Sacrosidase therapy for congenital sucrase-isomaltase deficiency

BACKGROUND: The purpose of this study was to determine if sacrosidase, a liquid produced from Saccharomyces cerevisiae containing 6000 IU of sucrase activity per mg protein, prevented symptoms of diarrhea, abdominal cramps, gas, and bloating in patients with congenital sucrase-isomaltase deficiency (CSID) consuming a normal sucrose and carbohydrate-containing diet. METHODS: Twenty-eight children (aged 5 months to 11 years) underwent a randomized, double-blind trial consisting of two phases: 1) three sucrose breath H2 tests with three single-dose treatments (placebo, sacrosidase, and sacrosidase plus milk), and 2) a dose-response phase consisting of four multidose treatments, each for 10 days of full-strength sacrosidase, 1:10 dilution, 1:100 dilution, and 1:1000 dilution. Patients who weighed less than or equal to 15 kg received a dose of sacrosidase and those who weighed more than 15 kg received 2 ml. For the dose-response phase each patient consumed a normal diet. The number of stools and severity of symptoms were recorded daily for each concentration of sacrosidase administered and compared to a baseline period during which the patient took no sacrosidase and consumed a sucrose/starch-free diet. Data were analyzed using an ANOVA model and the nonparameter Wilcoxon signed-rank test. RESULTS: Breath H2 excretion decreased significantly when patients received sacrosidase or sacrosidase plus milk compared to placebo during sucrose breath tests. During the dose-response phase significant treatment differences were observed between the two higher concentrations and the two lower concentrations of sacrosidase for both total stools (p < 0.001) and total symptom score (p = 0.003). Higher concentrations of sacrosidase were associated with fewer stools and a greater number of formed or hard stools compared to lower concentrations and compared to the baseline period. Higher concentrations were also associated with fewer symptoms of gas, abdominal cramps, or bloating, but no differences in vomiting. The only significant adverse event was wheezing in one child with a history of asthma. CONCLUSIONS: Sacrosidase is a safe, effective, well-accepted treatment to prevent gastrointestinal symptoms in patients with CSID consuming a normal diet.     

Effect of NbC and TiC precipitation on shape memory in an iron-based alloy

This paper examines the effects of TiC and NbC precipitation and prior cold rolling on the shape memory behaviour of an iron-based alloy. A precipitate-free alloy was used as a reference to investigate the relative contributions of prior-deformation and precipitation on shape memory. Heat treatment of the Nb- and Ti-containing alloys at 700 °C and 800 °C resulted in carbide precipitates between 120 nm and 220 nm in diameter. Bend testing of these samples showed a marginal increase in shape memory compared to the precipitate-free alloy. Under these conditions TiC precipitation exhibited slightly better shape memory than for NbC. However, this small increase was over-shadowed by the marked increase in shape memory that can be produced by subjecting the alloys to cold rolling followed by recovery annealing. When processed in this way, fine carbides are formed in the Ti- and Nb-containing alloys during the heat treatment. For particles >25 nm in diameter the shape memory is unaffected, but, it was found that small <5 nm particles have a detrimental effect on shape memory due to pinning of the martensite plates, thereby inhibiting their reversion to austenite. The optimum shape memory was observed in the precipitate-free alloy after cold rolling and recovery annealing.     

Differential Responses to Sigma-1 or Sigma-2 Receptor Ablation in Adiposity,Fat Oxidation,and Sexual Dimorphism

Obesity is increasing at epidemic rates across the US and worldwide, as are its co-morbidities, including type-2 diabetes and cardiovascular disease. Thus, targeted interventions to reduce the prevalence of obesity are of the utmost importance. The sigma-1 receptor (S1R) and sigma-2 receptor (S2R; encoded by Tmem97) belong to the same class of drug-binding sites, yet they are genetically distinct. There are multiple ongoing clinical trials focused on sigma receptors, targeting diseases ranging from Alzheimer’s disease through chronic pain to COVID-19. However, little is known regarding their gene-specific role in obesity. In this study, we measured body composition, used a comprehensive laboratory-animal monitoring system, and determined the glucose and insulin tolerance in mice fed a high-fat diet. Compared to Sigmar1+/+ mice of the same sex, the male and female Sigmar1−/− mice had lower fat mass (17% and 12% lower, respectively), and elevated lean mass (16% and 10% higher, respectively), but S1R ablation had no effect on their metabolism. The male Tmem97−/− mice exhibited 7% lower fat mass, 8% higher lean mass, increased volumes of O₂ and CO₂, a decreased respiratory exchange ratio indicating elevated fatty-acid oxidation, and improved insulin tolerance, compared to the male Tmem97+/+ mice. There were no changes in any of these parameters in the female Tmem97−/− mice. Together, these data indicate that the S1R ablation in male and female mice or the S2R ablation in male mice protects against diet-induced adiposity, and that S2R ablation, but not S1R deletion, improves insulin tolerance and enhances fatty-acid oxidation in male mice. Further mechanistic investigations may lead to translational strategies to target differential S1R/S2R regulations and sexual dimorphism for precision treatments of obesity.     

Evidence from microdialysis and synaptosomal studies of rat cortex for noradrenaline uptake sites with different sensitivities to SSRIs

1. Microdialysis of the frontal cortex of freely-moving rats and uptake of [3H]noradrenaline into cortical synaptosomes were used to evaluate changes in efflux of noradrenaline in vivo and uptake of [3H]noradrenaline in vitro, respectively, induced by the selective serotonin reuptake inhibitors (SSRIs), fluoxetine and citalopram, and the tricyclic antidepressant, desipramine. 2. Noradrenaline efflux was increased during local infusion into the cortex of each of these drugs. All three agents also inhibited synaptosomal uptake of [3H]noradrenaline; this inhibition was unaffected by a substantial (50%) lesion of central 5-hydroxytrytaminergic neurones induced by intracerebroventricular infusion of 5,7-DHT (150 microg). 3. A noradrenergic lesion (70%), induced by pretreatment with the selective neurotoxin, N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4, 40 mg kg(-1) i.p.), 5 days earlier, abolished the increase in noradrenaline efflux caused by local infusion of fluoxetine. In contrast, the desipramine-induced increase in efflux was greater than in non-lesioned rats whereas the effect of citalopram on noradrenaline efflux was unaffected by DSP-4 pretreatment. 4. The combined results of all these experiments suggest that there could be more than one, functionally distinct, noradrenaline uptake site in rat frontal cortex which can be distinguished by their different sensitivities to desipramine and the SSRIs, fluoxetine and citalopram.     

Biosignals offer potential for direct interfaces and health monitoring

We examine efforts to harness biosignals to enable enhanced computer interfaces. In particular, biosignals can serve for passive health monitoring for the elderly who want to remain at home but need some level of support as they age. Such devices can directly manipulate computer interfaces to give people with limited peripheral mobility some control over their environment. In contrast to the biosignal interfaces based on voluntary peripheral nerve signals, we also discuss about the brain-to-computer interfaces (BCI).     

Roll-to-roll plasma deposition machine for the production of tandem amorphous silicon alloy solar cells

A roll-to-roll plasma deposition machine for depositing multilayered amorphous alloys has been developed. The plasma deposition machine has multiple deposition areas and processes a stainless steel substrate 16 in wide continuously. Amorphous photovoltaic thin films (less than 1 μm thick) with a six-layer structure (p-i-n-p-i-n) are deposited continuously in a single pass onto a roll of stainless steel substrate 16 in wide and 1000 ft long. Mass production of low cost tandem solar cells utilizing roll-to-roll processes is now possible. A commercial plant utilizing this plasma deposition machine for manufacturing tandem amorphous silicon alloy solar cells is now in operation.     

Platform perturbations in above-water radiometry

A comparison of above- and in-water spectral measurements in coastal (but predominantly Case-1) conditions has shown that the uncertainty in above-water determinations of water-leaving radiances made from an offshore tower depends on the proximity of the above-water measurement with respect to the side of the platform. For purposes of this study the proximity of the sampling platform is parameterized as the perpendicular distance (denoted x) from the side of the sampling platform to the center of the area on the sea surface observed by the sea-viewing sensor, the so-called surface spot, which is set by the field of view of the radiometer (or the overlapping fields of view of a multiaperture sensor). Two above-water data processing methods were used to create a diagnostic variable (formulated for Case-1 waters only but also applicable to Case-2 conditions over short time scales) to quantify the presence of superstructure reflections. Based on the height of the tower, H, the analyses were partitioned into near- and far-field data sets (x < H and x > H, respectively). The primary conclusions of the radiometric intercomparisons are as follows: (a) the maximum perturbations occur very close to the tower ( x/H < 1), and, as x/H increases and approaches 1 (i.e., as the surface spot becomes as far away as the platform is high), the platform perturbations converge toward smaller and smaller values, and (b) within the far field (x > H) the platform perturbation is negligible, and a remote sensing 5% absolute accuracy objective can be satisfied.