Effect of partial and substantial denervation of locus coeruleus upon cocaine- and apomorphine-induced locomotion in rats

In the present study the effect of denervation of locus coeruleus (LC) upon cocaine and apomorphine induced locomotion and monoamine concentration in frontal cortex and hippocampus in rats were investigated. 72 male Wistar rats were divivded into three groups: 1) one third were injected with 50 mg/kg dose of neurotoxin DSP-4; 2) one third were injected with 10 mg/kg dose of DSP-4, to create respectively substantial and partial denervation of LC; 3) control group. In every group, one third of rats were injected with cocaine and one third with apomorphine to affect locomotion, and one third with distilled water. It was demonstrated that the substantial denervation (50 mg/kg DSP-4) of LC reduced cocaine-induced locomotion but did not have any effect on apomorphine-induced locomotion. Also, LC denervation affects at the most noradrenergic system, but has also noticeable effect on serotonergic and dopaminergic system. Keywords: cocaine, apomorphine, locomotion, Wistar rats, locus coeruleus, DSP-4, monoamineshttp://tartu.ester.ee/record=b2596662~S1*es

Mendelian Randomization Identifies the Potential Causal Impact of Dietary Patterns on Circulating Blood Metabolites

Nutrition plays an important role in the development and progress of several health conditions, but the exact mechanism is often still unclear. Blood metabolites are likely candidates to be mediating these relationships, as their levels are strongly dependent on the frequency of consumption of several foods/drinks. Understanding the causal effect of food on metabolites is thus of extreme importance. To establish these effects, we utilized two-sample Mendelian randomization using the genetic variants associated with dietary traits as instrumental variables. The estimates of single-nucleotide polymorphisms’ effects on exposures were obtained from a recent genome-wide association study (GWAS) of 25 individual and 15 principal-component dietary traits, whereas the ones for outcomes were obtained from a GWAS of 123 blood metabolites measured by nuclear magnetic resonance spectroscopy. We identified 413 potentially causal links between food and metabolites, replicating previous findings, such as the association between increased oily fish consumption and higher DHA, and highlighting several novel associations. Most of the associations were related to very-low-density, intermediate-density (IDL), and low-density lipoproteins (LDL). For example, we found that constituents of IDL particles and large LDL particles were raised by coffee and alcohol while lowered by an overall healthier diet and fruit consumption. Our findings provide a strong base of evidence for planning future RCTs aimed at understanding the role of diet in determining blood metabolite levels

A catalogue of omics biological ageing clocks reveals substantial commonality and associations with disease risk

Biological age (BA), a measure of functional capacity and prognostic of health outcomes that discriminates between individuals of the same chronological age (chronAge), has been estimated using a variety of biomarkers. Previous comparative studies have mainly used epigenetic models (clocks), we use ~1000 participants to compare fifteen omics ageing clocks, with correlations of 0.21-0.97 with chronAge, even with substantial sub-setting of biomarkers. These clocks track common aspects of ageing with 95% of the variance in chronAge being shared among clocks. The difference between BA and chronAge - omics clock age acceleration (OCAA) - often associates with health measures. One year’s OCAA typically has the same effect on risk factors/10-year disease incidence as 0.09/0.25 years of chronAge. Epigenetic and IgG glycomics clocks appeared to track generalised ageing while others capture specific risks. We conclude BA is measurable and prognostic and that future work should prioritise health outcomes over chronAge

Food neophobia associates with poorer dietary quality, metabolic risk factors, and increased disease outcome risk in population-based cohorts in a metabolomics study

Background: Food neophobia is considered a behavioral trait closely linked to adverse eating patterns and reduced dietary quality, which have been associated with increased risk of obesity and noncommunicable diseases. Objectives: In a cross-sectional and prospective study, we examined how food neophobia is associated with dietary quality, health-related biomarkers, and disease outcome incidence in Finnish and Estonian adult populations. Methods: The study was conducted based on subsamples of the Finnish DIetary, Lifestyle, and Genetic determinants of Obesity and Metabolic syndrome (DILGOM) cohort (n = 2982; age range: 25-74 y) and the Estonian Biobank cohort (n = 1109; age range: 18-83 y). The level of food neophobia was assessed using the Food Neophobia Scale, dietary quality was evaluated using the Baltic Sea Diet Score (BSDS), and biomarker profiles were determined using an NMR metabolomics platform. Disease outcome information was gathered from national health registries. Follow-up data on the NMR-based metabolomic profiles and disease outcomes were available in both populations. Results: Food neophobia associated significantly (adjusted P <0.05) with health-related biomarkers [e.g., omega-3 (n-3) fatty acids, citrate, alpha(1)-acid glycoprotein, HDL, and MUFA] in the Finnish DILGOM cohort. The significant negative association between the severity of food neophobia and omega-3 fatty acids was replicated in all cross-sectional analyses in the Finnish DILGOM and Estonian Biobank cohorts. Furthermore, food neophobia was associated with reduced dietary quality (BSDS: beta: -0.03 +/- 0.006; P = 8.04 x 10(-5)), increased fasting serum insulin (beta: 0.004 +/- 0.0013; P = 5.83 x 10(-3)), and increased risk of type 2 diabetes during the similar to 8-y follow-up (HR: 1.018 +/- 0.007; P = 0.01) in the DILGOM cohort. Conclusions: In the Finnish and Estonian adult populations, food neophobia was associated with adverse alteration of health-related biomarkers and risk factors that have been associated with an increased risk of noncommunicable diseases. We also found that food neophobia associations with omega-3 fatty acids and associated metabolites are mediated through dietary quality independent of body weight.Peer reviewe

Toitumine, vere metaboliidid ja tervis

Väitekirja elektrooniline versioon ei sisalda publikatsiooneTäpsem arusaam, kuidas ja mille kaudu toitumine tervist mõjutab, loob soodsa pinnase tervist edendavatele personaliseeritud toitumissoovitustele. Üks võimalus toitumise ja tervise vaheliste seoste selgitamiseks on uurida veres ringlevate metaboliitide tasemeid, kuna need on mõjutatud toitumisest ning on omakorda erinevate haiguste ennustajateks. Käesoleva doktoritöö eesmärgiks on anda vere metaboliitide uurimise kaudu lisateadmisi selle kohta, kuidas toitumine mõjutab tervist. Esmalt kasutasime Mendeli Randomiseerimise (MR) meetodit, et tuvastada, milline on toitumisvalikute potentsiaalselt põhjuslik mõju vere metaboliitidele. Kuna leitud tulemused ühtisid varasemate randomiseeritud uuringutega ning olid osalt vastuolus vaatlusuuringutega, tõestasime et MR on sobiv ja kasulik meetod toitumise mõju uurimiseks. Kokku leidsime 413 potentsiaalselt põhjuslikku seost. Muuhulgas viitavad tulemused, et nii kohvi kui ka alkohoolsete jookide suurem tarbimine tõstab madala ja keskmise tihedusega lipoproteiinidega seotud metaboliitide tasemeid, samas kui väga madala tihedusega lipoproteiinidega seotud metaboliitide tasemetele tundub mõju olevat vaid suuremal kohvi tarbimisel, aga mitte alkoholi tarbimisel. Teiseks vaatlesime toidu neofoobia (FN) ja vere metaboliitide vahelisi seoseid ning leidsime, et kõrgem tulemus FN skaalal seostub madalamate omega-3 rasvhapetega seotud mõõtmistega. Lisaks, FN mõju tüüp 2 diabeedile ja südameveresoonkonna haigustele vajab kinnitust tulevaste uuringute poolt, kuna mõlema haiguse osas oli FN riski tõstev mõju väljendunud vaid ühes vaadeldud kahest kohordist. Kolmandaks uurisime, kas vere metaboliitide profiil kirjeldab inimese bioloogilist vanust (BA) ning kas erinevus sellise BA ja kronoloogilise vanuse vahel ennustab tervisenäitajaid. Leidsime, et metaboliitide-põhine BA võib olla populatsiooni-spetsiifiline ning seostub kardiovaskulaarsete riskifaktoritega. Lisaks viitavad meie tulemused sellele, et metaboliitide-põhine BA võib olla seotud toitumiskäitumisega. Kokkuvõttes annavad leitud tulemused uusi teadmisi toitumise, metaboliitide ja tervise omavaheliste seoste kohta ning on seega aluseks tulevastele randomiseeritud uuringutele mis loovad omakorda pinnase teadlikele tervist edendavatele personaliseeritud toitumissoovitustele.Understanding the mechanisms of how diet affects health has the potential to provide grounds for personalized health-improving dietary advice. One possible option to enlighten the diet-disease interplay is to examine the blood metabolic profile, since it is known to be on the one hand affected by diet and on the other hand predictive of several health outcomes. Consequently, the aim of this thesis is to shed more light on how diet affects health by examining the metabolic profile of blood. Firstly, we studied the possibly causal effect of dietary choices on blood metabolites by using the method of Mendelian Randomization (MR). We demonstrated that MR approach is suitable for analyzing the effect of diet by our results agreeing with previous randomized trials and conflicting with some observational studies. In total we detected 413 potentially causal associations. For example, we found that coffee and alcohol traits pose similar elevating effects on measurements related to low-density and intermediate-density lipoproteins, whereas the measurements related to very-low-density lipoproteins seem to be elevated by coffee consumption and not by alcohol consumption. Secondly, we investigated the associations between food neophobia (FN) and blood metabolites, and found that FN is negatively associated with measurements related to omega-3 fatty acids. Additionally, the analysis of the effect of FN on type II diabetes and coronary heart disease yielded conflicting results between the two cohorts studied and the risk-elevating effects remain to be confirmed by future research. Thirdly, we examined whether blood metabolic profile is indicative of underlying biological age (BA), and whether the excess of such BA over the chronological age is predictive of health outcomes. We found that the metabolites-based BA can be population-specific, and is associated with cardiovascular risk factors. Further, our results propose that the metabolites-based BA can be associated with dietary behavior. In conclusion, our findings provide new knowledge about the diet, metabolites and health interplay and by this forms a basis for future randomized trials that can ultimately lead to well-informed personalized dietary recommendations.https://www.ester.ee/record=b550783

Competency in the management of women of childbearing age with epilepsy among primary care and specialist doctors in Estonia

Objective: Although abundant new information has emerged in the last decade(s) on the management of women with epilepsy (WWE), whether said knowledge has reached clinical practice remains largely unknown. We assessed knowledge of this matter among primary care and specialist doctors in Estonia. Methods: This study was conducted via an online questionnaire, which was used to explore healthcare specialists’ awareness in five domains: pre-pregnancy counseling, contraception, side effects of antiseizure medications (ASMs), and the management of epilepsy during pregnancy and in the peri- and postpartum periods. Results: The survey response rate was low − 8.14%. Knowledge of epilepsy management in WWE was inconsistent among different medical specialists. The median numbers of correctly answered questions among gynecologists, neurologists, and general practitioners were 7, 6.5, and 3 of 10, respectively. Gynecologists were more informed about appropriate contraceptive methods. Neurologists were more familiar with ASM side effects. General practitioners’ knowledge level for this topic was low. Surprisingly, only 30.8% of general practitioners were aware of the high teratogenic potential of valproate. Conclusions: We observed significant knowledge gaps regarding the optimal treatment of WWE of reproductive age. To improve epilepsy management, doctors’ awareness of treatment considerations for this patient group needs to be increased

Nonmotor Features in Parkinson’s Disease: What Are the Most Important Associated Factors?

Introduction. The purpose of this study was to demonstrate the frequency and severity of nonmotor symptoms and their correlations with a wide range of demographic and clinical factors in a large cohort of patients with Parkinson’s disease (PD). Methods. 268 PD patients were assessed using the validated Movement Disorders Society’s Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), the Beck Depression Inventory (BDI), Parkinson’s Disease Questionnaire (PDQ-39), the Hoehn and Yahr scale (HY), the Schwab and England Activities of Daily Living (SE-ADL) Scale, and the Minimental State Examination (MMSE). Results. Nonmotor symptoms had a strong positive relationship with depression and lower quality of life. Also, age, duration and severity of PD, cognitive impairment, daily dose, and duration of levodopa treatment correlated with the burden of nonmotor symptoms. Patients with postural instability and gait disorder (PIGD) dominance or with the presence of motor complications had higher MDS-UPDRS Part I scores expressing the load of nonmotor features, compared to participants with other disease subtypes or without motor complications. Conclusions. Though the severity of individual nonmotor symptoms was generally rated by PD patients as “mild” or less, we found a significant cumulative effect of nonmotor symptoms on patients’ mood, daily activities, and quality of life

Mortality in young adult patients with acute ischaemic stroke

Eesti Arst 2020; 99(8):50