Predictors of Coronary and Carotid Atherosclerosis in Patients with Severe Degenerative Aortic Stenosis

Background. Patients with degenerative aortic stenosis (AS) exhibit elevated prevalence of coronary artery disease (CAD) and internal carotid artery stenosis (ICAS). Our aim was to investigate prevalence of significant CAD and ICAS in relation to demographic and cardiovascular risk profile among patients with severe degenerative AS.Methods. We studied 145 consecutive patients (77 men and 68 women) aged 49-91 years (median, 76) with severe degenerative AS who underwent coronary angiography and carotid ultrasonography in our tertiary care center. The patients were divided into two groups according to the presence of either significant CAD (n=86) or ICAS (n=22).Results. The prevalence of significant CAD or ICAS was higher with increasing number of traditional risk factors (hypertension, hypercholesterolemia, diabetes, smoking habit) and decreasing renal function. We found interactions between age and gender in terms of CAD (p=0.01) and ICAS (p=0.06), which was confirmed by multivariate approach. With the reference to men with a below-median age, the prevalence of CAD or ICAS increased in men aged >76 years (89% vs. 55% and 28% vs. 14%, respectively), whereas the respective percentages were lower in older vs. younger women (48% vs. 54% and 7% vs. 17%).Conclusions. In severe degenerative AS gender modulates the association of age with coronary and carotid atherosclerosis with its lower prevalence in women aged >76 years compared to their younger counterparts. This may result from a hypothetical “survival bias”, i.e., an excessive risk of death in very elderly women with severe AS and coexisting relevant coronary or carotid atherosclerosis.     

Mandibular dental changes following serial and late extraction of mandibular second premolars

Objectives:To determine changes in occlusal curves and dental tipping occurring from mandibular second premolar serial extraction, early extraction of deciduous mandibular second molars with missing second premolars, and late second premolar extraction compared with untreated controls.Materials and Methods:Information was collected from 85 subjects at three time points: T0, prior to serial extraction; T1, after serial extraction and drift prior to orthodontic treatment, and pretreatment for the late premolar extraction patients; and T2, posttreatment. Untreated age- and gender-matched controls were used for comparison. Three occlusal curves were measured on digitized mandibular casts, and dental tipping was assessed using lateral cephalograms.Results:At T0, there were no significant differences among groups. At T1, there was significant steepening of Monson''s sphere and the curve of Wilson between early and late extraction and control groups. At T2, the differences in Monson''s sphere and the curve of Wilson were fully corrected. At T1, there were significant differences in the tipping of mandibular 6''s, 4''s, and 3''s between the early extraction groups compared with the late extraction and control groups. At T2, these differences in tipping were fully corrected. There were no differences in mandibular incisor tipping between groups at T1 or T2.Conclusions:Serial extraction produced steeper occlusal curves and significant tipping of mandibular first molars, first premolars, and canines after extraction and physiologic drift (T1). Accentuated occlusal curves and tooth tipping were fully corrected following orthodontic treatment (T2). Mandibular incisor position was unchanged by serial or late second premolar extraction.     

Temporal integration of melatonin infusion duration: signal averaging versus frequency dependence

Day length affects somatic and reproductive physiology of Siberian hamsters via regulation of the duration of nocturnal pineal melatonin secretion. Nightly 'long' (e.g. 12 hr) or 'short' (e.g. 6 hr) melatonin signals inhibit or stimulate gonadal growth, respectively. When long and short signals are presented in combination, however, neuroendocrine mechanisms exhibit a frequency-dependent response, stimulating gonadal growth only if short signals are presented every second night or more frequently. The present experiments further assessed formal models for the temporal integration of melatonin signals changing abruptly in duration from night to night. Photo-inhibited Siberian hamsters were housed in constant light and infused subcutaneously with various combinations of nightly short or long melatonin signals according to one of the several regimes that varied the frequency of short melatonin signal occurrence, average duration of the nightly melatonin signal, or both. Six weeks of nightly alternating short and long signals yielded different gonadal responses depending on the average melatonin signal duration. Moreover, when average melatonin signal duration was held constant between groups, gonadal stimulation was independent of the frequency of the constituent melatonin signals except when the duration of the short signal was reduced to 3 hr. Thus, neuroendocrine mechanisms do not solely categorize melatonin signals as either long or short but attend also to the duration of each component signal. In the majority (six of seven) of infusion regimes, reproductive responses to chimeric patterns of long and short melatonin signals were compatible with a simple signal-averaging mechanism.     

Factors associated with preservation of C-peptide levels at the diagnosis of type 1 diabetes

Aims

The level of C-peptide can identify individuals most likely to respond to immune interventions carried out to prevent pancreatic β-cell damage.The aim of the study was to evaluate factors associated with C-peptide levels at type 1 diabetes (T1D) diagnosis.

Interleukin 6 -174(G>C) gene polymorphism is related to celiac disease and autoimmune thyroiditis coincidence in diabetes type 1 children

The aim of the study was to assess the relationship between IL-6 gene polymorphism at -174(G>C) and the coincidence of celiac and autoimmune thyroid diseases with type 1 diabetes mellitus (DM1) in children. 200 children with DM1 aged 13.23+/-3.54 years and 172 healthy controls were analyzed. The IL-6 gene -174(G>C) polymorphism at the promoter region of the gene was analyzed by the PCR-RFLP method. The genotype distribution was significantly different in diabetic children as compared to the healthy controls (p=0.01). In DM1 patients GC heterozygotes were the most common (52.5%), while CC homozygotes accuted for 29% and GG homozygotes only for 18% of cases. In contrast, GG homozygotes were much more frequent among healthy children (31%). Besides, the GG homozygotes were significantly more frequent among diabetic children with celiac disease (p=0.04) in relation to those without autoimmune complications. In children with autoimmune thyroiditis, the distribution of the IL-6 genotypes was similar to that seen in diabetic patients without autoimmune complications (p=0.24). The results of our study suggest that the diabetic children, who have IL-6 gene -174GG genotype may have an increased risk for celiac disease development.     

Urinary tract infections in pregnancy: old and new unresolved diagnostic and therapeutic problems

Urinary tract infections (UTIs) are common in pregnant women and pose a great therapeutic challenge, since the risk of serious complications in both the mother and her child is high. Pregnancy is a state associated with physiological, structural and functional urinary tract changes which promote ascending infections from the urethra. Unlike the general population, all pregnant women should be screened for bacteriuria with urine culture, and asymptomatic bacteriuria must be treated in every case that is diagnosed, as it is an important risk factor for pyelonephritis in this population. The antibiotic chosen should have a good maternal and fetal safety profile. In this paper, current principles of diagnosis and management of UTI in pregnancy are reviewed, and the main problems and controversies are identified and discussed.     

In Vitro Differentiation and Expansion of Human Pluripotent Stem Cell-Derived Pancreatic Progenitors

Recent progress in understanding stem cell biology has been remarkable, especially in deciphering signals that support differentiation towards tissue-specific lineages. This achievement positions us firmly at the beginning of an era of patient-specific regenerative medicine and human disease modeling. It will be necessary to equip the progress in this era with a reliable source of self-renewing progenitor cells that differentiate into functional target cells. The generation of pancreatic progenitors that mature in vivo into functional beta-cells has raised the hope for new therapeutic options in diabetes, but key challenges still remain including the production of sufficient numbers of cells for research and transplantation. Recent approaches to this problem have shown that the presence of organ- and stage-specific mesenchyme improves the generation of progenitors, from endoderm to endocrine cells. Alternatively, utilization of three-dimensional culture may improve the efficiency and yield of directed differentiation. Here, we review the current knowledge of pancreatic directed differentiation and ex vivo expansion of pancreatic progenitors, including recent advances in differentiation strategies for the generation of pancreatic progenitors, and we discuss persistent challenges which will need to be overcome before personalized cell-based therapy becomes a practical strategy.     

Induction of immediate early genes expression in the mouse striatum following acute administration of synthetic cathinones

BackgroundSynthetic cathinones (SCs) form one of the most prominent group of the New Psychoactive Substances. SCs enhance central dopaminergic and noradrenergic neurotransmission, and are used as substitutes for illicit psychostimulants, namely cocaine, amphetamine, and methamphetamine. Changes in the expression of immediate early genes (IEGs) in the striatum underlie the addictive potential of drugs of abuse belonging to distinct pharmacologic groups. This work was aimed to assess the impact of acute administration of the prominent SCs on the mRNA levels of IEGs in the mouse striatum.MethodsEffects of 3,4-MDPV, 2,3-MDPV, α-PVP, PV8, PV9, methcathinone (MC) and 3-fluoromethcathinone (3-FMC) on the mRNA levels of ten IEGs, one and two hours after exposure, were measured in the mouse striatum using the quantitative RT-PCR technique.ResultsAll SCs used in the study produced increased mRNA levels of the following IEGs: Areg, c-fos, Csrnp1, Dusp1, Dusp14, Egr2, Egr4 and FosB. Additionally, the majority of SCs increased the expression of Homer1 and c-jun. The magnitude of observed changes varied by the drug, analyzed gene and, in many cases, by time after administration.ConclusionsThis study demonstrates that SCs increase the expression of IEGs in the mouse striatum, which may lead to a plethora of effects, as proteins encoded by the analyzed genes are involved in diverse actions, including an acute response to the drug and the neuroplasticity underlying the development of addiction.