[Validation of screening method based on EEG analysis for the risk assessment of psychiatric and behavioral disorders: a pilot study]. / Validatsiya skriningovogo metoda na osnove analiza EEG dlya otsenki riskov psikhicheskikh i povedencheskikh rasstroistv: pilotnoe issledovanie.

OBJECTIVE: To assess the validity of the screening method based on EEG analysis using predictive analytics algorithms with the calculation of linear discriminant functions (LDFs), in comparison with a classification system based on psychometric self-report scales. MATERIAL AND METHODS: A comparative cross-sectional study with partial blinding involving healthy volunteers was conducted at two investigational sites. The calculated scores of LDFs used to assess risks of impulsivity, depression and anxiety acted as quantitative characteristics of subjects' mental state. Testing included completing psychometric scales. RESULTS: As a result of the performed validation of the original screening method based on EEG analysis in comparison with the scores of psychometric scales chosen as a reference method, satisfactory results were obtained with the best parameters of sensitivity, specificity, and accuracy for detecting high levels of impulsivity associated with pronounced aggressiveness. Of considerable interest is also the direct correlation found between high levels of LDF impulsivity scores and high levels of self-rated aggression on a psychometric scale (BPAQ-24). CONCLUSION: The results open up the possibility of using the proposed method to predict a number of emotional and behavioral characteristics of subjects, including a high risk of aggressive behavior as part of professional selection.

General dynamics of the URT microbiome and microbial signs of recovery in COVID-19 patients.

COVID-19 is caused by an airborne virus, SARS-CoV-2. The upper respiratory tract (URT) is, therefore, the first system to endure the attack. Inhabited by an assemblage of microbial communities, a healthy URT wards off the invasion. However, once invaded, it becomes destabilised, which could be crucial to the establishment and progression of the infection. We examined 696 URT samples collected from 285 COVID-19 patients at three time-points throughout their hospital stay and 100 URT samples from 100 healthy controls. We used 16S ribosomal RNA sequencing to evaluate the abundance of various bacterial taxa, α-diversity, and ß-diversity of the URT microbiome. Ordinary least squares regression was used to establish associations between the variables, with age, sex, and antibiotics as covariates. The URT microbiome in the COVID-19 patients was distinctively different from that of healthy controls. In COVID-19 patients, the abundance of 16 genera was significantly reduced. A total of 47 genera were specific to patients, whereas only 2 were unique to controls. The URT samples collected at admission differed more from the control than from the samples collected at later stages of treatment. The following four genera originally depleted in the patients grew significantly by the end of treatment: Fusobacterium, Haemophilus, Neisseria, and Stenotrophomonas. Our findings strongly suggest that SARS-CoV-2 caused significant changes in the URT microbiome, including the emergence of numerous atypical taxa. These findings may indicate increased instability of the URT microbiome in COVID-19 patients. In the course of the treatment, the microbial composition of the URT of COVID-19 patients tended toward that of controls. These microbial changes may be interpreted as markers of recovery.

Genetic Diversity of the Amur Tiger (Panthera tigris altaica): Are There Differences between the 20th and the Early 21st Centuries?

Polymorphism of nine microsatellite loci in the Sikhote-Alin tiger population was analyzed in the modern and recent historical periods, using blood, excrement, and museum bone samples. Tests for excess heterozygosity to determine whether the population went through a period of low abundance and a low value of the Garza-Williamson coefficient indicated that such events were highly probable to occur in both recent and earlier history. The mean effective population size Ne of a current sample was 34.4 (95% confidence interval 17-106.8). This fact is of great interest in the contest of conservation and restoration of endangered large cat species.

Cognitive impairment in long-living adults: a genome-wide association study, polygenic risk score model and molecular modeling of the APOE protein.

Background: Cognitive impairment is an irreversible, aging-associated condition that robs people of their independence. The purpose of this study was to investigate possible causes of this condition and propose preventive options. Methods: We assessed cognitive status in long-living adults aged 90+ (n = 2,559) and performed a genome wide association study using two sets of variables: Mini-Mental State Examination scores as a continuous variable (linear regression) and cognitive status as a binary variable (> 24, no cognitive impairment; <10, impairment) (logistic regression). Results: Both variations yielded the same polymorphisms, including a well-known marker of dementia, rs429358in the APOE gene. Molecular dynamics simulations showed that this polymorphism leads to changes in the structure of alpha helices and the mobility of the lipid-binding domain in the APOE protein. Conclusion: These changes, along with higher LDL and total cholesterol levels, could be the mechanism underlying the development of cognitive impairment in older adults. However, this polymorphism is not the only determining factor in cognitive impairment. The polygenic risk score model included 45 polymorphisms (ROC AUC 69%), further confirming the multifactorial nature of this condition. Our findings, particularly the results of PRS modeling, could contribute to the development of early detection strategies for predisposition to cognitive impairment in older adults.

[Prospects for development of laparoscopic surgery in the Central Federal District of the Russian Federation]. / O perspektive razvitiya laparoskopicheskoi khirurgii v Tsentral'nom federal'nom okruge Rossiiskoi Federatsii.

OBJECTIVE: To analyze the achievements of laparoscopic surgery in the Central Federal District of Russia and outline perspective trends for further application. MATERIAL AND METHODS: The study included adult patients with abdominal surgical diseases hospitalized in general surgical departments of the Central Federal District between 2014 and 2021. We analyzed the prevalence of elective and emergency laparoscopic surgeries. Incidence and results of laparoscopic interventions between 2018 and 2021 were estimated considering primary statistical data presented in the annual collections of the Chief Surgeon of the Ministry of Health of Russia «Surgical care in the Russian Federation¼. RESULTS: The absolute number of laparoscopic surgeries in the Central Federal District increased from 23.686 to 80.489 (by 3.4 times) between 2014 and 2021. The annual number of elective laparoscopic surgeries exceeded the number of emergency ones up to 2019. In 2020-2021, this situation changed in favor of emergency abdominal procedures. Laparoscopic surgeries are the most common for in acute cholecystitis (71.06-81.10% of all laparoscopic interventions annually) and acute appendicitis (46.85-55.60%). In 2020 and 2021, the absolute number of laparoscopic appendectomies exceeded the number of laparoscopic cholecystectomies. These values are lower for perforated ulcers (15.44-20.39%) and acute pancreatitis (32.40-36.71%). Laparoscopic operations are rare for acute intestinal obstruction, strangulated hernia and ulcerative gastroduodenal bleeding. In elective surgery, high availability of laparoscopic surgeries was noted in patients with cholelithiasis (89.40-93.78%), hiatal hernia (62.12-77.27%) and adrenal gland diseases (64.23-87.25%). The most intensive increment of availability (by 2.4 times) was noted for inguinal hernia from minimum level (10.98%) in 2018 to 26.00% in 2021. Mortality after some laparoscopic operations decreased in comparison with laparotomy by 12-45 times (2018-2021). However, this aspect and results of laparoscopic surgeries in case of delayed hospitalization require additional study. CONCLUSION: Analysis of laparoscopic surgery showed the timeliness of beginning and development of this direction In Russia. The prospect of further development of laparoscopic surgery for abdominal diseases is determined by modern trends. These are increase in the number of laparoscopic operations for acute appendicitis, acute cholecystitis and perforated ulcers, as well as higher number of early (after admission) operations.

[Impact of late admission on mortality from acute abdominal diseases in the Central Federal District of the Russian Federation]. / Vliyanie pozdnei gospitalizatsii na letal'nost' pri ostrykh abdominal'nykh zabolevaniyakh v TsFO Rossiiskoi Federatsii.

OBJECTIVE: To analyze the effect of late hospitalization on mortality from acute abdominal diseases in the Central Federal District of the Russian Federation. MATERIAL AND METHODS: Analysis of late hospitalizations and in-hospital mortality was based on metadata (616.742 clinical observations between 2017 and 2021). Primary statistical data were obtained from reports of chief surgeons in 18 regions of the Central Federal District of the Russian Federation and presented in analytical collections «Surgical care in the Russian Federation¼. RESULTS: The number of patients admitted to surgical hospitals of the Central Federal District with acute abdominal diseases later than 24 hours from clinical manifestation varies depending on the underlying disease. The greatest number of late hospitalizations was observed in acute intestinal obstruction (50.82%), acute adhesive intestinal obstruction (48.49%) and acute pancreatitis (47.36%). In acute cholecystitis, gastrointestinal bleeding and acute appendicitis, admission after 24 hours was observed in 44.72, 38.65 and 33.83% of cases, respectively. Late hospitalization is even less typical for strangulated hernia (27.43%) and perforated ulcer (26.23%). In-hospital mortality significantly differs in both groups (within and after 24 hours) for all acute abdominal diseases. Extended surgery and widespread peritonitis increase these differences for strangulated hernia by 9.2 times (0.92% within 24 hours and 8.48% after 24 hours), for acute appendicitis by 8 times (0.05% within 24 hours and 0.40% after 24 hours) and for perforated ulcer by 6.3 times (4.50% within 24 hours and 28.59% after 24 hours). CONCLUSION: In the Central Federal District, about 25-50% of patients with acute abdominal diseases admitted to the hospital later than 24 hours after clinical manifestation depending on disease. We found the highest in-hospital mortality following late hospitalization in patients with strangulated hernia, acute appendicitis and perforated ulcers.

[In-hospital mortality in acute abdominal diseases in the Central Federal District of Russia depending on availability of laparoscopic procedures]. / Dinamika gospital'noi letal'nosti pri ostrykh abdominal'nykh zabolevaniyakh v Tsentral'nom federal'nom okruge Rossii v zavisimosti ot chastoty primeneniya laparoskopicheskikh operatsii.

OBJECTIVE: To study in-hospital mortality in acute abdominal diseases in the Central Federal District and compared effectiveness of laparoscopic and open surgeries. MATERIAL AND METHODS: The study was based on the previous data for 2017-2021. The odds ratio (OR) was used to assess significance of between-group differences. RESULTS: The absolute number of deceased patients with acute abdominal diseases increased significantly and exceeded 23 thousand in the Central Federal District between 2019 and 2021. This value approached 4% for the first time over the last 10 years. In-hospital mortality from acute abdominal diseases in the Central Federal District increased for 5 years and reached maximum value in 2021. The greatest changes occurred in perforated ulcers (mortality increased from 8.69% in 2017 to 14.01% in 2021), acute intestinal obstruction (from 4.7% to 9.0%) and ulcerative gastroduodenal bleeding (from 4.5% to 5.5%). In other diseases, in-hospital mortality is lower, but trends are similar. Laparoscopic surgeries are common in acute cholecystitis (71-81%). At the same time, in-hospital mortality is significantly lower in regions with more active use of laparoscopy (0.64% and 1.25% in 2020; 0.52% and 1.16% in 2021). Laparoscopic surgeries are significantly less actively used for other acute abdominal diseases. We analyzed availability of laparoscopic surgeries using the «Hype Cycle¼. Percentage range of introduction reached conditional «productivity plateau¼ only in acute cholecystitis. CONCLUSION: Most regions are stagnating in laparoscopic technologies for acute appendicitis and perforated ulcers. Laparoscopic operations are actively used for acute cholecystitis in most regions of the Central Federal District. Annual increase in the number of laparoscopic operations and their technical improvement are promising in reducing in-hospital mortality associated with acute appendicitis, perforated ulcers and acute cholecystitis.

Genetic Variants Associated with Bronchial Asthma Specific to the Population of the Russian Federation.

Bronchial asthma (BA) is a disease that still lacks an exhaustive treatment protocol. In this regard, the global medical community pays special attention to the genetic prerequisites for the occurrence of this disease. Therefore, the search for the genetic polymorphisms underlying bronchial asthma has expanded considerably. As the present study progressed, a significant amount of scientific medical literature was analyzed and 167 genes reported to be associated with the development of bronchial asthma were identified. A group of participants (n = 7,303) who had voluntarily provided their biomaterial (venous blood) to be used in the research conducted by the Federal Medical Biological Agency of Russia was formed to subsequently perform a bioinformatic verification of known associations and search for new ones. This group of participants was divided into four cohorts, including two sex-distinct cohorts of individuals with a history of asthma and two sex-distinct cohorts of apparently healthy individuals. A search for polymorphisms was made in each cohort among the selected genes, and genetic variants were identified whose difference in occurrence in the different cohorts was statistically significant (significance level less than 0.0001). The study revealed 11 polymorphisms that affect the development of asthma: four genetic variants (rs869106717, rs1461555098, rs189649077, and rs1199362453), which are more common in men with bronchial asthma compared to apparently healthy men; five genetic variants (rs1923038536, rs181066119, rs143247175, rs140597386, and rs762042586), which are more common in women with bronchial asthma compared to apparently healthy women; and two genetic variants (rs1219244986 and rs2291651) that are rare in women with a history of asthma.

[Impact of staffing on the results of treatment among surgical patients. Statistical study]. / Vliyanie kadrovoi ukomplektovannosti na rezul'taty lecheniya khirurgicheskikh bol'nykh. Statisticheskoe issledovanie.

OBJECTIVE: To study the influence of staffing index on the results of surgical treatment. MATERIAL AND METHODS: The study was based on the data of surgical service in the Russian Federation upon 2018 (A.Sh. Revishvili et al., 2019). Correlation and regression analysis was carried out using the Microsoft Excel 2019 software. To assess between-group differences, we analyzed odds ratio (OR) and contingency table using χ2 test. RESULTS: Correlation and regression analysis revealed strong direct functional relationships (r=0.889) between the staffing of surgical service and in-hospital mortality rates. We distinguished 3 formalized levels of surgical staffing (high, medium and low). Gradation of these categories depends on the annual average reference indicator of staffing (88.4% in 2018). In high level of surgical staffing (≥88.4%), in-hospital mortality was 2.19%. Low level of surgical staffing (<88.4%) is accompanied by in-hospital mortality of 2.65% (OR 0.83; 95% CI 0.81-0.84; p<0.05). CONCLUSION: We confirmed the hypothesis about correlation of in-hospital mortality and staffing of surgical personnel. Validation of scientific data requires further studies with multivariate analysis of various covariates. Long-term prospects of surgical personnel policy in Russia are associated with formulation of specific tasks for surgical services at each level of surgical care.

Influence of chitin nanofibrils ultrasonic treatment on structure and properties of chitosan-based composite materials.

The influence of ultrasonic treatment parameters of chitin nanofibrils aqueous suspension on structure, strength and deformation properties of chitosan-based composite films and fibers was investigated. Model calculations of ultrasound-induced cavitation parameters in the aqueous suspension of the chitin nanofibrils showed that an increase in the field power up to 630 W led to destruction of the cavity, to an increase in the temperature in the vicinity of cavitation area (up to 507 °C) and, as a consequence, to destruction of chitin glycoside ring (which is confirmed by the IR data). The results of light scattering, IR spectroscopy, and electron microscopy investigations indicated that the optimal duration of ultrasonic treatment of the chitin nanofibrils aqueous solution was 4-10 min (depending on oriented state of the scaffold). Tensile strength of the composites was 130 ± 11 MPa (films), 226 ± 4.8 MPa (fibers); deformation at break was 43 ± 7.5% (films), 10 ± 0.6% (fibers).

Biological Response to a Novel Hybrid Polyoligomer: in vitro and in vivo Models.

The aim of the study is to evaluate biocompatibility of a novel hybrid polyoligomer in in vitro and in vivo models. MATERIALS AND METHODS: Cytotoxicity of the material was investigated using the MTT assay with human dermal fibroblasts as test cultures. To study direct interaction of the hybrid polyoligomer with cells, the fibroblasts were cultured on the polymer samples for 96 h, the cultures were assessed every 24 h using fluorescence microscopy. To study the tissue reaction in the area of contact with the donor bed and the morphological features of the implanted sample restructuring, a case-control study was performed using a rabbit model. Samples of hybrid polyoligomer were implanted into the bone defect formed in the left iliac crest in 10 rabbits. In the control group, the prepared allograft samples were transplanted into similar defects in 10 animals. The rabbits were sacrificed 4 and 8 weeks after the operation. The standard morphological methods with hematoxylin and eosin staining and immunohistochemical Ki-67 proliferation marker evaluation were used to assess the state of tissues in the defect area. RESULTS: The results demonstrate that the hybrid polyoligomer is not cytotoxic (cytotoxicity score 0-1), cells adhere well to its surface, retain their viability and typical morphology throughout the entire observation period. No negative impact of material implantation on the health state and behavior of animals was detected. Morphological examination showed the absence of inflammatory changes, formation of thin-walled capillary vessels, and considerable proliferative activity of mesenchymal cells in the defect area, even though it was more intense than in the control group. CONCLUSION: No inflammation signs were detected by 8th week of the experiment. It was defined that new bone was beginning to form. The results of analysis support the conclusion that the developed hybrid materials are prospective for further research as potential bone substitute.

Influence of surface morphology of chitosan films modified by chitin nanofibrils on their biological properties.

The paper is devoted to the study of influence of chitin nanofibrils on the structure, surface morphology, mechanical properties, and electrical conductivity of chitosan-based composite films intended for use in biomedical technologies. It was demonstrated that the optimal concentration of chitin nanofibrils in the composite film is 5 wt.%. For the films of this composition, we observed orientation of structural elements on film surface, enhanced mechanical properties as well as an increase in both specific conductivity and proliferative activity of skin fibroblasts on film surface. These results are related to the appearance of oriented structure in nanocomposites and to self-organization of chitosan macromolecules on the surface of chitin nanofibrils. It was revealed that increase in surface energy and surface hydrophilicity did not facilitate effective adhesion, viability and proliferative activity of cells during cultivation on the surface of composite films.

[Modern aspects of the complex treatment of perforated gastric and duodenal ulcer]. / Sovremennye aspekty kompleksnogo lecheniya perforativnoi yazvy zheludka i dvenadtsatiperstnoi kishki.

OBJECTIVE: To study the effectiveness of pharmacotherapy for perforated gastric ulcer in a surgical hospital. MATERIAL AND METHODS: A retrospective analysis of the treatment of 693 patients with perforated gastric and duodenal ulcers was carried out. Laparoscopic and open surgeries were performed. Statistical analysis was performed using the Statistica and MS Excel software packages. Student t-test was applied for independent samples and Fisher's F-test was calculated. RESULTS: Combined therapy included surgical treatment (suturing of the ulcer as a rule) and medication with proton pump inhibitors, antibacterial drugs. Over the past 5 years, postoperative quality of life has been significantly improved in patients with perforated ulcers. Stomach resection and vagotomy for perforated ulcers will become historical in the near future. Laparoscopic and open procedures ensure similar periods of ulcer closure. CONCLUSION: Currently, successful treatment of perforated gastric and duodenal ulcers requires an integrated approach at all levels of specialized care and is impossible without modern pharmacotherapy.

[Ontogenetic forms of rheumatoid arthritis and behavioral type A.]

Disease onset and type A behavioral pattern (TABP) are important characteristics of the clinical manifestations of chronic diseases. The aim of this work is to study the prevalence and role of TABP in patients with rheumatoid arthritis (RA) with the onset of the disease at different periods of ontogenesis. 82 patients were examined, which were divided into groups depending on the age of RA onset. The first group included patients with RA onset at reproductive age (from 18 to 44 years). The second group included patients with the onset of RA in the middle age (from 45 to 59 years). The third group consisted of patients with the onset of RA in old age (from 60 to 74 years). The fourth group consisted of patients with the onset of RA in old age (75 years and older). Diagnosis of TABP was carried out using a special questionnaire. The group with a debut in the reproductive period had the largest number of patients with RA of the 1st and 2nd line of relationship, as well as the highest incidence of TABP, which was associated with a greater expression of such personal qualities as ambition and hostility. This group had the highest number of ankylosis, as well as the highest frequency of systemic lesions. The second group demonstrated classic rheumatoid patterns. The third group with debut in old age had the most favorable clinical picture, incl. the lowest immunological activity in terms of the сirculating immune complexes (CICs) level, associated with the lowest severity of articular syndrome, with the lowest number of erosions and the frequency of systemic manifestations. The fourth group with a debut in old age demonstrated the highest inflammatory activity and specific immunological activity in terms of rheumatoid factor and CICs levels, as well as the highest clinical severity of the articular syndrome. Thus, the ontogenetic debut of RA determines its clinical and laboratory features and is associated with the presence and characteristics of TABP.

[Treatment strategy for non-combat mine - explosive injury of the lower limbs]. / Sluchai minno-vzryvnoi travmy nizhnikh konechnostei mirnogo vremeni.

Mine-explosive trauma is one of the most serious types of combat lesion and injuries in peacetime. We report a patient with mine-explosive trauma of the lower limbs followed by injury of the vascular bundle. Well-coordinated work of a multidisciplinary team of specialists at all stages of treatment is presented. The management was effective to save patient's life, avoid amputation and restore lower limb function.

Thermodynamics of interaction between water and the composite films based on chitosan and chitin nanofibrils.

Interaction between water and composite films based on chitosan and chitin nanofibrils was studied. Isotherms of water vapor sorption by composite films were used to calculate partial values of entropy and enthalpy of sorbate; dependences of entropy and enthalpy on water sorption value were obtained. It was demonstrated that introducing chitin nanofibrils into chitosan matrix leads to decrease in sorption capacity of composite films. Apparently, this phenomenon is caused by formation of ordered structures consisting of chitosan macromolecules on the surface of chitin nanofibrils. The hypothesis was confirmed by calculations of thermodynamic parameters of the chitosan/chitin/water system. The calculations led to the conclusion that thermodynamically stable chitosan/chitin system is formed in composite films; in addition, it was revealed that the strongest chitosan-chitin interaction arises in the composite containing 1-5 wt.% of chitin nanofibrils. In this concentration range, Gibbs energy, entropy and enthalpy of mixing pass through a minimum; this result indicates that the highest affinity between chitosan and chitin exists when concentration of chitin nanofibrils varies from 1 to 5 wt.%.

[AUTOVENOUS REVASCULARIZATION OF THE LOWER EXTREMITY ARTERIES IN PATIENTS WITH VARIANT ANATOMY OF THE PERIPHERAL BLOOD FLOW AND THE PROGRESSIVE ATHEROSCLEROTIC PROCESS].

Obliterating diseases of the lower extremity arteries occupy a high proportion in the structure of cardiovascular morbidity in the population among the developed countries. The steadily progressing course of obliterating atherosclerosis leads to the critical lower limb ischemia and causes an unfavorable prognosis for preserving the extremity, as well as the patient's life. Nowadays, there are two ways of surgical management of this pathology: endovascular and open reconstructive interventions. The choice of the method is based on a comprehensive keeping of the patient-specific records, including the anatomical characterization of the arterial bed lesions. In case of extended occlusion of the superficial femoral artery, the open reconstructive surgery using a large saphenous vein as a transplant is recommended. This circumstance is confirmed by the autovein patency in the long term compared with a synthetic prosthesis according to the results of randomized clinical trials. Therefore, with the formation of a distal anastomosis below the gap of the knee joint, the patency of the autovein and synthetic prosthesis after 5 years is 71% and 44% respectively. In this article, we represent a clinical case of successful treatment of a patient with progression of atherosclerotic lesions of the infrainguinal segment arteries. A staged revascularization of the femoral-popliteal segment arteries using technique of a reversed vein on both lower extremities after attempts of the conservative treatment and x-ray endovascular intervention was performed. A feature of this case is the creation of a new bifurcation of the popliteal artery during the formation of a distal anastomosis below the fissure of the knee joint under the contitions of a high discharge of the anterior tibial artery.The given clinical case demonstrates the advantages of invasive surgical tactics with the aim of preserving the limb and improving the patient's quality of life.

[Large outpatient surgery. Are there prospects?] / Bol'shaia ambulatornaia khirurgiia. Est' li perspektivy?

AIM: To study frequency of 'hospital registry' operations in the polyclinics of the Central Federal district, to analyze previous experience of outpatient surgical care and to assess perspective directions of its development. MATERIAL AND METHODS: Over 48 million people who referred to polyclinics for medical care in 17 regions of Central Federal district for 6 years (2011-2016) were studied. RESULTS: Mean surgical activity in the polyclinics of Central Federal district is 4.5%. The annual number of 'hospital registry' operations does not exceed 150-200 (0.01%) for the entire district. Large outpatient surgery in Russia has evolved from active development to complete apathy and was almost always associated with health care reforming and attempts to reduce the volume of 24-hour in-patient surgical care. CONCLUSION: Advanced outpatient surgery is able to compensate routine in-hospital operations and to focus resources of these hospitals on the development of high-tech surgical care. It is necessary to change the insurance share of financing of patients operated in day surgical hospitals for successful development of 'large outpatient surgery'.

Study of the Osteoindictive Properties of Protein-Modified Polylactide Scaffolds.

Bone marrow mesenchymal stromal cells are multipotent and can differentiate into cells of various tissues, which determines their high importance for clinical application. We performed an in vitro study of the osteogenic potential of mesenchymal stromal cells cultured on intact polylactide scaffolds or scaffolds modified with collagen I or fibrin. Scanning electron microscopy showed that the cells formed osteogenic nodules or osteogenic nodules on both intact and fibrin-modified polylactide scaffolds. Spectrophotometric detection of alkaline phosphatase activity on days 7 and 11 showed that mesenchymal stromal cell grown on intact polylactide scaffolds and on scaffolds modified with collagen type I or fibrin more intensively synthesized alkaline phosphatase than in the control (culture plastic). This dependence increases in the presence of osteogenic differentiation factors in the medium. After long-term culturing (4 weeks), the presence of calcium deposits detected by alizarin red staining confirmed the osteoinductive properties of intact and protein-modified polylactide scaffolds. These findings suggest that polylactide scaffolds and collagen I increase the osteogenic differentiation potential of mesenchymal stromal cells.

Ramsey Spectroscopy with Displaced Frequency Jumps.

Sophisticated Ramsey-based interrogation protocols using composite laser pulse sequences have been recently proposed to provide next-generation high-precision atomic clocks with a near perfect elimination of frequency shifts induced during the atom-probing field interaction. We propose here a simple alternative approach to the autobalanced Ramsey interrogation protocol and demonstrate its application to a cold-atom microwave clock based on coherent population trapping (CPT). The main originality of the method, based on two consecutive Ramsey sequences with different dark periods, is to sample the central Ramsey fringes with frequency jumps finely adjusted by an additional frequency-displacement concomitant parameter, scaling as the inverse of the dark period. The advantage of this displaced frequency-jump Ramsey method is that the local oscillator (LO) frequency is used as a single physical variable to control both servo loops of the sequence, simplifying its implementation and avoiding noise associated with controlling the LO phase. When tested using a CPT cold-atom clock, the DFJR scheme reduces the sensitivity of the clock frequency to variations of the light shifts by more than an order of magnitude compared with the standard Ramsey interrogation. This simple method can be applied in a wide variety of Ramsey-spectroscopy based applications including frequency metrology with CPT-based and optical atomic clocks, mass spectrometry, and precision spectroscopy.