Antibody contributes to heterosubtypic protection against influenza A-induced tachypnea in cotton rats

<p>Abstract</p> <p>Background</p> <p>Influenza virus infection or vaccination evokes an antibody response to viral hemagglutinin (HA) and neuraminidase (NA) surface glycoproteins, which results in immunity against influenza A viruses of the same HA and NA subtype. A heterosubtypic immune response that offers some protection against different influenza A subtypes has been suggested from epidemiologic studies in human influenza outbreaks, and has been induced in experimental animal models. Original studies of such cross-protection showed that cytotoxic T lymphocytes (CTL) protect H3N2-immune mice from a lethal H1N1 infection. More recent studies in mice demonstrate that antibodies also contribute to heterosubtypic immunity (HSI). We previously demonstrated that HSI in cotton rats (<it>Sigmodon hispidus</it>) is characterized by protection of H3N2-immune animals from influenza H1N1-induced increase in respiratory rate (tachypnea). Alternatively, H1N1-immune animals are protected from H3N2-induced tachypnea. The experiments described in this report were designed to elucidate the immune mechanism that prevents this very early sign of disease.</p> <p>Results</p> <p>Our results show that cotton rats provided with H1N1-immune serum prior to challenge with an H3N2 virus were protected from influenza-associated tachypnea, with the degree of protection correlating with the antibody titer transferred. Immunization with an inactivated preparation of virus delivered intramuscularly also provided some protection suggesting that CTL and/or mucosal antibody responses are not required for protection. Antibodies specific for conserved epitopes present on the virus exterior are likely to facilitate this protection since prophylactic treatment of cotton rats with anti-M2e (the extracellular domain of M2) but not anti-nucleoprotein (NP) reduced virus-induced tachypnea.</p> <p>Conclusion</p> <p>In the cotton rat model of heterosubtypic immunity, humoral immunity plays a role in protecting animals from influenza-induced tachypea. Partial protection against respiratory disease caused by different influenza A subtypes can be attained with either live virus administered intranasally or inactivated virus delivered intramuscularly suggesting that either vaccine regimen may provide some protection against potential pandemic outbreaks in humans.</p

Water in Mid Ocean Ridge Basalts: Some Like it Hot, Some Like it Cold

The presence in the Earth’s mantle of even small amounts of water and other volatiles has major effects: first, it lowers drastically mantle’s viscosity, thereby facilitating convection and plate tectonics; second, it lowers the melting temperature of the rising mantle affecting the formation of the oceanic crust. H2O concentration in oceanic basalts stays below 0.2 wt% except for basalts sampled near “hot spots” that contain significantly more H2O than normal MORB, implying that their mantle plume sources are unusually H2O-rich. Basalts sampled in the Equatorial Atlantic close to the Romanche transform, a thermal minimum in the Ridge system, have a H2O content that increases as the ridge is cooled approaching the transform offset. These basalts are Na-rich, being generated by low degrees of melting of the mantle, and contain unusually high ratios of light versus heavy rare earth elements implying the presence of garnet in the melting region. H2O enrichment is due not to an unusually H2O-rich mantle source, but to a low extent of melting of the upwelling mantle, confined to a deep wet melting region. Numerical models predict that this wet melting process takes place mostly in the mantle zone of stability of garnet. This prediction is verified by the geochemistry of our basalts showing that garnet must indeed have been present in their mantle source. Thus, oceanic basalts are H2O-rich not only near “hot spots”, but also at “cold spots”

Petrology, Mineral and Isotope Geochemistry of the External Liguride Peridotites (Northern Apennines, Italy)

Mantle peridotites of the External Liguride (EL) units (Northern Apennines) represent slices of subcontinental lithospheric mantle emplaced at the surface during early stages of rifting of the Jurassic Ligurian Piemontese basin. Petrological, ion probe and isotopic investigations have been used to unravel the nature of their mantle protolith and to constrain the timing and mechanisms of their evolution. EL peridotites are dominantly fertile spinel Iherzolites partly recrystallizfd in the plagiodase Iherzplite stability field Clinopyroxenes stable in the spinel-facies assemblage have nearly fiat REE patterns (CeN/SmN=0·6-0·8) at (10-16)×C1 and high Na, Sr, Ti and Zr contents. Kaersutitic-Ti-pargasitic amphiboles also occur in the spinel-facies assemblage. Their LREE-depleted REE spectra and very low Sr, Zr and Ba contents indicate that they crystallized from hydrous fluids with low concentrations of incompatible elements. Thermometric estimates on the spinelfacies parageneses yield lithospheric equilibrium temperatures in the range 1000-1100°C, in agreement with the stability of amphibole, which implies T<1100°C. Sr and Nd isotopic compositions, determined on carefully handpicked clinopyroxene separates, plot within the depleted end of the MORB field (87Sr/86Sr=0·70222-0·70263; 143Nd/144Nd=0·513047-0·513205) similar to many subcontinental orogenic spinel Iherzolites from the western Mediterranean area (e.g. Ivrea Zpne and Lanzfl N). The interpretation of the EL Iherzolites as subcontinental lithospheric mantle is reinforced by the occurrence of one extremely depleted isotopic composition (87Sr/86Sr=0·701736; 143Nd/144Nd=0·513543). Sr and Nd model ages, calculated assuming both CHUR and DM mantle sources, range between 2·4 Ga and 780 Ma. In particular, the 1·2-Ga Sr age and the 780-Ma Nd age can be regarded as minimum ages of differentiation. The transition from spinel-to plagioclase-facies assemblage, accompanied by progressive deformation (from granular to tectonite-mylonite textures), indicate that the EL Iherzolites experienced a later, subsolidus decompressional evolution, starting from subcontinental lithospheric levels. Sm/Nd isochrons on plagioclase-clinopyroxene pairs furnish ages of ∽165 Ma. This early Jurassic subsolidus decompressional history is consistent with uplift by means of denudation in response to passive and asymmetric lithospheric extension. This is considered to be the most suitable geodynamic mechanism to account for the exposure of huge bodies of subcontinental lithospheric mantle during early stages of opening of an oceanic basi

A stepped-care approach to symptomatic endometriosis management : A participatory research initiative

Objective: To assess the proportion of patients with symptomatic endometriosis satisfied with their medical treatment 12 months after enrollment in a stepped-care management protocol. Design: Prospective, single-arm, self-controlled study. Setting: Academic department. Patient(s): A cohort of 157 consecutive patients referred or self-referred to our center for symptomatic endometriosis. Interventions(s): Systematic detailed information process on medical and surgical treatment followed by a shared decision to start a stepped-care protocol including three subsequent medical therapy steps (oral contraception [OC]; 2.5 mg/d norethindrone acetate [NETA]; 2 mg/d dienogest [DNG]) and a fourth surgical step. Stepping up was triggered by drug inefficacy/intolerance. Main Outcome Measure(s): Satisfaction with treatment was assessed according to a five-category scale (very satisfied, satisfied, neither satisfied nor dissatisfied, dissatisfied, very dissatisfied). Variations were measured in pain symptoms with the use of a 0\u201310-point numeric rating scale (NRS), in quality of life with the use of the Short Form 12 questionnaire (SF-12), and in sexual functioning with the use of the Female Sexual Function Index (FSFI). Result(s): At the end of the 12-month study period, 106 women were still using OC, 23 were using NETA, three were using DNG, and four had undergone surgery. Twenty-one participants (13%) dropped out from the study. In intention-to-treat analysis, excluding five drop-outs for pregnancy desire, the overall satisfaction rate with the stepped-care protocol was 62% (95/152; 95% CI 55%\u201370%). By 12-month follow-up, significant improvements were observed in all pain symptom scores and in SF-12 physical and mental component summary scores, whereas FSFI scores did not vary substantially. Conclusion(s): Most women with endometriosis-associated pelvic pain who chose a stepped-care approach were satisfied with OC and a low-cost progestin for the treatment of their symptoms. The need to step up to an expensive progestin or surgery was marginal

Wound care challenges in children and adults with spina bifida: An open-cohort study

Skin breakdown is a frequent concern for individuals with spina bifida. We explored wound incidence in patients with spina bifida and how it varies across a person\u27s life span and functional neurologic level. We examined the settings in which skin breakdown most commonly occurred, looking for evidence of chronic, non-healing wounds. We also sought to develop criteria to improve wound monitoring. We identified reported wound episodes in an open-cohort study over a 13-year period, examining the hospital and outpatient clinical records of spina bifida patients at Children\u27s National Medical Center (CNMC). Current age, age at wound presentation, sex, weight, functional neurologic level, wound location, setting in which the wound was acquired, the development of a chronic wound, and presence of a shunt were recorded. Of the 376 patients in our clinical population, 123 (average age: 18.8 years, range: infancy–56 years) developed a total of 375 wounds; the majority of patients who developed one wound went on to develop one or more additional wounds, and 20 patients developed chronic wounds. Our data suggest that age bracket (adolescents), wheelchair use, and bare feet, as well as possibly obesity and reduced executive functioning, are key risk factors for wound development. These findings have led to a focused effort to increase wound education and prevention. In addition we report on our early experience using a wound care specialist to champion this initiative

Virtual Reality for Pediatric Sedation: A Randomized Controlled Trial Using Simulation.

INTRODUCTION: Team training for procedural sedation for pediatric residents has traditionally consisted of didactic presentations and simulated scenarios using high-fidelity mannequins. We assessed the effectiveness of a virtual reality module in teaching preparation for and management of sedation for procedures. METHODS: After developing a virtual reality environment in Second Life® (Linden Lab, San Francisco, CA) where providers perform and recover patients from procedural sedation, we conducted a randomized controlled trial to assess the effectiveness of the virtual reality module versus a traditional web-based educational module. A 20 question pre- and post-test was administered to assess knowledge change. All subjects participated in a simulated pediatric procedural sedation scenario that was video recorded for review and assessed using a 32-point checklist. A brief survey elicited feedback on the virtual reality module and the simulation scenario. RESULTS: The median score on the assessment checklist was 75% for the intervention group and 70% for the control group (P = 0.32). For the knowledge tests, there was no statistically significant difference between the groups (P = 0.14). Users had excellent reviews of the virtual reality module and reported that the module added to their education. CONCLUSIONS: Pediatric residents performed similarly in simulation and on a knowledge test after a virtual reality module compared with a traditional web-based module on procedural sedation. Although users enjoyed the virtual reality experience, these results question the value virtual reality adds in improving the performance of trainees. Further inquiry is needed into how virtual reality provides true value in simulation-based education

Birth of an ocean in the Red Sea: Initial pangs

We obtained areal variations of crustal thickness, magnetic intensity, and degree of melting of the sub- axial upwelling mantle at Thetis and Nereus Deeps, the two northernmost axial segments of initial oceanic crustal accretion in the Red Sea, where Arabia is separating from Africa. The initial emplacement of oceanic crust occurred at South Thetis and Central Nereus roughly $2.2 and$2 Ma, respectively, and is taking place today in the northern Thetis and southern Nereus tips. Basaltic glasses major and trace element com- position suggests a rift-to-drift transition marked by magmatic activity with typical MORB signature, with no contamination by continental lithosphere, but with slight differences in mantle source composition and/or potential temperature between Thetis and Nereus. Eruption rate, spreading rate, magnetic intensity, crustal thickness and degree of mantle melting were highest at both Thetis and Nereus in the very initial phases of oceanic crust accretion, immediately after continental breakup, probably due to fast mantle upwelling enhanced by an initially strong horizontal thermal gradient. This is consistent with a rift model where the lower continental lithosphere has been replaced by upwelling asthenosphere before continental rupturing, implying depth-dependent extension due to decoupling between the upper and lower lithosphere with man- tle-lithosphere-necking breakup before crustal-necking breakup. Independent along-axis centers of upwell- ing form at the rifting stage just before oceanic crust accretion, with buoyancy-driven convection within a hot, low viscosity asthenosphere. Each initial axial cell taps a different asthenospheric source and serves as nucleus for axial propagation of oceanic accretion, resulting in linear segments of spreading

The role of cryptotephra in refining the chronology of Late Pleistocene human evolution and cultural change in North Africa

© 2014.Sites in North Africa hold key information for dating the presence of Homo sapiens and the distribution of Middle Stone Age (MSA), Middle Palaeolithic (MP) and Later Stone Age (LSA) cultural activity in the Late Pleistocene. Here we present new and review recently published tephrochronological evidence for five cave sites in North Africa with long MSA/MP and LSA cultural sequences. Four tephra horizons have been identified at the Haua Fteah (Cyrenaica, Libya). They include cryptotephra evidence for the Campanian Ignimbrite (CI) eruption dating to ~39 ka that allows correlation with other Palaeolithic sequences in the eastern Mediterranean and as far north as Russia. Cryptotephra have also been recorded from the Moroccan sites of Taforalt, Rhafas and Dar es-Soltane 1. At Taforalt the geochemical composition suggests a provenance in the Azores, while examples from Sodmein (Egypt) appear to derive from central Anatolia and another unknown source. In these latter examples chemical compositional data from relevant proximal volcanic centres is currently lacking so the identification of tephra in layers of known age and cultural association provides the first reliable age determinations for distal volcanic events and their geographical extent. The future potential for tephrochronological research in North Africa is also discussed

Body mass reduction markedly improves muscle performance and body composition in obese females aged 61-75 years: comparison between the effects exerted by energy-restricted diet plus moderate aerobic-strength training alone or associated with rGH or nandrolone undecanoate

OBJECTIVE: To investigate the effectiveness of a body mass reduction programme entailing diet caloric restriction and moderate physical activity with or without supplementary treatment with recombinant (r) GH or steroids to improve body composition and muscle performance in severely obese women aged 61-75 years. METHODS: Twenty women were randomly assigned to one of three groups: body mass reduction alone; body mass reduction plus rGH; body mass reduction plus nandrolone undecanoate. Body composition, isotonic muscle strength and anaerobic power output during jumping were determined before and after the 3-week period. RESULTS: Whatever the experimental group considered, body mass (P<0.01), body mass index (P<0.05) and fat mass (P<0.05) decreased significantly, whereas muscle strength and power increased significantly (P<0.05) after the intervention. CONCLUSION: Small body mass reductions after 3 weeks of energy-restricted diet combined with moderate aerobic and strength exercise are associated with significant improvements in upper and lower limb muscle strength and power and reduction of fat mass in severely obese women aged 61-75 years. Although the association of rGH or nandrolone undecanoate does not appear to exert additional effects on body composition and muscle performance attained by body mass reduction alone, further additional studies with larger study groups, different dosages and more prolonged periods are required for definitive conclusions to be drawn

Shifting from Oral Contraceptives to Norethisterone Acetate, or Vice Versa, because of Drug Intolerance : Does the Change Benefit Women with Endometriosis?

Background/Aims: Oral contraceptives (OC) and norethisterone acetate (NETA) are among first-line medical therapies for symptomatic endometriosis, but their use is sometimes associated with intolerable side effects. We investigated whether shifting from low-dose OC to NETA (2.5 mg/day), or vice versa, improved tolerability. Methods: Sixty-seven women willing to discontinue their treatment because of intolerable side effects despite good pain relief, were enrolled in a self-controlled study, and shifted from OC to NETA (n = 35) or from NETA to OC (n = 32). The main study outcome was satisfaction with treatment 12 months after the change. Tolerability, pain symptoms, health-related quality of life, psychological status, and sexual functioning were also evaluated. Results: After treatment change, good tolerability was reported by 37% of participants who shifted to NETA, and by 52% of those who shifted to OC. At 12-month assessment, 51% of women intolerant to OC were satisfied with NETA, and 65% of those intolerant to NETA were satisfied with OC (intention-to-treat analysis). Other study variables did not vary substantially. Conclusions: In selected endometriosis patients, shifting from OC to NETA, or vice versa, because of side effects, improved tolerability. Better results were observed when substituting NETA with OC rather than the other way round