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Dilated cardiomyopathy (DCM) is clinically characterized by dilated ventricular cavities and reduced ejection fraction, leading to heart failure and increased thromboembolic risk. Mutations in thin-filament regulatory proteins can cause DCM and have been shown in vitro to reduce contractility and myofilament Ca2+-affinity. In this work we have studied the functional consequences of mutations in cardiac troponin T (R131W), cardiac troponin I (K36Q) and α-tropomyosin (E40K) using adenovirally transduced isolated guinea pig left ventricular cardiomyocytes. We find significantly reduced fractional shortening with reduced systolic Ca2+. Contraction and Ca2+ reuptake times were slowed, which contrast with some findings in murine models of myofilament Ca2+ desensitization. We also observe increased sarcoplasmic reticulum (SR) Ca2+ load and smaller fractional SR Ca2+ release. This corresponds to a reduction in SR Ca2+-ATPase activity and increase in sodium-calcium exchanger activity. We also observe dephosphorylation and nuclear translocation of the nuclear factor of activated T cells (NFAT), with concordant RAC-α-serine/threonine protein kinase (Akt) phosphorylation but no change to extracellular signal‐regulated kinase activation in chronically paced cardiomyocytes expressing DCM mutations. These changes in Ca2+ handling and signaling are common to all three mutations, indicating an analogous pathway of disease pathogenesis in thin-filament sarcomeric DCM. Previous work has shown that changes to myofilament Ca2+ sensitivity caused by DCM mutations are qualitatively opposite from hypertrophic cardiomyopathy (HCM) mutations in the same genes. However, we find several common pathways such as increased relaxation times and NFAT activation that are also hallmarks of HCM. This suggests more complex intracellular signaling underpinning DCM, driven by the primary mutation.

Aleksander Kania,1 Rafał Krenke,2 Krzysztof Kuziemski,3 Małgorzata Czajkowska-Malinowska,4 Natalia Celejewska-Wójcik,1 Barbara Kuźnar-Kamińska,5 Małgorzata Farnik,6 Juliusz Bokiej,7 Marta Miszczuk,2 Iwona Damps-Konstańska,3 Marcin Grabicki,5 Marzena Trzaska-Sobczak,6 Krzysztof Sładek,1 Halina Batura-Gabryel,5 Adam Barczyk6 1Department of Pulmonology, II Chair of Internal Medicine, Faculty of Medicine, Jagiellonian University Medical College, Kraków, Poland; 2Department of Internal Medicine, Pulmonary Diseases and Allergy, Medical University of Warsaw, Warsaw, Poland; 3Department of Allergology and Pneumonology, Medical University of Gdańsk, Gdańsk, Poland; 4Department of Lung Diseases and Respiratory Failure, Regional Center of Pulmonology, Bydgoszcz, Poland; 5Department of Pulmonology, Allergology and Respiratory Oncology, Poznań University of Medical Sciences, Poznań, Poland; 6Department of Pneumology, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland; 7Department of Lung Diseases, Regional Hospital Center Jelenia Góra, Jelenia Góra, Poland Background: This study aimed to examine the distribution of predefined phenotypes, demographic data, clinical outcomes, and treatment of patients who were included in the Polish cohort of the Phenotypes of COPD in Central and Eastern Europe (POPE) study. Patients and methods: This was a sub-analysis of the data from the Polish cohort of the POPE study, an international, multicenter, observational cross-sectional survey of COPD patients in Central and Eastern European countries. The study included patients aged .40 years, with a confirmed diagnosis of COPD, and absence of exacerbation for at least 4 weeks before study inclusion. A total of seven Polish centers participated in the study. Results: Among the 430 Polish COPD patients enrolled in the study, 61.6% were non-exacerbators (NON-AE), 25.3% were frequent exacerbators with chronic bronchitis (AE CB), 7.9% were frequent exacerbators without chronic bronchitis (AE NON-CB), and 5.1% met the definition of asthma-COPD overlap syndrome (ACOS). There were statistically significant differences among these phenotypes in terms of symptom load, lung function, comorbidities, and treatment. Patients with the AE CB phenotype were most symptomatic with worse lung function, and more frequently reported anxiety and depression. Patients with the ACOS phenotype were significantly younger and were diagnosed with COPD earlier than those with other COPD phenotypes; those with the ACOS phenotype were also more often atopic and obese. Conclusion: There is significant heterogeneity among COPD patients in the Polish population in terms of phenotype and clinical outcome. The non-exacerbator phenotype is observed most frequently in Poland, while the frequent exacerbator with chronic bronchitis phenotype is the most symptomatic. Keywords: chronic obstructive pulmonary disease, asthma-COPD overlap syndrome, phenotypes

The aim of the present study was to determine the prevalence of Leptotrichia amnionii in cervical swabs of women and its possible correlation with HPV infection and the stage of cervical cancer. MATERIAL AND METHODS: A total of 139 cervical swabs from healthy women with normal cytology, with dysplastic changes and with cervical cancer were tested for the presence of L.amnionii and high-risk HPV DNA by PCR methods. RESULTS: L. amnionii was found in normal vaginal flora and in women with bacterial vaginosis (BV), which suggests that it may be oportunistic pathogen. L. amnionii infection was diagnosed in 13.7% (19/139). Statistical analysis showed that there was positive association (p < 0.01) between the presence of L.amnionii in women with cervical cancer (38.5%) and its presence in women without cancer (11.1%). On the other hand, there was no statistically significant association between L.amnionii and HPV infections. CONCLUSION: The data presented in this study show for the first time the prevalence of L. amnionii infection in cervical specimens collected from 2004-2006 in Poznan and Lublin, Poland, and its association with HPV infection and the stage of carcinogenesis of the cervix.

Granular Co₁₀Cu₉₀ alloys displaying giant magnetoresistance have been obtained by melt spinning followed by an appropriate heat treatment in the range 0–700 °C. Their structural and magnetic properties have been studied on a microscopic scale using ⁵⁹Co NMR technique and thermoremanent magnetization measurements. The study reveals that in the as-quenched samples Co is involved in two main structural components: small, irregular, strained Co particles (60% of the entire Co population) and a composition modulated CoCu alloy. A high modulation amplitude of the concentration profile in the alloy subdivides the latter in two parts with distinctly different properties. One part consists of ferromagnetic alloy (average Cu concentration of about 20%) with a blocking temperature of about 35 K (involving 6% of the entire Co population in a sample). The other part, containing the remaining 34% of the entire Co population, is a paramagnetic alloy with a blocking temperature below 4.2 K. The ferromagnetic alloy is magnetically soft—its transverse susceptibility is lower by a factor of 7 than the transverse susceptibility of the quenched-in Co particles. The latter population has a blocking temperature of about 150–200 K. During the heat treatment, each of the two main structural components undergoes respective decomposition processes: both of them display two temperature regimes. One process consists in dissolving the quenched-in Co particles after annealing at around 400 °C, followed at higher temperatures by a nucleation and growth of the more regular in shape Co particles. The other process resembles a spinodal decomposition of the quenched-in CoCu alloy, resulting in sharpening of the concentration profile and eventually leading to Co cluster formation in samples annealed above 450 °C. Both processes end at about Tan=700 °C, in formation of large, pure Co clusters that are ferromagnetic at least up to 400 K.