Multivariate analysis and digital twin modelling: Alternative approaches to evaluate molecular relaxation in photoacoustic spectroscopy.

A comparative analysis of two different approaches developed to deal with molecular relaxation in photoacoustic spectroscopy is here reported. The first method employs a statistical analysis based on partial least squares regression, while the second method relies on the development of a digital twin of the photoacoustic sensor based on the theoretical modelling of the occurring relaxations. Methane detection within a gas matrix of synthetic air with variable humidity level is selected as case study. An interband cascade laser emitting at 3.345 µm is used to target methane absorption features. Two methane concentration ranges are explored targeting different absorptions, one in the order of part-per-million and one in the order of percent, while water vapor absolute concentration was varied from 0.3 % up to 2 %. The results achieved employing the detection techniques demonstrated the possibility to efficiently retrieve the target gas concentrations with accuracy > 95 % even in the case of strong influence of relaxation effects.

Fasting mimicking diet in mice delays cancer growth and reduces immunotherapy-associated cardiovascular and systemic side effects.

Immune checkpoint inhibitors cause side effects ranging from autoimmune endocrine disorders to severe cardiotoxicity. Periodic Fasting mimicking diet (FMD) cycles are emerging as promising enhancers of a wide range of cancer therapies including immunotherapy. Here, either FMD cycles alone or in combination with anti-OX40/anti-PD-L1 are much more effective than immune checkpoint inhibitors alone in delaying melanoma growth in mice. FMD cycles in combination with anti-OX40/anti-PD-L1 also show a trend for increased effects against a lung cancer model. As importantly, the cardiac fibrosis, necrosis and hypertrophy caused by immune checkpoint inhibitors are prevented/reversed by FMD treatment in both cancer models whereas immune infiltration of CD3+ and CD8+ cells in myocardial tissues and systemic and myocardial markers of oxidative stress and inflammation are reduced. These results indicate that FMD cycles in combination with immunotherapy can delay cancer growth while reducing side effects including cardiotoxicity.

Widely-tunable mid-infrared fiber-coupled quartz-enhanced photoacoustic sensor for environmental monitoring.

A compact widely-tunable fiber-coupled sensor for trace gas detection of hydrogen sulfide (H2S) in the mid infrared is reported. The sensor is based on an external-cavity quantum cascade laser (EC-QCL) tunable between 7.6 and 8.3 µm wavelengths coupled into a single-mode hollow-core waveguide. Quartz-enhanced photoacoustic spectroscopy has been selected as detecting technique. The fiber coupling system converts the astigmatic beam exiting the laser into a TEM(00) mode. During a full laser scan, we observed no misalignment between the optical beam and the tuning fork, thus making our system applicable for multi-gas or broad absorber detections. The sensor has been tested on N2:H2S gas mixtures. The minimum detectable H2S concentration is 450 ppb in ~3 s integration time, which is the best value till now reported in literature for H2S optical sensors.

Advanced glycation end products and sorbitol in blood from differently compensated diabetic dogs.

Canine diabetes mellitus (DM) is a common metabolic disorder with long term complications, most of which are caused by glycosylation of structural proteins, decreases in antioxidant concentrations, altered osmotic balance and hypoxia due to impaired oxygen transport. Previous studies have demonstrated that under hyperglycemic conditions canine erythrocytes undergo swelling, probably due to activation of the polyol pathway. The present work aimed to assess the plasma concentration of advanced glycation end (AGE) products, stable Amadori-products generated by non-enzymatic glycosylation of proteins and the intracellular concentration of sorbitol, produced by the activation of polyol pathway in 34 blood samples from diabetic dogs and in 14 controls. AGE products were significantly higher (p<0.01) in plasma from diabetic dogs compared with control animals. The sorbitol concentration in erythrocytes was also significantly higher in diabetic dogs and, in particular, in poorly compensated animals and in dogs with ketonuria. In five cases that were analysed before and after clinical improvement, sorbitol concentration was found to correlate with improvement. These results suggest that non-specific glycosylation is increased and that the polyol pathway is activated in diabetic dogs in a manner that is proportionate to the severity of disease. Moreover, the concentration of AGE products and sorbitol may be useful for monitoring the onset of diabetic complications and assessing the most appropriate therapeutic approaches for management of canine DM.

Changes in some acute phase protein and immunoglobulin concentrations in cats affected by feline infectious peritonitis or exposed to feline coronavirus infection.

The possible role of some acute phase proteins (APPs) and immunoglobulins in both the pathogenesis and diagnosis of feline infectious peritonitis (FIP) has been investigated. Serum protein electrophoresis and the concentration of haptoglobin (Hp), serum amyloid A (SAA), alpha(1)-acid glycoprotein (AGP), IgG and IgM were evaluated in cats exposed to feline coronavirus (FCoV) and in cats with FIP. The highest concentration of APPs was detected in affected cats, confirming the role of these proteins in supporting a clinical diagnosis of FIP. Repeated samplings from both FIP affected and FCoV-exposed cats showed that when FIP appeared in the group, all the cats had increased APP levels. This increase persisted only in cats that developed FIP (in spite of a decrease in alpha(2)-globulins) but it was only transient in FCoV-exposed cats, in which a long lasting increase in alpha(2)-globulins was observed. These results suggest that changes in the electrophoretic motility of APPs or APPs other than Hp, SAA and AGP might be involved in the pathogenesis of FIP or in protecting cats from the disease.

Some aspects of erythrocyte metabolism in insulin-treated diabetic dogs.

Insulin-dependent diabetes mellitus (IDDM) is a common metabolic disease often complicated by a number of pathological conditions among which are haematological changes and alterations in blood cell function. Human and feline diabetes mellitus patients have been reported to be associated with oxidative stress that can lead to membrane alterations and to reduced erythrocyte life-span. Erythrocyte function in dogs affected by IDDM has been investigated during insulin therapy, paying attention to antioxidant status, membrane resistance, enzyme activities and 2,3-diphosphoglycerate (2,3DPG) concentration. Thirteen diabetic and 36 healthy dogs were bled and haematology and blood chemistry assays were performed to evaluate the degree of compensation. Osmotic fragility, the activities of the enzymes glucose-6-phosphate dehydrogenase (G6PD) and pyruvate-kinase (PK) and the concentrations of reduced glutathione (GSH) and 2,3DPG were evaluated in the erythrocytes. Diabetic dogs did not differ from controls in terms of haematological parameters, except for higher numbers of platelets. Higher values of fructosamine, glucose, protein, plasma potassium and calculated osmolality were detected in the plasma from diabetic dogs. No differences were detected in osmotic fragility, GSH concentration and PK activity between the two groups but 2,3DPG concentration and G6PD activity were statistically significantly higher in the diabetic group. The results indicate minimal alterations in erythrocyte functions occur in insulin-treated diabetic dogs. This contrasts with what has been reported for IDDM humans and cats.

Laboratory changes consistent with feline infectious peritonitis in cats from multicat environments.

The present study describes the prevalence of haematological and electrophoretic changes consistent with the diagnosis of feline infectious peritonitis (FIP) in cats without FIP living in six multicat environments with different prevalence of FIP and of other diseases. The results allow designing haematological and electrophoretic profiles typical of each group, most likely depending on the management and on the health status of the group rather than on the prevalence of FIP. In fact, many cats from the colonies with open management and frequent outbreaks of infectious diseases other than FIP had one or more haematological and/or electrophoretical changes consistent with FIP, compared with the reference ranges. In the case of non-specific clinical signs such as fever or neurological signs because of diseases other than FIP, these cats would be erroneously considered as affected by FIP and euthanasized. The use of internal ranges designed on the basis of repeated samplings from non-symptomatic cats allows avoiding these misinterpretations. Results from cats with symptoms consistent with FIP living in the same colonies were also compared with both the reference ranges and the internal ones: such a comparison demonstrated that the use of internal ranges rarely affected the possibility to correctly diagnose the disease in cats with symptoms suggestive of FIP.

Evaluation in vitro of canine neutrophil function.

Polymorphonuclear granulocyte (PMN) phagocytosis may be affected by many pathological changes. A panel of tests requiring relatively small volumes of blood was applied to 16 healthy dogs in order to obtain normal values and to standardize techniques. PMNs were isolated by discontinuous Percoll gradients; chemotaxis was tested in a modified Boyden chamber using the leading front method; fluorescinated yeast uptake was evaluated on a slide and superoxide (SO) production and adherence was carried out on a microtitre plate. The different aspects of phagocytosis showed no correlation with one another. Better results were obtained using a 60 min incubation period using interleukin-8 (25 ng/mL) as an activator for chemotaxis, and incubating plates for 30 min with phorbol myristate acetate (10(-6)mol/L) to assess SO production.

Optical Sensor for real-time Monitoring of CO(2) Laser Welding Process.

An optical sensor for real-time monitoring of laser welding based on a spectroscopic study of the optical emission of plasma plumes has been developed. The welding plasma's electron temperature was contemporarily monitored for three of the chemical species that constitute the plasma plume by use of related emission lines. The evolution of electron temperature was recorded and analyzed during several welding procedures carried out under various operating conditions. A clear correlation between the mean value and the standard deviation of the plasma's electron temperature and the quality of the welded joint has been found. We used this information to find optimal welding parameters and for real-time detection of weld defects such as crater formation, lack of penetration, weld disruptions, and seam oxidation.