Guidelines to inform the generation of clinically relevant and realistic blast loading conditions for primary blast injury research.

'Primary' blast injuries (PBIs) are caused by direct blast wave interaction with the human body, particularly affecting air-containing organs. With continued experimental focus on PBI mechanisms, recently on blast traumatic brain injury, meaningful test outcomes rely on appropriate simulated conditions. Selected PBI predictive criteria (grouped into those affecting the auditory system, pulmonary injuries and brain trauma) are combined and plotted to provide rationale for generating clinically relevant loading conditions. Using blast engineering theory, explosion characteristics including blast wave parameters and fireball dimensions were calculated for a range of charge masses assuming hemispherical surface detonations and compared with PBI criteria. While many experimental loading conditions are achievable, this analysis demonstrated limits that should be observed to ensure loading is clinically relevant, realistic and practical. For PBI outcomes sensitive only to blast overpressure, blast scaled distance was demonstrated to be a useful parameter for guiding experimental design as it permits flexibility for different experimental set-ups. This analysis revealed that blast waves should correspond to blast scaled distances of 1.75

Defining blast loading 'zones of relevance' for primary blast injury research: A consensus of injury criteria for idealised explosive scenarios.

Blast injuries remain a serious threat to defence and civilian populations around the world. 'Primary' blast injuries (PBIs) are caused by direct blast wave interaction with the human body, particularly affecting air-containing organs. Work to define blast loading conditions for injury research has received relatively little attention, though with a continued experimental focus on PBIs and idealised explosion assumptions, meaningful test outcomes and subsequent clinical applications, rely on appropriate simulated conditions. This paper critically evaluates and combines existing PBI criteria (grouped into those affecting the auditory system, pulmonary injuries and brain trauma) as a function of idealised blast wave parameters. For clinical blast injury researchers, analysis of the multi-injury criteria indicates zones of appropriate loading conditions for human-scale test items and demonstrates the importance of simulating blast conditions that are both realistic and relevant to the injury type. For certain explosive scenarios, spatial interpretation of the 'zones of relevance' could support emergency response and hazard preparedness by informing triage, patient management and resource allocation, thus leading to improved health outcomes. This work will prove useful to clinical blast injury researchers, blast protection engineers and clinical practitioners involved in the triage, diagnosis, and treatment of PBIs.

Fluorescent tagging for environmental surface cleaning surveillance in a veterinary hospital.

OBJECTIVES: To evaluate the use of fluorescent tagging for environmental surface cleaning surveillance in a small animal veterinary hospital and identify factors associated with tag removal. MATERIALS AND METHODS: Over 5.5 weeks, a commercial fluorescent dye (Glo Germ) was used to tag (mark) surfaces in a small animal veterinary teaching hospital. Twenty-four hours after tagging, cleaning was assessed with a black light (UV-A source). Surfaces were recorded as cleaned based on complete removal of fluorescent tagging at assessment. Proportions cleaned were calculated overall and by predictors (i.e. surface location/type, primary nature of surface contact - animal/human, week of study). RESULTS: A total of 4984 surfaces were tagged and assessed. Overall cleaning was 50%. Cleaning varied by surface/object (range: 2 to 100%) and hospital location (4 to 78%). Surfaces designated as having primarily animal contact were cleaned more frequently than those with primarily human contact (75%, 42%; P<0.001). Cleaning varied over the study period (range by week: 45 to 54%;); a significant trend was not identified. CLINICAL SIGNIFICANCE: Key surfaces in the small animal veterinary practice environment are unlikely to be adequately cleaned, posing a concern for animal and human health. Commercial products can be effectively used to asses environmental cleaning with findings used to target clinic-specific barriers to improve cleaning and reduce hospital-associated infections.

Applying Organizational Health Literacy to Maternal and Child Health.

Purpose Describe the development of an innovative teaching activity that applies organizational health literacy to maternal and child health (MCH). Description Health literacy is a strong predictor of health behavior and outcomes. While the study of health literacy has traditionally been confined to skills and capacities of individuals, the significant role of the social and physical environmental contexts in facilitating or hindering one's ability to obtain, understand, and make informed decision about their health has been recognized. MCH organizations play a critical role in influencing health literacy across system levels. This teaching activity aims to equip students with knowledge and skills needed to foster organizational health literacy. Assessment The teaching activity is assembled within a toolkit which includes the following: (1) instructor lesson plan; (2) interactive PowerPoint presentation with instructor notes; (3) field assignment description; (4) health literacy attribute assessment worksheets; and (5) grading rubric. The teaching tool was pilot tested by a student research team member to assess the educational value and assignment logistics, resulting in minor edits (i.e., addition of interviewer probes, and option of a group project-format to permit triangulation of multiple organizational interviews). Conclusion The field of MCH is expanding in complexity, and the demands of health systems on women, children, and families must be mediated by conscious efforts within organizations. Through teaching the importance and function of organizational health literacy to students in MCH, educators can prepare an emerging workforce to improve health literacy, and ultimately the quality of healthcare for women, children, and families.

Perceptions of Zika Virus Prevention Among College Students in Florida.

Zika virus in Florida prompted a strong public health response, due to its causal association with birth defects. While primarily spread by mosquitos, Zika can be transmitted sexually. The spread of Zika may influence reproductive behaviors among sexually active persons in Florida. This study examined factors associated with willingness to change birth control method use in response to Zika virus among college women and men in Florida. Women and men ages 18-44 at a Florida university (N = 328) were surveyed about Zika knowledge, beliefs about Zika, use of contraceptives and condoms, and socio-demographics between November 2016-April 2017. The outcome variable was willingness to change birth control method were Zika in their area. Logistic regression models in SAS 9.4 were used. Most participants were women (80%), and 47% were 20-22 years old. Only 27% of participants said they would change their birth control method if Zika were in their area. Participants who knew that Zika was sexually transmitted were more likely to be willing to change their birth control method (aOR = 1.71, 95%CI 1.01-2.91). Participants who agreed or strongly agreed that they were fearful of being infected with Zika virus were more likely to be willing to change their birth control methods (aOR = 1.98, 95%CI 1.07-3.67). This study found that, among Florida college students, Zika beliefs and knowledge were associated with a willingness to change birth control method in response to Zika. Understanding the factors that motivate individuals to change reproductive behaviors during an emerging health issue can help tailor preventative messages.

Using a Health Literacy Analytic Framework to Explore Zika Virus and Reproductive Health.

BACKGROUND: The emergence of Zika virus as sexually transmissible and associated with birth defects may affect reproductive planning and contraception use for people in Florida. OBJECTIVE: This exploratory study employed a health literacy analytic framework to explore knowledge, attitudes, beliefs, and behaviors related to reproductive health in the context of Zika among reproductive-age women and men in Florida. METHODS: Reproductive-age people in Florida (N = 40) were interviewed between September and December 2016 about their knowledge, attitudes, beliefs, and behaviors regarding Zika and reproductive health. Thematic analysis using a health literacy framework was employed. KEY RESULTS: Participants reported they would use reputable online sources to access Zika information. Whereas participants generally understood Zika outcomes, transmission, and symptoms, they reported hearing more prevention messages on mosquito transmission compared to sexual transmission. Overall, participants reported Zika was not concerning given their appraisal of personal circumstances. Participants were confident they could prevent Zika via sexual transmission despite not following the recommended guidelines. Participants discussed how their understanding of Zika changed their behaviors related to mosquito control but not through sexual transmission. CONCLUSIONS: This study illustrated a disconnect between reproductive-age people's understanding of Zika-related prevention information and their reproductive decision-making behavior. Strategies to promote appraisal of risk for sexual transmission of Zika, infection, and unintended pregnancy are needed. [HLRP: Health Literacy Research and Practice. 2018;2(2):e78-e87.]. PLAIN LANGUAGE SUMMARY: Men and women of reproductive age in Florida may be at risk for Zika virus and related negative health outcomes. This study assessed how Florida men and women find, understand, and evaluate Zika-related health information, and how that applies to their prevention behaviors. This study used health literacy as an analytic framework for an emerging health issue.

Racial disparities in cord blood vitamin D levels and its association with small-for-gestational-age infants.

OBJECTIVE: To examine the relationship of race and maternal characteristics and their association with cord blood vitamin D levels and small-for-gestational-age (SGA) status. STUDY DESIGN: Cord blood vitamin D levels were measured in 438 infants (276 black and 162 white). Multivariable logistic regression models were used to evaluate associations between maternal characteristics, vitamin D status and SGA. RESULTS: Black race, Medicaid status, mean body mass index at delivery and lack of prenatal vitamin use were associated with vitamin D deficiency. Black infants had 3.6 greater adjusted odds (95% confidence interval (CI): 2.4, 5.6) of vitamin D deficiency when compared with white infants. Black infants with vitamin D deficiency had 2.4 greater adjusted odds (95% CI: 1.0, 5.8) of SGA. Vitamin D deficiency was not significantly associated with SGA in white infants. CONCLUSION: Identification of risk factors (black race, Medicaid status, obesity and lack of prenatal vitamin use) can lead to opportunities for targeted prenatal vitamin supplementation to reduce the risk of neonatal vitamin D deficiency and SGA status.

The use of beat-to-beat electrocardiogram analysis to distinguish QT/QTc interval changes caused by moxifloxacin from those caused by vardenafil.

QT correction factors (QTc) can cause errors in the interpretation of drug effects on cardiac repolarization because they do not adequately differentiate changes when heart rate or autonomic state deviates from the baseline QT/RR interval relationship. The purpose of our study was to determine whether the new method of QT interval dynamic beat-to-beat (QTbtb) analysis could better discriminate between impaired repolarization caused by moxifloxacin and normal autonomic changes induced by subtle reflex tachycardia after vardenafil. Moxifloxacin produced maximum mean increases of 13-14 ms in QTbtb, QTcF, and QTcI after 4 h. After vardenafil administration, a 10-ms effect could be excluded at all time points with QTbtb but not with QTcF or QTcI. Subset analysis of the vardenafil upper pharmacokinetic quartile showed that the upper bound of QTcF and QTcI was >10 ms, whereas that of QTbtb was <8 ms. This study demonstrated that newer methods of electrocardiogram (ECG) analysis can differentiate changes in the QT interval to improve identification of proarrhythmia risk.

Th2 cytokines are associated with persistent hepatic fibrosis in human Schistosoma japonicum infection.

We conducted a prospective cohort study in Leyte, the Philippines, among 611 Schistosoma japonicum-infected participants 7-30 years old, all of whom were treated with praziquantel at baseline. To detect hepatic fibrosis, abdominal ultrasound was performed at baseline and 12 months after treatment. Stool for assessment of S. japonicum infection was collected at baseline and at 3, 6, 9, and 12 months after treatment. Cytokines (interleukin [IL]-4, IL-5, IL-10, IL-13, tumor necrosis factor- alpha , and interferon- gamma ) produced by peripheral-blood mononuclear cells in response to soluble worm antigen preparation (SWAP), soluble egg antigen (SEA), and control medium were measured once 4 weeks after treatment. IL-4 to SWAP and IL-10 to both SWAP and SEA were associated with the presence of baseline fibrosis after adjustment for potential confounding variables (P<.03, for all). In participants with fibrosis at baseline, IL-4 to SWAP and IL-5 and IL-13 to both SWAP and SEA were associated with persistent fibrosis at 12 months after treatment (P<.05, for all). Males showed consistently stronger T helper 2 (Th2) cytokine responses to both SWAP and SEA than did females (P<.02, for all). These results suggest an independent role for Th2-biased cytokine responses to S. japonicum antigens in persistent hepatic fibrosis and indicate that Th2 cytokines may contribute to the male-biased prevalence of fibrosis.

Monitoring the ingestion of anti-tuberculosis drugs by simple non-invasive methods.

This investigation retrospectively assessed inexpensive non-invasive qualitative methods to monitor the ingestion of anti-tuberculosis drugs isoniazid, rifampicin and rifapentine. Results showed that commercial test strips detected the isoniazid metabolites isonicotinic acid and isonicotinylglycine as efficiently as the isonicotinic acid method in 150 urine samples. The presence of rifamycins in urine samples (n=1085) was detected by microbiological assay techniques and the sensitivity compared to the n-butanol extraction colour test in 91 of these specimens. The proportions detected by the two methods were significantly different and the sensitivity of the n-butanol procedure was only 63.8% (95% CL 51.2-76.4%) as compared to that of the superior microbiological method. Final validation (n=691) showed that qualitative assays measure isoniazid and rifamycin ingestion with an efficiency similar to high-performance liquid chromatography. The qualitative procedures may therefore be valuable in clinical trials and in tuberculosis clinics to confirm drug ingestion.

Consecutive-dose pharmacokinetics of rifapentine in patients diagnosed with pulmonary tuberculosis.

OBJECTIVE: To characterise the pharmacokinetics of two consecutive doses of rifapentine (RPT) in patients diagnosed with pulmonary tuberculosis at a South African hospital. DESIGN: Forty-five patients received RPT doses of 600, 750 and 900 mg, based on body weight, after receiving a soup-based meal. Doses were administered to each subject on study days 1 and 5. All patients had already received not less than 4 weeks and not more than 6 weeks of standard antimycobacterial therapy (including isoniazid, rifampicin, pyrazinamide and ethambutol). Serial blood samples were collected between 0 and 72 h post-dose. RPT and 25-desacetyl-RPT concentrations were determined using validated high performance liquid chromatography methods. The plasma concentration-time data were analysed using a noncompartmental approach and compared to healthy volunteer data from a previous study. RESULTS: Median peak plasma concentrations for RPT in the patient cohort were 15.19 and 15.48 microg/ml on study days 1 and 5, respectively. Time to reach these concentrations was 5.00 and 5.08 h and plasma elimination half-lives were 11.63 and 12.03 h, respectively. Areas under the plasma concentration-time curve (0-72 h) were 355.81 and 371.89 microg x h/ml on the two occasions, respectively. CONCLUSION: A 15 mg/kg dose of RPT was well absorbed and well tolerated. The variability observed between individuals and between occasions was small, and similar to that seen in data from previous studies in healthy volunteers.

Anabaena apoflavodoxin hydrogen exchange: on the stable exchange core of the alpha/beta(21345) flavodoxin-like family.

An important issue in modern protein biophysics is whether structurally homologous proteins share common stability and/or folding features. Flavodoxin is an archetypal alpha/beta protein organized in three layers: a central beta-sheet (strand order 21345) flanked by helices 1 and 5 on one side and helices 2, 3, and 4 on the opposite side. The backbone internal dynamics of the apoflavodoxin from Anabaena is analyzed here by the hydrogen exchange method. The hydrogen exchange rates indicate that 46 amide protons, distributed throughout the structure of apoflavodoxin, exchange relatively slowly at pH 7.0 (k(ex) < 10(-1) min(-1)). According to their distribution in the structure, protein stability is highest on the beta-sheet, helix 4, and on the layer formed by helices 1 and 5. The exchange kinetics of Anabaena apoflavodoxin was compared with those of the apoflavodoxin from Azotobacter, with which it shares a 48% sequence identity, and with Che Y and cutinase, two other alpha/beta (21345) proteins with no significant sequence homology with flavodoxins. Both similarities and differences are observed in the cores of these proteins. It is of interest that a cluster of a few structurally equivalent residues in the central beta-strands and in helix 5 is common to the cores.

Bacteriocin AS-48, a microbial cyclic polypeptide structurally and functionally related to mammalian NK-lysin.

The solution structure of bacteriocin AS-48, a 70-residue cyclic polypeptide from Enterococcus faecalis, consists of a globular arrangement of five alpha-helices enclosing a compact hydrophobic core. The head-to-tail union lies in the middle of helix 5, a fact that is shown to have a pronounced effect on the stability of the three-dimensional structure. Positive charges in the side chains of residues in helix 4 and in the turn linking helix 4 to helix 5 form a cluster that most probably determine its antibacterial activity by promoting pore formation in cell membranes. A similar five-helix structural motif has been found in the antimicrobial NK-lysin, an effector polypeptide of T and natural killer (NK) cells. Bacteriocin AS-48 lacks the three disulfide bridges characteristic of the saposin fold present in NK-lysin, and has no sequence homology with it. Nevertheless, the similar molecular architecture and high positive charge strongly suggest a common mechanism of antibacterial action.

Sequence-specific 1H assignment and secondary structure of the bacteriocin AS-48 cyclic peptide.

The bacteriocin AS-48 is a cationic peptide (7149 Da) having a broad antimicrobial spectrum, encoded by the 68 kb conjugative plasmid pMB2 from Enterococcus faecalis S-48. It is a unique peptide since it has a cyclic structure, which is achieved by the formation of a tail-head peptide bond after ribosomal synthesis (Gálvez et al., 1989; Martínez-Bueno et al., 1994; Samyn et al., 1994). Preliminary CD and calorimetric studies (data not shown) pointed towards a highly helical and very stable three dimensional structure. All the information gathered until now indicates that the target of AS-48 is the cytoplasmic membrane in which it opens channels or pores, leading to dissipation of the proton motive force and cell death, which in some cases is also followed by bacterial lysis (Gálvez et al., 1991). This peptide is a suitable tool for studying protein-membrane interactions, and it also offers promising perspectives for biotechnological applications. Knowledge of the 3D structure of AS-48 is a first step in the conduct of further structure-function studies. Here we report the complete 1H NMR assignment of its proton resonances together with the resulting secondary structure pattern as prerequisites for the determination of a high-resolution 3D solution structure.

Cooperative stabilization of a molten globule apoflavodoxin fragment.

We have destabilized apoflavodoxin by site-specific excision of its C-terminal helix. The resulting flavodoxin fragment (Fld1-149) is compact and monomeric at pH 7.0, with spectroscopic properties of a molten globule and a low conformational stability. To study if Fld1-149 is cooperatively stabilized, we have measured the equilibrium urea unfolding by fluorescence, circular dichroism, and size-exclusion chromatography. The three techniques produced coincident unfolding curves. Furthermore, the thermal unfolding seems also to be cooperative as the same temperature of half-denaturation is obtained using fluorescence and circular dichroism. Fld1-149 displays cold denaturation. The equilibrium properties of Fld1-149 demonstrate that molten globules lacking well-defined tertiary interactions can still be cooperatively stabilized and that cooperatively may appear in protein conformations of very low stability. This suggests that protein folding intermediates, can, in principle, be cooperatively stabilized.

Comments on "Probability estimation in arithmetic and adaptive-Huffman entropy coders".

This comment points out some omissions in the work of Duttweiler and Chazmas (see ibid., vol.4, p.237, 1995) on credit related to scaled-count estimators that perform count-scaling when the count of the less probable symbol (LPS) reaches a limiting value.

Identification and changes in concentrations of prostaglandin H synthase (PGHS) isoforms in rat myometrium at parturition.

The isoform(s) of prostaglandin H synthase (PGHS) present in pregnant rat myometrium have been identified and the ontogeny of their expression studied during late gestation and parturition. Concentrations of PGHS have been related to changes in concentration of nuclear and cytosolic estrogen (ER) and progesterone receptors (PR) occurring at this time. Nuclear PR concentrations were maximal on days 16-18 of pregnancy, decreased from days 18 to 22 (delivery) and fell 24 hours postpartum. Nuclear ER concentrations increased significantly from days 20 to 22 of pregnancy and fell postpartum. Whereas the ratio of nuclear ER/PR was firmly in favour of progesterone action on days 16-20 it increased on day 22 corresponding to increased estrogen action. Western immunoblotting with specific antibodies revealed a single 72 kDa PGHS-1 isoform in myometrium at each timepoint. There was no evidence for the inducible PGHS-2 isoform in myometrium. Densitometric analysis showed the concentration of PGHS-1 increased significantly from day 16 to a maximum at the time of delivery on day 22 and decreased immediately afterwards. Expression of the constitutive PGHS-1 isoform is associated with the changing ratio of nuclear ER/PR and may therefore be hormonally regulated.

Constitutive calcium-dependent isoform of nitric oxide synthase in the human placental villous vascular tree.

We have characterized the NO synthase enzyme in the villous vasculature of the human placenta as part of our ongoing studies of the regulation of NO synthesis in this circulation. NO synthase activity was determined by conversion of 3H L-arginine to 3H L-citrulline in cellular homogenate, cytosolic and particulate fractions. Optimal NO synthase activity was measured in all fractions in the presence of 1 mM NADPH, 10 microM tetrahydrobiopterin, 2 microM FAD, 100 microM free calcium and 50 U/ml calmodulin. The calmodulin inhibitor calmidazolium (50 microM) and FAD inhibitor diphenyliodonium chloride (1 microM) significantly reduced enzyme activity. The EC50 for calcium was 0.1 microM and Km for L-arginine 2.00 +/- 0.49 microM with Vmax 55.8 +/- 28.3 pmoles/mg protein/min. Enzyme activity was inhibited in both cytosolic and particulate fractions by ng-nitro-L-arginine and ng-monomethyl-L-arginine in a concentration-dependent manner (10(-8)-10(-4) M). A calcium-independent NO synthase activity was also determined, but only constituted between 5-6 per cent of total activity. On Western blotting, a single 135 kda species was identified in each fraction with a monoclonal antibody raised against bovine aortic endothelial NO synthase. The NO synthase enzyme of the villous vasculature appears to correspond to the type III calcium-calmodulin dependent endothelial isoform.

Attenuation of the vasoconstrictor effects of thromboxane and endothelin by nitric oxide in the human fetal-placental circulation.

OBJECTIVE: We hypothesized that the endothelial-derived relaxing factor nitric oxide may contribute to low resting vascular tone and may attenuate vasoconstrictor action in the human fetal-placental circulation. STUDY DESIGN: Isolated human placental cotyledons were dually perfused in vitro, and the effects of N-monomethyl-L-arginine and N-nitro-L-arginine (3 x 10(-4) mol/L), which are nonmetabolizable analogs of L-arginine, the substrate for nitric oxide synthase, on resting perfusion pressure and on the fetal-placental circulation preconstricted with U46619 (10(-8) mol/L) or endothelin-1 (10(-8) mol/L) were established. Responses before and after inhibition were compared by paired t test. The effects of glyceryl trinitrate (10(-6) mol/L), acetylcholine (10(-4) mol/L), the calcium ionophore A23187 (10(-6) mol/L), and histamine (10(-8) to 10(-4) mol/L) were also determined in the preconstricted fetal-placental circulation. RESULTS: Both N-monomethyl-L-arginine and N-nitro-L-arginine (3 x 10(-4) mol/L) increased resting perfusion pressure (p less than 0.06), and N-nitro-L-arginine promptly and significantly increased perfusion pressure in the fetal-placental circulation preconstricted with U46619 (p less than 0.0004) or endothelin-1 (p less than 0.06). Nitric oxide generated by addition of glyceryl trinitrate (10(-6) mol/L) attenuated the vasoconstrictor effects of U46619 (p less than 0.026) or endothelin-1 (p less than 0.01). Neither acetylcholine nor the calcium ionophore A23187 had an effect on the fetal-placental circulation, whereas bradykinin further increased perfusion pressure. Histamine only relaxed the preconstricted preparations at concentrations (10(-6) to 10(-4) mol/L) above those shown to release nitric oxide in other systems. CONCLUSION: The stimulus to nitric oxide generation in the fetal-placental circulation may be hydrodynamic. Nitric oxide appears to contribute to maintenance of basal vascular tone and to attenuate the actions of vasoconstrictors in this circulation.

Endothelin-1-induced vasoconstriction is not mediated by thromboxane release and action in the human fetal-placental circulation.

The vasoconstrictor peptide endothelin-1 (8 x 10(-10) to 1 x 10(-8) mol/L) significantly increased fetal-placental perfusion pressure in vitro in a cumulative manner from 30 +/- 2 to 123 +/- 25 mm Hg (mean +/- SEM, n = 5, p less than 0.0005, analysis of variance). Accompanying this vasoconstriction was a corresponding reduction in fetal-placental perfusate flow rate. Measurement of thromboxane B2 and 6-keto-prostaglandin F1 alpha in the fetal-placental perfusate revealed a significant reduction in their release (p less than 0.0096 and p less than 0.0004, analysis of variance, respectively) when corrected for flow rate. Neither the thromboxane synthesis inhibitor dazoxiben (10(-6) mol/L) nor the thromboxane receptor antagonist SQ29548 (10(-6) mol/L) was able to block the vasoconstrictor actions of endothelin-1. Therefore endothelin-1-induced vasoconstriction in the human fetal-placental circulation does not appear to be mediated by thromboxane release or action. The stimulus to eicosanoid release in the fetal-placental circulation may be hydrodynamic, i.e., flow or shear stress.