Cerebellar extinction lesions can manifest themselves with cerebellar motor and cerebellar cognitive affective syndromes. For investigation of the functions of the cerebellum and the pathogenesis of cerebellar diseases, particularly hereditary neurodegenerative cerebellar ataxias, various cerebellar mutant mice are used. The Lurcher mouse is a model of selective olivocerebellar degeneration with early onset and rapid progress. These mice show both motor deficits as well as cognitive and behavioral changes i.e., pathological phenotype in the functional domains affected in cerebellar patients. Therefore, Lurcher mice might be considered as a tool to investigate the mechanisms of functional impairments caused by cerebellar degenerative diseases. There are, however, limitations due to the particular features of the neurodegenerative process and a lack of possibilities to examine some processes in mice. The main advantage of Lurcher mice would be the expected absence of significant neuropathologies outside the olivocerebellar system that modify the complex behavioral phenotype in less selective models. However, detailed examinations and further thorough validation of the model are needed to verify this assumption.
- MeSH
- cerebelární ataxie genetika patofyziologie patologie MeSH
- lidé MeSH
- modely nemocí na zvířatech * MeSH
- mozeček patologie patofyziologie MeSH
- myši - mutanty neurologické MeSH
- myši MeSH
- nemoci mozečku * patologie patofyziologie genetika MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
BACKGROUND: Nutrient deficiencies during pregnancy may affect offspring development. We aim to examine the association between prenatal vitamin B12 intake and children's cognitive development. METHODS: A total of 5151 mother-child pairs from the Czech part of ELSPAC study were included in the analysis. Dietary information was obtained during pregnancy using food frequency questionnaire. Parents reported on their child's speech and language development at 18 months, 3, 5 and 7 years. Intelligence quotient (IQ) was measured at 8 years in subcohort of 854 children. RESULTS: Children of mothers with higher vitamin B12 intake demonstrated higher scores in language (B = 0.20, 95% CI 0.06, 0.34) and talking and understanding (B = 2.39, 95% CI 0.97, 3.80) in a fully adjusted model at 18 months. Additionally, they were more likely to get maximum points in the intelligibility test at age 3 (OR = 1.05, 95% CI 1.01, 1.09) in unadjusted model, however, not in fully adjusted model. We found a positive effect of higher vitamin B12 intake on verbal IQ (B = 1.08, 95% CI 0.09, 2.08). CONCLUSIONS: We identified consistent associations between prenatal vitamin B12 intake and children's cognitive development. The results suggest that inadequate vitamin B12 during pregnancy may negatively affect children's cognitive development, particularly in speech and language.
- MeSH
- dítě MeSH
- dospělí MeSH
- inteligence * MeSH
- inteligenční testy * MeSH
- kojenec MeSH
- lidé MeSH
- předškolní dítě MeSH
- těhotenství MeSH
- vitamin B 12 * MeSH
- vývoj dítěte MeSH
- vývoj řeči MeSH
- zpožděný efekt prenatální expozice MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- kojenec MeSH
- lidé MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
Background/Objectives: Several gene targets were identified for psoriasis. Some are currently being explored as potential therapeutic targets, including CCL11. Our task was to prove a possible association of single-nucleotide polymorphisms +67 G/A and -426 T/C in the eotaxin gene (CCL11, 17q 21.3) with the development and clinical aspects of psoriasis as an immune-based dermatological disease and evaluate its relationship to potential comorbidities. Material and Methods: In total, 460 patients with psoriasis were included in the case-control and genotype-phenotype study together with 167 control persons of similar age and sex distributions without a personal and/or family history of chronic disease of the skin. Two eotaxin gene polymorphisms were detected from isolated DNA via standard PCR, restriction analysis methods, and horizontal electrophoresis. Results: No significant case-control differences in the frequency of the CCL11 genotype in both polymorphisms were observed. In polymorphism +67 G/A, a significant increase in the AA genotype in patients with psoriasis guttata compared to plaque psoriasis was found (p = 0.006). A significant association of the A allele in psoriatic patients with a personal history of allergy was found (p = 0.02). The A alle was also significantly associated with a family history of psoriasis (p = 0.00008). In men, a higher risk of a delayed start of psoriasis (later than 40 years) associated with the T allele of -426 T/C polymorphism (p = 0.0007) was found. When double genotypes of both polymorphisms were evaluated, we observed significant differences in double genotype distribution between men with and without a family history of allergy (Pdg = 0.0005) and between those with and without affected siblings (Pdg = 0.03). In women with psoriasis, a higher risk of the TT genotype of -426 T/C polymorphism in patients with a personal history of diabetes (p = 0.001) as well as in patients with both a personal history of cardiovascular disease and diabetes (p = 0.00005) was proved. When double genotypes of both polymorphisms were evaluated, the significance of double genotype difference between those with and without personal history of diabetes was very high (Pdg = 0.0002). Similarly, the significance of the double genotype difference between those with and without personal history of cardiovascular diseases and diabetes was very high (Pdg = 0.000001). Conclusions: CCL11 is considered one of the basic chemokines responsible for the origin and development of immune-based reactions. Based on our results, we suggest that the +67 G/A CCL11 polymorphism should be considered as a gene modulator of psoriasis in specific subgroups of patients.
- MeSH
- chemokin CCL11 * genetika MeSH
- dospělí MeSH
- fenotyp MeSH
- frekvence genu MeSH
- genetická predispozice k nemoci MeSH
- genetické asociační studie MeSH
- genotyp MeSH
- jednonukleotidový polymorfismus * MeSH
- lidé středního věku MeSH
- lidé MeSH
- psoriáza * genetika patologie MeSH
- senioři MeSH
- studie případů a kontrol MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
The immunohistochemical (IHC) or fluorescence/chromogenic in situ hybridization (FISH/CISH) assays for assessing HER2 are now recommended by the American Society of Clinical Oncologists and the College of American Pathologists, but there are an increasing number of published studies describing alternative diagnoses at the molecular level. Inspired by these studies, we established a laboratory-developed test (LDT) to analyze HER2 status not only at the gene expression level but also at the gene copy number. A precise copy number calculation was fulfilled including the Control Genomic DNA of known concentration, which allowed subsequent assay validation at the DNA level. The results were reported according to the concordant results of the DNA and RNA approaches. By comparing with IHC determination, completely identical results were found in ten blank samples, which underlines the legitimacy of molecular biological approaches in this diagnostic field. An equivocal sample that was positive by IHC and qPCR was found to be negative by the FISH and so it may change the choice of personalized medicine. The topic of this short communication will hopefully contribute to allowing IVD-certified diagnostics based on the HER2 gene expression profile or copy number to be tested in the Czech Republic as well.
- MeSH
- DNA genetika metabolismus MeSH
- genová dávka * MeSH
- hybridizace in situ fluorescenční * metody MeSH
- imunohistochemie * metody MeSH
- lidé MeSH
- nádorové biomarkery genetika metabolismus MeSH
- nádory prsu genetika metabolismus diagnóza MeSH
- receptor erbB-2 * genetika metabolismus MeSH
- RNA metabolismus genetika analýza MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
We designed and synthesized a set of four 2'-deoxyribonucleoside 5'-O-triphosphates (dNTPs) bearing cationic substituents (protonated amino, methylamino, dimethylamino and trimethylammonium groups) attached to position 5 of pyrimidines or position 7 of 7-deazapurines through hex-1-ynyl or propargyl linker. These cationic dNTPs were studied as substrates in enzymatic synthesis of modified and hypermodified DNA using KOD XL DNA polymerase. In primer extension (PEX), we successfully obtained DNA containing one, two, three, or (all) four modified nucleotides, each bearing a different cationic modification. The cationic dNTPs were somewhat worse substrates compared to previously studied dNTPs bearing hydrophobic or anionic modifications, but the polymerase was still able to synthesize sequences up to 73 modified nucleotides. We also successfully combined one cationic modification with one anionic and two hydrophobic modifications in PEX. In polymerase chain reaction (PCR), we observed exponential amplification only in the case of one cationic modification, while the combination of more cationic nucleotides gave either very low amplification or no PCR product. The hypermodified oligonucleotides prepared by PEX were successfully re-PCRed and sequenced by Sanger sequencing. Biophysical studies of hybridization, denaturation, and circular dichroism spectroscopy showed that the presence of cationic modifications increases the stability of duplexes.
BACKGROUND: Myelodysplastic Syndrome (MDS) is a devastating hematologic malignancy associated with advanced age. Diabetes Mellitus (DM) is one of the most common morbidities worldwide, with metformin serving as the first line therapy for several decades. However, the potential association between previous metformin use and the risk of developing MDS remains uncertain. METHODS: This cross-sectional study addressed the possible association between prior metformin use in DM patients and the subsequent development of MDS. RESULTS: Data from 54,869 DM patients was retrieved from their medical records from a tertiary medical center. Of these, 20,318 patients had been exposed at some point in time to metformin, with 133 (0.7%) subsequently developing MDS. In contrast, among 34,551 DM patients with no prior exposure to metformin, only 154 (0.4%) developed MDS later in life. The Odds Ratio (OR) for MDS development amongst metformin users compared to the entire study population was 1.48 (95% CI 1.17-1.86; p = 0.001). A multivariate analysis adjusting for gender, age, congestive heart failure and chronic kidney disease, past exposure to metformin remained an independent risk factor for MDS development (OR = 1.6, 95% CI 1.26-2.03; p < 0.001). CONCLUSION: Previous exposure to metformin amongst DM patients is associated with an increased risk for MDS development later in life. This is a preliminary, cross-sectional study that show that larger studies in variable MDS patient populations are warranted.
- MeSH
- diabetes mellitus epidemiologie chemicky indukované MeSH
- dospělí MeSH
- hypoglykemika * terapeutické užití škodlivé účinky MeSH
- lidé středního věku MeSH
- lidé MeSH
- metformin * terapeutické užití škodlivé účinky MeSH
- myelodysplastické syndromy * epidemiologie chemicky indukované MeSH
- průřezové studie MeSH
- rizikové faktory MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
INTRODUCTION: A comparison of body composition assessments using military circumferences to bioelectrical impedance analysis (BIA) and the reference standard dual-energy X-ray absorptiometry (DEXA) can gauge effectiveness of assessments. High-frequency (500 KHz) direct segmental multifrequency bioelectrical impedance analysis (DSM-BIA) accurately calculates total water mass and body fat% (BF%), but it is unknown whether higher frequencies (1,000 KHz) increase measurement accuracy. The purpose was to compare DSM-BIA 500, DSM-BIA 1000, the DoD Circumference Method (CM), and the reference-standard DEXA. MATERIALS AND METHODS: Design: Cross sectional, observational study. Participants/Setting: A total of 62 participants from the military healthcare system (n = 25 males, 38.8 ± 11.4 years, n = 37 females 43.7 ± 15.95 years) were measured in an outpatient clinic setting. Statistical Analysis: BF% was estimated via DEXA, DSM-BIA 500, DSM-BIA 1000, and CM to identify the relationship between methods using Pearson correlation, intraclass correlation coefficients (ICCs), and Bland-Altman plots. The study was approved by the IRB from Walter Reed National Military Medical Center at Bethesda and Concordia University Chicago. RESULTS: Circumference Method BF% was moderately correlated with DSM-BIA 500 (males r = 0.63, ICC = 0.76; females r = 0.77, ICC = 0.85), DSM-BIA 1000 (males r = 0.59, ICC = 0.74; females r = 0.77, ICC = 0.85), and DEXA (males r = 0.62, ICC = 0.62; females r = 0.73, ICC = 0.82). DSM-BIA 500 BF% was strongly correlated with DSM-BIA 1000 (males r = 0.99, ICC = 0.99; females r = 0.99, ICC = 0.99) and DEXA (males r = 0.93, ICC = 0.94; females r = 0.89, ICC = 0.89). Lastly, DSM-BIA 1000 BF% was also strongly correlated with DEXA (males r = 0.93, ICC = 0.94; females r = 0.84, ICC = 0.90) (P for each reported r < 0.01). Bland-Altman analysis confirmed an overall mean bias of -1.72% CM vs. DEXA in females, indicating the tendency of CM to underestimate BF% compared to DEXA limits of agreement from -14.24 to 10.8. There was an upward slope of the linear relationship between the bias and mean of the measures (Beta = 0.34, P = 0.01). In the full cohort, there was an overall mean bias of 1.14% of CM vs. DSM BIA 1000, with CM tending to overestimate BF% compared to DSM BIA 1000 with limits of agreement -11.13 to 13.41%. There is an upward slope line of the linear relationship between the bias and the mean of the measures (Beta = 0.17, P = .03). CONCLUSION: This study found that CM BF% was moderately correlated with DSM-BIA 500 kHz, DSM-BIA 1,000 kHz BIA, and DEXA. Both DSM-BIA 500 and DSM-BIA 1,000 kHz strongly correlated well with DEXA implying that there was no further increase in correlation with increased frequency. Additionally, there was proportional bias in BF% in the female group between CM and DEXA and in the total group between CM and DSM BIA 1000.
- MeSH
- absorpční fotometrie * metody statistika a číselné údaje MeSH
- dospělí MeSH
- elektrická impedance * MeSH
- index tělesné hmotnosti MeSH
- lidé středního věku MeSH
- lidé MeSH
- průřezové studie MeSH
- složení těla * fyziologie MeSH
- tuková tkáň diagnostické zobrazování fyziologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
- srovnávací studie MeSH
INTRODUCTION: The conflict in Ukraine, ongoing since 2014 and escalating with the Russian invasion in 2022, has unveiled profound challenges in prehospital care essential for the survival and recovery of warfighters and civilians alike, necessitating a detailed examination of the current medical response mechanisms and their effectiveness. MATERIALS AND METHODS: This study provides an overview of these challenges and examines how these critical vulnerabilities have impacted the delivery of medical care in war-torn regions. It also explores the role of NATO and its member states in addressing these challenges, focusing on the efforts to standardize prehospital care, enhance training, and foster interoperability among medical services. Furthermore, it explores the role of global heath engagement through NGOs in addressing these prehospital care gaps within the Ukrainian conflict zone, drawing from direct observations, expert testimonials, and secondary data. RESULTS: Findings reveal significant enhancements in prehospital care through improved training, interoperability, and logistics management, despite ongoing challenges in medical infrastructure and extended evacuation times, which continue to impact the quality of care. CONCLUSIONS: The study underscores the critical role of international collaboration and standardized protocols in bolstering prehospital medical responses in conflict settings, highlighting the need for continuous adaptation and support to mitigate the complexities of modern warfare. The insights gained from the Ukraine conflict offer valuable lessons for future military and humanitarian medical responses in similar conflict settings.
- MeSH
- celosvětové zdraví * MeSH
- lidé MeSH
- ozbrojené konflikty MeSH
- urgentní zdravotnické služby * metody normy trendy MeSH
- vedení války statistika a číselné údaje MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Ukrajina MeSH
INTRODUCTION: Human and animal skin is colonized by a complex microbial population. An imbalance of these microorganisms is often associated with dermatological diseases. METHODS: The aim of this work was to describe the skin bacterial microbiota composition of healthy dogs and dogs with inflammatory skin lesions. Genomic DNA was sequenced using primers that target the V4 region of the bacterial 16S rRNA gene. Superficial skin swabs were collected from eight body areas of six healthy dogs (n = 48) and directly from inflammatory altered canine skin (n = 16). RESULTS: The skin of healthy dogs was predominantly colonized by phylum Bacillota (34.4 ± 27.2%), followed by Actinomycetota (32.2 ± 20.3%), Pseudomonadota (16.4 ± 12.2%), and Bacteroidota (8.7 ± 11.6%). At the level of genera, Streptococcus spp. (19.4 ± 26.1%) was the most abundant genus across all samples collected from healthy skin, followed by Curtobacterium (5.4 ± 12.1%), Bacteroides (5.2 ± 11.1%) and Corynebacterium_1 (4.3 ± 13.2%). More specifically, Streptococcus spp. was the most abundant on the chin (49.0 ± 35.5%), nose (37.9 ± 32.1%), perianal region (21.1 ± 28.2%), abdomen (11.0 ± 12.8%), dorsal back (12.4 ± 10.3%) and interdigital area (5.5 ± 2.2%). Curtobacterium spp. was predominant on inner pinna (17.8 ± 24.8%) and axilla (6.7 ± 10.8%). Alpha diversity analysis (Shannon index) showed maximum on interdigital area but minimum on a chin (p-value: 0.0416). Beta diversity analysis showed clustering across samples from the individual skin sites but also across samples collected from individual dogs. Staphylococcus spp. was the most abundant genus in 12/16 samples collected from inflammatory skin. In addition, a lower bacterial diversity was observed in samples from skin lesions compared to samples from healthy canine skin. DISCUSSION: The results confirm the fact that the microbiome of healthy skin is very diverse. Compared to other studies, streptococci predominated on healthy canine skin. Shannon index showed only minor differences in diversity between different parts of canine skin. Results of beta-diversity showed the fact that the main force driving the skin microbiota composition is the individual, followed by the skin site. On the area of skin lesions, dysbiosis was observed with a significant predominance of staphylococci.
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Germline genetic susceptibilities of rare cancers of the esophagus, stomach, small intestine, testis, (nonmedullary) thyroid gland and bone with high familial risks are not well known. Here, we use familial risk data from the Swedish Family-Cancer Database which contains records of cancers in Swedish families obtained over a century. We compare familial risks for offspring diagnosed with any of these cancers when their parent had or had not that cancer. We review the global literature of the reported constitutional variants that may explain part of the familial risk. MAIN BODY: Familial risks for esophageal and stomach cancers are about 2.0 and apart from early-onset stomach cancer few high-risk variants are known. Genetic studies may be hampered by dominant environmental risk factors for these cancers. Small intestinal carcinoids have a very high familial risk (28 between siblings) but no high-risk genes have been identified to explain this. Low-risk polygenic variants have been identified. Small intestinal adenocarcinoma is a manifestation in Lynch syndrome. Testicular and thyroid cancers are characterized by high familial risk (about 5) which may be explained largely by a polygenic background, although thyroid cancer is a component in a number of rare cancer syndromes. Several predisposing genes have been identified for bone cancer (familial risk 7). CONCLUSIONS: The discussed cancers are rare and they present with a relatively high familial risk, in spite of lacking identified high-penetrant constitutional variants. It is possible that the polygenic component, already recognized for testis cancer, is stronger than previously expected. Thus polygenic models with rare high/moderate- and low-risk variants could fit the familial risk and shape the germline genetic landscape of these cancers. Polygenic background may have clinical implications.
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
