The Association of Time of Day of ChAdOx1 nCoV-19 Vaccine Administration With SARS-CoV-2 Anti-Spike IgG Antibody Levels: An Exploratory Observational Study.

Data from human and animal studies are highly suggestive of an influence of time of day of vaccine administration on host immune responses. In this population-based study, we aimed to investigate the effect of time of day of administration of a COVID-19 vector vaccine, ChAdOx1 nCoV-19 (AstraZeneca), on SARS-CoV-2 anti-spike S1 immunoglobulin (IgG) levels. Participants were 803 university employees who received their first vaccine dose in March 2021, had serology data at baseline and at 3 weeks, and were seronegative at baseline. Antibody levels were determined in binding antibody units (BAU/mL) using enzyme-linked immunosorbent assay (ELISA). Generalized additive models (GAM) and linear regression were used to evaluate the association of time of day of vaccination continuously and in hourly bins with antibody levels at 3 weeks. Participants had a mean age of 42 years (SD: 12; range: 21-74) and 60% were female. Time of day of vaccination was associated non-linearly ("reverse J-shape") with antibody levels. Morning vaccination was associated with the highest (9:00-10:00 h: mean 292.1 BAU/mL; SD: 262.1), early afternoon vaccination with the lowest (12:00-13:00 h: mean 217.3 BAU/mL; SD: 153.6), and late afternoon vaccination with intermediate (14:00-15:00 h: mean 280.7 BAU/mL; SD: 262.4) antibody levels. Antibody levels induced by 12:00-13:00 h vaccination (but not other time intervals) were significantly lower compared to 9:00-10:00 h vaccination after adjusting for potential confounders (beta coefficient = -75.8, 95% confidence interval [CI] = -131.3, -20.4). Our findings show that time of day of vaccination against SARS-CoV-2 has an impact on the magnitude of IgG antibody levels at 3 weeks. Whether this difference persists after booster vaccine doses and whether it influences the level of protection against COVID-19 needs further evaluation.

Ionizing radiation and volumetric mammographic density.

OBJECTIVES: Mammographic density (MD) refers to the percentage of dense tissue of an entire breast and was proposed to be used as a surrogate marker for breast cancer. High-dose ionizing radiation (IR) has been recognized as a breast cancer risk factor. The aim of our study was to investigate association between lifetime low dose ionizing radiation (LDIR) and MD. MATERIAL AND METHODS: A cross-sectional study included 467 women aged 40-60 years who underwent screening mammography in Lódz, Poland. The digital mammography examination of the breasts included both craniocaudal and mediolateral oblique views. The volumetric breast density (VBD) (%) and fibrograndular tissue volume (FG) (cm3) were determined based on the analysis of mammographic image ("for processing") using Volpara Imaging Software. The exposure to IR was estimated for each individual, based on the data from interviews about diagnostic or therapeutic medical procedures performed in the area of the neck, chest, abdomen and spine, which involved X-rays and γ rays and the data about the doses derived from literature. Linear and logistic regression were fitted with VBD and FG as the outcomes and organ breast dose, effective dose and number of mammographies as the determinants, adjusted for major confounders. RESULTS: The analyses showed no association between VBD or FG and the breast organ dose or the effective dose. The only significant finding observed concerned the association between the number of mammographies and the FG volume with ß coefficient: 0.028 (95% CI: 0.012-0.043), and predicted mean FG volume >13.4 cm3 among the women with >3 mammographies when compared to those with none. CONCLUSIONS: This study does not, in general, provide support for the positive association between LDIR and MD. The weak association of the FG volume with the number of mammographies warrants further verification in larger independent studies. Int J Occup Med Environ Health. 2022;35(5):635-49.

The association of age at menarche and adult height with mammographic density in the International Consortium of Mammographic Density.

BACKGROUND: Early age at menarche and tall stature are associated with increased breast cancer risk. We examined whether these associations were also positively associated with mammographic density, a strong marker of breast cancer risk. METHODS: Participants were 10,681 breast-cancer-free women from 22 countries in the International Consortium of Mammographic Density, each with centrally assessed mammographic density and a common set of epidemiologic data. Study periods for the 27 studies ranged from 1987 to 2014. Multi-level linear regression models estimated changes in square-root per cent density (√PD) and dense area (√DA) associated with age at menarche and adult height in pooled analyses and population-specific meta-analyses. Models were adjusted for age at mammogram, body mass index, menopausal status, hormone therapy use, mammography view and type, mammographic density assessor, parity and height/age at menarche. RESULTS: In pooled analyses, later age at menarche was associated with higher per cent density (ß√PD = 0.023 SE = 0.008, P = 0.003) and larger dense area (ß√DA = 0.032 SE = 0.010, P = 0.002). Taller women had larger dense area (ß√DA = 0.069 SE = 0.028, P = 0.012) and higher per cent density (ß√PD = 0.044, SE = 0.023, P = 0.054), although the observed effect on per cent density depended upon the adjustment used for body size. Similar overall effect estimates were observed in meta-analyses across population groups. CONCLUSIONS: In one of the largest international studies to date, later age at menarche was positively associated with mammographic density. This is in contrast to its association with breast cancer risk, providing little evidence of mediation. Increased height was also positively associated with mammographic density, particularly dense area. These results suggest a complex relationship between growth and development, mammographic density and breast cancer risk. Future studies should evaluate the potential mediation of the breast cancer effects of taller stature through absolute breast density.

Cigarette smoking and mammographic breast density among Polish women.

OBJECTIVES: High mammographic breast density (MBD) is one of the strongest breast cancer risk factors. The results of some epidemiological studies suggest that one of the lifestyle factors likely altering breast density is cigarette smoking. The aim of this study was to assess the association between active smoking, considering in detail the duration and intensity of smoking, and MBD among Polish women. MATERIAL AND METHODS: A cross-sectional study included 467 women aged 40-60 years who underwent screening mammography in Lódz, Poland. Volumetric mammographic density, fibroglandular tissue volume and non-fibroglandular tissue volume were determined based on the analysis of mammographic image (in the "for processing" format) using Volpara Imaging Software. Current and lifetime intensity of cigarette smoking was assessed based on the data from interviews. Linear and logistic regressions were fitted with estimated MBD parameters as the outcomes, and life-long smoking duration and intensity as the determinants, adjusted for major confounders. RESULTS: The former smokers had a significantly lower volumetric mammographic density compared to the non-smokers in the crude analysis (p = 0.022). However, the associations became insignificant after adjustments for important confounding factors. The analyses adjusted for important confounders revealed an inverse statistically significant association between the number of pack-years and volumetric mammographic density among the current smokers (p = 0.048). CONCLUSIONS: The observed result is consistent with the majority of previous studies that analyzed the associations between mammographic density and life-long smoking duration. Int J Occup Med Environ Health. 2021;34(6):805-15.

The Second-to-Fourth Digit (2D:4D) Ratio of Male Combat Athletes is Associated with the Choice of Sport.

The second-to-fourth-digit (2D:4D) ratio has been widely used as a putative marker of prenatal exposure to testosterone in health, behavioral and sport sciences, but it has only been used few times regarding combat athletes. This study involved 200 male elite combat athletes (Olympic wrestling, kickboxing, judo, taekwondo and karate) and 179 males not participating in any sports. The lengths of the index finger (2D) and ring (4D) finger were measured using computer-assisted image analysis (AutoMetric 2.2 software). The 2D:4D ratio of combat athletes was significantly lower than that of the controls. Moreover, a lower 2D:4D ratio was found among wrestlers, judo athletes and kickboxers than in the control group, and a higher 2D:4D ratio was found, but with borderline significance, among karate and taekwondo athletes. Moreover, multivariate analysis adjusted for age showed that judo, Olympic wrestling and kickboxing athletes combined had 2D:4D ratios significantly lower (by 0.035 on average) than those of the rest of the subjects and that karate and taekwondo athletes together had 2D:4D ratios significantly higher (by 0.014 on average) than those of the rest of the subjects. The research results and literature review indicate that knowledge about the functional meaning of the 2D:4D ratio is still too fragmentary and it is too early to use the 2D:4D ratio in the selection of sport talent; however, it may be a useful criteria when screening prospective athletes to be recruited to a team. That is why 2D:4D reference values should be defined for particular sports.

Common Myelin Regulatory Factor Gene Variants Predisposing to Excellence in Sports.

In all sport disciplines, excellent coordination of movements is crucial for achieving mastery. The ability to learn new motor skills quickly and effectively is dependent on efficient myelination which varies between individuals. It has been suggested that these differences may play a role in athletic performance. The process of myelination is under transcriptional control by Myelin Regulatory Factor (MYRF) as well as other transcription factors (SOX10 and OLIG2). We analyze a panel of 28 single nucleotide polymorphisms (SNPs) located within the frequencies of common variants of MYRF, SOX10 and OLIG2 genes in professional athletes compared to non-athletes. No significant differences were detected after correction for multiple testing by false discovery rate (FDR) for any of the models tested. However, some deviations from the expected distribution was found for seven SNPs (rs174528, rs139884, rs149435516 and rs2238001, rs7943728, rs61747222, and rs198459). The MYRF alleles rs7943728 and rs61747222 showed a correlation with the level of sport achievement among the athletes. Even though the athletes did not differ from the non-athlete controls in the distribution of most SNPs analyzed, some interesting differences of several variants were noted. Presented results indicate that genetic variants of MYRF and SOX10 could be genetic factors weakly predisposing for successful athletic performance.

Changes in the Hormonal Profile of Athletes following a Combat Sports Performance.

RESULTS: Following fighting, the adrenaline concentration was significantly higher in all athletes, most markedly in K (p < 0.001). Baseline cortisol and BDNF levels did not differ among the groups and rose significantly in all the groups after the performance. Baseline testosterone concentration was slightly higher in K than in JSW and rose in all the groups to reach similar levels; the increase in T was significantly higher than in K. CONCLUSIONS: Despite substantial differences in the characteristics of the combat sports investigated, including the type of physical effort and the required balance between restraint and aggression, the performance in each of them gives rise to similar hormonal changes with a possible exception of karate showing higher stress hormone levels.

Cadmium and volumetric mammographic density: A cross-sectional study in Polish women.

INTRODUCTION: Cadmium (Cd) is a heavy metal, which is widespread in the environment and has been hypothesized to be a metalloestrogen and a breast cancer risk factor. Mammographic density (MD) reflects the composition of the breast and was proposed to be used as a surrogate marker for breast cancer. The aim of our study was to investigate association between cadmium concentration in urine and mammographic density. METHODS: A cross-sectional study included 517 women aged 40-60 years who underwent screening mammography in Lódz, Poland. Data were collected through personal interviews and anthropometric measurements. Spot morning urine samples were obtained. The examination of the breasts included both craniocaudal and mediolateral oblique views. Raw data ("for processing") generated by the digital mammography system were analysed using Volpara Imaging Software, The volumetric breast density(%) and fibrograndular tissue volume(cm3) were determined. Cadmium concentration in urine was analysed using the standard ICP-MS method. RESULTS: After adjusting for key confounders including age, BMI, family breast cancer, mammographic device, season of the year of mammography, and age at menarche, an inverse association of Cd and volumetric breast density was found, which was attenuated after further adjustment for smoking. Associations of Cd with dense volume were null. CONCLUSIONS: These findings suggest that Cd is not positively associated with breast density, a strong marker of breast cancer risk, when examined in a cross-sectional fashion.

Night shift work and osteoporosis among female blue-collar workers in Poland - a pilot study.

Osteoporosis is an important public health problem worldwide. Although a number of factors that affect bone structure have been described; thus far, the current knowledge of occupational factors that may have an influence on bone tissue metabolism is strongly limited. Published studies indicate night shift work and the related circadian rhythm disruption may be considered as plausible underlying factors. The aim of the present study was to assess the potential association between night shift work and bone mineral density (BMD) among female blue-collar workers in Poland. A cross-sectional study was carried out among 194 female blue-collar workers >40 years of age employed in industrial plants. The operating system of work consisted of three work shifts clockwise rotation: morning (06:00-14:00 h), afternoon (14:00-22:00 h), and night (22:00-06:00 h), with five consecutive shifts per week followed by a free weekend. A questionnaire survey, based on a Polish version of The European vertebral osteoporosis study (EVOS) questionnaire, a validated instrument, was administered. Data on current job characteristics, job seniority, and lifetime duration of night shift work were also collected. BMD of the lumbar spine and hip (both total femur and femoral neck) was measured using dual-energy X-ray absorptiometry. Multivariate linear regression models were run, with bone mineralization parameters as dependent variables, as well as night work characteristics and important confounders. Statistical analysis was performed separately for premenopausal and postmenopausal women. The analyses adjusted for confounders did not reveal any significant differences between current or lifetime experience of night shift work and BMD among both premenopausal and postmenopausal women. However, the outcomes supported the well-established correlation with factors, such as age, BMI, and menopausal status. BMD at the three sites measured was significantly associated with BMI (p < .001) and inversely associated with age (p < .001) in the total study population. Postmenopausal women had significantly lower BMD than did premenopausal women (p < .001). The study findings indicate that in the population of Polish female blue-collar workers, the system of work does not seem to be associated with the development of osteoporosis.

Circadian Gene Polymorphisms Associated with Breast Cancer Susceptibility.

Breast cancer (BC) is a major problem for civilization, manifested by continuously increasing morbidity and mortality among women worldwide. Core circadian genes may play an important role in cancer development and progression. To evaluate the effects of single nucleotide polymorphism (SNP) in circadian genes in BC risk, 16 functional SNPs were genotyped in 321 BC patients and 364 healthy women using the TaqMan fluorescence-labelled probes or High-Resolution Melt Curve technique in the Real-Time PCR system. The selected SNPs were analyzed for the risk of BC, progression, and the influence on gene expression in BC tissue pairs to demonstrate the functionality of genetic variants. The study showed a relationship between an increased BC risk under the dominant genetic model of CRY2 rs10838524, PER2 rs934945, and recessive genetic model of PER1 rs2735611. A protective effect of BMAL1 rs2279287 was observed among carriers with at least one variant allele. Moreover, we found an increased risk of estrogen-/progesterone-positive tumors under the dominant genetic model of PER2 rs934945 and estrogen negative tumors under the variant genotype of CRY2 rs10838524, PER1 rs2735611. We demonstrated significantly altered gene expression of BMAL1, CRY2, PER1, PER2, PER3 according to particular genotypes in the BC tissue pairs. Our findings support the hypothesized role of circadian genes in breast carcinogenesis and indicate probable biomarkers for breast cancer susceptibility.

The association between night shift work and nutrition patterns among nurses: a literature review.

The shift work system may affect the temporal distribution of eating and diet quality. The paper aimed at reviewing a body of research examining the associations between night shift work and dietary habits among nurses. Data from the PubMed and Google Schoolar databases, as well as references lists in selected papers were searched. The authors used the following keywords: nurses, shift work, diet, nutrition. Papers published in English or Polish were selected for the review, and as many as 19 papers published in 2000-2017 were eventually identified. The studies varied greatly with respect to the study size, subjects' age and the duration of night shift work. The major problem was the heterogeneity of the tools used for dietary assessment. Self-administered questionnaires were used and analyses were rarely adjusted for confounders. Alcohol consumption was the most frequently analyzed aspect (N = 8 studies), followed by the total energy (N = 7), protein, fat (N = 6), and carbohydrate intake, coffee and fruit consumption (N = 5). The results showed quite a consistent association of night work with higher coffee (caffeine) consumption, as well as lower alcohol, and fruit and vegetables consumption. Few studies also reported more frequent snacks consumption, later time of the last meal, eating at night, meals irregularity, and a poorer diet quality among night shift nurses when compared to the reference. The review showed some poor nutritional habits among nurses working night shifts. However, the topic warrants further attention, owing to the relatively small number of the studies performed so far, and their numerous methodological limitations. Med Pr. 2019;70(3):363-76.

Rotating night shift work and nutrition of nurses and midwives.

Previous research points to some inappropriate nutritional habits among nurses working night shifts. However, the knowledge of specific nutritional components of their diet has been limited. In the present study, we aimed to investigate the association between rotating night shifts of nurses and midwives and their usual dietary intake of energy and nutrients. A cross-sectional study was conducted among 522 Polish nurses and midwives: 251 working rotating night shifts (i.e. working night shift followed by a day off on a subsequent day) and 271 day workers. Polish adaptation of the Food Frequency Questionnaire, regarding 151 food items, was used to assess the usual dietary energy and nutrient intake. Data on occupational history and potential confounders were collected via face-to-face interviews. Body weight, height, waist and hip circumference were measured. Linear regression models: univariate (crude) and multivariate (adjusted) were run, with the nutrient intake as dependent variables, night work characteristics, and important confounders. Among nurses and midwives working rotating night shifts, a significantly higher adjusted mean intake was found for the total energy (2005 kcal vs 1850 kcal) and total fatty acids (77.9 g vs 70.4 g) when compared to day workers, as well as for cholesterol (277 mg vs 258 mg), carbohydrates (266 g vs 244 g) and sucrose (55.8 g vs 48.6 g). Night shift work duration was inversely related to the consumption of calcium, phosphorus, vitamin A, vitamin C and % energy from proteins. The higher energy consumption may contribute to increase risk of overweight and obesity among nurses working night shifts.

Association of serotoninergic pathway gene variants with elite athletic status in the Polish population.

Genetic factors are known to influence sport performance. The aim of the present study was to assess genetic variants in genes coding for proteins potentially modulating activity of brain emotion centres in a group of 621 elite athletes (212 endurance, 183 power and 226 combat athletes) and 672 sedentary controls. Ten statistically significant variants were identified in genes encoding elements of serotoninergic, catecholaminergic and hypothalamic-pituitary-adrenal systems in different sport groups. Of those the rs860573 variant in the FEV gene coding for transcription factor exclusively expressed in neurons of the central serotonin system is the only one whose frequency significantly differentiates all the groups of athletes studied, regardless of discipline, from the controls (p = 0.000026). Our results support the hypothesis that genetic variants potentially affecting mental processes and emotions, particularly in the serotonergic pathway, also influence the predispositions to athletic performance.

Antibodies Against Chlamydia trachomatis and Ovarian Cancer Risk in Two Independent Populations.

BACKGROUND: Pelvic inflammatory disease (PID) has been associated with ovarian cancer risk. To clarify the role of Chlamydia trachomatis and other infectious agents in the development of ovarian cancer, we evaluated the association of serologic markers with incident ovarian cancer using a staged approach in two independent populations. METHODS: Studies included: 1) a case-control study in Poland (244 ovarian cancers/556 control subjects) and 2) a prospective nested case-control study in the PLCO Cancer Screening Trial (160 ovarian cancers/159 control subjects). Associations of serologic marker levels with ovarian cancer risk at diagnostic as well as higher thresholds, identified in Poland and independently evaluated in PLCO, were estimated using multivariable adjusted logistic regression. RESULTS: In the Polish study, antibodies (based on laboratory cut-point) against the chlamydia plasmid-encoded Pgp3 protein (serological gold standard) were associated with increased ovarian cancer risk (adjusted odds ratio [OR] = 1.63, 95% confidence interval [CI] = 1.20 to 2.22); when a positive result was redefined at higher levels, ovarian cancer risk was increased (cut-point 2: OR = 2.00, 95% CI = 1.38 to 2.89; cut-point 3 [max OR]: OR = 2.19, 95% CI = 1.29 to 3.73). In the prospective PLCO study, Pgp3 antibodies were associated with elevated risk at the laboratory cut-point (OR = 1.43, 95% CI = 0.78 to 2.63) and more stringent cut-points (cut-point 2: OR = 2.25, 95% CI = 1.07 to 4.71); cut-point 3: OR = 2.53, 95% CI = 0.63 to 10.08). In both studies, antibodies against other infectious agents measured were not associated with risk. CONCLUSIONS: In two independent populations, antibodies against prior/current C. trachomatis (Pgp3) were associated with a doubling in ovarian cancer risk, whereas markers of other infectious agents were unrelated. These findings lend support for an association between PID and ovarian cancer.

Night shift work and osteoporosis: evidence and hypothesis.

Osteoporosis is an important public health problem worldwide. Among the countries with a very high population risk of fractures, there are those with the highest level of economic development. Osteoporotic fractures are the main cause of disability among elderly people, and the resultant disabilities require particularly large financial support associated not only with the direct treatment of the fracture but also with the necessity for long-term rehabilitation and care for the disabled person. Many well-established factors can have impact on bone mass and fracture risk. Recently, it has been hypothesized that working during nighttime which leads to endocrine disorders may have an indirect impact on bone physiology among night shift workers. Therefore, it can be presumed that the night shift work may contribute to the etiology of osteoporosis. The aim of our work was to make a review of the epidemiological evidence on the association between night shift work and bone mineral density or fracture risk as well as to discuss the potential biological mechanisms linking the work under this system with the development of osteoporosis. We have identified only four studies investigating the association between system of work and bone mineral density or fracture risk among workers. The findings of three out of four studies support the hypothesis. None of the studies has investigated a potential relationship between night shift work and bone turnover markers. Given that there have been no epidemiological studies in European countries that would concern working populations and the noticeable difference in the risk of osteoporosis between communities, further studies are warranted to elucidate the problem. It is presumed that further in-depth studies will not only identify the underlying factors of the disease but also contribute to developing guidelines for policy makers and employers for primary prevention of osteoporosis in workplace.

[The prophylactic operational model integrated with occupational healthcare - Prophylactic of some types of cancers among women]. / Model dzialan profilaktycznych zintegrowany z opieka profilaktyczna nad pracownikami ­ zapobieganie niektórym typom nowotworów wsród kobiet.

Periodical medical examinations are mandatory for employees in Poland. This rule makes a unique opportunity during occupational health services for implementation of prophylactic activities focused on early diagnosis of various diseases, including cancers. Epidemiological data about cancers is alarming and what is more, further increase in development of cancers is being predicted in population overall. The highest incidence of cancers in the case of Polish women belongs to breast cancer (21.7% of diagnosed cancers in general), while the morbidity rate for uterine cancer, ovarian cancer and cervical cancer amounts to 7.4%, 4.7% and 3.5%, respectively. The aim of this study was to elaborate an algorithm of prophylactic activities integrated with the occupational healthcare system, based on medical literature review and guidelines concerning prophylaxis of selected cancers. Polish cancers' prophylaxis programs related to risk factors were presented in this publication and practical indications for occupational healthcare physicians were worked out. Med Pr 2018;69(4):439-455.

Regulatory region single nucleotide polymorphisms of the apolipoprotein E gene as risk factors for Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by a complex aetiology. The ε4 allel of the apolipoprotein E gene (APOE) is the only confirmed genetic risk factor for the development of AD. In addition, polymorphisms at the promoter region of the APOE gene are assumed to modulate the susceptibility to AD by their different affinity to the transcription factors thus affecting the expression of the gene. In the presented study, we investigated the association between -491 A/T (rs449647), -427C/T, (rs769446) and -219 T/G (rs405509) single nucleotide polymorphisms (SNPs) of APOE gene and AD risk in the Polish population. We found that only the -491 T allele and -491 A/T genotype acted as protective factors against AD, whereas the -219 T/G heterozygosity increased risk for AD in APOE ε4 carriers but not in APOE ε4 non-carriers. What is more, haplotype frequency estimation showed significant positive for A-T-T-C-C and A-T-G-C-C haplotypes or negative for A-T-T-T-C and T-T-T-T-C haplotypes associations with AD. These results contribute to the evidence that APOE promoter polymorphisms modulate risk for AD.

Hypermethylation of TRIM59 and KLF14 Influences Cell Death Signaling in Familial Alzheimer's Disease.

Epigenetic mechanisms play an important role in the development and progression of various neurodegenerative diseases. Abnormal methylation of numerous genes responsible for regulation of transcription, DNA replication, and apoptosis has been linked to Alzheimer's disease (AD) pathology. We have recently performed whole transcriptome profiling of familial early-onset Alzheimer's disease (fEOAD) patient-derived fibroblasts. On this basis, we demonstrated a strong dysregulation of cell cycle checkpoints and DNA damage response (DDR) in both fibroblasts and reprogrammed neurons. Here, we show that the aging-correlated hypermethylation of KLF14 and TRIM59 genes associates with abnormalities in DNA repair and cell cycle control in fEOAD. Based on the resulting transcriptome networks, we found that the hypermethylation of KLF14 might be associated with epigenetic regulation of the chromatin organization and mRNA processing followed by hypermethylation of TRIM59 likely associated with the G2/M cell cycle phase and p53 role in DNA repair with BRCA1 protein as the key player. We propose that the hypermethylation of KLF14 could constitute a superior epigenetic mechanism for TRIM59 hypermethylation. The methylation status of both genes affects genome stability and might contribute to proapoptotic signaling in AD. Since this study combines data obtained from various tissues from AD patients, it reinforces the view that the genetic methylation status in the blood may be a valuable predictor of molecular processes occurring in affected tissues. Further research is necessary to define a detailed role of TRIM59 and KLF4 in neurodegeneration of neurons.

TREM2 variants in neurodegenerative disorders in the Polish population. Homozygosity and compound heterozygosity in FTD patients.

Activation of the TREM2 receptor on microglia stimulates phagocytosis and decreases the microglial proinflammatory response. Mutations in exon 2 of the TREM2 gene have been reported to be associated with various neurodegenerative diseases characterized by chronic inflammation. The aim of our study was to evaluate exon 2 of TREM2 gene variants as a putative genetic risk factor for Alzheimer's disease (AD), frontotemporal dementia (FTD), and amyotrophic lateral sclerosis (ALS) in the Polish population. The results were interpreted using previously published data, especially highlighting differences in the prevalence of the variants among Caucasian subpopulations across different geographic regions. The DNA sequence of exon 2 of TREM2 was analyzed in 811 subjects (274 AD, 135 FTD, 194 ALS patients, and 208 neurologically healthy controls). Nine heterozygous variants were detected, including two novel ones: p.G29 = and c.41-2_3insA, found respectively in a control and an ALS patient. Additionally, we identified one homozygous and two compound heterozygous FTD patients. We confirm previous data that homozygous and compound heterozygous TREM2 mutations can be causative for FTD.