Suočavanje sa stresom u djece s epilepsijom - evaluacija kognitivno-bihevioralne intervencije

A pilot study was conducted to examine the efficiency and satisfaction of cognitive behavioral therapy (CBT) intervention in youth with epilepsy regarding coping strategies. The CBT intervention was based on the main principles and empirically supported cognitive-behavioral techniques. The intervention consists of epilepsy education, stress education, and coping skill strategies. Seventeen children and adolescents aged 9-17 diagnosed with epilepsy for at least one year, with at least average intelligence and no history of serious mental illness completed the CBT intervention during summer camp, providing data on the efficiency of and satisfaction with CBT intervention. Upon completion of the CBT intervention, study subjects achieved significantly higher scores on the following Scale of Coping with Stress subscales: Problem solving; Seeking for social support from friends; Seeking for social support from family; and Cognitive restructuring, for both measures of usage frequency and effectiveness of each subscale. The participants reported a high level of satisfaction with the CBT intervention. This study provided explanation of research limitations and recommendations for future clinical trials.U ovom istraživanju ispitivala se učinkovitost i zadovoljstvo kognitivno-bihevioralnom terapijom (KBT) za strategije suočavanja sa stresom kod djece i adolescenata s epilepsijom. Provedena intervencija KBT temelji se na osnovnim postulatima znanstveno utemeljene KBT. Intervencija se sastojala od edukativnih radionica o epilepsiji kao bolesti, stresu te o strategijama suočavanja sa stresom. Sveukupno 17 djece i adolescenata u dobi 9-17 godina, prosječnih kognitivnih sposobnosti, s dijagnosticiranom epilepsijom najmanje godinu dana te bez komorbiditeta psihičkih bolesti bilo je uključeno u intervenciju KBT tijekom ljetnog kampa. Nakon završetka intervencije KBT na Ljestvici suočavanja sa stresom za djecu i adolescente ispitanici su postigli značajno bolje rezultate na sljedećim podljestvicama: Rješavanje problema, Traženje socijalne podrške od prijatelja, Traženje socijalne podrške od obitelji te Kognitivno restrukturiranje, i to za obje mjere: frekvencija i učinkovitost svake spomenute podljestvice. Ispitanici su potvrdili visoko zadovoljstvo provedenom kognitivno-bihevioralnom intervencijom. Konačno, provedeno istraživanje definiralo je ograničenja u provedenom istraživanju te dalo smjernice i preporuke za slična buduća klinička ispitivanja

Grafičke tehnike

Grafika je oblik umjetničkog postupka prenošenja prikaza na matricu koji se potom otiskuje na ravnu podlogu. Grafika je u naravi reproduktivna tehnika (izuzmemo li monotipiju) koja podrazumijeva kreaciju željenog prikaza i usvajanje posebnosti i originalnosti tehnologije i tehnika grafi čkog postupka pri tome. Ona nije samo sredstvo umnažanja slikarskog motiva ili crteža, već svojom bogatom i složenom tehnologijom omogućuje jedinstven pristup i umjetnički doseg. Svaki otisak je na neki način i original koji svoju nepatvorenost duguje tehnici otiskivanja. S djecom predškolske dobi poželjno je raditi grafičke tehnike jer upravo je to onaj segment likovnog stvaralaštva u kojem djetetu pružamo mogućnost da nadogradi svoj likovni doživljaj i iskustvo, te da kroz ljepotu tehnike još bolje zaokruži svoje djelovanje na području likovnosti

Association of Adiponectin Receptors with Metabolic and Immune Homeostasis Parameters in Colorectal Cancer: In Silico Analysis and Observational Findings

Adiponectin (ADIPOQ) as both a regulator of metabolic homeostasis and a protein involved in immune response might be of particular interest to contemporary laboratory medicine, especially in terms of minimally invasive diagnostics. The diverse roles of ADIPOQ with regard to the immune and metabolic aspects of colorectal carcinogenesis have been proposed. However, the expression of its receptors ADIPOR1 and ADIPOR2 is scarcely explored in peripheral blood mononuclear cells (PBMCs). Moreover, ADIPORs’ relationships with the immune response mediator TNF-α have not been previously investigated in the PBMCs of CRC patients. This study used both in silico and observational case–control analyses with the aim of exploring the association of ADIPOR gene expression and ADIPOQ single nucleotide polymorphisms (SNPs) with the inflammatory marker TNF-α and lipid status parameters in patients with CRC. Publicly available transcriptomic datasets (GSE47756, GSE44076) obtained from analyses of monocytes and CRC tissue samples were employed for the in silico evaluation of ADIPORs’ specific genetic traits. GSE47756 and GSE44076 datasets were processed with GSEA software to provide a genetic fingertip of different signaling pathways associated with ADIPORs’ mRNA levels. The case–control aspect of the study included the PBMC samples of 73 patients diagnosed with CRC and 80 healthy volunteers. The PCR method was carried out for the PBMC gene expression analysis (ADIPOR1, ADIPOR2, TNF-α mRNA levels) and for the subjects’ genotyping (ADIPOQ rs266729, ADIPOR1 rs7539542). GSEA showed significant associations of ADIPOR mRNA expression with gene sets related to metabolic and immune homeostasis in both datasets. The case–control study revealed the association of ADIPOR1 rs7539542 with reduced lipid status parameters in CRC. In addition, PBMC ADIPOR1 mRNA levels decreased in CRC (p < 0.001), whereas ADIPOR2 mRNA did not differ between the groups (p = 0.442). A reduction in PBMC TNF-α mRNA levels was noted in CRC (p < 0.05). Our results indicate that ADIPOR1 and ADIPOR2 play a significant role in the alteration of both metabolic and immune homeostasis during the progression of CRC. For the first time, ADIPOR1 is shown to be a specific receptor for mediating ADIPOQ’s effects in the PBMCs of CRC patients

Bolest nealkoholne masne jetre kao metabolička posledica opstruktivne apneje u snu

Obstructive sleep apnea (OSA) as a worldwide prevalent condition carries risk for cardiovascular and metabolic diseases, ultimately increasingoverall mortality rates. Non-alcoholic fatty liver disease (NAFLD) can be considered as the primary metabolic disease, but also as a coexisting OSA comorbidity. Although prevalence of NAFLD covers quarter of world population, it increases with OSA presence. It can be speculated that chronic intermittent hypoxia (CIH) and sympathetic nervous system overactivity are involved in NAFLD pathogenesis and progression from simple steatosis throughsteatohepatitis to fibrosis. CIH provides the environment for liveroxidative stress, inflammation and increases the expression of genes involved in cholesterol and fatty acids synthesis. Catecholamines increase β-oxidation in liver and release free fatty acids from adipose tissue in plasma which inhibit insulin effects. Obesity and insulin resistance as key playersin NAFLD development and advancement, deepen vicious circle of oxidative stress, inflammation and dyslipidemia. If not treated, OSA in NAFLD patients has been associated with inflammation, hepatocytes’ necrosis, and fibrosis. Continuous positive airway pressure (CPAP) represents gold standard for OSA therapy, allowing the unimpeded air passage through upper parts of respiratory system. However, it has been demonstrated that CPAP therapyhave beneficial effects on cardiometabolic outcomes and slowliver degenerationOpstruktivna apneja u snu (OSA) kao oboljenje prevalentno u svetu nosi rizik za nastanak kardiovaskularnih i metaboličkih bolesti, povećavajući ukupnu smrtnost. Bolest nealkoholne masne jetre (eng. non-alcoholic fatty liver disease -NAFLD) se može smatrati primarnom metaboličkom bolešću, ali kao i komorbiditet OSA. Iako prevalenca NAFLD obuhvata četvrtinu svetske populacije, ona se povećava sa prisustvom OSA. Pretpostavlja se da su hronična intermitentna hipoksija (eng. chronic intermittent hypoxia -CIH) i prekomerna aktivnost simpatičkog nervnog sistema uključeni u patogenezu NAFLD i progresiju od steatoze preko steatohepatitisa do fibroze. U jetri CIH stvara uslove za oksidativni stres, inflamaciju i povećava ekspresiju gena koji učestvuju u sintezi holesterola i masnih kiselina. Kateholamini stimulišu b-oksidaciju masnih kiselina u jetri i oslobađaju slobodne masne kiseline iz masnog tkiva u plazmu, koje inhibiraju dejstva insulina. Gojaznost i insulinska rezistencija kao ključni faktori u razvoju i napredovanju NAFLD produbljuju začarani krug oksidativnog stresa, inflamacije i dislipidemije. Ako se ne leči, OSA kod pacijenata sa NAFLD je povezana sa inflamacijom, nekrozom hepatocita i fibrozom. Kontinuirani pozitivni pritisak vazduha (eng. continuous positive airway pressure -CPAP) predstavlja zlatni standard u terapiji OSA, koji omogućava neometani prolaz vazduha kroz gornje delove respiratornog sistema. Međutim, CPAP terapija je pokazala da ima povoljne efekte na kardiometaboličke ishode i da usporava degeneraciju jetre

Poremećaji metaboličke i inflamatorne homeostaze u patogenezi kolorektalnog karcinoma

In order to understand the metabolic and immune potential of adiponectin in colorectal cancer (CRC), attention is drawn to its receptors: adiponectin receptor 1 (ADIPOR1) and adiponectin receptor 2 (ADIPOR2). Gene set enrichment analysis (GSEA) of datasets based on malignant tissue samples and peripheral blood monocytes (PBMs) was used to explore mRNA fingerprints of different signaling pathways best associated with ADIPOR1/ADIPOR2 gene expression levels. Transcriptomic datasets GSE44076 (1) and GSE47756 (2) were downloaded from the NCBI Gene Expression Omnibus database. In the GSE44076 dataset, three groups were formed: 98 colon tumor tissue and matched tumor- adjacent mucosa samples and tissue samples from 50 healthy volunteers. The other set (GSE47756) contained information on PBMs' gene signature in CRC, by forming two groups: 38 samples from healthy subjects and 55 CRC patients. GSEA analysis of the GSE44076 dataset implied that ADIPOR1 mRNA levels were in negative association with MTORC1 and TNF-α NF-κB signaling pathways in tumor tissue. At the same time, ADIPOR2 was positively associated with metabolic gene sets such as cholesterol homeostasis, glycolysis and PPAR signaling. Quite opposite to the GSE44076 dataset, GSEA analysisis of GSE47756 revealed that ADIPOR1 was a metabolically active receptor in PBMs of CRC patients. Surprisingly, the TNF-α NF-κB signaling pathway gene sets were positively associated with ADIPOR1 mRNA levels in monocytes of the cancer group. Different types of metabolic and immune regulation achieved through ADIPOR1/ADIPOR2 in tumor and PBMs suggest possible novel therapeutic targets in CRC.Da bi se razumeo metabolički i imuni potencijal adiponektina u kolorektalnom karcinomu (CRC), pažnja se mora obratiti i na njegove receptore: adiponektinski receptor 1 (ADIPOR1) i adiponektinski receptor 2 (ADIPOR2). Gene set enrichment analiza (GSEA) dva skupa podataka, zasnovanih na uzorcima malignog tkiva i na monocitima periferne krvi (PBM) je korišćena da bi se obezbedili genetski otisci različitih signalnih puteva koji su bili najbolje povezani sa ekspresijom gena ADIPOR1/ADIPOR2. Skupovi transkriptomskih podataka GSE44076 (1) i GSE47756 (2) su preuzeti iz NCBI Gene Expression Omnibus baze podataka. U skupu podataka GSE44076 formirane su tri grupe: 98 uparenih uzoraka tumorskog tkiva debelog creva i susedne mukoze i uzorci tkiva 50 zdravih dobrovoljaca. Drugi set (GSE47756) je sadržao informacije o otisku gena PBM u CRC sa formiranim dvema grupama: 38 uzoraka zdravih subjekata i 55 pacijenata sa CRC. GSEA analiza skupa podataka GSE44076 je implicira da su nivoi iRNK ADIPOR1 negativno korelirali sa MTORC1 i TNF-α NF-κB signalnim putevima u tumorskom tkivu. Istovremeno, ADIPOR2 je bio pozitivno povezan sa skupovima gena metaboličkih puteva kao što su homeostaza holesterola, glikoliza i PPAR signalizacija. Nasuprot GSE44076 skupu podataka, GSEA analiza GSE47756 transkriptomskog seta je otkrila da je ADIPOR1 zapravo metabolički aktivan receptor u PBM pacijenata sa CRC. Iznenađujuć e, setovi gena koji su se odnosili na signalni put TNF-α NF-κB su bili pozitivno povezani sa nivoima iRNK ADIPOR1 u monocitima grupe sa karcinomom. Različite vrste metaboličke i imune regulacije koje se postižu preko ADIPOR1/ADIPOR2 u tumoru i PBM sugerišu moguć e nove terapeutske ciljeve u CRC.VIII Kongres farmaceuta Srbije sa međunarodnim učešćem, 12-15.10.2022. Beogra

Oxidative Stress and Inflammatory Biomarkers in Patients with Diabetic Foot

Background and Objectives: Diabetic foot (DF) development is driven by complex interactions of hyperglycemia, inflammation, and oxidative stress (OS). We aimed to investigate OS and inflammatory biomarkers in patients with DF and their potential to improve early diagnosis and management of DF. Materials and Methods: The prooxidant–antioxidant balance (PAB), superoxide dismutase (SOD), total oxidative status (TOS), total sulfhydryl groups (SHG), routine biochemical parameters, and complete blood count were determined in 42 patients with type-2 DM, of which 23 patients had DF, while 19 patients were without DF complications. The neutrophils-to-lymphocyte ratio (NLR) was evaluated as a biomarker of inflammation. Results: Patients with DF had significantly higher (p < 0.05) PAB levels (170 ± 33.9 U/L) compared to those without DF complications (142 ± 31.3 U/L). In addition, patients with DF had significantly reduced SOD activities (p < 0.01). NLR values were significantly higher in the DF group (median: 2.8; interquartile range: 2.0–4.3) than in the group without DF (median: 1.4; interquartile range: 1.4–2.1; p < 0.01). A positive correlation was found between the PAB and NLR index (r = 0.449; p < 0.05). The diagnostic accuracy of both PAB (AUC = 0.741; p < 0.01) and NLR (AUC = 0.760; p < 0.01) was estimated as acceptable. Conclusions: In conclusion, the development of DF is associated with enhanced OS and inflammation processes. PAB and NLR could be useful non-invasive biomarkers of DF development

Nishodna regulacija MAPK/MAK/MRK preklapajuće kinaze u mononuklearnim ćelijama periferne krvi pedijatrijskih pacijenata sa tip1 diiabetes mellitus-om

Background: Type 1 diabetes mellitus (T1DM) is one of the most common endocrine diseases in children. T-cell autore- activity toward b-cells is controlled by significant changes in metabolism of T cells. Mammalian target of rapamycin (mTOR) is an important intracellular regulator of metabolism and cell growth. MAPK/MAK/MRK overlapping kinase 1 (MOK1) is one of the less known regulators of mTOR. We sought to investigate if MOK1 and mTOR mRNA levels in peripheral blood mononuclear cells (PBMCs) of T1DM pedi- atric patients are different compared to healthy subjects. Methods: This study included 172 adolescents with T1DM and 36 healthy adolescent volunteers designated for control group (CG). MOK1 and mTOR mRNA levels were deter- mined in PBMCs by qPCR. Results: T1DM patients have significant downregulation of MOK1 mRNA levels in PBMCs compared CG (P=0.018), while there was no significant difference in mTOR mRNA levels (P=0.891). Furthermore, in T1DM patients, MOK1 significantly correlated with age, triglycerides and mTOR, while mTOR correlated significantly with BMI and systolic blood pressure. Overweight T1DM subjects had significantly lower MOK1 (P=0.034) and mTOR (P=0.017) mRNA levels, together with significantly higher levels of systolic blood pressure (P<0.001), total cholesterol (P=0.001), LDL-cholesterol (P=0.001) and CRP (P<0.001). Multi- variate analysis showed that MOK1 was independently negatively associated with T1DM when adjusted for sex, age, HDL-C and CRP (OR=0.417 (95%CI: 0.175–0.997), p=0.049). Conclusions: Our study demonstrated for the first time that T1DM is associated with MOK1 downregulation. In addition, downregulation of both mTOR and MOK1 gene expressions was associated with cardiovascular risk factors in overweight T1DM patients.Uvod: Dijabetes melitus tip 1 (T1DM) jedno je od najčešćih endokrinih oboljenja kod dece. Autoreaktivnost T-ćelija prema b-ćelijama kontroliše se značajnim promenama u metabolizmu T ćelija. Cilj delovanja rapamicina kod sisara je važan unutarćelijski regulator metabolizma i rasta ćelija. MAPK/MAK/MRK preklapajuće kinaze koja se preklapa (MOK1) jedan je od manje poznatih regulatora mTOR-a. Cilj istraživanja je bio da se ispita da li su nivoi iRNK MOK1 i mTOR u mononuklearnim ćelijama periferne krvi različiti kod pedijatrijskih pacijenata sa T1DM u odnosu na zdrave ispitanike. Metode: Ovo istraživanje je obuhvatilo 172 adolescenta sa T1DM i 36 zdravih adolescenata dobrovoljaca koji su činili kontrolnu grupu (CG). Nivoi MOK1 i mTOR mRNA određeni su u PBMC-ima pomoću qPCR-a. Rezultati: Pacijenti sa T1DM imali su značajno niže nivoe iRNK MOK1 u PBMC u odnosu na CG, dok razlike u nivoima iRNK mTOR nisu bile značajne (P = 0,891). Štaviše, kod pacijenata sa T1DM, MOK1 je značajno korelirao sa godinama, trigliceri dima i mTOR, dok je mTOR značajno korelirao sa BMI i sistolnim krvnim pritiskom. Ispitanici sa prekomernom težinom T1DM imali su značajno niže nivoe iRNK MOK1 (P = 0,034) i mTOR (P = 0,017), zajedno sa značajno većim nivoima sistolnog krvnog pritiska (P <0,001), ukupnog holesterola (P = 0,001), LDL-holesterola (P = 0,001) i CRP (P <0,001). Multivarijantna analiza je pokazala da je MOK1 nezavisno negativno povezan sa T1DM kada je prilagođen polu, starosti, HDL-C i CRP (OR = 0,417 (95%CI: 0,175-0,997), p = 0,049). Zaključak: Naša studija je prva koja je pokazala da je T1DM udružen sa nishodnom regulacijom MOK1. Pored toga, snižena regulacija ekspresije gena mTOR i MOK1 bila je povezana sa kardiovaskularnim faktorima rizika kod pacije nata sa T1DM sa prekomernom težinom

Association among resistin, adenylate cyclase-associated protein 1 and high-density lipoprotein cholesterol in patients with colorectal cancer: a multi-marker approach, as a hallmark of innovative predictive, preventive, and personalized medicine

Background: Elevated concentrations of resistin have been reported in colorectal cancer (CRC), but its interactions with adenylate cyclase-associated protein 1 (CAP-1) are largely unexplored. We investigated resistin plasma concentration, peripheral blood mononuclear cells (PBMCs) resistin messenger ribonucleic acid (mRNA), and CAP-1 mRNA levels in CRC patients, as well as the impact of resistin gene polymorphism rs1862513 on the examined markers. We also explored associations of resistin with high-density lipoprotein cholesterol (HDL-C) and predictive potential of our parameters for CRC. Methods: Eighty-six patients with CRC and 75 healthy adults were included. Commercial ELISA kit was used for obtaining resistin’s concentrations, while polymerase chain reaction (PCR) method was applied for evaluation of resistin and CAP-1 mRNA levels and rs1862513 polymorphism. Results: Plasma resistin and CAP-1 mRNA levels were higher in CRC patients (p < 0.001 and p < 0.05, respectively), while resistin mRNA levels were lower (p < 0.001). Negative association existed among plasma resistin and HDL-C concentrations (ρ = − 0.280; p < 0.05). A model including age, body-mass index, HDL-C, low-density lipoprotein cholesterol (LDL-C), and plasma resistin concentrations as independent predictors of CRC showed very good diagnostic accuracy (AUC = 0.898). We found no associations of rs1862513 with the examined markers. Conclusions: Our study demonstrated increased plasma resistin and CAP-1 mRNA levels, implying their possible interaction in CRC. The association among plasma resistin and HDL-C might indicate that HDL-C is involved in alterations of resistin’s secretion process. As a hallmark of personalized medicine, multi-marker approach in determination of resistin-related parameters might be useful for prediction and prevention of CRC development

Effects of Apnea, Obesity, and Statin Therapy on Proprotein Convertase Subtilisin/Kexin 9 Levels in Patients with Obstructive Sleep Apnea

Objectives: Obstructive sleep apnea (OSA) is a common condition closely related to obesity, insulin resistance, dyslipidemia, and cardiovascular disease. The aim of this study was to explore the possible relationship between OSA and proprotein convertase subtilisin/kexin type 9 (PCSK9). Methods: Full-night polysomnography was performed on 150 participants who were divided into three groups: controls, OSA patients on statin therapy, and OSA patients not on statin therapy. Biochemical markers, plasma low-density lipoprotein (LDL) and high-density lipoprotein (HDL) subclasses, and PCSK9 were determined. Results: PCSK9 was highest in OSA patients on statins compared to the control group and to OSA patients not on statins (p = 0.036 and p = 0.039, respectively), after adjustment for body mass index (BMI). LDL diameter was greater in OSA patients not on statins compared to OSA patients on statins (p = 0.032). PCSK9 was highest in the group of patients with all three risk factors (diagnosed OSA, statins, BMI ≥25 kg/m2) compared to groups with no, one, and two risk factors (p = 0.031, p = 0.001, and p = 0.029, respectively). Presence of OSA, statin therapy, and BMI ≥25 kg/m2 when combined were independently associated with higher levels of PCSK9 when adjusted for antihypertensive therapy, small dense LDL, and HDL 3c subclass (odds ratio = 2.849; interquartile range [1.026–7.912], p = 0.044). Conclusion: Statin therapy was closely related to PCSK9. OSA along with obesity and statin use induces elevation of PCSK9

Transforming growth factor-β1 and receptor for advanced glycation end products gene expression and protein levels in adolescents with type 1 diabetes mellitus

Objective: Type 1 diabetes (T1D) mellitus is one of the most frequent autoimmune diseases in childhood. Chronic complications are the main causes of cardiovascular morbidity and mortality in T1D. Although interactions between advanced glycation end products (AGE) and their receptors (RAGE) and transforming growth factor-β1 (TGF-β1) are implicated in development and progression of diabetic micro-and macro-vascular complications, they also have important roles in immune system regulation. Methods: Blood samples were obtained from 156 adolescents with T1D and 80 apparently healthy controls. T1D patients diagnosed with any other autoimmune disease and receiving any kind of drugs except insulin therapy were excluded from this study. Exclusion criteria for controls were positive family history of T1D and drugs/supplements application. TGF-β1 and transmembrane full-length RAGE (flRAGE) messenger ribonucleic acid (mRNA) levels in peripheral blood mononuclear cells (PBMC) were obtained by quantitative polymerase chain reaction (qPCR) method. Circulating levels of biochemical markers, TGF-β1 and soluble RAGE (sRAGE) levels were also determined. Results: TGF-β1 and flRAGE mRNA levels were significantly higher in controls compared to patients (p<0.001, for both). However, TGF-β1 and sRAGE levels were higher in patients than controls (p<0.001, for both). There were significant independent associations of all mRNA and protein levels with T1D. TGF-β1 mRNA was the only marker independently negatively associated with urinary albumin excretion rate in T1D adolescents (p=0.005). Conclusion: Our results indicated gene expression downregulation of TGF-β1 and flRAGE in PBMC of T1D adolescents. TGF-β1 mRNA downregulation may be useful for predicting early elevation of urinary albumin excretion rate