Correction of ADA-SCID by stem cell gene therapy combined with nonmyeloablative conditioning

Hematopoietic stem cell (HSC) gene therapy for adenosine deaminase (ADA)-deficient severe combined immunodeficiency (SCID) has shown limited clinical efficacy because of the small proportion of engrafted genetically corrected HSCs. We describe an improved protocol for gene transfer into HSCs associated with nonmyeloablative conditioning. This protocol was used in two patients for whom enzyme replacement therapy was not available, which allowed the effect of gene therapy alone to be evaluated. Sustained engraftment of engineered HSCs with differentiation into multiple lineages resulted in increased lymphocyte counts, improved immune functions (including antigen-specific responses), and lower toxic metabolites. Both patients are currently at home and clinically well, with normal growth and development. These results indicate the safety and efficacy of HSC gene therapy combined with nonmyeloablative conditioning for the treatment of SCID.     

Extractable iron and organic matter in the suspended insoluble material of fog droplets

In this work the formation and composition of aggregates between metals and organic material is studied in real fog samples. In a preliminary experiment it has been found that concentrated cloud samples form a yellow-brown precipitate in the presence of Fe(III). Standards of humic acids and fulvic acids co-precipitate with Fe(III), forming similar aggregates i.e. iron-humates (Fe-HA) and iron-fulvates (Fe-FA). By comparing the solubility properties of aggregates by extracting organic carbon (OC) in different pH conditions, it has been observed that fog droplet particulate samples are characterised by solubility properties more similar to those of Fe-HA than Fe-FA. Dilute alkaline solutions can also easily extract organic refractory substances that form aggregates with metals. The recoveries of the total extractable organic matter (accounting for 12% of total insoluble carbon and 15% of particulate mass) are similar to those of humic-like substances (HULIS) from particulate samples. The chromatographic behaviour and functional group characteristics measured in the alkali-extract fraction of precipitated aggregates with iron and in the insoluble particulate of fog samples, are those of humic-like material. Thus, soluble HULIS are able to interact with iron to form particulate, but the composition of a large fraction of insoluble organic carbon is still unknown. These findings have implications on the solubility and surface tension properties of fog droplets and can therefore potentially influence droplet formation, as well as cloud chemical and photochemical processes.     

Intracranial epidural mucocele in a cat

An 18-month-old, spayed female, domestic shorthaired cat was presented with clinical signs of depression and reluctance to walk, which progressed to nonambulatory tetraparesis. Increased opacification of both frontal sinuses and a cyst-like abnormality causing compression and displacement of the right frontal lobe were seen on computed tomography. Bilateral frontal sinus trephination and right transfrontal craniotomy revealed clear, viscous fluid in the right frontal sinus and rostral fossa, compatible with an intracranial mucocele. At a 6-month follow-up examination, no signs of recurrence were appreciated.     

Soil REE patterns as tracers of the emplacement of metal-rich anthropogenic materials. A case study in Moa (Cuba)

Purpose

Are rare earth element (REE) patterns employable as tracers in human interventions of bulk soil disturbances, when high concentrations of metals are involved in the in situ soil disturbance? In terms of bulk soil disturbance, it is difficult to distinguish between bulk soil disturbances and emplacement of new earthen material. Chemical fingerprinting, in particular REE plus yttrium, is applied across many fields, but predominantlyin tracking the sources of potential environmental contaminants.

Materials and methods

The REE normalised patterns (HNO₃:HF:HCl 3:1:1 digestion, ICP-MS) of two Calcaric Cambisols were compared with those of a Geric Ferralsol (Novic, Technic) originated from selective overburden of nickel mining (20°40′ N, 75°35′ W).

Results and discussion

The sum of REE, including Y and Sc, ranged between 48 and 101 mg kg^?1. Principal component analysis (PCA) shows a discriminant role of REE. REE signature normalised to the upper continental crust shows slight positive Eu and negative Ce anomalies in the case of both Calcaric Cambisols, while the Geric Ferralsol shows anomalous patterns with the same anomalies plus a slight positive anomaly of Y, as a consequence of the addition of mining by-products.

Conclusions

Here, we show that REE patterns of the individual horizons of a soil have characteristics that allow us to distinguish undisturbed from soils mixed with other soil materials, including those with different pH values and high metal contents (e.g. Cr, Mn, and Ni ≥?0.5%, Fe ??5 wt%). Our results demonstrate, by using soils with contrasting characteristics, that their origins can be traced via the patterns of their REEs, even in the presence of high concentrations of other metals. In perspective, when background maps of all REE elements in soils are available worldwide on an appropriate scale, this enables us to obtain a level of discriminatory detail on a local scale.

     

INTRAVENOUS ALFAXALONE ANAESTHESIA IN LEOPARD GECKOS (EUBLEPHARIS MACULARIUS)

Intravenous alfaxalone, administered at a dose of 5 mg/kg in the jugular vein, was evaluated in 20 leopard geckos (Eublepharis macularius) to ascertain its ability to provide anesthesia. The induction time, time to loss of mandibular tone, interval of deep anesthesia, and full recovery time were 27.5 ± 30.7 seconds (10 to 56 seconds), 1.3 ± 1.4 minutes (11 seconds to 4 minutes), 12.5 ± 2.2 minutes (11.11 to 15.39 minutes), and 18.8 ± 12.1 minutes (10.4 to 52.31 minutes), respectively. A significant reduction in heart rate (74 ± 12.9 beats/minute) was recorded between 2 and 24 minutes after alfaxalone administration. A significant decrease in respiratory rate (26.8 ± 10.1 breaths/minute) was recorded 2 minutes after alfaxalone administration, and respiratory rate remained lower than the basal rate (31.4 ± 3.1 breaths/minute) for 24 minutes but without statistical significance. The intravenous administration of alfaxalone in leopard geckos achieved a rapid onset of anesthesia and a suitable recovery time. Based on this investigation, an afaxalone dose of 5 mg/kg intravenously proved to be suitable for sedation before tracheal intubation. Moreover, the administration route via the jugular vein, was acceptable in leopard geckos; a species in which other venipuncture sites can be challenging or inaccessible.     

What is your diagnosis? Peritoneal effusion from a dog

Abstract: A 5‐year‐old, female Italian hound dog was presented with progressive weight loss, anorexia, and lethargy. Physical examination abnormalities included poor body condition, abdominal distension, splenomegaly, and areas of crusty alopecia on the head and limbs. Clinicopathologic abnormalities included mild normocytic normochromic anemia, moderate hyperproteinemia and hyperglobulinemia, mild hypoalbuminemia, and hyponatremia, a mild increase in serum alkaline phosphatase activity, and a moderate to marked increase in β‐ and γ‐globulins on serum protein electrophoresis. Abdominal ultrasonography revealed peritoneal effusion. Abdominocentesis yielded ～200 mL of serosanguinous, slightly turbid fluid with 2.6 × 10⁹ nucleated cells/L, and a protein concentration of 32 g/L. Cytologic specimens of the fluid contained a mixed population of inflammatory cells. Intracytoplasmic inclusions identified as Leishmania sp. amastigotes were observed in numerous macrophages and also free in the background. An ELISA for canine Leishmania sp. antibody was positive. The abdominal effusion resolved within a few days of beginning treatment with meglumine antimoniate and allopurinol. Finding Leishmania amastigotes in peritoneal fluid is rare in canine leishmaniasias and allows an easy, quick diagnosis of the disease.