts towards the promotion of Oral Hydration Therapy (OHT) and appropriate dietary management during the diarrheal episode and convalescent period, aimed at diminishing the mortality secondary to diarrhea. In developing countries, OHT is preventing, annually, one million of childhood deaths due to dehydration. Yet, only one fourth of the total population of children suffering diarrhea are being treated with this therapy. Among the strategies to decrease diarrhea morbidity, breast-feeding and hand washing are top priorities. The fundamental strategy has been to promote educational programs to train health personnel and community members. To continue these actions, we suggested the creation of more secondary and tertiary level hospitals and the installation of community units of OHT. They should become self-sufficient and self-manageable and include other programs of primary health care, such as immunization, growth and development surveillance, family planning and pregnancy control.

Acute Disease↗

An outbreak of hepatitis A during a military field training exercise.

Hepatitis A continues to pose a preventable threat to modern day military forces. We describe a food-borne outbreak of hepatitis A during a field training exercise resulting in 22 ill soldiers and over 300 lost work days. Among the population at risk, the secondary attack rate was 19.6%. Faced with epidemic disease occurrence, epidemiologic investigation of potential cases and aggressive use of post-exposure prophylaxis is recommended in a field setting. Although immune serum globulin is likely to reduce transmission, not all cases of acute hepatitis A will be prevented by this action.

Case-Control Studies↗

A survey of US chiropractors on clinical preventive services.

OBJECTIVE: To assess attitudes of current chiropractic students, public health faculty, and practitioners toward the topics of clinical preventive and health promotion services. DESIGN AND POPULATION: Survey of samples of students and faculty at 10 US chiropractic colleges and random sample of US chiropractors stratified by zip code region using proportional allocation. DATA ANALYSIS: Descriptive statistics were computed for all 3 samples and statistical modeling was used to explore relationships between practitioner characteristics and their responses concerning counseling on health indicators. RESULTS: A total of 582 students, 45 faculty, and 496 practitioners were surveyed; the response rate for practitioners was 27%. Over 80% of practitioners reported providing information to patients on musculoskeletal risk reduction, exercise, diet, stress reduction, and injury prevention. Over 80% also reported obtaining information from patients on physical activity, stress, dietary habits, obesity, medication use, and occupational hazards. Concerning immunization information, a much higher proportion of faculty (91%) and students (80%) than practitioners (62%) felt chiropractors should provide both pro and con information to patients. In general, female, younger, and more recently graduated practitioners appeared to be somewhat more likely to agree that chiropractors should provide counseling and to report providing it. An association was seen between attitudes toward health indicator counseling and respondent education. Practitioners with at least a bachelor's degree were statistically significantly more likely to report providing counseling for physical activity and to agree that chiropractors should provide counseling and to report actually providing counseling within the last month for substance abuse, responsible sexual behavior, mental health, and injury and violence prevention (P <.05). CONCLUSIONS: Our results indicate that a substantial proportion of the US chiropractors and students who completed our survey, as well as a number of key faculty, have a positive attitude toward providing clinical preventive services, particularly those related to physical activity and diet. However, the results also suggest that there may be areas where chiropractic training is not consistently meeting the newly established national guidelines for clinical preventive services.

Adult↗

Exercise intensity and duration affect blood soluble HSP72.

Soluble heat shock protein 72 (sHSP72) is suggested to play a role as a signalling molecule in the immune response to exercise. We were interested in whether duration and intensity of endurance running affect the level of inducible sHSP72 in the plasma/serum of endurance athletes. In the first part of the study, the influence of a continuous treadmill run of 60 min (CR) with an intensity of 75 % VO2max, a long treadmill run of 120 min (LR) with an intensity of 60 % VO2max, an extensive interval training program (IT; 10 x 1000 m, ca. 35 min, VO2max 88 %), and a competitive marathon run (MA) within 260 +/- 39 min (VO2max ca. 65 %) on the release of sHSP72 into the peripheral blood was tested. Blood samples were drawn before and directly after exercise, as well as 0.5, 1, 3, 24 h after exercise to determine sHSP72 levels. Secondly, we compared the effects of two exercise bouts with identical duration (23.7 +/- 7 min) but different intensities (Exhaustive exercise (ET) at 80 % VO2max vs. moderate exercise (MT) at 60 % VO2max) on sHSP72 concentration. The sHSP72 levels in plasma/serum were analyzed using an enzyme immunoassay specific for inducible HSP72 (Stressgen,Victoria, Canada). Early, significant increases of sHSP72 were detected immediately after all types of exercise with highest levels after MA. ET induced significantly higher levels of sHSP72 compared with MT. Long-lasting, competitive endurance exercise induced a more pronounced response of sHSP compared with more intensive but shorter exercise. Exercise intensity was also an important influencing factor. A duration- and intensity-dependent role for sHSP72 in the exercise-induced changes of the immune response may be assumed.

Adult↗

NICHD: AAP workshop on neonatology research and training areas of research in neonatal gastroenterology.

Future research in neonatal and developmental gastroenterology should include inquiry well beyond finding a cure or better preventative measures against necrotizing enterocolitis. The gastrointestinal (GI) tract acts not only as a digestive-absorptive organ; it also serves major endocrine and neural functions. It encompasses a vast surface area exposed to the external environment and plays a major role in both innate and adaptive immunity. Numerous short- and long-term health benefits could be derived from a better understanding of the developing GI tract.

Biomedical Research↗

The effect of 2 weeks vitamin C supplementation on immunoendocrine responses to 2.5 h cycling exercise in man.

An increased systemic concentration of stress hormones (of the hypothalamic-pituitary adrenal axis) and some cytokines may contribute to the depression of immune cell function typically observed after prolonged exercise. The aim of the present study was to determine the effect of 2 weeks of supplementation with vitamin C (VC) on cortisol, adrenocorticotrophic hormone, interleukin-6, oxidative stress and neutrophil responses to a single bout of endurance exercise. Nine healthy endurance-trained males exercised for 2.5 h at 60% VO2max after 2 weeks of placebo (PLA) or VC (1,000 mg day(-1)) supplementation. All participants completed both trials utilising a randomised crossover design with a minimum 14 day washout period between trials. There was a significant trial x time interaction effect for plasma cortisol concentration (P = 0.039) which tended to be lower in the VC trial but post hoc analysis found no specific between trial differences. There was a significantly lower post-exercise neutrophilia (P < 0.014) in the VC trial, compared with the PLA trial. There was no trial x time interaction for measures of neutrophil function (bacteria-stimulated elastase release, fMLP or PMA-stimulated oxidative burst). However, there was a trend for higher fMLP-stimulated neutrophil oxidative burst in the VC compared with PLA trial (trial x time interaction, P = 0.075). These results suggest that supplementation with VC for a period of up to 2 weeks provides little to no protection against the depression of neutrophil function which typically occurs after endurance exercise.

Adrenocorticotropic Hormone↗

Self-administration of heroin produces alterations in the expression of inducible nitric oxide synthase.

Nitric oxide plays a critical role in the immune response, and our studies have shown that heroin induces a reduction in the expression of iNOS, the enzyme responsible for nitric oxide production. The present study evaluated the effect of heroin self-administration on iNOS expression using a three-group design. Group one (self-administration) was trained to press a lever for i.v. administration of heroin. Group two (yoked heroin) received a simultaneous equivalent infusion of heroin determined by the responses of a 'partner' animal in the first group. A third group (yoked saline) also was yoked to the first group, but received i.v. injections of saline. Immediately following the last session, all rats received an injection of lipopolysaccharide (LPS) to induce iNOS expression. About 6 h after the injection of LPS, iNOS mRNA and protein expression were determined in spleen, lung, and liver. Additionally, the accumulation of plasma nitrite/nitrate, the more stable end products of nitric oxide degradation were measured. Although there was not a consistent difference between the self-administering and yoked-heroin animals, the results show that rats will self-administer a sufficient amount of heroin to induce a pronounced, widespread reduction in the expression of iNOS.

Animals↗

Psychoneuroimmunology and HIV-1.

Recent psychoneuroimmunologic findings have suggested that it may be useful to evaluate the influence of behavioral factors on immune functioning and disease progression among human immunodeficiency virus-Type 1 (HIV-1) infected individuals. Behavioral interventions with immunomodulatory capabilities may help restore competence and thereby arrest HIV-1 disease promotion at the earliest stages of the infectious continuum. Evidence describing benefits of behavioral interventions such as aerobic exercise training on both psychological and immunological functioning among high-risk HIV-1 seronegative and very early stage seropositive gay men is presented. The HIV-1 infection is cast as a chronic disease for which early immunomodulatory behavioral interventions may have important physical and psychological impact.

Acquired Immunodeficiency Syndrome↗

A pilot project for the effective delivery of HAART in rural China.

The purpose of this pilot study, conducted in rural Jilin Province in northeastern China, was to develop and test an infrastructure for the delivery of highly active antiretroviral therapy (HAART) that might be applicable to other such areas across the country. Earlier attempts to provide antiretroviral therapy in rural areas met with mixed success in large measure because of social stigma, a lack of adequate physician training, and problems with patient retention. In response to these problems, a highly integrated and family-centered approach was developed that placed emphasis on the primary care level for regimen delivery. Using this structure, a treatment naïve cohort of 22 male and 20 female (n = 42) volunteers with HIV/acquired immune deficiency syndrome (AIDS) was given government-provided HAART. After 12 months, all volunteers remained in the cohort, and there were significant changes in both CD4 levels and ability to return to work. Per patient cost for the 12-month study was Dollars 1,259.00, with Dollars 1,149 being spent on treatment and Dollars 110.00 on educational and administrative costs. This project demonstrated that HAART can be delivered successfully in resource-poor rural areas in China.

Acquired Immunodeficiency Syndrome↗

When all is said and done....

Dr. Benacerraf describes his experience in training immunologists for a period of over 30 years. He then analyzes the circumstances in which selected discoveries were made in his laboratory and the events and reasoning that led to these findings. The following topics are discussed: The phagocytic activity of the reticulo-endothelial system. The pathogenesis of immune complex diseases. The impact of activated macrophages on tumor rejection. The evidence that T-cell immunity is specific for internal protein determinants generated by antigen processing. The maturation of the antibody response in terms of antibody affinity. The discovery of Ir gene control of specific immune responses and the role of MHC molecules as presenters of peptide antigens to T cells. The generation of alloreactivity. Lastly, he addresses the administration of science and, particularly, the problems related to the transfer of technology to industrial partners.

Allergy and Immunology↗

Variation in implementation and use of computerized clinical reminders in an integrated healthcare system.

OBJECTIVES: To identify patterns of use of computerized clinical reminders (CCRs) across an integrated healthcare system and describe institutional factors associated with their implementation. STUDY DESIGN: Cross-sectional study. METHODS: At a national electronic health record (EHR) meeting, we surveyed 261 participants from 104 Veterans Health Administration (VHA) healthcare facilities regarding the number and types of CCRs available at each facility. Potential explanatory measures included perceived utility and ease of use of CCRs, training and personnel support for computer use, EHR functionalities, and performance data feedback to providers at each facility. RESULTS: The number of conditions with CCRs in use at a facility ranged from 1 to 15; most reported implementation of reminders for 10 of the 15 conditions surveyed. The most commonly implemented CCRs, used in more than 85% of facilities, were for conditions with VHA national performance measures (eg, tobacco cessation, immunizations, diabetes mellitus). The least commonly implemented CCRs were for post-deployment health evaluation and management, medically unexplained symptoms, and erectile dysfunction. Facilities that had implemented greater numbers of clinical reminders had providers who reported greater ease of use and utility of the reminders (P= .01). CONCLUSIONS: VHA facilities vary markedly in their implementation of CCRs. This effect may be partly explained by greater incorporation of clinical reminders for conditions with performance measures. Further study is needed to determine how to best implement clinical reminders and the institutional factors important in their use.

Attitude of Health Personnel↗

Impact of three different types of exercise on components of the inflammatory response.

It was hypothesized that muscle injury would be greater with eccentric than with all-out or prolonged exercise, and that immune changes might provide an indication that supplements the information provided by traditional markers such as creatine kinase (CK) or delayed-onset muscle soreness. Eight healthy males [mean (SE): age = 24.9 (2.3) years, maximum oxygen consumption (VO2(max)) = 43.0 (3.1) ml x kg(-1) x min(-1)] were each assigned to four experimental conditions, one at a time, using a randomized-block design: 5 min of cycle ergometer exercise at 90% VO2(max) (AO), a standard circuit-training routine (CT), 2 h cycle ergometer exercise at 60% VO2(max) (Long), or remained seated for 5 h. Blood samples were analyzed for CK, natural killer (NK) cell counts (CD3(-)/CD16(+)56(+)), cytolytic activity and plasma levels of the cytokines interleukin (IL)-6, IL-10, and tissue necrosis factor alpha (TNF-alpha). CK levels were only elevated significantly 72 h following CT. NK cell counts increased significantly during all three types of exercise, but returned to pre-exercise baseline values within 3 h of recovery. Cytolytic activity per NK cell was not significantly modified by any type of exercise. Prolonged exercise induced significant increases in plasma IL-6 and TNF-alpha. We conclude that the lack of correlation between traditional markers of muscle injury (plasma CK concentrations and muscle soreness rankings) and immune markers of the inflammatory response suggests that, for the types and intensities of exercise examined in this study, the exercise-induced inflammatory response is modified by humoral and cardiovascular correlates of exercise.

Adult↗

[Intervention with community health agents in immunization programs in the gypsy population].

OBJECTIVE: To measure how the vaccination coverage of the Gypsy child population in the Cartuja and Almanjayar quarters evolved throughout a Health Education Intervention using Community Health workers belonging to the Gypsy community. DESIGN: A descriptive study, pre-test/post-test, with no control group. SETTING: Community level. Primary Care. PATIENTS AND OTHER PARTICIPANTS: The whole of the Gypsy child population under 14, consisting of 1,073 children, and four Community Health workers. INTERVENTIONS: Health Education for mothers and carers, by means of home visits carried out by four Health workers, previously trained and contracted for this purpose for a year by the Andalusian School of Public Health. MEASUREMENTS AND MAIN RESULTS: We measured the Vaccination Coverage in September 1988 (42.2%) in order to establish the situation both at the start of the intervention in March 1990 (46.2%) and at its end in March 1991 (68.2%). We measured Vaccination Coverage of the different vaccine doses through frequency allocations. CONCLUSIONS: The Health Centre increased Vaccination Coverage by 4% in 18 months. The intervention increased it by 22.2% in 12 months. This demonstrates the intervention's effectiveness and underlines the importance of carrying out this kind of intervention when working with at-risk population groups.

Adolescent↗