Abstract Background In addition to its role in the endogenous control of erythropoiesis, recombinant human erythropoietin (rh-EPO) has been shown to exert tissue protective properties in various ...experimental models. However, its role in the cardiac arrest (CA) setting has not yet been adequately investigated. Aim The aim of this study is to examine the effect of rh-EPO in a pig model of ventricular fibrillation (VF)-induced CA. Methods Ventricular fibrillation was electrically induced in 20 piglets and maintained untreated for 8 minutes before attempting resuscitation. Animals were randomized to receive rh-EPO (5000 IU/kg, erythropoietin EPO group, n = 10) immediately before the initiation of chest compressions or to receive 0.9% Sodium chloride solution instead (control group, n = 10). Results Compared with the control, the EPO group had higher rates of return of spontaneous circulation (ROSC) (100% vs 60%, P = .011) and higher 48-hour survival (100% vs 40%, P = .001). Diastolic aortic pressure and coronary perfusion pressure during cardiopulmonary resuscitation were significantly higher in the EPO group compared with the control group. Erythropoietin-treated animals required fewer number of shocks in comparison with animals that received normal saline ( P = .04). Furthermore, the neurologic alertness score was higher in the EPO group compared with that of the control group at 24 ( P = .004) and 48 hours ( P = .021). Conclusion Administration of rh-EPO in a pig model of VF-induced CA just before reperfusion facilitates ROSC and improves survival rates as well as hemodynamic variables.
The incredible potential for fluorescent proteins to revolutionize biology has inspired the development of a variety of design strategies to address an equally broad range of photophysical ...characteristics, depending on potential applications. Of these, fluorescent proteins that simultaneously exhibit high quantum yield, red-shifted emission, and wide separation between excitation and emission wavelengths (Large Stokes Shift, LSS) are rare. The pursuit of LSS systems has led to the formation of a complex, obtained from the marriage of a rationally engineered protein (human cellular retinol binding protein II, hCRBPII) and different fluorogenic molecules, capable of supporting photobase activity. The large increase in basicity upon photoexcitation leads to protonation of the fluorophore in the excited state, dramatically red-shifting its emission, leading to an LSS protein/fluorophore complex. Essential for selective photobase activity is the intimate involvement of the target protein structure and sequence that enables Excited State Proton Transfer (ESPT). The potential power and usefulness of the strategy was demonstrated in live cell imaging of human cell lines.
This catalog summarizes 117 high-confidence > or =0.1 GeV gamma-ray pulsar detections using three years of data acquired by the Large Area Telescope (LAT) on the Fermi satellite. Half are neutron ...stars discovered using LAT data through periodicity searches in gamma-ray and radio data around LAT unassociated source positions. The 117 pulsars are evenly divided into three groups: millisecond pulsars, young radio-loud pulsars, and young radio-quiet pulsars. We characterize the pulse profiles and energy spectra and derive luminosities when distance information exists. Spectral analysis of the off-peak phase intervals indicates probable pulsar wind nebula emission for four pulsars, and off-peak magnetospheric emission for several young and millisecond pulsars. We compare the gamma-ray properties with those in the radio, optical, and X-ray bands. We provide flux limits for pulsars with no observed gamma-ray emission, highlighting a small number of gamma-faint, radio-loud pulsars. The large, varied gamma-ray pulsar sample constrains emission models. Fermi's selection biases complement those of radio surveys, enhancing comparisons with predicted population distributions.
Objective of this article is to review use of ultrasonographic examination in the uterus of ewes during the post-partum period. The technique has been employed for elucidating the process of uterine ...involution in that species, as well as in the diagnosis of various clinical entities. In general, there is a progressive, significant reduction in the size of the uterus, especially during the first week after lambing, in the size of the uterine lumen and the size of the caruncles of the endometrium. In cases of post-partum metritis, principal uterine characteristics that can be assessed by means of ultrasonographic examination for diagnosis and evaluation of the disorder are uterine distention, asymmetry of the organ, distention of uterine lumen, presence, quantity and texture of uterine content, thickness of uterine wall, localisation of inflammatory foci on the uterine wall, texture of uterine wall, alterations in uterine wall vascularisation and confirmation of uterine involution completion. The technique may also be applied for evaluation of the effect of treatment in cases of the disease.
Introduction: RSV-associated respiratory viral infections are a major public health problem affecting the immunologically naïve/compromised population. For example, RSV-induced bronchiolitis and ...pneumonia are the leading cause of hospitalization in infants and young children worldwide, while in adult allogeneic hematopoietic transplant (HCT) recipients the incidence of progression from upper to lower respiratory tract infection (LRTI) is 40-60%, with mortality rates as high as 80%. At the national level, the Fall 2022-Spring 2023 RSV surge translated into a sharp rise in hospitalization rates surpassing last season's respective rate by almost 5-fold (https://www.cdc.gov/rsv/research/rsv-net).
Our group has previously demonstrated the feasibility, safety and clinical efficacy of administering allogeneic ex vivo expanded multivirus-specific T cells (multi-VSTs) as a banked, off-the-shelf product for the treatment of EBV, CMV, BKV, HHV6, AdV and SARS-CoV-2 infections/disease in immunocompromised individuals. Given the RSV-associated morbidity and the paucity of therapeutic agents, we sought to characterize the cellular immune responses to RSV with a view to developing a targeted T-cell therapy product for those at highest risk of severe disease (i.e. HCT recipients, elderly/immunocompromised patients).
Methods: To first identify immunogenic and protective RSV antigens we exposed PBMCs from healthy adult donors to pepmixes (overlapping peptide libraries) spanning the 11 RSV-encoded antigens and found that 7 induced highly reactive T cells. However, Nucleoprotein (N) and Fusion Protein (F) proved to be immunogenic in all donors and were thus advanced for VST manufacturing. We subsequently utilized our optimized VST manufacturing process and culture in a G-Rex device in medium supplemented with activating cytokines to generate RSV-specific VSTs (RSV-STs) with activity against this combination of immunodominant targets.
Results: We achieved a mean 5.2±1-fold expansion (mean±SEM; n=13) of cells that were comprised almost exclusively of CD3+ T cells (94.08±1.15%), with a mixture of cytotoxic (CD8+; 28.91±5.16%) and helper (CD4+; 71.09±5.15%) T cells. These cells had a phenotype consistent with effector function and memory potential, as evidenced by upregulation of the activation markers CD25, CD69, and CD28 and expression of central (CD45RO+/CD62L+) and effector memory markers (CD45RO+/CD62L-) with minimal expression of exhaustion-related markers such as PD1, Tim3 and LAG3.
The anti-viral activity of the expanded cells was confirmed in an IFNγ ELISpot using both stimulating antigens as an immunogen and all lines proved to be reactive against the target antigens (N: 3587±939 SFC/2x10 5; F: 3526±743). As demonstrated by surface and intracellular flow cytometry, the immune response was mediated by both CD4+ and CD8+ T cell subsets through IFNγ/TNFα production and upregulation of activation/costimulatory markers. Reactive cells were polyfunctional and primarily Th1-polarized as evidenced by IFNγ, Granzyme-B, IL-2 and GM-CSF production measured by FluoroSpot and Luminex array. Finally, the expanded cells were able to kill viral pepmix-loaded autologous PHA blasts with minimal/no activity against non-antigen-expressing autologous and allogeneic targets.
Conclusion: Healthy donor-derived RSV-STs are Th1-polarized, polyfunctional and selectively able to kill viral antigen-expressing targets with no auto- or alloreactivity, indicative of their safety for clinical use. A clinical trial evaluating their safety and activity in HCT recipients as part of an off-the-shelf multi-respiratory virus-directed product is currently underway (NCT04933968, https://clinicaltrials.gov).
Results are presented of a harmonic analysis of the large-scale cosmic-ray (CR) anisotropy as observed by the Milagro observatory. We show a two-dimensional display of the sidereal anisotropy ...projections in right ascension (R.A.) generated by the fitting of three harmonics to 18 separate declination bands. The Milagro observatory is a water Cherenkov detector located in the Jemez mountains near Los Alamos, New Mexico. With a high duty cycle and large field of view, Milagro is an excellent instrument for measuring this anisotropy with high sensitivity at TeV energies. The analysis is conducted using a seven-year data sample consisting of more than 95 billion events, the largest such data set in existence. We observe an anisotropy with a magnitude around 0.1% for CRs with a median energy of 6 TeV. The dominant feature is a deficit region of depth (2.49 - 0.02 stat. - 0.09 sys.) X10-3 in the direction of the Galactic north pole centered at 189 deg R.A. We observe a steady increase in the magnitude of the signal over seven years.
A thermal-metallurgical-mechanical model was developed to study the effects of dilution in each weld pass for multipass gas tungsten arc and submerged arc welding in low alloy steel (i.e. SA508) ...plates. Hardness distributions and residual stresses were measured on the transverse sections perpendicular to the welding direction of the manufactured weldments. The predicted hardness and residual stresses were compared with the measurement data and shown to be reasonably accurate. The results showed that dilution can significantly affect both the hardness and the residual stress field in the weld metal. It was found that, for the base and filler materials used, increased dilution led to greater weld-metal hardness and reduced the magnitude of tensile stress or promoted compressive stress in the as-deposited and reheated weld metals. This mechanical behaviour is associated with the tendency for diluted weld metal to experience delayed austenite decomposition, owing to the high hardenability of SA508 steel relative to the filler materials used. Although dilution is irrelevant for the hardness of the base material and its transformation products adjacent to the weld metal, it affected the full-field residual stresses via the equilibrium interaction between the stresses in the base and weld metals.
•Dilution effect is investigated for multipass arc welds with base material having higher hardenability than filler material.•Predictions of hardness and residual stresses are in reasonable agreement with measurements.•Higher dilution leads to higher hardness of the studied weld metal in both as-deposited and reheated states.•Higher dilution reduces tensile stress or promotes compressive stress in the as-deposited and reheated weld metals.
Ultrasonographic examination has been established as the most valuable method for early and accurate pregnancy diagnosis in ewes. Early and accurate diagnosis of pregnancy is particularly useful for ...correct health management of flocks during gestation. It is also important to study pregnancy processes and foetal development with a non-invasive method, as ultrasonographic examination, because various events might affect normal development of foetus and viability of offspring. Evaluation of normal physiological pregnancy progress and outcome, as well as pregnancy disorders and peri-parturient disorders are significant in sheep health management. Hence, ability to perform pregnancy diagnosis and to identify common pathological conditions of pregnant ewes is of importance to clinicians active in sheep practice. Further, monitoring of foetal growth during pregnancy is useful for those working with sheep. Moreover, various disorders of pregnant ewes (e.g., pregnancy toxaemia) can lead to dystocia and it would be beneficial to predict such cases, if any of these disorders has been diagnosed. In all the above circumstances, ultrasonographic examination can support the veterinarian in reaching a diagnosis and in taking decisions for management of each situation.
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