Univerzitet u Beogradu - Medicinski fakultet, Beograd
Examination of changes in body composition depending on the training process in athelets
Introduction: It is well known that continuous physical activity causes adaptive changes in all organ systems, and they are most noticeable in the body composition parameters. Therefore, it is important to monitor the body composition parameters of top athletes, considering that their overall result depends on them. Aim: Examination of dynamics of changes in body composition depending on the period of the training process in athletes. Material and Methods: The research included 152 top athletes - male soccer players (18 to 40 years old), who at the time of the investigation were actively involved in competitive sports and trained at least 3 times and more than 10 hours a week. All data were analyzed from available medical records over a period of 16 years. Results: There is no significant statistical difference at the beginning and end of the season for all variables except for the amount of fat in kilograms and the percentage of fat. Conclusion: According to the results in the examined group of top athletes, the change in body composition does not depend on the training process. The only notable changes were observed in the amount of fat and body fat percentage. Keywords: body composition; athletes; BMI; BF
An Investigation Of The Epstein-Barr Virus Serological Status In The Adult Population
Introduction: Epstein-Barr virus is an ubiquitous virus from the family Herpesviridae, with seroprevalence ˃90% of world population. Primary infection is asymptomatic or in the form of infectious mononucleosis, depending on the age of patient and immune status. EBV establishes a latent infection in B-lymphocytes with occasional reactivation and because of its oncogenic potential, there is an association with numerous malignancies. Data on the EBV seroprevalence in our population is scarce. Аim: The aim of the study is to investigate the EBV serological status in the adult population by detecting specific antibodies against viral antigens. Material and methods: Serum samples of 58 individuals (age: 30.8±13.7 years; gender: M=41.4%, F=58.6%) were tested with comercial ELISA kits for presence of four antibodies against EBV (anti-VCA-IgM, anti-VCA-IgG, anti-EA-IgG, anti-EBNA-IgG). Based on recommendations from literature, every patient was, depending on serology results, classified in appropriate profile of EBV infection (primary, latent, reactivation). Results: In the 89.5% serum samples, antibodies against EBV were detected, with increasing trend of seropositive patients with age: from 87% seropositive samples in population 18-30 years, to 100% in elderly population. The profile of latent infection was detected in 81% of patients, 3.4% profile of primary infection, 3.4% profile of reactivated infection and 1.7% of unknown profile. There was no significant difference (p˃0.05) between titers of anti-VCA-IgG or anti-EBNA-IgG antibodies in different age groups, nor between genders. The significant difference was not found (p˃0.05) in the number of EBV seropositive samples between genders nor between age groups. Conclusion: Our study showed a high rate of latent EBV infection of 81%, which stipulates high grade of EBV infection in studied population. Differeneces in the seroprevalence among genders weren’t found nor among different age groups. Follow-up investigation of EBV seroprevalence in our population is needed in order to monitor the number of reactivated infections and development of malignancies associated with EBV. Keywords: Epstein-Barr virus; seroprevalence; latency; anti-EBV antibodies
DETERMINATION OF THE SEROPREVALENCE OF IgG ANTIBODIES AGAINST MEASLES VIRUS AMONG MEDICAL STUDENTS IN BELGRADE
Introduction: The measles virus is a negative-sense single-stranded RNA virus belonging to the family Paramyxoviridae. It causes measles, also known as rubeola or childhood rash fever. Before the introduction of mandatory vaccination, around 2 million people worldwide died from this disease annually. However, with the implementation of the MMR (measles, mumps, and rubella) live attenuated vaccine, that number has dropped to around 100 thousand deaths per year. The Aim: The aim of this study was to determine the seroprevalence of antibodies against the measles virus in the population of medical students at the University of Belgrade. Material and Methods: In the study, sera of 99 voluntarily enrolled students from the Faculty of Medicine, University of Belgrade, were examined. Commercial ELISA kits from Euroimmun Medical Diagnostics (Lübeck, Germany) were used according to the manufacturer's instructions. Data obtained from an anonymous survey were also analyzed. Normality of distribution was evaluated using mathematical methods (coefficient of variation, Shapiro-Wilk test) and graphical methods (histogram and boxplot). Results: In our study, 92 out of 99 participants (93%) reported being vaccinated with the MMR vaccine. Thirteen students reported having had measles, while positive antibodies were confirmed in 89% of the participants. The application of statistical tests did not prove a significant difference in the representation of positive findings between genders, or between persons who attended preschool institutions compared to those who did not. Conclusion: The study’s results demonstrated the seroprevalence of antibodies to the Measles virus in medical students aged 19 to 29 years. The lack of seroconversion in 4% of the vaccinated population can be considered an indication for the introduction of an additional dose of measles vaccine in this population.
Prevalence and predictors of Helicobacter pylori infection in patients with dyspepsia and their association with treatment outcome
Abstract Introduction: Helicobacter pylori (H. pylori) infection is one of the most common infectious diseases and an established risk factor for gastric cancer. Alongside dyspepsia, it represents a rising global medical burden. Treatment failure of H. pylori infection eradication imposed an imperative to determine risk factors and potential predictors that can be related to its prevalence and treatment outcome. Aim: Our aim was to assess the prevalence and potential predictors of H. pylori infection in patients with dyspepsia, most prescribed treatment regimens and their effectiveness. Material and methods: A retrospective study including 324 patients with dyspeptic symptoms, who presented at the gastroenterology outpatient unit of the University Clinical Center of Serbia, was conducted. H. pylori diagnosis was made following upper endoscopy and histology. Socio-epidemiologic, clinical and laboratory data was analyzed. Results: The overall prevalence of H. pylori infection in dyspeptic patients was 19.7%. Hematological comorbidities were found to be more common in H. pylori positive patients as compared to the overall sample (15.6% vs 8.1 %, p<0.01), with total iron binding capacity (TIBC) levels significantly correlating to H. pylori positivity (p<0.05). Duodenitis (37.5% vs. 26%, p< 0,01), superficial chronic gastritis (71.9% vs. 25%, p< 0,01), and nonspecific inflammation (73.4% vs 58.9%, p= 0,01) were significant predictors of H. pylori infection. Overall H. pylori eradication rate was 88.4%. Most commonly prescribed regimen was quadruple clarithromycin/ amoxicillin/ metronidazole therapy (45%) while pantoprazole was the most prescribed proton pump inhibitors (PPIs). Conclusions: The prevalence of H. pylori infection was relatively low. Anemia, appearance of duodenitis, chronic superficial gastritis and nonspecific inflammation on gastric mucosa were found to be significant predictors of H. pylori infection. Overall eradication rate was satisfactory with quadruple therapies options being the most prescribed regimens.
Analysis of nasal septum deviation and nasal pyramid Based on computed tomography (CT) scans
Introduction: Among all radiological diagnostic methods for assessing nasal function, multidetector computed tomography (MDCT) of paranasal and nasal cavities has the highest sensitivity. The Aim: The aim of our research was to describe different types and types of deviation of the nasal septum and their influence on the size of nasal passages in relation to the concha and nasal mucosa, by analyzing computed tomographic (CT) images. Material and Methods: The study included 50 patients aged 21 to 65, 28 were women and 22 were men. On CT scans, we measured the flow of the nasal passages, the degree and type of the curvature of nasal septum, the size and ratio of the nasal shells in relation to the nose and their influence on the size of nasal passages, the curvature (deviation) of the cartilaginous and bony parts of the nasal septum and described their relationship and the relationship with nasal passages and nasal concha. Results: Through our research and statistical analysis, we found there are 7 types of nose deviation 1. Deviation in the shape of the letter “C”, 2. Deviation in the shape of the letter “S”. 3. Deviation in the shape of the inverted letter “C” 4. Deviation in the shape of the letter inverted letter “S” 5. Deviation of the caudal part of the cartilaginous nasal septum in the form of a ridge, 6. Deviation in the form of a “thorn” and 7. perforated nasal septum. In 46 examinees (92% of cases) with septal deviation, we found the mucosa was more thickened and hypertrophic on the side opposite to septal deviation (p<0.05). Conclusion: We found that there are seven types of deviation of the nasal septum, and that the patency of nasal passages directly depends on the ratio of the curvature of nasal septum, the thickness of mucosa and their mutual relationship with lower concha
MULTIFRACTAL ANALYSIS OF THE MORPHOLOGY OF THE RETINAL ARTERIES AT DIFFERENT DEGREES OF GLAUCOMATOUS DAMAGE
Abstract Introduction: Glaucoma is the second leading cause of blindness worldwide. Due to its asymptomatic progression and irreversible consequences, early diagnosis is crucial. Beyond elevated intraocular pressure, retinal vascularization and morphological changes in arterial blood vessels play a significant role in the disease's pathophysiology. Aim: To determine the potential of multifractal analysis of binary images of retinal arterial blood vessels in differentiating patients with varying degrees of glaucomatous damage. Material and Methods: The study included 90 binarized images of retinal arterial blood vessels from patients with primary open-angle glaucoma, divided into three groups based on the severity of visual field damage: mild (MD < -6 dB), moderate (MD between -6 and -12 dB), and severe (MD > -12 dB). Multifractal analysis was performed using ImageJ software with the FracLac plugin. Generalized dimensions (DQ) were calculated for Q values ranging from -10 to 10. Statistical differences were analyzed using the non-parametric Kruskal-Wallis test. Results: Multifractal spectra exhibited a sigmoidal shape, confirming their multifractal nature. Significant differences between groups were observed in the central part of the spectrum (Q = 0, 1, and 2), with the severe-damage group being most distinct from the lower-damage groups. However, differences between the mild and moderate groups were not statistically significant. Conclusion: Multifractal analysis can distinguish the severe glaucomatous damage group from the lower-damage groups. The method's limited sensitivity in early stages and the relatively small sample size highlight the need for further research, including expanded analysis of additional spectra, such as Hölder exponents and singularity spectra. Keywords: multifractal analysis, retinal arteries, glaucoma, binary images
EFFECT OF HUMAN IMMUNODEFICIENCY VIRUS INFECTION AND COMBINATION ANTIRETROVIRAL THERAPY ON TELOMERE LENGTH
Introduction: Due to combination antiretroviral therapy (cART), human immunodeficiency virus (HIV) infection has been transformed into a chronic disease. Despite effective therapy, the virus continues to replicate in the body. Chronic inflammation caused by the constant presence of the virus and cumulative toxicity caused by the therapy lead to changes in the body, potentially associated with an accelerated aging process. Objective: The objective of this paper was to review and analyze the most common mechanisms by which HIV infection and cART can affect telomere length. Material and Methods: This review used targeted searches of the MEDLINE and PubMed bibliographic databases using the keywords "telomeres", "telomere length", "telomere attrition", "aging" and "cellular senescence" in combination with the words "HIV", " HIV infection", "antiretroviral", "cART" and "HAART". Results: HIV-infection-related parameters affecting telomere shortening are the presence of viral Tat protein in the cell, oxidative stress, comorbidities and aberrant methylation. Drugs within cART that stand out as important for telomere shortening are efavirenz, tenofovir and dolutegravir. Conclusion: Tat and Vpr proteins, oxidative stress, DNA methylation, efavirenz administration, tenofovir administration, and dolutegravir administration can significantly affect telomere shortening in HIV-infected patients.
POLYOXOMETALATES: A NEW CLASS OF STAINING AGENTS
For decades, transmission electron microscopy (TEM) has been one of the most valuable methods for analysing the ultrastructure of biological specimens, especially in the research field of medicine. Samples for TEM need quality preparation to obtain a contrast that can be detected in electron micrographs. Substances that make it possible to achieve a quality contrast in TEM are salts of heavy metals. One of the most successful substances for achieving contrast in TEM is uranyl acetate (UAc), because of very detectable contrast properties. Nevertheless, the latest change in regulations about radioactivity of materials gravely prohibits the use of UAc, although it would be applied exclusively for scientific reasons. Considering that UAc is dangerous because of both its toxicity and radioactivity, buildout of new secure substitute is essential. This is the present problem in TEM procedure which urges to be solved. The aim of this review is to show the probability of use of polyoxometalates (POMs) as new potential contrast reagents. POMs are heavy atoms sources with wide range of biological activities. Extensive chemical characterization of POMs brings promising use of these substances as new contrast agents for TEM observation of biological samples.
RISK FACTORS FOR THE OCCURENCE OF CARDIOVASCULAR DISEASES
According to the World Health Organization (WHO) report from 2018, cardiovascular diseases (CVD) with 17.9 million deaths had a share of as much as 41% among the causes of mortality from non-communicable diseases with a representation of 31% in all causes of mortality. With a share of 45% of all deaths annually, i.e. 3.9 million, CVD is the leading cause of death in Europe according to the latest data from the European Heart Disease Network. Mortality is slightly higher in the female population with 2.1 million or 49%, compared to men with 1.8 or 40% of the causes of death. According to the latest published data According to the latest published data from the Institute for Public Health of Serbia "Dr. Milan Jovanović Batut" from 2018, mortality caused by CVD in Serbia is estimated at 51.8%, and due to poor implementation of preventive measures, Serbia is classified as a high-risk country. Non-modifiable risk factors for CVD are: age, gender, age, ethnicity and family history. Modifiable risk factors include: high systolic blood pressure, high low-density lipoprotein (LDL), dietary risks, high glucose, tobacco smoking (active and passive), high body mass index (BMI), low level of physical activity, kidney dysfunction, excessive alcohol use, lead exposure, air pollution, high or low temperatures. Prevention and treatment of CVD is based on lifestyle modification, dietary intervention, improvement of physical activity and eventual use of medications. A minimum intake of 500 grams of fruit and vegetables per day is recommended, limiting salt intake to less than 5 grams per day, limiting sugar and fat intake to 10% and 30% of total energy intake, as well as balancing between total energy intake and energy consumption. The results of the PRIMED study showed significant positive effects of the Mediterranean diet on the primary prevention of CVD. The recommended physical activity is 150 minutes of moderate to high intensity physical activity per week, 75 minutes of high intensity physical activity per week, or the equivalent of a combination of moderate and high intensity physical activity.
AUTONOMOUS NERVOUS SYSTEM-RELATED VITAL REACTIONS IN SHORT-DROP HANGINGS
There are many anatomopathological signs forensic pathologists take into account in autopsy evaluation of deaths by hangings, having in mind one of the most important tasks: to prove the person was alive at the moment of suspension. Forensic medicine textbooks describe in detail many routinely observed findings, but some phenomena were not of particular interest. This may be, of course, due to the unreliability or impracticability of the finding interpretation. Nevertheless, some signs of vitality that may be related to the autonomous nervous system (ANS) in hangings could be useful. We may consider these as general ANS-related vitality phenomena, associated with the agonal sequence, and those directly associated with the specific neck region injury by the ligature. The former is primarily the non-specific increase in blood catecholamine levels and the hypersalivation with saliva dropping on the face skin from the lips’ angles, which is associated with agonal convulsions and deep terminal “abdominal” respirations. The latter, probably more interesting, is the so-called facies sympathique: the lesion of the sympathetic fibers in the neck region may lead to myosis and partial upper eyelid ptosis on the side of the lesion. However, this sign was not of great interest in research and remained incompletely understood regarding the postmortem appearance interpretation. This demands further studies but, if properly analyzed, may prove useful, as proof of vitality and for reconstructing the event, too, in case the other findings are subtle or absent.
DIETARY PATTERNS IN PREVENTION OF CHRONIC NON-COMMUNICABLE DISEASES: CURRENT FINDINGS
Dietary patterns are currently intensively studied, since they take into account interactions of different foods during intake and give a more comprehensive overview on the health impact compared to studying the individual foods’ and nutrients’ intake. They are also important considering their contribution to the etiology of chronic non-communicable diseases. The two most common methods of their assessment are calculation of indices and data processing through statistical methods. It has been shown that the Mediterranean diet, the DASH diet, as well as plant-based healthy dietary patterns have the greatest beneficial effect in the prevention of cardiovascular diseases, and there is increasing evidence of the beneficial effect of the Nordic and traditional Asian diets. The Mediterranean diet is also associated with a reduced risk of developing type 2 diabetes, while an unhealthy, Western diet is associated with an increased risk. The Mediterranean diet combined with reduced energy intake and regular physical activity is considered to be the most effective approach for body weight loss and control. It is considered the gold standard for the prevention of non-alcoholic fatty liver disease, and it is also recommended for the prevention of depression. Adherence to the MIND diet has been described as being associated with a reduced risk of developing Alzheimer's disease and a slower decline in cognitive function, and diets such as the Mediterranean, DASH and Japanese diets, have also been shown to be beneficial. A Mediterranean-like diet is also advised in the literature to reduce the risk of fractures. Plant-based diets are also associated with a reduced risk of cancer. Despite a lot of evidence of significant effects of certain dietary patterns, especially those that are plant-based, in chronic non-communicable diseases’ prevention, further research is needed to reach valid conclusions about their effects, especially in some less studied chronic non-communicable diseases.
The role of disturbed redox homeostasis in COVID-19
Coronavirus disease (COVID-19) is an acute respiratory disease caused by the SARS-CoV-2 that has spread throughout the world causing millions of deaths. COVID-19 is characterized by the interplay of inflammation and oxidative stress, which may be one of the main mechanisms by which SARS-CoV-2 infection leads to severe acute respiratory failure. Main components of enzymatic antioxidant protection are: superoxide dismutase (SOD), glutathione peroxidase (GPX) and glutathione transferase (GST). Nrf2, a transcription factor that controls the basal activity and coordinated gene expression of specific antioxidant enzymes, is one of the most significant regulatory antioxidant proteins. The activity and antioxidant enzymes and regulatory protein expression is influenced by the polymorphism of the genes that encode them. In this review we tried to acknowledge the role of disturbed redox homeostasis and antioxidant gene profile in COVID-19 susceptibility and disease severity.
The role of the gut microbiota in inflammatory bowel diseases
The gut microbiota plays a pivotal role in maintaining gastrointestinal homeostasis and regulating immune responses. Inflammatory bowel diseases (IBD), Crohn’s disease and ulcerative colitis, are associated with significant alterations in the composition and function of the intestinal microbiota—referred to as dysbiosis. Dysbiosis may contribute to impaired mucosal barrier function, heightened inflammation, and abnormal immune responses. The mechanisms by which microbiota influences the course of IBD include altered production of short-chain fatty acids, reduced microbial diversity, and an imbalance between protective and pathogenic bacteria. Interactions between the microbiota and immune cells, and their roles in initiating and sustaining inflammation, are subjects of ongoing research. Therapeutic strategies aiming to modulate gut microbiota, such as probiotics, prebiotics, dietary interventions, and fecal microbiota transplantation (FMT), show promise in alleviating symptoms and prolonging remission in IBD patients. A deeper understanding of the complex role of the microbiota paves the way for personalized medicine and novel therapeutic approaches in the management of inflammatory bowel diseases.
Gut microbiome and bacterial resistance to antibiotics: reservoir or defence?
Antibiotics have fundamentally transformed modern medicine, but their widespread use and misuse have led to the escalating crisis of antimicrobial resistance (AMR) in bacteria. Today, bacterial AMR represents a critical global health threat with severe medical and economic consequences. It is estimated that nearly five million deaths worldwide are linked to bacterial AMR each year. While vital for maintaining host health, the human gut microbiome also harbors a collection of antibiotic resistance genes (ARGs), collectively known as the gut resistome. Numerous studies have shown that the gut resistome serves as a reservoir for ARGs, which can be mobilized and transferred to both commensal and pathogenic bacteria through horizontal gene transfer. Antibiotic exposure is major factor that disrupts the diversity and function of the gut microbiome, leading to the proliferation of resistant bacteria and the accumulation of ARGs. These changes, in turn, facilitate the further spread of resistance among bacterial populations. Conversely, one of the gut microbiome’s key functions is to prevent the colonization and proliferation of both external pathogens and resident pathobionts, including bacteria resistant to antibiotics. This protection is mediated through mechanisms such as resource competition, metabolic interactions, and modulation of the host immune response. By limiting the colonization and expansion of resistant bacteria, the gut microbiome helps reduce the incidence of related infections and may contribute to lowering the overall burden of AMR. This review explores the dual role of gut microbiome in the dynamics of bacterial AMR, both as a reservoir for the emergence of AMR and a critical line of defense against its spread. The review also highlights key research gaps that need to be addressed to promote development of targeted microbiome-based strategies for combating bacterial AMR effectively.
Microbiota and Alzheimer’s disease: toward new clinical approaches
Alzheimer’s disease (AD) is now viewed as a systemic disorder in which genetics, the gut microbiome and immune dysregulation converge to accelerate amyloid-β (Aβ) and tau pathology. Genetic studies have identified 70 risk loci. APOE ε4 is the strongest AD risk loci, conferring dose-dependent risk through impaired cholesterol trafficking, reduced Aβ clearance and heightened neuroinflammation. Rare mutations in TREM2 and CD33 further illustrate the centrality of microglia-mediated innate immunity. Importantly, peripheral Th17 skewing, neutrophil hyper-activation and loss of regulatory myeloid cells amplify neuroinflammation. Growing evidence links gut dysbiosis to these genetic factors. APOE ε4 carriers show depletion of Short-Chain Fatty Acids (SCFA)-producing taxa (Gemmiger, Roseburia, Faecalibacterium) and enrichment of pro-inflammatory Proteobacteria (Escherichia/Shigella, Morganella). In mice, APOE4-dependent loss of butyrate-producing bacteria lowers colonic and serum SCFA levels and worsens tauopathy, whereas Germ-free housing, early antibiotics and SCFA supplementation rescue pathology. Large meta-analyses correlate Collinsella and Veillonella with higher AD risk, and Eubacterium nodatum and Prevotella 9 with protection. Metabolomic shifts mirror these compositional changes: acetate, propionate and butyrate, as well as trimethylamine N-oxide (TMAO) promote epigenetic regulation, blood–brain-barrier (BBB) integrity and microglial homeostasis, whereas secondary bile acids compromise cognition. The microbial amyloids and lipopolysaccharide can cross-seed Aβ, activate the NLRP3 inflammasome, and breach the blood-brain barrier. Intermittent fasting, ketogenic diets, specific probiotics (Bifidobacterium breve A1, Lacticaseibacillus rhamnosus CBT-LR5), sodium oligomannate (GV-971) or fecal microbiota transplantation can remodel gut ecology, raise beneficial SCFAs, dampen pro-inflammatory cytokines and improve cognition in patients with AD or mild cognitive impairment. Collectively, the data support a gut–immune system-brain axis in which host genotype shapes microbiota, and microbial metabolites or antigens contribute to neurodegeneration. Future work must define responder phenotypes, optimise next-generation probiotics and integrate multi-omics profiling with biomarker-driven clinical trials to translate microbiota modulation into disease-modifying therapy for AD.
Cutaneous microbiota: role in skin diseases
Koža je najveći organ čoveka i predstavlja višestruku barijeru prema agensima iz spoljašnje sredine, ali ujedno i kompleksan ekosistem koji naseljava raznovrsna mikrobiota, koja igra ključnu ulogu u održavanju homeostaze kože i zaštiti domaćina od patogena. Mikrobiota kože je druga najveća po obimu kod čoveka, nakon mikrobiote creva, i obuhvata oko 40 triliona mikroorganizama, sa sledećim dominantnim filumima: - Bakterije: Actinobacteria, Firmicutes, Proteobacteria i Bacteroidetes - Gljivice: dominira rod Malassezia - Virusi: uglavnom bakteriofagi, ali i humani virusi, kao što je humani papiloma virus - Arheje: dominira klasa Nitrososphaeria. Kutana mikrobiota je manje raznovrsna od crevne, ali izuzetno složena. Na njen sastav utiču brojni endogeni (uzrast, pol, varijacije u genomu i imunskom odgovoru) i egzogeni faktori (geografski i klimatski faktori, razlike u životnim navikama, uzimanje lekova). Zahvaljujući svojoj topografskoj organizaciji sa zonama koje imaju različite mikroklimatske uslove, na koži postoje različita područja (“niše”) koje imaju specifičnu strukturu mikrobiote. Među najvažnijim ekološkim faktorima koji utiču na sastav mikrobiote jedne zone kože spadaju: količina sebuma u toj zoni, fluktuacije temperature, nivo vlažnosti, prisustvo pregiba i prevoja kože, sastav antimikrobnih lipida i peptida. Osim dokazane uloge u očuvanju kutane barijere, mikrobiota kože svojim uticajem na imunski sistem, metaboličkom aktivnošću i uzajamnom regulacijom sa drugim mikrobiomima, dodatno doprinosi održavanju zdravlja kože i celog organizma. Poremećaj homostaze mikrobiote sa poremećajem diverziteta u ekosistemu kože (disbioza) se danas smatra važnim faktorom u patogenezi različitih oboljenja kože, kao što su atopijski i seboroični dermatitis, psorijaza, supurativni hidradenitis, akne, rozacea. Takođe, razumevanje uticaja mikrobiote na razvoj različitih kutanih oboljenja dovelo je i do pojave prvih terapijskih modaliteta koji su zasnovani na modulaciji profila mikroorganizama, kao što su transplantacija mikrobiote i terapija bakteriofagima.
Obesity represents a multifactorial, systemic disorder strongly associated with adverse health outcomes, including cardiometabolic syndrome. Beyond caloric imbalance between caloric intake and expenditure, recent evidence highlights the essential role of gut microbiota in the development and progression of obesity and related metabolic dysfunctions. The gut microbiota, composed of diverse bacterial species, archaea, fungi, and viruses, influences host metabolism through the production of low-molecular-weight metabolites and gastrointestinal hormones, significantly modulating energy homeostasis, appetite regulation, and insulin sensitivity. Specific bacterial taxa are implicated in either promoting metabolic health or contributing to obesity through mechanisms involving chronic systemic low-grade inflammation, increased intestinal permeability, and altered energy harvest. Dysbiosis—marked by reduced microbial diversity and compositional imbalance—is consistently linked to enhanced adiposity and systemic inflammation. Dietary patterns are key modulators of gut microbial composition and function. This review underscores the complex interplay between dietary patterns, gut microbiota-derived metabolites and host endocrine responses, that contribute to dysregulation of gut–brain axis communication observed in obesity.
Oral microbiome: physiological and pathological impact on oral and systemic health
Oralni mikrobiom predstavlja kompleksan i dinamičan ekosistem različitih mikrobnih zajednica čija je raznolikost rezultat specifičnih anatomskih i fizioloških uslova usne duplje. Očuvanje ravnoteže mikrobioma, eubioze, od suštinskog je značaja za humano zdravlje. Komensalne vrste sprečavaju kolonizaciju patogena, moduliraju imuni odgovor, učestvuju u održavanju metaboličke homeostaze, te doprinose pravilnom fiziološkom funkcionisanju. Poremećaj ravnoteže oralnog mikrobioma, disbioza, povezan je sa razvojem oralnih oboljenja poput karijesa, parodontopatije, gingivitisa, kandidijaze i malignih promena ali i sa sistemskim oboljenjima, uključujući kardiovaskularna i respiratorna oboljenja, dijabetes melitus, reumatoidni artritis, komplikacije u trudnoći i neurodegenerativne poremećaje. Takođe, hronična sistemska oboljenja mogu dodatno narušiti mikrobiološku ravnotežu usne duplje, stvarajući začarani krug patoloških promena. Prevencija disbioze zasniva se na pravilnoj oralnoj higijeni, redovnim stomatološkim kontrolama, uravnoteženoj ishrani sa ograničenim unosom rafinisanih šećera, kontrolisanoj primeni antibiotika i, potencijalno, na probiotskim i prebiotskim terapijskim pristupima. Savremena istraživanja sve više ukazuju na mogućnost personalizovane stomatološke prakse zasnovane na analizi mikrobiomskog profila pacijenta, što bi moglo unaprediti prevenciju i terapiju kako oralnih, tako i sistemskih oboljenja.
The role of gut microbiome modulation in the management of neurodevelopmental disorders: current evidence and future directions
Neurodevelopmental disorders (NDDs), including autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and other cognitive and behavioral impairments, are increasing globally, placing significant burdens on individuals and healthcare systems. Traditional therapeutic strategies, primarily pharmacologic and behavioral, offer limited efficacy and often fail to address the multifactorial etiology of these conditions. Recent advances in microbiome research highlight the gut microbiota as a potential modulator of brain function via the microbiota–gut–brain axis (MGBA). This bidirectional network influences neurodevelopment through neural, immune, endocrine, and metabolic pathways. Dysbiosis, or microbial imbalance, has been consistently reported in individuals with NDDs, particularly in ASD and ADHD, correlating with symptom severity and gastrointestinal comorbidities. Emerging interventions aimed at restoring microbial balance, such as probiotics, prebiotics, synbiotics, faecal microbiota transplantation (FMT), and dietary modifications - demonstrate potential in modulating behaviour and cognition. However, the current evidence is limited by small sample sizes, heterogeneous methodologies, and a lack of long-term follow-up. This mini-review synthesizes current findings on the role of gut microbiome modulation in NDDs, evaluates the therapeutic efficacy of microbiome-based interventions, and discusses future directions, including personalized microbiome-targeted strategies and the need for robust randomized controlled trials.
Human microbiome: pathophysiological and clinical aspects
Trilioni mikroorganizama koji žive u i na telu čoveka, njihovi geni i metaboliti, jednim imenom nazvani humani mikrobiom, danas su prepoznati kao aktivni učesnici u gotovo svakom aspektu ljudske biologije. Ovaj raznovrstan i dinamičan ekosistem funkcioniše poput skrivenog organa i duboko je integrisan u fiziologiju i očuvanje zdravlja čoveka. Tokom poslednje dve decenije humani mikrobiom, nekada pozicioniran u marginalnim sferama istraživanja, postao je centralna tema biomedicinskih nauka. Otkriće da mikrobne zajednice imaju ključnu ulogu ne samo u metabolisanju nutrijenata već i u modulaciji imunskog sistema, neuroendokrinoj komunikaciji i održavanju sistemske homeostaze, značajno je promenilo naše razumevanje zdravlja i bolesti. Koncept mikrobioma kao centralnog aktera u održavanju zdravlja i razvoju bolesti više se ne posmatra kao hipoteza već kao potvrđena naučna realnost koja transformiše savremenu medicinsku praksu.
Čovek predstavlja složen biološki ekosistem koji čine sopstveni organizam i mikrobiom koji ga naseljava. Mikrobiom obuhvata trilione mikroorganizama, uključujući bakterije, viruse, gljive i arhee, zajedno sa njihovim metaboličkim produktima, genima i pripadajućim genskim produktima. Ovaj složeni ekosistem obavlja brojne fiziološki važne funkcije, učestvujući u procesima varenja, sintezi vitamina, zaštiti od patogena i interakciji sa supstancama iz spoljašnje sredine. Među njegovim najznačajnijim ulogama ističe se doprinos mikrobiote razvoju i sazrevanju imunskog sistema. Odnos između imunskog sistema i mikrobiote izuzetno je višestruk i dvosmeran, pri čemu ostvaruje sistemske efekte koji prevazilaze lokalna tkiva u kojima se te interakcije primarno odvijaju. Narušavanje ove ravnoteže dovodi do disbioze, stanja koje je povezano sa nastankom različitih inflamatornih i autoimunskih poremećaja. Rasvetljavanje uzajamnih regulatornih mehanizama koji povezuju imunski sistem i mikrobiotu ključno je za razumevanje patofizioloških procesa koji nastaju kada dođe do poremećaja u njihovoj interakciji. Ovaj pregledni rad ima za cilj da predstavi ulogu mikrobiote u razvoju i fiziološkom funkcionisanju imunskog sistema radi boljeg razumevanja posledica disbalansa unutar ovog odnosa.
EXPRESSION OF ENDOTHELIN-1 IN UNAFFECTED COLON MUCOSA 10CM AND 20CM FROM ADENOCARCINOMA OF THIS ORGAN
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Locked="false" Priority="21" SemiHidden="false" UnhideWhenUsed="false" QFormat="true" Name="Intense Emphasis"/> <w:LsdException Locked="false" Priority="31" SemiHidden="false" UnhideWhenUsed="false" QFormat="true" Name="Subtle Reference"/> <w:LsdException Locked="false" Priority="32" SemiHidden="false" UnhideWhenUsed="false" QFormat="true" Name="Intense Reference"/> <w:LsdException Locked="false" Priority="33" SemiHidden="false" UnhideWhenUsed="false" QFormat="true" Name="Book Title"/> <w:LsdException Locked="false" Priority="37" Name="Bibliography"/> <w:LsdException Locked="false" Priority="39" QFormat="true" Name="TOC Heading"/> </w:LatentStyles> </xml><![endif]--><!-- [if gte mso 10]> <![endif]--> Introduction: Endothelin-1 is a vasoconstrictor peptide primarily synthesized by endothelial and smooth muscle cells. Increased expression of this peptide has been observed in inflammation, hypoxia, ischemia, various cardiovascular diseases and various types of cancer. In addition to vasoconstrictive, significant mitogenic, proangiogenic and anti-apoptotic effects have also been proven. The Aim: To examine the expression of endothelin-1 in the unaffected mucosa 10cm and 20cm away from colon adenocarcinoma and the lamina propria of the colon mucosa of healthy subjects. Material and Methods: The samples were obtained by biopsy at the Center for Gastroenterology, Clinical and Hospital Center "Dr. Dragiša Mišović-Dedinje" in Belgrade from patinets with malignant colon tumors. During the diagnostic colonoscopy, colon mucosa samples were taken 10cm and 20cm distal to the primary tumor lesion (n=10). A control group of samples (n=10) was obtained by endoscopic biopsy of the healthy subjects in the same institution. Immunohistochemical staining on paraffin samples was performed according to the established protocol. For statistical analysis of frequency, Fisher's exact probability test was used, using 2x2 contingency tables. Results: Statistically significant difference in the frequency of endothelin-1 expression was detected neither in the surface epithelium nor in the endothelial cells of the lamina propria of the colon mucosa at a distance of 10cm (p=0.38) or 20cm (p=0.67) from the tumor compared to the lamina propria of colon mucosa of healthy subjects. Also, no statistically significant difference was detected in the frequency of high and low expression of endothelin-1 in the epithelium and blood vessels of the lamina propria of the colon mucosa at a distance of 10cm and 20cm from the tumor (p=0.82) Conclusion: Endothelin-1 is variably expressed in the colon mucosa, predominantly by epithelial and endothelial cells. A statistically significant difference in the frequency of high and low expression of endothelin-1 between the groups was not detected.
ASSOCIATION OF PPARGC1A GLY482SER POLYMORPHISM WITH OBESITY, TYPE II DIABETES AND METABOLIC SYNDROME DURING POSTMENOPAUSE
Uvod: Metabolički sindrom predstavlja poremećaj koji obuhvata kompleks simptoma kao što su centralna gojaznost, insulinska rezistencija, dislipidemija i hipertenzija i povezan je sa povećanim rizikom od kardiovaskularnih bolesti i dijabetes melitusa tipa II. Pojava metaboličkog sindroma zavisi kako od faktora spoljašnje sredine tako i genetičkih faktora. Promene u ekspresiji gena za peroksizomni proliferatorom aktivirani receptor γ koaktivator 1α (PGC-1α) jedan su od faktora koji mogu uticati na pojavu insulinske rezistencije, gojaznosti, dislipidemije pa posledično i metaboličkog sindroma i dijabetesa tip II. Cilj rada: Cilj ovog istraživanja bio je da se ispita udruženosti polimorfizma Gly482Ser u genu za PGC-1α sa lipidnim statusom i pojavom gojaznosti, dijabetesa tip II i metaboličkog sindroma kod žena u postmenopauzi. Materijal i metode: U istraživanje je uključeno 112 žena u postmenopauzi starosti 65,01±6,16 godina. Za sve ispitanice prikupljeni su demografski i antropometrijski (visina, indeks telesne mase, odnos obima struka i kuka) podaci kao i rezultati biohemijskih analiza (lipidni status, glikemija). Genotipizacija je sprovedena metodom RealTime PCR, primenom standardizovanog TaqMan eseja za genotipizaciju. Rezultati: Analizom dokazano je postojanje statistički značajne razlike u srednjim vrednostima ukupnog holesterola u zavisnosti od genotipa ispitanica. Ispitanice sa AA genotipom su imale statistički značajno više vrednosti ukupnog holesterola (p=0,030). Analiza udruženosti Gly482Ser genotipa sa ostalim analiziranim parametrima nije pokazala statističku značajnost. Zaključak: Rezultati naše studije ukazuju na moguću udruženost AA genotipa polimorfizma Gly482Ser u genu za PGC-1α sa višim vrednostima ukupnog holesterola kod žena u postmenopauzi.
AST-to-platelet ratio as a prognostic factor in patients with decompensated liver cirrhosis
Introduction: Decompensated liver cirrhosis is a symtomatic, terminal stadium of liver cirrhosis, which occurs by the excange of healthy liver parenhime with fibrous tissue due to longterm inflamation. Many studies have been exploring the role of various factors in transition from stabile to decompensated liver cirrhosis. AST and platelet ratios (APRI score) turned up as a promising one to be further explored. Aim: Our study aims to determine if there is correlation between the APRI score and the prognosis of decompensated liver cirrhosis. Material and Methods: A retrospective study was conducted in the Gastroenterology department in KBC „Bežanijska kosa“ in period from june 2022. to july 2023. This study includes 67 patients, about whom the data were collected from their medical history documents. All patients underwent comprenhensive biochemical blood analyses including hepatogram, and complete blood count upon admission. During hospitalization, abdominal ultrasound and esophagogastroduodenoscopy were also performed. For each patient, based on the available analysis results, the APRI score was calculated. All data were processed using the SPSS statistical program and presented graphically. Results: Based on the results of logistic regression, we find that there is not enough evidence to consider the APRI score a significant predictor of mortailty in patients in this data set (p>0,05). Conclusion: The APRI score can be significantly useful in everyday clinical practice for control and treatment of chronic inflammatory liver diseases, as it is an easily asccessible and a simple method. Further research is needed to explore and confirm its importance on a significantly larger dataset. Keywords: decompensated liver cirrhosis, APRI score, AST, platelets, ethylism
THE ROLE OF JNK IN THE PROINFLAMMATORY ACTION OF THE SARS-CoV-2 PROTEIN ORF3a
Introduction: Coronavirus disease 2019 (COVID-19) is a contagious respiratory infection caused by the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A significant contributor to the pathogenesis of COVID-19 is the SARS-CoV-2 regulatory protein open reading frame 3a (ORF3a), which drives an excessive inflammatory response associated with adverse clinical outcomes and mortality. Notably, c-Jun N-terminal kinase (JNK), a part of the mitogen-activated protein kinase (MAPK) family, is essential in orchestrating the cellular innate and adaptive immune response initiated by diverse viral infections. Aim: This study aims to elucidate the involvement of JNK in the proinflammatory response induced by SARS-CoV-2 ORF3a in the H460 non-small cell lung cancer cell line, specifically focusing on the expression of proinflammatory cytokines IL-1β and IL-8. Material and Methods: The H460 cell line was transfected with a DNA plasmid encoding the SARS-CoV-2 ORF3a. Pharmacological inhibition of JNK in H460 cells was achieved using JNK inhibitor SP600215. The expression of p-JNK and JNK was confirmed by immunoblotting, while RT-qPCR was used to quantify IL-1β and IL-8 mRNA levels. Student's t-test was used for statistical analysis. Results: H460 cells expressing SARS-CoV-2 ORF3a displayed a significant increase in JNK phosphorylation and IL-1β and IL-8 mRNA levels, as verified by immunoblot analysis and RT-qPCR respectively (p <0.05). Subsequently, JNK inhibition in SARS-CoV-2 ORF3a -expressing cells resulted in a significant reduction of IL-1β and IL-8 mRNA expression (p <0.05), thus confirming its involvement in the proinflammatory response elicited by SARS-CoV-2 ORF3a. Conclusion: The results of our study demonstrated that JNK plays a crucial role in the expression of proinflammatory cytokines IL-1β and IL-8 triggered by SARS-CoV-2 ORF3a. Therefore, targeted JNK inhibition holds promise for mitigating SARS-CoV-2 ORF3a-driven inflammation and providing innovative treatment alternatives for severe COVID-19 cases.
SIGNIFICANCE OF HISTOPATHOLOGICAL PARAMETERS IN FEMALE PATIENTS AFTER PLACEMENT OF BREAST IMPLANTS
Introduction: Mammoplasty is a surgical procedure of placement of breast implants for aestetic reasons or because of breast reconstruction after mastectomy after cancer. As the implant represents a foreign body, there is an inflammatory reaction and complications (most often capsule contractures, most rarely anaplastic large cell lymphoma), with different histopathological presentations (synovial metaplasia, chronic inflammation, dystrophic calcifications, granulomas around a foreign body type). Clinically, these complications are presented as tumor-like changes. Aim: Aim of the paper is to show the most significant histopathological parameters, age of the patients at the time of the complications, period that passed from the placement of the implant to the onset of complications and the existence of previous cancer. Material and methods: This study included patients with breast implants in the period of January 2019 to December 2023. Evaluating data from medical records, we performed a retrospective study, which included: age of the patient at the time of complications, reasons for performing mammoplasty, period that passed from mammoplasty to the appearance of complications. Archived material was used (paraffin molds and histopathological material stained with the hematoxylin-eosin method, as well as immunochistochemical stainings). Descriptive statistics methods (Fishers exact probability test) were used for data analysis. Results: Average age of the patients was 50.1 years, and the period that passed from the placement of the implant to the appearence of complications was 16.7 years. The breast cancer previously had 22%. Most common histopathological parameters were synovial metaplasia (100%) followed by chronic inflammation (76%), foreign material (52%) and granuloma around a foreign body (32%). The breast surgery was performed for cosmetic reasons in 88% of the patients. Conclusion: This study proved that the patients were older and that more time passed before complications occurred than was shown in literature. Large percent of patients had the procedure only because of cosmetic reasons.
GLANDULAR AND EXTRAGLANDULAR MANIFESTATIONS IN PATIENTS WITH SJÖGREN'S SYNDROME AND THEIR CORRELATION WITH IMMUNOLOGICAL PARAMETERS
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SemiHidden="true" UnhideWhenUsed="true" Name="Mention"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Smart Hyperlink"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Hashtag"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Unresolved Mention"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Smart Link"/> </w:LatentStyles> </xml><![endif]--><!-- [if gte mso 10]> <![endif]--> Introduction: Sjögren’s syndrome (SS) is a chronic systemic autoimmune disease. The disease spectrum extends from sicca syndrome to systemic involvement and extraglandular manifestations. Patients with SS present a broad spectrum of serologic features. Certain serological findings are highly correlated with specific clinical features, and can be used as prognostic markers. The Aim of this paper was analysis of glandular and extraglandular clinical manifestations of primary SS (pSS) and their association with laboratory findings. Material and Methods: The research was conducted as a retrospective cross-sectional study involving 30 patients with pSS hospitalized at the Clinic for Allergology and Immunology University Clinical Center of Serbia in Belgrade. Demographic, clinical and laboratory characteristics of patients were analyzed, as well as association between them. Results: Dry eyes and mouth were experienced by all subjects included in the study. Arthralgia and/or myalgia were the most common extraglandular manifestation of pSS, which was present in all patients. This was followed by: chronic fatigue (83.3%), skin manifestations (66.67%), neuropsychiatric manifestations (60%), Raynaud's phenomenon (40%), gastrointestinal manifestations (33.3%), thyroid (26.67%), and respiratory disorders (23.3%). Paraprotein was identified in 13.33%, and proteinuria in 10% of patients. Antinuclear antibodies (ANA) were positive in 80%, anti-Ro/SSA in 76.67%, anti-La/SSB in 20%, and RF in 16.67% of patients. Raynaud's phenomenon was associated with the presence of chronic fatigue (p=0.047), gastrointestinal with neuropsychiatric manifestations (p=0.017), and chronic fatigue was also associated with involvement of exocrine glands of other locations (except lacrimal and salivary glands). Thyroid dysfunction was inversely associated with SSB antibody findings (p=0.024). Conclusion: Dry eyes and mouth, arthralgia and/or myalgia were the most common manifestation of pSS. ANA and SSA antibodies were the most common immunoserological findings. There was no statistically significant association of any examined immunoserological findings with the presence of glandular and extraglandular manifestations of pSS. Keywords: Sjögren's syndrome; glandular features; extraglandular features; ANA; anti-Ro/SSA; anti-La/SSB
SURGICAL TREATMENT OF FOOT DROP AFTER PERONEAL NERVE INJURY
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<w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Document Map"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Plain Text"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="E-mail Signature"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="HTML Top of Form"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="HTML Bottom of Form"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Normal (Web)"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="HTML Acronym"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="HTML Address"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="HTML Cite"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="HTML Code"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="HTML Definition"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="HTML Keyboard"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="HTML Preformatted"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="HTML Sample"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="HTML Typewriter"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="HTML Variable"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Normal Table"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="annotation subject"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="No List"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Outline List 1"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Outline List 2"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Outline List 3"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Table Simple 1"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Table Simple 2"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Table Simple 3"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Table Classic 1"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Table Classic 2"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Table Classic 3"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Table Classic 4"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Table Colorful 1"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Table Colorful 2"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Table Colorful 3"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Table Columns 1"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Table Columns 2"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Table Columns 3"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Table Columns 4"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Table Columns 5"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Table Grid 1"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Table Grid 2"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Table Grid 3"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Table Grid 4"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Table 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UnhideWhenUsed="true" Name="Table List 8"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Table 3D effects 1"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Table 3D effects 2"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Table 3D effects 3"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Table Contemporary"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Table Elegant"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Table Professional"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Table Subtle 1"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Table Subtle 2"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Table Web 1"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Table 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Locked="false" Priority="67" Name="Medium Grid 1"/> <w:LsdException Locked="false" Priority="68" Name="Medium Grid 2"/> <w:LsdException Locked="false" Priority="69" Name="Medium Grid 3"/> <w:LsdException Locked="false" Priority="70" Name="Dark List"/> <w:LsdException Locked="false" Priority="71" Name="Colorful Shading"/> <w:LsdException Locked="false" Priority="72" Name="Colorful List"/> <w:LsdException Locked="false" Priority="73" Name="Colorful Grid"/> <w:LsdException Locked="false" Priority="60" Name="Light Shading Accent 1"/> <w:LsdException Locked="false" Priority="61" Name="Light List Accent 1"/> <w:LsdException Locked="false" Priority="62" Name="Light Grid Accent 1"/> <w:LsdException Locked="false" Priority="63" Name="Medium Shading 1 Accent 1"/> <w:LsdException Locked="false" Priority="64" Name="Medium Shading 2 Accent 1"/> <w:LsdException Locked="false" Priority="65" Name="Medium List 1 Accent 1"/> <w:LsdException Locked="false" SemiHidden="true" Name="Revision"/> <w:LsdException Locked="false" Priority="34" QFormat="true" Name="List Paragraph"/> <w:LsdException Locked="false" Priority="29" QFormat="true" Name="Quote"/> <w:LsdException Locked="false" Priority="30" QFormat="true" Name="Intense Quote"/> <w:LsdException Locked="false" Priority="66" Name="Medium List 2 Accent 1"/> <w:LsdException Locked="false" Priority="67" Name="Medium Grid 1 Accent 1"/> <w:LsdException Locked="false" Priority="68" Name="Medium Grid 2 Accent 1"/> <w:LsdException Locked="false" Priority="69" Name="Medium Grid 3 Accent 1"/> <w:LsdException Locked="false" Priority="70" Name="Dark List Accent 1"/> <w:LsdException Locked="false" Priority="71" Name="Colorful Shading Accent 1"/> <w:LsdException Locked="false" Priority="72" Name="Colorful List Accent 1"/> <w:LsdException Locked="false" Priority="73" Name="Colorful Grid Accent 1"/> <w:LsdException Locked="false" Priority="60" Name="Light Shading Accent 2"/> <w:LsdException Locked="false" Priority="61" Name="Light List 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Name="Colorful Grid Accent 3"/> <w:LsdException Locked="false" Priority="60" Name="Light Shading Accent 4"/> <w:LsdException Locked="false" Priority="61" Name="Light List Accent 4"/> <w:LsdException Locked="false" Priority="62" Name="Light Grid Accent 4"/> <w:LsdException Locked="false" Priority="63" Name="Medium Shading 1 Accent 4"/> <w:LsdException Locked="false" Priority="64" Name="Medium Shading 2 Accent 4"/> <w:LsdException Locked="false" Priority="65" Name="Medium List 1 Accent 4"/> <w:LsdException Locked="false" Priority="66" Name="Medium List 2 Accent 4"/> <w:LsdException Locked="false" Priority="67" Name="Medium Grid 1 Accent 4"/> <w:LsdException Locked="false" Priority="68" Name="Medium Grid 2 Accent 4"/> <w:LsdException Locked="false" Priority="69" Name="Medium Grid 3 Accent 4"/> <w:LsdException Locked="false" Priority="70" Name="Dark List Accent 4"/> <w:LsdException Locked="false" Priority="71" Name="Colorful Shading Accent 4"/> <w:LsdException Locked="false" Priority="72" Name="Colorful List Accent 4"/> <w:LsdException Locked="false" Priority="73" Name="Colorful Grid Accent 4"/> <w:LsdException Locked="false" Priority="60" Name="Light Shading Accent 5"/> <w:LsdException Locked="false" Priority="61" Name="Light List Accent 5"/> <w:LsdException Locked="false" Priority="62" Name="Light Grid Accent 5"/> <w:LsdException Locked="false" Priority="63" Name="Medium Shading 1 Accent 5"/> <w:LsdException Locked="false" Priority="64" Name="Medium Shading 2 Accent 5"/> <w:LsdException Locked="false" Priority="65" Name="Medium List 1 Accent 5"/> <w:LsdException Locked="false" Priority="66" Name="Medium List 2 Accent 5"/> <w:LsdException Locked="false" Priority="67" Name="Medium Grid 1 Accent 5"/> <w:LsdException Locked="false" Priority="68" Name="Medium Grid 2 Accent 5"/> <w:LsdException Locked="false" Priority="69" Name="Medium Grid 3 Accent 5"/> <w:LsdException Locked="false" Priority="70" Name="Dark List Accent 5"/> <w:LsdException Locked="false" Priority="71" Name="Colorful Shading Accent 5"/> <w:LsdException Locked="false" Priority="72" Name="Colorful List Accent 5"/> <w:LsdException Locked="false" Priority="73" Name="Colorful Grid Accent 5"/> <w:LsdException Locked="false" Priority="60" Name="Light Shading Accent 6"/> <w:LsdException Locked="false" Priority="61" Name="Light List Accent 6"/> <w:LsdException Locked="false" Priority="62" Name="Light Grid Accent 6"/> <w:LsdException Locked="false" Priority="63" Name="Medium Shading 1 Accent 6"/> <w:LsdException Locked="false" Priority="64" Name="Medium Shading 2 Accent 6"/> <w:LsdException Locked="false" Priority="65" Name="Medium List 1 Accent 6"/> <w:LsdException Locked="false" Priority="66" Name="Medium List 2 Accent 6"/> <w:LsdException Locked="false" Priority="67" Name="Medium Grid 1 Accent 6"/> <w:LsdException Locked="false" Priority="68" Name="Medium Grid 2 Accent 6"/> <w:LsdException Locked="false" Priority="69" Name="Medium Grid 3 Accent 6"/> <w:LsdException Locked="false" Priority="70" Name="Dark List Accent 6"/> <w:LsdException Locked="false" Priority="71" Name="Colorful Shading Accent 6"/> <w:LsdException Locked="false" Priority="72" Name="Colorful List Accent 6"/> <w:LsdException Locked="false" Priority="73" Name="Colorful Grid Accent 6"/> <w:LsdException Locked="false" Priority="19" QFormat="true" Name="Subtle Emphasis"/> <w:LsdException Locked="false" Priority="21" QFormat="true" Name="Intense Emphasis"/> <w:LsdException Locked="false" Priority="31" QFormat="true" Name="Subtle Reference"/> <w:LsdException Locked="false" Priority="32" QFormat="true" Name="Intense Reference"/> <w:LsdException Locked="false" Priority="33" QFormat="true" Name="Book Title"/> <w:LsdException Locked="false" Priority="37" SemiHidden="true" UnhideWhenUsed="true" Name="Bibliography"/> <w:LsdException Locked="false" Priority="39" SemiHidden="true" UnhideWhenUsed="true" QFormat="true" Name="TOC Heading"/> <w:LsdException Locked="false" Priority="41" Name="Plain Table 1"/> <w:LsdException Locked="false" Priority="42" Name="Plain Table 2"/> <w:LsdException Locked="false" Priority="43" Name="Plain Table 3"/> <w:LsdException Locked="false" Priority="44" Name="Plain Table 4"/> <w:LsdException Locked="false" Priority="45" Name="Plain Table 5"/> <w:LsdException Locked="false" Priority="40" Name="Grid Table Light"/> <w:LsdException Locked="false" Priority="46" Name="Grid Table 1 Light"/> <w:LsdException Locked="false" Priority="47" Name="Grid Table 2"/> <w:LsdException Locked="false" Priority="48" Name="Grid Table 3"/> <w:LsdException Locked="false" Priority="49" Name="Grid Table 4"/> <w:LsdException Locked="false" Priority="50" Name="Grid Table 5 Dark"/> <w:LsdException Locked="false" Priority="51" Name="Grid Table 6 Colorful"/> <w:LsdException Locked="false" Priority="52" Name="Grid Table 7 Colorful"/> <w:LsdException Locked="false" Priority="46" Name="Grid Table 1 Light Accent 1"/> <w:LsdException Locked="false" Priority="47" Name="Grid Table 2 Accent 1"/> 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Priority="46" Name="Grid Table 1 Light Accent 3"/> <w:LsdException Locked="false" Priority="47" Name="Grid Table 2 Accent 3"/> <w:LsdException Locked="false" Priority="48" Name="Grid Table 3 Accent 3"/> <w:LsdException Locked="false" Priority="49" Name="Grid Table 4 Accent 3"/> <w:LsdException Locked="false" Priority="50" Name="Grid Table 5 Dark Accent 3"/> <w:LsdException Locked="false" Priority="51" Name="Grid Table 6 Colorful Accent 3"/> <w:LsdException Locked="false" Priority="52" Name="Grid Table 7 Colorful Accent 3"/> <w:LsdException Locked="false" Priority="46" Name="Grid Table 1 Light Accent 4"/> <w:LsdException Locked="false" Priority="47" Name="Grid Table 2 Accent 4"/> <w:LsdException Locked="false" Priority="48" Name="Grid Table 3 Accent 4"/> <w:LsdException Locked="false" Priority="49" Name="Grid Table 4 Accent 4"/> <w:LsdException Locked="false" Priority="50" Name="Grid Table 5 Dark Accent 4"/> <w:LsdException Locked="false" Priority="51" Name="Grid Table 6 Colorful Accent 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Priority="50" Name="Grid Table 5 Dark Accent 6"/> <w:LsdException Locked="false" Priority="51" Name="Grid Table 6 Colorful Accent 6"/> <w:LsdException Locked="false" Priority="52" Name="Grid Table 7 Colorful Accent 6"/> <w:LsdException Locked="false" Priority="46" Name="List Table 1 Light"/> <w:LsdException Locked="false" Priority="47" Name="List Table 2"/> <w:LsdException Locked="false" Priority="48" Name="List Table 3"/> <w:LsdException Locked="false" Priority="49" Name="List Table 4"/> <w:LsdException Locked="false" Priority="50" Name="List Table 5 Dark"/> <w:LsdException Locked="false" Priority="51" Name="List Table 6 Colorful"/> <w:LsdException Locked="false" Priority="52" Name="List Table 7 Colorful"/> <w:LsdException Locked="false" Priority="46" Name="List Table 1 Light Accent 1"/> <w:LsdException Locked="false" Priority="47" Name="List Table 2 Accent 1"/> <w:LsdException Locked="false" Priority="48" Name="List Table 3 Accent 1"/> <w:LsdException Locked="false" Priority="49" Name="List Table 4 Accent 1"/> <w:LsdException Locked="false" Priority="50" Name="List Table 5 Dark Accent 1"/> <w:LsdException Locked="false" Priority="51" Name="List Table 6 Colorful Accent 1"/> <w:LsdException Locked="false" Priority="52" Name="List Table 7 Colorful Accent 1"/> <w:LsdException Locked="false" Priority="46" Name="List Table 1 Light Accent 2"/> <w:LsdException Locked="false" Priority="47" Name="List Table 2 Accent 2"/> <w:LsdException Locked="false" Priority="48" Name="List Table 3 Accent 2"/> <w:LsdException Locked="false" Priority="49" Name="List Table 4 Accent 2"/> <w:LsdException Locked="false" Priority="50" Name="List Table 5 Dark Accent 2"/> <w:LsdException Locked="false" Priority="51" Name="List Table 6 Colorful Accent 2"/> <w:LsdException Locked="false" Priority="52" Name="List Table 7 Colorful Accent 2"/> <w:LsdException Locked="false" Priority="46" Name="List Table 1 Light Accent 3"/> <w:LsdException Locked="false" Priority="47" Name="List Table 2 Accent 3"/> 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6"/> <w:LsdException Locked="false" Priority="52" Name="List Table 7 Colorful Accent 6"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Mention"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Smart Hyperlink"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Hashtag"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Unresolved Mention"/> <w:LsdException Locked="false" SemiHidden="true" UnhideWhenUsed="true" Name="Smart Link"/> </w:LatentStyles> </xml><![endif]--><!-- [if gte mso 10]> <![endif]--> Foot drop is a common clinical condition presented as an inability to lift the forefoot, characterized by the loss of ankle dorsiflexion from the tibialis anterior and loss of foot eversion from the peroneus longus and brevis muscles, followed by sensory loss or numbness of the foot dorsum. Causes of a foot drop can happen at any level of the nerve path. By their nature, lesions can be divided into compressive disorders, traumatic injuries, and neurologic disorders. Peroneal palsy, due to compression, is the most common peripheral cause. Treatment and diagnosis of foot drop still need to be better standardized, given that foot drop is still considered a clinical sign in other conditions. Regarding the multidisciplinary nature of foot drop, it can be challenging to determine the cause. Surgical and conservative treatments have their own respective places. Conservative procedures used for foot drop treatment include physical therapy, functional electrical stimulation, orthosis and braces, assistive devices, and gait training. Depending on a different etiological factor that causes foot drop, a few different surgical techniques are available for successful surgical treatment. Peroneal nerve release is considered a low-risk procedure with excellent results, such as pain relief and return of function. If the nerve continuity is not preserved nerve repair with epineural stitches under magnification is performed. Another surgical approach proven successful in literature is nerve transfer. Sural nerve is usually donor graft. For tendon transfer tibialis posterior muscle is usually chosen. As it is inserted at the dorsum of the foot, it helps with dorsiflexion. After all surgical procedures, it is advised for patients to start with early mobilization and postoperative physical therapy. Better treatment standardization of foot drop is still needed. However, surgical procedures show high success rates, better results, and faster recovery if performed within the first months of injury.
SIGNIFICANCE OF MOLECULAR BIOMARKERS IN THE DIAGNOSIS OF NEUROMYELITIS OPTICA SPECTRUM DISORDER
Discovery of antibodies to aquaporin-4 channels as a laboratory or molecular biomarker for neuromyelitis optica spectrum disorder contributed to a better understanding of the etiopathogenesis with a clear separation of the clinical, neuroradiological and laboratory characteristics of this disease, which resulted in the definition of criteria for establishing the diagnosis of neuromyelitis optica spectrum disorder and a clear distinction in relation to multiple sclerosis. Clinical presentation of the inflammatory diseases of the central nervous system may be highly variable, with numerous, often overlapping symptoms and signs. Therefore, in the differential diagnostic, in addition to the clinical presentation, it is necessary to consider paraclinical characteristics, such as laboratory findings of the blood and cerebrospinal fluid and the neuroradiological examination findings. Since aquaporin-4 is a clearly defined crucial diagnostic biomarker in the neuromyelitis optica spectrum disorder, different methodological approaches were developed to test antibodies to aquaporin-4 taking into account the specificity and sensitivity of the tests themselves. One of the first tests that was routinely applied in clinical practice for the detection of antibodies to aquaporin-4 were tests in the form of an immunoenzymatic assay that showed great variability in the degree of specificity and sensitivity. The second group of tests for the detection of antibodies to aquaporin-4 applied the technique of indirect immunofluorescence on a substrate of animal origin, which achieved a higher degree of sensitivity and specificity with certain disadvantages such as the impossibility of precise quantification as well as difficulties in the interpretation of the results. Special methodological principles of immunoprecipitation such as fluorescent and radioimmunoprecipitation did not achieve a satisfactory level of sensitivity in the detection of antibodies to aquaporin-4. The highest level of sensitivity with absolute specificity has been achieved via developing a cell assay methodology based on the application of human aquaporin-4 transfected cells fixed on a biochip with a negative control when antibodies to aquaporin-4 from serum are detected by indirect immunofluorescence methodology or special cellular assays when these antibodies are quantified by flow cytometry method. The possibility to use this cell assaymethodology is extremely important in order to establish the correct diagnosis of seropositive neuromyelitis optica spectrum disorder.
Connection between type 2 diabetes and depression and their common influence on quality of life
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</xml><![endif]--><!-- [if gte mso 10]> <![endif]--> Type 2 diabetes mellitus (DM2) and depression are chronic non-communicable diseases that affect millions of people worldwide. The comorbidity of these two diseases is a complex phenomenon and has a huge clinical significance. The association between DM2 and depression was recognized decades ago, however the cause of the high prevalence of this comorbidity is not fully understood. It is assumed that shared genetic and environmental risk factors play a role, such as certain gene polymorphisms related to the secretion and effects of cortisol, obesity and others. Pathophysiological mechanisms underlying depression, such as HPA axis dysregulation and inflammation, impair insulin resistance and contribute to the development of DM2, while on the other hand, chronic stress linked to DM2 may cause depression. This relationship, which is often described as bidirectional, leads to the formation of the so-called "vicious cycle" that results in poor health outcomes of both conditions. Patients with DM2 and comorbid depression have a higher incidence of long-term complications, primarily macrovascular, lower quality of life and a higher mortality rate. Therefore, the prevention, early detection and treatment of depression in DM2 is extremely important. The treatment of comorbidity of these diseases include a multidisciplinary approach aimed at the simultaneous improvement of mental and physical health. Treatment involves pharmacotherapy, psychotherapy and psychosocial interventions, with the main goal of reducing the incidence of DM2 complications and improving the quality of life of affected individuals.