INTRODUCTION: The retrospective study evaluated the clinical and radiological outcomes of conservative treatment for type II odontoid C2 fractures in octogenerians. The study aimed to assess the clinical outcomes and quality of survival of patients treated using conservative methods. Additionally, the study sought to define radiological outcomes, fracture healing success and the development of complications in correlation with clinical outcomes. MATERIALS AND METHODS: Patients aged ≥80 with dens C2 fracture were fixed with a hard cervical collar for 6 weeks, followed by early mobilization. Patients showing delayed fracture healing on computed tomography (CT) scan were subsequently immobilized in a soft neck collar for additional 6 weeks. The follow-up CT scan was then performed with consequential rehabilitation. Patients with nonunion of the C2 on the follow-up CT scan and clinical symptoms were contraindicated for physical rehabilitation for cervical spine till next CT scan after another 12 weeks. Clinical and radiographic evaluations were performed during follow-up visits, with a median follow-up was 109 days, with the range extending from 1 day to 1 year. RESULTS: In total, 33 patients were included in the study and were followed for 1 year. The 30-day mortality rate was 21.2%, and between 30 days and one year post-treatment, it was 18.2%. Mortality was higher during the study period in displaced fractures (>2 mm; 9 out of 16 patients died) compared to non-displaced fractures (≤2 mm; 4 out of 17 patients died). The Japanese Orthopaedic Association (JOA) score remained unchanged between admission (mean 16.9; SD ± 0.5) and the end of follow-up (mean 16.9; SD ± 0.5; P > 0.05), the Visual Analogue Scale (VAS) score showed improvement from values measured upon admission to the hospital (mean 7.97; SD ± 1.33) to values measured at the end of follow-up (mean 1.58; SD ± 1.62; P < 0.001) and the Neck Disability Index (NDI) showed a statistically significant difference between admission (mean 41.3; SD ± 14.92) and the end of follow-up (mean 14.29; SD ± 4.65; P < 0.001). The standard measurement of Posterior Atlantodental Interval (PADI) had an average value of 18.6 (range 16-22 mm) and primary bony union of odontoid fractures occurred in eleven cases (33.3%), while six patients (18.2%) had fibrous union with minimal clinical difficulties. CONCLUSION: This study demonstrates the safety and efficacy of conservative treatment for odontoid fractures in octogenerians and underscores the critical role of conservative management in a polymorbid elderly population.
- Publikační typ
- časopisecké články MeSH
Menopause brings about profound physiological changes, including the acceleration of insulin resistance and other abnormalities, in which adipose tissue can play a significant role. This study analyzed the effect of ovariectomy and estradiol substitution on the metabolic parameters and transcriptomic profile of adipose tissue in prediabetic females of hereditary hypertriglyceridemic rats (HHTgs). The HHTgs underwent ovariectomy (OVX) or sham surgery (SHAM), and half of the OVX group received 17β-estradiol (OVX+E2) post-surgery. Ovariectomy resulted in weight gain, an impaired glucose tolerance, ectopic triglyceride (TG) deposition, and insulin resistance exemplified by impaired glycogenesis and lipogenesis. Estradiol alleviated some of the disorders associated with ovariectomy; in particular, it improved insulin sensitivity and reduced TG deposition. A transcriptomic analysis of perimetrial adipose tissue revealed 809 differentially expressed transcripts in the OVX vs. SHAM groups, mostly pertaining to the regulation of lipid and glucose metabolism, and oxidative stress. Estradiol substitution affected 1049 transcripts with overrepresentation in the signaling pathways of lipid metabolism. The principal component and hierarchical clustering analyses of transcriptome shifts corroborated the metabolic data, showing a closer resemblance between the OVX+E2 and SHAM groups compared to the OVX group. Changes in the adipose tissue transcriptome may contribute to metabolic abnormalities accompanying ovariectomy-induced menopause in HHTg females. Estradiol substitution may partially mitigate some of these disorders.
- Publikační typ
- časopisecké články MeSH
Several corresponding regions of human and mammalian genomes have been shown to affect sensitivity to the manifestation of metabolic syndrome via nutrigenetic interactions. In this study, we assessed the effect of sucrose administration in a newly established congenic strain BN.SHR20, in which a limited segment of rat chromosome 20 from a metabolic syndrome model, spontaneously hypertensive rat (SHR), was introgressed into Brown Norway (BN) genomic background. We mapped the extent of the differential segment and compared the genomic sequences of BN vs. SHR within the segment in silico. The differential segment of SHR origin in BN.SHR20 spans about 9 Mb of the telomeric portion of the short arm of chromosome 20. We identified non-synonymous mutations e.g., in ApoM, Notch4, Slc39a7, Smim29 genes and other variations in or near genes associated with metabolic syndrome in human genome-wide association studies. Male rats of BN and BN.SHR20 strains were fed a standard diet for 18 weeks (control groups) or 16 weeks of standard diet followed by 14 days of high-sucrose diet (HSD). We assessed the morphometric and metabolic profiles of all groups. Adiposity significantly increased only in BN.SHR20 after HSD. Fasting glycemia and the glucose levels during the oral glucose tolerance test were higher in BN.SHR20 than in BN groups, while insulin levels were comparable. The fasting levels of triacylglycerols were the highest in sucrose-fed BN.SHR20, both compared to the sucrose-fed BN and the control BN.SHR20. The non-esterified fatty acids and total cholesterol concentrations were higher in BN.SHR20 compared to their respective BN groups, and the HSD elicited an increase in non-esterified fatty acids only in BN.SHR20. In a new genetically defined model, we have isolated a limited genomic region involved in nutrigenetic sensitization to sucrose-induced metabolic disturbances.
- MeSH
- apolipoproteiny M genetika MeSH
- celogenomová asociační studie MeSH
- hypertenze * metabolismus MeSH
- krysa rodu rattus MeSH
- lidé MeSH
- lidské chromozomy, pár 20 metabolismus MeSH
- mastné kyseliny MeSH
- metabolický syndrom * genetika metabolismus MeSH
- nutrigenomika MeSH
- omezení příjmu potravy MeSH
- potkani inbrední BN MeSH
- potkani inbrední SHR MeSH
- proteiny přenášející kationty * genetika MeSH
- sacharosa škodlivé účinky MeSH
- savci genetika MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Complex metabolic conditions such as type 2 diabetes and obesity result from the interaction of numerous genetic and environmental factors. While the family of Nme proteins has been connected so far mostly to development, proliferation, or ciliary functions, several lines of evidence from human and experimental studies point to the potential involvement of one of its members, NME7 (non-metastatic cells 7, nucleoside diphosphate kinase 7) in carbohydrate and lipid metabolism. As a complete lack of Nme7 is semilethal in rats, we compared morphometric, metabolic, and transcriptomic profiles of standard diet-fed heterozygous Nme7+/- on male rats vs. their wild-type Nme7+/+ controls. Nme7+/- animals showed increased body weight, adiposity, higher insulin levels together with decreased glucose tolerance. Moreover, they displayed pancreatic islet fibrosis and kidney tubular damage. Despite no signs of overt liver steatosis or dyslipidemia, we found significant changes in the hepatic transcriptome of Nme7+/- male rats with a concerted increase of expression of lipogenic enzymes including Scd1, Fads1, Dhcr7 and a decrease of Cyp7b1 and Nme7. Network analyses suggested possible links between Nme7 and the activation of Srebf1 and Srebf2 upstream regulators. These results further support the implication of NME7 in the pathogenesis of glucose intolerance and adiposity.
- MeSH
- adipozita genetika MeSH
- diabetes mellitus 2. typu metabolismus MeSH
- dyslipidemie genetika MeSH
- glukosa metabolismus MeSH
- játra metabolismus MeSH
- krysa rodu rattus MeSH
- lipogeneze genetika MeSH
- metabolismus lipidů fyziologie MeSH
- nukleosiddifosfátkinasa genetika metabolismus MeSH
- obezita metabolismus MeSH
- porucha glukózové tolerance genetika metabolismus MeSH
- potkani Sprague-Dawley MeSH
- transkriptom MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
NME7 (non-metastatic cells 7, nucleoside diphosphate kinase 7) is a member of a gene family with a profound effect on health/disease status. NME7 is an established member of the ciliome and contributes to the regulation of the microtubule-organizing center. We aimed to create a rat model to further investigate the phenotypic consequences of Nme7 gene deletion. The CRISPR/Cas9 nuclease system was used for the generation of Sprague Dawley Nme7 knock-out rats targeting the exon 4 of the Nme7 gene. We found the homozygous Nme7 gene deletion to be semi-lethal, as the majority of SDNme7-/- pups died prior to weaning. The most prominent phenotypes in surviving SDNme7-/- animals were hydrocephalus, situs inversus totalis, postnatal growth retardation, and sterility of both sexes. Thinning of the neocortex was histologically evident at 13.5 day of gestation, dilation of all ventricles was detected at birth, and an external sign of hydrocephalus, i.e., doming of the skull, was usually apparent at 2 weeks of age. Heterozygous SDNme7+/- rats developed normally; we did not detect any symptoms of primary ciliary dyskinesia. The transcriptomic profile of liver and lungs corroborated the histological findings, revealing defects in cell function and viability. In summary, the knock-out of the rat Nme7 gene resulted in a range of conditions consistent with the presentation of primary ciliary dyskinesia, supporting the previously implicated role of the centrosomally located Nme7 gene in ciliogenesis and control of ciliary transport.
- MeSH
- cilie metabolismus ultrastruktura MeSH
- fenotyp MeSH
- genetická predispozice k nemoci * MeSH
- genetické asociační studie MeSH
- genotyp MeSH
- genový knockdown MeSH
- imunohistochemie MeSH
- krysa rodu rattus MeSH
- letální geny * MeSH
- modely nemocí na zvířatech MeSH
- nukleosiddifosfátkinasa nedostatek genetika metabolismus MeSH
- poruchy ciliární motility diagnóza genetika MeSH
- potkani Sprague-Dawley MeSH
- potkani transgenní MeSH
- regulace genové exprese MeSH
- rentgenová mikrotomografie MeSH
- stanovení celkové genové exprese MeSH
- transkriptom MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Overnutrition in pregnancy and lactation affects fetal and early postnatal development, which can result in metabolic disorders in adulthood. We tested a hypothesis that variation of the Zbtb16 gene, a significant energy metabolism regulator, modulates the effect of maternal high-sucrose diet (HSD) on metabolic and transcriptomic profiles of the offspring. We used the spontaneously hypertensive rat (SHR) strain and a minimal congenic rat strain SHR-Zbtb16, carrying the Zbtb16 gene allele originating from the PD/Cub rat, a metabolic syndrome model. Sixteen-week-old SHR and SHR-Zbtb16 rat dams were fed either standard diet (control groups) or a high-sucrose diet (HSD, 70% calories as sucrose) during pregnancy and 4 weeks of lactation. In dams of both strains, we observed an HSD-induced increase of cholesterol and triacylglycerol concentrations in VLDL particles and a decrease of cholesterol and triacylglycerols content in medium to very small LDL particles. In male offspring, exposure to maternal HSD substantially increased brown fat weight in both strains, decreased triglycerides in LDL particles, and impaired glucose tolerance exclusively in SHR. The transcriptome assessment revealed networks of transcripts reflecting the shifts induced by maternal HSD with major nodes including mir-126, Hsd11b1 in the brown adipose tissue, Pcsk9, Nr0b2 in the liver and Hsd11b1, Slc2a4 in white adipose tissue. In summary, maternal HSD feeding during pregnancy and lactation affected brown fat deposition and lipid metabolism in adult male offspring and induced major transcriptome shifts in liver, white, and brown adipose tissues. The Zbtb16 variation present in the SHR-Zbtb16 led to several strain-specific effects of the maternal HSD, particularly the transcriptomic profile shifts of the adult male offspring.
- Publikační typ
- časopisecké články MeSH
Excessive methylglyoxal (MG) production contributes to metabolic and vascular changes by increasing inflammatory processes, disturbing regulatory mechanisms and exacerbating tissue dysfunction. MG accumulation in adipocytes leads to structural and functional changes. We used transcriptome analysis to investigate the effect of MG on metabolic changes in the visceral adipose tissue of hereditary hypetriglyceridaemic rats, a non-obese model of metabolic syndrome. Compared to controls, 4-week intragastric MG administration impaired glucose tolerance (p < 0.05) and increased glycaemia (p < 0.01) and serum levels of MCP-1 and TNFα (p < 0.05), but had no effect on serum adiponectin or leptin. Adipose tissue insulin sensitivity and lipolysis were impaired (p < 0.05) in MG-treated rats. In addition, MG reduced the expression of transcription factor Nrf2 (p < 0.01), which controls antioxidant and lipogenic genes. Increased expression of Mcp-1 and TNFα (p < 0.05) together with activation of the SAPK/JNK signaling pathway can promote chronic inflammation in adipose tissue. Transcriptome network analysis revealed the over-representation of genes involved in insulin signaling (Irs1, Igf2, Ide), lipid metabolism (Nr1d1, Lpin1, Lrpap1) and angiogenesis (Dusp10, Tp53inp1).
- Publikační typ
- časopisecké články MeSH
Both prenatal and postnatal excessive consumption of dietary sucrose or fructose was shown to be detrimental to health and contributing to pathogenesis of metabolic syndrome. Our knowledge of genetic determinants of individual sensitivity to sucrose-driven metabolic effects is limited. In this study, we have tested the hypothesis that a variation of metabolic syndrome-related gene, Zbtb16 (Zinc Finger and BTB Domain Containing 16 will affect the reaction to high-sucrose diet (HSD) content in "matched" nutritional exposition settings, i.e. maternal HSD with re-exposition to HSD in adulthood vs. standard diet. We compared metabolic profiles of adult males of spontaneously hypertensive rats (SHR) and a single-gene, minimal congenic strain SHR-Zbtb16 fed either standard diet or exposed to HSD prenatally throughout gestation and nursing and again at the age of 6 months for the period of 14 days. HSD exposition led to increased adiposity in both strains and decrease of glucose tolerance and cholesterol (Ch) concentrations in majority of low-density lipoprotein (LDL) particle classes and in very large and large high-density lipoprotein (HDL) in SHR-Zbtb16 male offspring. There was a similar pattern of HSD-induced increase of triacylglycerols in chylomicrons and very low-density lipoprotein (VLDL) of both strains, though the increase of (triacylglycerol) TAG content was clearly more pronounced in SHR. We observed significant STRAIN*DIET interactions for the smallest LDL particles as their TAG content decreased in SHR-Zbtb16 and did not change in SHR in response to HSD. In summary, we provide evidence of nutrigenetic interaction between Zbtb16 and HSD in context of pathogenesis of metabolic syndrome.
- MeSH
- cholesterol metabolismus MeSH
- hypertenze genetika metabolismus MeSH
- konzumní sacharóza metabolismus MeSH
- krysa rodu rattus MeSH
- metabolický syndrom etiologie metabolismus patologie MeSH
- modely nemocí na zvířatech MeSH
- nutrigenomika metody MeSH
- potkani inbrední SHR MeSH
- protein promyelocytické leukemie s motivem zinkového prstu genetika metabolismus MeSH
- sladidla metabolismus MeSH
- těhotenství MeSH
- triglyceridy metabolismus MeSH
- zvířata kongenní MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
