Evaluation of acute phase proteins, adiponectin and endothelin-1 to determine vascular damage in dogs with heartworm disease (Dirofilaria immitis), before and after adulticide treatment.

Previous studies have shown the existence of an acute phase response in dogs with heartworm (Dirofilaria immitis), probably caused by the vascular inflammation that occurs during the pathogenesis of this disease. In addition, it has been seen that this acute phase response persists after finishing treatment, especially in dogs with pulmonary hypertension (PH). Furthermore, echocardiographic studies have shown that PH and endarteritis appear to persist for at least 10 months after completion of adulticide treatment, suggesting that the vascular changes in these dogs may not be reversible. Therefore, the objective of this study was to evaluate the serum concentrations of different positive acute phase proteins (APP) [C reactive-protein (CRP), haptoglobin and ferritin] and negative APP (albumin and paraoxonase-1 (PON-1)), and the usefulness of the endothelin-1 (ET-1) and adiponectin, in dogs infected by D. immitis to evaluate their usefulness as diagnostic biomarkers of vascular damage and PH and their progression throughout therapy up to 7 months after the end of adulticide treatment. Twenty-five heartworm-infected dogs received adulticide treatment, and serum measurements were performed on the day of diagnosis (day 0), day of discharge (day 90), and 6 months after discharge (day 270). In addition, presence or absence of PH was also echocardiographically determined using the Right Pulmonary Artery Distensibility Index. PH was present in 44% of the dogs on day 0 and day 90, and in 48% of dogs on day 270. Alterations were observed in the concentrations of all APP throughout the study, persisting the alterations in PON-1 and ferritin on day 270. Depending on the presence or absence of PH, CRP showed significant differences throughout the study, as did ET-1. On the other hand, adiponectin did not show variations throughout the study, so it did not seem a useful marker in this disease. These results could reflect the possible persistence of vascular inflammation up to 7 months after finishing treatment, whether or not there was PH, and consolidate the study of APP as useful markers in heartworm disease. Moreover, persistent PH could be the consequent clinical manifestation in dogs with more severe vascular alterations so the study of APP, especially CRP, and ET-1 could be especially advantageous in these patients in the early evaluation of the disease, as well as for the determination of disease severity, monitoring therapeutic responses, and predicting outcomes.

3D trapping of microbubbles by the Marangoni force.

In this Letter, we show 3D steady-state trapping and manipulation of vapor bubbles in liquids employing a low-power continuous-wave laser using the Marangoni effect. Light absorption from photodeposited silver nanoparticles on the distal end of a multi-mode optical fiber is used to produce bubbles of different diameters. The thermal effects produced by either the nanoparticles on the fiber tip or the light bulk absorption modulate the surface tension of the bubble wall and creates both longitudinal and transversal forces just like optical forces, effectively creating a 3D potential well. Using numerical simulations, we obtain expressions for the temperature profiles and present analytical expressions for the Marangoni force. In addition, using an array of three fibers with photodeposited nanoparticles is used to demonstrate the transfer of bubbles from one fiber to another by sequentially switching on and off the lasers.

Synergy of diffraction and spectroscopic techniques to unveil the crystal structure of antimonic acid.

The elusive crystal structure of the so-called 'antimonic acid' has been investigated by means of robust and state-of-the-art techniques. The synergic results of solid-state magic-angle spinning nuclear magnetic resonance spectroscopy and a combined Rietveld refinement from synchrotron X-ray and neutron powder diffraction data reveal that this compound contains two types of protons, in a pyrochlore-type structure of stoichiometric formula (H3O)1.20(7)H0.77(9)Sb2O6. Some protons belong to heavily delocalized H3O+ subunits, while some H+ are directly bonded to the oxygen atoms of the covalent framework of the pyrochlore structure, with O-H distances close to 1 Å. A proton diffusion mechanism is proposed relying on percolation pathways determined by bond-valence energy landscape analysis. X-ray absorption spectroscopy results corroborate the structural data around Sb5+ ions at short-range order. Thermogravimetric analysis and differential scanning calorimetry endorsed the conclusions on the water content within antimonic acid. Additional 0.7 water molecules per formula were assessed as moisture water by thermal analysis.

Correction and verification of x-ray imaging crystal spectrometer analysis on Wendelstein 7-X through x-ray ray tracing.

X-ray ray tracing is used to develop ion-temperature corrections for the analysis of the X-ray Imaging Crystal Spectrometer (XICS) used at Wendelstein 7-X (W7-X) and perform verification on the analysis methods. The XICS is a powerful diagnostic able to measure ion-temperature, electron-temperature, plasma flow, and impurity charge state densities. While these systems are relatively simple in design, accurate characterization of the instrumental response and validation of analysis techniques are difficult to perform experimentally due to the requirement of extended x-ray sources. For this reason, a ray tracing model has been developed that allows characterization of the spectrometer and verification of the analysis methods while fully considering the real geometry of the XICS system and W7-X plasma. Through the use of ray tracing, several important corrections have been found that must be accounted for in order to accurately reconstruct the ion-temperature profiles. The sources of these corrections are described along with their effect on the analyzed profiles. The implemented corrections stem from three effects: (1) effect of sub-pixel intensity distribution during de-curving and spatial binning, (2) effect of sub-pixel intensity distribution during forward model evaluation and generation of residuals, and (3) effect of defocus and spherical aberrations on the instrumental response. Possible improvements to the forward model and analysis procedures are explored, along with a discussion of trade-offs in terms of computational complexity. Finally, the accuracy of the tomographic inversion technique in stellarator geometry is investigated, providing for the first time a verification exercise for inversion accuracy in stellarator geometry and a complete XICS analysis tool-chain.

Strongly reduced lattice thermal conductivity in Sn-doped rare-earth (M) filled skutterudites M x Co4Sb12-y Sn y , promoted by Sb-Sn disordering and phase segregation.

CoSb3 thermoelectric skutterudite has been filled with rare-earth metals (M = La, Ce, Yb) and partially doped with Sn in specimens of M x Co4Sb12-y Sn y stoichiometry. This has been achieved under high-pressure conditions at 3.5 GPa in a piston-cylinder hydrostatic press. A structural investigation using synchrotron X-ray diffraction data reveals a phase segregation in twin skutterudite phases with filling fraction fluctuation and different unit-cell sizes. As a result of three effects acting as phonon scatterers, namely the rattling effect of M at the wide 8a cages of the cubic Im3̄ structure, the phase segregation, and the intrinsic disorder introduced by Sn substitution at the Sb sublattice, the total thermal conductivity (κ) dramatically falls to reach minimum values under 2 W m-1 K-1, well below those typically exhibited by other thermoelectric materials based upon single-filled skutterudites. The power factor is substantially enhanced to 1.11 mW m-1 K-2 in Yb0.5Co4Sb11.6Sn0.4 with respect to the unfilled composition, as a result of the charge transfer promoted by the filler.

A comprehensive examination of the local- and long-range structure of Sb6O13 pyrochlore oxide.

The crystal structure of the Sb6O13 oxide, exhibiting a defect pyrochlore crystal structure with atomic vacancies, has been studied using a complete set of state-of-the-art techniques. The degree of antimony disproportionation in Sb3+ and Sb5+ valence states has been directly determined around 36% and 64%, respectively, using X-ray absorption near edge structure (XANES). These findings are in excellent agreement with our Rietveld analysis of synchrotron X-ray (SXRD) and neutron powder diffraction (NPD) results. Moreover, the highly distorted Sb3+ coordination due to its lone electron pair has been critically revisited. The bonding distances and coordination of Sb3+ and Sb5+ species closely agree with an extensive dynamic and crystallographic determination using the Extended X-ray Absorption Fine Structure (EXAFS) technique. Most importantly, the specific local disorder of the two distinctive Sb ions has been crosschecked monitoring their unusual Debye-Waller factors.

Topotactic Oxidation of Perovskites to Novel SrMo1-xMxO4-δ (M = Fe and Cr) Deficient Scheelite-Type Oxides.

New polycrystalline SrMo1-xMxO4-δ (M = Fe and Cr) scheelite oxides have been prepared by topotactical oxidation, by annealing in air at 500 °C, from precursor perovskites with the stoichiometry SrMo1-xMxO3-δ (M = Fe and Cr). An excellent reversibility between the oxidized Sr(Mo,M)O4-δ scheelite and the reduced Sr(Mo,M)O3-δ perovskite phase accounts for the excellent behavior of the latter as anode material in solid-oxide fuel cells. A characterization by X-ray powder diffraction (XRD) and neutron powder diffraction (NPD) has been carried out to determine the crystal structure features. The scheelite oxides are tetragonal, space group I41/a (No. 88). The Rietveld-refinement from NPD data at room temperature shows evidence of oxygen vacancies in the structure, due to the introduction of Fe3+/Cr4+ cations in the tetrahedrally-coordinated B sublattice, where Mo is hexavalent. A thermal analysis of the reduced perovskite (SrMo1-xMxO3-δ) in oxidizing conditions confirms the oxygen stoichiometry obtained by NPD data; the stability range of the doped oxides, below 400-450 °C, is lower than that for the parent SrMoO3 oxide. The presence of a Mo4+/Mo5+ mixed valence in the reduced SrMo1-xMxO3-δ perovskite oxides confers greater instability against oxidation compared with the parent oxide. Finally, an XPS study confirms the surface oxidation states of Mo, Fe, and Cr in the oxidized samples SrMo0.9Fe0.1O4-δ and SrMo0.8Cr0.2O4-δ.

Optical trapping in the presence of laser-induced thermal effects.

The inclusion of thermal effects in optical manipulation has been explored in diverse experiments, increasing the possibilities for applications in diverse areas. In this Letter, the results of combined optical and thermal manipulation in the vicinity of a highly absorbent hydrogenated amorphous silicon layer, which induces both the generation of convective currents and thermophoresis, are presented. In combination with the optical forces, thermal forces help reduce the optical power required to trap and manipulate micrometric polystyrene beads. Moreover, the inclusion of these effects allows the stacking and manipulation of multiple particles with a single optical trap along with the beam propagation, providing an extra tool for micromanipulation of a variety of samples.

Optothermal generation, trapping, and manipulation of microbubbles.

The most common approach to optically generate and manipulate bubbles in liquids involves temperature gradients induced by CW lasers. In this work, we present a method to accomplish both the generation of microbubbles and their 3D manipulation in ethanol through optothermal forces. These forces are triggered by light absorption from a nanosecond pulsed laser (λ = 532 nm) at silver nanoparticles photodeposited at the distal end of a multimode optical fiber. Light absorbed from each laser pulse quickly heats up the silver-ethanol interface beyond the ethanol critical-point (∼ 243 °C) before the heat diffuses through the liquid. Therefore, the liquid achieves a metastable state and owing to spontaneous nucleation converted to a vapor bubble attached to the optical fiber. The bubble grows with semi-spherical shape producing a counterjet in the final stage of the collapse. This jet reaches the hot nanoparticles vaporizing almost immediately and ejecting a microbubble. This microbubble-generation mechanism takes place with every laser pulse (10 kHz repetition rate) leading to the generation of a microbubbles stream. The microbubbles' velocities decrease as they move away from the optical fiber and eventually coalesce forming a larger bubble. The larger bubble is attracted to the optical fiber by the Marangoni force once it reaches a critical size while being continuously fed with each bubble of the microbubbles stream. The balance of the optothermal forces owing to the laser-pulse drives the 3D manipulation of the main bubble. A complete characterization of the trapping conditions is provided in this paper.

Evaluation of serum biomarkers and proteinuria for the early detection of renal damage in dogs with heartworm (Dirofilaria immitis).

Glomerulonephropathy associated with Dirofilaria immitis (heartworm) is relatively frequent in infected dogs. Given the importance and the scarcity of studies focused on its prevalence and diagnosis, the objective was to determine the prevalence of proteinuria and functional indicators of glomerular filtration rate in dogs with heartworm disease and discuss its utility in the detection of renal impairment. Sera and urine from 47 infected dogs were analyzed in a reference laboratory. Urea, creatinine, plasma proteins and serum symmetric dimethylarginine (SDMA) were analyzed in sera, while the UPC ratio was performed in urine. Dogs were further evaluated for the presence/absence of microfilariae, pulmonary and systemic hypertension, and the parasite burden was assessed. The results showed that 19.1 % of dogs showed proteinuria (UPC > 0.5) and 17 % showed borderline proteinuria (UPC 0.2-0.5). Creatinine and SDMA were high (>1.8 mg/dl and ≥18 µg/dl, respectively) in 4.2 % of dogs. UPC ratio was significantly increased in dogs with high parasite burden and in dogs with microfilariemia (p < 0.05). Dogs with pulmonary hypertension showed higher increases in proteinuria as well, which was probably due to the chronicity of the infection. No significant differences were found in serum and urine values regarding systemic blood pressure. Despite the limitations of this study, proteinuria/borderline proteinuria was present in 36.2 % of dogs with heartworm disease, and this may be due to glomerular disease. Therefore, the detection of proteinuria, along with other renal biomarkers in the diagnostic protocols, could help identify kidney alterations or risk of renal damage in heartworm disease.

Evaluation of different dosages of doxycycline during the adulticide treatment of heartworm (Dirofilaria immitis) in dogs.

The endosymbiont bacteria Wolbachia plays an important role in the pathogenesis and inflammatory immune response to heartworm (Dirofilaria immitis) infection in dogs. Doxycycline is used to reduce Wolbachia from all life stages of heartworm to avoid large releases of the bacteria during the death of the worms. However, the dose and duration currently recommended have been extrapolated from the treatment of other rickettsial infections. Therefore, the aim was to study the dynamics of Wolbachia IgG antibodies in heartworm-infected dogs under adulticide treatment using different dosages of doxycycline. Forty-nine heartworm-infected dogs were recruited. On day 0 (diagnosis), monthly ivermectin (6 µg/kg) was prescribed, as well as daily doxycycline for 30 days, at 10 mg/kg/12 h (n = 13), 5 mg/kg/12 h (n = 19), and 10 mg/kg/24 h (n = 17). Dogs underwent adulticide treatment and blood samples were collected on days 0, 30, 90, and 120. All dogs had antibodies against recombinant Wolbachia surface protein (rWSP), confirming the important role of the bacteria in heartworm. No significant differences were found in anti-rWSP response by presence/absence of microfilariae, or by parasite burden on day 0. In all treated groups, the anti-rWSP antibody response was not significantly different between days 0 and 30 but was significantly lower between days 0 and 120 (p < 0.05). The results of the present study suggest that the administration of a lower dose than currently recommended is sufficient to achieve a significant reduction of Wolbachia in dogs infected by D. immitis.

Charge exchange recombination spectroscopy at Wendelstein 7-X.

The Charge Exchange Recombination Spectroscopy (CXRS) diagnostic has become a routine diagnostic on almost all major high temperature fusion experimental devices. For the optimized stellarator Wendelstein 7-X (W7-X), a highly flexible and extensive CXRS diagnostic has been built to provide high-resolution local measurements of several important plasma parameters using the recently commissioned neutral beam heating. This paper outlines the design specifics of the W7-X CXRS system and gives examples of the initial results obtained, including typical ion temperature profiles for several common heating scenarios, toroidal flow and radial electric field derived from velocity measurements, beam attenuation via beam emission spectra, and normalized impurity density profiles under some typical plasma conditions.

Exposure of humans to the zoonotic nematode Dirofilaria immitis in Northern Portugal.

Dirofilariosis caused by Dirofilaria immitis (heartworm) is a zoonosis, considered an endemic disease of dogs and cats in several countries of Western Europe, including Portugal. This study assesses the levels of D. immitis exposure in humans from Northern Portugal, to which end, 668 inhabitants of several districts belonging to two different climate areas (Csa: Bragança, Vila Real and Csb: Aveiro, Braga, Porto, Viseu) were tested for anti-D. immitis and anti-Wolbachia surface proteins (WSP) antibodies. The overall prevalence of seropositivity to both anti-D. immitis and WSP antibodies was 6.1%, which demonstrated the risk of infection with D. immitis in humans living in Northern Portugal. This study, carried out in a Western European country, contributes to the characterisation of the risk of infection with D. immitis among human population in this region of the continent. From a One Health point of view, the results of the current work also support the close relationship between dogs and people as a risk factor for human infection.

Stray Dogs of Sofia (Bulgaria) Could be an Important Reservoir of Heartworm (Dirofilaria Immitis).

Dirofilaria immitis (heartworm) is a zoonotic and an emerging disease, expanding in Europe. In Bulgaria, the presence of the parasite has been described in many regions. However, canine heartworm has hardly been evaluated in the capital of the country and, therefore, the aim of this study was to evaluate the prevalence and distribution of canine heartworm in Sofia. Eighty stray dogs from the city of Sofia and the metropolitan area were analysed for circulating D. immitis antigens. The prevalence was 31.25 %, being 34.7 % in the metropolitan area and 25.8 % in the city of Sofia. The current results are among the highest reported in the country. This could be due to the lack of prophylactic measures against infection in these dogs, but also to the spread of D. immitis into non-endemic countries. Stray dogs may act as an important reservoir of heartworm being a risk for client-owned animals and for the development of pulmonary dirofilariosis in inhabitants. The results show the need to establish further epidemiological studies and prophylactic campaigns for stray and client-owned animals, as well as to create awareness campaigns about the severity and importance of this disease for both animals and humans.

Persistence of pulmonary endarteritis in canine heartworm infection 10 months after the eradication of adult parasites of Dirofilaria immitis.

Pulmonary endarteritis caused by Dirofilaria immitis and pulmonary hypertension (PH) are closely linked and the determination of PH could be validated to assess the severity and chronicity of the vascular damage, i.e. by the use of the Right Pulmonary Artery Distensibility (RPAD) Index. The aim was to evaluate the RPAD Index in dogs 10 months after the last dose of adulticide. The study included 23 client-owned dogs with heartworm brought for adulticide treatment. Echocardiographic exam was carried out to estimate worm burden, RPAD Index as well as other routine echocardiographic values on day 0 (diagnosis), day 120 (discharge), and 10 months after the last dose of adulticide. No significant differences were observed in the RPAD Index over time, neither when microfilaremic status and parasite burden were evaluated. An RPAD Index <29% was found in 52.2% of the dogs on day 0, day 120, and 10 months after the last dose of adulticide. Regarding other echocardiographic parameters, only significant differences were observed on tricuspid annular plane systolic excursion (TAPSE) values between day 0:day 120 (p = 0.008), and day 0:end of the study (p = 0.037). There was not significant improvement in pulmonary damage 10 months after the elimination of the parasites (p = 0.296), suggesting that, once the endarteritis has developed, the vascular changes are chronic and may not be reversible. The modifications of the TAPSE value suggest an improvement in the systolic function of the right ventricle after the disappearance of the worms, independently of the presence of PH. The endarteritis causes a decrease in the elasticity in the pulmonary vasculature and an increase in the resistance that, chronically, and depending on the severity, will cause the development of PH and later right heart failure. This complication of the disease is one of the most damaging and frequent, so it is necessary to adequately monitor PH in dogs undergoing adulticide treatment. Furthermore, knowing the pulmonary status could provide valuable information to help provide an objective prognosis and help assess the need to add additional treatments, once the worms have been eliminated.

Variation of the adulticide protocol for the treatment of canine heartworm infection: Can it be shorter?

The treatment of canine heartworm has been modified over the years, adding improvements for greater efficacy, safeness and better prognosis. Currently, the recommended adulticidal protocol consists of the administration of three doses of melarsomine dihydrochloride, preceded by the administration of macrocyclic lactones over two to three months. The objective of this study was to evaluate a variation of the adulticide protocol of heartworm in 76 dogs infected by Dirofilaria immitis, which consists of the pre-administration of macrocyclic lactones (ivermectin) during a single month. On the day of diagnosis, presence of circulating microfilariae was determined and an echocardiography was performed to assess the parasite burden. Treatment began on day 0, with doxycycline for 30 days (10 mg/kg BID) and monthly ivermectin (6mcg/kg). On day 30, the first dose of melarsomine dihydrochloride was administered, followed by a second and third dose on days 60 and 61, respectively. On day 90, the dogs were examined and discharged. Six months after the last dose, all dogs were negative to the presence of antigens and amicrofilaremic. Also, 38.1% of animals were evaluated by echocardiography, showing absence of adult parasites. It is considered that the ineffectiveness of melarsomine against worms <4 months should be avoided by the previous administration of macrocyclic lactones for two to three months, killing larvae <2 months while older filariae are allowed to mature to be susceptible to melarsomine dihydrochloride. With this protocol, this gap would be covered for the 2nd and 3rd injections, when worms would be four months and older. In addition, there is evidence that melarsomine is effective against worms under four months and macrocyclic lactones have some efficacy against heartworms older than two months. This modification allows a faster elimination of heartworms and a better compliance from the owners of the infected dogs.

Prospects of X-ray imaging spectrometers for impurity transport: Recent results from the stellarator Wendelstein 7-X (invited).

This paper reports on the design and the performance of the recently upgraded X-ray imaging spectrometer systems, X-ray imaging crystal spectrometer and high resolution X-ray imaging spectrometer, installed at the optimized stellarator Wendelstein 7-X. High resolution spectra of highly ionized, He-like Si, Ar, Ti, and Fe as well as H-like Ar have been observed. A cross comparison of ion and electron temperature profiles derived from a spectral fit and tomographic inversion of Ar and Fe spectra shows a reasonable match with both the spectrometers. The also measured impurity density profiles of Ar and Fe have peaked densities at radial positions that are in qualitative agreement with the expectations from the He-like impurity fractional abundances, given the measured temperature profiles. Repeated measurements of impurity decay times have been demonstrated with an accuracy of 1 ms via injection of non-recycling Ti, Fe, and Mo impurities using a laser blow-off system.