Univerzitet u Beogradu - Medicinski fakultet, Beograd
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.
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.
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.
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.
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.
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.
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.
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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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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Name="List Table 4 Accent 3"/> <w:LsdException Locked="false" Priority="50" Name="List Table 5 Dark Accent 3"/> <w:LsdException Locked="false" Priority="51" Name="List Table 6 Colorful Accent 3"/> <w:LsdException Locked="false" Priority="52" Name="List Table 7 Colorful Accent 3"/> <w:LsdException Locked="false" Priority="46" Name="List Table 1 Light Accent 4"/> <w:LsdException Locked="false" Priority="47" Name="List Table 2 Accent 4"/> <w:LsdException Locked="false" Priority="48" Name="List Table 3 Accent 4"/> <w:LsdException Locked="false" Priority="49" Name="List Table 4 Accent 4"/> <w:LsdException Locked="false" Priority="50" Name="List Table 5 Dark Accent 4"/> <w:LsdException Locked="false" Priority="51" Name="List Table 6 Colorful Accent 4"/> <w:LsdException Locked="false" Priority="52" Name="List Table 7 Colorful Accent 4"/> <w:LsdException Locked="false" Priority="46" Name="List Table 1 Light Accent 5"/> <w:LsdException Locked="false" Priority="47" Name="List Table 2 Accent 5"/> 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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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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.
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.
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.
CONGENITAL CLUBFOOT: ETIOPATHOGENETIC MECHANISMS AND TREATMENT CHALLENGES
Clubfoot is recognized as one of the most frequent musculoskeletal deformities. Being characterized by ankle equinus, hindfoot varus, forefoot adduction, cavus and calf muscles’ atrophy, it occurs in 1 to 2 per 1000 newborns. The concrete etiology of the deformity is not completely known but different studies suggest multifactorial pathogenesis, including numerous genetic and environmental risk factors. The most frequent clubfoot clinical presentation is isolated while it may also be associated with other neurologic conditions as the part of a syndrome. The disease is easy seen at birth and its degree may vary from mild to an extremely rigid foot that is not reducible to manipulation. The challenge of identifyng the best clubfoot treatment method has become less demanding as Ponseti invented his method that is today thought to be the gold standard, including weekly stretching and casting while following tenotomy of the Achilles tendon is mandatory for rigid equinus. Foot abduction brace treatment for four to five years is indicated in order to prevent relapse. Surgical soft-tissue releases might be necessary for those resistant clubfeet, where conservative treatment is not suffucient. If untreated, clubfoot leads to lifelong disability so it is essentially important to aware parents about the importance of persistent and patient commitment and compliance during the treatment period. The aim of this paper is to show the significance of multifactorial clubfoot etiology as well as different clubfoot therapeutic modalities.
GOAL-DIRECTED FLUID THERAPY IN MAJOR THORACO-ABDOMINAL SURGERY
Goal-directed fluid therapy (GDFT) in the thoracic-abdominal surgery has proven to be very challenging for many years. Minimal-invasive hemodynamic monitoring has become the standard at the Enhanced recovery after surgery – ERAS protocols. Additionally, established protocols in anesthetic management for major surgery recommend goal-directed fluid therapy. However, the use of GDFT remains controversial in certain surgical operations due to specific conditions (pneumoperitoneum or caponothorax in endoscopic procedures, open chest, protective mechanical ventilation in one lung ventilation). The modern advanced hemodynamic monitoring is less invasive and provides numerous hemodynamic variables for simple interpretation. Numerous studies have demonstrated the use of goal-directed therapy in intraoperative fluid replacement and its beneficial effects on lower postoperative morbidity and treatment costs. Using available literature performed different medical search strategies, the present review shows potential solutions to overcome the application limitations of advanced minimally invasive hemodynamic monitoring during toraco-abdominal surgery. With these options, hemodynamic monitoring will be used extensively to reduce postoperative complications and mortality. The customized strategy for patients, surgical intervention, and intraoperative losses is essential for both monitoring decision-making and achieving previously given goals for intraoperative fluid balance. This strategy has a direct impact on improving postoperative outcomes following surgery.
SIGNIFICANCE OF LEFT ATRIAL STRAIN ASSESSMENT OF IN THE PEDIATRIC POPULATION
The clinical outcome of chronic mitral regurgitation (MR) in children and adolescents, specifically the time it takes for MR to develop significant changes in the configuration and function of the left atrium (LA), is a relatively understudied area. There are numerous echocardiographic parameters that demonstrate significant changes in the size, volume, and functional behavior of the LA, but they lack the ability for early and fine detection of LA dysfunction. Left atrial strain (LAS) analysis represents a newer non-invasive technique for assessing LA function and early detection of its deformation and dysfunction. In the analysis of patients with chronic and significant MR, it emerges as a method that could verify early deformative, functional, and possibly fibrotic changes in the LA and thus predispose rhythm disturbances and clinical manifestations. This study related to strain analysis of LA function which can have prognostic and clinical implications in pediatric cardiology and be of great assistance in deciding when to initiate MR treatment.
MORPHOMETRIC ANALYSIS OF SUBMUCOSAL AND MYENTERIC NERVE PLEXUSES IN CHRONIC INFLAMMATORY BOWEL DISEASE IN CHILDREN
ABSTRACT Introduction: Chronic inflammatory bowel diseases (IBD) include ulcerative colitis (UC) and Crohn's disease (CD), characterized by relapses and an insufficiently clarified etiology. The enteric nervous system (ENS) consists of neuronal cells distributed along the gastrointestinal tract, organized into the submucosal Meissner's and myenteric Auerbach's plexuses. The glial cell index (GCI) represents the ratio of the number of glial cells to ganglion cells within the ganglia of the ENS. Aim: The aim of this study is a morphometric analysis of the ENS in intestinal samples from surgically treated pediatric patients with CD and UC. Material and methods: Histological slides from the archives of the Institute of Pathology, Faculty of Medicine, University of Belgrade, were analyzed. The study included an analysis of intestinal wall sections from pediatric patients with IBD (experimental group) and those with uncomplicated familial adenomatous polyposis syndrome (control group). Using the ImageJ software, five microphotographs of submucosal and myenteric nerve plexuses stained with Masson trichrome and captured with an Olympus DP70 digital camera at x400 magnification were analyzed. Results: A significant difference in the GCI value in the myenteric plexus of the colon was observed between the experimental and control groups. No significant difference in the GCI value in the submucosal plexus of the colon was found between the two groups. A minimal difference in the GCI value within the experimental group was observed in the submucosal plexus sections. Conclusion: This study presents a unique analysis of glial cells in CD, UC, and the control group in the submucosal and myenteric plexuses. The results indicate a disruption of GCI in the ENS in IBD, which likely represents the morphological substrate for intestinal motility disorders in these conditions.
PREDICTORS OF ADVANCED LARYNGEAL SQUAMOUS CELL CARCINOMA INVASION ON THYROID GLAND TISSUE
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</xml><![endif]--><!-- [if gte mso 10]> <![endif]--> Total laryngectomy presents the standard therapeutic protocol in the treatment of advanced laryngeal cancer. There is not enough research in this area to indicate the necessity of performing thyroidectomy in patients with advanced squamous cell carcinoma of the larynx, although some studies indicate that unilateral thyroidectomy is performed routinely in some centers. The National Comprehensive Cancer Network (NCCN) recommends ipsilateral hemithyroidectomy with laryngectomy for advanced squamous cell carcinoma of the larynx. However, in these cases, the risk of hypothyroidism and hypoparathyroidism is significantly higher, which requires postoperative monitoring of hormone status and thyroid replacement therapy. Invasion of the thyroid gland can occur due to direct or lymphovascular spread of advanced squamous cell carcinoma of the larynx, and the risk of locoregional recurrence and distant metastases in these cases increases significantly. The incidence of thyroid gland invasion in patients with advanced laryngeal squamous carcinoma is relatively low, and the most common predictors for infiltration are subglottic and transglottic extension of the laryngeal tumor, as well as direct invasion of the thyroid cartilage. Preservation of thyroid tissue during laryngectomy significantly reduces postoperative morbidity, however, thyroidectomy may be indicated if the presence of risk factors for thyroid invasion is assessed based on clinical, radiological and intraoperative findings. A careful assessment of risk factors is necessary to avoid the occurrence of locoregional recurrence, and thus a significantly worse prognosis.
RECOARCTATION AFTER SURGICAL CORRECTION OF COARCTATION OF THE AORTA IN CHILDREN AND ADOLESCENTS
Introduction: Coarctation of the aorta (CoA) is a narrowing of the thoracic aorta, most often localized at the junction of ductus arteriosus. Data on risk factors for the development of recoarctation remain contradictory in literature. The aim: To determine the frequency of recoarctation and to identify risk factors for the recoarctation after surgical correction of CoA. Material and methods: The research included 94 patients who underwent surgery for coarctation of the aorta from 2012 to 2017. Demographic and clinical characteristics, preoperative, intraoperative, postoperative and echocardiographic parameters were observed. Pressure gradient over 25 mmHg immediately after operation is considered predictоr for recoarctation of the aorta. The data was processed using methods of descriptive and analytical statistics. Results: The median age at the time of surgery was 2 months (4 days-19 years). The dominant technique was extended end-to-end anastomosis (90.4%). Kaplan Meier survival analysis showed higher incidence of recoarctation in the group of patients with immediate postoperative gradient >25 mmHg (p<0.001). Also, Cox logistic regression showed higher immediate postoperative gradient to be a predictor (HR 4.57, p=0.009, 95% CI 1.47 -14.22). After correction for other cofactors, including sex, genetic syndrome, small body weight, administration of prostaglandine E1, presence of bicuspid aortic valve, surgical technique, it was shown that group of patients with higher immediate postoperative gradient has 4-fold higher probability for recoarctation (HR 4.37, p=0.035, 95% CI 1,11 -17,16) . Conclusion: Immediate postoperative pressure gradient > 25 mmHg is an independent predictor for recoarctation after surgical correction of the coarctation of the aorta.
Analysis of anxiety depending on the status of complications in patients with diabetes mellitus
Introduction: Anxiety disorders are one of the leading types of disorders in the general population whose symptoms often have a significant impact on people's daily lives. Additionally, anxiety symptoms have been shown in studies conducted around the world to be a significant factor that affects the course of diabetes, as well as the development of possible complications of the disease itself. Aim: The aim of this work is to examine the impact of anxiety symptoms on diabetic foot complications in the Serbian population in order to see the need for psychological support as a form of prevention of this type of complication. Material and methods: This research is a retrospective-prospective study conducted in the period from October 15, 2023. until February 15, 2024. The study included 87 patients divided into three groups depending on the status of complications of diabetes mellitus. All subjects were patients of the Endocrinology Clinic University Clinical Center of Serbia (UCCS) and the Institute of Orthopedic Surgery and Traumatology UCCS. Respondents were surveyed with the GAD-7 (General Anxiety Disorder-7) questionnaire. Data on gender, age, duration of illness, complications and comorbidities were collected for all subjects. Statistical analysis was performed in the program EZR: R Commander. Results: The analysis showed that there is a statistically significant difference in the results of the GAD-7 test between the group of patients with amputations and the control group, as well as the group of patients with amputations and the group on conservative treatment, while there is no statistical difference between the control group and the group whose diabetic foot is treated conservatively. Conclusion: The results of our study indicate the possible influence of anxiety on the development of diabetes mellitus in patients as well as on the faster progression of the disease itself and the possible need for support for certain patients. Keywords: anxiety, diabetes mellitus, diabetic foot
ASSOCIATION OF LIPID LEVELS DURING GESTATION COMPLICATED WITH GESTATIONAL DIABETES MELLITUS AND EARLY PREDICTION OF GESTATIONAL DIABETES MELLITUS BY FIRST TRIMESTER LIPID VALUES
Pregnancy induces intricate physiological changes, including alterations in lipid profiles crucial for fetal development. The transition from an anabolic to a catabolic phase in the third trimester reflects increasing insulin resistance, facilitating lipid breakdown for fetal energy. Physiological pregnancy exhibits significant lipid profile changes, with dyslipidemia linked to negative effects on maternal and fetal health. Dyslipidemia in pregnancy correlates strongly with cases of pregnancy-related high blood pressure and diabetes. Gestational diabetes mellitus (GDM) introduces distinctive lipid alterations, including elevated triglycerides (TG) and low-density lipoprotein particles. Mixed dyslipidemia in GDM, exceptionally high TG, and reduced levels of high-density lipoprotein cholesterol (HDL-C) are linked to negative perinatal outcomes, emphasizing the importance of lipid profile assessment. Evaluating lipid profiles, especially TG levels, in early pregnancy proves valuable in predicting GDM. The ratio of triglycerides to high-density lipoprotein cholesterol (TG/HDL-C) shows potential as a predictive marker for GDM, demonstrating commendable sensitivity and specificity. Elevated TG levels, even before 28 weeks, increase GDM risk, emphasizing the role of lipid markers in early detection. Early predictions of GDM through plasma lipid profiling offer a promising avenue for enhancing antenatal care. While standardized markers and thresholds require further research, integrating lipid profiles into routine screenings may optimize GDM management, ultimately benefiting both the mother and fetus.
THE MOST COMMON ENDOCRINOLOGICAL DISORDERS IN PREGNANCY
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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 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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 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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]--> Pregnancy is a state of disturbed physiological mechanisms, affecting almost all systems of organs. Endocrine disorders that occur during pregnancy can significantly impact maternal and fetal health, necessitating a comprehensive understanding of their etiology, diagnosis, and management. The most common endocrinological disorders during pregnancy are gestational diabetes and thyroid gland dysfunctions. Diabetes during pregnancy carries a higher risk of complications, such as preeclampsia, preterm birth, macrosomia, and cesarean delivery. However, with careful management, numerous women with diabetes can have healthy pregnancies and deliver healthy babies. Hypothyroidism during pregnancy refers to an underactive thyroid gland function, where the thyroid gland doesn't produce enough thyroid hormones, particularly thyroxine (T4) and triiodothyronine (T3). This condition can have significant implications for the mother and the developing fetus. Untreated hypothyroidism may lead to severe complications, including intellectual and developmental issues in the child, preeclampsia, anemia, miscarriage, or preterm birth. Aside from these two of the most common endocrinological dysfunctions, maternal and fetal well-being can be significantly affected by other endocrine gland disorders, such as parathyroid, adrenal, and pituitary gland disturbances. If unrecognized or untreated, all these conditions can lead to poor pregnancy and maternal outcomes. Endocrinological disorders during pregnancy represent a complex and critical area of concern for both maternal health and fetal development. Furthermore, they can have far-reaching implications that extend beyond the duration of pregnancy, having lifelong implications for the future mother and the offspring. Effective management of endocrinological disorders in pregnancy requires a multidisciplinary team approach involving obstetricians, endocrinologists, nutritionists, and other healthcare professionals. Timely interventions, personalized treatment plans, and close monitoring are at the core of optimal obstetric care for these patients. Lifestyle modifications, medication adjustments, and regular prenatal care play crucial roles in optimizing maternal health and birth outcomes.
SIGNIFICANCE OF INTERACTIONS BETWEEN GENETIC AND ENVIRONMENTAL FACTORS IN ETIOLOGY OF MULTIPLE SCLEROSIS
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It most frequently occurs in young female adults, and the prevalence increases with latitude. So far, over 200 genes, loci and single nucleotide polymorphisms (SNPs) have been linked with MS, although each one contributing only slightly in the overall etiology of the disease. The HLA-DRB1*15:01 haplotype has been shown to have the strongest association with MS occurrence risk in genome-wide association studies (GWAS), while HLA-A*02 has been shown to have a protective effect. The exact etiology of MS is still unclear, but there seems to exist interplay between genetic burden of an individual, and environmental factors which contribute to MS occurrence such as Epstein-Barr virus (EBV) infection, vitamin D levels, smoking status, and early life obesity. An interaction between HLA-DRB1*15:01 and EBV infection, the strongest environmental risk factor for MS, has been observed. It has been suggested that this interaction is a result of HLA-DRB1*15:01 acting as a coreceptor for EBV, thus providing a pathophysiological explanation connecting environmental with genetic MS risk factors. A recent study including participants from two case-control studies with over 13.000 individuals showed that an interaction exists between sun exposure, vitamin D levels, and HLA-DRB*15:01 carrier status, leading to increased risk of MS in individuals with lower sun exposure, vitamin D deficient, and HLA-DRB*15:01 positive. The interaction of HLA-DRB1*15:01 with smoking has been observed in a meta-analysis, while the same study only showed an interaction of smoking with the absence of HLA-A*02 in a subset of studies. The risk of MS has been show to vary in obese individuals, with obese individuals with the susceptible genotype (HLA-DRB1*15:01+, HLA-A*02-) having 16x higher odds of having MS compared with non-obese persons with a non-susceptible genotype.
Cardiac computed tomography in infective endocarditis
Infective endocarditis is a rare disease with an increasing incidence and an unchanged high mortality rate, despite the rapid medical development. Imaging plays integrative part in diagnosis of IE, with echocardiography as main diagnostic test. Rising research data in utility of Cardiac Computed Tomography (CCT) in diagnostic algorithm of IE, indicates its importance in detection of IE-related lesion along with the exclusion of coronary artery disease. The latest 2023 European Society of Cardiology Guidelines in management of IE classified CCT as class of recommendation I and level of evidence B in detection of both valvular and paravalvular lesions in native and prosthetic valve endocarditis. This review article provides comprehensive and contemporary review of role of CCT in diagnosis of IE, optimization of acquisition protocols, morphology characteristics of IE-related lesions, published data of diagnostic performance of CCT in comparison to echocardiography as the state-of-art method, limitation and future possibilities.
CONTEMPORARY DIAGNOSIS OF CORONARY MICROVASCULAR DYSFUNCTION IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION
Coronary microvascular dysfunction (CMD) is encountered in up to 50% of patients presenting with ST-segment elevation acute myocardial infarction (STEMI) and treated with primary percutaneous coronary intervention (PCI). The current reference standard to diagnose microvascular injury in this setting is cardiac magnetic resonance (CMR) imaging. The extent of microvascular injury, termed microvascular obstruction (MVO) on CMR, increases over time after recanalization of the infarct-related artery (IRA), until it reaches its peak around day 3, and it subsides by day 10. Most of the current research evaluated MVO on CMR on days 2-7 after primary PCI, and showed its association with cardiac death and heart failure independently of the infarct size. As microvascular injury becomes a new therapeutic target in STEMI, given the plateauing mortality curves despite widespread access to timely reperfusion, the question of early diagnosis of CMD grows in importance. To this end, invasive coronary microcirculation assessment in the recanalized IRA immediately after primary PCI, has been tested in terms of its association with MVO and infarct size on CMR, as well as its ability to predict adverse clinical outcomes. Both invasive thermodilution- and Doppler wire-derived indices of microvascular resistance were successful in stratifying patients according to the risk of cardiac death and heart failure in the follow-up. Recently, a coronary angiography-based method, which unlike thermodilution and Doppler derives indices of microvascular resistance from a computational dynamics software and does not require additional wiring of the epicardial artery, has demonstrated the ability to predict adverse clinical outcomes. The described diagnostic tools for stratification of patients according to the risk of CMD and consequently impaired prognosis after STEMI, still remain a subject of on-going research, in terms of both the most relevant cut offs for different indices and the optimal time point of assessment.