[Bile duct repair after complete intersection]. / Opyt vosstanovleniya nepreryvnosti zhelchnykh protokov pri polnom ikh peresechenii.

OBJECTIVE: To determine the training period for imposing hepaticojejunostomy for bile duct repair. MATERIAL AND METHODS: Reconstructive surgery on the bile ducts was performed in 53 patients. We analyzed the learning curves based on the incidence of anastomotic leakage after hepaticojejunostomy. RESULTS: The learning curve has a downward nature. The number of anastomotic failures decreases by 2 times after 42 procedures. Surgeon had to perform 39-42 operations to reduce the incidence of this complication. CONCLUSION: Treatment of patients with iatrogenic intersections of the bile ducts should be provided in appropriate hospitals.

Comparative roadmaps of reprogramming and oncogenic transformation identify Bcl11b and Atoh8 as broad regulators of cellular plasticity.

Coordinated changes of cellular plasticity and identity are critical for pluripotent reprogramming and oncogenic transformation. However, the sequences of events that orchestrate these intermingled modifications have never been comparatively dissected. Here, we deconvolute the cellular trajectories of reprogramming (via Oct4/Sox2/Klf4/c-Myc) and transformation (via Ras/c-Myc) at the single-cell resolution and reveal how the two processes intersect before they bifurcate. This approach led us to identify the transcription factor Bcl11b as a broad-range regulator of cell fate changes, as well as a pertinent marker to capture early cellular intermediates that emerge simultaneously during reprogramming and transformation. Multiomics characterization of these intermediates unveiled a c-Myc/Atoh8/Sfrp1 regulatory axis that constrains reprogramming, transformation and transdifferentiation. Mechanistically, we found that Atoh8 restrains cellular plasticity, independent of cellular identity, by binding a specific enhancer network. This study provides insights into the partitioned control of cellular plasticity and identity for both regenerative and cancer biology.

[Diagnostic efficiency of transcutaneous laryngeal ultrasound in assessing the mobility of vocal cord in patients with thyroid disease]. / Diagnosticheskaya effektivnost' ul'trasonografii gortani u patsientov s zabolevaniyami shchitovidnoi zhelezy.

OBJECTIVE: To assess the diagnostic efficiency of transcutaneous laryngeal ultrasound. MATERIAL AND METHODS: Ultrasound examination of the larynx and laryngoscopy was performed in 103 patients with thyroid disease. 26 (34.21%) patients who underwent surgery on the thyroid gland direct laryngoscopy and ultrasound of the vocal folds were performed twice, before and after the operation. RESULTS: Voice folds were visualized in 76 (73.8%) people. Of the 24 men, these anatomical structures were visualized in 8 (33.3%) and in 68 (86.1%) women out of 79 cases. Violations of the function of the vocal cords during laryngoscopy were detected in 5 people, sonographically in 6 people. The coincidence of the revealed pathology with ultrasound was in 4 patients, in 3 - with sonography the diagnosis was erroneous, in 1 patient it was falsely negative and in 2 cases it was falsely positive. CONCLUSIONS: In connection with the diagnostic capabilities of the method, it is advisable to use it as a screening study in the perioperative period in patients with diseases of the thyroid gland. Laryngoscopy is indicated for patients with non-visualized vocal folds, with identified pathology with ultrasound, and with clinical signs of dysfunction of the vocal cords.

[Joint work of surgeon and assistant in minimally invasive video-assisted hemithyroidectomy and its effect on duration of surgeries and learning period]. / Sovmestnaya rabota khirurga i assistenta pri vypolnenii mini-invazivnykh videoassistirovannykh gemitireoidektomii i ee vliyanie na prodolzhitel'nost' vypolnennykh operatsii i perioda osvoeniya metodiki.

OBJECTIVE: To analyze assistants` influence on duration of surgery and learning period in minimally invasive video-assisted hemithyroidectomy. MATERIAL AND METHODS: The same surgeon performed 67 minimally invasive video-assisted hemithyroidectomies. Duration of surgery was analyzed in assistants with various number of interventions. Learning curves were designed using logarithmic function. RESULTS: Eight specialists with the same professional skill assisted to surgeon. Each of these specialists performed certain number of operations. Learning period made up 19, 26 and 44 procedures for mean numbers of assistances 21, 8 and 3, respectively. Duration of surgery in the group with 21 assistances was 63.96±2.94 min, for 3 assistances - 80.53±7.07 min in each of 6 assistants (z= -2.38; p<0.017). CONCLUSION: Constant surgeon`s assistants is a factor reducing surgery time. Higher number of operations with the same assistant has a reliable inverse correlation with surgery time and duration of learning period.

[Learning curves in acquisition of experience for new technologies]. / Izuchenie opyta osvoeniya novykh tekhnologii metodom postroeniya krivykh obucheniya.

OBJECTIVE: Analysis of national and foreign trials investigating accumulation of experience in innovative technologies using the learning curves. MATERIAL AND METHODS. S: Earching for Russian-language manuscripts was carried out within the references of the articles and in the ELIBRARY database. Foreign trials were selected from the PubMed database according to the keywords «learning curves in surgical practice¼. The discovered publications were studied for accordance with the objectives of this study. RESULTS: Accumulation of experience in new technologies by using of learning curves is valuable to improve the training, determine duration of development of new technology and the factors affecting its characteristics. CONCLUSION: The method is high-quality for comprehensive analysis of experience accumulation in new surgical technologies.

[Evaluation of experience acquisition in video-assisted hemithyroidectomy]. / Sposoby otsenki priobreteniya opyta pri osvoenii videoassistirovannykh gemitireoidektomii.

OBJECTIVE: To determine validity and adequacy of the assessment of experience acquisition in video-assisted hemithyroidectomy, to compare surgical outcomes at the learning stage and in delayed period. MATERIAL AND METHODS: Experience acquisition was studied via assessment of the duration of video-assisted hemithyroidectomy in 67 patients who were operated by the same surgeon. Time of surgery was analyzed through between-group comparison of surgical outcomes. These groups were defined arbitrarily, in exponential fashion, using the logarithm method and moving average. Risks of failure regarding duration of surgery and postoperative complications were investigated using CUSUM analysis. RESULTS: Minimum period of experience accumulation in video-assisted hemithyroidectomy (26 procedures) was determined using logarithmic analysis, maximum period (66 interventions) - using CUSUM analysis. Other approaches also showed sharp nature of the learning curve.CUSUM analysis of failures at the learning stage showed 2-fold decrease of their probability after 66 operations. However, even experience acquisitiondoes not exclude risk of failures in hemithyroidectomy. CONCLUSION: Arbitrary division of the cohort of patients seems to be unreasonable because clear number of operations necessary to achieve sustainable results does not follow it.Mathematical methods adequately reflect experience accumulation and allow determining the required number of interventions for stable results and minimum complication rate.

[Experience of reconstructive laparoscopic procedures in patients with terminal colostomy]. / Opyt osvoeniia vosstanovitel'nykh operatsii laparoskopicheski-assistirovannym sposobom u bol'nykh s kontsevoi kolostomoi.

AIM: To analyze the ways and terms of training for laparoscopy-assisted reconstruction operations via learning curves analysis and to compare the outcomes obtained both during training for technique and after that. MATERIAL AND METHODS: There were 93 reconstructive laparoscopic procedures in 58 (62.36%) patients with terminal colostomy. All patients were operated by the same surgeon. Learning curves have been created and analyzed. RESULTS: Analysis showed that all surgical features are achieved by the 30th intervention indicating the end of learning period. Significantly less surgical trauma has been observed along with development of surgery. CONCLUSION: Improved results are achieved by reduced dissection of adhesions, the use of mechanical suture for intestinal anastomosis and increased number of anastomoses made in intracorporeal fashion.

[Damage of reconstructive operations in patients after urgent obstructive resection of colon].

It was performed comparative analysis of results of reconstructive operations in 116 patients with terminal colostomy after urgent obstructive resection of colon. Damage of reconstructive operations which differ by only access was estimated. Midline access was used in 49 patients, parastomal - in 51 cases. Laparoscopic operation was applied in 16 patients. The most traumatic method was middle laparotomy for restoration of colonic integrity. Laparoscopic operations and parastomal access are less invasive. Laparoscopic operations are accompanied by longer duration, greater blood loss and later restoration of intestinal motility pattern in comparison with surgery through parastomal access. It is associated with duration and damage of adhesiotomy stage.

HspB1 dynamic phospho-oligomeric structure dependent interactome as cancer therapeutic target.

Human HspB1 (Hsp27), a molecular chaperone bearing tumorigenic and metastatic roles, is characterized by its dynamic phosphorylation and heterogenous oligomerization in response to changes in cell physiology. The phenomenon is particularly intense and specific when cells are exposed to different death inducers. This favors the hypothesis that the structural organization of HspB1 acts as a sensor which, through reversible modifications, allows cells to adapt and/or mount a protective response. A large number of HspB1 interacting partners have already been described in the literature. Specific changes in oligomerphosphorylation organization may therefore allow HspB1 to interact with the more appropriate polypeptides and to subsequently modulate their folding/activity and/or half-life. This could indirectly link HspB1 to multiple cellular functions and could explain the apparently unrelated effects associated to its over- or underexpression. In cancer, HspB1 is tumorigenic, stimulates metastasis and provide cancer cells with resistance to many anti-cancer drugs, so compounds aimed at disrupting HspB1 deleterious pro-cancer activity are actively looked for. One example, is brivudine that impairs HspB1 ability to recognize pathological protein substrates and appears as a promising anti-cancer drug. Similarly, we have observed that peptide aptamers that specifically interfere with HspB1 structural organization reduced its anti-apoptotic and tumorigenic activities. We propose that, in addition to RNA interference approaches, the tumorigenic activity of HspB1 could be inhibited by altering HspB1 structural organization and consequently its interaction with inappropriate procancerous polypeptide partners. Hence, developping HspB1 structure-based interfering strategies could lead to new anti-cancer drugs discovery.

Targeting heat shock protein 27 (HspB1) interferes with bone metastasis and tumour formation in vivo.

BACKGROUND: The small stress heat shock protein 27 (Hsp27) has recently turned as a promising target for cancer treatment. Hsp27 upregulation is associated with tumour growth and resistance to chemo- and radio-therapeutic treatments, and several ongoing drugs inhibiting Hsp27 expression are under clinical trial. Hsp27 is now well described to counteract apoptosis and its elevated expression is associated with increased aggressiveness of several primary tumours. However, its role in the later stage of tumour progression and, more specifically, in the later and most deadly stage of tumour metastasis is still unclear. METHODS/RESULTS: In the present study, we showed by qRT-PCR that Hsp27 gene is overexpressed in a large fraction of the metastatic breast cancer area in 53 patients. We further analysed the role of this protein in mice during bone metastasis invasion and establishment by using Hsp27 genetically depleted MDA-MB231/B02 human breast cancer cell line as a model. We demonstrate that Hsp27 silencing led to reduced cell migration and invasion in vitro and that in vivo it correlated with a decreased ability of breast cancer cells to metastasise and grow in the skeleton. CONCLUSION: Altogether, these data characterised Hsp27 as a potent therapeutic target in breast cancer bone metastasis and skeletal tumour growth.

Inhibition of heat shock protein 27 (HspB1) tumorigenic functions by peptide aptamers.

Human heat shock protein 27 (Hsp27, HspB1) is an anti-apoptotic protein characterized for its tumorigenic and metastatic properties, and now referenced as a major therapeutic target in many types of cancer. Hsp27 biochemical properties rely on a structural oligomeric and dynamic organization. Downregulation by small interfering RNA or inhibition with dominant-negative mutant have proven their efficiency to counteract the anti-apoptotic and protective properties of Hsp27. In this study, we report the isolation and characterization of Hsp27-targeted molecules interfering with its structural organization. Using the peptide aptamer (PA) strategy, we isolated PAs that specifically interact with Hsp27 and not with the other members of the small heat shock protein family. In mammalian cell cultures, PAs expression perturbed the dimerization and oligomerization of Hsp27, and acted as negative regulators of the anti-apoptotic and cytoprotective activities of this protein. Further studies analyzing SQ20B cell xenografts in immunocompromised mice showed that PAs strongly reduced tumor development through cell cycle arrest. Our data suggest that PAs could provide a potential tool to develop strategies for the discovery of Hsp27 chemical inhibitors.

[Adhesive process in the abdominal cavity in patients with end colostomies and its influence on the reestablishment of the large intestine continuity].

Under analyses there were reparative operations on 79 patients with end colostomies performed using medial access in 42 patients and parastomal access in 37 patients. The investigation of prevalence of the adhesive process in 61 patients has shown that marked adhesions were formed in the area of the medial scar in 41 (67.2%) patients, the stump of the suppressed gut--in 31 (50.9%) patients and colostomy--in 27 (44.3%) Reestablishment of intestine continuity from the parastomal access allowed avoidance of adhesions in the zone of the medial postoperative scar which shortened the time of operation and decreased the level of intra- and postoperative complications.

Experimental study of carbon sequestration reactions controlled by the percolation of CO2-rich brine through peridotites.

Carbonation of ultramafic rocks in geological reservoirs is, in theory, the most efficient way to trap CO2 irreversibly; however, possible feedback effects between carbonation reactions and changes in the reservoir permeability must be considered to realistically assess the efficiency and sustainability of this process. We investigated changes in the hydrodynamic properties of sintered dunite samples by means of percolation experiments, under conditions analogous to that of in situ carbonation. Our results show that carbonation efficiency is controlled by the local renewal of the reactants and the heterogeneity of the pore structure. Preferential flow zones are characterized by the formation of magnetite and of a silica-rich layer at the olivine surfaces, which eventually inhibits olivine dissolution. Conversely, sustainable olivine dissolution together with coprecipitation of magnesite, siderite, and minor Mg-TOT-phyllosilicates, occur in reduced-flow zones. Thus carbonate precipitation only decreases porosity in zones where diffusion-controlled transport is dominant. Consequently, while high flow rates will decrease the carbonation efficiency of the reservoir and low flow rates may reduce the permeability irreversibly close to the injection point, moderate injection rates will ensure a partial carbonation of the rock and maintain the reservoir permeability.

Protection against heat and staurosporine mediated apoptosis by the HSV-1 US11 protein.

US11 protein, one of herpes simplex virus type 1 (HSV-1) true late gene products, plays a role in the virally induced post-transcriptional control of gene expression. In addition, US11 expression also interferes with the cellular response to HSV-1 infection that can lead to apoptosis. We have previously shown that US11 expression enhanced the recovery of cellular protein synthesis and increased cell survival in response to thermal stress. Since heat shock can activate apoptosis, we tested for a possible anti-apoptotic behavior of US11. Here, we show that, in HeLa cells, US11 expression strongly reduced heat induced apoptosis, a phenomenon independent of Hsp expression and characterized by a delayed cytochrome c efflux from mitochondria and reduced caspase 3 activation. Moreover, US11 expression also protected against staurosporine induced apoptosis. Hence, our results favor an anti-apoptotic activity of US11 polypeptide that appears to be located at the level of mitochondria or upstream signaling pathways.

[Urgent resection of the colon with compressive anastomosis and afferent colostoma].

Thirty patients with colon disease in need of urgent surgery have undergone resection of the colon with formation of terminal afferent colostomy and compressive colon-colon anastomosis using oval and linear nikelid-titanium implants. Complications were seen in 6 (20%) patients, lethality was 6,7% due to multiorgan failure in the presence of generalized peritonitis. There were no complications due to colon-colon anastomosis. The above method permits one to reduce surgical trauma of future reconstructive surgeries.

Anisotropy of thermal diffusivity in the upper mantle.

Heat transfer in the mantle is a key process controlling the Earth's dynamics. Upper-mantle mineral phases, especially olivine, have been shown to display highly anisotropic thermal diffusivity at ambient conditions, and seismic anisotropy data show that preferred orientations of olivine induced by deformation are coherent at large scales (>50 km) in the upper mantle. Thus heat transport in the upper mantle should be anisotropic. But the thermal anisotropy of mantle minerals at high temperature and its relationship with deformation have not been well constrained. Here we present petrophysical modelling and laboratory measurements of thermal diffusivity in deformed mantle rocks between temperatures of 290 and 1,250 K that demonstrate that deformation may induce a significant anisotropy of thermal diffusivity in the uppermost mantle. We found that heat transport parallel to the flow direction is up to 30 per cent faster than that normal to the flow plane. Such a strain-induced thermal anisotropy implies that the upper-mantle temperature distribution, rheology and, consequently, its dynamics, will depend on deformation history. In oceans, resistive drag flow would result in lower vertical diffusivities in both the lithosphere and asthenosphere and hence in less effective heat transfer from the convective mantle. In continents, olivine orientations frozen in the lithosphere may induce anisotropic heating above mantle plumes, favouring the reactivation of pre-existing structures.

[Initial experiences in creation of anastomoses in abdominal surgery using implants with shape "memory"]. / Pervyi opyt formirovaniia anastomozov v briushnoi khirurgii implantatami s "pamiat'iu" formy.

The article analyses the first experience in 230 operations for creation of compression anastomoses in abdominal surgery of the esophagus, stomach, gallbladder, and common bile duct by means of implants with shape "memory". Complications occurred in 10% of cases, the mortality rate was 3.04%. The suggested method simplifies the operative technique, shortens the duration of the operation, and reduces the incidence of postoperative complications (anastomositis, incompetence of sutures, reflux gastritis, dumping syndrome).