Comparison of chromosome centromere topology in differentiating cells with myogenic potential.

Chromosome territories (CT's) constitute the critical element of the intranuclear architecture. Position of these compartmentalized structures plays an important role in functioning of entire genome. Present study was to examine whether the centromeres position of chromosomes 4, X and Y can be changed during differentiation from myoblasts to myotubes. Topological analysis of these centromeres was based on two-dimensional fluorescent hybridization in situ (2D-FISH). During differentiation process the majority of X chromosome centromeres analyzed shifted to the peripheral part of a nucleus and similar phenomenon was observed with one of the chromosome 4 centromeres. Completely different tendency was noticed when investigating the location of the chromosome Y centromeres. Centromeres of this chromosome migrated to the centre of a nucleus. The results obtained demonstrated visible changes in chromosome topology along the myogenic stem cells differentiation

Cytogenetic and molecular analyses of de novo translocation dic(9;13)(p11.2;p12) in an infertile male

BACKGROUND: Whole arm t(9;13)(p11;p12) translocations are rare and have been described only a few times; all of the previously reported cases were familial. RESULTS: We present here an infertile male carrier with a whole-arm reciprocal translocation dic(9;13)(p11.2;p12) revealed by GTG-, C-, and NOR-banding karyotypes with no mature sperm cells in his ejaculate. FISH and genome-wide 400 K CGH microarray (Agilent) analyses demonstrated a balanced chromosome complement and further characterised the abnormality as a dicentric chromosome (9;13): dic(9;13)(pter→p11.2::p12→qter),neo(9)(pter→p12→neo→p11.2). An analysis of the patient’s ejaculated cells identified immature germ cells at different phases of spermatogenesis but no mature spermatozoa. Most (82.5%) of the germ cells were recognised as spermatocytes at stage I, and the cell nuclei were most frequently found in pachytene I (41.8%). We have also undertaken FISH analysis and documented an increased rate of aneuploidy of chromosomes 15, 18, X and Y in the peripheral blood leukocytes of our patient. To study the aneuploidy risk in leukocytes, we have additionally included 9 patients with non-obstructive azoospermia with normal karyotypes. CONCLUSIONS: We propose that the azoospermia observed in the patient with the dic(9;13)(p11.2;p12) translocation was most likely a consequence of a very high proportion (90%) of association between XY bivalents and quadrivalent formations in prophase I

Progressive skin fibrosis is associated with a decline in lung function and worse survival in patients with diffuse cutaneous systemic sclerosis in the European Scleroderma Trials and Research (EUSTAR) cohort.

Objectives To determine whether progressive skin fibrosis is associated with visceral organ progression and mortality during follow-up in patients with diffuse cutaneous systemic sclerosis (dcSSc). Methods We evaluated patients from the European Scleroderma Trials and Research database with dcSSc, baseline modified Rodnan skin score (mRSS) ≥7, valid mRSS at 12±3 months after baseline and ≥1 annual follow-up visit. Progressive skin fibrosis was defined as an increase in mRSS >5 and ≥25% from baseline to 12±3 months. Outcomes were pulmonary, cardiovascular and renal progression, and all-cause death. Associations between skin progression and outcomes were evaluated by Kaplan-Meier survival analysis and multivariable Cox regression. Results Of 1021 included patients, 78 (7.6%) had progressive skin fibrosis (skin progressors). Median follow-up was 3.4 years. Survival analyses indicated that skin progressors had a significantly higher probability of FVC decline ≥10% (53.6% vs 34.4%; p<0.001) and all-cause death (15.4% vs 7.3%; p=0.003) than non-progressors. These significant associations were also found in subgroup analyses of patients with either low baseline mRSS (≤22/51) or short disease duration (≤15 months). In multivariable analyses, skin progression within 1 year was independently associated with FVC decline ≥10% (HR 1.79, 95% CI 1.20 to 2.65) and all-cause death (HR 2.58, 95% CI 1.31 to 5.09). Conclusions Progressive skin fibrosis within 1 year is associated with decline in lung function and worse survival in dcSSc during follow-up. These results confirm mRSS as a surrogate marker in dcSSc, which will be helpful for cohort enrichment in future trials and risk stratification in clinical practice

Racial differences in systemic sclerosis disease presentation: a European Scleroderma Trials and Research group study

Objectives. Racial factors play a significant role in SSc. We evaluated differences in SSc presentations between white patients (WP), Asian patients (AP) and black patients (BP) and analysed the effects of geographical locations.Methods. SSc characteristics of patients from the EUSTAR cohort were cross-sectionally compared across racial groups using survival and multiple logistic regression analyses.Results. The study included 9162 WP, 341 AP and 181 BP. AP developed the first non-RP feature faster than WP but slower than BP. AP were less frequently anti-centromere (ACA; odds ratio (OR) = 0.4, P < 0.001) and more frequently anti-topoisomerase-I autoantibodies (ATA) positive (OR = 1.2, P = 0.068), while BP were less likely to be ACA and ATA positive than were WP [OR(ACA) = 0.3, P < 0.001; OR(ATA) = 0.5, P = 0.020]. AP had less often (OR = 0.7, P = 0.06) and BP more often (OR = 2.7, P < 0.001) diffuse skin involvement than had WP.AP and BP were more likely to have pulmonary hypertension [OR(AP) = 2.6, P < 0.001; OR(BP) = 2.7, P = 0.03 vs WP] and a reduced forced vital capacity [OR(AP) = 2.5, P < 0.001; OR(BP) = 2.4, P < 0.004] than were WP. AP more often had an impaired diffusing capacity of the lung than had BP and WP [OR(AP vs BP) = 1.9, P = 0.038; OR(AP vs WP) = 2.4, P < 0.001]. After RP onset, AP and BP had a higher hazard to die than had WP [hazard ratio (HR) (AP) = 1.6, P = 0.011; HR(BP) = 2.1, P < 0.001].Conclusion. Compared with WP, and mostly independent of geographical location, AP have a faster and earlier disease onset with high prevalences of ATA, pulmonary hypertension and forced vital capacity impairment and higher mortality. BP had the fastest disease onset, a high prevalence of diffuse skin involvement and nominally the highest mortality

Immunological Aspects of Systemic Sclerosis and New Strategies in Therapy

Abstract Systemic sclerosis is a chronic autoimmune disease characterized by multiorgan symptoms such as skin thicken− ing, pulmonary fibrosis, pulmonary arterial hypertension, renal crisis, and gastrointestinal complications. There are two major subtypes of systemic sclerosis: limited and diffuse. The pathogenic process includes inflammatory cell activation, vascular damage, and fibroblast activation. Recent research has focused on understanding its patholog− ical pathways. A new strategy in therapy is developing substances which interfere with the main pathogenic path− ways and which will be able to improve prognostics in systemic sclerosis. The efficacy of current therapies is restricted (Adv Clin Exp Ned 2008, 17, 4, 441-446). Key words: systemic sclerosis, vascular damage, cyclophosphamide, fibrosis, pathogenesis. Streszczenie Twardzina układowa jest autoimmunologiczną, przewlekłą chorobą, która charakteryzuje się zajęciem narządów wewnętrznych. Poważne następstwa choroby to włóknienie skóry i płuc, nadciśnienie płucne, kryza nerkowa oraz zaburzenia układu pokarmowego. Istnieją dwie postacie kliniczne choroby: twardzina układowa ograniczona i uo− gólniona. Na patogenezę choroby składają sie trzy główne procesy: aktywacja immunologiczna, uszkodzenie na− czyń oraz aktywacja fibroblastów. Ostatnie badania koncentrują się na zrozumieniu szlaków patogenetycznych twardziny układowej. Nowymi kierunkami w leczeniu tej choroby wydają się substancje, które zablokują specy− ficzny szlak patologiczny choroby, co poprawi rokowanie. Skuteczność obecnie stosowanych leków jest niestety ograniczona (Adv Clin Exp Ned 2008, 17, 4, 441-446). Słowa kluczowe: twardzina układowa, uszkodzenie naczyń, cyklofosfamid, zwłóknienie, patogeneza

Verification of Geometric Model-Based Plant Phenotyping Methods for Studies of Xerophytic Plants

This paper presents the results of verification of certain non-contact measurement methods of plant scanning to estimate morphological parameters such as length, width, area, volume of leaves and/or stems on the basis of computer models. The best results in reproducing the shape of scanned objects up to 50 cm in height were obtained with the structured-light DAVID Laserscanner. The optimal triangle mesh resolution for scanned surfaces was determined with the measurement error taken into account. The research suggests that measuring morphological parameters from computer models can supplement or even replace phenotyping with classic methods. Calculating precise values of area and volume makes determination of the S/V (surface/volume) ratio for cacti and other succulents possible, whereas for classic methods the result is an approximation only. In addition, the possibility of scanning and measuring plant species which differ in morphology was investigated

„Długoterminowa ocena bezpieczeństwa i skuteczności leczenia biologicznego młodzieńczego idiopatycznego zapalenia stawów” – prezentacja polskiego rejestru elektronicznego

Pacjenci, u których stosuje się terapie lekami biologicznymi, wymagająszczególnej opieki. W trakcie licznych, systematycznie powtarzanychwizyt monitorujących w dokumentacji pacjentów groma dzonajest ogromna liczba danych na temat pacjenta, jego choroby i terapii.Analiza tych danych może służyć wielokierunkowej ocenie skutecznościi bezpieczeństwa terapii. Fakt ten stał się inspiracją do powstaniapolskiego naukowego elektronicznego rejestru dzieci leczonych lekami biologicznymi: „Długoterminowa ocena bezpieczeństwa i skutecznościleczenia młodzieńczego idiopatycznego zapalenia stawów”.Rejestr rozpoczął działanie w kwietniu 2009 r. Po roku funkcjonowaniaw rejestrze znalazły się dane dotyczące 218 pacjentówchorujących na młodzieńcze idiopatyczne zapalenie stawów (MIZS),u których stosowano terapie biologiczne: etanercept zastosowanou 210 pacjentów, a adalimumab u 8 pacjentów. Główne cele prowadzeniarejestru to: 1) długoterminowa ocena bezpieczeństwa stosowanegoleczenia przez prowadzenie rejestracji i analizy zdarzeń niepożądanych,2) długoterminowa ocena skuteczności leczenia napodstawie oceny aktywności choroby oraz jakości życia pacjentów.W rejestrze zawarte są dane z wywiadu pacjenta, dotyczącepoczątku i przebiegu MIZS, uprzedniego leczenia, oceny jego skutecznościi tolerancji, aktywności choroby, występowania choróbautoimmunizacyjnych w rodzinie oraz ocena jakości życia przedrozpoczęciem terapii biologicznej. Na podstawie danych zebranychw czasie wizyt kontrolnych lekarz uzupełnia elektroniczny kwestionariusz,składający się z 35 pytań dotyczących rozwoju somatycznegooraz prowadzonego leczenia. Oceniana jest aktywność choroby(wg Gianinniego) i wyliczany wskaźnik poprawy ACR Ped.Dodatkowo skuteczność leczenia oceniają lekarz, pacjent i jegorodzice, pod uwagę bierze się absencje w szkole i liczbę hospitalizacji.Bezpieczeństwo jest określane przez odnotowywanie zdarzeńniepożądanych.W pracy przedstawiono główne założenia rejestru, jego strukturę,kierunki analizy zebranych danych oraz listę uczestniczących w nimośrodków (tab. I i II)

Ebbing Strength, Fading Power: Unveiling the Impact of Persistent Fatigue on Muscle Performance in COVID-19 Survivors

The total number of confirmed cases of COVID-19 caused by SARS-CoV-2 virus infection is over 621 million. Post-COVID-19 syndrome, also known as long COVID or long-haul COVID, refers to a persistent condition where individuals experience symptoms and health issues after the acute phase of COVID-19. The aim of this study was to assess the strength and fatigue of skeletal muscles in people recovered from COVID-19. A total of 94 individuals took part in this cross-sectional study, with 45 participants (referred to as the Post-COVID Cohort, PCC) and 49 healthy age-matched volunteers (Healthy Control Cohort, HCC). This research article uses the direct dynamometry method to provide a detailed analysis of post-COVID survivors’ strength and power characteristics. The Biodex System 4 Pro was utilized to evaluate muscle strength characteristics during the fatigue test. The fatigue work in extensors and flexors was significantly higher in the PCC. The PCC also showed significantly less power in both extensors and flexors compared to the HCC. In conclusion, this study provides compelling evidence of the impact of post-COVID-19 fatigue on muscle performance, highlighting the importance of considering these effects in the rehabilitation and care of individuals recovering from the virus. PCC achieved lower muscle strength values than HCC