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•PGC1A rs8192678 variant is associated with multiple sclerosis (MS) susceptibility.•Male patients carriers of LEPR rs1137101 G allele have increased MSSS.•Relapsing-remitting MS ...carriers of rs7799039 A allele have increased LEP mRNA level.
Leptin (LEP), leptin receptor (LEPR) and peroxisome proliferator-activated receptor gamma co-activator 1-alpha (PGC1A) are involved in the pathogenesis of multiple sclerosis (MS) by affecting the inflammatory response and reactive oxygen species production. LEP rs7799039 and LEPR rs1137101 genetic variants modify the serum LEP levels and PGC1A rs8192678 alters the PGC1A activity. The study objective was to explore the associations of these variants with susceptibility to MS, disease course/clinical parameters and also with peripheral blood mononuclear cell expression of the target genes and plasma LEP concentrations, in the study subjects.
The study groups included 528 patients with MS and 429 controls. TaqMan® assays were used for genotyping and gene expression quantification. The Chi-square, parametric and nonparametric tests and simple/multiple logistic regression were performed for the statistical analysis of data.
A multiple logistic regression model including all three investigated variants, applied to patients (RRMS + SPMS) and controls, showed that PGC1A rs8192678 minor allele had an increased risk for the occurrence of disease, with OR (95%CI) = 1,32 (1,01–1,73), P = 0,04. Between-effect of gender and LEPR variant on the multiple sclerosis severity score (MSSS) was identified (P = 0,005). In male patients (relapsing-remitting and secondary progressive), LEPR minor allele carriers had increased MSSS (GG + AG vs AA, median (minimum–maximum) = 5,38 (0,64–9,88) vs 4,27 (0,78–9,63); P = 0,01, Padj = 0,03). In relapsing-remitting patients LEP rs7799039 affected the LEP gene expression (P = 0,006; Padj = 0,04).
The current findings implicate an impact of investigated genetic variants on the pathogenesis of MS.
Febrilne konvulzije najčešći su konvulzivni poremećaj u djetinjstvu, zbog čega bi liječnici trebali biti upoznati s pravilnom procjenom i liječenjem ovoga uobičajenog stanja. Definira se kao bilo ...koji napadaj popraćen vrućicom, bez infekcije središnjega živčanog sustava, koji se javlja kod djece između šest mjeseci i pet godina. U upotrebi je pet kriterija prema kojima se klasificiraju kao jednostavne ili složene febrilne konvulzije. Ova klasifikacija nudi drugačije smjernice za kliničku praksu, poglavito odluku o provođenju lumbalne punkcije kako bi se isključila intrakranijalna infekcija. Hrvatsko društvo za dječju neurologiju izradilo je 2012. godine prve smjernice za racionalnu dijagnostiku i terapiju febrilnih konvulzija koje su trebale biti izvedive u svim bolničkim ustanovama u Republici Hrvatskoj. Iako su smjernice bile od velike pomoći mnogim kliničarima, dobivanjem novih medicinskih dokaza i razumijevanjem kliničkih entiteta koju se prezentiraju febrilnim konvulzijama, a variraju od samolimitirajućeg poremećaja bez dugoročnih posljedica preko samoograničavajućih i medikamentima kontroliranih entiteta pa sve do teških epileptičkih encefalopatija, nove smjernice pridonose postavljanju dijagnoze u hitnoj ambulanti, uključuju preporuke o hospitalizaciji, primjeni elektroencefalografije, neuroslikovnih pretraga, profilaksi diazepamom i antipireticima. Iako nove smjernice sadrže nove kliničke preporuke, ostavljaju neka neriješena pitanja na koja buduća klinička istraživanja trebaju ponuditi odgovore.
Epilepsy is one of the most common chronic diseases in children, and cannot be controlled with conventional antiepileptic drugs in 30% of cases. Therefore, in these cases, alternative approach such ...as corticosteroid therapy (CT) is used. The aim of this study was to analyze different types of CT used to treat drug-resistant childhood epilepsies, treated at Rijeka University Hospital Centre during a 5-year period (2016-2020). This retrospective study included 32 patients. The following parameters were analyzed: number of patients with a particular diagnosis, average age (in months) at the onset of epilepsy, average epilepsy duration (in months) prior to CT, average number of antiepileptic drugs used prior to CT, presence of changes on magnetic resonance imaging (MRI), presence of comorbidities, and types of CT. The average age at the onset of epilepsy was 14 months and average epilepsy duration prior to CT was 16 months. On average, 5 antiepileptic drugs were used prior to CT. MRI changes were present in 53.13% and comorbidities in 81.25% of study patients. Prednisone therapy was used in 28.13%, combined therapy with prednisone and methylprednisolone in 65.63%, and methylprednisolone in 6.25% of patients. Study results revealed the use of CT for particular diagnosis to differ among the centers, as well as within the same center, so it is important to highlight the importance of reaching universal guidelines for CT therapy of childhood epilepsies.
: The incidence of severe and moderate forms of DKA as the initial presentation of type 1 diabetes mellitus (T1D) is increasing, especially during the COVID-19 pandemic. This poses a higher risk of ...developing cerebral edema as a complication of diabetic ketoacidosis (DKA), as well as morbidity and mortality rates. The aim of this study was to determine the trend and clinical features of children treated in the last 10 years in the Pediatric Intensive Care Unit (PICU) due to the development of DKA.
: This retrospective study was performed in the PICU, Clinical Hospital Centre Rijeka, in Croatia. All children diagnosed with DKA from 2011-2020 were included in this study. Data were received from hospital medical documentation and patient paper history. The number of new cases and severity of DKA were identified and classified using recent International Society for Pediatric and Adolescent Diabetes (ISPAD) guidelines.
: In this investigation period, 194 children with newly diagnosed T1D were admitted to our hospital: 58 of them were treated in the PICU due to DKA; 48 had newly diagnosed T1D (48/58); and ten previously diagnosed T1D (10/58). DKA as the initial presentation of T1D was diagnosed in 24.7% (48/194). Moderate or severe dehydration was present in 76% of the children at hospital admission. Polyuria, polydipsia, and Kussmaul breathing were the most common signs. Three patients (5.2%) developed cerebral edema, of whom one died.
: During the investigation period a rising trend in T1D was noted, especially in 2020. About one quarter of children with T1D presented with DKA at initial diagnosis in western Croatia, most of them with a severe form. Good education of the general population, along with the patients and families of children with diabetes, is crucial to prevent the development of DKA and thus reduce severe complications.
Leptin (LEP) may contribute to the pathogenesis of multiple sclerosis (MS) by its immunomodulatory, proinflammatory and prooxidant effects. Therefore, plasma LEP levels and mRNA expression of five ...genes related to the LEP signaling pathway (LEP, LEP receptor (LEPR), peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PGC1A), superoxide dismutase 2, tumor necrosis factor-alpha) were investigated in relapsing-remitting MS. In patients (N = 64), compared to healthy subjects (N = 62), relative LEP mRNA levels were significantly increased (p = 0,01), while LEPR and PGC1A mRNA levels were decreased (p = 0,001 and p = 0,04, respectively). Significant positive correlation was observed between LEPR mRNA levels and clinical parameters of MS progression (EDSS, MSSS).
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•Significantly higher pLEP is observed in female than in male RRMS patients.•PBMC LEP mRNA is significantly increased in patients, compared to controls.•PBMC LEPR and PGC1A mRNAs are significantly lower in patients than in controls.•Positive correlation is observed between LEPR mRNA levels and both EDSS and MSSS.
Rano suzbijanje, prekidanje epileptičkih napadaja središnji je stup u strategiji njihova liječenja. Većina epileptičkih napadaja događa se izvan medicinske ustanove, najčešće u kućnom okruženju. ...Stoga smo izradili i predložili ovaj algoritam zbrinjavanja motoričkih/konvulzivnih epileptičkih napadaja u izvanbolničkom okruženju, prvenstveno s ciljem pružanja uniformne informacije i edukacije roditelja/skrbnika te za olakšavanje snalaženja liječnicima primarne zdravstvene zaštite i timovima hitne medicinske pomoći. Za potrebe pisanja ovog rada analizirali smo i sintetizirali postojeće smjernice u cilju preporuke jednostavnog, razumljivog i racionalnog terapijskog algoritma koji savjetujemo i primjenjujemo kao službeni algoritam preporuka naše ustanove. U njegovoj izradi usmjerili smo se na svjetske i nacionalne preporučene algoritme kao i dostupne studije koje su, koliko je to moguće, temeljene na dokazima. Prema našim saznanjima ovo je prvi pisani nacionalni algoritam takve vrste te do sada nisu postajale pisane smjernice/upute za liječenje epileptičkih napadaja, produljenih epileptičkih napadaja i epileptičkog statusa u izvanbolničkom okruženju uzimajući u obzir dostupnost, racionalnost i primjenjivost pojedinih lijekova u izvanbolničkim uvjetima, uvažavajući kliničku praksu u Republici Hrvatskoj. Sukladno navedenom,
primjena benzodiazepina (BZD), vremenski jasno definirana, smatra se prvom linijom liječenja epileptičkog napadaja. Izvanbolnička primjena BZD-a, prvenstveno midazolama za orkomukuznu primjenu ili diazepama za rektalnu primjenu, povezana je s kraćim trajanjem generaliziranih konvulzivnih napadaja, smanjenjem vjerojatnosti ponavljajućih napadaja i smanjenjem broja posjeta hitnoj pomoći. Ukoliko napadaj potraje >3 minuta, svakako je potrebno žurno primijeniti jedan od BZD-a, pod pretpostavkom da ga se posjeduje (midazolam oromukozno – prednost! ili diazepam rektalno), te isto ponoviti u slučaju daljnjeg trajanja napadaja duljeg od pet minuta te pozvati/alarmirati sustav hitne medicinske pomoći. Uz provođenje mjera održavanja vitalnih funkcija potrebno je inzistirati na intravaskularnom pristupu za ponovljenu primjenu BZD-a, no doza BZD-a može se ponoviti intramuskularno. U rijetkim slučajevima može se primijeniti fenobarbiton intramuskularno, kao i levetiracetam intravenozno, a u slučaju izostanka njihova učinka započeti s primjenom midazolama u trajnoj infuziji. Dostupnost primjerenih oblika BZD-a, sukladno smjernicama, u izvanbolničkom okruženju kao i njihova pravilna uporaba – pravodobna primjena i odgovarajuće doziranje početkom napadaja – dva su ključna koraka prema poboljšanju
cjelokupne zdravstvene skrbi u djece s visokim rizikom za pojavu epileptičkih napadaja i djece s epilepsijom. Navedeno ujedno predstavlja i pravovremeno suzbijanje produljenih epileptičkih napadaja i prevenciju epileptičkog statusa.
Prenatal exposure of long chain polyunsaturated fatty acids (LCPUFA) are essential for normal fetal growth and neurodevelopment. Availability of LCPUFA depends mostly on maternal fish consumption. ...Fish consumption also exposes the fetus to mercury which is well known neurotoxicant. We analyzed the associations of combined LCPUFA and mercury from fish consumption during pregnancy on newborn's brain measures and child neurodevelopment in a northern Adriatic coastal area.
The prospective cohort study included 257 mother – infant pairs enrolled in a susceptible population of the Public Health Impact on long-term, low-level, Mixed Element exposure (PHIME) EU Sixth Framework Programme from 2 recruitment areas of the northern part of the Adriatic coast. Umbilical cord blood taken at delivery was used for measuring concentration of total mercury (THg) and specific LCPUFA - docosahexaenoic acid (DHA) and arachidonic acid (ARA). Neonatal cranial sonography was performed at the age of 3 days in 57 newborns. Neurodevelopmental assessment of cognitive, motor and language skills were conducted at 257 children at the age of 18 months using the Bayley Scales of Infant and Toddler Development, Third Edition. The participants were divided into two groups depending on the THg concentration in the umbilical cord blood (exposed > 5.8 μg/L and unexposed < 5.8 μg/L). Dietary habits and exposures to environmental and social factors were assessed through questionnaires.
There is a statistically significant difference in the cerebellum length (p = 0.032) and the superior frontal gyrus width (p = 0.023) between the exposed and the unexposed group. In combined analysis, including possible protective variables as DHA and ARA (R2 = 0.22, p = 0.001), the negative contribution of THg on cerebellum length (beta = −0.16, p = 0.001) persisted. We found no correlation between THg concentration in umbilical cord blood and child neurodevelopment scores at the age of 18 months. Language score with receptive and expressive subscores was significantly associated with fish consumption (p < 0.05).
This analysis demonstrates the existence of morphological brain changes in newborns that are prenatally exposed at mercury concentrations what was diminished in combined analyse including LCPUFA. Our results emphasizes the importance of LCPUFA's and mercury common influence as a predictor of developmental outcome. Fish consumption, not solely LCPUFA contributes to better language development of children at the age of 18 months.
•Fish consumption enables the availability of LCPUFA but also exposes to neurotoxic mercury.•Results showed negative contribution of mercury on cerebellum length in combined analysis with LCPUFA.•No correlation between mercury concentration and child neurodevelopment scores at the age of 18 months.•Language score positively correlated with prenatally fish consumption.
Foods and food products that contain polyphenols are proposed to modulate risk of cardiovascular disease. The aim of this three-arm, crossover, randomized, double-blind, placebo-controlled ...intervention study was to examine the impact of
juice (AMJ), high-polyphenol (AMJ treatment, 1.17 g/100 mL polyphenols) and low-polyphenol (dAMJ treatment, 0.29 g/100 mL polyphenols) dose, on the transcriptome in peripheral blood mononuclear cells (PBMC) of 19 subjects at cardiovascular risk. Transcriptome data were obtained by microarray. Bioinformatic functional annotation analysis was performed on both the whole transcriptome datasets and the differentially expressed genes (DEGs). Expression of selected DEGs was validated by RT-qPCR. Administration of AMJ and dAMJ treatments during the two consecutive four-week treatment periods had additive effects on PBMC transcriptome profiles, with the most pronounced and specific effect noticed for AMJ in the last treatment period (TP3) of the trial. Between the high-dose and low-dose treatments in TP3, there was a multitude of overlapping DEGs and DEG-enriched biological processes and pathways, which primarily included immunomodulation and regulation of cell proliferation/death. Increased expression of
,
,
,
,
, and
in TP3 was confirmed by RT-qPCR. The results suggest the immunomodulatory effects of prolonged habitual consumption of polyphenol-rich aronia juice in individuals at cardiovascular risk.
Chronic otitis media (COM) is followed by irreversible tissue damage and destruction of the middle ear structures, with the possibility of complications under the maintenance of inflammation. ...Inflammatory mediators such as cytokines play a crucial role in the initial stage of inflammation. The aim of this study was to evaluate the association of the polymorphisms in two innate immunity/inflammation cascade genes from interleukin-1 (IL-1) gene cluster with COM with regard to cholesteatoma.
In the cross-sectional case-control study, DNA samples were collected from 189 patients with COM and 119 controls from a population of Serbia. The +3953 C/T (rs1143634), TaqI polymorphism in interleukin-1 beta (IL-1β) gene and 86 bp variable number tandem repeat (VNTR, rs2234663) polymorphism in the IL-1 receptor antagonist (IL-1RA) gene were analyzed by polymerase chain reaction.
The IL-1β TaqI polymorphism was not significantly different in patients compared with the control group. The significant difference between patients and controls was observed for both, genotype and allele frequencies of IL-1RA VNTR polymorphism (chi-square
<0.01). We found that carriers of IL-1RA allele 2 (odds ratio, 0.47; 95% confidence interval, 0.29 to 0.76;
=0.004) have a favorable association with COM, using multivariate logistic analysis that included both polymorphisms, age and sex. The IL-1RA allele frequency distribution was significantly different with regard to cholesteatoma.
The carriers of allele 2 of VNTR IL-1RA polymorphism had a decreased odds ratio for COM, which is in agreement with findings in other inflammatory disease and its previous association with higher IL-1RA levels. Possible down-regulation of IL-1 mediated proinflammatory signaling pathways via IL-1RA in COM as well as results of our study should be further investigated and replicated.
Semi-hard cheese was made from fresh domestic cow milk and treated with pumpkin seed oil and coffee during its ageing. The energy value and composition of the cheese were examined by determining the ...content of dry matter, minerals, proteins, fat, caffeine and fatty acids. During the ageing period, the cheese was dipped into a sweet, freshly-prepared, high-quality coffee drink and coated with a mixture of milled coffee grains and cold pressed pumpkin seed oil to improve the sensory properties of the cheese, but also to improve its nutritional value. It is considered that treated cheese could have greater nutritional and pro-health properties then untreated cheese, due to nutritional and healing properties of pumpkin seed oil and coffee used during the maturation period. Pumpkin seed oil contains carbohydrates, minerals, proteins, and important unsaturated fatty acids, while coffee is rich in antioxidants and helps in the prevention of type 2 diabetes, Parkinson's and Alzheimer's disease, and high cholesterol. To determine the impact of the treatment, the fatty acid and caffeine contents were determined by the GC-FID and the UPLC-DAD method. The cheese treated with pumpkin seed oil and coffee had a higher amount of unsaturated fatty acids (UFA) and a lower amount of saturated fatty acids (SFA) than the untreated cheese. The proportions of long-chain UFA, such as the C18:2n6c (Omega 6) and the C18:3n3 (Omega 3), were higher in the treated cheese than those in the untreated cheese, as well as the C20:1, the C22:2 and the C24:1, which were not detected in the untreated cheese. Caffeine concentration in the treated cheese was 33.08 mg/L.
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