Apolipoprotein A5 gene promoter region T-1131C polymorphism associates with elevated circulating triglyceride levels and confers susceptibility for development of ischemic stroke

The possible pathogenic role of triglycerides (TG) in the development of ischemic stroke is still under extensive investigation. Recently, apolipoprotein (apo)A5 gene promoter region T-1131C polymorphism has been shown to associate with elevated serum TG levels. In the current work, a total of 302 subjects were classified as being large vessel-associated, small vessel-associated, or belonging to a mixed group of ischemic stroke-affected patients. The level of TG was increased in all groups (p<0.01). The apoA5-1131C allele frequency was approximately twofold in all groups of stroke patients compared with the controls (5 vs 10–12%; p<0.05); and the apoA5-1131C allele itself was also found to associate with increased TG levels in all groups. In a multivariate logistic regression analysis model adjusted for differences in age, gender, serum cholesterol, hypertension, pressence of diabetes mellitus, smoking and drinking habits, and ischemic heart disease, a significantly increased risk of developing stroke disease was found in patients carrying the apoA5-1131C allele (p<0.05; odds ratio OR=2.1 [1.3–4.7]); this association was also proven for all subtypes of the stroke. The results presented here suggest that the apoA5-1131C allele is an independent risk factor for the development of stroke. Being that apoA5 gene is under the control of the peroxisome proliferator-activated receptor α, theoretically, the current observations also can have long-term therapeutic consequences.     

Congenital lung malformations in the second trimester: prenatal ultrasound diagnosis and pathologic findings

PURPOSE: To correlate prenatal sonographic diagnosis of cystic lung malformations with fetopathologic findings after termination of pregnancy. METHODS: We retrospectively analyzed the data of 16 terminated cases in which a cystic lung lesion was diagnosed pre- or postnatally. RESULTS: On average, prenatal diagnosis was established on the 21(st) gestational week (range, 19-26 weeks). The cause of termination was severe polyhydramnios in 4 cases, nonimmune fetal hydrops in 4 cases, other congenital malformation in 5 cases (renal malformation, 2 cases; congenital diaphragmatic hernia, 3 cases), and obstetrical conditions (intrauterine death, placental abruption, spontaneous abortion) in 3 cases. In 11 cases, congenital cystic adenomatoid malformation (CCAM) was the presumptive prenatal diagnosis. Autopsy confirmed the prenatal diagnosis in 6 of them, while in the other 5 cases, an enteric cyst, a laryngeal atresia, an unidentified tumor, a pulmonary hypoplasia, and an extralobar pulmonary sequestration were found on histologic examination. On the other hand, the autopsy revealed CCAM in those 5 cases in which other malformations were suggested prenatally. CONCLUSION: The prenatal sonographic diagnosis of CCAM is difficult. Our cases emphasize the important role of fetopathology even today in the verification of prenatal diagnosis based on sonographic examinations.     

Radiotherapy Confined to the Tumor Bed Following Breast Conserving Surgery

BACKGROUND: The standard technique of radiotherapy (RT) after breast conserving surgery (BCS) is to treat the entire breast up to a total dose of 45-50 Gy with or without tumor bed boost. The majority of local recurrences occur in close proximity to the tumor bed. Thus, the necessity of whole breast radiotherapy has been questioned, and several centers have evaluated the feasibility and efficacy of sole tumor bed irradiation. The aim of this study was to review the current status, controversies, and future prospects of tumor bed irradiation alone after breast conserving surgery. MATERIAL AND METHODS: Published prospective trials evaluating the feasibility and efficacy of radiotherapy confined to the tumor bed following breast conserving surgery were reviewed in order to analyze treatment results. RESULTS: In three earlier studies, using tumor bed radiotherapy for unselected patients, the incidence of intra-breast relapse was reported in the range of 15.6-37%. However, in nine prospective phase I-II trials, sole brachytherapy (BT) with different dose rates, strict patient selection, and meticulous quality assurance, resulted in 95.6-100% local control rates. To date, only one phase III protocol has been initiated comparing the efficacy of tumor bed brachytherapy alone with conventional whole breast radiotherapy. The ideal extend of the planning target volume (PTV) for tumor bed radiotherapy alone has not been established yet. In most series, PTV was defined as the excision cavity with generous (1-3 cm) safety margins. Minimal requirement for PTV localization is the use of titanium clips to mark the walls of the excision cavity intraoperatively, but the combination of clip demarcation and three-dimensional (3-D) visual information obtained from cross-sectional images seems to be the best method to determine the target volume. 3-D virtual brachytherapy is also a promising method to minimize the chance of geographic miss. Recently developed techniques, such as intraoperative radiotherapy (IORT), as well as accelerated 3-D conformal external beam radiation therapy (3-D-CRT) were also found to be feasible for tumor bed radiotherapy alone. CONCLUSIONS: In spite of the existing arguments against limiting radiotherapy to the tumor bed after breast conserving surgery, results of phase I-II studies suggest that tumor bed radiotherapy alone might be an appropriate treatment option for selected breast cancer patients. Whole breast radiotherapy remains the standard radiation modality used in the treatment of breast cancer, and brachytherapy as the sole modality should be considered as investigational. Further phase-III trials are suggested to determine the equivalence of sole tumor bed radiotherapy, compared with whole breast radiotherapy. Preliminary results with recently developed techniques (CT-image based conformal brachytherapy, 3-D virtual brachytherapy, IORT, 3-D-CRT) are promising. However, more experience is required to define whether these methods might improve outcome for patients treated with tumor bed radiotherapy alone.     

Accelerated recovery of 5-fluorouracil-damaged bone marrow after rosiglitazone treatment

Our preliminary data indicate that rosiglitazone may be myeloprotective. We investigated whether it can modify bone marrow recovery. Five-day pre-treatment with rosiglitazone significantly accelerated recovery of 5-fluorouracil-damaged bone marrow in mice. Frequency and femoral content of granulocyte-macrophage progenitors reached mean baseline faster in pre-treated groups than in 5-fluorouracil-treated controls. Consequently, neutropenia was milder. Five-day insulin pre-treatment had similar effects in vivo. Insulin supports in vitro hematopoiesis. The observed myeloprotection demonstrated the importance of insulin in vivo. Clinical use of insulin to moderate myelotoxicity is impractical but rosiglitazone, an insulin sensitizer, could offer hope. Although rosiglitazone tends to increase plasma insulin levels, the significant myeloprotection was partly due to direct effects on progenitors. In vitro rosiglitazone enhanced the survival of both murine progenitor and human mobilized blood stem cells in the presence of 5-fluorouracil, the effect of which was neutralized by a peroxisome-proliferator-activated receptor-gamma antagonist.     

The effect of social distance measures on COVID-19 epidemics in Europe: an interrupted time series analysis

GeroScience - Following the introduction of unprecedented “stay-at-home” national policies, the COVID-19 pandemic recently started declining in Europe. Our research aims were to...     

Impact of obesity on autoimmune arthritis and its cardiovascular complications

Obesity can instigate and sustain a systemic low-grade inflammatory environment that can amplify autoimmune disorders and their associated comorbidities. Metabolic changes and inflammatory factors produced by the adipose tissue have been reported to aggravate autoimmunity and predispose the patient to cardiovascular disease (CVD) and metabolic comorbidities. Rheumatoid arthritis (RA) and psoriatic arthritis (PsA) are autoimmune arthritic diseases, often linked with altered body mass index (BMI). Severe joint inflammation and bone destruction have a debilitating impact on the patient's life; there is also a staggering risk of cardiovascular morbidity and mortality. Furthermore, these patients are at risk of developing metabolic symptoms, including insulin resistance resulting in type 2 diabetes mellitus (T2DM). In addition, arthritis severity, progression and response to therapy can be markedly affected by the patient's BMI. Hence, a complex integrative pathogenesis interconnects autoimmunity with metabolic and cardiovascular disorders. This review aims to shed light on the network that connects obesity with RA, PsA, systemic lupus erythematosus and Sj?gren's syndrome. We have focused on clarifying the mechanism by which obesity affects different cell types, inflammatory factors and traditional therapies in these autoimmune disorders. We conclude that to further optimize arthritis therapy and to prevent CVD, it is imperative to uncover the intricate relation between obesity and arthritis pathology.     

Presence and distribution of three calcium binding proteins in projection neurons of the adult rat cochlear nucleus

The presence and distribution of three cytoplasmic calcium binding proteins, calbindin, calretinin, and parvalbumin, have been investigated in the projection neurons of the cochlear nucleus complex in adult rats by using immunohistochemistry in free-floating slices. Identification of the individual cell types was carried out on the basis of their intranuclear localization, morphological characteristics, and (in the cases of pyramidal and bushy neurons) by retrograde labeling with rhodamine-dextran. The most important findings were confirmed by using confocal microscopy. The data obtained in these experiments are the first to demonstrate the presence of parvalbumin in pyramidal neurons and globular and spherical bushy cells of rat cochlear nucleus, whereas octopus and giant cells did not show positivity for parvalbumin. Calretinin was not present in either Purkinje-like cells or giant neurons. According to the double immunolabeling co-localization experiments, the pyramidal neurons, Purkinje-like cells, globular bushy cells, and octopus cells express two different calcium binding proteins in their cytoplasm (although in different combinations) whereas giant cells and spherical bushy cells contain solely calbindin and parvalbumin, respectively. The presence of calretinin in globular bushy cells provides a tool for distinguishing them from spherical bushy cells. The immunolabeling of the fibers and axonal endings of the acoustic nerve in the ventral part of the cochlear nucleus indicated that these structures are also parvalbumin positive. It is concluded that the heterogenous cell composition of the cochlear nucleus is accompanied by a rather complex expression pattern of the cytoplasmic calcium binding proteins.     

Preliminary studies of the effects of vascular adhesion protein-1 inhibitors on experimental corneal neovascularization

Vascular adhesion protein-1 (VAP-1) controls the adhesion of lymphocytes to endothelial cells and is upregulated at sites of inflammation. Moreover, it expresses amine oxidase activity, due to the sequence identity with semicarbazide-sensitive amine oxidase. Recent studies indicate a significant role for VAP-1 in neovascularization, besides its contribution to inflammation. Pathological blood vessel development in severe ocular diseases (such as diabetes, age-related macula degeneration, trauma and infections) might lead to decreased visual acuity and finally to blindness, yet there is no clear consensus as to its appropriate treatment. In the present case study, the effects of two VAP-1 inhibitors on experimentally induced corneal neovascularization in rabbits were compared with the effects of a known inhibitor of angiogenesis, bevacizumab, an anti-vascular endothelial growth factor antibody. In accordance with recent literature data, the results of the preliminary study reported here indicate that the administration of VAP-1 inhibitors is a potentially valuable therapeutic option in the treatment of corneal neovascularization.     

Visual-perceptual dysfunctions are possible endophenotypes of schizophrenia: evidence from the psychophysical investigation of magnocellular and parvocellular pathways

Visual information processing is impaired in schizophrenia patients and their biological relatives. The authors measured vernier thresholds in 72 schizophrenia patients, their 86 siblings, and 60 healthy control subjects. Subjects were asked to detect the direction of the horizontal displacement of 2 stimuli (left or right). During magnocellular (M) pathway tests, stimuli were dots with low contrast (5%) or counterphase-modulated gratings (25 Hz). For parvocellular (P) pathway tests, isoluminant blue-red dots with yellow-green background were used. Results revealed that patients with schizophrenia and their siblings were more impaired in M pathway conditions than in P pathway conditions. There was no color-specific impairment. The patients and their siblings displayed lower performances on tests of executive functions, psychomotor speed, and verbal memory compared with the controls. Visual-perceptual and neuropsychological data did not correlate. In conclusion, M pathway dysfunction is a potential endophenotype of schizophrenia.