Genetic structuring and differentiation of Echinococcus multilocularis in Slovakia assessed by sequencing and isoenzyme studies

Summary Nucleotide sequencing of the mitochondrial cytochrome c oxidase subunit 1 (CO1) gene and isoenzyme analysis were used to survey the genetic variability in Echinococcus multilocularis populations from Slovakia. A sample of 12 isolates acquired from 10 different districts from red foxes exhibited identical sequences. Compared with the previously described E. multilocularis variants, one base substitution was consistently observed relative to the M1 variant (detected in China, Alaska, North America, Japan) and three base substitutions were recorded relative to the M2 variant (detected in Germany) in the CO1 fragment. These data, along with the recently gathered data from French isolates, are indicative of a genetically unique population occurring in Central and Western Europe. Electrophoretic examination of enzymes produced by 14 gene loci revealed intraspecific polymorphism only with the glucose-phosphate isomerase (two distinct patterns) and the mannosephosphate isomerase (four genotypes composed of three alleles) enzyme systems. To allow a fast species differentiation of E. multilocularis and E. granulosus (specifically, the G7 genotype occurring in Slovakia), discriminative electrophoretic characters between the species were obtained by isoenzyme analysis. Fixed genetic differences between the species were detected in the glucose-phosphate isomerase, esterase and aldolase systems, and partial differences were detected in four additional systems.     

HER-2 [Ile655Val] polymorphism in association with breast cancer risk: a population-based case-control study in Slovakia

Breast cancer belongs to the most frequent types of cancer affecting women and it occurs at any age. Around 1600-1800 women are getting ill annually in the Slovak republic. One of the most important factors in connection with cancer genesis refers to changes in specific genes. HER-2 proto-oncogene belongs to low penetrating genes, which increase susceptibility to breast cancer genesis. Clinical studies demonstrated an association between polymorphism at codon 655 of this gene and increased risk for breast cancer development. The aim of this case-control based prospective study was to determine the distribution of HER-2 genotype and its association with risk factors of breast cancer in the population of women in Slovak republic. HER-2 genotypes were determined with PCR-RFLP method. The DNA was isolated from white blood cell nuclei. The frequency of Val allele in the cancer group was 29.79% and was higher than in the control group 15.84% (p<0.05). The presence of the heterozygote (Ile/Val) genotype was identified in 46.81% of patients in the case group and in 28.33% in healthy individuals, and the homozygote (Val/Val) genotype in 6.38% and 1.67, respectively (p<0.01). The risk of breast cancer development for carriers of one valine (Val) allele in genotype was two-times lower (OR=2.47) than for carriers of two Val alleles (OR=5.73) (p<0.05). Risk of cancer genesis for Val allele carriers was higher in multiparas (OR=2.90), among women with positive family history of breast cancer (OR=5.0), BMI>24 (kg/m2), and late menopause (OR=1.5). Contraceptives in anamnesis contrariwise showed tend to decrease the risk in Val allele carriers (OR=0.3). In conclusion, this study revealed relatively high frequency of the Val allele among the women population of the Slovak republic. Ile655Val polymorphism of HER-2 gene was associated with a statistically significantly increased risk of breast cancer all above in homozygotes for Val allele.     

Glucose Control in the ICU: Is There a Time for More Ambitious Targets Again?

During the last 2 decades, the treatment of hyperglycemia in critically ill patients has become one of the most discussed topics in the intensive medicine field. The initial data suggesting significant benefit of normalization of blood glucose levels in critically ill patients using intensive intravenous insulin therapy have been challenged or even neglected by some later studies. At the moment, the need for glucose control in critically ill patients is generally accepted yet the target glucose values are still the subject of ongoing debates. In this review, we summarize the current data on the benefits and risks of tight glucose control in critically ill patients focusing on the novel technological approaches including continuous glucose monitoring and its combination with computer-based algorithms that might help to overcome some of the hurdles of tight glucose control. Since increased risk of hypoglycemia appears to be the major obstacle of tight glucose control, we try to put forward novel approaches that may help to achieve optimal glucose control with low risk of hypoglycemia. If such approaches can be implemented in real-world practice the entire concept of tight glucose control may need to be revisited.     

Complications of circumferential pulmonary vein isolation using the cryoballoon technique: Incidence and predictors

Background

Cryoballoon ablation technique for the treatment of atrial fibrillation (AF) is a complex procedure consisting of several procedural steps associated with significant risk of complications. The aim of this single-centre study was to give detailed analysis of the complication rate and corresponding risk factors of pulmonary veins cryoisolation (PVI) procedures.

Methods and results

A total of 158 consecutive patients (71.5% men, aged 57 ± 9 years, 73.3% paroxysmal atrial fibrillation) were enrolled. Out of 632 pulmonary veins, 96.7% were targeted and isolated by 2–7 applications of cryothermal energy guided with intracardiac echocardiography and fluoroscopy. The additional ablation of cavotricuspid isthmus was performed in 14.6% of procedures. In total, 29 complications were recorded in peri-procedural or early post-procedural period, 8 (5.1%) of them being evaluated as major. No case of permanent injury, disability or death was registered. Multivariate logistic regression showed the persistence of pre-ablation AF as the risk factor of major complications (OR = 5.0; ± 95% CI: 1.14–21.97, P = 0.033); lower body height was the significant risk factor of any complications (OR = 0.95; ± 95% CI: 0.91–0.99, P = 0.026) with rapid increase of complication risk with body height ≤ 162 cm. Embolic complications were significantly associated with the pre-ablation AF, while patients with low body height had a trend towards increased risk of phrenic nerve palsy.

Conclusion

Our study confirmed that the cryoballoon pulmonary vein isolation can be safely performed with low incidence of life-threatening complications which may be further decreased if the mentioned risk factors are handled appropriately.     

Late coronary stent thrombosis and clopidogrel

The existence of late coronary stent thrombosis is a topical issue in cardiology today. The synoptic article discusses current definition of the above phenomenon, its delimitation in time and actual incidence. Based on data from available observation and randomised studies, long-term safety of conventional bare metal and drug-eluting stents is evaluated, as well as the safety profile following implantation. The length of thienopyridin treatment after percutaneous coronary intervention (PCI) varies according to the type of stent used. While a conventional bare metal stent (BMS) implant provides long-term safety with one month treatment, the implantation of a drug-eluting stent (DES) should be complemented with a 12-month period of clopidogrel administration. This approach may be in the future influenced by further progress in drug-eluting stents development and by prospectively acquired information on long-term administration of clopidogrel to such patients.     

Periodontal care may improve endothelial function

BackgroundPeriodontitis is a chronic, infectious, insidious disease of the tooth-supporting structures that causes a general inflammatory response. The aims of this study were to determine whether periodontitis is associated with endothelial dysfunction leading to cardiovascular events and whether proper management of periodontal disease would improve endothelial function and prevent cardiovascular events in the future.MethodsTwenty-two patients (12 women, 10 men; 40 ± 5 years old) took part in the study. All had severe periodontitis (without systemic disorders) and were all treated conservatively. Thirteen patients returned for a second visit after 3 months of treatment. Endothelial function and periodontal status were evaluated on entry into the study and 3 months following treatment. Ten age-matched, healthy volunteers without periodontal disease served as the control group.ResultsThere was a significant difference between the patient group and the healthy controls: FMD% 4.12 ± 3.96 vs. 16.60 ± 7.86% (p = 0.0000). Periodontitis improved significantly in all 13 patients who completed 3 months of treatment, and their endothelial function improved as well: FMD% 4.12 ± 3.96% vs. 11.12 ± 7.22% (p = 0.007). No difference was found in FID% before and after 3 months of treatment: 20.97 ± 10.66% vs.17.94 ± 6.23% (p = NS).ConclusionsPeriodontitis may be an insidious cause of endothelial dysfunction and cardiovascular events. Treating periodontitis can improve endothelial function and be an important preventive tool for cardiovascular disease.     

Internal jugular venous thrombosis after in vitro fertilization

Internal jugular vein thrombosis is an uncommon entity with high morbidity and an increased risk of mortality. Spontaneous clotting of the internal jugular vein without any known risk factors is virtually unheard of, and intravenous drug use is the most common cause for thrombosis. Assisted reproductive techniques alone or in conjunction with ovarian hyperstimulation syndrome seem to predispose patients for thrombosis of the internal jugular vein. We present the case of a patient who, after in vitro fertilization, developed ovarian hyperstimulation syndrome and clotted the internal jugular vein. In the setting of the Emergency Department, the norm should be to "rule out internal jugular venous thrombosis" in pregnant patients who have undergone in vitro fertilization and present with neck pain, with or without swelling or distended collaterals.     

Overview of the university-based addiction studies programs in the United States

Background: The field of addiction studies (AS) has grown in the last several decades. However, little is known about the structure and conditions of current academic programs. Only two studies have examined AS programs in the U.S., and both were conducted almost 15 years ago. The current study was designed to identify AS programs existing in the U.S. universities.

Methods: We conducted an Internet search to identify university-based programs according to defined key words. The university program websites were then subjected to content analysis.

Results: A total of 333 U.S. universities were identified that offered 392 different academic programs in AS of which 302 were degree programs. Out of these, 161 (53%) programs were offered at the associate degree level, 48 (15,9%) at the bachelor’s level, 55 (18.2%) at the master’s level, and 5 (1.6%) at the doctorate level. The largest number of programs was in California. Two states in the U.S. had no identifiable programs. Only one university located in the state of New York offered comprehensive academic programs across the educational spectrum. Many of the academic programs offered certificates. The most common phrases used in program titles were “substance abuse”, “addiction studies/counseling”, and “chemical dependency”.

Conclusions: There is a wide range of academic AS programs in the U.S., although their focus is mostly on clinical training rather than on research or drug policy. Future surveys such as this one would benefit from greater attention to issues related to certification, licensing, and academic curricula.     

Palmitoylation regulates raft affinity for the majority of integral raft proteins

The physical basis for protein partitioning into lipid rafts remains an outstanding question in membrane biology that has previously been addressed only through indirect techniques involving differential solubilization by nonionic detergents. We have used giant plasma membrane vesicles, a plasma membrane model system that phase separates to include an ordered phase enriching for raft constituents, to measure the partitioning of the transmembrane linker for activation of T cells (LAT). LAT enrichment in the raft phase was dependent on palmitoylation at two juxtamembrane cysteines and could be enhanced by oligomerization. This palmitoylation requirement was also shown to regulate raft phase association for the majority of integral raft proteins. Because cysteine palmitoylation is the only lipid modification that has been shown to be reversibly regulated, our data suggest a role for palmitoylation as a dynamic raft targeting mechanism for transmembrane proteins.     

Two novel fibrinogen variants in the C-terminus of the Bβ-chain: fibrinogen Rokycany and fibrinogen Znojmo

Hereditary dysfibrinogenemia is a rare disorder wherein an inherited abnormality in fibrinogen structure may result in defective fibrin function and/or structure. Congenital hypofibrinogenemia is a rare autosomal bleeding disorder, either recessive or dominant, characterized by a low fibrinogen plasma level. A 28-year-old asymptomatic woman (fibrinogen Rokycany) and a 54-year-old man with thrombosis and pulmonary embolism (fibrinogen Znojmo) were investigated for a suspected fibrinogen mutation after abnormal coagulation tests results were obtained. DNA sequencing showed the heterozygous point mutation Bβ Asn351Lys in fibrinogen Rokycany and the heterozygous point mutation Bβ Arg237Ser in fibrinogen Znojmo, respectively. The kinetics of fibrinopeptide release was found to be normal in both cases. Fibrinolysis was impaired in the Znojmo variant. The average fibril diameters of Znojmo fibrin was slightly increased, but not differing significantly from normal; formed by less fibrils with abrupt fibril terminations. Rheological studies revealed a softer clot. Rokycany fibrin was formed by significantly narrower fibrils than normal fibrin; and the clot was denser than the control clot. Rheological studies revealed a stiffer clot. Impaired fibrinolysis and abnormal clot morphology may be the cause of thrombotic episodes in the patient with Znojmo mutation. New cases of hypofibrinogenemia and dysfibrinogenemia, found by routine coagulation testing, were genetically identified as a novel fibrinogen variants Bβ Asn351Lys (fibrinogen Rokycany) and Bβ Arg237Ser (fibrinogen Znojmo), respectively.