Genetic studies on functional redundancy between profilin1 and profilin2 im mice and the role of the profilin ligand Mena in neuronal cell function and mouse behavior

Genetic studies on functional redundancy between profilin1 and profilin2 in mice and the role of the profilin ligand Mena in neuronal cell function and mouse behavior Profilin1 and profilin2 are two actin-binding proteins. Biochemically, proflin1 and profilin2 are similar in respect to their interactions with actin, phosphatidylinositol-4,5-bisphosphate (PIP2), and proteins containing poly-L-proline rich motives among which the Ena/VASP protein family members such as Mena. While profilin1 is highly expressed throughout development and adulthood in most tissues including brain, profilin2 is the neuronal specific isoform. Lack of profilin1 results in early embryonic lethality, while profilin2 KO mice are viable and show behavioral abnormalities. In this thesis I aimed to address three major questions: 1.Is there functional redundancy between profilin1 and profilin2 in vivo? 2.What is the role of the profilin ligand Mena in neuronal cell function and mouse behavior? 3.Is there a common functional pathway for profilin2 and Mena? In order to address functional redundancy between profilin1 and 2 I generated two different knock-in mouse lines in which profilin1 was substituted by mouse profilin2. However, for unknown reasons expression of profilin2 from the transgene was not detectable in tissues isolated from mice targeted with both knock-in strategies. My studies on Mena KO mice suggested an involvement of this protein in re-organization of the actin cytoskeleton and axon path-finding. In hippocampal neurons isolated from Mena KO mice, I showed that Mena is normally inhibiting the outgrowth of dendritic processes and cell spreading. In the mutant animals these alterations lead to axonal path-finding defects and behavioral abnormalities. My behavioral analysis showed that lack of Mena leads to impairment of locomotor activity, motor coordination and balance as well as to alteration in stress response. The severity of the phenotype was found to be age-dependent. Since Mena and profilin2 are known to interact in vitro I tried to investigate if both proteins act in common physiological pathways. Therefore, I compared the neuronal cell phenotype and the behavior of Mena KO and profilin2 KO mice. Interestingly, the morphological alterations are very similar in hippocampal neurons from Mena KO and profilin2 KO mice (longer primary processes and faster spreading). In terms of behavior, both KO lines showed alterations in locomotor activity, impairments in motor coordination and balance as well as altered stress response. The overlap and the differences of phenotypes suggest that profilin2 and Mena are linked in common functional pathways, but also that Mena and profilin2 have unique functions in mouse brain physiology

Łagodna hipotermia terapeutyczna po nagłym zatrzymaniu krążenia w przebiegu ostrego zespołu wieńcowego — doświadczenia z wdrażania metody

Introduction. A mild therapeutic hypothermia (MTH) is a promising adjunct treatment in patients suffering from cardiac arrest.Material and methods. In 2012–2013 a 13 out of 216 consecutive patients admitted due to cardiac arrest were qualified to MTH. Cooling was started at the admission with the intravenous infusion of saline at a degree of 4°C, then continued with intravascular automated cooling system.Results. The study group consisted of five women and eight men (mean age 59 years). The most common mechanism of cardiac arrest was ventricular fibrillation or ventricular tachycardia due to acute myocardial infarction (92.3%). The mean time of return of spontaneous circulation (ROSC) was 15 min 54 s. The mean time from cardiac arrest to the start of the cooling was 1h 10 min. During MTH an increase in white blood cell count and serum level of amylase and CRP was observed. The in-hospital mortality was 7/13 patients (53.8%). Patients who survived were younger (53.8 vs. 63.6 years), had lower incidence of coronary artery disease and ventricular fibrillation was the mechanism of cardiac arrest. In addition, patients who survived had prolonged time to ROSC (median time 19 min vs. 13 min) and reduced time: to the start of cold saline infusion (median time 58 min vs. 85 min), from cardiac arrest to the beginning of the intravascular cooling (median time 3 h 20 min vs. 3 h 50 min) and hospital stay (median time 471 h vs. 1232 h) in comparison with patients with fatal outcome. Five patients were discharged from the hospital in a good neurological condition (4 patients — 0 points and 1 patient — 1 point in Rankin scale).Conclusions. All the patients who survived and were treated with MTH, were discharged in a good neurological condition. The implementation of endovascular cooling device greatly improves precise temperature control in patients undergoing MTH.Mild therapeutic hypothermia after cardiac arrest due to ACS.Wstęp. Łagodna hipotermia terapeutyczna (MTH) jest obiecującą metodą wspomagającą leczenie chorych po nagłym zatrzymaniu krążenia (NZK).Materiał i metody. W latach 2012–2013 spośród kolejnych 216 chorych po NZK do MTH zakwalifikowano 13 pacjentów. Schładzanie rozpoczynano w chwili przyjęcia wlewem dożylnym soli fizjologicznej o temperaturze 4°C, następnie kontynuowano hipotermię za pomocą zautomatyzowanego systemu wewnątrznaczyniowego.Wyniki. Badaną grupę stanowiło 5 kobiet i 8 mężczyzn (średni wiek 59 lat). Najczęstszym mechanizmem NZK były migotanie komór lub częstoskurcz komorowy w przebiegu zawału serca (92,3%). Średni czas do uzyskania spontanicznego krążenia (ROSC) wynosił 15 min 54 s, a od NZK do rozpoczęcia chłodzenia — 1 h 10 min. Podczas MTH obserwowano zwiększone leukocytozę, aktywności amylazy i stężenie CRP. W szpitalu zmarło 7 chorych (53,8%). Grupę pacjentów, którzy przeżyli, charakteryzowały: młodszy wiek (53,8 v. 63,6 roku), rzadszy wywiad choroby niedokrwiennej serca, częstsze występowanie migotania komór jako mechanizmu NZK, dłuższy czas do ROSC (mediana 19 v. 13 min), krótszy czas do rozpoczęcia wlewu zimnej soli fizjologicznej (mediana 58 v. 85 min), krótszy czas od NZK do rozpoczęcia chłodzenia śródnaczyniowego (mediana 3 h 20 min v. 3 h 50 min) oraz krótszy czas pobytu w szpitalu (mediana 471 v. 1232 h). Pięć osób wypisano ze szpitala w bardzo dobrym stanie neurologicznym (4 pacjentów — 0 pkt., 1 pacjent — 1 pkt w skali Rankina).Wnioski. Wszyscy pacjenci, którzy przeżyli, a byli leczeni za pomocą MTH, zostali wypisani w bardzo dobrym stanie neurologicznym. Stosowanie urządzenia do wewnątrznaczyniowego chłodzenia pozwala na precyzyjną kontrolę temperatury u pacjentów poddanych procedurze

Whole-body cryostimulation impact on blood serum thermal denaturation profiles of cross-country skiers

Blood plasma and serum are important diagnostic materials as they clearly reflect an individual’s metabolism. The study has evaluated the effect of whole-body cryostimulation (WBC) on the blood serum of professional cross-country skiers. The experiment involved eight athletes (two women and six men) who underwent a series of ten WBC treatments. Aqueous solutions of human blood serum samples before WBC procedures, after one treatment and after a series of ten treatments were measured by means of differential scanning calorimetry (DSC), a relatively novel diagnostic tool. DSC results showed rather little impact of cryostimulation on heat capacity changes accompanying the process of thermal denaturation of blood serum proteins in elite athletes. However, the statistically significant reduction in the intensity of the serum denaturation transition in its low temperature range has been observed after ten WBC treatments. The results have been interpreted by changes in the serum proteome profile, notably in the ratio of ligated to unligated albumin molecules. As a side result, the relationships between the relative change in body fat mass after ten WBC treatments and the levels of alpha2-globulins and beta2-globulins fractions have been found

Draft Genome Sequence of Shewanella baltica M1 Isolated from Brackish Surface Water of the Gulf of Gdańsk

Here, we present the 5.168-Mbp draft genome sequence of Shewanella baltica M1, the first Shewanella strain from the Gulf of Gdańsk to have its genome sequenced and annotated. The availability of the genome sequence of strain M1 will promote further global analyses of bacterial stress responses in the unique Gulf of Gdan´ sk ecosystem

Safety of dental extractions in patients on dual antiplatelet therapy : a meta-analysis

Introduction: Safety of dental extractions in patients on chronic antiplatelet therapy either with only acetylsalicylic acid (ASA) or clopidogrel or with both combined has been a matter of debate, with no clearly conclusive studies published. Aim: To perform a meta-analysis of published observational studies in order to study the effect of single and double antiplatelet therapy in comparison to controls on the occurrence of immediate local bleeding complications during dental extractions. Material and methods: PubMed/Scopus/Embase database search revealed 22 papers (13 original and 9 review), 3 of which were finally included in the meta-analysis. Phrases searched: dual[All Fields] AND antiplatelet[All Fields] AND (“therapy”[Subheading] OR “therapy”[All Fields] OR “therapeutics”[MeSH Terms] OR “therapeutics”[All Fields]) AND (“tooth extraction”[MeSH Terms] OR (“tooth”[All Fields] AND “extraction”[All Fields]) OR “tooth extraction”[All Fields]). Results: The overall event incidence (bleeding complication after extraction) in the entire population was 1.59% (42 events in 2637 patients). As compared to the control group, the use of double antiplatelet therapy DAPT was associated with on odd ratio OR of 40.23 (95% CI: 4.37–370.36) increase in risk of bleeding events occurrence (p = 0.0011). Significant heterogeneity was observed (p < 0.001; I2 of 76.7%). Conclusions: Dental extractions following strict procedural protocols in patients on double antiplatelet therapy with clopidogrel and ASA are associated with an additional risk of immediate local bleeding complications

Gender-related benefit of transport to primary angioplasty: Is it equal?

Background. Infarct size is correlated with duration of coronary artery occlusion. Evidence suggests that transport for primary angioplasty improves outcomes, but there is no agreement regarding differences in prognosis between men and women. We compared outcomes in men and women with ST-segment elevation myocardial infarction (STEMI) transferred from another hospital against those who had been transported directly to an invasive treatment center. Methods. Data was collected between June 2005 and May 2006 from a registry of 26,035 patients with STEMI and in whom primary angioplasty had been performed. Results. A total of 10,708 patients underwent primary angioplasty. Of these, 3,359 men and 1,469 women were transported directly, while 4,135 men and 1,745 women were transferred from another site. In-hospital mortality and at one month, six months and 12 months after hospital discharge was significantly higher in women than in men. The prognosis of women transported directly was similar to that of women transferred from another site. However, there was a tendency, albeit insignificant, towards higher mortality at six and 12 months in women transported from another hospital. Conclusions. To reduce mortality in STEMI, an immediate reperfusion must not be delayed. This conclusion is valid particularly for women who are at greater risk of death. (Cardiol J 2011; 18, 3: 254&#8211;260

Identification of phenolic compounds and determination of antioxidant activity in extracts and infusions of salvia leaves

Francik, Slawomir/0000-0002-4535-9450; NZEYIMANA, Abdoul/0000-0002-1887-510X; Knapczyk, Adrian/0000-0002-1134-6299; Francik, Renata/0000-0002-7071-8072; Bystrowska, Beata/0000-0001-6501-8656WOS:000602822400001PubMed: 33352787The influence of harvest period and drying method of Salvia officinalis L. leaves on the content of essential oils, polyphenols and antioxidant properties was investigated. Sage leaves were collected twice during plant blossoming (in June and July) and dried traditionally in natural conditions and at 35 degrees C. Antioxidant activity was assayed in methanol-acetone extracts and infusions of dried leaves with the use of free radical scavenging activity (DPPH) and ferric reducing antioxidant power (FRAP) technique. Total phenolic content in extracts as well as in infusions was determined by the means of Folin-Ciocalteu method. Based on the LC/MS analysis, the polyphenol compounds present in both extracts and in infusions were identified. The extracts contained more polyphenols and were characterized by higher antioxidant activity than infusions. in the extracts significant amount of ferulic acid was found, which was influenced both by the harvest period and drying method. The amount of ferulic acid found in extracts obtained from the June leaves dried traditionally was three times lower (6.185 mu g/g DW) than in extracts from July leaves dried in the same conditions. Harvest period had a significant effect on the essential oils' content, leaves collected in July contained 15% more oils than those collected in June.Ministry of Science and Higher Education of the Republic of PolandMinistry of Science and Higher Education, PolandThe study was financed by Ministry of Science and Higher Education of the Republic of Poland

Multiple malignancies and Richter's transformation in patient with small lymphocytic B-cell lymphoma – diagnostic and therapeutic dilemmas

A clonal lymphocyte proliferation in patients with NHL interferes with the immune system, disturbing both humoral and cellular immunity. An antileukemic therapy additionally affects the immune system functioning. A higher than expected in general population incidence of infections and other malignancies is the consequence of impaired immunological surveillance. The fate of patients is also influenced by the possibility of low grade NHL transformation in more aggressive large B cell lymphoma, called the Richter's transformation.We present the case of patient with multiple malignancies small lymphocytic B-cell lymphoma (SLL), renal cell carcinoma (RCC), pulmonary adeno-carcinoma and recurrent laryngeal papillomas, that occurred in different stages of lymphoma diagnosis and treatment. He also developed SLL transformation in large B-cell lymphoma 7 years after the initial diagnosis.A clinical course, together with diagnostic and therapeutic difficulties we faced, are discussed in relation to the literature data