An Intriguing Case of Anaemia and Splenomegaly

Objectives: Thrombocytopenia and splenomegaly are common features in several haematological disorders. Gaucher disease (GD) is a rare lysosomal storage disorder frequently characterized by thrombocytopenia and splenomegaly, which represents a clinical challenge for haematologists and internists. Case: We describe the case of a 37-year-old patient with a diagnosis of spherocytosis since childhood, who developed hepatic failure and presented striking features of GD including hepatosplenomegaly, bone fractures and post-partum bleeding. We reconsidered the diagnosis of spherocytosis and investigated Gaucher disease. Conclusion: GD should be considered in the differential diagnosis of thrombocytopenia and splenomegaly

Evaluarea influenţei genelor modificatoare a metabolismului asupra manifestărilor proceselor miopatice (pe exemplul distrofiei musculare Duchenne/Becker)

Prezenta lucrare este dedicată cercetării factorilor genetici modif catori la pacienţii MDD/B. Estimarea rolului lor asupra vitezei progresiei procesului miopatic, determinarea tipului şi forţei de interacţiuni intergenice, precum şi modelarea matematică a vitezei de progresie a procesului miopatic, vor îmbogăţi datele actuale cu privire la mecanismele moleculare ale procesului miopatic şi va deschide posibilitatea prognozării individuale a evoluţiei procesului patologic cu indicarea corecţiei metabolice corespunzătoare. S-a efectuat un studiu epidemiologic- cercetare retrospectivă de cohortă, iar prelucrarea statistică a datelor obţinute a fost realizată cu ajutorul programelor SPSS (versiunea 20) şi MDR. Metoda regresiei logistice multinomiale a permis alegerea modelului optim al intensităţii legăturilor parametrilor genetici şi a altor date clinice cu viteza progresiei procesului patologic. Un rezultat pozitiv pentru genotipul heterozigot al genei MTHFR C677T şi homozigot după mutaţia MTHFR A1298C semnifică faptul că aceste categorii acţionează în calitate de categorii superioare a variabilei dependente (p=0,004 şi 0,039 respectiv). Valoarea matematică a estimărilor parametrilor regresiei a arătat o valoare statistic semnifi cativă pentru compound heterozigot MTHFR C677T, MTHFR A1298C, MTR A2756G (ß=33,7) şi MTHFR C677T, MTRR A66G, MTR A2756G (ß=34,7). Sinergismul pronunţat al interacţiunilor dintre genele ciclurilor folat, metioninic şi genei sintazei endoteliale NO constituie baza genetică a predispoziţiei către progresia procesului miopatic şi invaliditate timpurie (până la 9 ani). Concluzii. Estimarea efectului modificator al unui şir de sisteme genice asupra manifestărilor fenotipice ale patologiei monogenice prezintă o însemnătate fundamentală. Tipul şi forţa interacţiunilor dintre genele cercetate cu variante alelice- diferite la pacienţii MDD/B, imobilizaţi la vârstele de până la 9 şi 12 ani, cel mai probabil joacă un rol important în determinarea predispoziţiei de evoluţie a bolii spre stadiul imobilizării în scaunul cu rotile. Modificarea principiului consultului medico-genetic va permite identifi carea formelor clinice potenţial-grave de MDD/B, precum şi oferă posibilitatea de a alege tratamentul individual timpuriu şi în anumite cazuri ‒ efectuarea terapiei preventive

Synthesis of Quercetin Functionalized Chitosan and Determination of Antioxidant Properties

This paper is dedicated to the synthesis of a copolymer with reducing properties obtained by functionalizing chitosan with quercetin and determining the antioxidant activity of the derivatives obtained depending on the molar mass of the polymer. For this purpose, low molecular weight chitosan was obtained by oxidizing commercial chitosan with hydrogen peroxide and further functionalization with quercetin by the covalent grafting method. The functionalization process was performed through the following steps: functionalization of chitosan with ethyl chloroformate to increase the reactivity of the amine group to the hydroxyl group of quercetin and grafting the quercetin molecule to the synthesized intermediate. The comparative antioxidant properties of the composite obtained by grafting technical chitosan with quercetin and by grafting low molecular weight chitosan were studied by the DPPH (2,2-diphenyl-1-picrylhydrazyl radical) method. The obtained results indicate that a decrease in the molecular weight of chitosan contributed to its grafting with quercetin. As a result, the functionalized polymer composite acquired a higher antioxidant activity and can be successfully used to inhibit the oxidation of various organic substrates in the cosmetic, food and pharmaceutical industries

INDEX OF UNDERGROUND WATER POLLUTION WITH NITRATES: SPRINGS AND PUMPS IN THE NISTRU BASIN

Assessing the springs and pumps water quality (in the Nistru basin) it was found that in most of the districts there are sources of unpolluted water (8-58%), poorly polluted (10-56%) and moderately polluted (4-42%) waters with nitrates. Springs with significantly polluted water were found in Causeni district (33%) and with very significant pollution were identified in Ialoveni districts (26%), Anenii Noi (20%), Criuleni (15%), Rezina (14%) and Soldanesti (12%) districts, demonstrating the impact of the landfills on the accumulation of nitrates in the groundwater.</p

Fibrosis progression in paired liver biopsies from HIV/HCV co-infected patients

BACKGROUND: Chronic hepatitis C is more aggressive during HIV infection. Available data about risk factors of liver fibrosis in HIV/HCV co-infected patients derive from studies based on a single liver biopsy. OBJECTIVES: To evaluate the risk factors of liver fibrosis progression (LFP) and to investigate the role of antiretroviral therapy (ARV) in HIV/HCV patients who underwent paired liver biopsy. PATIENTS AND METHODS: We retrospectively studied 58 patients followed at two Infectious Diseases Departments in Northern Italy during the period 1988-2005. All specimens were double-blinded and centrally examined by two pathologists. LFP was defined when an increase of at least one stage occurred in the second biopsy, according to the Ishak-Knodell classification. RESULTS: In a univariate analysis, serum levels of alanine aminotransferase (ALT) > 150 IU/L at the first biopsy (P = 0.02), and a > 20% decrease in CD4+ cell count between the two biopsies (P = 0.007), were significantly associated with LFP. In multivariate analysis, a > 20% decrease in CD4+ cell count remained independently associated to LFP (Odds Ratio, 3.99; 95% confidence interval, 1.25-12.76; P < 0.02). Analysis of life survival curves confirmed the correlation between CD4+ cell count and LFP. CONCLUSIONS: Our findings highlight that in HIV/HCV coinfected patients, an effective antiretroviral therapy that assures a good immune-virological profile contributes to reducing the risk of LF

Ritlecitinib, a JAK3/TEC family kinase inhibitor, stabilizes active lesions and repigments stable lesions in vitiligo.

The efficacy of ritlecitinib, an oral JAK3/TEC family kinase inhibitor, on active and stable lesions was evaluated in patients with active non-segmental vitiligo in a phase 2b trial (NCT03715829). Patients were randomized to placebo or daily ritlecitinib 50&nbsp;mg (with or without 4-week 100-mg or 200-mg loading dose), 30&nbsp;mg, or 10&nbsp;mg for 24 weeks. Active lesions showed greater baseline expression of inflammatory/immune markers IFNG and CCL5, levels of CD103, and T-cell infiltrates than stable lesions. Patients with more active than stable vitiligo lesions showed higher baseline serum levels of CXCL9 and PD-L1, while patients with more stable than active lesions showed higher baseline serum levels of HO-1. At Week 24, ritlecitinib 50&nbsp;mg significantly stabilized mean percent change from baseline in depigmentation extent in both active lesions and stable lesions vs. placebo-response, with stable lesions showing greater repigmentation. After 24 weeks of treatment, ritlecitinib 50&nbsp;mg increased expression of melanocyte markers in stable lesions, while Th1/Th2-related and co-stimulatory molecules decreased significantly in both stable and active lesions. Serum from patients with more active than stable lesions showed decreased levels of ICOS and NK cell activation markers. These data, confirmed at transcription/protein levels, indicate that stable lesion repigmentation occurs early with ritlecitinib, while active lesions require stabilization of inflammation first. ClinicalTrials.gov: NCT03715829

Preferably Plinian and Pumaceous: Implications of Microbial Activity in Modern Volcanic Deposits at Askja Volcano, Iceland, and Relevancy for Mars Exploration

To search more efficiently for a record of past life on Mars, it is critical to know where to look and thus maximize the likelihood of success. Large-scale site selection for the Mars 2020 mission has been completed, but small (meter to 10 cm)-scale relationships of microenvironments will not be known until the rover reaches the surface. Over a 2 m transect at a modern volcanic deposit on the flank of Askja volcano in the barren highlands of Iceland, we compared two biological indicators (ATP activity and 16SrRNA amplicon sequence composition) to physical characteristics including bulk chemical composition, spectral signatures of mineralogy, and grain size. Using analytical instrumentation analogous to those available on Mars rovers, we were able to characterize the geological setting of the deposits and link physical parameters to microbial abundance and diversity. In general, methanogenesis, methanotrophy/methylotrophy, and nitrate reduction were the functional traits most associated with microbial community shift along the transect. Core microbiome members tended to be associated with nitrate reduction, and relative abundance of core microbes was strongly related to free water in the deposit. Community compositional shift of the rare microbiome was related to microenvironmental changes such as change in grain size, geochemistry, and age of deposit. These correlations lead us to suggest a sampling strategy that accounts for Martian geology, looking for undisturbed (not remobilized) explosive volcanic ash below pumice that could maximize diversity and abundance of different bioindicators. Our study also illustrates the importance of studying the variability across microenvironments in low biomass settings on earth

Biomarker and Geochemical Assay Validation in Mars Analog Sites: Lessons from the FELDSPAR (Field Exploration and Life Detection Sampling for Planetary Analog Research) Project

Missions looking for signs of life on other worlds can often only take a few samples once they arrive. Making sense of these "few and far between" observations is easier if we know what a "normal" level of variation for that kind of planet is. Recent eruption sites in Iceland are good places to learn about this, because they have very little life present and the same types of rocks as many places on Mars. We have visited several of these sites in Iceland and tested many different kinds of measurements: the energy available for life, the amount of DNA (an important biological molecule) present, the relative amounts of different kinds of micro-organisms, and the specific minerals that make up the rocks and ground. In addition to recommendations for future expeditions, we have also shown that using early on-site measurements to choose later on-site sample sites is very helpful in reducing the number of sample sites needed