Systemic inflammatory markers for the detection of infectious complications and safe discharge after cytoreductive surgery and HIPEC.

INTRODUCTION: Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS + HIPEC) in patients with ovarian peritoneal carcinomatosis may be associated with a high postoperative morbidity. An early discrimination of postoperative complications is crucial for both improving clinical outcomes and proposing a safe discharge. MATERIAL AND METHODS: In a cohort of 122 patients with advanced ovarian cancer (FIGO III-IV), we analyzed the diagnostic performance of three systemic inflammatory markers (C-reactive protein, white blood cell count and systemic immune-inflammation index) between the 5th to 8th postoperative days to prediction postoperative infectious complications. An optimal cut-off value was established in order to discriminate between the group of patients who developed infectious complications or not during the postoperative period. RESULTS: The median peritoneal carcinomatosis index (PCI) was 15. The overall infectious morbidity was 25.4% (31 patients out of 122), of which, 32% (10 patients out of 31) had suffered severe postoperative complications (Dindo-Clavien III-IV). The most accurate results for detecting infectious complications were obtained by using C-reactive protein, which presented an excellent diagnostic performance, especially on the 7th and 8th postoperative days (AUC = 0,857 and 0,920; respectively). CONCLUSIONS: These results support that it is safe to discharge patients with C-reactive protein concentrations lower than 88 mg/L and 130 mg/L, on the 7th and 8th postoperative days, respectively.

Metal Nanoparticles in Infection and Immunity.

Background Enthusiasm for the use of metal nanoparticles in human and veterinary medicine is high. Many articles describe the effects of metal nanoparticles on microbes in vitro, and a smaller number of articles describe effects on the immune system, which is the focus of this review. Methods Articles were retrieved by performing literature searches in Medline, of the National Institute of Medicine, as well as via Google Scholar. Results In vitro studies show that metal nanoparticles have antimicrobial effects. Some metal nanoparticles augment innate host immune defenses, such as endogenous antimicrobial peptides, and nitric oxide. Metal nanoparticles may also function as vaccine adjuvants. Metal nanoparticles can migrate to locations distant from the site of administration, however, requiring careful monitoring for toxicity. Conclusions Metal nanoparticles show a great deal of potential as immunomodulators, as well as direct antimicrobial effects. Before metal particles can be adopted as therapies; however, more studies are needed to determine how nanoparticles migrate though the body and on possible adverse effects.

Vitamin D and Immunity in Infants and Children.

The last couple of decades have seen an explosion in our interest and understanding of the role of vitamin D in the regulation of immunity. At the molecular level, the hormonal form of vitamin D signals through the nuclear vitamin D receptor (VDR), a ligand-regulated transcription factor. The VDR and vitamin D metabolic enzymes are expressed throughout the innate and adaptive arms of the immune system. The advent of genome-wide approaches to gene expression profiling have led to the identification of numerous VDR-regulated genes implicated in the regulation of innate and adaptive immunity. The molecular data infer that vitamin D signaling should boost innate immunity against pathogens of bacterial or viral origin. Vitamin D signaling also suppresses inflammatory immune responses that underlie autoimmunity and regulate allergic responses. These findings have been bolstered by clinical studies linking vitamin D deficiency to increased rates of infections, autoimmunity, and allergies. Our goals here are to provide an overview of the molecular basis for immune system regulation and to survey the clinical data from pediatric populations, using randomized placebo-controlled trials and meta-analyses where possible, linking vitamin D deficiency to increased rates of infections, autoimmune conditions, and allergies, and addressing the impact of supplementation on these conditions.

Nutritional interventions to reduce rates of infection, necrotizing enterocolitis and mortality in very preterm infants.

Observational studies demonstrating reduced rates of infections, necrotizing enterocolitis (NEC), and mortality in preterm infants fed their own mother's milk, as opposed to formula, have prompted endeavors to achieve similar effects with the right choice of food and food additives. In a systematic review of meta-analyses and randomized controlled trials (RCTs), we considered nutritional interventions aimed at reducing the rates of infections, NEC, or mortality in very preterm infants. The overall effects of particular interventions were presented as risk ratios with 95% confidence intervals. In RCTs, pasteurized human donor milk, as opposed to formula, reduced NEC but not infections or mortality. No differences emerged between infants receiving human or bovine milk-based fortifiers. Pooled data of small trials and a recent large RCT suggested that bovine lactoferrin reduced rates of fungal sepsis without impact on other infections, NEC, or mortality. Pooled data of RCTs assessing the use of prebiotic oligosaccharides found reduced infection but not mortality. Enteral L-glutamine (six RCTs) lowered infection rates, and enteral L-arginine (three RCTs) reduced NEC. A meta-analysis sensitivity approach found multiple-strain (but not single-strain) probiotics to be highly effective in reducing NEC and mortality. Thus, selected food components may help to improve outcomes in preterm infants.

Association of Initial Low Serum Selenium Level with Infectious Complications and 30-Day Mortality in Multiple Trauma Patients.

Low serum selenium levels are commonly observed in critically injured multiple trauma patients. This study aimed to identify the association between initial serum selenium levels and in-hospital infectious complications in multiple trauma patients. We retrospectively reviewed multiple trauma patients admitted between January 2015 and November 2017. We selected 135 patients whose serum selenium levels were checked within 48 h of admission. Selenium deficiency was defined as a serum selenium level <70 ng/mL. Survival analyses of selenium deficiency and 30-day mortality were performed. Multivariate logistic regression analysis was performed to identify the association between initial serum selenium level and in-hospital infectious complications. Thirty-day mortality (8.3% vs. 0.0%; p = 0.018) and incidence rates of pneumonia (66.7% vs. 28.3%; p < 0.001) and infectious complications (83.3% vs. 46.5%; p < 0.001) were higher in patients with selenium deficiency than in patients without selenium deficiency. Kaplan-Meier survival cures also showed similar results (log rank test, p = 0.021). Of 135 patients, 76 (56.3%) experienced at least one infectious complication during admission. High injury severity score (ISS, odds ratio (OR) 1.065, 95% confidence interval (CI) 1.024-1.108; p = 0.002) and selenium deficiency (OR 3.995, 95% CI 1.430-11.156; p = 0.008) increased the risk of in-hospital infectious complications in multiple trauma patients. Patients with selenium deficiency showed higher 30-day mortality and higher risks of pneumonia and infectious complications.

Iron deficiency anaemia: experiences and challenges.

Iron deficiency remains the largest nutritional deficiency worldwide and the main cause of anaemia. Severe iron deficiency leads to anaemia known as iron deficiency anaemia (IDA), which affects a total of 1·24 billion people, the majority of whom are children and women from resource-poor countries. In sub-Saharan Africa, iron deficiency is frequently exacerbated by concomitant parasitic and bacterial infections and contributes to over 120 000 maternal deaths a year, while it irreparably limits the cognitive development of children and leads to poor outcomes in pregnancy.Currently available iron compounds are cheap and readily available, but constitute a non-physiological approach to providing iron that leads to significant side effects. Consequently, iron deficiency and IDA remain without an effective treatment, particularly in populations with high burden of infectious diseases. So far, despite considerable investment in the past 25 years in nutrition interventions with iron supplementation and fortification, we have been unable to significantly decrease the burden of this disease in resource-poor countries.If we are to eliminate this condition in the future, it is imperative to look beyond the strategies used until now and we should make an effort to combine community engagement and social science approaches to optimise supplementation and fortification programmes.

Olive Oil and Soybean Oil Based Intravenous Lipid Emulsions, Liver Biochemistry and Clinical Outcomes.

Intravenous lipid emulsions are an essential component of parenteral nutrition (PN). Omega-6 reducing strategies may improve outcomes, including reduced PN associated liver disease, however evidence to support this recommendation is insufficient. The primary objective was to compare serum alkaline phosphatase (ALP), among patients provided with either soybean oil (Intralipid) or predominantly olive oil (Clinoleic) lipid emulsions. In this quasi-experimental study, we reviewed the medical records of surgical and medical adult patients who received lipid emulsions for at least seven consecutive days. Among the 206 patients (110-Intralipid, 96-Clinoleic) there was no significant difference in ALP and remaining liver function tests within 2 weeks of PN therapy initiation between groups, even after control for lipid doses. Macronutrient dosing was similar. Triglyceride level was higher by 0.7 mmol/L in the Clinoleic group; confidence interval 0.21 to 1.1; p = 0.004. The 30-day mortality, length of hospital stay, and proportion of patients admitted to intensive care were not significantly different. The Clinoleic group had a higher infection rate (36% vs. 22%, p = 0.031) and longer intensive care stays (p = 0.045). Well-designed randomized clinical trials comparing these lipid emulsions are necessary to confirm Intralipid superiority over Clinoleic in relation to infections and serum triglycerides.

Exploring the Human Microbiome: The Potential Future Role of Next-Generation Sequencing in Disease Diagnosis and Treatment.

The interaction between the human microbiome and immune system has an effect on several human metabolic functions and impacts our well-being. Additionally, the interaction between humans and microbes can also play a key role in determining the wellness or disease status of the human body. Dysbiosis is related to a plethora of diseases, including skin, inflammatory, metabolic, and neurological disorders. A better understanding of the host-microbe interaction is essential for determining the diagnosis and appropriate treatment of these ailments. The significance of the microbiome on host health has led to the emergence of new therapeutic approaches focused on the prescribed manipulation of the host microbiome, either by removing harmful taxa or reinstating missing beneficial taxa and the functional roles they perform. Culturing large numbers of microbial taxa in the laboratory is problematic at best, if not impossible. Consequently, this makes it very difficult to comprehensively catalog the individual members comprising a specific microbiome, as well as understanding how microbial communities function and influence host-pathogen interactions. Recent advances in sequencing technologies and computational tools have allowed an increasing number of metagenomic studies to be performed. These studies have provided key insights into the human microbiome and a host of other microbial communities in other environments. In the present review, the role of the microbiome as a therapeutic agent and its significance in human health and disease is discussed. Advances in high-throughput sequencing technologies for surveying host-microbe interactions are also discussed. Additionally, the correlation between the composition of the microbiome and infectious diseases as described in previously reported studies is covered as well. Lastly, recent advances in state-of-the-art bioinformatics software, workflows, and applications for analysing metagenomic data are summarized.

Nutritional modulation of age-related changes in the immune system and risk of infection.

The immune system undergoes some adverse alterations during aging, many of which have been implicated in the increased morbidity and mortality associated with infection in the elderly. In addition to intrinsic changes to the immune system with aging, the elderly are more likely to have poor nutritional status, which further impacts the already impaired immune function. Although the elderly often have low zinc serum levels, several manifestations commonly observed during zinc deficiency are similar to the changes in immune function with aging. In the case of vitamin E, although its deficiency is rare, the intake above recommended levels is shown to enhance immune functions in the elderly and to reduce the risk of acquiring upper respiratory infections in nursing home residents. Vitamin D is a critical vitamin in bone metabolism, and its deficiency is far more common, which has been linked to increased risk of infection as demonstrated in a number of observational studies including those in the elderly. In this review, we focus on zinc, vitamin E, and vitamin D, the 3 nutrients which are relatively well documented for their roles in impacting immune function and infection in the elderly, to discuss the findings in this context reported in both the observational studies and interventional clinical trials. A perspective will be provided based on the analysis of information under review.

Interfacing brain with computer to improve communication and rehabilitation after brain damage.

Communication and control of the external environment can be provided via brain-computer interfaces (BCIs) to replace a lost function in persons with severe diseases and little or no chance of recovery of motor abilities (ie, amyotrophic lateral sclerosis, brainstem stroke). BCIs allow to intentionally modulate brain activity, to train specific brain functions, and to control prosthetic devices, and thus, this technology can also improve the outcome of rehabilitation programs in persons who have suffered from a central nervous system injury (ie, stroke leading to motor or cognitive impairment). Overall, the BCI researcher is challenged to interact with people with severe disabilities and professionals in the field of neurorehabilitation. This implies a deep understanding of the disabled condition on the one hand, and it requires extensive knowledge on the physiology and function of the human brain on the other. For these reasons, a multidisciplinary approach and the continuous involvement of BCI users in the design, development, and testing of new systems are desirable. In this chapter, we will focus on noninvasive EEG-based systems and their clinical applications, highlighting crucial issues to foster BCI translation outside laboratories to eventually become a technology usable in real-life realm.

High-throughput proteomics and the fight against pathogens.

Pathogens pose a major threat to human and animal welfare. Understanding the interspecies host-pathogen protein-protein interactions could lead to the development of novel strategies to combat infectious diseases through the rapid development of new therapeutics. The first step in understanding the host-pathogen crosstalk is to identify interacting proteins in order to define crucial hot-spots in the host-pathogen interactome, such as the proposed pharmaceutical targets by means of high-throughput proteomic methodologies. In order to obtain holistic insight into the inter- and intra-species bimolecular interactions, apart from the proteomic approach, sophisticated in silico modeling is used to correlate the obtained large data sets with other omics data and clinical outcomes. Since the main focus in this area has been directed towards human medicine, it is time to extrapolate the existing expertise to a new emerging field: the 'systems veterinary medicine'. Therefore, this review addresses high-throughput mass spectrometry-based technology for monitoring protein-protein interactions in vitro and in vivo and discusses pathogen cultivation, model host cells and available bioinformatic tools employed in vaccine development.

Chemical and Plant-Based Insect Repellents: Efficacy, Safety, and Toxicity.

Most emerging infectious diseases today are arthropod-borne and cannot be prevented by vaccinations. Because insect repellents offer important topical barriers of personal protection from arthropod-borne infectious diseases, the main objectives of this article were to describe the growing threats to public health from emerging arthropod-borne infectious diseases, to define the differences between insect repellents and insecticides, and to compare the efficacies and toxicities of chemical and plant-derived insect repellents. Internet search engines were queried with key words to identify scientific articles on the efficacy, safety, and toxicity of chemical and plant-derived topical insect repellants and insecticides to meet these objectives. Data sources reviewed included case reports; case series; observational, longitudinal, and surveillance studies; and entomological and toxicological studies. Descriptive analysis of the data sources identified the most effective application of insect repellents as a combination of topical chemical repellents, either N-diethyl-3-methylbenzamide (formerly N, N-diethyl-m-toluamide, or DEET) or picaridin, and permethrin-impregnated or other pyrethroid-impregnated clothing over topically treated skin. The insecticide-treated clothing would provide contact-level insecticidal effects and provide better, longer lasting protection against malaria-transmitting mosquitoes and ticks than topical DEET or picaridin alone. In special cases, where environmental exposures to disease-transmitting ticks, biting midges, sandflies, or blackflies are anticipated, topical insect repellents containing IR3535, picaridin, or oil of lemon eucalyptus (p-menthane-3, 8-diol or PMD) would offer better topical protection than topical DEET alone.

[The disease and treatment of the frontline soldiers in Han dynasty].

This paper purports to identify and analyze the medical information of the frontline soldiers in the Northwest borderland provinces of Han Dynasty, especially Juyan and Dunhuang region, through an heuristic reading of the Juyan Bamboo Slips and the Dunhuang Bamboo Slips of the Han Dynasty. My findings are as follows. The most frequent disease found in the bamboo slips was the external injury. The injury of the frontline soldiers mainly occurred from the quarrels among armed soldiers using weapons. The bamboo slips also demonstrate that the quarrels usually arose due to the fierce tension caused by the frontier line service such as heavy guard activity and labour duty. Undernourishment and chronic stress the soldiers suffered might be another reasons. The second most common disease harassing the soldiers was exogenous febrile disease. In most cases reviewed in this paper, the exogenous febrile disease was usually concurrent with complex symptoms such as chills, fever, headache, etc. The bamboo slips show that the exogenous febrile disease was related to the harsh climate of the Northwest provinces, featuring extremely dry weather and the large magnitude of diurnal temperature fluctuations. In addition, the annual temperature range in the Northwest province was huge, fluctuating between very cold and dry winter and very hot and dry summer. The third most common disease this study identified was the disorder of the digestive system and respiratory system. However, these two types of disease were virtually indistinguishable in the bamboo slips, because the ancient Chinese chroniclers did not distinguish them, usually dubbing both diseases simply 'abdominal pain.' It should be mentioned that a few slips mention contagious disease such as dysentery and dermatolosis, and sudden death, as well. Overall, the bamboo slips demonstrate extremely poor status of the soldiers' heath condition and poor medical environment surrounding the soldiers stationing in the Northwest borderland military camps. The records also show that acupuncture, applying a plaster, drugs were the most common medical treatment. Drugs among them was the most frequently used. Whereas Acupuncture, applying a plaster were very rarely used. Medication has been used in three ways: powdered medicine, medicinal decoction and pill. Medicinal decoction was the most commonly used way.

Oral zinc and common childhood infections--An update.

Zinc is an essential micronutrient important for growth and for normal function of the immune system. Many children in developing countries have inadequate zinc nutrition. Routine zinc supplementation reduces the risk of respiratory infections and diarrhea, the two leading causes of morbidity and mortality in young children worldwide. In childhood diarrhea oral zinc also reduces illness duration and risk of persistent episodes. Oral zinc is therefore recommended for the treatment of acute diarrhea in young children. The results from the studies that have measured the therapeutic effect of zinc on acute respiratory infections, however, are conflicting. Moreover, the results of therapeutic zinc for childhood malaria also are so far not promising.This paper gives a brief outline of the current evidence from clinical trials on therapeutic effect of oral zinc on childhood respiratory infections, pneumonia and malaria and also of new evidence of the effect on serious bacterial illness in young infants.

Impact of Providing a Combination Lipid Emulsion Compared With a Standard Soybean Oil Lipid Emulsion in Children Receiving Parenteral Nutrition: A Systematic Review and Meta-Analysis.

BACKGROUND: Soybean oil lipid emulsion may compromise immune function and promote hepatic damage due to its composition of long-chain fatty acids, phytosterols, high proportion of ω-6 fatty acids, and low α-tocopherol levels. Combination lipid emulsions have been developed using medium-chain triglyceride oil, fish oil, and/or olive oil, which provide adequate essential fatty acids, a smaller concentration of ω-6 fatty acids, and lower levels of phytosterols. The purpose of this systematic review is to determine if combination lipid emulsions have a more favorable impact on bilirubin levels, triglyceride levels, and incidence of infection compared with soybean oil lipid emulsions in children receiving parenteral nutrition. METHODS: This study comprises a systematic review of published studies. Data were sufficient and homogeneous to conduct a meta-analysis for total bilirubin and infection. RESULTS: Nine studies met the inclusion criteria. Meta-analysis showed that combination lipid emulsion decreased total bilirubin by a mean difference of 2.09 mg/dL (95% confidence interval, -4.42 to 0.24) compared with soybean oil lipid emulsion, although the result was not statistically significant (P = .08). Meta-analysis revealed no statistically significant difference in incidence of infection between the combination lipid emulsion and the soybean oil lipid emulsion groups (P = .846). None of the 4 studies that included triglyceride as an outcome detected a significant difference in triglyceride levels between the combination lipid emulsion and soybean oil lipid emulsion groups. CONCLUSION: There is inadequate evidence that combination lipid emulsions offer any benefit regarding bilirubin levels, triglyceride levels, or incidence of infection compared with soybean oil lipid emulsions.

Pharmacological approaches to chronic spinal cord injury.

Although research on neural tissue repair has made enormous progress in recent years, spinal cord injury remains a devastating condition for which there is still no cure. In fact, recent estimates of prevalence in the United States reveal that spinal cord injury has undergone a five-fold increase in the last decades. Though, it has become the second most common neurological problem in North America after Alzheimer's disease. Despite modern trauma units and intensive care treatments, spinal cord injury remains associated with several comorbid conditions and unbearable health care costs. Regular administration of a plethora of symptomatic drug treatments aimed at controlling related-secondary complications and life-threatening problems in chronic spinal cord-injured patients has recently been reported. This article provides a thorough overview of the main drug classes and products currently used or in development for chronic spinal cord injury. Special attention is paid to a novel class of drug treatment designed to provide a holistic solution for several chronic complications and diseases related with spinal cord injury. There is clear evidence showing that new class can elicit 'on-demand' episodes of rhythmic and stereotyped walking activity in previously completely paraplegic animals and may consequently constitute a simple therapy against several physical inactivity-related comorbid problems. Understanding further pharmacological approaches to chronic spinal cord injury may improve both life expectancy and overall quality of life while reducing unsustainable cost increases associated with this debilitation condition.

Translational research in infectious disease: current paradigms and challenges ahead.

In recent years, the biomedical community has witnessed a rapid scientific and technologic evolution after the development and refinement of high-throughput methodologies. Concurrently and consequentially, the scientific perspective has changed from the reductionist approach of meticulously analyzing the fine details of a single component of biology to the "holistic" approach of broadmindedly examining the globally interacting elements of biological systems. The emergence of this new way of thinking has brought about a scientific revolution in which genomics, proteomics, metabolomics, and other "omics" have become the predominant tools by which large amounts of data are amassed, analyzed, and applied to complex questions of biology that were previously unsolvable. This enormous transformation of basic science research and the ensuing plethora of promising data, especially in the realm of human health and disease, have unfortunately not been followed by a parallel increase in the clinical application of this information. On the contrary, the number of new potential drugs in development has been decreasing steadily, suggesting the existence of roadblocks that prevent the translation of promising research into medically relevant therapeutic or diagnostic application. In this article, we will review, in a noninclusive fashion, several recent scientific advancements in the field of translational research, with a specific focus on how they relate to infectious disease. We will also present a current picture of the limitations and challenges that exist for translational research, as well as ways that have been proposed by the National Institutes of Health to improve the state of this field.

Formal adult infectious disease specialist consultations in the outpatient setting at a comprehensive cancer center (1998-2008): diverse and impactful.

PURPOSE: The literature on the impact of infectious disease (ID) consulations in the outpatient treatment of cancer is scarce. METHODS: The medical records of consecutive adult patients with cancer formally evaluated by two board-certified ID specialists in an outpatient setting at our institution over a 10-year period (1998-2008) were reviewed retrospectively. The patients' demographics, referring departments, purposes for consultation, ID specialist recommendations, and overall impact of consultations on outcome were analyzed. RESULTS: We identified 598 patients who underwent ID specialist consultations. Most of them had solid tumors (53%), predominantly breast cancer, whereas non-Hodgkin's lymphoma was the most common hematologic malignancy. Almost half of the patients (45%) had active malignancies, but few of them were severely neutropenic (8%) or had been receiving high doses of corticosteroids (17%). The most frequent requests for consultation were culture or serologic test (15%), and treatment of cellulitis and/or surgical wound infections (14%). Of 337 isolated pathogens, the most prevalent were methicillin-resistant Staphylococcus aureus (13%) and Pseudomonas aeruginosa (8%), as well as atypical mycobacteria (16%) and Aspergillus species (11%). ID specialists provided alternative diagnoses in 53% of the cases, including identification of a different infection (46%), a noninfectious etiology (29%), colonization (16%), and drug-related toxic effects (9%). Overall, we deemed the contribution of the ID specialist to be significant in 62% of the consultations. CONCLUSIONS: ID specialists contribute significantly to the outpatient care of individuals with cancer.

Surveillance for waterborne disease and outbreaks associated with recreational water use and other aquatic facility-associated health events--United States, 2005-2006.

PROBLEM/CONDITION: Since 1971, CDC, the U.S. Environmental Protection Agency, and the Council of State and Territorial Epidemiologists have collaboratively maintained the Waterborne Disease and Outbreak Surveillance System for collecting and reporting data related to waterborne-disease outbreaks (WBDOs) associated with drinking water. In 1978, WBDOs associated with recreational water (natural and treated water) were added. This system is the primary source of data regarding the scope and effects of disease associated with recreational water in the United States. In addition, data are collected on individual cases of recreational water-associated illnesses and infections and health events occurring at aquatic facilities but not directly related to water exposure. REPORTING PERIOD: Data presented summarize WBDOs and case reports associated with recreational water use that occurred during January 2005--December 2006 and previously unreported disease reports and outbreaks during 1978--2004. DESCRIPTION OF THE SYSTEM: Public health departments in the states, territories, localities, and the Freely Associated States (i.e., the Republic of the Marshall Islands, the Federated States of Micronesia, and the Republic of Palau, formerly parts of the U.S.-administered Trust Territory of the Pacific Islands) have primary responsibility for detecting, investigating, and voluntarily reporting WBDOs to CDC. Although the surveillance system includes data for WBDOs and cases associated with drinking water, recreational water, and water not intended for drinking, only cases and outbreaks associated with recreational water and health events at aquatic facilities are summarized in this report. RESULTS: During 2005--2006, a total of 78 WBDOs associated with recreational water were reported by 31 states. Illness occurred in 4,412 persons, resulting in 116 hospitalizations and five deaths. The median outbreak size was 13 persons (range: 2--2,307 persons). Of the 78 WBDOs, 48 (61.5%) were outbreaks of gastroenteritis that resulted from infectious agents or chemicals; 11 (14.1%) were outbreaks of acute respiratory illness; and 11 (14.1%) were outbreaks of dermatitis or other skin conditions. The remaining eight were outbreaks of leptospirosis (n = two), primary amebic meningoencephalitis (n = one), and mixed or other illnesses (n = five). WBDOs associated with gastroenteritis resulted in 4,015 (91.0%) of 4,412 illnesses. Fifty-eight (74.4%) WBDOs occurred at treated water venues, resulting in 4,167 (94.4%) cases of illness. The etiologic agent was confirmed in 62 (79.5%) of the 78 WBDOs, suspected in 12 (15.4%), and unidentified in four (5.1%). Thirty-four (43.6%) WBDOs had a parasitic etiology; 22 (28.2%), bacterial; four (5.1%), viral; and two (2.6%), chemical or toxin. Among the 48 gastroenteritis outbreaks, Cryptosporidium was confirmed as the causal agent in 31 (64.6%), and all except two of these outbreaks occurred in treated water venues where Cryptosporidium caused 82.9% (29/35) of the gastroenteritis outbreaks. Case reports associated with recreational water exposure that were discussed and analyzed separately from outbreaks include three fatal Naegleria cases and 189 Vibrio illnesses reported to the Cholera and Other Vibrio Illness Surveillance System. For Vibrio reporting, the most commonly reported species were Vibrio vulnificus, V. alginolyticus, and V. parahaemolyticus. V. vulnificus illnesses associated with recreational water exposure had the highest Vibrio illness hospitalization (77.6%) and mortality (22.4%) rates. In addition, 32 aquatic facility-related health events not associated with recreational water use (e.g., pool chemical mixing accidents) that occurred during 1983--2006 were received from New York. These events, which caused illness in 364 persons, are included in this report but analyzed separately. INTERPRETATIONS: The number of WBDOs summarized in this report and the trends in recreational water-associated disease and outbreaks demonstrate a substantial increase in number of reports from previous years. Outbreaks, especially the largest ones, occurred more frequently in the summer at treated water venues and caused gastrointestinal illness. Deficiencies leading to WBDOs included problems with water-quality, venue design, usage, and maintenance. Case reports of illness associated with recreational water use expand our understanding of the scope of waterborne illness by further underscoring the contribution of less well-recognized swimming venues (e.g., oceans) and illness (e.g., nongastrointestinal illness). Aquatic facilities are also a focus for injuries involving chemicals or equipment used routinely in the operation of swimming venues, thus illustrating the lack of training of some aquatics staff. PUBLIC HEALTH ACTIONS: CDC uses WBDO surveillance data to 1) identify the etiologic agents, types of aquatic venues, water-treatment systems, and deficiencies associated with outbreaks and case reports; 2) evaluate the adequacy of efforts (i.e., regulations and public awareness activities) to provide safe recreational water; 3) expand the scope of understanding about waterborne disease and health events associated with swimming and aquatics facilities; and 4) establish public health prevention priorities, data, and messaging that might lead to improved regulations, guidelines, and prevention measures at the local, state, and federal levels.

Toll-like receptors, transduction-effector pathways, and disease diversity: evidence of an immunobiological paradigm explaining all human illness?

Membrane-bound Toll-like receptors (TLRs) are frontline guardians in the mammalian innate immune system. They primarily function to recognize pathogen-associated molecular patterns (PAMPs) of invading microorganisms and on activation mount rapid, nonspecific innate responses and trigger sequential delayed specific adaptive cellular responses, which are mediated by complex signal transduction pathways involving adaptor molecules, costimulatory ligands and receptors, kinases, transcription factors, and modulated gene expression. Increasing evidence of multiple functionality and diversity suggests TLRs play critical roles in noninfective medical conditions such as cardiovascular, gastrointestinal, neurologic, musculoskeletal, obstetric, renal, liver, and dermatologic diseases, allergy, autoimmunity, and tissue regeneration. The significance of TLR heterogeneity underscores the possibility for establishing a universal immunobiological model to explain all human disease. Novel immunomodulatory therapies targeting specific or multiple TLRs may in the future offer new tools to combat or eradicate pathogenesis potentially transforming the landscape of current medical treatments.