The influence of the initial reinforcement value on physiological parameters of conditioned respiratory reflex

BACKGROUND: Most of the studies of the role of reinforcement in the formation of adaptive behavior were performed on animals. At the same time, such an experimental model as a conditioned respiratory reflex to resistive load, has not been sufficiently studied, although an unconditioned reflex to additional resistance to breathing, on the basis of which a conditioned one is formed, is a stable reaction that has clear quantitative evaluation criteria, and the conditioned reflex itself is relatively strong, easily normalized, reluctantly extinguished and does not require observance of a number of methodological conditions. AIM: To study the influence of the initial value of reinforcement on the physiological parameters of the conditioned respiratory reflex. MATERIALS AND METHODS: The work was carried out on people of both genders, 16 people, aged 18 to 44, practically healthy. The unconditioned stimulus was applied in four gradations of external respiratory resistance: 11; 28; 54; 76 cm water • l/sec. The conditioned reflex was formed by the classic type, the duration of application of the conditioned stimulus was not fixed and its end coincided with the end of the action of the unconditioned stimulus, the period of the isolated action of the conditioned signal was 10 sec. As physiological parameters, we studied the ventilatory and motor parameters of respiration, the temporal parameters of the conditioned reaction. RESULTS: The influence of the unconditioned stimulus on the value of the tidal volume after the combination in all subjects depended on the absolute reinforcement values used in this combination, and was weakly connected with the initial reinforcement value. The influence of the external resistance on breathing used in this combination was significantly higher on such parameters as intraoral pressure of inspiration and expiration; the role of the initial reinforcement value in the dynamics of the given parameters was not confirmed. CONCLUSIONS: Most “sensitive” to the action of the initial value of the resistive load were the temporal parameters of the conditioned respiratory reflex — the latent period and the time of the conditioned reaction; the parameters of the “ventilatory” and “motor” outputs of the external respiration system changed noticeably, the spirometric parameters showed very little dynamics, and the capnographic parameters practically did not change. The dynamics of the parameters of the conditioned respiratory reflex to increased external respiratory resistance permits to single out groups of signs that have the greatest semantic significance for evaluation of the system-forming and discriminating role of the initial gradation of the reinforcement factor.

Sniffer dogs can identify lung cancer patients from breath and urine samples

Background Lung cancer is the most common oncological cause of death in the Western world. Early diagnosis is critical for successful treatment. However, no effective screening methods exist. A promising approach could be the use of volatile organic compounds as diagnostic biomarkers. To date there are several studies, in which dogs were trained to discriminate cancer samples from controls. In this study we evaluated the abilities of specifically trained dogs to distinguish samples derived from lung cancer patients of various tumor stages from matched healthy controls. Methods This single center, double-blind clinical trial was approved by the local ethics committee, project no FF20/2016. The dog was conditioned with urine and breath samples of 36 cancer patients and 150 controls; afterwards, further 246 patients were included: 41 lung cancer patients comprising all stages and 205 healthy controls. From each patient two breath and urine samples were collected and shock frozen. Only samples from new subjects were presented to the dog during study phase randomized, double-blinded. This resulted in a specific conditioned reaction pointing to the cancer sample. Results Using a combination of urine and breath samples, the dog correctly predicted 40 out of 41 cancer samples, corresponding to an overall detection rate of cancer samples of 97.6% (95% CI [87.1, 99.9%]). Using urine samples only the dog achieved a detection rate of 87.8% (95% CI [73.8, 95.9%]). With breath samples, the dog correctly identified cancer in 32 of 41 samples, resulting in a detection rate of 78% (95% CI [62.4, 89.4%]). Conclusions It is known from current literature that breath and urine samples carry VOCs pointing to cancer growth. We conclude that olfactory detection of lung cancer by specifically trained dogs is highly suggestive to be a simple and non-invasive tool to detect lung cancer. To translate this approach into practice further target compounds need to be identified.

A New Mathematical Framework for Describing Thin-Reaction-Zone Regime of Turbulent Reacting Flows at Low Damköhler Number

Recently, Sabelnikov et al. (2019) developed a phenomenological theory of propagation of an infinitely thin reaction sheet, which is adjacent to a mixing layer, in a constant-density turbulent flow in the case of a low Damköhler number. In the cited paper, the theory is also supported by Direct Numerical Simulation data and relevance of such a physical scenario to highly turbulent premixed combustion is argued. The present work aims at complementing the theory with a new mathematical framework that allows for appearance of thick mixing zones adjacent to an infinitely thin reaction sheet. For this purpose, the instantaneous reaction-progress-variable c ( x , t ) is considered to consist of two qualitatively different zones, that is, (i) mixture of products and reactants, c ( x , t ) < 1 , where molecular transport plays an important role, and (ii) equilibrium products, c ( x , t ) = 1 . The two zones are separated by an infinitely thin reaction sheet, where c ( x , t ) = 1 and | ∇ c | is fixed in order for the molecular flux into the sheet to yield a constant local consumption velocity equal to the speed of the unperturbed laminar reaction wave. Exact local instantaneous field equations valid in the entire spaceare derived for the conditioned (to the former, mixing, zone) reaction progress variable, its second moment, and instantaneous characteristic functions. Averaging of these equations yields exact, unclosed transport equations for the conditioned reaction-progress-variable moments and Probability Density Function (PDF), as well as a boundary condition for the PDF at the reaction sheet. The closure problem for the derived equations is beyond the scope of the paper.

Learning-induced plasticity in the barrel cortex is disrupted by inhibition of layer 4 somatostatin-containing interneurons

ABSTRACTLearning-related plasticity in the cerebral cortex is linked to the action of disinhibitory circuits of interneurons. Pavlovian conditioning, in which stimulation of the vibrissae is used as conditioned stimulus, induces plastic enlargement of the cortical functional representation of vibrissae activated during conditioning, visualized with [14C]-2-deoxyglucose (2DG). Using layer-specific, cell-selective DREADD transductions, we examined the involvement of somatostatin- (SOM-INs) and vasoactive intestinal peptide (VIP-INs)-containing interneurons in the development of learning-related plastic changes. We injected DREADD-expressing vectors into layer IV (L4) barrels or layer II/III (L2/3) areas corresponding to activated vibrissae. The activity of interneurons was modulated during training, and 2DG maps were obtained 24 h later. In mice with L4 but not L2/3 SOM-INs suppressed during conditioning, the plastic change of whisker representation and the conditioned reaction were absent. No effect of inhibiting VIP-INs was found. We report that the activity of L4 SOM-INs is indispensable for learning-induced plastic change.

The inhibitory effects of orexin antagonists on the reinforcing properties of amphetamine during brain self-stimulation and the development of a conditioned place preference in rats

Purpose. In experiments on rats, we studied the self-stimulation reaction of the lateral hypothalamus and the conditioned reaction of place preference upon activation (orexin) and blockade of the orexin receptor by SB-408124 or Orexin B18-28 in rats. Methods. As behavioral methods, self-stimulation of the lateral hypothalamus and a conditioned reaction of place preference were chosen. Orexin and its antagonists SB-408124 or Orexin B18-28 (Sigma, USA) were used for pharmacological analysis. All preparations were used in 3 dosages: 0.1, 1.0, 10 g, injecting into the lateral ventricle of the brain (i.v.) through the implanted cannula. Results. It has been shown that peptide substances of orexin and its antagonists modulate the conditional and unconditional reinforcing properties of the brain. The studied orexin antagonists showed a dose-dependent (0.1-1-10 g, i.v.) inhibitory effect on the self-stimulation of the lateral hypothalamus, activated by indirect adrenergic agonist amphetamine (-phenylisopropylamine). The inhibitory effect of orexin antagonists also manifested itself in relation to the generation and expression of a preference for amphetamine place, especially when using high doses of the peptide (10 g i.v.). Conclusion. The effect of orexin antagonists can be used in the development and study of antinarcotic drugs.

Diagnosis of lung cancer by canine olfactory detection in urine and breath samples.

e13067 Background: Lung cancer is the leading oncological cause of death in western countries. The WHO estimated 2.09 million newly diagnosed lung cancer patients in 2018 worldwide. Although early detection is crucial for patients outcome, no surveillance tools exist. Dogs have a highly sensitive olfactory system which is already used in several ways, such as drug and ketone detection. The aim of the study was to evaluate the capability of a classically conditioned domestic dog to accurately distinguish samples of lung cancer patients of all tumor stages in urine and breath from healthy controls. Methods: This monocentric clinical trial was an original study and approved by the local ethics committee. After conditioning a domestic dog with samples of 186 patients (36 cancer patients and 150 control patients), further 246 patients aged between 45 and 80 entered into the study: 41 patients with a histologically proven lung cancer comprising all different stages and 205 control samples of healthy individuals with no cancer history. Two urine and two breath samples were collected of each patient and immediately shock frozen at -80°C. Urine and breath samples were separately exposed to the dog in a randomized, double-blinded manner, resulting in a specific conditioned reaction indicating the cancer sample. Results: The dog correctly predicted cancer in 36 of 41 urine samples, corresponding to a sensitivity of 87.8% and a specificity of 97.6%. Concerning the breath samples, the dog correctly predicted cancer in 32 of 41 samples, corresponding to a sensitivity of 78% and a specificity of 95.6%. Combining both techniques, the dog correctly identified 40 of 41 cancer samples, leading to an overall sensitivity of 97.6%. The specificity is not evaluable. Conclusions: Urine and breath carry volatile organic compounds indicating cancer growth, as previously reported. Canine olfactory detection of lung cancer is a simple tool to detect lung cancer non-invasively. Further identification of target compounds for technical translation of this approach is under way, with the potential for the development of a bionic electronic nose.

Gypsum Dehydration to Alpha-Gypsum in Mixed Chloride Solutions

Brno University of Technology solves in the long term the problem of alpha gypsum preparation by dehydrating the gypsum in the solution of chloride salts. This study verified that alpha-gypsum can be trouble free prepared by gypsum dehydration in solution of a number chloride salts, among others CaCl2, MgCl2 or NaCl. In the same time it was found that owing to the different electro-chemical behavior of Potassium ions, the by heat conditioned reaction of gypsum with the KCl solution the dehydration doesn’t take place, but a partial substitution of Potassium ions by Calcium ions takes place. The product of this reaction is the mineral görgeyit, K2SO4.5CaSO4.H2O.This important problem was solved by reduction of the extremely electro-chemical high mobility of Potassium ions by the method of the mixed chloride solution with Potassium and Sodium ions, the mobility of which is in comparison with the preceding only one third. Samples of hemihydrate in the solution of mixed salts were prepared and tested in conclusion of the research.

Short article: Rats learn to eat more to avoid hunger

Several recent experiments have provided evidence that the ingestion of a distinctive food by rats can be a learnt instrumental act as well as an associatively conditioned reaction. In the previous work, maintenance food was withheld for shorter and longer durations on different days following access to the training food. Extra eating before the longer fast was interpreted as avoidance of hunger. This interpretation was based on the evidence showing that extra eating as a result of classical conditioning comes from pairing food stimuli with the presence of little or no hunger because of repletion with energy nutrients. The theory that the extra eating arose from a response-depletion contingency was tested in the present experiment by training rats on only a long fast or only a short fast. Greater increase in intake was seen before the longer fast. The results also replicated previously seen cycles of increase, decrease, and renewed increase in putative deficit-avoidant eating over about three trials, indicating that the extra eating reduces the response-reinforcing hunger and that the consequent part-extinction restores reinforcement. The shape of the learning curve was consistent with these cycles occurring from the start of training, further supporting the view that the increase in food intake before a long delay in refeeding is hunger-reinforced instrumental behaviour.