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Objective. The present study assessed the impact of type 2 diabetes mellitus (T2DM) duration on the serum asymmetric dimethylarginine (ADMA) and C-reactive protein (CRP) concentration in Bosnian patients. Methods. Participants for this cross-sectional study were randomly selected from the Family Medicine Clinic (Sarajevo, Bosnia and Herzegovina). Serum ADMA concentration was determined by ELISA. Serum high-sensitivity (hs-CRP) was determined by particle-enhanced immunonephelometry. ANOVA test followed by Scheffe post-hoc test or Kruskal-Wallis test followed by Man-Whitney test were used for statistical analysis. Results. The study included 38 patients in up to 10 years diabetes duration (≤10 years T2DM) group, 22 patients in greater than 10 years diabetes duration (>10 years T2DM) group, and 60 controls. Serum ADMA concentration in the >10 years T2DM group (1.81±0.15 µmol/L) was significantly higher compared to serum ADMA concentration in the ≤10 years T2DM group (1.38±0.41 µmol/L; p<0.001) and in controls (0.62±0.15 µmol/L; p<0.001). A significant difference in serum ADMA concentration was found between the <10 years T2DM group and the controls (p<0.001). The serum CRP concentration in the >10 years T2DM group [5.95 (4.20-9.12) mg/L] was significantly higher compared to serum CRP concentration in the <10 years T2DM group [2.35 (1.40-4.30) mg/L; p<0.001] and controls [0.85 (0.50-1.30) mg/L; p<0.001]. Significant difference in serum CRP concentration was observed between the <10 years T2DM group and controls (p<0.001). Conclusions. The present study showed an increase in the serum ADMA and CRP concentrations with the advancement of T2DM. These results suggest that ADMA and CRP may serve as indicators of endothelial dysfunction and chronic low-grade inflammation progression in patients with T2DM. Larger prospective studies are required to confirm the observed findings.
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Proteína C-Reativa , Diabetes Mellitus Tipo 2 , Humanos , Proteína C-Reativa/análise , Estudos Transversais , Arginina , InflamaçãoRESUMO
BACKGROUND: CYP3A5 enzyme encoded by CYP3A5 is important for drug metabolism in gut and liver, whereas P-glycoprotein by ABCB1, is an ATP-dependent drug efflux pump which exports endo- and exogenous substances outside the cell. AIM: The study was to assess the prevalence of CYP3A5 alleles: *1, *2, *3, *4, *6 and *7, and C and T of ABCB1 in Poles, Belarusians and Bosnians and to compare it with the data reported from other European populations. SUBJECTS AND METHODS: Overall, 511 unrelated healthy subjects from Poland (n = 239), Belarus (n = 104) and Bosnia and Herzegovina (n = 168) were included in this study. Allele frequencies and statistical parameters (AMOVA version 2.9.3) were determined. RESULTS: In Poles, Belarusians and Bosnians the *3 allele of CYP3A5 was the most common, and wild-type allele *1, were: 5.8%, 1.6% and 2.1%, respectively. Allele *2 was very rare, and alleles *4, *6 and *7 were not detected. For the populations mentioned above, the ABCB1 allele C was: 48.1%, 51.4%, 52.4%, respectively. CONCLUSION: In compared populations, the distribution of CYP3A5 variants but not ABCB1, differed significantly. Alleles *4, *6 and *7 of CYP3A5 did not occur or occurred rarely.
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Citocromo P-450 CYP3A , Tacrolimo , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Trifosfato de Adenosina , Citocromo P-450 CYP3A/genética , Variação Genética , Genótipo , Humanos , Polimorfismo de Nucleotídeo ÚnicoRESUMO
BACKGROUND: Cerebrospinal levels of isoprostanes (IsoPs) have been established as biomarkers of oxidative stress in Alzheimer's disease (AD) and vascular dementia (VD). The value of peripheral levels in the diagnostics of these diseases is less conclusive. The aim of this study was to determine serum 8-iso-prostaglandin-F2alpha (8-iso-PGF2α) levels in Bosnian AD and VD patients and to establish whether there is an association between 8-iso-PGF2α serum concentration and cognitive impairment (CI) in patients with dementia. SUBJECTS AND METHODS: Serum levels of 8-iso-PGF2α were measured by enzyme immunoassay method in AD (n=30) and VD patients (n=30) and control subjects (CG, n=30). The AD and VD group were further stratified according to the level of CI. RESULTS: The serum 8-iso-PGF2α levels were significantly higher in the AD (74.00 pg/mL) and VD groups (38.00 pg/mL) compared to the CG (17.50 pg/mL). A significant difference in serum 8-iso-PGF2α levels between patients with moderate and severe CI was not established in either AD or VD. CONCLUSION: Serum 8-iso-PGF2α proved to be a good biomarker in AD and VD, however it cannot be recommended for the differentiation of moderate and severe CI.
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Doença de Alzheimer/diagnóstico , Demência Vascular/diagnóstico , Dinoprosta/análogos & derivados , Estresse Oxidativo , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/análise , Bósnia e Herzegóvina , Dinoprosta/análise , Feminino , HumanosRESUMO
BACKGROUND: The ε2, ε3 and ε4 alleles of APOE gene have been associated with several diseases in different populations. Data on the frequency of alleles are used in both a clinical and evolutionary context. Although the data on frequency of these alleles are numerous, there are no reports for the population of Bosnia and Herzegovina. AIM: To estimate the frequency of APOE alleles in a healthy Bosnian population and compare it to data for other European populations. SUBJECTS AND METHODS: Overall, 170 unrelated Bosnian subjects (108 female and 62 male), aged 53.0 (±5.0) years were included in this study. Genotypes were determined by real-time PCR. RESULTS: In our group the prevalence of heterozygotes E2/E3, E2/E4 and E3/E4 was 20.6%, 3.5% and 12.9%, respectively, while the prevalence of homozygotes E2/E2, E3/E3, E4/E4 was 0.6%, 61.2% and 1.2%, respectively, with a mean frequency of ε2, ε3 and ε4 alleles of 12.6%, 78.0% and 9.4%, respectively. CONCLUSIONS: In studied European populations we observed a linear, gradually increasing trend in the frequency of ε4 allele from South to North (Pearson's test 0,7656, p value <0.00001), and the Bosnian population fits into this pattern perfectly.
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Apolipoproteínas E/genética , Frequência do Gene , Polimorfismo Genético , Alelos , Bósnia e Herzegóvina , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
INTRODUCTION: Renalase is a protein secreted in kidneys and considered as a blood pressure modulator. High rates of hypertension and its regulation in patients on hemodialysis demands search for potential cause and treatment. The aim of this study was to determine the genotype and allele frequencies of renalase gene rs2576178 polymorphism in population from Bosnia and Herzegovina. Also, the objective of present study was to find the possible association between renalase gene rs2576178 polymorphism and hypertension in patients on hemodialysis. MATERIAL AND METHODS: The genotype of renalase gene rs2576178 polymorphism was determined in 137 participants (100 patients on hemodialysis and 37 controls), using polymerase chain reaction (PCR) and subsequent cleavage with MspI restriction endonuclease. Genotype and allele frequencies were assessed for Hardy-Weinberg equilibrium using a Chi-squared test. The value of P<0.05 was considered as statistically significant. RESULTS: Comparison of genotype distribution and allele frequency in participants on hemodialysis with and without hypertension, and healthy control showed no statistical difference. CONCLUSION: The results of the study suggest that renalase gene rs2576178 polymorphism is not a factor that influences blood pressure in patients on hemodialysis.
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Monoaminoxidase/genética , Polimorfismo Genético , Diálise Renal , Insuficiência Renal Crônica/genética , Insuficiência Renal Crônica/terapia , Adolescente , Adulto , Idoso , Biomarcadores/sangue , Bósnia e Herzegóvina , Estudos de Casos e Controles , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Diálise Renal/métodos , Insuficiência Renal Crônica/sangueRESUMO
BACKGROUND: Venous thrombosis (VT) affects 1-2 out of 10(3) individuals each year. Mutations of 1691G > A FV gene, 20210G > A PT gene and 677C > T gene MTHFR are common in Europe and increase the risk of venous thrombosis. To the authors' knowledge, this is the first report on the prevalence of these mutations in the general population of Bosnia and Herzegovina. AIM: The aim of this study was to simultaneously analyse main VT associated polymorphisms and compare the results with those published for other European populations. DATA SOURCES: Electronic databases including Medline and Embase were searched from 1995 to December 2013. SUBJECTS AND METHODS: The subjects of the study consisted of 100 unrelated healthy people from Bosnia and Herzegovina (82 female and 18 male). The mean age of the cohort was 58.8 (± 10.7) years. PCR-RFLP was used for measurement of allele frequencies. RESULTS: All three SNPs were found to be polymorphic, with allele frequencies of 6.0%, 6.0% and 37.5% for 1691A FV, 20210A PT and 677T MTHFR, respectively. CONCLUSION: Further studies on larger cohorts with an adequate female-to-male ratio are necessary to confirm a high prevalence of hereditary thrombophilia in the Bosnian population.
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Fator V/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Polimorfismo de Nucleotídeo Único , Protrombina/genética , Trombofilia/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Bósnia e Herzegóvina , Fator V/metabolismo , Feminino , Frequência do Gene , Humanos , Masculino , Metilenotetra-Hidrofolato Redutase (NADPH2)/metabolismo , Pessoa de Meia-Idade , Mutação , Prevalência , Protrombina/metabolismo , Fatores de Risco , Trombofilia/genética , Adulto JovemRESUMO
OBJECTIVES: The purpose of this study was to determine endothelin (ET)-1 and nitric oxide (NO) serum concentration levels at baseline and after 1 year of peritoneal dialysis (PD) treatment. A further aim was to evaluate the association between ET-1 and NO with parameters of echocardiography and the common carotid artery (CCA) ultrasound, and to assess their impact on cardiovascular remodeling. We also aimed to evaluate the influence of dialysis adequacy and residual renal function (RRF) on cardiovascular remodeling. METHODS: This study included 40 PD patients in whom we measured serum ET-1 and NO concentrations, echocardiography and CCA ultrasound parameters. RESULTS: ET-1 decreased and NO serum concentration levels increased (p < 0.01) after 12 months of PD treatment compared to baseline values. Left ventricular (LV) hypertrophy was observed in 77.5% of patients at baseline with significant reduction in LV mass index (LVMI), CCA intima media thickness (IMT) and plaque score after 12 months of PD treatment (p < 0.001). The dialysis adequacy and RRF were significantly associated with LVMI and CCA IMT after 12 months on PD. CONCLUSION: In our study, ET-1 significantly decreased while NO increased during PD treatment and both were independently related to the cardiovascular remodeling parameters in PD patients.
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Hipertrofia Ventricular Esquerda/sangue , Hipertrofia Ventricular Esquerda/complicações , Falência Renal Crônica/complicações , Diálise Peritoneal , Remodelação Ventricular/fisiologia , Adulto , Idoso , Biomarcadores/sangue , Doenças das Artérias Carótidas/sangue , Doenças das Artérias Carótidas/complicações , Doenças das Artérias Carótidas/diagnóstico por imagem , Diabetes Mellitus Tipo 2/complicações , Endotelina-1/sangue , Feminino , Seguimentos , Humanos , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Óxido Nítrico/sangue , Estudos Prospectivos , UltrassonografiaRESUMO
Aim This study aimed to assess the impact of forced repeated swimming stress on serum adiponectin and endothelin-1 levels in Wistar rats, comparing the effects between those fed a standard diet and those on a high-fat diet. Methods Twenty adult male Wistar rats were divided into two dietary groups: a standard food diet group (NFD, n=10) and a high-fat diet group (HFD, n=10). Both groups underwent daily forced swimming stress for six days, with durations increasing from 5 to 30 minutes. The protocol finished in an acute bout of swimming exercise on the seventh day with a duration of 40 minutes. Adherence to ethical guidelines was strictly maintained, and serum adiponectin and endothelin-1 levels were measured pre- and post-exercise using the ELISA method. Results Before swimming, the mean adiponectin levels were 4.30±1.50 ng/mL in the NFD group and 3.53±0.70 ng/mL in the HFD group. Post-exercise, these levels significantly decreased to 2.4±0.84 ng/mL (p=0.003) and 1.58±0.23 ng/mL (p=0.001), respectively. Endothelin-1 levels also showed significant decreases from 0.86 pg/mL (0.74-0.87) to 0.49 pg/mL (0.43-0.62) (p=0.003) in the NFD group, and from 0.89 pg/mL (0.86-0.93) to 0.69 pg/mL (0.60-0.75) (p=0.027) in the HFD group after swimming. Conclusion The study highlighted the significant effects of forced swimming stress on lowering serum adiponectin and endothelin-1 levels in Wistar rats, with more pronounced decreases observed in rats on a high-fat diet. The results of the study suggest the potential of exercise as a crucial component of strategies aimed at managing obesity and improving cardiovascular health, emphasizing the interaction between physical stress and dietary factors on metabolic and cardiovascular biomarkers.
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Musculoskeletal research should synergistically investigate bone and muscle to inform approaches for maintaining mobility and to avoid bone fractures. The relationship between sarcopenia and osteoporosis, integrated in the term 'osteosarcopenia', is underscored by the close association shown between these two conditions in many studies, whereby one entity emerges as a predictor of the other. In a recent workshop of Working Group (WG) 2 of the EU Cooperation in Science and Technology (COST) Action 'Genomics of MusculoSkeletal traits Translational Network' (GEMSTONE) consortium (CA18139), muscle characterization was highlighted as being important, but currently under-recognized in the musculoskeletal field. Here, we summarize the opinions of the Consortium and research questions around translational and clinical musculoskeletal research, discussing muscle phenotyping in human experimental research and in two animal models: zebrafish and mouse.
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Fenótipo , Animais , Humanos , Músculo Esquelético/metabolismo , Peixe-Zebra , Camundongos , Sarcopenia/metabolismo , Sarcopenia/fisiopatologia , Doenças Musculoesqueléticas/fisiopatologia , Doenças Musculoesqueléticas/genética , Osteoporose/metabolismo , Osteoporose/patologiaRESUMO
The advent of multicellular organisms was accompanied by the development of short- and long-range chemical signalling systems, including those provided by the nervous and endocrine systems. In turn, the cells of these two systems have developed mechanisms for interacting with both adjacent and distant cells. With evolution, such mechanisms have diversified to become integrated in a complex regulatory network, whereby individual endocrine and neuro-endocrine cells sense the state of activity of their neighbors and, accordingly, regulate their own level of functioning. A consistent feature of this network is the expression of connexin-made channels between the (neuro)hormone-producing cells of all endocrine glands and secretory regions of the central nervous system so far investigated in vertebrates. This review summarizes the distribution of connexins in the mammalian (neuro)endocrine systems, and what we know about the participation of these proteins on hormone secretion, the life of the producing cells, and the action of (neuro)hormones on specific targets. The data gathered since the last reviews on the topic are summarized, with particular emphasis on the roles of Cx36 in the function of the insulin-producing beta cells of the endocrine pancreas, and of Cx40 in that of the renin-producing juxta-glomerular epithelioid cells of the kidney cortex. This article is part of a Special Issue entitled: The Communicating junctions, composition, structure and characteristics.
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Conexinas/fisiologia , Hormônios/metabolismo , Neurônios/metabolismo , Animais , Dopamina/metabolismo , Sistema Endócrino/fisiologia , Feminino , Hormônio Liberador de Gonadotropina/metabolismo , Humanos , Insulina/metabolismo , Córtex Renal/metabolismo , Masculino , Modelos Biológicos , Ocitocina/metabolismo , Renina/metabolismo , Transdução de Sinais , Vasopressinas/metabolismoRESUMO
Serum thyreoglobulin (Tg) and whole body scintigraphy (I-131 WBS) have been used to detect recurrent and metastatic thyroid cancers postoperatively. However, discordant results of Tg measurement and 131I WBS have been reported. Negative 131I WBS and a positive Tg test are usually found, but less common occurrence of positive 131I WBS and a negative Tg test has also been demonstrated in a small but significant number of cases. Therefore, the aim of the study was to retrospectively analyse patients with positive 131I WBS after total thyreoidectomy and again 1 year after the radioactive iodine. There were 52 patients included in the study. Four weeks after surgery, during which thyroid hormone treatment was not introduced, each patient received an ablative dose of 131I. The evaluation of the WBS was qualitative and considered positive if thyroid remnant, lymphatic node or metastasis were detected. WBS and serum Tg was measured 12 months after 131I ablation with thyroid hormone suppression. We considered positive any Tg level above the sensitivity values and negative if lower than this level. Tg levels were related to the existence of a positive scan or a negative one. In our 52 WBS positive patients concordant positive Tg levels were observed in 42 patients while in 10 patients we found a negative Tg levels after the surgery. After 1-year follow-up, out of initially 42 concordant patients 8 patients showed remaining concordant positive Tg and WBS values. Discordant results were observed in 13 patients (4 patients were Tg- and WBS+ while 9 patients were Tg+ and WBS-). In the majority of patients (50%) remained with concordant results but changed from Tg+ and WBS+ to Tg- and WBS-. Diagnostic WBS is an additional valuable tool, besides Tg levels, in the follow up of patients after total thyreoidectomy.
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Radioisótopos do Iodo , Tireoglobulina/sangue , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia , Seguimentos , Humanos , Metástase Neoplásica , Cintilografia , Recidiva , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/sangue , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/patologiaRESUMO
Background: Conflicting data exist on traditional lipid profiles in patients with Alzheimer's disease (AD) and vascular dementia (VD), whereas scarce number of studies evaluated non-traditional lipid profiles in patients with AD and VD. Studies have shown that ethnic background may affect lipid profile. Objective: The aim of the present study was to conduct comparative assessment of traditional and non-traditional lipid profiles in Bosnian patients with AD and VD. Methods: A controlled, cross-sectional study was performed with 66 patients with AD, 50 patients with VD, and 60 control subjects. The Montreal Cognitive Assessment (MoCA) test was used for an evaluation of the global cognitive function. The Hachinski ischemic score was used to distinguish patients with VD from those with AD. Plasma total cholesterol (TC), high-density lipoprotein -cholesterol (HDL-C), and triglycerides (TG) levels were determined using standard enzymatic colorimetric techniques, whereas the Friedewald formula was used to calculate low-density lipoprotein-cholesterol (LDL-C) levels. The non-traditional lipid indices such as TG/HDL-C, TC/HDL-C, and LDL-C/HDL-C ratio were separately calculated. The differences between the groups were analyzed with ANOVA followed by the Tuckey posthoc test or with the Kruskal Wallis test followed by the Mann-Whitney test. Results: Results of the present study have shown that patients in AD group had significantly lower level of TC, TG, LDL-C, VLDL-C, Non-HDL-C and significantly lower atherogenic index compared to the control group (CG) and compared to the VD patients. Significant difference in values of TG and VLDL-C was observed between VD and the CG, whereas no significant difference in values of TC, LDL-C, atherogenic index and Non-HDL-C was observed between these two groups. Our results have also shown that TG/HDL-C, TC/HDL-C, and LDL-C/HDL-C ratios were significantly lower in AD patients compared to the VD and CG. Moreover, TG/HDL-C ratio was significantly lower in VD compared to the CG. However, a significant difference in TC/HDL-C and LDL-C/HDL-C was not observed between VD and the CG. Conclusion: Based on the results of the present study it can be deduced that there is a difference in traditional and non-traditional lipid profiles between AD and VD patients of Bosnian descent. Obtained results suggest that lipids are decreased in AD and in VD to a certain extent. However, since there is an inconsistence in literature whether there is an association between cholesterol and cognition, large prospective studies are required to elucidate this controversy.
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Doença de Alzheimer , Demência Vascular , Humanos , LDL-Colesterol , Triglicerídeos , Doença de Alzheimer/diagnóstico , Demência Vascular/diagnóstico , Estudos Transversais , HDL-Colesterol , ColesterolRESUMO
Background: Lipids and lipoproteins are significantly involved in maintaining structural and functional components of the human brain and neurons, but their role in the development of Alzheimer's disease (AD) and vascular dementia (VD) remains unclear. Objective: The aim of the present study was to explore the differences in the standard and novel lipid profile parameters in patients with AD and VD, stratified by the degree of cognitive impairment (CI). Methods: Present study included 66 patients with AD, 50 patients with VD, and 60 control subjects. For an evaluation of the global cognitive function the Montreal Cognitive Assessment (MoCA) test was used. In order to distinguish patients with VD from those with AD the Hachinski ischemic score was used. Plasma total cholesterol (TC), high-density lipoprotein -cholesterol (HDL-C), and triglycerides (TG) levels were determined using standard enzymatic colorimetric techniques, whereas the Friedewald formula was used to calculate low-density lipoprotein-cholesterol (LDL-C) levels. The non-traditional lipid indices such as TG/HDL-C, TC/HDL-C, and LDL-C/HDL-C ratio were separately calculated. The differences between the groups were analyzed with the Kruskal Wallis test followed by the Mann-Whitney test or with ANOVA followed by the Tuckey posthoc test. Results: Results of the conducted study have found that the patients in AD group with moderate CI and patients in AD group with severe CI exhibited significantly lower levels of serum TC, TG, LDL-C, VLDL-C, Non- HDL-C, atherogenic index, TG/HDL-C, TC/HDL-C and LDL-C/HDL-C compared to cognitively normal control subjects. Moreover, patients in VD group with severe and moderate CI had significantly lower level of TG compared to control group of subjects. Our results have also shown that patients in AD group with moderate CI had significantly lower level of TC, TG, LDL-C, Non-HDL-C, atherogenic index, TG/HDL-C, TC/HDL-C compared to VD patients with moderate CI. In addition, patients in AD group with severe CI had significantly lower level of TC, LDL-C, Non-HDL-C and TC/HDL-C compared to VD patients with severe CI. Conclusion: The results of this study have shown dysregulation of lipid metabolism in AD and VD patients with different degree of CI. In both moderate and in severe CI, patients with AD had lower levels of majority of standard and novel lipid parameters compared to patients with VD. Further larger prospective studies are required to elucidate the accuracy of standard and novel lipid parameters in the assessment of different degree of CI in AD and VD.
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PURPOSE: Vitamin D3 (vit-D3) is a potent immunomodulator with anti-inflammatory and antioxidative properties. We used streptozotocin (STZ)-induced rat model of diabetes (DM) to evaluate the effects of vit-D3. We measured serum biochemical parameters, interleukin-17 (IL-17), osteocalcin (OC), malondialdehyde (MDA), and immune cell count on the 21st day of experiment. METHOD: A total of 24 Wistar rats were randomly divided into three groups. Each group had eight rats. During the 1st day of the experiment, the control group was injected intraperitoneally with citrate buffer, while STZ group and STZ + vit-D3 group were injected by a single i.p. dose (35 mg/kg) of STZ dissolved in citrate buffer (pH 4,5; 0,1 M). Vitamin D3 was applied via oral gavage once daily to the STZ + vit-D3 group for a total period of 14 days, starting from the 7th day of the experiment. RESULTS: STZ rats showed a significant reduction in OC and an increase in MDA and IL-17 serum concentrations compared to the control rats. We also observed a significant STZ-associated decrease in the number of lymphocytes and a significant increase in monocyte and eosinophil number. Oral treatment with vit-D3 to STZ-induced diabetic rats significantly increased OC and decreased MDA serum levels. Furthermore, vit-D3 treatment resulted in a good regulation of hematopoiesis such as increase in the number of segmented granulocytes and lymphocytes and a reduction in the number of monocytes and eosinophils. CONCLUSION: Vit-D3 treatment has important therapeutic effects; among many others it can attenuate oxidative stress and ameliorate the hyperglycemic state in the STZ-induced rat diabetic model, which is promising for further clinical trials.
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Musculoskeletal research has been enriched in the past ten years with a great wealth of new discoveries arising from genome wide association studies (GWAS). In addition to the novel factors identified by GWAS, the advent of whole-genome and whole-exome sequencing efforts in family based studies has also identified new genes and pathways. However, the function and the mechanisms by which such genes influence clinical traits remain largely unknown. There is imperative need to bring multidisciplinary expertise together that will allow translating these genomic discoveries into useful clinical applications with the potential of improving patient care. Therefore "GEnomics of MusculoSkeletal traits TranslatiOnal NEtwork" (GEMSTONE) aims to set the ground for the: 1) functional characterization of discovered genes and pathways; 2) understanding of the correspondence between molecular and clinical assessments; and 3) implementation of novel methodological approaches. This research network is funded by The European Cooperation in Science and Technology (COST). GEMSTONE includes six working groups (WG), each with specific objectives: WG1-Study populations and expertise groups: creating, maintaining and updating an inventory of experts and resources (studies and datasets) participating in the network, helping to assemble focus groups defined by phenotype, functional and methodological expertise. WG2-Phenotyping: describe ways to decompose the phenotypes of the different functional studies into meaningful components that will aid the interpretation of identified biological pathways. WG3 Monogenic conditions - human KO models: makes an inventory of genes underlying musculoskeletal monogenic conditions that aids the assignment of genes to GWAS signals and prioritizing GWAS genes as candidates responsible for monogenic presentations, through biological plausibility. WG4 Functional investigations: creating a roadmap of genes and pathways to be prioritized for functional assessment in cell and organism models of the musculoskeletal system. WG5 Bioinformatics seeks the integration of the knowledge derived from the distinct efforts, with particular emphasis on systems biology and artificial intelligence applications. Finally, WG6 Translational outreach: makes a synopsis of the knowledge derived from the distinct efforts, allowing to prioritize factors within biological pathways, use refined disease trait definitions and/or improve study design of future investigations in a potential therapeutic context (e.g. clinical trials) for musculoskeletal diseases.
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Inteligência Artificial , Loci Gênicos , Genômica/métodos , Sistema Musculoesquelético/metabolismo , Fenótipo , Biologia Computacional , Estudo de Associação Genômica Ampla , HumanosRESUMO
A synoptic overview of scientific methods applied in bone and associated research fields across species has yet to be published. Experts from the EU Cost Action GEMSTONE ("GEnomics of MusculoSkeletal Traits translational Network") Working Group 2 present an overview of the routine techniques as well as clinical and research approaches employed to characterize bone phenotypes in humans and selected animal models (mice and zebrafish) of health and disease. The goal is consolidation of knowledge and a map for future research. This expert paper provides a comprehensive overview of state-of-the-art technologies to investigate bone properties in humans and animals - including their strengths and weaknesses. New research methodologies are outlined and future strategies are discussed to combine phenotypic with rapidly developing -omics data in order to advance musculoskeletal research and move towards "personalised medicine".
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Osso e Ossos/metabolismo , Genômica/métodos , Fenômenos Fisiológicos Musculoesqueléticos/genética , Animais , Osso e Ossos/patologia , Redes Reguladoras de Genes/fisiologia , Humanos , Camundongos , Modelos Animais , Fenótipo , Proteômica/métodos , Peixe-ZebraRESUMO
Aim To evaluate vertebral bone marrow adiposity (BMA) using magnetic resonance spectroscopy (MRS) in postmenopausal women and to determine an association of bone density with bone marrow fat content. Methods This cross-sectional study included 120 postmenopausal women referred for osteoporosis screening. All women underwent assessment of bone mineral density by dual X-ray absorptiometry (DXA), who were divided based on T scores into osteoporosis (OST; n=60) and control group (CG; n=60). MRS was used to measure fat fraction (FF), lipid/water ratio (LWR) and fat content (FC) at vertebral spine (L1-L4). Results Mean age, menopause or reproductive period duration was not significantly different between women in OST and control group. Median LWR in OST group was significantly higher compared to CG, 31.5 (22.9-38.8) vs. 28.7 (13.7-37.3) (p=0.039). Median FC was significantly higher in OST compared to the control group, 47.0 (46.3-78.8) and 46.4 (44.3-48.6), respectively (p=0.011). FC was significantly negatively associated with BMD at lumbar spine (Rho=-0.042; p<0.001) and with BMD at hip (Rho=-0.64; p<0.001). In logistic regression model, FC remained independently associated with osteoporosis after controlling for confounders (age, menopause duration, reproductive period duration and body mass index) (OR=1.3; 95% CI 1.1-1.6). Conclusion Bone marrow adiposity is an independent predictor of low bone mass in postmenopausal women suggesting its role as a therapeutic target in postmenopausal osteoporosis management.
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Densidade Óssea , Medula Óssea , Adiposidade , Medula Óssea/diagnóstico por imagem , Estudos Transversais , Feminino , Humanos , Vértebras Lombares/diagnóstico por imagem , Pós-MenopausaRESUMO
OBJECTIVES: Although Dual-energy X-ray Absorptiometry (DXA) is gold standard for osteoporosis diagnosis, several reports have shown discordant T-score values measured by Quantitative Computed Tomography (QCT) and DXA especially in obese subjects, but it is still not clear whether BMD measurement by two modalities is affected by overall obesity or central obesity in postmenopausal females. Therefore, the aims of this study were to compare BMD and T-scores by DXA and QCT and to evaluate whether these two osteoporosis assessment modalities yield different T-score values in postmenopausal females with obesity and central obesity. METHODS: This cross-sectional study enrolled 44 postmenopausal females, referred for osteoporosis screening. Anthropometric indices (BMI-body mass index, WC-waist circumference and ICOindex of central obesity) were measured and females underwent an assessment of bone mineral density by DXA and QCT. RESULTS: Lumbar Spine (LS) T-score values were observed to be significantly lower by DXA compared to qCT in females with BMI >25 kg/m2, (-1.9±1.5 vs. -2.3±1.2; p=0.039), in females with WC>88 cm(-1.9±1.5 vs. -2.4±1.2; p=0.008) and in females with ICO>0.5(-1.96±1.4 vs. -2.5±1.2; p=0.004). However, in normal-weight females and in those without central obesity, LS T-scores by DXA were not different than qCT. DXA at lumbar spine and proximal femur revealed osteoporosis in 47.7% and 11.4% respectively, while QCT detected osteoporosis in 61.4% of females (p<0.001). Measures of central obesity; ICO and WC were not associated with QCT bone mineral density (BMD) (r=0.14 and r=0.21, respectively), but were positively associated with both DXALS BMD (r=0.29 and r=0.31; p<0.05) and DXA proximal femur BMD (r=0.41 and r=0.44; p<0.01). CONCLUSION: Our results suggest that obesity is associated with lower T-scores by DXA compared to QCT. Caution is needed when assessing osteoporosis status in obese postmenopausal females. However, further studies with larger sample size are needed to confirm the findings.
Assuntos
Densidade Óssea , Obesidade Abdominal , Absorciometria de Fóton , Estudos Transversais , Feminino , Humanos , Obesidade/complicações , Obesidade/diagnóstico por imagem , Obesidade/epidemiologia , Obesidade Abdominal/diagnóstico por imagem , Pós-MenopausaRESUMO
Aim To examine whether preoperative tumour size may serve as a biomarker for the occurrence of lymphovascular invasion (LVI) in centrally and peripherally located lung adenocarcinoma. Method The study included 261 patients surgically treated for diagnosed lung adenocarcinoma. A ROC curve was used to determine the biomarker potential of tumour size relative to the occurrence of LVI. Binary logistic regression was used to show changes of tumour size impact on the status of LVI. Result Tumour prevalence according to localization had no statistical significance (p=0.464), while the presence of LVI in central, as well as peripheral positions, was statistically significantly different (p<0.001). The area under the curve of 0.978 highlights the fact that tumour size is an excellent marker of the presence of LVI in centrally located adenocarcinomas of the lung. A similar finding was confirmed in peripherally located lung adenocarcinomas with an area below the curve of 0.943. Binary logistical regression showed that in centrally localized adenocarcinomas of the lung, each additional centimetre of tumour growth represents an increase in the likelihood of LVI+ by 17.14 times. In peripherally located adenocarcinomas of the lung, this increase in likelihood of LVI for each centimetre of growth was 5.46 times. Conclusion With a high degree of sensitivity and specificity, preoperative tumour size may serve as an important biomarker and positive predictor of the presence of LVI in lung adenocarcinoma of any location.
Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/patologia , Metástase Linfática , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Prognóstico , Estudos RetrospectivosRESUMO
INTRODUCTION: Symptomatic and etiopathologic heterogeneity of schizophrenia (SCH) and bipolar disorder (BD) can be adequately addressed using a dimensional approach to psychopathology, as well as interpreting physiological properties and markers as predictors of disease onset and relapse. Risk factors, genetic and environmental, are likely to modify the neurobiological processes characteristic of certain physiological processes that manifest to a greater degree of overlapping symptoms. One of the most common laboratory tests in psychiatric patients is a standard laboratory blood test. It gives us an insight into the general somatic condition of the patient. It assesses the ability to transport oxygen to tissues and carbon dioxide back to the lungs via erythrocytes (RBC) and hemoglobin (HGB) as their most important constituents, and is also an indicator of iron status and blood oxygenation. AIM: Schizophrenia (SCH) and bipolar disorder (BD) are psychiatric disorders whose complex etiology and pathogenesis are still far from known. A correlation between red blood cell abnormalities and these diseases has been recognized in some studies. One of the most common laboratory tests in psychiatric patients is a standard laboratory blood test. However, so far there is a small number of published papers that relate to the relationship between laboratory parameters of blood and the aim of this paper is to reveal more light in this subject. METHODS: The research was done as an observational prospective clinical study that has evaluated different physiological and pathological parameters in patients with BD and SCH over a two-year period. A total of 159 patients with schizophrenia, 61 patients diagnosed with bipolar disorder and 82 healthy subjects participated in this study. RESULTS: At baseline, BD compared to SCH patients had higher mean lymphocyte count (2,6±0,7 vs. 2,0±0,6x109; p=0,006) and haemoglobin concentration (146,8±12,2 vs. 140,2±14,7 g/L; p=0,03), and significantly lower red cell distribution width (13,6±2,2 vs. 14,7±1,8%; p=0,008). In both BD and SCH patients there was a significant number of patients with low red blood cells count and low haemoglobin concentration, and high MCH and MCHC at baseline and at 3 and 6 months of follow up. CONCLUSIONS: The finding that SCH as well as BD differed from controls with respect to red blood cells, hemoglobin, lymphocytes, and average platelet count was consistent with previous findings and could be understood as a qualitative measure in the evaluation of this sample. The fact that no association with other parameters was found, as well as an association with the diagnosis, does not exclude that these associations can be found in larger samples.