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A bacteriolytic agent that detects and kills Bacillus anthracis.

The dormant and durable spore form of Bacillus anthracis is an ideal biological weapon of mass destruction. Once inhaled, spores are transported by alveolar macrophages to lymph nodes surrounding the lungs, where they germinate; subsequent vegetative expansion causes an overwhelming flood of bacteria and toxins into the blood, killing up to 99% of untreated victims. Natural and genetically engineered antibiotic-resistant bacilli amplify the threat of spores being used as weapons, and heighten the need for improved treatments and spore-detection methods after an intentional release. We exploite

A simple and rapid protein array based method for the simultaneous detection of biowarfare agents.

A protein chip has been developed that allows the simultaneous detection of a multitude of different biowarfare agents. The chip was developed for the ArrayTube platform providing a cheap and easy to handle technology solution that combines a microtube-integrated protein chip with the classical procedure of a sandwich-enzyme-linked immunosorbent assay and signal amplification by streptavidin-poly-horseradish peroxidase. Specific immunoassays for Staphylococcus enterotoxin B, ricin, Venezuelan equine encephalitis virus, St. Louis encephalitis virus, West Nile virus, Yellow fever virus, Orthopox

Posttraumatic stress disorder in war veterans: a discussion of the Neuroevolutionary Time-depth Principle.

INTRODUCTION: Trauma is a universal phenomenon. Violence is a type of trauma and war is one of the ways in which violence is expressed. The "Neuroevolutionary Time-depth Principle" of innate fears, based on prevalence data, suggests that high rates of posttraumatic stress disorder (PTSD) after combat exposure can be due to the fact that this fear-stress response appeared as a reaction to inter-group male-to-male and intra-group killings after the rising of population densities in the Neolithic period. MATERIAL AND METHODS: Studies of PTSD prevalence available in MEDLINE, Institute for Scienti

Safety and immunogenicity of a trivalent virus-like particle vaccine against western, eastern, and Venezuelan equine encephalitis viruses: a phase 1, open-label, dose-escalation, randomised clinical trial.

BACKGROUND: Western (WEEV), eastern (EEEV), and Venezuelan (VEEV) equine encephalitis viruses are mosquito-borne pathogens classified as potential biological warfare agents for which there are currently no approved human vaccines or therapies. We aimed to evaluate the safety, tolerability, and immunogenicity of an investigational trivalent virus-like particle (VLP) vaccine, western, eastern, and Venezuelan equine encephalitis (WEVEE) VLP, composed of WEEV, EEEV, and VEEV VLPs. METHODS: The WEVEE VLP vaccine was evaluated in a phase 1, randomised, open-label, dose-escalation trial at the Hope …

Skin cancer incidence among atomic bomb survivors from 1958 to 1996.

The radiation risk of skin cancer by histological types has been evaluated in the atomic bomb survivors. We examined 80,158 of the 120,321 cohort members who had their radiation dose estimated by the latest dosimetry system (DS02). Potential skin tumors diagnosed from 1958 to 1996 were reviewed by a panel of pathologists, and radiation risk of the first primary skin cancer was analyzed by histological types using a Poisson regression model. A significant excess relative risk (ERR) of basal cell carcinoma (BCC) (n = 123) was estimated at 1 Gy (0.74, 95% confidence interval (CI): 0.26, 1.6) for

Blast-induced phenotypic switching in cerebral vasospasm.

Vasospasm of the cerebrovasculature is a common manifestation of blast-induced traumatic brain injury (bTBI) reported among combat casualties in the conflicts in Afghanistan and Iraq. Cerebral vasospasm occurs more frequently, and with earlier onset, in bTBI patients than in patients with other TBI injury modes, such as blunt force trauma. Though vasospasm is usually associated with the presence of subarachnoid hemorrhage (SAH), SAH is not required for vasospasm in bTBI, which suggests that the unique mechanics of blast injury could potentiate vasospasm onset, accounting for the increased inci

CD28 Deficiency Ameliorates Blast Exposure-Induced Lung Inflammation, Oxidative Stress, Apoptosis, and T Cell Accumulation in the Lungs via the PI3K/Akt/FoxO1 Signaling Pathway.

Although CD28 is associated with the expression of inflammatory mediators, apoptosis-related protein, immunosuppression, and tumorigenesis, the effects of CD28 deficiency on blast exposure-induced lung injury have not been investigated. In this study, we have explored the effects of CD28 on blast exposure-induced lung injury and studied its potential molecular mechanisms. A mouse model of blast exposure-induced acute lung injury was established. Sixty C57BL/6 wild-type (WT) and CD28 knockout (CD28-/-) mice were randomly divided into control or model groups. Lung tissue samples were collected 2

Recent trends in specialty pharma business model.

The recent rise of specialty pharma is attributed to its flexible, versatile, and open business model while the traditional big pharma is facing a challenging time with patent cliff, generic threat, and low research and development (R&D) productivity. These multinational pharmaceutical companies, facing a difficult time, have been systematically externalizing R&D and some even establish their own corporate venture capital so as to diversify with more shots on goal, with the hope of achieving a higher success rate in their compound pipeline. Biologics and clinical Phase II proof-of-concept (POC

Targeting Oncoproteins for Molecular Cancer Therapy

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Demographic, epidemiological, and health transitions: are they relevant to population health patterns in Africa?

BackgroundStudies of trends in population changes and epidemiological profiles in the developing world have overwhelmingly relied upon the concepts of demographic, epidemiological, and health transitions, even though their usefulness in describing and understanding population and health trends in developing countries has been repeatedly called into question. The issue is particularly relevant for the study of population health patterns in Africa and sub-Saharan Africa, as the history and experience there differs substantially from that of Western Europe and North America, for which these conce

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… This stage is a manifestation of the increasing prevalence of man-made diseases (e.g. radiation injury, occupational and health care hazards, chemical and biological warfare, environmental pollutants, motor vehicle and aviation accidents, carcinogens in the environment and in industry and food additives …

Alkylating anticancer agents and their relations to microRNAs.

Alkylating agents represent an important class of anticancer drugs. The occurrence and emergence of tumor resistance to the treatment with alkylating agents denotes a severe problem in the clinics. A detailed understanding of the mechanisms of activity of alkylating drugs is essential in order to overcome drug resistance. In particular, the role of non-coding microRNAs concerning alkylating drug activity and resistance in various cancers is highlighted in this review. Both synthetic and natural alkylating agents, which are approved for cancer therapy, are discussed concerning their interplay w

Mutual connected IL-6, EGFR and LIN28/Let7-related mechanisms modulate PD-L1 and IGF upregulation in HNSCC using immunotherapy

The development of techniques and immunotherapies are widely applied in cancer treatment such as checkpoint inhibitors, adoptive cell therapy, and cancer vaccines apart from radiation therapy, surgery, and chemotherapy give enduring anti-tumor effects. Minority people utilize single-agent immunotherapy, and most people adopt multiple-agent immunotherapy. The difficulties are resolved by including the biomarkers to choose the non-responders’ and responders’ potentials. The possibility of the potential complications and side effects are examined to improve cancer therapy effects. The Head and Ne

Clinical development of gene therapy: results and lessons from recent successes.

Therapeutic gene transfer holds the promise of providing lasting therapies and even cures for diseases that were previously untreatable or for which only temporary or suboptimal treatments were available. For some time, clinical gene therapy was characterized by some impressive but rare examples of successes and also several setbacks. However, effective and long-lasting treatments are now being reported from gene therapy trials at an increasing pace. Positive outcomes have been documented for a wide range of genetic diseases (including hematological, immunological, ocular, and neurodegenerativ

DNA Damaging Drugs

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Selenium Compounds as Novel Potential Anticancer Agents.

The high number of new cancer incidences and the associated mortality continue to be alarming, leading to the search for new therapies that would be more effective and less burdensome for patients. As there is evidence that Se compounds can have chemopreventive activity, studies have begun to establish whether these compounds can also affect already existing cancers. This review aims to discuss the different classes of Se-containing compounds, both organic and inorganic, natural and synthetic, and the mechanisms and molecular targets of their anticancer activity. The chemical classes discussed

Evolution of Cancer Pharmacological Treatments at the Turn of the Third Millennium.

The medical history of cancer began millennia ago. Historical findings of patients with cancer date back to ancient Egyptian and Greek civilizations, where this disease was predominantly treated with radical surgery and cautery that were often ineffective, leading to the death of patients. Over the centuries, important discoveries allowed to identify the biological and pathological features of tumors, without however contributing to the development of effective therapeutic approaches until the end of the 1800s, when the discovery of X-rays and their use for the treatment of tumors provided the

Therapeutic potential of alpha-tocopherol in reducing oxidative stress and inflammatory damage after experimental traumatic brain injury and pentylenetetrazol-induced seizures.

The effects of alpha-tocopherol on seizure parameters, locomotor-cognitive functions, inflammatory response, oxidative stress response, histopathological changes, immunohistochemical parameters, and miRNA fold changes were investigated in rats with traumatic brain injury (TBI) and pentylenetetrazol (PTZ)-induced seizures. Sprague-Dawley male rats were randomly divided into three groups: Control (n = 8), TBI + PTZ (n = 10), and TBI + PTZ + tocopherol (n = 10). After inducing TBI in animals using the weight-drop method, increased post-injury seizure susceptibility was achieved by administering s

Pleuropulmonary Changes Induced by Drugs in Patients with Hematologic Diseases

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