Cannabinoid receptor CB1 mediates baseline and activity-induced survival of new neurons in adult hippocampal neurogenesis

<p>Abstract</p> <p>Background</p> <p>Adult neurogenesis is a particular example of brain plasticity that is partially modulated by the endocannabinoid system. Whereas the impact of synthetic cannabinoids on the neuronal progenitor cells has been described, there has been lack of information about the action of plant-derived extracts on neurogenesis. Therefore we here focused on the effects of Δ9-tetrahydrocannabinol (THC) and Cannabidiol (CBD) fed to female C57Bl/6 and Nestin-GFP-reporter mice on proliferation and maturation of neuronal progenitor cells and spatial learning performance. In addition we used cannabinoid receptor 1 (CB1) deficient mice and treatment with CB1 antagonist AM251 in Nestin-GFP-reporter mice to investigate the role of the CB1 receptor in adult neurogenesis in detail.</p> <p>Results</p> <p>THC and CBD differed in their effects on spatial learning and adult neurogenesis. CBD did not impair learning but increased adult neurogenesis, whereas THC reduced learning without affecting adult neurogenesis. We found the neurogenic effect of CBD to be dependent on the CB1 receptor, which is expressed over the whole dentate gyrus. Similarly, the neurogenic effect of environmental enrichment and voluntary wheel running depends on the presence of the CB1 receptor. We found that in the absence of CB1 receptors, cell proliferation was increased and neuronal differentiation reduced, which could be related to CB1 receptor mediated signaling in Doublecortin (DCX)-expressing intermediate progenitor cells.</p> <p>Conclusion</p> <p>CB1 affected the stages of adult neurogenesis that involve intermediate highly proliferative progenitor cells and the survival and maturation of new neurons. The pro-neurogenic effects of CBD might explain some of the positive therapeutic features of CBD-based compounds.</p

Review of the incidence of Crimean-Congo hemorrhagic fever for 18 years in 2005-2023 based on ProMED-RUS reports

Introduction: ProMED-mail Service in Russian (ProMED-RUS) informs readers about the most important events related to infectious diseases in the world with especial focus to countries of the former Soviet Union and other countries of the WHO European Region (WHO/EURO). There are several countries in WHO/EURO, which territories are endemic for Crimean-Congo hemorrhagic fever (CCHF). Objective: To estimate the incidence of CCHF in WHO/EURO region within 2005-2023 based on ProMED-RUS data. Methods and materials: We reviewed 345 ProMED-RUS CCHF reports published between 2005 and 2023. Comments from moderators were also taken into account. Results: According to ProMED-RUS, total of 2047 cases of CCHF were recorded during the observation period, including 60 deaths (CFR 2.8%) in the Southern and North Caucasus Federal Districts of Russia. During 2005-2023 cases of CCHF were registered in the Astrakhan, Volgograd, Stavropol, Rostov regions, the republics of Dagestan, Ingushetia, Kabardino-Balkaria, Kalmykia. The expansion of the epidemically active territory of the CCHF natural focus continues in Russia. Thus, in 2023, for the first time, 1 case of CCHF was registered in the Botlikh and Novolaksky districts of the Republic of Dagestan. In total, 26 cases of CCHF were identified in Russia in 2023 (25 endemic cases, 1 case was imported to Moscow from Georgia (lethal). The number of people infected with CCHF in RF in 2023 is 2.3 times less than in 2022 (59 cases), and 71.6% lower than the long-term average. In 2013-2022 this figure averaged 88.8 cases per year.There are 10-20 cases of CCHF registered in Kazakhstan annually, more than 297 in total. In 2023, 19 cases of CCHF were registered in the Republic of Kazakhstan: 6 cases in the each of Kyzylorda, Turkestan and Zhambyl regions, 1 case in the Aktobe region.Cases of CCHF were also recorded in Georgia (12 cases in 2023), Tajikistan (10 cases, 3 - fatal in 2007- 2009), Uzbekistan (7 cases in 2014-2022, 4 - fatal), Kyrgyzstan (imported from Kazakhstan in 2019). Case of CCHF was registered in Greece (2008). Since 2016 CCHF cases also started to record in Spain (8 cases, 3 - fatal). Annually CCHF cases (from 1 to 6) record in Bulgaria. In France (Corsica) in 2023 cases of CCHF were recorded in cattle (imported from Senegal). Discussion: The expansion of the epidemically active territory of the CCHF has been observed in recent years in the WHO/EURO, which probably connected with global warning, fitness of ticks and CCHV virus, intensification of people, and cattle migration. Conclusion: ProMED-RUS reports on CCHF in the countries of the former USSR and other countries of the WHO European Region contain relevant and useful information and allow to monitor the epidemiological situation of CCHF

Dirofilariasis in stray dogs in southern Russia: improvement of laboratory studies

Introduction: Dirofilariasis is a relatively new medical problem caused by changes in natural, climatic and social conditions. Methods: In 2023, venous blood of 233 dogs was collected from shelters for homeless animals in the city of Rostov-on-Don and the Rostov region. Testing the blood of dogs for dirofilariasis was carried out using two Methods: the morphological (Knott's method with 3% acetic acid solution) and real-time polymerase chain reaction (RT-PCR). RT-PCR was performed using primers developed by us for Dirofilaria repens and Dirofilaria immitis in accordance with improved isolation protocols.The preparation of the PCR mixture for the reaction was carried out using a set of reagents for RT-PCR in the presence of EVAGreen (SINTOL) with highly specific primer pairs. For D. repens: (F2690DR) 5’-АAGTGTTGATGGTCAACCTGAA-3’ and (R2812DR) 5’- GTAGAACGCATATTCTGAGT-3’. For D. immitis: (F2690DI) 5’- GAGTGTAGAGGGTCAGCCTGAG-3’ and (R2812DI) 5’- GTAGAACGTATATTCTGAAC- 3’. DNA amplification modes were selected empirically. Results: As a result of research using larvoscopy, dirofilaria larvae were found in 53 samples with an intensity of invasion from one to one hundred larvae in 0.2 ml of blood, the extent of invasion was 22.75%. The PCR method detected dirofilaria in 60 samples. The prevalence of dogs was 25.75%, of which D. repens – 21.67%, D. immitis – 41.67%, mixed invasion was 36.67%. The results obtained were analyzed in a four-field contingency table. As the analysis showed, the sensitivity of the PCR method was 90.57%, and the microscopy method was 81.36%. The specificity of the first method was 93.33%, the second – 97.13%. Discussion: Despite the increase in the quality and quantity of deworming activities for dogs, which are the most epidemiologically significant source of dirofilaria infection, in recent decades there has been an increase in the prevalence of these nematodes in definitive hosts in Europe. The expansion of the range of dirofilariasis has been facilitated by animal migration and climate change, which affects mosquito vectors. The main factor in the unfavorable epidemiological situation is the significant number of stray dogs infected with dirofilaria that have not undergone veterinary examination. Direct diagnostic methods remain the «gold standard», but require highly qualified specialists. The polymerase chain reaction (PCR) method is also a direct diagnostic method that can detect the DNA of parasitic pathogens in various biological substrates. Conclusion: The results of our study indicate a continuing high risk of dirofilariasis in the population of a number of regions of southern Russia. The main cause of epizootological problems remains the high intensity of invasion of animals not covered by veterinary examination.The developed test system allows you to determine the presence of two species of dirofilaria in real time and in a short time. This system can improve the work of veterinary laboratories

Choice of treatment tactics in patients with acute diarrhea of bacterial etiology at high risk of irritable bowel syndrome

Introduction: It is known that acute diarrhea, especially of bacterial etiology, can cause irritable bowel syndrome (IBS), which develops in the period of convalescence in more than 10% of cases. One of the therapeutic approaches regulating visceral hypersensitivity, which occurs in IBS, is the use of butyric acid. Purpose of the study: To provide a comprehensive assessment of the effect of calcium butyrate and inulin on reducing the risk of postinfectious IBS in patients with acute diarrhea of bacterial etiology (ADBE) with a high risk of its development in the convalescent period Materials and Methods: The study was conducted in 60 patients (ADBE) aged 18 to 60 years with a high risk of developing IBS, established on the basis of a discriminant equation including triglycerides (TG), cholesterol (CH) and urea (U) levels at the 3th day disease. YIBS=-6,441+1,065*XTG+0,197*XU+0,753*XCH. If YIBS³0,5375 the high risk of IBS is predicted (The sensitivity of the predictive model was 78.6%, the specificity - 100%). Patients were randomized into two groups: one group received conventional therapy, including probiotics, the other group additionally received Zacofalc, consisting of calcium butyrate 250 mg and inulin 250 mg (CB+I) during 30 days. The efficacy of therapy was assessed by measuring TG levels at the acute period of ADBE and at hospital discharge, fecal calprotectin and I-FABP (Intestinal fatty acid binding protein) at the acute period and one month after discharge. The data systematization and statistical processing of the results were performed using binary logistic regression and ROC analysis. The obtained differences were considered statistically significant at p < 0.05. Results: The most common pathogens of ADBE were S.enteritidis (46.7% in the group receiving CB+I and 50.0% in the group of comparison), Protei (36.7% in the group receiving CB+I and 30% in group of the comparison). Citrobacter (20% in each group). The occurrence of such representatives of opportunistic flora as campylobacter, S.typhimurium, P. aeruginosa varied from 3.3 to 13.3%. There were no statistically significant differences in the duration of the main clinical symptoms and laboratory parameters between the groups. However, fecal calprotectin and I-FABP levels decreased statistically significantly 30 days after hospital treatment in the CB+I group. Triglyceride levels were also lower during the recovery period in patients receiving CB+I. The incidence of IBS during the next 6 months of follow-up was 38.5 times lower in the CB+I group compared to patients receiving conventional therapy. Conclusions: The use of CB+I accelerates the normalization of inflammatory markers and reduces the risk of IBS development after ADBE. Therefore, CB+I may be an effective method of treatment and prevention of IBS development in patients with ADBE

Monitoring the risks of infections associated with medical care in a hospital in Rostov-on-Don

Introduction: One of the comprehensive measures to prevent cases of healthcare-associated infections (HAI) in hospitals is a modern science-based approach to monitoring the circulation of opportunistic antibiotic-resistant microorganisms in medical organizations. Methods: During 2022 -2023 158 samples were taken from the oropharynx of medical staff. 64 samples from the skin of the hands of medical personnel and 132 swabs from inventory and equipment in hospital departments. We investigated intensive care unit (injection pillow, ventilation grille); surgical department (treatment room: central heating radiator, couch, table for manipulations; dressing room: couch, cabinet for sterile material; ward: refrigerator, fluorescent lamp); geriatric department: couch; treatment room: split system, tourniquet; registration desk at the nurse's station, doctors' desks)were examined Differential diagnostic media were used to isolate microorganisms. Isolates were identified by mass spectrometry using the MALDI-TOFF method (Byotyper Microflex, Bruker Germany). The main criterion for the risk of HAI was the determination of antibiotic resistance in isolated cultures, tested by the disk diffusion method. Results: An examination of the hospital inventory showed that gram-positive microorganisms dominated, including staphylococci in 58% of cases. Non-fermentative gram-negative bacteria (NFB) (A. lwoffii, S. maltophilia, P. montelii) were detected in 9% of cases.In 2023, there was an increase in the number of sterile sampling points from hospital facilities.The dominant microorganisms in the oropharynx of employees during the study periods were: Staphylococcus spp. (29%), Streptococcus spp. (19%), Candida spp. (11%), NGOB (7%). Compared to 2022, in 2023, the content of bacteria of the family Enterobacteriacae and Neisseria spp. in the oropharynx of employees decreased, against the background of an increase in the content of Streptococcus spp., pathogenic S. aureus and hemolyzing S. epidermidis.Among the microorganisms isolated from the hands of hospital employees, the dominant species were: Staphylococcus spp. (71%), E.coli (11%), Lactobacillus spp. (6%), Candida spp. (2%), as well as mold fungi (2%). Discussion: The results obtained may indicate an increase in the risk of HAI in this hospital associated with potentially pathogenic and pathogenic representatives of their own microflora circulating among employees.The analysis of antibiograms of microorganism strains isolated from the hands of personnel and from hospital inventory showed increase in the degree of resistance of isolates in relation to antibiotics of later generations (fluoroquinolones, aminoglycosides of the second generation, cephalosporins of the third generation, semisynthetic penicillins of the second generation, macrolides). Conclusion: Changes in the species composition and sensitivity to antibiotics of microflora isolated from medical personnel and microflora from hospital facilities and equipment suggest the presence of an epidemiological connection that increases the risk of developing HAI in this hospital