Serum Amyloid Biomarkers, Tau Protein and YKL-40 Utility in Detection, Differential Diagnosing, and Monitoring of Dementia.

Introduction: The diagnosis and treatment of dementia is one of the greatest challenges in contemporary health care. The widespread use of dementia biomarkers would improve the quality of life of patients and reduce the economic costs of the disease. The aim of the study was to evaluate the usefulness of proteins related to the Alzheimer's disease pathogenesis-amyloid beta isoform (Aß) and total tau protein (t-tau), as well as the quite recently discovered marker YKL-40 in the most common types of dementia. Methods: 60 dementia (AD-Alzheimer's disease, VaD-vascular dementia, MxD-mixed dementia) and 20 cognitively normal subjects over 60 years old were examined. Subjects with dementia of etiology different than AD or VaD and with neoplastic or chronic inflammatory diseases were excluded. Concentrations of Aß40, Aß42, t-tau, and YKL-40 were measured in serum using ELISA kits on admission and after 4 weeks of inpatient treatment. ANOVA and Tukey's test or Dunn's test were used to perform comparison tests between groups. Correlations were measured using Pearson's coefficient. Biomarker diagnostic utility was assessed with ROC analysis. Results: YKL-40 differentiates between cognitively normal and mild dementia patients with 85% sensitivity and specificity and t-tau with 72% sensitivity and 70% specificity. YKL-40 and t-tau concentrations correlate with each other and with the severity of clinically observed cognitive decline. Conclusions: YKL-40 is a sensitive and specific biomarker of early dementia and, to a lesser extent, of dementia progression, however, many comorbidities may influence its levels. In such conditions, less specific but still reliable t-tau may serve as an alternative marker. Obtained results did not confirm the diagnostic utility of amyloid biomarkers.

Salivary Carbohydrate-Deficient Transferrin in Alcohol- and Nicotine-Dependent Males.

Serum carbohydrate-deficient transferrin (CDT), an 80 kDa glycoprotein, is one of the most commonly employed biomarkers to detect alcohol dependence. Some salivary glycoproteins such as α-amylase, clusterin, haptoglobin, light/heavy-chain immunoglobulin, and transferrin, which alter glycosylation in alcohol-dependent persons, have been suggested to be potential alcohol markers. However, their identification is based on indirect analysis of lectin glycosidic bonds and molecular weight. We investigated the CDT content in the saliva of alcohol- and nicotine-dependent men. The CDT concentration (ng/mL, ng/mg protein) was determined by an Enzyme-Linked Immunosorbent Assay (ELISA) commercial kit in 55 men: 20 healthy social drinkers (C), 10 chronic cigarette smokers (S), 10 alcohol-dependent non-smokers (A), and 15 alcohol-dependent smokers (AS). Surprisingly, there were no differences in the concentrations of CDT between the studied groups. Salivary pH was the lowest in the AS and the highest in the A group. Therefore, salivary CDT cannot be used as an alcohol dependence marker as measured by ELISA. We suggest that direct identification of glycoproteins is necessary to search for potential salivary alcohol biomarkers. Molecules smaller than 40 kDa, which easily translocate from blood to the saliva, might be preferred as salivary alcohol markers.

Diagnostic Utility of Selected Serum Dementia Biomarkers: Amyloid ß-40, Amyloid ß-42, Tau Protein, and YKL-40: A Review.

INTRODUCTION: Dementia is a group of disorders that causes dysfunctions in human cognitive and operating functions. Currently, it is not possible to conduct a fast, low-invasive dementia diagnostic process with the use of peripheral blood biomarkers, however, there is a great deal of research in progress covering this subject. Research on dementia biomarkers in serum validates anticipated health and economic benefits from early screening tests. Biomarkers are also essential for improving the process of developing new drugs. METHODS: The result analysis, of current studies on selected biomarker concentrations (Aß40, Aß42, t-tau, and YKL-40) and their combination in the serum of patients with dementia and mild cognitive disorders, involved a search for papers available in Medline, PubMed, and Web of Science databases published from 2000 to 2020. RESULTS: The results of conducted cross-sectional studies comparing Aß40, Aß42, and Aß42/Aß40 among people with cognitive disorders and a control group are incoherent. Most of the analyzed papers showed an increase in t-tau concentration in diagnosed Alzheimer's disease (AD) patients' serum, whereas results of mild cognitive impairment (MCI) groups did not differ from the control groups. In several papers on the concentration of YKL-40 and t-tau/Aß42 ratio, the results were promising. To date, several studies have only covered the field of biomarker concentrations in dementia disorders other than AD. CONCLUSIONS: Insufficient amyloid marker test repeatability may result either from imperfection of the used laboratorial techniques or inadequate selection of control groups with their comorbidities. On the basis of current knowledge, t-tau, t-tau/Aß42, and YKL-40 seem to be promising candidates as biomarkers of cognitive disorders in serum. YKL-40 seems to be a more useful biomarker in early MCI diagnostics, whereas t-tau can be used as a marker of progress of prodromal states in mild AD. Due to the insignificant number of studies conducted to date among patients with dementia disorders other than AD, it is not possible to make a sound assessment of their usefulness in dementia differential diagnostics.

Selective mutism - an overview of the condition and etiology: is the absence of speech just the tip of the iceberg? / Mutyzm wybiórczy ­ opis zaburzenia i etiologia: czy wybiórczy brak mowy jest zaledwie wierzcholkiem góry lodowej?

The inability to speak in certain situations, as one may briefly characterize selective mutism (SM), according to the most recent classifications (DSM-5, ICD-11) belongs to the anxiety disorder spectrum. The onset of mutism in early childhood may impair further development and adversely affect educational achievements. It is essential that psychiatrists, as well as other physicians, speech therapists, nurses and teachers are familiar with this disorder, since the early start of treatment is associated with better prognosis. This literature review aims to present the contemporary view of this relatively rare psychopathological syndrome. In light of most recent studies on the etiology of SM, the sole symptom of mutism appears to represent an underlying heterogenic group of disorders. Based on the developmental psychopathology, the interrelations between overlapping abnormalities favor SM manifestation in some crucial moment in an individual's life. The etiologic complexity strongly suggests multimodal approach in the diagnostic and treatment process, which has been postulated by many authors.

KIR and HLA-C genes in male infertility.

PURPOSE: Approximately 50% of men reporting to clinics for assisted reproduction have abnormal sperm parameters; we therefore considered whether they differ from fertile males in terms of the frequency of KIR and HLA-C genes, suggesting the involvement of NK cells and some T cells in the inflammatory reaction that can occur in the testes, vas deferens, or epididymis. METHOD: We tested a total of 1064 men: 445 of them were patients who, together with their female partners, participated in in vitro fertilization (IVF), 298 men whose female partners suffered from recurrent spontaneous abortion. Three hundred twenty-one fertile men constituted the control group. KIRs were genotyped using KIR Ready Gene kits and HLA-C by PCR-SSP methods. RESULTS: We found differences in KIR gene frequencies between men who became fathers via natural conception and men who participated in in vitro fertilization for KIR2DL2 (p/pcorr. = 0.0015/0.035, OR = 1.61), KIR2DL5 gr.2 (p/pcorr. = 0.0023/0.05, OR = 1.64), KIR2DS2 (p/pcorr. = 0.0019/0.044, OR = 1.59), and KIR2DS3 (p/pcorr. = 0.0016/0.037, OR = 1.67). KIRs in Cen AA region were significantly overrepresented in fertile males than in IVF males (p/pcorr. = 0.0076/0.03, OR = 0.67), whereas Cen AB + Cen BB frequency was higher in IVF males than in fertile males (p/pcorr. = 0.0076/0.03, OR = 1.50). We also observed a limited association in KIR-HLA-C combinations. CONCLUSION: Fertile men differ in profile of KIR genes and KIR-HLA-C combinations from men participating in IVF.

Is the TAP2 single nucleotide polymorphism rs241447 truly associated with psoriasis in Poles?

Psoriasis vulgaris (PsV) is strongly associated with HLA-C*06:02. HLA class I molecules present antigenic peptides to CD8+ T lymphocytes. Peptide transport from cytosol to the endoplasmic reticulum is mediated by a transporter associated with antigen processing (TAP) composed of TAP1 and TAP2 polymorphic proteins. Here, we compared the distribution of three coding single nucleotide polymorphisms (SNPs), rs1057141 in TAP1 and rs1800454 and rs241447 in TAP2 as well as the HLA-C*06:02 allele in 438 patients diagnosed with PsV and 493 control individuals. In patients and controls non-stratified by HLA-C*06:02, TAP2 rs241447 was associated with PsV but other TAP1 and TAP2 SNPs were not. By contrast, stratification according to the Svejgaard and Ryder formula, as well as a logistic regression approach and haplotype analysis demonstrated that the effect of TAP2 rs241447 was entirely related to the presence of HLA-C*06:02. The secondary effect of TAP2 rs241447 in relation to primary effect of HLA-C*06:02 resulted from linkage disequilibrium (albeit not strong) between both markers. We conclude that joint coexistence of HLA-C*06:02 and the TAP2 rs241447C risk allele on the extended haplotype might explain the effect of TAP2 observed by us.

Designer drugs ­ still a threat?

INTRODUCTION: In Poland, an increasing number of psychoactive substances are becoming prohibited by law as psychotropic or narcotic substances, or as new psychoactive substances (NPSs). Owing to the enormous technological possibilities offered by today's science, synthesis of new derivatives of prohibited compounds is no longer a problem. The moment a dangerous substance is outlawed, new designer drugs (in Poland known as 'dopalacze') appear on the market. STATE OF KNOWLEDGE: An amendment to the Act on Counteracting Drug Addiction issued in July 2018 made it possible for the NPS to be considered drugs by law. Synthetic cannabinoids and cathinone derivatives make up the majority of NPSs identified by the authorities in Poland. Synthetic cannabinoids which can, unlike cannabinoid receptor agonists of plant origin, cause death by somatic toxicity, are particularly dangerous. The ability to quickly recognize poisoning with synthetic opioids is crucial, since an antidote reversing the depressive effect of opioids on the respiratory center can be administered. SUMMARY: This work collects the most important and up-to-date information on designer drugs, based on reports and articles published between 2015 and 2019. The covered aspects include: the current definition of designer drugs in relation to the Polish law, their exact division due to the clinical effects they cause and the description of the threats they pose. Emphasis was given to the current situation of the designer drug market in Poland.

Letter to Editor. The importance of anxiety component in the etiopathogenesis of selective mutism, classified as an "anxiety and fear-related disorder" in the upcoming 11th Revision of the International Classification of Diseases. Substantive comments. Comment on the article The controversy around the diagnosis of selective mutism - a critical analysis of three cases in the light of modern research and diagnostic criteria by Justyna Holka-Pokorska et al. / List do redakcji. Znaczenie skladowej lekowej w etiopatogenezie mutyzmu wybiórczego, klasyfikowanego jako "zaburzenie lekowe i zwiazane ze strachem", w planowanej do wdrozenia 11. wersji Miedzynarodowej Klasyfikacji Chorób ICD. Uwagi merytoryczne. Komentarz do artykulu Justyny Holki-Pokorskiej i wsp. Kontrowersje wokól diagnozy mutyzmu wybiórczego ­ krytyczna analiza trzech przypadków w swietle wspólczesnych badan oraz kryteriów diagnostycznych.

no summary.

ERAP1-ERAP2 haplotypes are associated with ankylosing spondylitis in Polish patients.

The objective of this case-control study was to evaluate the role of four single-nucleotide polymorphisms in the ERAP1 (rs2287987, rs30187, rs27044) and ERAP2 (rs2248374) genes and their haplotypes in predicting the risk for ankylosing spondylitis (AS) on a well-defined Polish population. Our study confirmed the strong association between the HLA-B*27 allele and the disease. For all tested ERAP1 SNPs we found significant differences in the minor allele and genotype distribution between patients and controls. The strongest association with AS was observed for rs30187. The minor T allele and homozygous TT genotype of this SNP significantly increased disease risk (OR = 1.56, 95%CI = 1.22-1.99, p = 0.0004 and OR = 2.52, 95%CI = 1.50-4.25, p = 0.001, respectively). In the case of rs2287987, minor C allele exerted a protective effect (OR = 0.64, 95%CI = 0.46-0.88, p = 0.008). In contrast to ERAP1, we observed no effect of rs2248374 in ERAP2 on the disease. We also carried out ERAP1-ERAP2 haplotype analysis to demonstrate a possible association of both genes with AS. Results showed that the haplotype H4, containing ERAP1 SNPs associated with high enzymatic activity, together with the presence of ERAP2 expression, significantly increased the risk of AS (OR = 1.97, 95% CI = 1.21-3.21, pcorr = 0.048). By contrast, the haplotype H5 coding for low activity of ERAP1 and the lack of ERAP2 expression was strongly protective (OR = 0.41, 95% CI = 0.23-0.72, pcorr = 0.008).

ERAP, KIR and HLA-C gene interaction in susceptibility to recurrent spontaneous abortion in the Polish population.

Endoplasmic reticulum aminopeptidases ERAP1 and ERAP2 trim peptides to generate stable antigenic epitopes for their presentation by HLA class I (HLA-I) molecules to T cell receptor. By influencing the peptide repertoire of HLA-I molecules, they affect also the interactions of HLA-I with killer cell immunoglobulin-like receptors (KIRs) of natural killer (NK) cells. HLA-C is the only polymorphic HLA-I molecule present on the trophoblast. In this study we investigated the role of ERAP1 and ERAP2 polymorphisms in the context of KIR and HLA-C genes in women suffering from recurrent spontaneous abortion (RSA) in the Polish population. We used TaqMan genotyping assays for ERAP1 rs27044, rs30187, rs2287987, rs26618, rs2665 and ERAP2 rs2248374; PCR-SSP methods for KIR and HLA-C genotyping. We tested 285 women who experienced recurrent spontaneous abortion (RSA) and 319 fertile women. We observed a significant association of ERAP1 rs30187TT genotype with RSA (p = 0.02, OR = 1.89, 95%CI = 1.11-3.21), however the most striking association was found in comparison of patients and controls with ERAP1 rs30187TT and KIR Bx genotypes (p = 0.006, pcorr. = 0.036, OR = 2.40, 95%CI = 1.27-4.52). Moreover, this effect was even stronger in HLA-C2 positive patients (p = 0.0031, pcorr. = 0.019, OR = 3.46, 95%CI = 1.48-8.11). Other weaker associations of the remaining tested ERAP single nucleotide polymorphisms with RSA were also presented. In conclusion, ERAP1 rs30187TT genotype itself increased susceptibility to RSA but this effect was much stronger in patients positive for HLA-C2 and KIR Bx genotypes.

In search of optimal psychoactivation: stimulants as cognitive performance enhancers.

An increasing number of people, students in particular, seek substances that improve their cognitive functioning. The most popular group of pharmacological cognitive enhancers (PCEs) are stimulants. Available studies suggest a small beneficial effect of methylphenidate and amphetamine on memory, executive functions, and processing speed. However small, this effect can make the difference between success and failure. In recent years, research has focused on the additional beneficial effect on the emotional state, increased motivation, and placebo-induced cognitive enhancement. This paper briefly reviews the latest and most important research on the relationship between popular stimulants and cognitive enhancement. One cannot understand this relationship without understanding the Yerkes-Dodson law, which explains the relationship between the degree of arousal and performance. It suggests that the effect of stimulants is a dose-dependent continuum. This law has repeatedly been confirmed by studies in which an optimal level of psychoactivation for cognitive enhancement was obtained with low stimulant doses, whereas exceeding the effective dose resulted in cognitive deficits, psychomotor agitation, and addiction. A separate section has been devoted to modafinil, an increasingly popular stimulant that differs from the rest in neurochemical profile and behavioural effects.

Association of Soluble HLA-G Plasma Level and HLA-G Genetic Polymorphism With Pregnancy Outcome of Patients Undergoing in vitro Fertilization Embryo Transfer.

Infertility is currently a growing problem observed around the world and is estimated to affect between 8 and 12% of reproductive-aged couples worldwide. Artificial reproductive techniques are the last chance for couples seeking their own child. Human leukocyte antigen (HLA)-G expression has been suggested as an immunomodulatory molecule that influences pregnancy outcome. The HLA-G gene encodes either membrane-bound or/and soluble proteins. The aim of this study was the evaluation of the role of soluble HLA-G (sHLA-G) and its gene polymorphism in successful implantation after in vitro fertilization embryo transfers (IVF-ETs) in different clinical protocols. We tested the HLA-G polymorphism in three positions: rs1632947: c.-964G>A; rs1233334: c.-725G>C/T in promoter region; rs371194629: c.*65_*66insATTTGTTCATGCCT in 3' untranslated region of exon 8, in 389 patients who underwent IVF-ETs and 320 women with healthy children born after natural conception. Among the patient group, 239 women were with recurrent implantation failure and 117 women had an ongoing pregnancy or a child born after IVF-ET. We found that certain rs1632947-rs1233334-rs371194629 HLA-G haplotypes and diplotypes were associated with infertility, while others were protective. The lowest secretors of sHLA-G were G-C-ins haplotype carriers (37.21 IU/ml), while the highest -G-C-del carriers (73.80 IU/ml). Other haplotype carriers were intermediate secretors. In our study, regardless of possessed haplotype by the patient, 59.73 IU/ml sHLA-G was the threshold value with the best sensitivity (58.82%) and specificity (66.10%) to discriminate patients who achieved and maintained pregnancy from those who did not conceive or they had miscarriage (p = 0.0085; likelihood ratio, 1.74; 95% CI = 0.55-0.78). However, we do not exclude that factors other than sHLA-G may also contribute to complications in pregnancy. In addition, we found that IVF patients in cycles when frozen/thawed embryo was transferred secreted higher soluble HLA-G levels than patients with fresh embryo transferred (p = 0.021). Moreover, correlation analysis of sHLA-G concentration measured before and after embryo transfer for particular patients indicated short ovarian stimulation with gonadotropin-releasing hormone antagonist as more beneficial than long protocol with gonadotropin-releasing hormone agonist. Our study confirms a role of HLA-G polymorphism in infertility and soluble HLA-G in the early stages of pregnancy.

Morphological changes of the brain in mood disorders. / Zmiany morfologiczne mózgu w zaburzeniach nastroju.

Brain morphological changes in affective disorders occur mainly in the fronto-limbic cortex, hippocampus and amygdala - the structures regulating emotional and cognitive functioning, as well as development of somatic symptoms in the course of disorders. The largest number of reports of structural changes in the cerebral cortex include the dorsolateral prefrontal cortex, the orbitofrontal cortex and the anterior cingulate cortex. The results of neuroimaging and sectional studies reveal changes in the volume of structures involved in the creation of neuronal circuits that affect development of mood disorders. Microscopic studies show changes in cell count, density, and morphology in these areas. Some of those changes are observed only in certain layers of the cerebral cortex. A valuable addition to this data are histochemical studies of neuronal survival markers, proinflammatory cytokines, trophic factors, and markers specific for particular cellular structures. The role of monoaminergic, GABA-ergic and glutamatergic neurotransmission is confirmed by the studies on concentration of neurotransmitters, their receptors and transporters. Some of the results correlate quantitatively with the type and severity of symptoms, duration of the disorder, as well as pharmacotherapy and nonpharmacological treatment.

Neurobiological Effects of Binge Drinking Help in Its Detection and Differential Diagnosis from Alcohol Dependence.

The prevalence of binge drinking in the general population is 3-4 times higher than that of alcohol dependence. Neuroimaging studies show that binge drinking in adolescence impairs brain development and white matter integrity. Regions with reduced functional activity include the limbic system, ventral diencephalon, frontal lobe, and middle and inferior temporal lobes, whereas the right superior frontal and parietal lobes are typically hyperactivated. The observed activation of the frontoparietal areas might reflect the alternative memory system operating, whereas the reduced occipito-hippocampal response is associated with impaired visual and linguistic processing/learning. Some other findings from literature research include a decrease of N-acetylaspartate (NAA) in the frontal lobe and its increase in the parietal lobes, as well as the reduced components of event-related potentials, reflecting deficit in attention, working memory, inhibition, and executive functioning. Animal studies show that even a single day of binge drinking results in a neurodegeneration and reactive gliosis in the limbic cortex as well as in gene expression dysregulation and histone acetylation. Another biological evidence on binge drinking effect include inflammatory response, oxidative stress, formation of toxic ceramides, activation of caspase 3, and secretion of corticoliberin. Some of the binge drinking-induced cognitive abnormalities can be reversible after three weeks of abstinence. Although binge drinkers have a similar pattern of neuropsychological deficits with chronic alcohol consumers (mainly memory deficits), binge drinkers have prominent impairment of inhibitory control, which may be a marker of binge pattern of alcohol drinking. The optimal therapeutic strategies should target the inhibitory control processes to facilitate discontinuation of alcohol consumption and to block its possible progression to the alcohol dependence syndrome.

The assessment of the nutritional value of meals consumed by patients with recognized schizophrenia

Background: As studies show, changes in diet - so important in the therapy of psychiatric disorders and related to changes in appetite and nutritional preferences, including avoiding of the consumption of specific groups of products and dishes - are much more frequent among patients affected by schizophrenia. Objective: The aim of the study was to assess the chosen nutritional habits, including the number and type of meals usually consumed during a day, snacking between meals and the energy value and content of the chosen nutrients in the diets of persons with recognized schizophrenia. Material and methods: The study was carried out in a group of 85 patients with recognized schizophrenia, and 70 healthy volunteers ranging in age from 18-65 years without mental or nutritional disorders. For the purpose of the study, we used a questionnaire containing questions on nutritional habits. A 24-hour diet recall was used in the quantitative nutritional assessment with the use of the computer program Dieta 5.0. Results: Female patients with recognized schizophrenia were having 3 meals a day significantly more frequently as compared to healthy women. They were also having an afternoon snack much more frequently as compared to the control group. The food rations of female patients were characterized by a significantly higher energy value and the content of most of the assessed nutrients as compared to the food rations of healthy women. The food rations of men with recognized schizophrenia were characterized by a much lower energy intake and the content of the majority of assessed nutrients as compared to the food rations of healthy men. In all compared groups, we observed an energetic structure of food rations with the breakdown by specific meals that was inconsistent with the applicable recommendations. Conclusions: Despite of differences between the nutritional value of the meals of patients with recognized schizophrenia and those of healthy subjects, it seems advisable to involve patients with recognized schizophrenia in the education of forming appropriate nutritional habits.

The impact of HLA-G, LILRB1 and LILRB2 gene polymorphisms on susceptibility to and severity of endometriosis.

Endometriosis is a disease in which endometriotic tissue occurs outside the uterus. Its pathogenesis is still unknown. The most widespread hypothesis claims that ectopic endometrium appears as a result of retrograde menstruation and its insufficient elimination by immunocytes. Some reports have shown expression of non-classical HLA-G molecules on ectopic endometrium. HLA-G is recognized by KIR2DL4, LILRB1 and LILRB2 receptors on natural killer (NK) and other cells. These receptors are polymorphic, which may affect their activity. In this study we investigated whether HLA-G, KIR2DL4, LILRB1 and LILRB2 polymorphisms may influence susceptibility to endometriosis and disease progression. We used polymerase chain reaction (PCR), PCR-restriction fragment length polymorphism (PCR-RFLP) and allelic discrimination methods with TaqMan SNP Genotyping Assays for typing of 276 patients with endometriosis and 314 healthy fertile women. The HLA-G rs1632947:GG genotype was associated with protection against the disease and its severe stages; HLA-G rs1233334:CT protected against progression; LILRB1 rs41308748:AA and LILRB2 rs383369:AG predisposed to the disease and its progression. No effect of KIR2DL4 polymorphism was observed. These results support the role of polymorphisms of HLA-G and its receptors LILRB1 and LILRB2 in susceptibility to endometriosis and its progression.

The methylenetetrahydrofolate reductase c.c.677 C>T and c.c.1298 A>C polymorphisms in reproductive failures: Experience from an RSA and RIF study on a Polish population.

Almost 1600 individuals from the Polish population were recruited to this study. Among them 319 were fertile couples, 289 were recurrent spontaneous abortion (RSA) couples, and 131 were in the group of recurrent implantation failure (RIF) following in vitro fertilization. The aim of this study was to evaluate the MTHFR c.c.677 C>T and c.c.1298 A>C polymorphisms' association with RSA and RIF. We used PCR-RFLP with HinfI (677 C>T) and MboII (1298 A>C) digestion. We observed a protective effect of the female AC genotype (OR = 0.64, p = 0.01) and the C allele (AC+CC genotypes; OR = 0.65, p = 0.009) against RSA. Moreover, 1298 AA/677 CT women were more frequent in RSA (31.14%) and RIF (25.20%) groups in comparison to fertile women (22.88%), although this difference was significant only in the case of RSA (p = 0.022, OR = 1.52). Male combined genotype analysis revealed no association with reproductive failure of their partners. Nevertheless, the female/male combination AA/AC of the 1298 polymorphism was more frequent in RSA couples (p = 0.049, OR = 1.49). However, the significant results became insignificant after Bonferroni correction. In addition, analysis of haplotypes showed significantly higher frequency of the C/C haplotype (1298 C/677 C) in the female control group than in the female RSA group (p = 0.03, OR = 0.77). Moreover, the association between elevated homocysteine (Hcy) level in plasma of RSA and RIF women and MTHFR polymorphisms was investigated but did not reveal significant differences. In conclusion, for clinical practice, it is better to check the homocysteine level in plasma and, if the Hcy level is increased, to recommend patients to take folic acid supplements rather than undergo screening of MTHFR for 1298 A>C and 677 C>T polymorphisms.

Antioxidant Defence, Oxidative Stress and Oxidative Damage in Saliva, Plasma and Erythrocytes of Dementia Patients. Can Salivary AGE be a Marker of Dementia?

Oxidative stress plays a crucial role in dementia pathogenesis; however, its impact on salivary secretion and salivary qualities is still unknown. This study included 80 patients with moderate dementia and 80 healthy age- and sex-matched individuals. Salivary flow, antioxidants (salivary peroxidase, catalase, superoxide dismutase, uric acid and total antioxidant capacity), and oxidative damage products (advanced oxidation protein products, advanced glycation end products (AGE), 8-isoprostanes, 8-hydroxy-2'-deoxyguanosine and total oxidant status) were estimated in non-stimulated and stimulated saliva, as well as in plasma and erythrocytes. We show that in dementia patients the concentration/activity of major salivary antioxidants changes, and the level of oxidative damage to DNA, proteins and lipids is increased compared to healthy controls. Non-stimulated and stimulated salivary secretions were significantly reduced in dementia patients. The deterioration in mini mental state examination (MMSE) score correlated with salivary AGE levels, which when considered with receiver operating characteristic (ROC) analysis, suggests their potential role in the non-invasive diagnosis of dementia. In conclusion, dementia is associated with disturbed salivary redox homeostasis and impaired secretory function of the salivary glands. Salivary AGE may be useful in the diagnosis of dementia.

KIR, LILRB and their Ligands' Genes as Potential Biomarkers in Recurrent Implantation Failure.

Reproductive failure in humans is a very important social and economic problem, because nowadays women decide to conceive later in life and delay motherhood. Unfortunately, with increasing age they have less chance for natural fertilization and maintenance of pregnancy. Many of them need assisted reproductive technology. Approximately 10% of women after in vitro fertilization-embryo transfers experience recurrent implantation failure (RIF). Multiple factors may contribute to RIF, including oocyte and sperm quality, parental chromosomal anomalies, genetic or metabolic abnormalities of the embryo, poor uterine receptivity, immunological disturbances in the implantation site, and some gynecologic pathologies such as endometriosis, uterine fibroids, hydrosalpinx and endometrial polyps. Moreover, the procedure of in vitro fertilization itself could adversely influence the implantation. Nowadays, many studies are focused on the role of natural killer (NK) cells in normal and pathologic pregnancy because NK cells constitute the dominant cell population in the endometrium and they come in close contact with the allogeneic extravillous trophoblast cells in early pregnancy decidua. The majority of these cells are of CD56bright phenotype. These cells can express killer immunoglobulin-like receptors (KIRs), which, upon recognition of HLA class I molecules (HLA-C and HLA-G) on trophoblasts, may either stimulate or inhibit NK cells to produce soluble factors, and display low cytotoxicity necessary for maintenance of the allogeneic embryo and fetus in the next steps of pregnancy. Moreover, some members of the leukocyte immunoglobulin-like receptor (LILR) family, also named ILT (immunoglobulin-like transcript), are present in the human placenta. LILRB1 (ILT2) was described mainly on stromal cells, while LILRB2 (ILT4), in addition to stromal cells, was also found around vessels in the smooth muscle layer. In this review we focus on the possible role of polymorphism of KIR, LILRB and their ligands (HLA-C, HLA-G) in susceptibility to recurrent implantation failure, which could serve as diagnostic biomarkers of this disease.