Standardizing a method for functional assessment of neural networks in brain organoids.

During the last decade brain organoids have emerged as an attractive model system, allowing stem cells to be differentiated into complex 3D models, recapitulating many aspects of human brain development. Whilst many studies have analysed anatomical and cytoarchitectural characteristics of organoids, their functional characterisation has been limited, and highly variable between studies. Standardised, consistent methods for recording functional activity are critical to providing a functional understanding of neuronal networks at the synaptic and network level that can yield useful information about functional network phenotypes in disease and healthy states. In this study we outline a detailed methodology for calcium imaging and Multi-Electrode Array (MEA) recordings in brain organoids. To illustrate the utility of these functional interrogation techniques in uncovering induced differences in neural network activity we applied various stimulating media protocols. We demonstrate overlapping information from the two modalities, with comparable numbers of active cells in the four treatment groups and an increase in synchronous behaviour in BrainPhys treated groups. Further development of analysis pipelines to reveal network level changes in brain organoids will enrich our understanding of network formation and perturbation in these structures, and aid in the future development of drugs that target neurological disorders at the network level.

Generation of the iPSC line FINi002-A from a male Parkinson's disease patient carrying compound heterozygous mutations in the PRKN gene.

The most common cause of autosomal recessive familial Parkinson's disease (PD) are mutations in the PRKN/PARK2 gene encoding an E3 ubiquitin protein-ligase PARKIN. We report the generation of an iPSC cell line from the fibroblasts of a male PD patient carrying a common missense variant in exon 7 (p.Arg275Trp), and a 133 kb deletion encompassing exon 8, using transiently-present Sendai virus. The established line displays typical human primed iPSC morphology and expression of pluripotency-associated markers, normal karyotype without SNP array-detectable copy number variations and can give rise to derivatives of all three embryonic germ layers. We envisage the usefulness of this iPSC line, carrying a common and well-studied missense mutation in the RING1 domain of the PARKIN protein, for the elucidation of PARKIN-dependent mechanisms of PD using in vitro and in vivo models.

Generation of an iPSC line (FINi001-A) from a girl with developmental and epileptic encephalopathy due to a heterozygous gain-of-function p.R1882Q variant in the voltage-gated sodium channel Nav1.2 protein encoded by the SCN2A gene.

A range of epilepsies, including the most severe group of developmental and epileptic encephalopathies (DEEs), are caused by gain-of-function variants in voltage-gated channels. Here we report the generation and characterisation of an iPSC cell line from the fibroblasts of a girl with early infantile DEE carrying heterozygous missense gain-of-function mutation (R1882Q) in Nav1.2(SCN2A) protein, using transient transfection with a single mRNA molecule. The established iPSC line displays typical human primed pluripotent stem cell characteristics: typical colony morphology and robust expression of pluripotency-associated marker genes, ability to give rise to derivatives of all three embryonic germ layers, and normal karyotype without any SNP array-detectable copy number variations. We anticipate that this iPSC line will be useful for the development of neuronal hyperactivity-caused human stem cell-based DEE models, advancing both understanding and potential therapy development for this debilitating condition.

[Professor Boris Petrovich Ugryumov is a prominent military pathologist]. / Professor Boris Petrovich Ugryumov ­ vidnyi voennyi patologoanatom.

The biographical article is dedicated to the memory of Boris Petrovich Ugryumov, a graduate of the Imperial Military Medical Academy (1914), a prominent military pathologist, the First Head of the Department of Pathological Anatomy, Ryazan Medical Institute. The paper presents the major milestones in the life of B.P. Ugryumov; his service on the fronts of the First and Second World Wars and his teaching activity at the Military Medical Academy and the Naval Medical Academy occupy an important place. For about 10 years, he was in charge of the Pathology Department, S.P. Botkin Clinical Infectious Diseases Hospital in Leningrad, which largely determined the area of his professional interests, such as the pathomorphology of infectious diseases, tuberculosis in particular. The archiving and personal photographic documents that have been previously unknown to the public are published for the first time.

[Prostate cancer and dogs sense of smell: opportunities of noninvasive diagnostics].

INTRODUCTION: A screening of prostate cancer is an important problem of healthcare system worldwide. AIM: To evaluate a possibility and efficiency of Belgian Malinois dogs sense of smell in diagnosis of prostate cancer. MATERIALS AND METHODS: Urine samples from 176 men were assessed. Of these, 112 samples were taken from patients with biopsy-proven prostate cancer, and 64 from healthy young men. The study with two Belgian Malinois dogs consisted of two stages. The first stage was to train the dogs to distinguish the urine of patients with prostate cancer. A total of 66 urine samples were used at this stage (from 42 patients with prostate cancer and 24 healthy people). At the second detection stage, urine samples of patients with prostate cancer was identified. A total of 110 urine samples were evaluated (70 patients with prostate cancer and 40 healthy people). RESULTS: The first dog correctly identified 68 samples from patients with prostate cancer, and in 37 cases it indicated the absence of disease (sensitivity 97.1%, specificity 92.5%, accuracy 95.4%). The second animal correctly identified 69 and 39 samples, respectively (sensitivity 98.6%, specificity 97.5%, accuracy 98.2%). CONCLUSION: A possibility of training dogs to identify patients with prostate cancer has been demonstrated. Further studies dedicated to the detection of volatile organic compounds in the urine using specialized analyzers of "electronic nose" type, as well as gas chromatography in combination with mass spectrometry, are of both scientific and practical interest.

Correction to: A PRISMA-compliant systematic review of the endpoints employed to evaluate symptomatic treatments for primary headaches.

Following publication of the original article [1], we have been notified that the name of author five was spelled incorrectly as M. Ferrili, when the correct spelling is MAN Ferilli.

A PRISMA-compliant systematic review of the endpoints employed to evaluate symptomatic treatments for primary headaches.

BACKGROUND: Primary headache are prevalent and debilitating disorders. Acute pain cessation is one of the key points in their treatment. Many drugs have been studied but the design of the trials is not usually homogeneous. Efficacy of the trial is determined depending on the selected primary endpoint and usually other different outcomes are measured. We aim to critically appraise which were the employed outcomes through a systematic review. METHODS: We conducted a systematic review of literature focusing on studies on primary headache evaluating acute relief of pain, following the PRISMA guideline. The study population included patients participating in a controlled study about symptomatic treatment. The comparator could be placebo or the standard of care. The collected information was the primary outcome of the study and all secondary outcomes. We evaluated the studied drug, the year of publication and the type of journal. We performed a search and we screened all the potential papers and reviewed them considering inclusion/exclusion criteria. RESULTS: The search showed 4288 clinical trials that were screened and 794 full articles were assessed for eligibility for a final inclusion of 495 papers. The studies were published in headache specific journals (58%), general journals (21.6%) and neuroscience journals (20.4%). Migraine was the most studied headache, in 87.8% studies, followed by tension type headache in 4.7%. Regarding the most evaluated drug, triptans represented 68.6% of all studies, followed by non-steroidal anti-inflammatories (25.1%). Only 4.6% of the papers evaluated ergots and 1.6% analyzed opioids. The most frequent primary endpoint was the relief of the headache at a determinate moment, in 54.1%. Primary endpoint was evaluated at 2-h in 69.9% of the studies. Concerning other endpoints, tolerance was the most frequently addressed (83%), followed by headache relief (71.1%), improvement of other symptoms (62.5%) and presence of relapse (54%). The number of secondary endpoints increased from 4.2 (SD = 2.0) before 1991 to 6.39 after 2013 (p = 0.001). CONCLUSION: Headache relief has been the most employed primary endpoint but headache disappearance starts to be firmly considered. The number of secondary endpoints increases over time and other outcomes such as disability, quality of life and patients' preference are receiving attention.

[Cognitive dysfunction and content of inflammatory markers in patients after coronary artery bypass graft]. / Kognitivnaia disfunktsiia i soderzhanie v krovi markerov vospalitel'nogo otveta u patsientov, perenesshikh aortokoronarnoe shuntirovanie.

AIM: To study the relationship between the content of inflammatory biomarkers and cognitive function in patients after coronary artery bypass graft (CABG) performed in condition of artificial blood circulation (ABC) or open-heart surgery (OHS). MATERIAL AND METHODS: Twenty-nine patients with ischemic heart disease who survived CABG, mean age 62.4±6.2 years, were studied. The ABC group (n=18) and OHS group (n=11) were matched for age and sex. Patients underwent standard clinical examination as well as neurological examination and neuropsychological testing. Concentrations of pro- and anti-inflammatory cytokines (IL-1ß, IL-2, IL-4, IL-6, IL-10, IL-12, IL-17, IL-1RA, IFN-γ, IP-10; MCP-1, MIP-1α, MIP-1ß, RANTES, TNF) were determined in blood plasma obtained 24 h before and 2h after surgery using multiplex immunofluorescence assay. RESULTS: In both groups, an increase in concentrations of IL-6, IL-8, IL-10, IL-12, IP-10, MCP-1, MIP-1ß and RANTES was observed at point T1. Concentration of IL-1RA was significantly higher only in the ABC group but not in the OHS group. After CABG, an increase in concentrations of IL-8, IP-10, MIP-1ß, IL-1RA was significantly higher in the ABC group. The Montreal scale was the most sensitive test for assessment of cognitive functions in post CABG patients. A significant decrease in scores (>3) was noted in 8 out of 18 patients in the ABC group and in one patient of the OHS group. The correlations between the decrease in cognitive functioning in the 7th day after surgery and plasma cytokine concentration 2 h after surgery were identified for IL-6 (r=0.472; p=0.01); IL-8 (r=0.403; p=0.03); IP-10 (r=0.372; p=0.047); MCP-1 (r=0.470; p=0.01). CONCLUSION: CABG is accompanied by the systemic inflammatory reaction, with the more marked inflammatory effect in patients operated under condition of extracorporeal circulation. CABG with ABC causes an impairment of cognitive functions during the first week in many patients. Impaired cognitive status was associated with the increase in concentrations of proinflammatory cytokines in blood plasma.

[Forum of military physicians of Asia Pacific region].

Forum of military physicians of Asia Pacific region. Authors proviae a report about the 3rd Military medical Asia Pacific congress, which was held in August 2016 in Saint Petersburg under the authority of the International military medical committee. Within the frame of the congress was held regional workshop, in the course of which was heard a report of the Thailand representative, requests of observer states for the entry. The country, which will hold the 4th Military medical Asia Pacific congress, is Iran. On the last day of the congress delegates visited the finals of the Military-medical race of the military physicians profession skill competition within <.

[Recovery after deep defects of the fingers covering tissues in daily surgical hospital].

The article describes the experience of reconstructive and restorative operative treatment of patients with, defects of the skin of the fingers at the daily surgical hospital. It is shown that surgeons applying standard instruments and having additional training in hand surgery, using a technique non -free skin plastic flap on a temporary pedicle and using inpatient technology, get cosmetic and functional results compared to-those of treatment in hospitals. Cited in -the article data on the direct and separate treatment outcomes, quility of life of patients, the estimated non-specfic and organ-specific method, clearly show that non-free skin plastic flap on a temporary pedicle - a reliable and effective method of restoration of the skin fingers defects which can be accompanied wit the use of resource-saving technologies in health care.

[Anniversary of the science regulatory body of the S. M. Kirov Military medical academy].

Anniversary of the science regulatory body of the S.M.Kirov Military medical academy. In the nineteenth century the Military-medical scientific committee was responsible for organization of scientific activity in the system of medical service of the Armed Forces; in the soviet period - the Military-scientific committee of the Main military-medical authority (since 1930) and scientific department of the S.M.Kirov Military medical academy (since 1931). In 1931-1936 and in 2010-2014 the Military-scientific committee of the Main military- medical authority was dissolved, and in 1936-1940 and in 2014-2015 conducted a supernumerary activity, during these periods the scientific department of the S.MKirov Military medical academy was responsible for coordination of scientific work in the Armed Forces. An experience of organization of the scientific regulatory bodies brought positive results and allows developing medical science further in the interests of the Army and the Navy.

[Graduate of the S.M.Kirov Military-medical academy Fedor Levin: on the way to discovery of DNA].

Biochemist Fedor Aronovich LeviN (1869-1940) graduated with honours from the S.M.Kirov Military Medical Academy in St. Petersburg in 1891 where he had received a fundamental knowledge from A.P.Dianin and I.P.Pavlov, and then he immigrated to the US. More than three and a half decades of his successful research at the Rockefeller Institute for Medical Research contributed to the foundation of the doctrine of nucleic acids. Scientists, who continued to research nucleic acids, were awarded the Nobel Prize, but Levin and his contribution were forgotten. The authors of the given article didn't found any source in Russian about this prominent biochemist of the 20th century and member of the Russian scientific school. The purpose of the article is to acquaint the reader with a scientific biography of the scientist. who became, without exaggeration, one of the founders of modern genetics.

[The use of percutaneous endoscopic gastrostomy for provision of the long-term enteral nutrition].

Percutaneous endoscopic gastrostomy for provision of the long-term enteral nutrition is well established in clinical practice because unlike from traditional gastrostomy and jejunostomy allowed to avoid many complications. The technique is used for enteral tube feeding in the absence of real positive predictive recovery of consciousness and swallowing function. During presented study from 387 patients with a gastrostomy imposed by percutaneous endoscopic technique, observed only 1,8% of suppurative complications and in 1% of cases - uncontrolled removal of the tube by the patient. Our experience allows us to recommend this technique for wide implementation in practice of medical institutions in case when it is necessity in enteral feeding more than 3 weeks of patients with impaired

[Diagnosis and treatment of achalasia cardiae].

Achalasia is a progressive oesophageal motility disorder of unstudied aetiology involving the smooth muscle layer of the oesophagus. Insufficient knowledge of the pathogenesis of achalasia and the lack of clear treatment approaches has led to an increase of advanced disease forms. Common clinical manifestations of the disease are: incomplete LES relaxation, non-specific initial manifestations and as a result late medical seeking. Occurrence of achalasia cardiae is significantly low, therefore it is important to analyse the available clinical data. The article presents an experience of treatment of 30 patients over the last 16 years of observation. The average age of patients was 50, 5 years; insignificant male predominance is noted. III or IV disease state was diagnosed in 86.7% of patients; this diagnosis was confirmed by esophagogastroduodenoscopy. In the group of 24 patients who underwent attempted endoscopic dilatation of the cardiae, most of the included patients with stage II and III disease. Immediate good and satisfactory results of endoscopic treatment were obtained in 20 patients (83.3%), in 4 cases (16.7%) developed recurrent disease.

Activity of succinate dehydrogenase in the neocortex and hippocampus of Mongolian gerbils with ischemic and reperfusion brain injury.

We analyzed changes in activity of SDH, one of the most important enzymes of the Krebs cycle, in the cytoplasm of hippocampal and cortical neurons of Mongolian gerbils (Meriones unguiculatus) at the early and delayed reperfusion period after global brain ischemia. The data indicate that SDH activity in pyramidal neurons of various hippocampal areas and in neurons of II, III and V layers of cerebral cortex after 7-min forebrain ischemia depends on both the localization of these neurons and duration of the postischemic reperfusion. SDH activity in neurons significantly increased on days 2 and 7 after reperfusion.

[Treatment of benign esophageal stricture].

The article presents an analysis of long-term experience of treatment of 128 patients with benign esophagus and esophageal anastomosis strictures in Kirov Military Medical Academy. This significant data included all possible variations of scarry esophageal strictures according their etiology, localization and the extension. The wide range of methods, which involved the different variants of bouginage, balloon dilation, stenting, electrosurgical dissection and resection of the stomach, were applied in treatment of the patients. The analysis of immediate and long-term results allowed detecting the criteria of choice and indication for use of the methods or their combination. Practical recommendations reflect the strategy of each variant of treatment and have the specific character. Possible complications and negative results of irrational application of different methods were presented. The immediate and long-term results gave evidence of the successful treatment of the patients with scarry esophagus and esophageal anastomosis strictures.

[Military postgraduate courses at the Military Medical Academy: history, current state and prospects].

Training of scientific and scientific-pedagogical staff is one of the most important tasks of any high school. The problem of staff training arose in the Kirov Military Medical (Medical Surgical) Academy before its official foundation. In 1741 first scholars were sent abroad for the preparation of theses. The scholars were supposed to return to the hospital schools for teaching activity. Since 1802 scholars have defended their theses in the Academy. In 1858 special medical institute, the prototype of the Institute for postgraduate military studies was established. Many outstanding scientists studied in the Academy and brought name of the Academy into repute. At the present time, the Institute of postgraduate military studies (postgraduate) of the Kirov Military Medical Academy continues to train scientific staff. The Institute of postgraduate military studies remains one of the most successful institutes in Russia.

[Department of training of physicians (for Missile Forces and Army) of Military-medical academy n. a. S.M.Kirov celebrates the 70th anniversary].

The article is dedicated to the history of the one of educational units of the Kirov Medical Academy. Department of training of physicians (for Missile Forces and Army) traces its origins to 1942 published in the resolution of the State Committee of Defense of the USSR, but in fact is the successor to hospital schools in the land and the Admiralty hospitals.

[From the history of military-medical education in XVIII century].

The article deals with the development of national medical education. The above materials are based mainly on archival material, published documents and publications of military history topics. The authors have shown that even with the publication of the decree on the construction (01.24.1715), and the tab (Spring 1715), Overland, and hospitals Admiralty in St. Petersburg, Peter the Great planned to their clinical status. However, construction was delayed until 1732, when it became a possibility of teaching, and almost immediately was royally endorsed a report on the state Medical Collegium, which determined the number of teaching staff and students. In the 1730's attempts to prepare highly qualified teachers of special schools for the hospital, and in 1742 already appears first full-time professor. Completed the period of formation can be considered in 1754, when P.Z.Kondoidi signed a decree on a new preparation for doctors with a 7-year period of training.

A new rat model of reversible global cerebral ischemia.

A new rat model of global cerebral ischemia-reperfusion was proposed via reversible occlusion of the major vessels originating from the aortic arch and supplying the brain. This technique can be used for the search and study of exogenous (pharmacological) and endogenous methods of brain protection from ischemia-reperfusion injury.