Forecasting Response to Treatment with Global Deep Learning and Patient-Specific Pharmacokinetic Priors.

Forecasting healthcare time series is crucial for early detection of adverse outcomes and for patient monitoring. Forecasting, however, can be difficult in practice due to noisy and intermittent data. The challenges are often exacerbated by change points induced via extrinsic factors, such as the administration of medication. To address these challenges, we propose a novel hybrid global-local architecture and a pharmacokinetic encoder that informs deep learning models of patient-specific treatment effects. We showcase the efficacy of our approach in achieving significant accuracy gains for a blood glucose forecasting task using both realistically simulated and real-world data. Our global-local architecture improves over patient-specific models by 9.2-14.6%. Additionally, our pharmacokinetic encoder improves over alternative encoding techniques by 4.4% on simulated data and 2.1% on real-world data. The proposed approach can have multiple beneficial applications in clinical practice, such as issuing early warnings about unexpected treatment responses, or helping to characterize patient-specific treatment effects in terms of drug absorption and elimination characteristics.

Wave-Like Dose-Dependence of the Stimulating Effects of Dimebon on Cognition in a Wide Dose Range.

Comparison of the cognition-stimulating effects of Dimebon in a wide dose range revealed a non-monotonic and nontrivial wave-like dose-dependence of its activity. Positive results were obtained at low (0.02-0.05 mg/kg) or high (5-10 mg/kg) doses of Dimebon, while intermediate doses were ineffective. This type of the dose dependence of the pharmacological effect can indicate that the substance has several targets. This fact should be taken into consideration when selecting the doses and concentrations of the substance and its analogues for further studies, and for planning treatment schemes and administration doses in clinical studies.

α-Synuclein knockout mice have cognitive impairments.

α-Synuclein is a member of the synuclein family of cytoplasmic, predominantly neuron-specific proteins. Considerable amount of α-synuclein is found in axons and presynaptic terminals of neurons located in brain areas responsible for emotions and memory. In the present study we have carried out behavioral evaluation of spatial and working long-term memory of α-synuclein knockout mice. Our data shows that α-synuclein knockout mice have reduced learning ability in tests requiring both working and spatial memory. For the first time we have demonstrated that α-synuclein is necessary for these types of learning.

[Targeted inactivation of gamma-synuclein gene affects anxiety and exploratory behaviour of mice].

Gamma(gamma)-synuclein is a member of synuclein family of cytoplasmic and predominantly neuronal proteins found only in vertebrates. Gamma-synuclein is abundant in axons and presynaptic terminals of neurons localized in brain regions involved in emotions, learning and memory. However, the role of gamma-synuclein in these brain functions was not previously assessed. We have demonstrated for the first time that the loss of gamma-synuclein results in a significant increase in the level of orientation response in novel environment and decrease in the level of state anxiety.

[Changed functional ability of the lungs after lobectomy in patients with concomitant chronic obstructive disease of the lungs].

Lobectomy is the operation of choice for many diseases of pulmonary pathology, lung cancer being the most frequent indication to it. Smoking, as a common etiological factor, leads to a frequent combination of chronic obstructive disease of the lungs (CODL) and lung cancer. The expected disturbance of lung function after operation in such patients can make it not necessary. However, the functional results of lobectomy in CODL patients still remain not studied. The aim of this prospective investigation was to study effects of lobectomy in patients with diseases of the lung parenchyma without hypoventilation or partial atelectasis. 76 patients were divided into 2 groups: 35 patients with CODL and 41 patients without CODL. In patients with CODL after lobectomy the external ventilation function was less affected than in patients without it. The generally accepted formula for the calculation of the postoperative VFE 1 reliably increased the prognosed reduction of this index. Reduction of the indices of the external ventilation function after lobectomy was less pronounced in patients with the medium and severe degree of CODL.

The effects of estrogens on learning in rats with chronic brain cholinergic deficiency in a Morris water test. Identification of the "passive swimming" component.

Chronic decreases in brain cholinergic functions due to intraventricular administration of the neurotoxin AF64A were accompanied by increases in the latent period of locating an invisible platform during training of rats in a Morris water test, as compared with control sham-operated animals. Recordings of the animals' movement trajectories using a video camera along with an original computer program (Behavioral Vision) showed that administration of 17beta-estradiol and its synthetic analog J-861 (0.2 mg/kg p.o. daily for seven days before and 10 days after single intraventricular injections of AF64A) improved learning. The directivity of platform search trajectories was assessed quantitatively using a new parameter--trajectory straightness. Introduction of the "passive swimming" parameter allowed periods of immobility in water to be identified within the total latent period in animals after administration of AF64A; 17beta-estradiol but not J-861 "eliminated" these periods. The new parameters (especially trajectory straightness) allowed the ability to learn to be discriminated from decreases in mobility, including mobility losses due to study agents, in the Morris water test.

[Effects of estrogens on learning of rats with chronic brain cholinergic deficit in Morris water maze]. / Vliianie éstrogenov na obuchenie krys s khronicheskim kholinergicheskim defitsitov v mozge v vodnom teste Morrisa. Vydelenie komponenta "passivnogo plavaniia".

A chronic deprivation of brain cholinergic functions in rats caused by intracerebroventricular injection of neurotoxin AF64A increases the escape latency in Morris water maze test as compared to control sham-operated animals. Measurements and analysis of rat movement tracks using an original computerized "Behavioral Vision" system revealed the ability of 17 beta-Estradiol and its synthetic isomer J-861 (both administered daily in per os dose 0.2 mg/kg during 7 days before and 10 days after a single intracerebroventricular injection of AF64A) to improve learning of the animals. Directivity of search trajectories was estimated by a novel index of track straightness. The introduction of an index of "passive swimming" made it possible to reveal episodes of immobility in water-maze behavior of AF64A-injected animals. Unlike J-861, 17 beta-Estradiol almost completely eliminated these episodes. The newly developed indices (especially straightness) seem to be very useful in differentiating learning ability of rats from a decrease in their mobility in the Morris water-maze test, in particular, in case of the estrogens under study.

Comparison of the effect of NT-0409 and antidementia drugs on learning and memory in rats with chronic cerebral cholinergic deficiency.

Systemic oral administration of NT-0409, a new synthetic agonist of AMPA subtype glutamate receptor, to rats with chronic partial AF64A-induced deprivation of cholinergic functions improved their learning in a Morris water maze. NT-0409 is close to memantine by the effect on learning and, in contrast to cholinomimetic arisept, ensures longer retention of the developed habit.

Effects of 17 beta-estradiol and its isomer 17 alpha-estradiol on learning in rats with chronic cholinergic deficiency in the brain.

It was shown for the first time that estrogens 17 beta- and 17 alpha-estradiols compensate impaired cognitive functions in rats with partial chronic deprivation of cholinergic functions in the central nervous system induced by intracerebral administration of selective cholinergic neurotoxin AF64A. 17 beta-Estradiol produced strong dose-dependent changes in the weights of hormone-sensitive endocrine glands, while 17 alpha-estradiol did not affect the weight of the gonads and slightly influenced (in high concentration) the weights of the adrenal glands and thymus. The positive effects of exogenous 17 beta- and 17 alpha-estradiols on cognitive functions are due to their antioxidant properties, rather than due to specific action on hormone-sensitive endocrine glands.

[Stimulation of medical personnel work in operating rooms]. / Stimulirovanie truda meditsinskogo personala v operatsionnoi.

Preliminary results of experimental trial on stimulation of medical staff's labour in the operation unit, held in medical institutions of Chelyabinsk, has been analysed. As a basis for calculation of the payments for the work, the labour expenditures of each member of surgical team (surgeon, assistant, anesthesiologist, surgical nurse, anesthesist, litter bearer nurse) and the cost of 1 hour work were assessed, the degree of the difficulty of each operation, as well as the total cost of the procedure was determined. Registration of the work of all members of the surgical team and its payment, according to the quantity and the quality of the performed operations, demonstrates the stage of transition to the system of payment for the labour, i.e.--for the concrete work, done by somebody of the staff (for the treatment of some patient, etc.). The evaluation of the work according to the number of treated patients (operations being done) and to the quality of the treatment provides the conditions for personal financial incentive of surgical staff to intensification of their work and contributes to the achievements of favourable final results and in the same time--it provides decrease of the terms for patients' stay in the hospital, saving money and material resources.

Endoscopic resection of rectal carcinoid tumors using aspiration lumpectomy.

BACKGROUND AND STUDY AIMS: Although carcinoid tumors have malignant potential, complete resection can be curative if the lesion is located within the submucosal layer. In this study, we evaluated the effectiveness of endoscopic aspiration lumpectomy for the treatment of small rectal carcinoid tumors. PATIENTS AND METHODS: Eight patients with rectal carcinoid tumors less than 10 mm in diameter and located within the submucosa were treated by aspiration lumpectomy. It was confirmed that none of the patients had any metastatic lesions before treatment. The procedure was carried out using an endoscope with a cylinder attached to the tip and a Teflon tube along its outer axis. The lesion was aspirated into the cylinder, grasped by a snare passed through the tube, and then resected. RESULTS: All lesions were excised completely, without any complications. The resected specimens were circular, with the lesions located in the center of the surrounding mucosa. The diameter of the specimens (mean +/- SD) was 18.3 +/- 6.2 mm. All tumors were histologically typical, and the lateral and bottom margins of the specimens were free of tumor cells. No recurrences or distant metastases were found in any of the patients during the mean observation period of 13.3 months. CONCLUSIONS: We conclude that aspiration lumpectomy is a useful and safe technique for the treatment of small rectal carcinoid tumors contained within the submucosa.

[Treatment of undeveloped external intestinal fistulas]. / Lechenie nesformirovannykh haryzhnykh svishcheí.

135 patients with undeveloped intestinal fistulas (116-85.9%-males, and 19-14.1%-females) were followed up by the authors. The patients underwent surgery for acute appendicitis-17 (12.6%), traumatic injuries of abdominal organs-78 (57.8%), acute intestinal obstruction-33 (24.4%), inflammatory processes of the uterus and adnexites-7 (5.2%). Small bowel fistulas were observed in 88 (65.2%) of patients, large bowel fistulas-in 47 (34.8%). The optimal mode of treatment for the fistula seems the obturation of fistula duct by means of catheter of Petzer of Foley. It is guite necessary to perform a simultaneous broad exploration of abscesses of anterior abdominal wall and their sanatation by the method of flowing-aspiration therapy by N.N. Kanshin. For elimination of endotoxicosis the ultraviolet irradiation of autologous blood was used as well as intravenous laser irradiation of blood, hemosorption, plasmapheresis, infusions of plasma and plasma substitutional solutions. The patients were given 2-3 antibiotics of a broad spectrum of action, one of which being obligatory introduced intravenously. From 135 patients 104 (77.0%) underwent surgery. The method of choice in small bowel fistulas the authors suggest intraabdominal resection of the bowel, and in large bowel fistulas-resection of 3/4 by the method of A.V. Melnikov. 17 patients (17.3%) died after the surgery.

Endosonographic characterization of duodenal elevated lesions.

BACKGROUND: Endoscopic diagnosis of duodenal elevated lesions is problematic for two reasons. Endoscopic biopsy often fails to confirm a histologic diagnosis of submucosal lesions. Moreover, a biopsy specimen is often insufficient to verify a differential diagnosis of mucosal lesions. In this study, we evaluated the usefulness of endosonography in the resolution of these problems. METHODS: The endoscopic and endosonographic features of 15 duodenal elevated lesions that had been confirmed histologically in our hospital were reviewed retrospectively. RESULTS: Of the 15 cases, 8 were submucosal lesions (lipoma, Brunner's gland hyperplasia, lymphangioma, carcinoid tumors, leiomyoma, and malignant lymphoma); the rest were mucosal lesions. A correct histologic diagnosis based on endoscopic biopsies was obtained in only 6 cases (three submucosal lesions and three mucosal lesions). On the other hand, ultrasonography was useful in the characterization of all submucosal lesions based on their echo level, layer of origin, and tissue homogeneity. As for mucosal lesions, the depth of infiltration was correctly estimated with endosonography. Either endoscopic resection or surgery was selected on the basis of endosonographic information. CONCLUSIONS: We conclude that endosonography is useful in the differential diagnosis of submucosal lesions and in determining suitable treatment methods for duodenal mucosal and submucosal lesions.

[Kinetics of serum albumin adsorption on the macroporous glass MPS-250 GKH]. / Kinetika sorbtsii cyvorotochnogo al'bumina na makroporistom stekle MPS-250 GKH.

Intrinsic diffusion (defined as diffusion within micropores or microgranules) was shown to be a major factor that determines the kinetics of bovine serum albumin adsorption to macroporous silica MPS-250 GKh. The effective coefficient of intrinsic diffusion (within the silica phase) was calculated (Def = 7 x 10(-7) cm2/s).

Endoscopic aspiration lumpectomy of esophageal leiomyomas derived from the muscularis mucosae.

OBJECTIVES: There is still much debate about the indications and best technique for endoscopy for the treatment of esophageal leiomyomas. We developed a novel technique for endoscopic aspiration lumpectomy and used it in patients with esophageal leiomyomas derived from the muscularis mucosae. METHODS: Nine patients with esophageal leiomyomas were treated with informed consent. The indication for intervention was based on the endosonographic confirmation of a tumor originating from the 2nd layer of the esophagus. We attached a transparent cylinder to the tip of an endoscope and a snare-guide tube to the outer axis of the scope. After endoscopic suction of the tumor into the cylinder, the snare was pushed open. The tumor was grabbed at its base with the entire surrounding mucosa, and removed. RESULTS: The overall procedure time averaged 18 minutes, and there were no complications in any of the subjects. The resected specimens were elliptical with a mean long diameter of 22 +/- 4 mm and a mean short diameter of 17 +/- 4 mm. Complete resection was possible in eight of the nine tumors that were under 2 cm in diameter. After a follow-up period of 4 to 27 months (mean 11 months), no recurrence was found in any of the completely resected cases. CONCLUSIONS: Endoscopic aspiration lumpectomy has been proven to be a safe, effective, and less invasive procedure for small esophageal leiomyomas derived from the muscularis mucosae.