Integrated Genetic Epidemiology of Infectious Diseases: The Chagas Model

Genetic typing of pathogenic agents and of vectors has known impressive developments in the last 10 years, thanks to the progresses of molecular biology, and to the contribution of the concepts of evolutionary genetics. Moreover, we know more and more on the genetic susceptibility of man to infectious diseases. I propose here to settle a new, synthetic field of research, which I call `integrated genetic epidemiology of infectious diseases' (IGEID). I aim at evaluating, by an evolutionary genetic approach, the respective impact, on the transmission and pathogenicity of infectious diseases, of the host's, the pathogen's and the vector's genetic diversity, and their possible interactions (co-evolution phenomena). Chagas' disease constitutes a fine model to develop the IGEID methodology, by both field and experimental studies.

Mitotic figure counts are significantly overestimated in resection specimens of invasive breast carcinomas.

Several authors have demonstrated an increased number of mitotic figures in breast cancer resection specimen when compared with biopsy material. This has been ascribed to a sampling artifact where biopsies are (i) either too small to allow formal mitotic figure counting or (ii) not necessarily taken form the proliferating tumor periphery. Herein, we propose a different explanation for this phenomenon. Biopsy and resection material of 52 invasive ductal carcinomas was studied. We counted mitotic figures in 10 representative high power fields and quantified MIB-1 immunohistochemistry by visual estimation, counting and image analysis. We found that mitotic figures were elevated by more than three-fold on average in resection specimen over biopsy material from the same tumors (20±6 vs 6±2 mitoses per 10 high power fields, P=0.008), and that this resulted in a relative diminution of post-metaphase figures (anaphase/telophase), which made up 7% of all mitotic figures in biopsies but only 3% in resection specimen (P<0.005). At the same time, the percentages of MIB-1 immunostained tumor cells among total tumor cells were comparable in biopsy and resection material, irrespective of the mode of MIB-1 quantification. Finally, we found no association between the size of the biopsy material and the relative increase of mitotic figures in resection specimen. We propose that the increase in mitotic figures in resection specimen and the significant shift towards metaphase figures is not due to a sampling artifact, but reflects ongoing cell cycle activity in the resected tumor tissue due to fixation delay. The dwindling energy supply will eventually arrest tumor cells in metaphase, where they are readily identified by the diagnostic pathologist. Taken together, we suggest that the rapidly fixed biopsy material better represents true tumor biology and should be privileged as predictive marker of putative response to cytotoxic chemotherapy.

Environmental determinants of infectious and parasitic diseases

A review of the role of the environment as a determinant of infectious and parasitic diseases is presented. Historical considerations and the several environmental classifications of diseases are introduced. In a broader perspective the subject is analyzed in view of the emergence of the environmental health area, with its new paradigms. A review of epidemiological studies about environmental sanitation conditions and measures is presented, analyzing the conclusions derived from 256 studies. Finally, an epidemiological study carried out in Betim, Minas Gerais is briefly described, in order to illustrate the potentiality of this kind of study. Setting priorities of interventions regarding diarrhea control was the aim of this investigation. Conclusion about the role of this approach to optimize preventive measures for the control of infectious and parasitic diseases, of sound importance to the reality of the developing world, is stated.

Epidemiology and Anthropology: an integrated approach dealing with bio-socio-cultural aspects as strategy for the control of endemic diseases

The control of endemic diseases has not attained the desired level of effectiveness in spite of the use of modern efficient thecnologies. The classic interventionist approach for the control of schistosomiasis is centered on systemic control of the snail hosts combined to large scale medical treatment and is usually carried out without social preocupation due to the assisted communities. It is easy to understand the interest and the ethical compromise of public health research while producing studies in which the biological and social determinants as well as the cultural components should be considered and also encompass the historical dimensions and symbolic representations. In face of the recent political decision in favor of decentralizations of health administration to municipal level, we suggest, in the present paper, an integrated approach for the epidemiological diagnosis of an endemic situation at local level. Theoretical and methodological aspects from both, epidemiology and anthropology are discussed. Epidemiological methods can be used to detect the dependent variables (those related to the human infection) and the independent variables (demographic, economic, sanitary and social). Another methodological approach of anthropological /etnographic nature can be conducted in order to make an articulation of the knowledge on the various dimensions or determinant levels of the disease. Mutual comprehension, between researchers and the people under investigation, on the dynamic transmission process would be relevant for a joint construction, at local level, of programmed actions for the control of endemic diseases. This would extend reflections on the health/disease process as a whole.

Neues aus Diagnostik und Therapie der spinalen Erkrankungen [Novel aspects of diagnostics and therapy of spinal cord diseases].

BACKGROUND: Both non-traumatic and traumatic spinal cord injuries have in common that a relatively minor structural lesion can cause profound sensorimotor and autonomous dysfunction. Besides treating the cause of the spinal cord injury the main goal is to restore lost function as far as possible. AIM: This article provides an overview of current innovative diagnostic (imaging) and therapeutic approaches (neurorehabilitation and neuroregeneration) aiming for recovery of function after non-traumatic and traumatic spinal cord injuries. MATERIAL AND METHODS: An analysis of the current scientific literature regarding imaging, rehabilitation and rehabilitation strategies in spinal cord disease was carried out. RESULTS: Novel magnetic resonance imaging (MRI) based techniques (e.g. diffusion-weighted MRI and functional MRI) allow visualization of structural reorganization and specific neural activity in the spinal cord. Robotics-driven rehabilitative measures provide training of sensorimotor function in a targeted fashion, which can even be continued in the homecare setting. From a preclinical point of view, defined stem cell transplantation approaches allow for the first time robust structural repair of the injured spinal cord. CONCLUSION: Besides well-established neurological and functional scores, MRI techniques offer the unique opportunity to provide robust and reliable "biomarkers" for restorative therapeutic interventions. Function-oriented robotics-based rehabilitative interventions alone or in combination with stem cell based therapies represent promising approaches to achieve substantial functional recovery, which go beyond current rehabilitative treatment efforts.

Role of defensins and cathelicidin LL37 in auto-immune and auto-inflammatory diseases.

Defensins and cathelicidins are anti-microbial peptides (AMPs) that act as natural antibiotics and are part of the innate immune defence in many species. We consider human defensins and LL37, the only human member of the cathelicidin family. In particular, we refer to the human alpha-defensins called human neutrophil peptides (HNP1 through 4), which are produced by neutrophils, HD5 and HD6, mainly expressed in Paneth cells of intestine, the human beta-defensins HBD1, HBD2 and HBD3, synthesized by epithelial cells and LL37, which is located in granulocytes, but is also produced by epithelial cells of the skin, lungs, and gut. In the last years, the study of AMPs activity and regulation has allowed to understand the important role of these peptides not only in the innate defence mechanisms against bacteria, viruses, fungi, but also in the regulation of immune cell activation and migration. Complementary studies have disclosed a role for AMPs in modulating many physiological processes that involve non-immune cells, such as activation of wound healing, angiogenesis, cartilage remodeling. Due to the pleiotropic tasks of these peptides, many of them are now being discovered to contribute to immune pathology of chronic diseases that affect skin, gut, joints; this is supported by many examples of immune-mediated pathologies in which their expression is disregulated. In this article we review the current literature that suggests a role for human defensins and LL37 in pathogenic mechanisms of several chronic diseases that are considered of auto-immune or auto-inflammatory origin.

Patient-ventilator asynchrony during non-invasive ventilation for acute respiratory failure: a multicenter study.

OBJECTIVE : To determine the prevalence of patient-ventilator asynchrony in patients receiving non-invasive ventilation (NIV) for acute respiratory failure. DESIGN : Prospective multicenter observation study. SETTING : Intensive care units in three university hospitals. METHODS: Patients consecutively admitted to ICU were included. NIV, performed with an ICU ventilator, was set by the clinician. Airway pressure, flow, and surface diaphragmatic electromyography were recorded continuously for 30 min. Asynchrony events and the asynchrony index (AI) were determined from visual inspection of the recordings and clinical observation. RESULTS: A total of 60 patients were included, 55% of whom were hypercapnic. Auto-triggering was present in 8 (13%) patients, double triggering in 9 (15%), ineffective breaths in 8 (13%), premature cycling 7 (12%) and late cycling in 14 (23%). An AI > 10%, indicating severe asynchrony, was present in 26 patients (43%), whose median (25-75 IQR) AI was 26 (15-54%). A significant correlation was found between the magnitude of leaks and the number of ineffective breaths and severity of delayed cycling. Multivariate analysis indicated that the level of pressure support and the magnitude of leaks were weakly, albeit significantly, associated with an AI > 10%. Patient comfort scale was higher in pts with an AI < 10%. CONCLUSION: Patient-ventilator asynchrony is common in patients receiving NIV for acute respiratory failure. Our results suggest that leaks play a major role in generating patient-ventilator asynchrony and discomfort, and point the way to further research to determine if ventilator functions designed to cope with leaks can reduce asynchrony in the clinical setting.

Syndrome métabolique, diabète sucré et vulnérabilité: une approche "syndémique" de la maladie chronique [Metabolic syndrome, diabetes mellitus and vulnerability: a syndemic approach of chronic diseases].

The pandemic metabolic syndrome is generally attributed to our lifestyle. The current therapeutic strategies are centered on the behavioral changes and pharmacotherapy. A deeply analysis reveals the importance of the socio-cultural determinants with a "dose-responses effect according to the socio-economic level. The "syndemic" theory, which puts at the same level the socio-cultural environment, the behaviors and biomedecine, suggests a more holistic approach. This theory suggests introducing other partners of care, such cultural-mediators and welfare workers trained in the care, to have finally an approach centered on the roots of the causes. The healthcare networks centered on the management of the costs of health should not forget the socio-cultural dimension, unless wanting to select the good cases.

Underreporting of needlestick and sharps injuries among healthcare workers in a Swiss University Hospital.

OBJECTIVES: To determine 1) rates of needlestick and sharps injuries (NSSIs) not reported to occupational health services, 2) reasons for underreporting and 3) awareness of reporting procedures in a Swiss university hospital. MATERIALS AND METHODS: We surveyed 6,367 employees having close clinical contact with patients or patient specimens. The questionnaire covered age, sex, occupation, years spent in occupation, history of NSSI during the preceding twelve months, NSSI reporting, barriers to reporting and knowledge of reporting procedures. RESULTS: 2,778 questionnaires were returned (43.6%) of which 2,691 were suitable for analysis. 260/2,691 employees (9.7%) had sustained at least one NSSI during the preceding twelve months. NSSIs were more frequent among nurses (49.2%) and doctors performing invasive procedures (IPs) (36.9%). NSSI rate by occupation was 8.6% for nurses, 19% for doctors and 1.3% for domestic staff. Of the injured respondents, 73.1% reported all events, 12.3% some and 14.6% none. 42.7% of doctors performing invasive procedures (IPs) underreported NSSIs and represented 58.6% of underreported events. Estimation that transmission risk was low (87.1%) and perceived lack of time (34.3%) were the most common reasons for non-reporting. Regarding reporting procedures, 80.1% of respondents knew to contact occupational health services. CONCLUSION: Doctors performing IPs have high rates of NSSI and, through self-assessment that infection transmission risk is low or perceived lack of time, high rates of underreporting. If individual risk analyses underestimate the real risk, such underreporting represents a missed opportunity for post-exposure prophylaxis and identification of hazardous procedures. Doctors' training in NSSI reporting merits re-evaluation.