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Epigenetics and testicular germ cell tumors
Get PDFMalignant testicular germ cell tumors (TGCTs) are the most frequent testicular cancers in Caucasian males,
developing at the most productive age of man. We are briefly reviewing TGCT-tumorigenesis with an emphasis
on epigenetics. Epigenetic mechanisms such as DNA methylation and histone modifications together with RNA
interference that all change gene expression are driving early spermatogenesis. Deregulation of normal development
might lead to a testicular germ cell neoplasia in situ (GCNIS), from which TGCTs originate. The
breakthrough epigenetic research, both in normal development and TGCT tumorigenesis, has been going on to
find better biomarkers and therapy for this type of tumors
Celijakija - nedovoljno prepoznat javnozdravstveni problem [Celiac disease - insufficiently recognized public health problem]
Get PDFCeliac disease is a chronic autoimmune disease characterized by gluten intolerance. Clinical presentation
includes several clinical types of the disease and symptoms of various organ systems. The prevalence of the disease is
rising and there is no mass screening. Gold standard in diagnostics are small intestinal mucosal biopsy and determination
of specifi c serum antibodies, although most patients are not diagnosed on time and have the wrong diagnosis which
increases the frequency of complications, number of hospitalizations, disability and expenses. The quality of life is also
reduced. The treatment is gluten-free diet and continuous adherence to it. In Croatia in 2015 there were several thousand
patients registered with the diagnosis of celiac disease. On the Croatian Health Insurance Fund lists there is gluten-free
fl our available for diagnosed patients. Total therapy expenses rise up to several million kuna but they are still smaller
than expenses before making the right diagnosis. In conclusion it can be said that celiac disease is not yet recognized as
a global public health burden that is rising in its importance. The main goal should be raising the awareness about this
disease for better supervision and timely diagnosis and treatment
Reconstructing the life of a Roman soldier buried in Resnik near Split, based on the anthropological analysis of his skeleton
Get PDFContinuous heavy physical labor and the habitual performance of specific actions during everyday activities affects bone and modifies its morphology, particularly if these activities were time consuming and began at an early age. Analysis and interpretation of these changes provides a unique view into the quality of life, the quantity and type of labor, as well as the risks associated with specific occupations or activities. Here we present the results of an anthropological analysis of a skeleton excavated from the antique necropolis in Resnik. Recovered archaeological finds from the grave (a socketed spear head) suggest that the buried individual was in some way related to the Roman army, possibly as a legionary or as a beneficiary. Osteological data from the skeleton was compared to a theoretical and idealized representation of a perfect Roman soldier, as reported by Vegetius Renatus in his work "Summary of military skill" (Epitome rei militaris), in order to reconstruct the life of a real Roman legionary who served in the Roman province of Dalmatia at the end of the 2nd c. AD. The skeleton provides information on general living conditions in the 2nd c. AD, as well as on the specific risks associated with military life. General living conditions include parasitic infestations and subsequent anemia that resulted in numerous viral and bacterial infections, while specific risks related to military life include numerous osteological indicators of physical stress and heavy physical labor. The presences of two remodeled antemortem fractures show that the risk of traumatic injuries was high in Roman soldiers
Cardiovascular markers of inflammation and serum lipid levels in HIV-infected patients with undetectable viremia
Get PDFPatients successfully treated for HIV infection still have an increased risk for cardiovascular morbidity and mortality, which might be related not only to traditional risks, but also to inflammation and dyslipidemia. We examined the relationship of serum lipid levels with plasma biomarkers of inflammation using a composite inflammatory burden score (IBS) based on individual (>75th percentile) measurements from the following seven markers: CD40L, tPA, MCP-1, IL-8, IL-6, hCRP and P-selectin. IBS was categorized as 0 (none of the biomarkers >75th percentile), 1, 2 and 3 or more scores. Correlations between the IBS and lipid parameters were examined by ordered logistic regression proportional odds models to estimate the odds of more elevated biomarkers. 181 male patients with undetectable HIV-viremia were included into the study. In the multivariate model, a one-unit increase (mmol/L) of total cholesterol and triglycerides was associated with a 1.41-fold (95% CI, 1.13-1.76) and 1.37-fold (95% CI, 1.18-1.60) increased odds of having a greater IBS, respectively. Those with an IBS score ≥1 compared to none had 2.14 (95% CI, 1.43-3.20) higher odds of having a one-unit increased total cholesterol/HDL-cholesterol ratio. In successfully treated HIV-infected persons dyslipidemia was associated with inflammation
Management of measurable variable cardiovascular disease' risk factors
Get PDFAIM:
To summarize the main findings on variable cardiovascular risk factors and their management in everyday practice. ----- METHODS:
A narrative review of the relevant literature known to the authors and incorporation of healthy changes tips in defined variable cardiovascular risk factors. ----- RESULTS:
There are known variable cardiovascular risk factors to be claimed as those that should be changed in order to achieve a better prevention of cardiovascular disease development. But, most papers are informative and they didn't incorporate exact measures for each variable risk factor. Our paper shows exact measures for each variable cardiovascular risk factor that should be incorporate in everyday practice of family practitioners and cardiologists as well. ----- CONCLUSION:
The best cardiovascular disease' prevention should include a multidisciplinary team of experts and the entire community with the support of governmental and non-governmental organizations that will contribute to improving the lifestyle of individuals and the entire community through their activities and legal provisions. The most important factors in cardiovascular disease management are: recognizing individual risk factors, monitoring them, and assisting in changes in life-style habits that directly affect the defined risk factors of a patient. The simplest and most practicable guidelines for CV prevention in accordance with the national, cultural and socioeconomic aspects of their country of work are needed
Effects of metabolic syndrome on arterial function in different age groups
Get PDFOBJECTIVE:
The aim of the Advanced Approach to Arterial Stiffness study was to compare arterial stiffness measured simultaneously with two different methods in different age groups of middle-aged and older adults with or without metabolic syndrome (MetS). The specific effects of the different MetS components on arterial stiffness were also studied. ----- METHODS:
This prospective, multicentre, international study included 2224 patients aged 40 years and older, 1664 with and 560 without MetS. Patients were enrolled in 32 centres from 18 European countries affiliated to the International Society of Vascular Health & Aging. Arterial stiffness was evaluated using the cardio-ankle vascular index (CAVI) and the carotid-femoral pulse wave velocity (CF-PWV) in four prespecified age groups: 40-49, 50-59, 60-74, 75-90 years. In this report, we present the baseline data of this study.
----- RESULTS:
Both CF-PWV and CAVI increased with age, with a higher correlation coefficient for CAVI (comparison of coefficients P < 0.001). Age-adjusted and sex-adjusted values of CF-PWV and CAVI were weakly intercorrelated (r = 0.06, P < 0.001). Age-adjusted and sex-adjusted values for CF-PWV but not CAVI were higher in presence of MetS (CF-PWV: 9.57 ± 0.06 vs. 8.65 ± 0.10, P < 0.001; CAVI: 8.34 ± 0.03 vs. 8.29 ± 0.04, P = 0.40; mean ± SEM; MetS vs. no MetS). The absence of an overall effect of MetS on CAVI was related to the heterogeneous effects of the components of MetS on this parameter: CAVI was positively associated with the high glycaemia and high blood pressure components, whereas lacked significant associations with the HDL and triglycerides components while exhibiting a negative association with the overweight component. In contrast, all five MetS components showed positive associations with CF-PWV.
----- CONCLUSION:
This large European multicentre study reveals a differential impact of MetS and age on CAVI and CF-PWV and suggests that age may have a more pronounced effect on CAVI, whereas MetS increases CF-PWV but not CAVI. This important finding may be due to heterogeneous effects of MetS components on CAVI. The clinical significance of these original results will be assessed during the longitudinal phase of the study
Association of autonomic nervous system abnormalities on head-up tilt table test with joint hypermobility
Get PDFAIM:
The aim of this study was to investigate the association of autonomic nervous system abnormalities on head-up tilt table test (HUTT) with generalized joint hypermobility, expressed by Beighton score (BS). ----- METHODS:
This was a prospective study that included 115 consecutive patients (91 females; mean age 34.35 ± 14.11) referred either for the HUTT or testing of the cardiovascular autonomic reflexes together with HUTT. Generalized joint hypermobility was evaluated according to the BS system after which HUTT was performed. Clinically significant BS was considered if ≥4.
----- RESULTS:
Fifteen patients (15.1%) had BS ≥4. Results of the HUTT were normal in 58 (50.4%) patients and in 57 (49.6%) patient HUTT was abnormal. Fifteen (13.0%) patients fulfilled criteria for orthostatic hypotension, 30 (26.1%) for reflex syncope and 21 (18.3%) for postural orthostatic tachycardia syndrome. Patients with pathological findings on HUTT had significantly higher BS compared to patients with normal HUTT (median 1 vs. 0, p = 0.001). There was a significant association between participants with BS ≥4 and pathological HUTT (χ[1] = 6.392, p = 0.011). Results of the multivariate regression analysis revealed that increase in the BS is associated with the increased likelihood of HUTT pathology (Exp[B] 1.44, 95% CI 1.084-1.922, p = 0.012), while increase in age is associated with lower risk of HUTT pathology (Exp[B] 0.968, 95% CI 0.939-0.998, p = 0.036).
----- CONCLUSION:
There is an association between autonomic nervous system abnormalities on HUTT test and generalized joint hypermobility
Serum chitotriosidase: a circulating biomarker in polycythemia vera
Get PDFObjectives: Serum chitotriosidase activity (CHIT1) is a biomarker of macrophage activation with an important role in inflammation-induced tissue remodeling and fibrosis. Macrophages have been described to play a crucial role in regulating pathological erythropoiesis in polycythemia vera (PV). The aim of this study was to evaluate CHIT1 in patients diagnosed with Philadelphia-negative myeloproliferative neoplasms (MPNs). -----
Methods: Using fluorometric assay, we measured CHIT1 in 28 PV, 27 essential thrombocythemia (ET), 17 primary myelofibrosis (PMF), 19 patients with secondary myelofibrosis and in 25 healthy controls. -----
Results: CHIT1 was significantly higher in PV (p < .001) and post-PV myelofibrosis (MF) transformation (post-PV MF) (p = .020), but not in ET (p = .080), post-ET MF transformation (p = .086), and PMF patients (p = .287), when compared to healthy controls. CHIT1 in PV was positively correlated with hemoglobin (p = .026), hematocrit (p = .012), absolute basophil count (p = .030) and the presence of reticulin fibrosis in the bone marrow (p = .023). -----
Discussion: A positive correlation between CHIT1 and these distinct laboratory PV features might imply macrophages closely related to clonal erythropoiesis as cells of CHIT1 origin. In addition, a positive association between CHIT1 and reticulin fibrosis might indicate its potential role in PV progression. -----
Conclusion: CHIT1 might be considered as a circulating biomarker in PV. Additional studies are needed to clarify the role of CHIT1 in promoting disease progression and bone marrow fibrosis in PV
Utjecaj odgođene funkcije presatka na progresiju kroničnih histoloških promjena u presađenom bubregu [The impact of delayed graft function on progression of chronic histological changes in transplanted kidney]
Get PDFBackground and objectives: Delayed graft function (DGF) is a manifestation of acute kidney injury resulting from ischemia-reperfusion
injury. It has usually been defined as the need for dialysis within 7 days after transplantation.
Aim of our study was to evaluate effect of delayed graft function on the progression of fybrosis
in transplanted kidney after deceased donor kidney or kidney pancreas transplantation.
Methods and materials: Our study was retrospective. We included 163 consecutive patients transplanted in our center from 2007
to 2014. Kidney graft only, and kidney pancreas transplanted patients were included. Patients
without paired biopsies (day 0 and 12 moths postransplant) were excluded. The primary
outcome was the one year progression of chronic histology changes based on protocol biopses
performed on the day of transplantation and at 12 months postransplant. We used composite
chronic histological score as a marker of chronic allograft injury, and separate chronic scores
ci and ct. The composit score is a sum of Banff chronic scores ci,ct,ah and cv (therefore, score
value range 0–12). We analysed the distribution of the change (Δ score) in the composite score
between group of patients with and without delayed graft function on paired biopsies, and
distribution of change for separate scores. We also analysed impact of DGF on graft survival and
graft function in our cohort of patients.
Results: There were 60 patients with DGF (36.8%) in our cohort. Follow up was 1665 ± 590 days. Chronic
composite histological score were statisticaly significantly higher in all biopsies at 12 months
after transplantation (1.92 ± 2.16 at 0 biopsies vs. 3.56 ± 2.93 at 12 months biopses, p<0.001).
In univariate analysis DGF was correlated with composite chronic histological score and with
the change of the score (Δ). In a multivariate analysis DGF was not correlated with composite
chronic histological score at 12 months (p=0.417) but it was correlated with change of the score
(Δ) (p=0.012). DGF was not correlated with ci and ct at 12 months, and it was also not correlated
with change of ci and ct score (Δ). Graft and patient survival was similar in both groups.
Conclusion: Chronic allograft injury, as measured by a composite score and separate scores, ci and ct increased only
mildly in the first post-transplant year. Delayed graft function does not seem to be a major drive
of a chronic allograft injury during first post-transplant year