bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular expression of insulin signal transduction components in brain cells in an experimental model of Alzheimer’s disease
Authors: Gorina Yana V. , Komleva Yuliya K. , Lopatina Olga L. , Chernykh Anatolii I. , Salmina Alla B.
Published: January 2025

Introduction. The risk of Alzheimers disease (AD) is increased with cerebral insulin resistance, which may be caused by the impaired function of the cerebrovascular system, and may also have a direct effect on -amyloid aggregation and Tau protein phosphorylation.
Aim. To study the molecular expression of insulin signal transduction components (IRS1, GSK3B and PKC) in the brain cells in an experimental model of AD.
Materials and methods. Experiments were conducted on 4-month-old C57BL/6 and B6.129S6-Nlrp3tm1Bhk/JJ male mice (NLRP3 knockout mice) with 5 animals in each group. AD was modelled in the experimental group of mice by administering -amyloid; mice in the control group received sham surgery. IRS1, GSK3B and PKC expression in the amygdala was studied using immunohistochemistry methods.
Results. The C57BL/6 mice with AD had reduced IRS1 expression compared with the mice who received sham surgery (0.620.13 and 0.890.17; р=0.045), while the -amyloid did not produce the same result in NLRP3 knockout mice. GSK3B expression was increased in C57BL/6 mice with AD (0.600.12) when compared with both the control group (0.200.02; p0.0001) and the NLRP3 knockout mice with AD (0.270.08; p0.0001). PKC expression in C57BL/6 mice with AD was reduced (0.520.14) when compared with the NLRP3 knockout mice with AD (0.890.18; p0.05) and the control group (0.840.12; p0.05).
Conclusion. The development of Alzheimer type-neurodegeneration is accompanied by disruptions in IRS1 and GSK3B expression, which is associated with impaired signal transmission along the PKC pathway. The suppression of neuroinflammation through NLRP3inflammasome deletion has a protective effect in AD.
Group I metabotropic glutamate receptors (mGluR1/5) and neurodegenerative diseases
Authors: Solntseva Elena I. , Rogozin Pavel D. , Skrebitsky Vladimir G.
Published: January 2025

This overview describes how group mGluR1/5 metabotropic glutamate receptors are involved in neurodegenerative diseases; it also touches upon their use as therapeutic targets in animal models. mGluR1/5 are primarily located on the neuronal postsynaptic membrane, where they communicate with two proteins, Gq/11 and Homer, which, in turn, initiate several biochemical cascades. The Gq/11 protein cascade includes Са2+ release from the endoplasmic reticulum (ER) through the inositol trisphosphate receptors (IP3R) and the activation of depot-controlled Са2+ entry. The Gq/11 protein cascade also includes the production of diacylglycerol with subsequent activation of various protein kinases, which, in turn, provide influences on the genome. The Homer protein communicates directly with the NMDA receptors and Shank scaffold proteins, through which it regulates the activity of various protein kinases, including Akt and ERK1/2. The activation of mGluR1/5 triggers long-term depression of glutamatergic transmission through the endocytosis of AMPA receptors, caused by changes in the level of protein phosphorylation and genome activation.
It is thought that mGluR1/5 play an important role in the development of neurodegenerative diseases. In Alzheimer's disease, mGluR1/5 acts as a target for the -amyloid peptide. mGluR1/5 antagonists have a neuroprotective effect in transgenic mice with Alzheimer's disease. The pathogenesis of Alzheimer's disease includes increased Са2+ release from the ER due to the pathological activity of mGluR1/5, as well as the influence of mutated presenilin on Са2+ homeostasis in the ER. At the same time, restoration of Са2+ levels in the ER is disrupted by the effect of presenilin on depot-activated Са2+ entry.
mGluR5 (but not mGluR1) is being studied as a potential therapeutic target in Parkinson's disease. Numerous studies on rodent and primate models of Parkinson's disease have demonstrated a significant antiparkinsonian effect when mGluR5 antagonists were used. It is thought that the neuroprotective mechanisms of action of mGluR5 antagonists involve limiting the increase in intracellular Са2+ by reducing IP3 and NMDA receptor activation. Huntingtons disease is related to a mutation in the HTT gene and the ability of the mutant huntingtin protein to sensitise IP3 and NMDA receptors, thus triggering Са2+ overload in the neurons. A neuroprotective effect in transgenic mice with Huntingtons disease was achieved by using positive allosteric modulators of mGluR5, capable of selectively activating cascades associated with the Homer protein and triggering Akt activation.
Nonconvulsive status epilepticus with triphasic wave EEG pattern: a case report
Authors: Baranova Elena A. , Danilova Tatyana V. , Khalitov Ilyas R. , Sinkin Mikhail V.
Published: January 2025

Introduction. Triphasic waves in an electroencephalogram (EEG) in patients with decreased alertness traditionally is associated with hepatic encephalopathy. The development of digital technologies and the introduction of systems that allow long-term EEG monitoring of the neurocritical care patients has led to accumulation of significant experience in recording triphasic waves in various metabolic, toxic, and structural brain disorders, as well as in nonconvulsive status epilepticus.
Materials and methods. We present a case of diagnosis and successful treatment of a nonconvulsive status epilepticus, that developed in a female patient after CABG, and that presented electrographically as a triphasic wave pattern.
Results. Description of the patients EEG according to the classification of rhythmic and periodic patterns of the American Clinical Neurophysiology Society and the use of clinical and EEG criteria of nonconvulsive status epilepticus of the International League Against Epilepsy enabled us to correctly diagnose the cause of her decreased alertness and other neurological symptoms. Proper selection of the antiepileptic drugs along with monitoring of daily EEG recordings led to a recovery of consciousness in the patient and to normalization of the EEG pattern, which confirmed the clinical hypothesis of a nonconvulsive status epilepticus.
Conclusions. Utilization of the modern clinical and electrographic classifications enables the diagnosis of a nonconvulsive epileptic seizure and status epilepticus when the EEG pattern is ambiguous and traditionally associated with other conditions. EEG monitoring must be performed in patients with a sudden deterioration of consciousness that cannot be explained by brain imaging studies.
Clinical, molecular, and genetic characteristics of the hereditary spastic paraplegia type 3
Authors: Rudenskaya Galina E. , Kadnikova Varvara A. , Beetz Christian , Proskokova Tatyana N. , Sermyagina Irina G. , Stepanova Anna A. , Fedotov Valery P. , Dadaly Elena L. , Guseva Darya M. , Markova Тatiana V. , Ryzhkova Oksana P.
Published: January 2025

Introduction. The autosomal dominant hereditary spastic paraplegia type 3 (SPG3), associated with the ATL1 gene, is a common form of the hereditary spastic paraplegia (HSP). The molecular genetic and clinical features of the SPG3 have not been sufficiently studied.
Study aim: to conduct the first clinical, molecular, and genetic study of HSP in Russia, using a high-throughput exome sequencing technology massively parallel sequencing (MPS).
Materials and methods. Study subject: 14 identified families with SPG3. Clinical and molecular genetic methods used: Sanger sequencing, MPS panel for spastic paraplegia, multiplex ligation-dependent probe amplification.
Results. SPG3 made up 7.2% of the 195 examined families, 13.6% of 103 molecularly identified cases, and 16.9% of the dominant forms, coming in second place after SPG4 (50%). We found 9 missense mutations in 14 families (7 in hot exons), with 4 new ones and the known p.Arg415Trp mutation identified in 4 families. One case was caused by a de novo mutation, the others were familial; incomplete penetrance was found in 5 families (subclinical cases). Gender distribution of the probands was equal, but there were more males among the affected relatives. Most of the 25 examined patients, as well as the relatives with clinical data, had early-onset (in the first decade of life, often at the age of 1 to 3 years), uncomplicated HSP with slow progression; many of those subjects were initially diagnosed with a cerebral palsy. Subclinical axonal polyneuropathy was found in 3 out of 6 cases using EMG. Atypical severe paraparesis was combined with skeletal pathology (likely independent of the major condition) in one female patient. Intellectual disability in males of another family was also considered to be an independent condition.
Conclusion. SPG3 has a significant prevalence among HSP in Russian patients. The clinical features in most cases are similar and relatively non-severe; clinical diagnosis may be challenging, especially in non-familial and non-apparent familial (incomplete penetrance) cases, as well as when combined with other conditions. An incorrect diagnosis of cerebral palsy is often made. A verified diagnosis is necessary for genetic counselling and is important for patient management. MPS methods are the most informative in the molecular genetic diagnosis of HSP.
The impact of DRD3, HS1-BP3, and LINGO1 gene mutations on the development and clinical heterogeneity of essential tremor in the Sakha Republic (Yakutia)
Authors: Govorova Tatyana G. , Popova Tatyana E. , Tappakhov Alexey A. , Golikova Polina I. , Danilova Anastasya L. , Antipina Ulyana D. , Samorseva Vera N. , Petrova Alena Yu. , Andreev Michil E. , Lyasheeva Nadezhda N.
Published: January 2025

Introduction. The ETM1, ETM2 and ETM3 loci are linked with the development of essential tremor (ET). It has been established that a mutation in the LINGO1 gene is a significant risk factor for ET development.
The aim of the study was to investigate the role of Ser9Gly polymorphism in the DRD3 gene, the Ala265Gly mutation in the HS1-BP3 gene and rs9652490 polymorphism in the LINGO1 gene in the development and clinical heterogeneity of ET in the Sakha Republic population (Yakutia).
Materials and methods. Thirty-nine patients with a confirmed diagnosis of ET and 48 patients with Parkinson disease were examined. The control group consisted of 87 healthy individuals. Polymorphism carrier status and gene mutations were identified using real-time polymerase chain reaction.
Results. The Ser/Gly genotype with Ser9Gly polymorphism in the DRD3 gene and the A/A genotype with rs9652490 polymorphism in the LINGO1 gene increases the risk of developing ET by 2.35 (p = 0.02) and 2.42 (p = 0.04) times, respectively. Moreover, the A/A genotype of the rs9652490 in the LINGO1 gene increases the risk for ET-plus syndrome by 2.17 times (p = 0.02). Our data didnt confirm the role of the Ala265Gly mutation in the HS1-BP3 gene in development of the ET.
The role of long noncoding RNAs in ischaemic stroke
Authors: Novikova Lilia B. , Gareev Ilgiz F. , Raskurazhev Anton A. , Beylerli Ozal A. , Minibaeva Guzel M
Published: January 2025

Ischaemic stroke (IS) is one of the leading causes of death and disability in the world. The consequences of IS manifest as severe and persistent neurological symptoms. The currently used methods for the management of IS are insufficient, partly because of incomplete understanding of the molecular mechanisms that occur in IS. Long noncoding RNA (lncRNAs) are noncoding RNAs that are longer than 200 nucleotides. It has been shown that lncRNAs control many processes: transcription, translation, regulation of gene expression, cell cycle regulation, apoptosis, cell proliferation, and differentiation. There is plenty of evidence that lncRNAs play a direct role in the pathogenesis of many human diseases, including IS. LncRNAs are found in the human bodily fluids, such as blood, urine, cerebrospinal fluid, and saliva. The expression profile of these circulating lncRNAs consists of a certain part of the cells, where they are modified and secreted in accordance with the physiological and pathological status of those cells. Due to their various ways of transport from cells into bodily fluids within exosomes or liposomes, lncRNAs are protected from the effect of RNases and remain in a stable form. Because of this, circulating lncRNAs are considered as novel biomarkers, which are of interest in many diseases, including IS. It likely appears that lncRNAs have the potential to be used in the diagnosis, management, and prevention of IS.
Interventional therapies for the chronic pain in degenerative spine conditions
Authors: Gushcha Artem O. , Gerasimova Elizaveta V. , Vershinin Andrey V.
Published: January 2025

Back pain due to degenerative spine conditions is one of the most common causes for seeking medical care. Standard pharmaceutical and physiotherapy interventions are offered to manage the pain. However, those approaches can be insufficient, and interventional therapies may be used in addition to standard treatment. The main principle of the interventional therapy is administering the medication directly to the affected part of the spinal segment. The article reviews the main interventional techniques, their indications, and differences between them.
Leukoencephalopathy with Brainstem and Spinal Cord Involvement and Lactate Elevation (LBSL) on Magnetic Resonance Spectroscopy: A Clinical Observation
Authors: Kazantsev Alexander Yu. , Matveeva Tatiana V.
Published: January 2025

Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL) on magnetic resonance spectroscopy is a rare and little-known form of hereditary leukoencephalopathy, a significant portion of which is probably obscured by the label of primary progressive multiple sclerosis. The article presents a clinical case of an adult form of LBSL and a review of the literature on this disease, discusses the particular pyramidal syndrome lesions in LBSL and multiple sclerosis, and presents the MRI criteria for LBSL. The difficulty in differential diagnosis with Krabbe disease is highlighted. Clinical observation confirms the difficulty of diagnosing LBSL and the lack of medical awareness about this disease.
The Diagnostic Significance of Intrathecal Synthesis of Antibodies Against Measles, Rubella, and Varicella Zoster Viruses in the Differential Diagnosis of Demyelinating Diseases of the Central Nervous System
Authors: Moshnikova Anna N. , Lapin Sergey V. , Nazarov Vladimir D. , Krasnov Vladimir S. , Dovidenko Ksenia S. , Surkova Elena A. , Savostyanova Valeria N.
Published: January 2025

Introduction. The basis of autoimmune inflammation in multiple sclerosis (MS) is the polyclonal activation of B lymphocytes in the central nervous system, followed by intrathecal immunoglobulin production, caused by the synthesis of antibodies to measles, rubella, and varicella zoster viruses (MRZ reaction).
The study aimed to assess the possibility of using the IgG index, oligoclonal immunoglobulin synthesis, the permeability coefficient of the blood-brain barrier, specific indices of antibodies against measles, rubella, and varicella zoster viruses with the calculation of the MRZ reaction in the diagnosis of MS, neuromyelitis optica, and acute disseminated encephalomyelitis.
Materials and methods. The study included 40 patients with the following diagnoses: MS (n = 19), acute disseminated encephalomyelitis (n = 11), and neuromyelitis optica (n = 10). Intrathecal synthesis indicators were measured in all patients in paired samples of cerebrospinal fluid and serum.
Study results. In the study group, the MRZ reaction was a specific test for the diagnosis of MS and was not found in neuromyelitis optica or acute disseminated encephalomyelitis. An increase in the IgG synthesis index was observed in only 90.5% of patients with MS, and oligoclonal IgG was detected in only 71.4% of cases. Elevated albumin quotient values are not typical for MS, which characterizes the degree of permeability of the blood-brain barrier.
Conclusion. The MRZ reaction is a highly specific laboratory marker for verifying MS. It also enables differential diagnosis of MS and other demyelinating diseases.
Somatosensory evoked potentials in the evaluation of motor rehabilitation efficacy in patients with ischaemic stroke
Authors: Alifirova Valentina M. , Tolmachev Ivan V. , Koroleva Ekaterina S. , Kucherova Kristina S.
Published: January 2025

Introduction.The quality of rehabilitation measures used during early functional recovery can be assessed by registering somatosensory evoked potentials (SSEP). In many patients, SSEP are either not recorded, or the results are poorly reproducible. To overcome these difficulties, we proposed to modify the method of recording SSEP in patients post ischaemic stroke.
Theaimof the study was to evaluate changes in SSEP after patients with ischaemic stroke underwent motor rehabilitation in the early recovery period.
Materials and methods.We examined 36 patients with acute ischaemic stroke in the middle cerebral artery territory. The severity of neurological deficits and the functional state of the nervous system were assessed using international clinical scales, based on electrophysiological and neuroimaging studies. The motor rehabilitation consisted of 10 sessions. SSEP were measured before and after the full motor rehabilitation course. We calculated the standard values for SSEP.
Results.Before rehabilitation, SSEP were not detected in the ipsilateral hemisphere in 40% of patients. After a course of rehabilitation, SSEP were detected in the majority (83%) of patients, but the values showed significant inter-individual variation, and in such patients, SSEP cannot be used as an indicator of rehabilitation effectiveness. In the group of patients whose SSEP could be reliably recorded and the main components P and N were measurable, we found that the average component latency in the ipsilateral hemisphere was N = 48 15 msec and P = 55 16 msec. These values are significantly higher than in the healthy population. The amplitude parameters corresponded to the published normal values. No statistically significant changes in the latency of components N and P were observed after the course of rehabilitation.
Conclusion.Using a method for measuring SSEP with spatiotemporal separation will significantly expand the range of patients whose condition, as well as the effectiveness of the rehabilitation procedures aimed at restoring lost motor function caused by ischaemic brain damage, can be monitored over time.
Non-pharmacological prevention and correction of cognitive disorders
Authors: Raskurazhev Anton A. , Kuznetsova Polina I. , Tanashyan Marine M.
Published: January 2025

This review deals with research on the effect of board games on the prevention of cognitive disorders in the older population. It is known that activities using board games significantly enhance educational and intellectual abilities in children. However, data on the effect of such interventions in older patients (including those at risk for developing dementia) are few and equivocal. In the Bronx Aging Study, reading, board games, playing musical instruments, and dancing were associated with a reduced risk of cognitive disorders. The MoVIES study assessed the cognitive status of 942 participants aged 65 years and older, and a lower risk of dementia was found in those who devoted more than 1 hour per day to 'recreational activities'. The French study of the PAQUID cohort showed that those who regularly played board games had a 15% lower risk of developing dementia than those who did not.
This review attempts to systematize the known data (including functional MRI data) on how playing board games influences changes in cognitive function. The article covers memory mechanisms that are necessary components of cognitive health. Structures that are directly involved in long-term memory formation, especially explicit memory, including the hippocampus, parahippocampal gyrus, and entorhinal cortex, are described.
The article includes studies covering not only geographical, economic and social status, age, gender, and level of cognitive load, but also the different assessments measuring the effect board games have on the brain. Different assessment methods and functional MRI data have demonstrated the potential effectiveness of using board games in the prevention of both age-related and pathological intellectual ageing.
Ultrasound imaging of the brachial plexus in healthy adults and those with neurogenic thoracic outlet syndrome
Authors: Mukhambetalieva Irina Kh. , Druzhinina Evgeniya S. , Druzhinin Dmitry S.
Published: January 2025

Ultrasound of the brachial plexus (BP) is a readily available and informative imaging method. Good knowledge of normal BP anatomy and its variations, as well as the ultrasound technique for examining the BP, is the key to success. We present an ultrasound technique for BP assessment in healthy adults and patients with neurogenic thoracic outlet syndrome.
Surgical treatment of epilepsy secondary to a hypothalamic hamartoma: a case report
Authors: Areshkina Irina G. , Dmitrenko Diana V. , Dmitrenko Alexey I. , Narodova Ekaterina A.
Published: January 2025

A hypothalamic hamartoma is a benign, congenital, heterotopic, neoplastic space-occupying mass located in the interpeduncular fossa, corresponding to a gangliocytoma according to the morphological classification. Patients with hypothalamic hamartoma often experience gelastic seizures and early puberty. Increasing evidence that hypothalamic hamartomas are the cause of gelastic seizures and secondary epileptogenesis has led to surgery being used more often as a permanent cure. Several minimally invasive procedures have been developed, including neuroendoscopic approaches and various stereotactic techniques in radiofrequency and laser ablation. Each method can lead to its own unique side effects. We conducted a review of the available Russian and international literature. This case report describes the surgical treatment of epilepsy secondary to a hypothalamic hamartoma.
Glutamate biomarkers in comprehensive diagnostics of acute and chronic brain ischemia
Authors: Ponomarev Grigory V. , Vozniuk Igor A. , Izumi Marina A. , Skoromets Alexander A.
Published: January 2025

The development and implementation of biomarkers of ischaemic brain damage at the pre-hospital and hospital stages, as well as during screening and regular medical examinations, are a priority in neurology. This review describes the role of NR2 peptide, a subunit of the NMDA ionotropic glutamate receptors, in the pathogenesis of cerebral ischemia. Experimental data are presented, showing that NR2 peptide expression increases in brain ischemia, its fragments passing through the blood-brain barrier and entering the bloodstream, thus stimulating the immune response and autoantibody production. Key studies are reviewed that have demonstrated the possibility of using glutamate receptors and their antibodies as potential biomarkers of acute and chronic cerebral ischemia. The sensitivity and specificity of NR2 peptide and NR2 antibodies in these studies averaged 90%. It has been shown that NR2A/B is the only marker with high negative and positive predictive value in people with suspected ischaemic stroke. Monitoring treatment effectiveness is another promising area of application for glutamate biomarkers.
Previous studies have shown that the NR2 peptide and its antibodies are potential biomarkers of cerebral infarction, transient ischaemic attack, and chronic cerebral ischemia and may become important components in a successful and comprehensive approach to treatment, screening, and monitoring of disease outcomes.
Effects of zolpidem and protons on GABA-induced current in the hippocampal pyramidal neurons in the presence of penicillin
Authors: Solntseva Elena I. , Bukanova Julia V. , Skrebitsky Vladimir G.
Published: January 2025

Introduction. Type A receptors activated by gamma-aminobutyric acid (GABAAR) play an inhibitory role in the nervous system due to the generation of chlorine current (IGABA). Penicillin is a sequential blocker of the GABAAR open channel, which can inhibit dissociation of the GABA-receptor complex. This GABA site modulation suggests that the effects of competitive GABAAR modulators may change in the presence of penicillin.
The aim of the study was to evaluate the effect of zolpidem, the positive competitive GABAAR modulator, and hydrogen ions (protons), the negative competitive GABAAR modulator, on IGABA in the presence of penicillin.
Materials and methods. IGABA was measured on isolated pyramidal neurons of the rat hippocampus, using the patch clamp technique and fast application system. GABA, penicillin, and zolpidem were applied to the neuron for 600 msec via a lateral shift pipette. To study the effect of protons on IGABA, the GABA solution in the application pipette was acidified to pH 6.07.0.
Results. The application of 1 mmol of penicillin reduced the IGABA amplitude to 67 4% of the control value. Zolpidem, with a concentration of 0.5 mol,increased the IGABA amplitude to 167 9% of the control value. When penicillin and zolpidem were co-applied, the stimulating effect of zolpidem was not observed, and the IGABA amplitude was 68 4%. Reducing the pH of the GABA solution to 7.0 or 6.0 caused the IGABA amplitude to decrease to 804 and 35 4%, respectively. The effect of protons on IGABA did not change in the presence of penicillin.
Conclusion. For the first time, it has been shown that the stimulating effect of zolpidem on IGABA is cancelled out by penicillin, while the inhibitory effect of protons on IGABA is preserved.
Results of percutaneous rhizotomy for trigeminal neuralgia in patients with multiple sclerosis
Authors: Tyurnikov Vladimir M. , Askarova Lola Sh. , Trifonova Olga V. , Zakharova Maria N. , Gushcha Artem O.
Published: January 2025

Introduction. Neuropathic pain in trigeminal neuralgia (TN) is one of the most common and debilitating symptoms in patients with multiple sclerosis (MS). This condition in MS is due to the demyelination of pontine afferent fibers in the sensory root of the trigeminal nerve. The area of demyelination is usually located in the ventrolateral pons between the exit of the trigeminal nerve root and the trigeminal nucleus, which is confirmed on MRI. In some cases, neurovascular compression also plays a role in afferent fiber injury, leading to the so-called double crush effect. Conservative therapy for TN in patients with MS is often insufficiently effective, thus increasing the pertinence of surgical treatment.
Materials and methods. The article reviews current pharmacological and surgical approaches to treating TN, findings from the literature, and our data on the safety and efficacy of percutaneous radiofrequency rhizotomy (PRR) for TN, based on the surgical treatment of 52 patients with MS at the Research Center of Neurology.
Results. PRR works by interrupting the connection between peripheral receptor zones and the hyperactive trigeminal structures in the brainstem. All patients were discharged from the hospital on day 23 after surgery, with complete pain resolution. There were early and late relapses in some instances, which required a repeated PRR.
Conclusion. PRR is a symptomatic surgical method that is safe, repeatable, and effective for treating TN in patients with MS, in whom pharmacological therapy has been ineffective or who could not tolerate it.
The effect of modifiable stroke risk factors on systemic thrombolytic therapy in patients with acute stroke
Authors: Kotov Sergey V. , Isakova Elena V. , Kolchu Inessa G. , Belkina Svetlana N.
Published: January 2025

Introduction. Systemic thrombolytic therapy (STT) is an effective and accessible method of reperfusion treatment for ischaemic stroke. However, it is not yet evident how the risk factors preceding ischaemic stroke affect disease progression and outcome, as well as the efficacy of STT.
The study aimed to examine the results of STT in stroke patients, depending on their risk factors, severity of those risk factors, and the success in managing them at the prehospital stage.
Materials and methods. We examined 229 patients who underwent SST, of whom 201 survived and 28 died. The presence of hypertension, type 2 diabetes mellitus, atrial fibrillation, or metabolic syndrome, as well as blood sugar level, lipid panel results, and body mass index were assessed.
Results. Ischaemic stroke subtype, the length of time from symptom onset to start of STT, or the presence of hypertension did not have a statistically significant effect on 28-day mortality. Patient age, NIHSS score, presence/absence of type 2 diabetes mellitus and atrial fibrillation, modified Rankin Scale score, blood sugar level, body mass index, and the presence of metabolic syndrome had a statistically significant influence on 28-day mortality. Data from the survived 201 patients were used to analyze the correlation between risk factors and functional recovery after ischaemic stroke. For patients with moderate and mild ischaemic stroke, statistically significant inverse correlations were found for age, blood sugar level, and body mass index.
Conclusion. An inverse correlation was found between 28-day mortality and age, severity of neurological impairment, blood sugar level at onset, body mass index, and the presence of the metabolic syndrome. The obesity paradox was not identified in regard to survival, but patients with hypercholesterolemia had more significant regression of neurological symptoms and better functional recovery. Receiving statins and having a target cholesterol level were not found to have a positive effect on patient recovery in the first 28 days after disease onset, likely because of greater severity of the overall vascular disease.
Does gender influence the clinical characteristics of ischaemic stroke in patients aged 45–74 years?
Authors: Maksimova Marina Yu. , Airapetova Aleksandra S.
Published: January 2025

Introduction. Modern studies seek to determine how age and gender affect morbidity and mortality, risk factors, causes, disease severity, and functional brain recovery after ischaemic stroke.
The study aimed to investigate the effect of gender on the main clinical characteristics of carotid territory infarction in patients aged 4574 years who did not undergo thrombolysis or mechanical thrombectomy.
Materials and methods. We examined 124 patients: 77 (62.1%) men and 47 (37.9%) women of middle age and older, with carotid territory infarction, who were admitted to the Research Center of Neurology in the first 48 hours after neurological symptom onset. The ischaemic stroke subtype, stroke severity, level of functional dependence, and level of daily and motor activity in patients were established.
Results. In our group, women were older than men by 4 years on average (p = 0.018). The mean female age was 67 years (5871 years), while the mean male age was 63 years (5866 years). Women were more often diagnosed with cardioembolic stroke, while men were more often diagnosed with an atherothrombotic stroke. Ipsilateral internal carotid artery stenosis 50% and left ventricular hypertrophy were more common in men than women, while left atrial dilation was more common in women. No significant differences were found between the two genders in the clinical presentation, acute stroke severity, and functional brain recovery.
Conclusion. In middle and older age patients, gender does not affect ischaemic stroke morbidity and rate of functional brain recovery by the end of the acute stroke period.
Giftedness and cytoarchitecture of the prefrontal cortex of the outstanding scientist and physiologist I.P. Pavlov
Authors: Piradov Mikhail A. , Illarioshkin Sergey N. , Bogolepova Irina N. , Malofeeva Lydia I. , Agapov Pavel A. , Malofeeva Irina G.
Published: January 2025

The aim of this study was to examine the cytoarchitecture of area 10 in the frontal lobe of I.P. Pavlov, an outstanding scientist, physiologist, and Nobel Prize winner.
Materials and methods. We studied the cortical cytoarchitecture of area 10 in the brain's frontal region belonging to the scientist and physiologist I. P. Pavlov (aged 86 years), compared with similar brain cortices of 4 elderly males (7590 years). Modern morphometric methods were used, on the basal surface of each cerebral hemisphere, to study the cortical thickness of area 10, thickness of the associated layer III, area of the specialized neural field in this layer, the number density of contained neurons, total glial cells, satellite glial cells, and the neurons surrounded by them.
Results. It was found that area 10 of the cerebral cortex of I.P. Pavlov is characterized by good preservation, pronounced radial striation, and significant asymmetry of the macroscopic and cytoarchitectural structure. Compared with ordinary men, area 10 of I.P. Pavlovs brain has a significantly thicker cortex and associative layer III, as well as a higher proportion of large neurons, number density of neurons, total glial cells, satellite glial cells, and neurons surrounded by them.
Sphenopalatine ganglion stimulation in refractory cluster headache: clinical case and literature review
Authors: Dzhafarov Vidzhai M. , Dmitriev Alexander B. , Moysak Galina I. , Rzaev Jamil A.
Published: January 2025

Cluster headache is characterized by specifically intense pain when compared to other types of headache. About 1020% of patients report no effect from conservative therapy. Research in this area has led to the use of sphenopalatine ganglion stimulation. The authors provide an up-to-date review of this method, how to select suitable patients, indications for surgery, determining its efficacy, and the risk of complications. The article presents a clinical case of a patient with cluster headache who was implanted with a stimulation system and followed up for 17 months.
Mitochondrial arteriopathy, a suspected cause of spontaneous dissection of the internal carotid and vertebral arteries
Authors: Kalashnikova Ludmila A. , Sakharova Alla V. , Chaikovskaya Roksana P. , Dobrynina Larisa A. , Gulevskaya Tat'yana S. , Gubanova Mariia V. , Voronkova Anastasiya S. , Sukhorukov Vladimir S.
Published: January 2025

Dissection of the internal carotid artery and vertebral artery (ICA/VA) is one of the leading causes of ischaemic stroke in young people. The reason for the arterial wall weakness leading to its dissection remains unclear. Morphological study of the ICA/VA, and clinical data, indicate the presence of connective tissue dysplasia in patients, which is not associated with any known hereditary diseases.
In this article, the authors summarize the results of their studies (histological and histochemical examination of muscle biopsies, electron microscopy of skin arteries) and observations (stroke-like episode, A3243G mutation in the mitochondrial genome in a patient with repeat ICA/VA dissections; increased peak lactate during MR spectroscopy in a patient who suffered an ICA dissection, then lobar hemorrhages a few years later). Based on these, the authors propose mitochondrial arteriopathy as the cause of arterial wall dysplasia leading to dissection. This article provides data on the presence of mitochondrial disorders in patients with ICA/VA dissection.
Principles of personalized medicine and modern pharmaceutical technologies to optimize levodopa therapy of Parkinson's disease
Authors: Abaimov Denis А. , Fedotova Ekaterina Yu. , Poleshchuk Vsevolod V. , Andreev Maksim N. , Trifonova Oxana P. , Lokhov Petr G. , Illarioshkin Sergey N.
Published: January 2025

Levodopa (3-hydroxy-L-tyrosine, the levorotatory isomerof 3,4-dihydroxyphenylalanine) is a biological precursor of the neurotransmitter dopamine and has been the "gold standard" in the treatment of Parkinsons disease for over 50 years. The widespread use of levodopa in clinical practice has not only provided neurologists with unique data from many years of symptomatic replacement therapy for a severe neurodegenerative disease but has also clearly identified several serious problems associated with levodopa absorption and metabolism. This article discusses the modern approaches to personalized medicine, which aim to overcome the numerous difficulties in managing patients with Parkinsons disease and long-term levodopa use. A major focus is the review of strategies for selecting the optimal levodopa dosage regimen in specific patients and the main innovative dosage forms of this drug that improve its pharmacokinetics.
Heuristic Modeling of Material Properties in Nano/Angstrom-Scale Channels: Integrating Experimental Observations and MD Simulations
Authors: Mishra Himanshu , Garg Ashish
Published: January 2025

Nanofluidics, the study of fluids confined within nanoscale channels, holds immense potential for various applications. However, these fluids exhibit unique properties (density, viscosity, and slip length) that deviate from their bulk counterparts and critically impact flow dynamics. Understanding and characterizing these properties is essential for designing efficient nanofluidic systems. Traditionally, numerous models, often complex and disparate, have been used to describe these properties. The current abundance of models makes selecting the most suitable one for numerical simulations a challenging task. In this paper, we propose a simpler, unified framework: a single power-law model for each property such as for density $\displaystyle \rho(H)/\rho_o = 1+ m_1~H^{-n_1}$, viscosity $\displaystyle \eta(H)/\eta_o = 1+ m_2~H^{-n_2}$, and the slip length $\lambda(H) = \lambda_o + m_3~H^{-n_3}$ (where $m_1, m_2, m_3, n_1, n_2, n_3, \lambda_o$ are the free fitting parameters). This model effectively captures data from experiments and simulations, even where existing literature employed diverse models. A key advantage of our model lies in its mathematical properties. Continuity and a continuous derivative ensure seamless implementation into numerical simulations and theoretical predictions, leading to more understable, stable and accurate results. Additionally, the model adheres to physical principles, predicting convergence to bulk properties as channel size increases. Further this proposed unified power-law model for density, viscosity, and slip length compared to existing exponential models, offers flexibility where it captures non-linear relationships and diverse data curvatures. Interpretability with clear physical meaning for parameters. Adaptability to combine with other functions for complex phenomena. Simplicity for easy parameter estimation, model interpretation, and computations. Robustness and less sensitive to outliers and noise in data and with fewer parameters to easy relate to underlying physics and scaling-laws. Hence proposed model's simplicity, smoothness, physical validity and generality make it a significant heuristic model for efficient design and optimization of nanoscale devices using theory and simulations across a wide range of applications.
Predicting Molecular Energies of Small Organic Molecules with Multifidelity Methods
Authors: Vinod Vivin , Lyu Dongyu , Ruth Marcel , Kleinekathöfer Ulrich , R. Schreiner Peter , Zaspel Peter
Published: January 2025

Multifidelity methods in machine learning (ML) have seen an increasing usage for the prediction of quantum chemical properties. These methods, such as ∆-ML and multifidelity ML, have been shown to significantly reduce the computational cost of generating training data. This work implements and analyzes several multifidelity methods including ∆-ML and multifidelity ML for the prediction of electronic molecular energies at DLPNO-CCSD(T) level, i.e., at the level of coupled cluster theory including single and double excitations and perturbative triples corrections. The models for small organic molecules are evaluated not only on the basis of accuracy of prediction, but also on efficiency in terms of the time-cost of generating training data. In addition, the models are evaluated for the prediction of energies for molecules sampled from a public dataset, in particular for atmospherically relevant molecules, isomeric compounds, and highly conjugated complex molecules.
Expediting hit-to-lead progression in drug discovery through reaction prediction and multi-objective molecular optimization
Authors: Nippa David F. , Atz Kenneth , Stenzhorn Yannick , Müller Alex T. , Tosstorff Andreas , Benz Jörg , Binch Hayley , Bürkler Markus , Haider Achi , Heer Dominik , Hochstrasser Remo , Kramer Christian , Reutlinger Michael , Schneider Petra , Shem Thierry , Topp Andreas , Walter Alexander , Wittwer Matthias B. , Wolfard Jens , Kuhn Bernd , van der Stelt Mario , Martin Rainer E. , Grether Uwe , Schneider Gisbert
Published: January 2025

The rapid and economical synthesis of novel bioactive compounds remains a significant hurdle in drug discovery efforts. This study demonstrates an integrated medicinal chemistry workflow that effectively diversifies hit and lead structures, enabling an efficient acceleration of the critical hit-to-lead optimization phase. Employing high-throughput experimentation (HTE), we generated a comprehensive data set encompassing 13,490 novel Minisci-type C-H alkylation reactions. This data set served as the foundation for training deep graph neural networks to accurately predict reaction outcomes. Scaffold-based enumeration of potential Minisci reaction products, starting from moderate inhibitors of monoacylglycerol lipase (MAGL), yielded a virtual library containing 26,375 molecules. This virtual chemical library was evaluated using reaction prediction, physicochemical property assessment, and structure-based scoring, identifying 212 potential MAGL inhibitor candidates. Of these, 14 ligands were synthesized and exhibited subnanomolar activity, representing a potency improvement of up to 4500 times over the original hit compound. These compounds also displayed favorable pharmacological profiles. Co-crystallization of three computationally designed ligands with the MAGL protein provided valuable structural insights into their preferred binding poses. This study demonstrates the potential of combining miniaturized HTE with deep learning and molecular property optimization to reduce cycle times in drug discovery.
Circularly Polarized Luminescence Control through Molecular Rotation in Crystalline Chiral Binuclear N-Heterocyclic Carbene Au(I) Complexes
Authors: Jiang Pingyu , Mikherdov Alexander , Ito Hajime , Jin Mingoo
Published: January 2025

The rotational motion within molecular crystals can affect not only their internal structure and symmetry, but also often results in the alteration of bulk properties such as thermal expansion, macroscopic motion, change in electromagnetic, optical, and photophysical properties. In this work, we demonstrate how the thermally activated molecular rotation within the crystals of chiral binuclear N-Heterocyclic carbene (NHC) Au(I) complexes can modulate their circularly polarized luminescence (CPL). The enantiomeric pair of chiral binuclear NHC Au(I) complexes, 1-R and 1-S, exhibit a distinct C2-symmetric conformation, derived from non-equivalent orientations of phenyl moieties at the chiral NHC ligands. The variable-temperature solid-state 2H NMR studies revealed that these non-equivalent phenyl moieties undergo fast rotational motion above 273K, potentially promoting symmetrization of molecular structures in the crystal. The latter, in combination with the inherent chirality of 1-R and 1-S complexes, results in the emergence of the temperature-dependent CPL behavior in the crystalline state with a noticeable increase of luminescence intensity and dissymmetry factors upon cooling from 333K to 213K (|ΔICPL|: + ~300%; |glum|: + ~50%). Such thermo-responsive behavior can be attributed not only to thermal rotation-induced luminescence quenching but also to the potential effect of phenyls rotation on the symmetry of the complexes.
A Liga Acadêmica como Instrumento para Consolidação do Ensino no Processo do Desenvolvimento Multiprofissional: Relato de Experiência
Authors: Barros Mateus Gomes de , Almeida Thiago Glória de , Timote Ana Clara de Sousa , Lavich Tatiana Ramos
Published: January 2025

As doenças cardiovasculares vêm, ao longo dos anos, sendo a principal causa de mortalidade no mundo, portanto se faz necessário um aperfeiçoamento dos estudos e consecução de conhecimentos em cardiologia dentro das universidades. Neste sentido, as ligas acadêmicas multiprofissionais voltadas para a área da cardiologia funcionam como uma ferramenta que auxilia na aquisição do conhecimento.  Além de possibilitar, a divulgação de informações referentes a diversos aspectos da saúde cardiovascular aos membros participantes para uma assistência integral aos pacientes e à família. O objetivo do estudo foi relatar as experiências da Liga Acadêmica Multiprofissional de Cardiologia da Universidade de Brasília (LACARDIO UnB) através das atividades desenvolvidas pela liga durante seu primeiro ano de atuação. Trata-se de um estudo qualitativo, descritivo, do tipo relato de experiência sobre as ações da liga. O presente artigo evidencia portanto, que a LACARDIO UnB possibilita a expansão da extensão universitária que vai além das barreiras da universidade e possibilita a formação de recursos humanos qualificados para o enfrentamento de doenças cardiovasculares dentro dos sistemas de saúde.
Projeto Vida Saudável: a importância da educação em saúde para alunos do ensino médio
Authors: Teixeirense Matheus Diniz , Araújo Nadjar Nitz Silva Lociks de , Melo Ana Estrela , Ferreira Luna Vitória Gondim
Published: January 2025

O projeto Vida Saudável, desenvolvido como uma ação de extensão da Faculdade de Medicina (FM/UnB), tem como objetivo principal conscientizar jovens do ensino médio da importância de serem adotados estilos de vida que redundem em bem-estar, tanto físico quanto psicossocial. A fim de se atingir esse objetivo, foram organizadas visitas desse público-alvo à FM, nas quais foram desenvolvidas atividades lúdicas e informativas a respeito das consequências de um estilo alimentar baseado em produtos ultraprocessados, bem como riscos associados a arboviroses comuns no Distrito Federal (DF) e entorno, e também formas de combate ao vetor e formas de identificar a doença. Isso permitiu que esses alunos adquirissem conhecimentos mais detalhados sobre os assuntos abordados; somado a isso, que pudessem refletir sobre o estilo de vida por eles adotado.
Análise Sobre a Extensão Universitária “Dromologia e seus Efeitos nas Estruturas Sociais Modernas”
Authors: Santos Diego de Medeiros Santos , Soares Ubirathan Rogerio
Published: January 2025

A dromologia está presente no espaço, tempo, velocidade, política, na sociedade. Nesse sentido, os encontros de discussões acerca dessa ciência atingiu como público-alvo discentes ingressantes à universidade, fator de grande relevância, posto que assim como a dromologia está presente na velocidade das modificações sociais, os participantes sofreram este impacto ao vivenciarem novas perceptivas de vida em âmbito acadêmico e afetados pela pandemia da Covid-19. A investigação, de caráter qualitativo se utilizou da análise descritiva sobre pontos que permeiam a dromologia, aspectos metodológicos e de experiência com a ação de extensão, esta vinculada ao componente curricular Antropologia Jurídica. Quanto aos resultados, pode-se elencar fatores como elevado engajamento dos discentes no projeto onde estavam motivados a entender os impactos da dromologia e extraírem uma nova percepção do mundo e sua constante transformação.
Terapeutas Populares ou Tradicionais e o cuidado com as pessoas e o Cerrado: ações de extensão
Authors: Guimarães Sílvia Maria Ferreira , Maués Clarice , Fonseca Clara , Fonseca Julia , Rocha Welitânia , Passold Sirlene , Santos Rosiene
Published: January 2025

A partir de uma aproximação com as comunidades da região da Chapada dos Veadeiros, esta ação de extensão pretende mapear e compreender os ofícios desenvolvidos pelos terapeutas populares ou tradicionais, buscando identificar suas práticas de cuidado que relacionam pessoas e o Cerrado; divulgar a importância desses ofícios em garantir uma vida plena nas comunidades; aprofundar o diálogo com a universidade com a possibilidade de fomentar diálogos inter-epistêmicos. Está baseado metodologicamente em rodas de conversas e ações voltadas para o fortalecimento dos conhecimentos tradicionais nas comunidades, tendo como base a construção conjunta de ações com a comunidade (mapeamento, acervo fotográfico, trocas de sementes e mudas).