Ebola vaccine trials back on track

Annals of the New York Academy of SciencesVolume 890, Issue 1 p. 330-335 Benzamide, a Poly(ADP-Ribose) Polymerase Inhibitor, Is Neuroprotective against Soman-Induced Seizure-Related Brain Damagea H. L. MEIER, Corresponding Author H. L. MEIER Pharmacology Division, US Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, Maryland 21010-5400, USAdAddress for correspondence: Commander, USAMIRCD, Attn.: MCMR-UV-PB (Dr. Meier), 3100 Ricketts Pt. Rd., APG, MD 21010-5400. Fax, 410/436-1960. e-mail, Henry.Meier@AMEDD.Army.MilSearch for more papers by this authorG.P. H. BALLOUGH, G.P. H. BALLOUGH La Salle University, Department of Biology, Philadelphia, Pennsylvania 19141-1199, USASearch for more papers by this authorJ. S. FORSTER, J. S. FORSTER Pharmacology Division, US Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, Maryland 21010-5400, USASearch for more papers by this authorM. G. FILBERT, M. G. FILBERT Pharmacology Division, US Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, Maryland 21010-5400, USASearch for more papers by this author H. L. MEIER, Corresponding Author H. L. MEIER Pharmacology Division, US Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, Maryland 21010-5400, USAdAddress for correspondence: Commander, USAMIRCD, Attn.: MCMR-UV-PB (Dr. Meier), 3100 Ricketts Pt. Rd., APG, MD 21010-5400. Fax, 410/436-1960. e-mail, Henry.Meier@AMEDD.Army.MilSearch for more papers by this authorG.P. H. BALLOUGH, G.P. H. BALLOUGH La Salle University, Department of Biology, Philadelphia, Pennsylvania 19141-1199, USASearch for more papers by this authorJ. S. FORSTER, J. S. FORSTER Pharmacology Division, US Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, Maryland 21010-5400, USASearch for more papers by this authorM. G. FILBERT, M. G. FILBERT Pharmacology Division, US Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, Maryland 21010-5400, USASearch for more papers by this author First published: 06 February 2006 https://doi.org/10.1111/j.1749-6632.1999.tb08010.xCitations: 5Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume890, Issue1NEUROPROTECTIVE AGENTS: FOURTH INTERNATIONAL CONFERENCEDecember 1999Pages 330-335 RelatedInformation

Zika in Africa—the invisible epidemic?

Evaluation of 16 molecular assays for the detection of orthopox and mpox viruses

Purpose: Using the dual ionization chamber (IC) method we compare the neutron and combined gamma + proton (γ+p) components of absorbed dose in water due to secondary radiation produced by passively scattered and uniformly scanned proton beams collimated by a tungsten MLC. Methods: We adapt the dual IC method of mixed field dosimetry for use in measuring the components of absorbed dose due to secondary radiation produced by proton beams. Measurements are performed in water 5 cm beyond the distal edge and 15 cm lateral to the beam isocenter for passively scattered/uniformly scanned proton beams. Beams with ranges of 15 cm or 25 cm and modulation 10 cm (R15M10 and R25M10) are employed, collimated to 10 × 10 cm field size at isocenter with the MLC. Results: Measured neutron dose per primary proton dose ranges from 0.2–0.4 mGy/Gy for R15M10 and 0.3–0.8 mGy/Gy for R25M10 beams. The secondary γ+p dose is 0.3–0.7 mGy/Gy for R15M10 and 0.5–2.0 mGy/Gy for R25M10. Doses are reported here as physical dose without application of a radiation quality factor. Conclusion: The largest difference in secondary radiation dose for the two modalities is seen at 5 cm beyond the distal edge for R15M10, with increases of 40–50% for neutron dose and 20% for γ+p for scattered over scanned beams. For the R25M10 beam the difference is smaller, about 10% higher neutron and γ+p doses for scattered over scanned beams. Outside the beam at 15 cm lateral to isocenter, the γ+p dose dominates the neutron dose and smaller differences are observed between the two beam delivery modalities. This work was supported by the US Army Medical Research and Materiel Command under Contract Agreement No. DAMD17‐W81XWH‐07‐2‐0121. Opinions, interpretations, conclusions and recommendations are those of the author and are not necessarily endorsed by the US Army. This work was supported by the US Army Medical Research and Materiel Command under Contract Agreement No. DAMD17‐W81XWH‐07‐2‐0121. Opinions, interpretations, conclusions and recommendations are those of the author and are not necessarily endorsed by the US Army.

Ebola vaccine trial in west Africa faces criticism

COVID-19 vaccine prioritisation for people with disabilities

An army medical field laboratory presently has the capability of performing standard protocols developed at the US Army Medical Research Institute of Chemical Defense for verification of nerve agent or sulfur mustard exposure. The protocols analyze hydrolysis products of chemical warfare agents using gas chromatography/mass spectrometry. Additionally, chemical warfare agents can produce alkylated or phosphorylated proteins following human exposure that have long biological half-lives and can be used as diagnostic biomarkers of chemical agent exposure. An analytical technique known as matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF/MS) currently is being examined for its potential to analyze these biomarkers. The technique is capable of detecting large biomolecules and modifications made to them. Its fast analysis time makes MALDI-TOF/MS technology suitable for screening casualties from chemical or biological attacks. Basic operation requires minimal training and the instrument has the potential to become field-portable. The limitation of the technique is that the generated data may require considerable expertise from knowledgeable personnel for consultation to ensure correct interpretation. The interaction between research scientists and field personnel in the acquisition of data and its interpretation via advanced digital telecommunication technologies can enhance rapid diagnosis and subsequently improve patient care in remote areas.

Serum GFAP and UCH-L1 for prediction of absence of intracranial injuries on head CT (ALERT-TBI): a multicentre observational study

PURPOSE: We sought to describe cerebrovascular responses to incremental exercise and test the hypothesis that changes in cerebral oxygenation influence maximal performance. METHODS: Eleven men cycled in three conditions: 1) sea level (SL); 2) acute hypoxia (AH: hypobaric chamber, Pbar 460 mmHg); and 3) chronic hypoxia (CH: 4,300 m, Pbar 460 mmHg). At maximal work rate (Wmax), FIO2 was surreptitiously increased to 0.60 while subjects were encouraged to continue pedaling. Changes in cerebral (frontal lobe) and muscle (vastus lateralis) oxygenation (COX, MOX; near infrared spectroscopy), middle cerebral artery blood flow velocity (CBFv; transcranial Doppler) and end-tidal CO2 (PETCO2) were analyzed across %Wmax and condition (α=0.05). RESULTS: At SL, PETCO2, CBFv and COX fell as work rate rose from 75 to 100% Wmax. During AH, PETCO2 and CBFv declined from 50 to 100% Wmax while COX fell from rest. With CH, PETCO2 and COX dropped throughout exercise, while CBFv fell only from 75 to 100% Wmax. MOX fell from rest to 75% Wmax at SL and AH, and throughout exercise in CH. Of note, the magnitude of fall in COX, but not MOX, was different between conditions (CH>AH>SL). FIO2 0.60 at Wmax did not prolong exercise at SL, yet allowed subjects to continue for 96±18 s in AH and 162±27 s in CH. During FIO2 0.60,COX and PETCO2 rose, CBFv fell and MOX remained constant as work rate increased. CONCLUSIONS: Changes in cerebral oxygenation influence maximal exercise performance during hypobaric hypoxia, but are only weakly correlated with PETCO2 and CBFv. Funding provided by US Army Medical Research Materiel Command ATO IV.MD.2006.01. Authors' views; not official U.S. Army or DoD policy.

Man is tactually literate! This has been known for some time-for at least as long as the blind have been known to read with their finger tips scanning Braille symbols. Helen Adams Keller not only reads with her fingers and writes wich them through a typewriter, but also she listens with the skin of her hands and speaks with her fingers in a semiprivate system of encoding and decoding the kinds of informarion ordinarily called or literate, Man's integument can be substituted in linguistic matters for his ears, his eyes, or for both. Geldard (1957) has referred to rhe work of both Gaulc (1936) and Katz (1930, pp. 90-104) who thirty years ago investigated the feasibility of circurnventing deafness by applying sounds directly to the surface of the skin through stimulus-producing electromechanical transducers. Their results, and those of more recent investigations (Wiener, et al., 1949-195 1 ) , suggest that this is not feasible. In spite of the many similarities between hearing and skin sensations-and there are many as Bekesy (1959) has shown-such attempts appear futile in the light of our present knowledge. It does not appear possible to make any simple direct transcriptions of speech-patterned sound energy that when applied to the skin result in meaningful percepts of patterns. The limiting features of the skin seem to be the slowness wich which its nerves react relative to the auditory nerves, and the nonindependence of stimulus frequency and intensity in the cutaneous sense (Anderson & Munson, 1951; Bekesy, 1959; Geldard, 1957). A caution is necessary, however, that this conclusion not be overgeneralized. There is at least one datum to indicate that sounds may be directly perceived through the skin, albeit the sensory transcriptions may nor be simple and direct. Whether complex or simple, cutaneous transcriptions of such speechpatterned sound energies apparently are perceived and interpreted directly as speech in at least one instance! Specifically, Helen Keller is able to interpret that she hears through whatever stimuli act on three fingers--one placed on the throat just over che larynx, one placed just in front of the lips, and the third placed just beside the nose of the speaker. The resulting cutaneous sensations are ap'This paper is based on a presentation made by the author during an invitational research symposium on cutaneous sensitivity held at the US Army Medical Research Laboratory, Fort Knox, Ky., February, 1960. 'The author expresses his appreciation to the Emory University Research Committee for providing funds in support of this publication.

Introduction We recently reported findings from a project that used a form of repetitive transcranial magnetic stimulation (rTMS) known as continuous theta burst stimulation (cTBS) to modulate connectivity within the brain’s Default Mode Network (DMN) as a potential treatment for insomnia. Continuous theta-burst stimulation(cTBS) was used to reduce cortical excitability within the DMN. Our prior analyses showed that the approach significantly improved total sleep time, sleep efficiency, N3 latency, and the arousal index, but rapid eye-movement (REM) did not appear affected. Based on growing evidence that REM sleep may show changes in the third decade and beyond, and that the effects of rTMS may be, at least partially, influenced by age, we further explored the potential effect of age in this dataset. Methods cTBS was administered to a total of 20 participants with self-reported insomnia symptoms (Mage=26.90, SD=6.56). Each participant underwent one round of sham stimulation and one round of active cTBS in a randomized order with one week in between. Participants were monitored with polysomnography (PSG) during a 7-hour sleep window. We first examined the association between age and REM sleep at each visit. A repeated measures ANOVA was employed, incorporating age as a covariate to assess potential age-dependent effects on cTBS effects. Results REM duration was positively correlated with age for the active cTBS visits (r=0.506, p=0.023) but not for the sham (r=-0.059, p= .806). With age as a covariate, the ANOVA revealed a significant effect of TMS treatment on REM sleep duration, F(1,18)=7.507, p=0.013. Participants in the TMS treatment group experienced an increase in REM sleep duration compared to the sham group when age was controlled in the analysis. Conclusion Age significantly influenced the effect of cTBS on REM sleep outcomes. The finding that older individuals demonstrated a greater effect of stimulation on REM duration suggests potential implications for clinical application in individuals with insomnia. Future work may focus on refining therapeutic strategies for sleep modulation, advocating for a personalized and age-aware approach. Support (if any) US Army Medical Research Acquisition Activity Grant: W81XWH2010173

Background: Tissue hypoxia due to reduced tissue perfusion is hallmark pathophysiology of hemorrhagic shock. However, since capillary dysfunction is a common complication during shock, it is unclear whether oxygen diffusion from capillaries to surrounding tissue is also impaired. We hypothesized that oxygen diffusion is impaired during prolonged hemorrhagic shock and that treatment targeting both capillary perfusion and oxygen diffusion can effectively correct tissue hypoxia under hypovolemic conditions. Methods: Male rats were randomized into five groups: Control (saline vehicle), albumin (25%), PEG (polyethylene glycol-20k), XC (PEG + trans-sodium crocetinate), and XCD (XC + 50% dextrose; n = 7-8 for each group). Albumin and PEG were used to enhance capillary perfusion, and trans-sodium crocetinate was applied to increase oxygen diffusion. Trauma was induced in anesthetized (inactin) rats with unilateral muscle injury and fibula fracture, followed by pressure-controlled hemorrhagic shock (mean arterial pressure (MAP) = 55 mmHg) for 45 minutes. Rats then received a single intravenous injection (0.3 ml/kg) of saline, albumin, XC, or XCD. MAP, skeletal muscle perfusion and oxygen partial pressure (PO 2 ), and mortality were monitored for another 2 hours without further resuscitation. The animals were remained under anesthesia and the survived animals were euthanized at the end of the experiment. Results: The hypotensive shock resulted in an about 50% decrease in skeletal muscle capillary perfusion but >80% decrease in the tissue PO 2 compared to the baseline values. Saline had no effect on MAP, tissue perfusion, or PO 2 . All control group animals died approximately one hour after injection with severe hyperlactatemia, hyperkalemia, and renal injury (GFR 0.05 ± 0.01 ml/min/100g with undetectable urinary flow). Survival was markedly improved in all the other treated groups (63% in albumin, 87% in PEG, and 100% in XC and XCD groups). MAP was rapidly improved in albumin, PEG, XC, and XCD groups from 10min to 60min after injection. The capillary flows were similarly improved in these groups to the levels comparable to 85% of baseline for 30 minutes. Tissue PO 2 was slightly and transiently improved (< 50% of baseline for 20 minutes) in albumin and PEG groups, but the increase in PO 2 was more profound and prolonged (up to 75% baseline for 2 hours, P < 0.01) in XC and XCD groups. In addition, the high dose of dextrose in XCD group failed to delay glucose depletion, but the accelerated glycolysis did not increase lactate levels compared to XC group. Conclusion: Our data suggest that tissue hypoxia during hemorrhagic shock is not only due to decreased oxygen delivery but also to impaired oxygen diffusion. XC is effective in maintaining tissue oxygen levels and aerobic metabolism for over 2 hours by improving both tissue perfusion and oxygen diffusion under hypovolemic conditions without resuscitation. Due to its rapid- and long-acting beneficial effects on organ oxygenation, XC may be a potential option to protect organ function and extend survival during prolonged hemorrhagic shock when timely resuscitation with blood and blood products is unavailable. DoD disclaimer: The views expressed in this abstract are those of the author(s) and do not reflect the official policy or position of the U.S. Army Medical Department, Department of the Army, DoD, or the U.S. Government. US Army Medical Research and Development Command This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

Ischemia/reperfusion injury (I/RI) is associated with trauma and various diseases including stroke, heart attack and hemorrhagic shock. This study investigated the extent of DNA damage in an in vitro system of hypoxia/reoxygenation that may be useful for screening for drugs to reduce this form of injury. The usual method of subjecting cells to reduced oxygen (O2) by purging with nitrogen is a slow process and does not reproduce the rapid local reduction in O2 that occurs in vivo during ischemia. Glucose oxidase (GOX), however, rapidly oxidizes extracellular glucose producing a very low O2 level (< 0.4 μM) within 5 min with only minor reductions in glucose levels. We previously showed 10 min of anoxia followed by reoxygenation of human umbilical vein endothelial cells (HUVEC) damaged various biomolecules, such as lipids, proteins, and DNA. In the present study, human umbilical vein endothelial cells (HUVEC) were subjected to GOX‐induced hypoxia for 10 min and returned to medium and normoxia for up to 6 hrs. The most commonly used biomarker of DNA oxidation, in epidemiological as well as experimental studies, is 8‐oxo‐7,8‐dihydro‐2′‐deoxyguanosine (8‐oxodGuo), however this methods requires large amounts of DNA. Here we used a high‐throughput assessment of DNA damage utilizing a high‐sensitivity long‐run real‐time PCR technique for DNA‐damage quantification in both the mitochondrial and nuclear genome. Following hypoxia cells were provided normoxia (3% oxygen) for up to 6 hours, fixed in 50% isopropanol and DNA extracted with DNAzol (MRC, Cincinnati, OH). The isolated DNA was subjected to real‐time polymerase chain reaction (RT‐PCR) with primers designed to amplify large and small regions of mitochondrial and nuclear DNA where the extent of template amplification is inversely proportional to the lesion frequency within a given DNA sequence. Detected lesions per 10kb DNA were determined. Compared to hydrogen peroxide induced DNA damage, the test conditions produced extensive damage to both mitochondrial and nuclear DNA that could readily be detected by 4 and 6 hours. These results were also correlated with HPLC analysis of 8‐oxoguanine that indicated that this biomarker to oxidative stress was enhanced about 50%. This in vitro system of hypoxia/reoxygenation can be used to further understand responses of cells to I/RI and identify drugs and potential therapeutic windows in vitro that may be translated to ameliorate ischemia/reperfusion injury in vivo.Support or Funding InformationFunded by US Army Medical Research Materiel Command

The hypothermia and hemostasis in severe trauma (HYPOSTAT): a new crossroads workshop was convened to evaluate the interplay among hypothermia, hemostasis, and severe trauma/hemorrhage. Trauma is the major cause of death in young individuals in the United States, with uncontrolled hemorrhage representing the major cause of preventable deaths. This workshop organized by the National Heart, Lung, and Blood Institute and the US Army Medical Research and Material Command as a forum for exchange of ideas among experts from diverse fields. The specific workshop goals were to (1) identify state-of-the-art and needs in knowledge of biology of hypothermia and hemostasis in the setting of significant traumatic injury; (2) provide an interdisciplinary forum to enhance knowledge regarding early detection of traumatic shock and monitoring of the level and effect of controlled hypothermia in severe trauma settings; and (3) identify future research directions of the role of therapeutic-oriented hypothermia and hemostasis in trauma with severe blood loss. Not applicable. Expert opinion and literature review. This document provides a summary of the expert opinion and highlights the recommendations that came out of the discussions at this workshop to guide scientific efforts in basic, translational, and clinical research in this area.

BackgroundMalaria is one of the most serious health problems in Kenya. In 2004, the Kenya Medical Research Institute and the US Army Medical Research Unit – Kenya surveyed adults in Samburu, Malindi, and Busia districts to determine socioeconomic risk factors for infection.MethodsSociodemographic, health, and antimalarial data were collected along with blood for malaria testing. A smear was considered negative only if no Plasmodium falciparum parasites were observed in 100 high-powered fields. Univariate analysis was performed with Pearson's Chi-square test and univariate logistic regression. A multivariate logistic regression model was then created which included only variables found to be at least marginally significant in univariate analysis.ResultsA total of 1,141 subjects were recruited: 238 from Samburu, 442 from Malindi, and 461 from Busia. Smear positivities for P. falciparum were 1.7% in Samburu, 7.2% in Malindi and 22.3% in Busia. Interdistrict differences were statistically significant (p < 0.001) in univariate analysis and in a multivariate logistic regression model which included district, literacy, occupation, and recent illness as independent variables. In the model, literacy and recent diarrhoeal illness were positively and at least marginally significantly associated with parasitaemia (p = 0.023 and p = 0.067, respectively). Neither age, sex, occupation, history of malaria in the previous three months, nor use of antimalarials in the previous four weeks were significantly associated with parasitaemia.ConclusionWhile district of residence was the variable most highly predictive for parasitaemia among Kenyan adults surveyed, both a recent history of diarrhoeal illness and literacy were at least marginally statistically significant predictors.