Puncture mechanics of cnidarian cnidocysts: a natural actuator

Background Cnidocysts isolated from cnidarian organisms are attractive as a drug-delivery platform due to their fast, efficient delivery of toxins. The cnidocyst could be utilized as the means to deliver therapeutics in a wearable drug-delivery patch. Cnidocysts have been previously shown to discharge upon stimulation via electrical, mechanical, and chemical pathways. Cnidocysts isolated from the Portuguese Man O' War jellyfish ( Physalia physalis ) are attractive for this purpose because they possess relatively long threads, are capable of puncturing through hard fish scales, and are stable for years. Results As a first step in using cnidocysts as a functional component of a drug delivery system, the puncture mechanics of the thread were characterized. Tentacle-contained cnidocysts were used as a best-case scenario due to physical immobilization of the cnidocysts within the tentacle. Ex vivo tentacle-contained cnidocysts from Physalia possessed an elastic modulus puncture threshold of approximately 1-2 MPa, based on puncture tests of materials with a gamut of hardness. Also, a method for inducing discharge of isolated cnidocysts was found, utilizing water as the stimulant. Preliminary lectin-binding experiments were performed using fluorophore-conjugated lectins as a possible means to immobilize the isolated cnidocyst capsule, and prevent reorientation upon triggering. Lectins bound homogeneously to the surface of the capsule, suggesting the lectins could be used for cnidocyst immobilization but not orientation. Conclusion Cnidocysts were found to puncture materials up to 1 MPa in hardness, can be discharged in a dry state using water as a stimulant, and bind homogeneously to lectins, a potential means of immobilization. The information gained from this preliminary work will aid in determining the materials and design of the patch that could be used for drug delivery.

Impaired immune function in Gulf War Illness

Background Gulf War Illness (GWI) remains a serious health consequence for at least 11,000 veterans of the first Gulf War in the early 1990s. Our understanding of the health consequences that resulted remains inadequate, and this is of great concern with another deployment to the same theater of operations occurring now. Chronic immune cell dysfunction and activation have been demonstrated in patients with GWI, although the literature is not uniform. We exposed GWI patients and matched controls to an exercise challenge to explore differences in immune cell function measured by classic immune assays and gene expression profiling. Methods This pilot study enrolled 9 GWI cases identified from the Department of Veterans Affairs GWI registry, and 11 sedentary control veterans who had not been deployed to the Persian Gulf and were matched to cases by sex, body mass index (BMI) and age. We measured peripheral blood cell numbers, NK cytotoxicity, cytokines and expression levels of 20,000 genes immediately before, immediately after and 4 hours following a standard bicycle ergometer exercise challenge. Results A repeated-measures analysis of variance revealed statistically significant differences for three NK cell subsets and NK cytotoxicity between cases and controls (p < 0.05). Linear regression analysis correlating NK cell numbers to the gene expression profiles showed high correlation of genes associated with NK cell function, serving as a biologic validation of both the in vitro assays and the microarray platform. Intracellular perforin levels in NK and CD8 T-cells trended lower and showed a flatter profile in GWI cases than controls, as did the expression levels of the perforin gene PRF1. Genes distinguishing cases from controls were associated with the glucocorticoid signaling pathway. Conclusion GWI patients demonstrated impaired immune function as demonstrated by decreased NK cytotoxicity and altered gene expression associated with NK cell function. Pro-inflammatory cytokines, T-cell ratios, and dysregulated mediators of the stress response (including salivary cortisol) were also altered in GWI cases compared to control subjects. An interesting and potentially important observation was that the exercise challenge augments these differences, with the most significant effects observed immediately after the stressor, possibly implicating some block in the NK and CD8 T-cells ability to respond to "stress-mediated activation". This has positive implications for the development of laboratory diagnostic tests for this syndrome and provides a paradigm for exploration of the immuno-physiological mechanisms that are operating in GWI, and similar complex syndromes. Our results do not necessarily elucidate the cause of GWI, but they do reveal a role for immune cell dysfunction in sustaining illness.

Diarrhoea and acute respiratory infections prevalence and risk factors among under-five children in Iraq in 2000

Background Diarrhoea and acute respiratory conditions are common medical conditions among under-five children in resource-limited and conflict situations. The present study was conducted to estimate the prevalence and associated factors for acute respiratory conditions and diarrhoea among children under the age of five years in Iraq in 2000. Methods Data for the Iraqi Multiple Indicator Cluster Survey were obtained from UNICEF. We estimated the prevalence of acute respiratory conditions and diarrhoea. Assessment of the associations between these two medical conditions on one hand and socio-demographic and environmental variables on the other was done using logistic regression analysis. Weighted analysis was conducted to account for complex survey design. Results A total of 14,676 children under the age of 5 years were reported by their mothers in the study. Of these 50.4% were males. About half (53.9%) of the children had complete vaccination status. Overall, 21.3% of the children had diarrhoea, and 6.9% had acute respiratory infection (ARI) in the last two weeks. In multivariate analysis, diarrhoea was associated with age of child, area of residence, maternal education, source of water, toilet facility, disposal of children' stool and disposal of dirty water. Compared to children aged 48–59 months, children in the age groups 6–11 months and 12–23 months were 2.22 (95%CI [2.02, 2.44]) and 1.84 (95%CI [1.71, 2.00]) times more likely, respectively, to have diarrhoea. Children whose mothers had no formal education were 11% (AOR = 1.11, 95%CI [1.04, 1.18]) more likely to have diarrhoea compared to children with mothers who had attained secondary level of education. Compared to children who belonged to households with unprotected well or river as the main source of water, children who belonged to households with piped water were 32% (AOR = 1.32, 95%CI [1.17, 1.48]) more likely to have diarrhoea while those who belonged to households with protected well were 26% (AOR = 0.74, 95%CI [0.62, 0.89]) less likely to have diarrhoea. Age of child, toilet facility, wealth, and sex of child were significantly associated with ARI. Conclusion In a study of under-five children in Iraq in 2000, we found that history of diarrhoea and ARI were negatively associated with lower socio-economic status, adequate disposal of children's stool and dirty water, but the results were inconsistent in terms of access to potable water and sanitation facilities possibly due to non-functioning of water and sewage plants after the war. Improvement in water quality and sanitation are vital in the reduction of diarrhoeal diseases.

Development, Implementation, and Assessment of a Lecture Course on Cancer for Undergraduates

The war on cancer has been waged for nearly 40 years, yet the cancer burden remains high, especially among minority and underserved populations. One strategy to make strides in the war on cancer and its disparate impacts is to increase the diversity of the cancer research workforce. We describe an approach to recruit a diverse population of future cancer researchers from an undergraduate student population at a minority-serving land-grant institution. Specifically, we have addressed the following questions: Given the dearth of published reports of undergraduate cancer courses, is it possible for undergraduates at a land-grant institution (rather than a research or medical institution) to successfully learn cancer biology from a lecture-based course? Can we develop a template that has the potential to be used by others to develop and implement an undergraduate cancer course? Can such a course stimulate interest in careers in cancer research? Based on a learning gains analysis, students were able to learn cancer content and related skills, and based on student surveys, students' interest in cancer research was stimulated by course participation. We have identified aspects of our course development process that were critical for the successful development, implementation, and assessment of the course.

Delayed-onset post-traumatic stress disorder among war veterans in primary care clinics

Only limited empirical data support the existence of delayed-onset post-traumatic stress disorder (PTSD).

Inequity and poverty: everyday emotional disturbances and mental disorders in the Mexican urban population

1Researcher, National Institute of Psychiatry Ramón de la Fuente Muñíz, Mexico 2Director of the National Institute of Psychiatry Ramón de la Fuente Muñíz, Mexico Several studies have reported the frequency of mental disorders in the war-affected populations of East Africa, the most common ones being PTSD, depression, anxiety, somatisation disorder, and alcohol and substance use disorders (Neuner et al, 2004; Njenga et al, 2006); the reported prevalence of PTSD has ranged between 28% and 80.2% of the study populations. The World Health Organization (2001) estimated that, in the context of armed conflict, 10% of the people who experience traumatic events will have serious mental health problems and another 10% will develop behaviour that will hinder their ability to function effectively, and thus be unable to contribute significantly to the economic growth of that population. The most common conditions are similar to those reported above. Northern Uganda, which has seen war for the past two decades, and which has nearly 50% of its population on the move or categorised as IDPs, has one of the world’s highest rates of mental illness. In a study in two northern Uganda districts, more than 54% of the adults screened had PTSD (Njenga et al, 2006). Furthermore, the physical and mental health problems of the survivors of the genocide in Rwanda have been well documented. In a community-based study examining 2091 people, 24.8% met the DSM–IV symptom criteria for PTSD (Srinivasa & Lakshminarayana, 2006).

The Amiens Strategy: Small Phase III Trials for Clinically Relevant Progress in the War Against Cancer

Emerging Subspecialties in Neurology: Neuroinfectious diseases

Infection as a cause of neurologic disease is a prominent feature in the history of medicine. The training of the practitioner called to care for these patients has changed throughout the years. To understand the history of in- fectious disease in neurologic practice, consider the rela- tive infancy of the specialty of neurology in the United States. Neurology as an independent specialty board did not emerge from the cloak of neuropsychiatry and in- ternal medicine until after World War II and the founding of the American Academy of Neurology (AAN). Neuropathology was an integral part of the cur- riculum, and neuroinfectious diseases were taught pri- marily from the pathologic perspective. In 1964, H. Merritt1 thought infectious disease was sufficiently im- portant to be the subject of the first chapter in the third edition of his Textbook of Neurology. The increasing im- portance of infectious disease in neurology is evident from the more recent publication of dedicated text- books on both pediatric and general neuroinfectious disorders.2-4 Early practitioners in the field of neurology were first recognized for their work with neuroinfections. A major purpose of the Pasteur institute that opened in Paris in 1888 was to care for the multitude of patients with ra- bies.5 In the same year, the first neurologist at Johns

Neuromodulation in Patients Deployed to War Zones

Four active duty military personnel and two retired soldiers/military contractors were treated with spinal or peripheral nerve stimulators. All six personnel were able to deploy after the stimulators were placed. Five patients had no incidents during their deployments. One patient completed four deployments but had mechanical complications that necessitated eventual revisions. Considering the risks and limitations of reoperation, nerve blocks, and pharmacotherapy in a forward-deployed area, spinal cord stimulation provides an appealing alternative in soldiers who desire to remain deployable on active duty.

The Pequot Conspirator

Historical interpretations of the Anglo-Pequot War have oscillated between ethnographic and conspiratorial explanations, arguing that it resulted either from cultural differences and misunderstandings or from scheming and provocation. But seventeenth-century accounts of the conflict demonstrate the interconnectedness of the ethnographic and conspiratorial frameworks, going as far as to suggest that the Pequots, one of the first Native American groups referred to by name, conspiratorially used their “Indianness” as a weapon. Tracing this connection, from the narratives of Philip Vincent and John Mason to those of John Underhill and Lion Gardiner, helps us better appreciate the racial origins of seventeenth-century conspiracy thought.