A partial epithelial-mesenchymal transition signature for highly aggressive colorectal cancer cells that survive under nutrient restriction.

Partial epithelial-mesenchymal transition (p-EMT) has recently been identified as a hybrid state consisting of cells with both epithelial and mesenchymal characteristics and is associated with the migration, metastasis, and chemoresistance of cancer cells. Here, we describe the induction of p-EMT in starved colorectal cancer (CRC) cells and identify a p-EMT gene signature that can predict prognosis. Functional characterisation of starvation-induced p-EMT in HCT116, DLD1, and HT29 cells showed changes in proliferation, morphology, and drug sensitivity, supported by in vivo studies using the chorioallantoic membrane model. An EMT-specific quantitative polymerase chain reaction (qPCR) array was used to screen for deregulated genes, leading to the establishment of an in silico gene signature that was correlated with poor disease-free survival in CRC patients along with the CRC consensus molecular subtype CMS4. Among the significantly deregulated p-EMT genes, a triple-gene signature consisting of SERPINE1, SOX10, and epidermal growth factor receptor (EGFR) was identified. Starvation-induced p-EMT was characterised by increased migratory potential and chemoresistance, as well as E-cadherin processing and internalisation. Both gene signature and E-cadherin alterations could be reversed by the proteasomal inhibitor MG132. Spatially resolving EGFR expression with high-resolution immunofluorescence imaging identified a proliferation stop in starved CRC cells caused by EGFR internalisation. In conclusion, we have gained insight into a previously undiscovered EMT mechanism that may become relevant when tumour cells are under nutrient stress, as seen in early stages of metastasis. Targeting this process of tumour cell dissemination might help to prevent EMT and overcome drug resistance. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

An Augmented Reality Visualization System for Simulated Multirotor Aerial Vehicles.

Multirotors Aerial Vehicles are special class of Unmanned Aerial Vehicles with many practical applications. The growing demand for this class of aircraft requires tools that speed up their development. Simulated environments have gained increasing importance, as they facilitate testing and prototyping solutions, where virtual environments allow real-time interaction with simulated models, with similar behavior to real systems. More recently, the use of Augmented Reality has allowed an increasing experience of immersion and integration between the virtual world and a real scenario. This work proposes the use of Augmented Reality technology and a simulated model of a multirotor to create an interactive flight environment, aiming to improve the user experience in the analysis of simulated models. For this purpose, a smartphone was adopted as a hardware platform, a game engine is used as a basis for the development of the Augmented Reality application, that represents a numerical simulation of the flight dynamics and the control system of a multirotor, and a game controller is adopted for user interaction. The resulting system demonstrates that Augmented Reality is a viable technology that can be used to increase the possibilities of evaluating simulated systems.

Expression of Mn-sod, PAL1, aos1 and HPL genes in soybean plants overexpressing the NmDef02 defensin.

Plant defensins are a potential tool in crop improvement programs through biotechnology. Their antifungal action makes them attractive molecules for the production of transgenic plants. Information is currently lacking on what happens to the expression of defense genes in transgenic plants that overexpress a defensin. Here we show the relative expression of four defense-related genes: Mn-sod, PAL1, aos1 and HPL evaluated in two transgenic soybean events (Def1 and Def17) constitutively expressing the NmDef02 defensin gene from Nicotiana megalosiphon. The expression of these defense genes showed a differential profile in the transgenic events, with the increased expression of the aos1 gene and the repression of the Mn-sod gene in both events, when compared to the non-transgenic control. Furthermore, the expression of the PAL1 gene only increased in the Def17 event. The results indicate that although there were some changes in the expression of defense genes in transgenic plants overexpressing the defensin NmDef02; the morphoagronomic parameters evaluated were similar to the non-transgenic control. Understanding the molecular changes that occur in these transgenic plants could be of interest in the short, medium and long term.

Fecal microbiota composition is related to brown adipose tissue 18F-fluorodeoxyglucose uptake in young adults.

OBJECTIVE: Human brown adipose tissue (BAT) has gained considerable attention as a potential therapeutic target for obesity and its related cardiometabolic diseases; however, whether the gut microbiota might be an efficient stimulus to activate BAT metabolism remains to be ascertained. We aimed to investigate the association of fecal microbiota composition with BAT volume and activity and mean radiodensity in young adults. METHODS: 82 young adults (58 women, 21.8 ± 2.2 years old) participated in this cross-sectional study. DNA was extracted from fecal samples and 16S rRNA sequencing was performed to analyse the fecal microbiota composition. BAT was determined via a static 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography-computed tomography scan (PET/CT) after a 2 h personalized cooling protocol. 18F-FDG uptake was also quantified in white adipose tissue (WAT) and skeletal muscles. RESULTS: The relative abundance of Akkermansia, Lachnospiraceae sp. and Ruminococcus genera was negatively correlated with BAT volume, BAT SUVmean and BAT SUVpeak (all rho ≤ - 0.232, P ≤ 0.027), whereas the relative abundance of Bifidobacterium genus was positively correlated with BAT SUVmean and BAT SUVpeak (all rho ≥ 0.262, P ≤ 0.012). On the other hand, the relative abundance of Sutterellaceae and Bifidobacteriaceae families was positively correlated with 18F-FDG uptake by WAT and skeletal muscles (all rho ≥ 0.213, P ≤ 0.042). All the analyses were adjusted for the PET/CT scan date as a proxy of seasonality. CONCLUSION: Our results suggest that fecal microbiota composition is involved in the regulation of BAT and glucose uptake by other tissues in young adults. Further studies are needed to confirm these findings. CLINICAL TRIAL INFORMATION: ClinicalTrials.gov no. NCT02365129 (registered 18 February 2015).

Determination of the appropriate concentration of sodium alginate used for in vitro culture of cat preantral follicles in a serum-free medium containing FSH, EGF and IGF-I.

Culture of domestic cat preantral follicles can be a suitable technology to assist oocyte conservation strategies in the family Felidae. This research was aimed to comparatively analyse cat preantral follicular development of follicles directly seeded on growth surface or encapsulated in 0.5 or 1% of sodium alginate in a serum-free medium containing FSH, EGF and IGF-I. Preantral follicles were isolated from cat ovarian cortical tissue after ovariectomy. Alginate was dissolved at 0.5 or 1% in PBS. Follicles, 4 per well, with 0% (G-0%), 0.5% (G-0.5%) or 1% (G-1%) of sodium alginate were cultured in M199 with FSH (100 ng/mL), EGF (100 ng/mL) and IGF-I (100 ng/mL) for 7 days at 37°C, 5% CO2 and 99% humidity. Culture medium was replaced every 48 h and samples were stored at -20°C until ELISA of steroid hormones. Morphometric evaluation of follicles was performed every 24 h. G-0% follicles showed granulosa cell migration away from the oocyte and disrupted morphology, whereby they reached apparently larger diameters (203.70 ± 5.82 µm; p < .05) than G-0.5% and G-1% follicles (157.89 ± 8.47 µm and 95.23 ± 1.67 µm, respectively) which maintained three-dimensional organization, being larger in G-0.5% than in G-1% (p < .05). G-0.5% follicles attained the multi-layer preantral follicle stage on day 7 of culture, whereas G-1% follicles underwent progressive atresia. On day 6, steroid concentrations were higher (p < .05) in G-0% than in G-1%: 60 ± 19 vs 0.88 ± 0.32 pg/mL oestradiol; 2.6 ± 0.84 vs 0.04 ± 0.02 ng/mL progesterone; 1.3 ± 0.22 vs 0.61 ± 0.04 ng/mL testosterone and 1.6 ± 0.54 vs 0.22 ± 0.07 ng/mL androstenedione respectively. Steroid concentrations in G-0.5% were comprised between those of G-0% and G-1% (p > .05). In conclusion, two-layer cat preantral follicles encapsulated in 0.5% alginate cultured in medium containing FSH, EGF and IGF-I can develop up to the multi-layer preantral stage in 7 days of culture, whereas follicles directly seeded on growth surface or encapsulated in 1% alginate lost their three-dimensional organization, and experienced regression with compromised steroidogenesis, respectively.

Pulse-Picking Multimodal Nonlinear Optical Microscopy.

Nonlinear optical microscopy techniques can map chemical compositions in biological samples in a label-free manner. Commonly used nonlinear optical processes for imaging include multiphoton excitation fluorescence (MPEF), second harmonic generation (SHG), and coherent Raman scattering (CRS). Femtosecond lasers are typically used for MPEF and SHG due to the requirement of high peak power for excitation, while picosecond lasers are preferred for CRS due to the need for high spectral resolution. Therefore, it is challenging to integrate CRS with MPEF and SHG for chemical imaging. We develop a pulse-picking strategy based on an acousto-optic modulator that can program the duty cycle of the laser pulse train, significantly increasing the pulse peak power at low input average power. This approach offers strong enhancement of nonlinear optical signals and makes hyperspectral coherent anti-Stokes Raman scattering (CARS) microscopy compatible with MPEF and SHG for multimodal imaging at low laser average power. The pulse-picking method also enables the evaluation and comparison of phototoxicity of laser pulses at different average and peak power levels. The photo-perturbations to biological samples are evaluated using cellular dynamics and sample morphological changes, allowing the selection of optimal laser power for the best sensitivity and minimal phototoxicity.

Lessons from outbreaks of COVID-19 at Israeli military bases.

BACKGROUND: To mitigate the spread of coronavirus disease 2019 (COVID-19), national guidelines, in accordance with international health authorities, mandated 14 days of quarantine for every close contact of a confirmed COVID-19 patient. Although health benefits are obvious, consequences are profound, especially for organizations required to maintain operational preparedness. OBJECTIVES: To present the Israel Defense Force (IDF) experience with outbreaks regarding quarantined individuals. To weigh the consequences of quarantined individuals needed for workforce and operation. METHODS: All positive COVID-19 cases in the IDF, as measured by a positive rRT-PCR test result, between 29 February and 18 May 2020 were evaluated. Numbers of positive individuals, quarantined individuals, and confirmatory exams conducted were collected. We compared the events in four units with the largest outbreaks and assessed the impact of confirmed cases, tests conducted, and workforce loss due to quarantine. RESULTS: Of the 187 soldiers who tested positive for COVID-19, source of infection was traced to 140 soldiers (75%). Almost no medical treatment was delivered, and hospitalization was rare. We found a median of 15.2% (interquartile range 5.3-34) for decline in unit workforce due to quarantine measures. Maximum reduction reached 47% of the workforce in one unit. CONCLUSIONS: Despite a relatively small number of confirmed cases, units underwent a substantial change in mode of operation due to the toll of quarantined individuals. In certain populations and organizations, perhaps a more liberal application of isolation and contact tracing is suitable due to the heavy economic burden and consequences in term of operational readiness.

Relationship between type 2 diabetes mellitus and markers of cutaneous melanoma aggressiveness: an observational multicentric study in 443 patients with melanoma.

BACKGROUND: Some studies have suggested a relationship between type 2 diabetes mellitus (T2DM) and increased incidence of melanoma. Efforts are under way to identify preventable and treatable factors associated with greater melanoma aggressiveness, but no studies to date have examined the relationship between T2DM and the aggressiveness of cutaneous melanoma at diagnosis. OBJECTIVES: To explore potential associations between T2DM, glycaemic control and metformin treatment and the aggressiveness of cutaneous melanoma. METHODS: We conducted a cross-sectional multicentric study in 443 patients diagnosed with cutaneous melanoma. At diagnosis, all patients completed a standardized protocol, and a fasting blood sample was extracted to analyse their glucose levels, glycated haemoglobin concentration and markers of systemic inflammation. Melanoma characteristics and aggressiveness factors [Breslow thickness, ulceration, tumour mitotic rate (TMR), sentinel lymph node (SLN) involvement and tumour stage] were also recorded. RESULTS: The mean (SD) age of the patients was 55·98 (15·3) years and 50·6% were male. The median Breslow thickness was 0·85 mm. In total, 48 (10·8%) patients were diagnosed with T2DM and this finding was associated with a Breslow thickness > 2 mm [odds ratio (OR) 2·6, 95% confidence interval (CI) 1·4-4·9; P = 0·004)] and > 4 mm (OR 3·6, 95% CI 1·7-7·9; P = 0·001), TMR > 5 per mm2 (OR 4·5, 95% CI 1·4-13·7; P = 0·009), SLN involvement (OR 2·3, 95% CI 1-5·7; P = 0·038) and tumour stages III-IV (vs. I-II) (OR 3·4, 95% CI 1·6-7·4; P = 0·002), after adjusting for age, sex, obesity, alcohol intake and smoking habits. No significant associations emerged between glycated haemoglobin levels, metformin treatment and melanoma aggressiveness. CONCLUSIONS: T2DM, rather than glycaemic control and metformin treatment, is associated with increased cutaneous melanoma aggressiveness at diagnosis.

A global reference for human genetic variation.

The 1000 Genomes Project set out to provide a comprehensive description of common human genetic variation by applying whole-genome sequencing to a diverse set of individuals from multiple populations. Here we report completion of the project, having reconstructed the genomes of 2,504 individuals from 26 populations using a combination of low-coverage whole-genome sequencing, deep exome sequencing, and dense microarray genotyping. We characterized a broad spectrum of genetic variation, in total over 88 million variants (84.7 million single nucleotide polymorphisms (SNPs), 3.6 million short insertions/deletions (indels), and 60,000 structural variants), all phased onto high-quality haplotypes. This resource includes >99% of SNP variants with a frequency of >1% for a variety of ancestries. We describe the distribution of genetic variation across the global sample, and discuss the implications for common disease studies.

Data Empowerment of Decision-Makers in an Era of a Pandemic: Intersection of "Classic" and Artificial Intelligence in the Service of Medicine.

BACKGROUND: The COVID-19 outbreak required prompt action by health authorities around the world in response to a novel threat. With enormous amounts of information originating in sources with uncertain degree of validation and accuracy, it is essential to provide executive-level decision-makers with the most actionable, pertinent, and updated data analysis to enable them to adapt their strategy swiftly and competently. OBJECTIVE: We report here the origination of a COVID-19 dedicated response in the Israel Defense Forces with the assembly of an operational Data Center for the Campaign against Coronavirus. METHODS: Spearheaded by directors with clinical, operational, and data analytics orientation, a multidisciplinary team utilized existing and newly developed platforms to collect and analyze large amounts of information on an individual level in the context of SARS-CoV-2 contraction and infection. RESULTS: Nearly 300,000 responses to daily questionnaires were recorded and were merged with other data sets to form a unified data lake. By using basic as well as advanced analytic tools ranging from simple aggregation and display of trends to data science application, we provided commanders and clinicians with access to trusted, accurate, and personalized information and tools that were designed to foster operational changes and mitigate the propagation of the pandemic. The developed tools aided in the in the identification of high-risk individuals for severe disease and resulted in a 30% decline in their attendance to their units. Moreover, the queue for laboratory examination for COVID-19 was optimized using a predictive model and resulted in a high true-positive rate of 20%, which is more than twice as high as the baseline rate (2.28%, 95% CI 1.63%-3.19%). CONCLUSIONS: In times of ambiguity and uncertainty, along with an unprecedented flux of information, health organizations may find multidisciplinary teams working to provide intelligence from diverse and rich data a key factor in providing executives relevant and actionable support for decision-making.

Supplementation with liquid whey and ACIDAL® ML in drinking water affect gut pH and microflora and productive performance in laying hens.

1. As the use of antibiotics as growth promoters has been banned in many regions, there has been an on-going search for possible alternative compounds, such as prebiotics and organic acids. 2. This study was conducted to investigate the influence of liquid whey (LW) and organic acid (ACIDAL® ML) supplementation on performance, eggs characteristics, gut pH and health status in laying hens. 3. Seven hundred and fifty, Isa Brown chicks were randomly assigned to five treatments groups (n = 150) and each treatment had five replicates of 30 birds each. The birds were reared for 48 weeks. The treatments were administered in the drinking water at doses of: 250 ml/l of LW (Lacto25), 500 ml/l of LW (Lacto50) or 1 ml/l of ACIDAL® ML (Aci). A positive control group (T+) was treated with 500 mg/l of Tetracolivit (an antibiotic). The negative control group (T-) did not receive any treatment in the drinking water. 4. Administration of LW or ACIDAL® ML in the drinking water reduced (P < 0.05) the pH in the crop, proventriculus, ileum and caeca, as well as total coliform bacteria and E. coli, but increased Lactobacillus spp. in the ileum and caecum, compared to the negative control. 5. Oviposition was earlier in the birds in both the Lacto50 and Aci groups. The weight of birds at first lay and point of lay in the four treated groups was higher than those in negative control group. Furthermore, egg production was increased by 10.44% in birds receiving Lacto25, but the weight and quality traits were unaffected, while the egg shell ratio was higher in the Aci group compared to the other treatments. 6. The data indicated that addition of LW or ACIDAL® ML improved hens' performance by modifying gut pH and microflora.

[Three-month functional prognosis of patients hospitalised due to acute ischaemic stroke in Aragon: Rregional analysis of the impact of COVID-19]. / Pronóstico funcional a 3 meses de pacientes hospitalizados por ictus isquémico agudo en Aragón: análisis regional de la repercusión de la COVID-19.

Introduction: The COVID-19 pandemic has had an impact on ischaemic stroke management, with a reported decrease in hospital admissions, and even disruptions in healthcare and increased in-hospital mortality. However, there is a lack of evidence on the impact of the pandemic on functional prognosis. The aim of this study is to analyse the effect of the COVID-19 pandemic on the 3-month functional outcomes of patients hospitalised due to acute ischaemic stroke in Aragon (Spain). Materil and methods: We reviewed the data of all patients admitted due to ischaemic stroke to any hospital in our regional healthcare system between 30 December 2019 and 3 May 2020. We compared modified Rankin Scale scores and mortality at 3 months in patients hospitalised before and after the declaration of a state of emergency due to the COVID-19 pandemic. Results: In total, 318 patients with acute ischaemic stroke met our inclusion criteria. No differences were observed between periods in global or specific characteristics, with the exception of a higher proportion of patients older than 80 years during the first period (42.2% vs. 29.0%, P=.028). In the comparative analysis, we found no significant differences in mortality (12.3 vs. 7.9, P=.465) or in the proportion of patients with modified Rankin Scale scores ≤ 2 (57.7% vs. 57.1%, P=.425) at 3 months. Conclusion: To our knowledge, this is the first study to analyse the impact of COVID-19 pandemic on the 3-month functional outcomes of patients with ischaemic stroke. In our region, there has been no increase in rates of mortality or disability at 3 months in patients admitted due to ischaemic stroke during the pandemic.

[The use of surrogate alcohol by individuals with disorders related to alcohol abuse as exemplified by the subject of The Russian Federation].

The purpose of the study was to describe the types of non-beverage alcohol consumed, to evaluate socio-demographic factors associated with its use and to establish effectiveness of the alcohol policy measures taken since 2005 and targeted on reducing non-beverage alcohol consumption. From December 2015 to April 2017, 302 patients of the narcological dispensary were interviewed. The prevalence of non-beverage alcohol drinking among those who reported on their non-beverage alcohol consumption status amounted to 75.8% among males and 57.7% among females. The highest prevalence of non-beverage alcohol consumption (86.9%) was identified among males employed in irregular paid work. According to multivariate analysis, the factors positively associated with the use of non-beverage alcohol were male gender (OR 2.48, 95% CI 1.14-5.43), employment on irregular paid work (or 5.0, 95% CI 2.16-11.56), unemployment in case of seeking work (or 3.55, 95% CI 1.45-8.71), unemployment in case of non-seeking work (OR 3.90, 95% CI 1.09-13.95). The types of non-beverage alcohol used for drinking included medicinal tinctures in 25, 40 and 100 ml vials, spirit cosmetic lotions, colognes, technical/medical ethanol, hygienic spirit solutions, alcohol-containing food flavor enhancers. The lower price as compared with conventional alcoholic beverages was indicated as main reason of non-beverage alcohol consumption (61.7%). The enhancement of previously introduced restrictive measures as well as the implementation of new legislative initiatives are required for more effective control of non-beverage alcohol consumption.

Ischaemic stroke in the time of coronavirus disease 2019.

BACKGROUND AND PURPOSE: Stroke assistance is facing changes and new challenges since COVID-19 became pandemic. A variation on the patient influx might be one of the greater concerns, due to fewer people coming to emergency departments or coming too late. However, no data quantifying this have been published until now. The aim was to analyse the impact of the COVID-19 epidemic outbreak on hospital stroke admissions and their characteristics in our region. METHODS: The data of every patient admitted to any hospital of our healthcare system with a diagnosis of ischaemic stroke between 30 December 2019 and 19 April 2020 were reviewed. Demographic and clinical data were recorded and compared between periods before and after the setting of the state of emergency secondary to the COVID-19 outbreak. RESULTS: In total, 354 patients with ischaemic stroke were admitted in our study period. There was a weekly average of 27.5 cases before the setting of the state of emergency against 12 afterwards (P < 0.001). This drop in stroke cases occurred progressively from week 11, persisting in time despite the decrease in confirmed cases of COVID-19. No differences in the proportion of intravenous thrombolysis (21.1% vs. 21.5%, P = 0.935) or endovascular therapy (12.4% vs. 15.2%, P = 0.510) were found, nor in other demographic or clinical characteristics except for median onset-to-door time (102 vs. 183 min, P = 0.015). CONCLUSIONS: This observational study offers the perspective of a whole region in one of the countries more heavily stricken by the SARS-CoV-2 epidemic and shows that the decrease of stroke events, since the beginning of the COVID-19 outbreak, happened globally and without any specific patient distribution.

Impact of COVID-19 outbreak in reperfusion therapies of acute ischaemic stroke in northwest Spain.

BACKGROUND AND PURPOSE: Spain has been one of the countries more heavily stricken by SARS-CoV-2, which has had huge implications for stroke care. The aim was to analyse the impact of the COVID-19 epidemic outbreak on reperfusion therapies for acute ischaemic stroke in the northwest of Spain. METHODS: This was a Spanish multicentre retrospective observational study based on data from tertiary hospitals of the NORDICTUS network. All patients receiving reperfusion therapy for ischaemic stroke between 30 December 2019 and 3 May 2020 were recorded, and their baseline, clinical and radiological characteristics, extra- and intra-hospital times of action, Code Stroke activation pathway, COVID-19 status, reperfusion rate, and short-term outcome before and after the setting of the emergency state were analysed. RESULTS: A total of 796 patients received reperfusion therapies for ischaemic stroke. There was a decrease in the number of patients treated per week (46.5 patients per week vs. 39.0 patients per week, P = 0.043) and a delay in out-of-hospital (95.0 vs. 110.0 min, P = 0.001) and door-to-needle times (51.0 vs. 55.0, P = 0.038). Patients receiving endovascular therapy obtained less successful reperfusion rates (92.9% vs. 86.6%, P = 0.016). COVID-19 patients had more in-hospital mortality. CONCLUSION: A decrease in the number of patients benefiting from reperfusion therapies was found, with a delay in out-of-hospital and door-to-needle times and worse reperfusion rates in northwest Spain. COVID-19 patients had more in-hospital mortality.

Prognostic factors in patients with primary cutaneous anaplastic large cell lymphoma: a multicentric, retrospective analysis of the Spanish Group of Cutaneous Lymphoma.

BACKGROUND: Reliable prognostic factors for patients with primary cutaneous anaplastic large cell lymphoma (PCALCL) are lacking. OBJECTIVE: To identify prognostic factors for specific survival in patients with PCALCL. METHODS: Using the convenience sampling method, patients with PCALCL diagnosed from May 1986 to August 2017 in 16 University Departments were retrospectively reviewed. RESULTS: One hundred eight patients were included (57 males). Median age at diagnosis was 58 years. All of them showed T1-3N0M0 stages. Seventy per cent of the cases presented with a solitary lesion, mostly at the limbs. Complete response rate after first-line treatment was 87%, and no advantage was observed for any of them (surgery, radiotherapy, chemotherapy or other approaches). Nodal and visceral progression rate was 11% and 2%, respectively. 5-year specific survival (SSV) reached 93%; 97% for T1 patients and 84% for T2/T3 patients (P = 0.031). Five-year SSV for patients developing early cutaneous relapse was 64%; for those with late or no relapse, 96% (P = 0.001). Estimated median SSV for patients showing nodal progression was 103 months (95% CI: 51-155 months); for patients without nodal progression, estimated SSV did not reach the median (P < 0.001). Nodal progression was an independent predictive parameter for shorter survival (P = 0.011). CONCLUSION: Multiple cutaneous lesions at presentation, early skin relapse and nodal progression portrait worse prognosis in patients with PCALCL.

[The analysis of drug abuse situation in the Khanty-Mansi Autonomous Okrug - Yugra].

The article presents the analysis of drug abuse situation in municipalities and districts of the Khanty-Mansi Autonomous Okrug - Yugra (KHMAO-Yugra) in 2017-2018, as well as the dynamics of changes of the drug abuse situation in KHMAO-Yugra as a whole in 2015-2018. By 2018, the drug abuse situation in the KHMAO-Yugra improved as compared with previous years of the study period and corresponded to the "tense" level, which indicates the need to continue systematic and targeted intersectoral work aimed at reducing morbidity and mortality associated with the use of drugs and psychoactive substances in this northern region of Russia.

[The organization of chemical toxicological service and medical examination of persons for condition of alcohol drunkenness, fact of consumption of drug and other psychoactive substances in the Khanty-Mansi Autonomous Okrug-Yugra].

The article presents the analysis of organization of chemical-toxicological service and in the Khanty-Mansi Autonomous Okrug-Yugra. The introduction of three-level system for provision of addiction medical care of population and implementation of the principle of zoning made it possible to organize three-level system of chemical-toxicological service that permitted to achieve equal access to chemical-toxicological and addiction care services in all territories of the region. The investments in chemical-toxicological laboratories, supply of modern equipment, advanced training of laboratory specialists, cooperation with leading research centers and professional communities outside of the region allowed timely and accurately identify psychoactive substances, prompt response in cases of mass poisoning with novel psychoactive substances, and quick introduction of advanced methods of chemical-toxicological examination to the medical organizations of the large industrial northern region of Russia.

Metabolic profiling in children with autism spectrum disorder with and without mental regression: preliminary results from a cross-sectional case-control study.

INTRODUCTION: It is challenging to establish the mechanisms involved in the variety of well-defined clinical phenotypes in autism spectrum disorder (ASD) and the pathways involved in their pathogeneses. OBJECTIVES: The aim of the present study was to evaluate the metabolomic profiles of children with ASD subclassified by mental regression (AR) phenotype and with no regression (ANR). METHODS: The present study was a cross-sectional case-control study. Thirty children aged 2-6 years with ASD were included: 15 with ANR and 15 with AR. In addition, a control group of 30 normally developing children was selected and matched to the ASD group by sex and age. Plasma samples were analyzed with a metabolomics single platform methodology based on liquid chromatography-mass spectrometry. Univariate and multivariate analysis, including orthogonal partial least squares-discriminant analysis modeling and Shared-and-Unique-Structures plots, were performed using MetaboAnalyst 4.0 and SIMCA-P 15. The primary endpoint was the metabolic signature profiling among healthy children and autistic children and their subgroups. RESULTS: Metabolomic profiles of 30 healthy children, 15 ANR and 15 AR were compared. Several differences between healthy children and children with ASD were detected, involving mainly amino acid, lipid and nicotinamide metabolism. Furthermore, we report subtle differences between the ANR and AR groups. CONCLUSIONS: In this study, we report, for the first time, the plasmatic metabolomic profiles of children with ASD, including two different phenotypes based on mental regression status. The use of a liquid chromatography-mass spectrometry platform approach for metabolomics in ASD children using plasma appears to be very efficient and adds further support to previous findings in urine. Furthermore, the present study documents several changes related to amino acid, NAD+ and lipid metabolism that, in some cases, such as arginine and glutamate pathway alterations, seem to be associated with the AR phenotype. Further targeted analyses are needed in a larger cohort to validate the results presented herein.

Differences between diabetic and non-diabetic patients with community-acquired pneumonia in primary care in Spain.

BACKGROUND: Diabetes is one of the underlying risk factors for developing community-acquired pneumonia (CAP). The high prevalence of diabetes among population and the rising incidence of this illness, converts it as an important disease to better control and manage, to prevent its secondary consequences as CAP. The objective of this research is to describe the characteristics of the patients with diabetes and the differences with the no diabetes who have had an episode of CAP in the context of the primary care field. METHODS: A retrospective, observational study in adult patients (> 18 years-old) who suffer from CAP and attended at primary care in Spain between 2009 and 2013 was developed using the Computerized Database for Pharmacoepidemiological Studies in Primary Care (BIFAP). We carried out a descriptive analysis of the first episodes of CAP, in patients with or without diabetes as comorbidity. Other morbidity (CVA, Anaemia, Arthritis, Asthma, Heart disease, Dementia, Depression, Dysphagia, Multiple sclerosis, Epilepsy, COPD, Liver disease, Arthrosis, Parkinson's disease, Kidney disease, HIV) and life-style factors were also included in the study. RESULTS: A total of 51,185 patients were included in the study as they suffer from the first episode of CAP. Of these, 8012 had diabetes as comorbidity. There were differences between sex and age in patients with diabetes. Patients without diabetes were younger, and had less comorbidities including those related to lifestyles such as smoking, alcoholism, social and dental problems than patients with diabetes. CONCLUSIONS: Patients who developed an episode of CAP with diabetes have more risk factors which could be reduced with an appropriate intervention, including vaccination to prevent successive CAP episodes and hospitalization. The burden of associated factors in these patients can produce an accumulation of risk. Health care professional should know this for treating and control these patients in order to avoid complications. Diabetes and those other risk factors associated could be reduced with an appropriate intervention, including vaccination to prevent the first and successive CAP episodes and the subsequent hospitalization in severe cases.