236 research outputs found

    Abundance Modeling and Movement of smallmouth bass in a Regulated Section of the Broad River, SC

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    Dams and altered flow regimes impact riverine fish. In addition to ecological impacts, unpredictable changes in flow influence the ability to access rivers and effectively sample fish populations. Fisheries management practices are often influenced by water regulation and hydropower generation, thus designing distinct methods of monitoring populations in regulated rivers is critical for effective management. Recurrent changes in river flow also influence behavior of fish inhabiting the flow-regulated portions of rivers, and such individual behavior may ultimately have population-level effects (e.g. fish abundance). I investigated population abundance and movement of smallmouth bass (Micropterus dolomieu) within a regulated portion of the Broad River, SC, located below a small hydropower dam. In Chapter 1, I developed a novel approach to estimating bass abundance within a 4.2-km section immediately below the dam where fluctuations in discharge might influence capture efficiency over different sampling days. The number of smallmouth bass was estimated based on mark-recapture data utilizing two gears, angling and electrofishing. The closed population assumption was confirmed using radio telemetry, and closed population capture-mark-recapture models were fit in the Bayesian hierarchical modelling framework with an estimated number of 2,380 bass (95% Credible Interval: 1,578-3,693) over 200 mm TL. Integrating the two gear types into a mark-recapture study can be an effective method for assessing abundance in spatially or temporally heterogeneous habitats where changing conditions can cause variable sampling environments. In Chapter 2, to inform the sampling strategy to detect a temporal trend in bass abundance, I implemented a power analysis comparing the ability to detect a 2.5% or 5% annual declining trend in abundance after 5, 10, and 15 years based on various levels of sampling effort. The primary interest was to optimize the allocation of effort in terms of number of survey occasions within a year and intensity of effort for each survey occasion. Results indicated that increased effort intensity of each survey occasion (e.g. more boats to be used on each survey to increase capture probability) was more important than adding more occasions with lower effort/bass detection levels within each. In general, power increased with the larger decline (5%) and more sampling effort. In the third and final chapter, I evaluated the effects of river discharge variation on diurnal fish movement every 30 minutes during daylight hours to establish linkage between hydro-power generation and fish behavior. Generalized additive mixed models (GAMMs) suggested that movement distances slightly increased with river discharge associated with hydro-power generation in winter, but not in summer. The physiological impacts of this altered behavior was not known, but if rapid and major changes in flow magnitude act as a stressor to individual bass, then population-level effects could follow and impact fisheries resources within the study area

    B cell targeting therapies in MS patients during the SARS-CoV-2 pandemic — when immunosuppression meets infection?

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    Introduction. Research into the mechanisms of autoimmune demyelination have highlighted B cells in this process. Therapies targeting this population were a recent addition to the multiple sclerosis (MS) drugs portfolio. The SARS-CoV-2 pandemic and the risk of severe COVID-19 have challenged the safety of B cell depletion in MS patients.State of the art. Selective depletion of B cells by monoclonal antibodies as monotherapy in MS has been shown to profoundly suppress disease activity among relapsing-remitting MS patients. Furthermore ocrelizumab, a humanised anti-CD20 monoclonal antibody, was the first licensed therapy in primary progressive MS. Based on the concept of the role of B cells in MS, many therapeutic approaches are emerging as novel ways to treat autoimmune demyelination. However, during the SARS-CoV-2 pandemic, a conservative approach toward limiting immune suppression in MS patients has been proposed.Clinical implications. Emerging evidence does not support the notion of increased susceptibility among MS patients to the SARS-CoV-2 infection, or any predisposition toward greater severity of COVID-19. This also does not appear to be the case for MS patients undergoing B cell depletion therapies. Thus, any decision to withhold immune suppression in MS patients during the SARS-CoV-2 pandemic is probably incorrect. MS therapeutic decision-making should focus on the danger of poorly controlled autoimmune demyelination rather than perceived risks from COVID-19.Future directions. The current pandemic highlights the need to develop more selective and safer methods of immunomodulation in MS. B cells represent several functionally different populations. Further research into the different role of these cells during autoimmune demyelination should yield better, safer strategies to control the encephalitogenic process

    Patogeneza stwardnienia rozsianego

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    Stwardnienie rozsiane (SM, sclerosis multiplex) jest postępującym schorzeniem ośrodkowego układu nerwowego (OUN). Mechanizmy leżące u podstaw rozsianych zmian demielinizacyjnych charakterystycznych dla tej choroby nie zostały jak dotąd w pełni poznane. Uważa się, że w podatności na występienie SM duże znaczenie ma skomplikowane podłoże genetyczne, najprawdopodobniej różniące się w poszczególnych populacjach. Za jeden z kluczowych składników procesu patologicznego uznaje się powszechnie układ immunologiczny, a zwłaszcza takie jego składowe, jak autoreaktywne limfocyty T, komórki o charakterze regulatorowym oraz cytokiny i chemokiny prozapalne. Rozważa się także zaangażowanie czynników środowiskowych w tym wirusów i bakterii, jednak dotąd nie udało się zidentyfikować patogenu związanego bezspornie z występowaniem choroby. Poznanie złożonych mechanizmów chorobowych w SM wymaga dalszych szczegółowych badań, jednak uzyskana dotychczas wiedza pozwala na znacznie lepsze zrozumienie patogenezy tego schorzenia

    Severe vitamin B12 deficiency of unknown origin in 10-months-old girl

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    Niedobór witaminy B12 jest u dzieci dość rzadką przyczyną niedokrwistości makrocytarnej. W ciężkich przypadkach może prowadzić do wystąpienia zaburzeń neurologicznych i psychicznych, a także zmian troficznych błon śluzowych jamy ustnej i języka. Do najczęstszych przyczyn niedoboru witaminy B12 należą dieta uboga w tę witaminę (wegetariańska, a zwłaszcza wegańska), zaburzenia wchłaniania w żołądku i jelicie cienkim (choroba Addisona-Biermera, stan po resekcji żołądka, bezkwaśność soku żołądkowego, choroba Leśniowskiego-Crohna, celiakia, zakażenia pasożytnicze), wrodzone niedobory transkobalaminy II oraz zaburzenia metabolizmu witaminy B12. U dzieci jako przyczynę należy wziąć pod uwagę karmienie wyłącznie piersią przez matki z utajonym bądź jawnym niedoborem tej witaminy. W pracy opisano przypadek 10-miesięcznej dziewczynki z ciężkim niedoborem witaminy B12 o nieznanej etiologii, u której oprócz zaburzeń hematologicznych (pancytopenia) stwierdzono ciężkie zaburzenia neurologiczne, a także niewydolność krążenia. Wszystkie objawy całkowicie ustąpiły po wyrównaniu niedoboru witaminy. Hematologia 2011; 2, 1: 92–97Vitamin B12 is quite rare reason of macrocytic anemia in children. In severe cases it can lead to neurological and psychotic symptoms or trophic lesions of tongue and mucous membranes. The most common reasons of vitamin B12 deficiency are diet (vegetarians, and especially vegans), malabsorption (i.e. pernicious anemia, gastric resection, achlorhydria, Crohn’s disease, celiac disease, parasitic infections), congenital transcobalamin II deficiency or vitamin B12 metabolic disorders. Breast-feeding by mothers with vitamin B12 deficiency must be also considered as a reason of severe vitamin B12 deficiency in infants. We describe the case of 10-months-old child with severe vitamin B12 deficiency of unknown origin. We observed not only severe hematological problems (pancytopenia), but also neurological symptoms and heart failure. All the symptoms disappeared after compensation of vitamin B12 deficiency. Hematologia 2011; 2, 1: 92–9

    Intrathecal administration of mesenchymal stem cells in patients with adrenomyeloneuropathy

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    Background and objectivesX-linked adrenomyeloneuropathy (AMN) is an inherited neurodegenerative disorder associated with mutations in the ABCD1 gene and the accumulation of very long-chain fatty acids (VLFCAs) in plasma and tissues. Currently, there is no effective treatment for AMN. We have aimed to evaluate the therapeutic effects of mesenchymal stem cell (MSC) transplantation in patients with AMN.MethodsThis is a small cohort open-label study with patients with AMN diagnosed and treated at the University Hospital in Olsztyn, Poland. All patients met clinical, biochemical, MRI, and neuropsychological criteria for AMN. MSCs derived from Wharton jelly, 20 × 106 cells, were administered intrathecally three times every 2 months, and patients were followed up for an additional 3 months. The primary outcome measures included a blinded assessment of lower limb muscle strength with the Medical Research Council Manual Muscle Testing scale at baseline and on every month visits until the end of the study. Additional outcomes included measurements of the timed 25-feet walk (T25FW) and VLFCA serum ratio.ResultsThree male patients with AMN with an age range of 26–37 years participated in this study. All patients experienced increased muscle strength in the lower limbs at the end of the study versus baseline. The power grade increased by 25–43% at the baseline. In addition, all patients showed an improvement trend in walking speed measured with the T25FW test. Treatment with MSCs in patients with AMN appeared to be safe and well tolerated.DiscussionThe results of this study demonstrated that intrathecal administration of WJ-MSC improves motor symptoms in patients with AMN. The current findings lend support to the safety and feasibility of MSC therapy as a potentially viable treatment option for patients with AMN

    MLL-rearranged B lymphoblastic leukemias selectively express the immunoregulatory carbohydrate-binding protein galectin-1

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    Leukemias with 11q23 translocations involving the Mixed Lineage Leukemia (MLL) gene exhibit unique clinical and biological features and have a poor prognosis. In a screen for molecular markers of MLL rearrangement, we identified the specific overexpression of an immunomodulatory lectin Galectin-1 (Gal1) in MLL-rearranged B lymphoblastic leukemias (B-ALL) compared to other MLL-germline ALLs. To assess the diagnostic utility of Gal1 expression in identifying MLL-rearranged B-ALLs, we performed Gal1 immunostaining on a large series of primary ALLs with known MLL status. All 11 MLL-rearranged B-ALLs had abundant Gal1 expression; in marked contrast, only 1 of 42 germline-MLL B-ALLs expressed Gal1. In addition, Gal1 was readily detected in diagnostic samples of MLL-rearranged B-ALLs by intracellular flow cytometry. Since deregulated gene expression in MLL-rearranged leukemias may be related to the altered histone methyltransferase activity of MLL fusion protein complex, we analyzed histone H3 lysine 79 (H3K79) dimethylation in the Gal1 promoter region using chromatin immunoprecipitation. Gal1 promoter H3K79diMe was ≈ 5 fold higher in a MLL-rearranged B-ALL cell line than in a B-ALL line without the MLL translocation. Furthermore, the Gal1 promoter H3K79 was significantly hypermethylated in primary MLL-rearranged B-ALLs compared to MLL-germline B-ALLs and normal pre-B cells, implicating this epigenetic modification as a mechanism for Gal1 overexpression in MLL B-ALL.Fil: Juszczynski, Przemyslaw. Dana Farber Cancer Institute; Estados UnidosFil: Rodig, Scott J.. Brigham & Women; Estados UnidosFil: Ouyang, Jing. Dana Farber Cancer Institute; Estados UnidosFil: O´Donnell, Evan. Dana Farber Cancer Institute; Estados UnidosFil: Takeyama, Kunihiko. Dana Farber Cancer Institute; Estados UnidosFil: Mlynarski, Wojciech. Dana Farber Cancer Institute; Estados UnidosFil: Mycko, Katarzyna. Dana Farber Cancer Institute; Estados UnidosFil: Szczepanski, Tomasz. Dana Farber Cancer Institute; Estados UnidosFil: Gaworczyk, Anna. Medical University of Lodz; PoloniaFil: Krivtsov, Andrei. Medical University of Lodz; PoloniaFil: Faber, Joerg. Medical University of Silesia; PoloniaFil: Sinha, Amit U.. Medical University of Lublin; PoloniaFil: Rabinovich, Gabriel Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; ArgentinaFil: Armstrong, Scott A.. Children; Estados UnidosFil: Kutok, Jeffery. Children; Estados UnidosFil: Shipp, Margaret A.. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; Argentin

    Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.

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    Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis
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