The rational design of topical formulations

This thesis addresses the development of topical formulations designed to treat atopic dermatitis (AD) using nicotinamide (NA). A rational approach to the development of topical formulations based on the physical and chemical properties of the drug and vehicle components is studied. This approach is an alternative to the model of formulation development where the drug is added into an existing vehicle without optimisation of the formulation in terms of the active delivery to its site of action. The work encompasses preliminary pre-formulation studies, in vitro uptake and permeation studies using a model silicone membrane and pig ear skin. Moreover, the influence of topical formulations containing the model drug on the parameters indicative of skin health is tested in the in vivo studies. The primary objective is to optimise the skin delivery of NA with the use of appropriate excipients. The solvents are chosen on the basis of their physicochemical parameters, namely solubility parameter (δ), mutual miscibility and ability to dissolve the model drug. The performance of rationally developed simple formulations is tested in vitro and compared with prototype formulations containing more complex vehicles. In vitro uptake and permeation studies using silicone are performed to determine the influence of chosen solvents on NA permeation in a membrane which is less complex than skin. In addition NA skin delivery is evaluated with in vitro and in vivo techniques and the relationship between the physicochemical parameters of the solvents used and the drug percutaneous absorption is examined. Finally, the efficacy of prototype NA formulations in improving the skin state in vivo is investigated. The performance of prototype formulations in terms of NA percutaneous absorption is determined with reference to their influence on the skin condition

Multinational prospective cohort study of rates and risk factors for ventilator-associated pneumonia over 24 years in 42 countries of Asia, Africa, Eastern Europe, Latin America, and the Middle East: Findings of the International Nosocomial Infection Control Consortium (INICC)

Objective: Rates of ventilator-associated pneumonia (VAP) in low- and middle-income countries (LMIC) are several times above those of high-income countries. The objective of this study was to identify risk factors (RFs) for VAP cases in ICUs of LMICs. Design: Prospective cohort study. Setting: This study was conducted across 743 ICUs of 282 hospitals in 144 cities in 42 Asian, African, European, Latin American, and Middle Eastern countries. Participants: The study included patients admitted to ICUs across 24 years. Results: In total, 289,643 patients were followed during 1,951,405 patient days and acquired 8,236 VAPs. We analyzed 10 independent variables. Multiple logistic regression identified the following independent VAP RFs: male sex (adjusted odds ratio [aOR], 1.22; 95% confidence interval [CI], 1.16-1.28; P <.0001); longer length of stay (LOS), which increased the risk 7% per day (aOR, 1.07; 95% CI, 1.07-1.08; P <.0001); mechanical ventilation (MV) utilization ratio (aOR, 1.27; 95% CI, 1.23-1.31; P <.0001); continuous positive airway pressure (CPAP), which was associated with the highest risk (aOR, 13.38; 95% CI, 11.57-15.48; P <.0001)Revisión por pare

International Nosocomial Infection Control Consortium report, datasummary of 50 countries for 2010-2015 : Device-associated module

Q3Artículo original1495-1504Background: We report the results of International Nosocomial Infection Control Consortium (INICC) sur-veillance study from January 2010-December 2015 in 703 intensive care units (ICUs) in Latin America,Europe, Eastern Mediterranean, Southeast Asia, and Western Pacific.Methods:During the 6-year study period, using Centers for Disease Control and Prevention National Health-care Safety Network (CDC-NHSN) definitions for device-associated health care-associated infection (DA-HAI), we collected prospective data from 861,284 patients hospitalized in INICC hospital ICUs for an aggregateof 3,506,562 days.Results:Although device use in INICC ICUs was similar to that reported from CDC-NHSN ICUs, DA-HAIrates were higher in the INICC ICUs: in the INICC medical-surgical ICUs, the pooled rate of central line-associated bloodstream infection, 4.1 per 1,000 central line-days, was nearly 5-fold higher than the 0.8per 1,000 central line-days reported from comparable US ICUs, the overall rate of ventilator-associatedpneumonia was also higher, 13.1 versus 0.9 per 1,000 ventilator-days, as was the rate of catheter-associated urinary tract infection, 5.07 versus 1.7 per 1,000 catheter-days. From blood cultures samples,frequencies of resistance ofPseudomonasisolates to amikacin (29.87% vs 10%) and to imipenem (44.3%vs 26.1%), and ofKlebsiella pneumoniaeisolates to ceftazidime (73.2% vs 28.8%) and to imipenem (43.27%vs 12.8%) were also higher in the INICC ICUs compared with CDC-NHSN ICUs.Conclusions:Although DA-HAIs in INICC ICU patients continue to be higher than the rates reported inCDC-NSHN ICUs representing the developed world, we have observed a significant trend toward the re-duction of DA-HAI rates in INICC ICUs as shown in each international report. It is INICC’s main goal tocontinue facilitating education, training, and basic and cost-effective tools and resources, such as stan-dardized forms and an online platform, to tackle this problem effectively and systematically

Education of the youngest - the long-term investment for environment. The author's programme [...] realised in the Stolowe Mountains National Park [Polish Sudetes]

Kształtowanie właściwych postaw człowieka wobec przyrody jest jednym z kluczowych celów ochrony środowiska. Edukację ekologiczną można i powinno się realizować na każdym szczeblu procesu zdobywania wiedzy przez człowieka, jednak największy efekt osiągniemy wychodząc do najmłodszych dzieci. Dodatkowo, jeśli edukacja ta nie jest okazjonalna a cykliczna, to wyraźnie kształtuje w odbiorcy pozytywne nawyki względem przyrody. Młody człowiek tym, czym za młodu nasiąknie, będzie procentował w późniejszym życiu. Park Narodowy Gór Stołowych w 2006 r. przystąpił do realizacji programu edukacji środowiskowej Czym skorupka za młodu nasiąknie… czyli jak pokochać przyrodę, żeby ona pokochała nas. Jest to program autorski Gorczańskiego Parku Narodowego. Adresatami są nauczyciele i uczniowie klas I – III szkoły podstawowej. Główne założenia programu określają, że najbardziej efektywną metodą w procesie edukacji jest praca z jedną grupą dzieci przez kilka lat. Program obejmuje cykl 10 zajęć w każdej z klas. W klasie I uczniowie są uwrażliwiani na przyrodę, w klasie II zdobywają wiedzę, a w III uczą się chronić przyrodę w swoim otoczeniu. Od 2006 roku programem objętych zostało ok. 2000 nauczycieli nauczania zintegrowanego. Pieczę nad tą rzeszą ludzi sprawuje ponad 60 koordynatorów terenowych z całego kraju, którzy mają za zadanie między innymi przeszkolić grono pedagogiczne do prowadzenia zajęć z dziećmi oraz wyposażyć w materiały dydaktyczne do pracy. W listopadzie 2006 r. w Parku Narodowym Gór Stołowych odbyły się pierwsze warsztaty dla nauczycieli biorących udział w programie – rozpoczęto tym samym długoterminową współpracę z okolicznymi szkołami – jako niewątpliwą inwestycję w środowisko w trosce o jego stan dzisiaj jak i w przyszłości.The main goal of the environment protection is to form proper attitude of man towards the nature. This is why the ecological education should be realised on each level of the man teaching process, but the best effect is achieved when we work with the youngest children. Additionally, distinctly positive habits towards nature, are created when the education in not accidental, but cyclic. In the year 2006 Stolowe Mountains National Park started the realisation of the environmental education programme What is bred in the bone... ... that is to say – how to fall in love with nature, in order it falls in love with us. Gorce National Park is an author of the programme. Teachers and pupils of I – III elementary school classes are the receivers of it. According the main assumption of the programme, the work with the very same group of children for several years is the most effective method of the education. Programme includes the cycle of 10 trainings in each class. During the first year of education pupils are sensibilized with nature, during the second one they gather natural knowledge, but in the period of the third they are learning how to protect the nature in their neighbourhood. Since 2006 the programme have been realised for about 2000 elementary school teachers. More than 60 co-ordinators have them in care in the terrain of all over the country. The co-ordinators tasks are training of teaching staff and providing didactic materials for the work. The first workshop for teachers taking part in programme took place in Stolowe Mountains National Park in November 2006 – thereby the long lasting co-operation with local schools started. We feel sure that it is very good investment for environmental protection in our days as it is in the future

Reproductive Genetics and Epigenetics of F1 hybrid triploids of Arabidopsis thaliana L.

Polyploidy, the occurrence of more than two complete sets of chromosomes in a single nucleus, is an important process contributing to eukaryotic evolution. Polyploidy is also a widespread speciation mechanism and is common among plants, fish and amphibians. Polyploidy can be advantageous, and lead to heterosis, gene redundancy, and asexual reproduction (apomixis). However, polyploidy makes the completion of mitosis and meiosis more challenging, which often results in production of aneuploid cells and gametes. Improved understanding of the biology of polyploids is essential because many economically important crops are polyploid, including Solanum tuberosum (potato), Triticum (wheat) and Gossypium (cotton). Polyploid crops also include triploid crops such as Musa (banana), Malus domestica (apple) and Beta vulgaris (sugar beet). Chromosome segregation during triploid meiosis is particularly complicated by the need for the three sets of chromosomes to be resolved to two poles which results in the production of gametes with frequent chromosome loss and fragmentation. Hence, the immediate progeny of triploids can have complex karyotypes, which can differ in the number of copies of each chromosome. Imbalanced dosage effects resulting from aneuploidy can be deleterious to development, and contribute to the dramatic reduction in fertility of triploids. In this thesis, genome dosage and hybridity effects on reproduction, seed size heterosis and seed development were investigated using a set of F1 hybrid and isogenic triploids of Arabidopsis thaliana. These were generated by reciprocal inter-ploidy crosses, incorporating 90 different accessions that can differ genetically and epigenetically. Relative triploid reproductive traits of selfed F1 triploids were analysed by collecting ANU data (A aborted F2 seeds, N normal F2 seeds, U- unfertilized ovules) and by converting the datasets to %A, %N, %U with respect to the total number of ovules per silique (E = A+N+U). It was discovered that, depending on genotype, selfed F1 isogenic triploids and F1 hybrid triploids exhibit differing levels of fertility defects at the pre-fertilisation (unfertilised F1 ovules) and post-fertilisation stages (normal vs aborted F2 seeds). It was further discovered that epigenetic parent-of-origin effects on reproduction and seed development can occur between reciprocal F1 triploids which have differing contributions of maternal- vs paternal-derived chromosomes. Such epigenetic parent-of-origin effects were observed for both isogenic F1 triploids (Col-0) and for a wide range of hybrid F1 triploid genotypes. The epigenetic parent-of-origin effects either caused greater fertility defects in the maternal excess F1 triploid or in the paternal excess F1 triploid. Flow cytometric analysis of single seed indicated that the surviving F2 seed progeny comprised a wide range of DNA contents, including likely aneuploids with incomplete sets of chromosomes. This supports the proposed role for triploids as evolutionary bridges between plant populations of different ploidy levels. The 89 diploid accessions used to generate the F1 hybrid triploids have been extensively characterised for SNPs (Single Nucleotide Polymorphisms) across the Arabidopsis thaliana genome. This allowed the use of genome wide association (GWA) mapping for the identification of loci involved in control of reciprocal F1 hybrid triploid reproduction and production of normal F2 seed sets (%N). Two candidate loci involved in the phenotypic variation in %N among F2 seeds produced by paternal excess F1 triploids and maternal excess F1 triploids were identified by GWA mapping and named POT (Paternal Overdose Triploid) and MOT (Maternal Overdose Triploid) respectively. Candidate protein-coding genes at the POT and MOT loci were selected based on their known involvement in the plant reproductive pathways and seed development. Some of these genes are involved in epigenetic processes including DNA methylation, histone modification, and siRNA mediated gene silencing and are strong candidates for explaining the epigenetic parent-of-origin effects which are controlling triploid reproductive success

Reproductive Genetics and Epigenetics of F1 hybrid triploids of Arabidopsis thaliana L.

Polyploidy, the occurrence of more than two complete sets of chromosomes in a single nucleus, is an important process contributing to eukaryotic evolution. Polyploidy is also a widespread speciation mechanism and is common among plants, fish and amphibians. Polyploidy can be advantageous, and lead to heterosis, gene redundancy, and asexual reproduction (apomixis). However, polyploidy makes the completion of mitosis and meiosis more challenging, which often results in production of aneuploid cells and gametes. Improved understanding of the biology of polyploids is essential because many economically important crops are polyploid, including Solanum tuberosum (potato), Triticum (wheat) and Gossypium (cotton). Polyploid crops also include triploid crops such as Musa (banana), Malus domestica (apple) and Beta vulgaris (sugar beet). Chromosome segregation during triploid meiosis is particularly complicated by the need for the three sets of chromosomes to be resolved to two poles which results in the production of gametes with frequent chromosome loss and fragmentation. Hence, the immediate progeny of triploids can have complex karyotypes, which can differ in the number of copies of each chromosome. Imbalanced dosage effects resulting from aneuploidy can be deleterious to development, and contribute to the dramatic reduction in fertility of triploids. In this thesis, genome dosage and hybridity effects on reproduction, seed size heterosis and seed development were investigated using a set of F1 hybrid and isogenic triploids of Arabidopsis thaliana. These were generated by reciprocal inter-ploidy crosses, incorporating 90 different accessions that can differ genetically and epigenetically. Relative triploid reproductive traits of selfed F1 triploids were analysed by collecting ANU data (A aborted F2 seeds, N normal F2 seeds, U- unfertilized ovules) and by converting the datasets to %A, %N, %U with respect to the total number of ovules per silique (E = A+N+U). It was discovered that, depending on genotype, selfed F1 isogenic triploids and F1 hybrid triploids exhibit differing levels of fertility defects at the pre-fertilisation (unfertilised F1 ovules) and post-fertilisation stages (normal vs aborted F2 seeds). It was further discovered that epigenetic parent-of-origin effects on reproduction and seed development can occur between reciprocal F1 triploids which have differing contributions of maternal- vs paternal-derived chromosomes. Such epigenetic parent-of-origin effects were observed for both isogenic F1 triploids (Col-0) and for a wide range of hybrid F1 triploid genotypes. The epigenetic parent-of-origin effects either caused greater fertility defects in the maternal excess F1 triploid or in the paternal excess F1 triploid. Flow cytometric analysis of single seed indicated that the surviving F2 seed progeny comprised a wide range of DNA contents, including likely aneuploids with incomplete sets of chromosomes. This supports the proposed role for triploids as evolutionary bridges between plant populations of different ploidy levels. The 89 diploid accessions used to generate the F1 hybrid triploids have been extensively characterised for SNPs (Single Nucleotide Polymorphisms) across the Arabidopsis thaliana genome. This allowed the use of genome wide association (GWA) mapping for the identification of loci involved in control of reciprocal F1 hybrid triploid reproduction and production of normal F2 seed sets (%N). Two candidate loci involved in the phenotypic variation in %N among F2 seeds produced by paternal excess F1 triploids and maternal excess F1 triploids were identified by GWA mapping and named POT (Paternal Overdose Triploid) and MOT (Maternal Overdose Triploid) respectively. Candidate protein-coding genes at the POT and MOT loci were selected based on their known involvement in the plant reproductive pathways and seed development. Some of these genes are involved in epigenetic processes including DNA methylation, histone modification, and siRNA mediated gene silencing and are strong candidates for explaining the epigenetic parent-of-origin effects which are controlling triploid reproductive success

Devonskie foraminifery Vydryshova (Sventokrzhiskie gory)

Seven species of Foraminifera are described from the Couvinian of Wydryszów, four of which are considered new. These are: Hyperammina couviniana. Ammodiscus similis, Reophax wydryszowiensis and Pseudopalmula polonica.Autorka opisuje 7 gatunków otwornic, znalezionych w osadach marglistych kuwinu, w miejscowość Wydryszow. Występują tu 4 nowe gatunki: Hyperammina couviniana. Ammodiscus similis, Reophax wydryszowiensis i Pseudopalmula polonica.Dalsze 3 gatunki znane są juz z literatury : Semitextularia thomasi występuje w żywecie Polski w profilu Grzegorzowice-Skały i w Czechosłowacji, w dewonie górnym - w Ameryce, w stanie Iowa , oraz w ZSRR, w rejonie woroneżskim; Pseudopalmula palmuloides znana jest z górnego dewonu Ameryki, w stanie Iowa , jak również w ZSRR, w rejonie woroneżskim; Pseudopalmula aff. extremitata znana jest z franu ZSRR, w rejonie woroneżskim.Otwornice dewońskie na terenie Polski były znane dotychczas tylko z łupku brachiopodowego w profilu Grzegorzowice-Skały, gdzie stwierdzono 3 gatunki ; w Wydryszowie natomiast występuje ich 7. Są one lepiej zachowane, a mianowicie nie są wypełnione tlenkami żelaza, co ułatwia badania. Spośród tych siedmiu gatunków, opisanych z Wydryszowa, cztery były znane w dewonie,lecz w piętrach młodszych (żywet , fran, famen). Pozostałe trzy są nowe i należą do rodzajów : Hyperammina, Ammodiscus i Reophax . Rodzaje Hyperammina Ammodiscus, których dwa gatunki opisano w niniejszej pracy, dotychczas nie były cytowane z dewonu. Znano je z syluru, a następnie od karbonu wzwyż. Znalezienie wymienionych rodzajów w dewonie Wydryszowa wypełnia zatem tę lukę. Także znalezienie Reophax w kuwinie pozwala na przesunięcie dolnej granicy występowania tego rodzaju, znanego dotychczas dopiero od karbonu. Poniżej podane są diagnozy nowych gatunków. Hyperammina couviniana n.sp. (fig.1) Skorupka jednokomorowa w postaci rurki, nieco wygiętej, zwykle otwartej na obu końcach. Jeden koniec jest trochę węższy, drugi zaś nieco szerszy. Ujście znajduje się na całej średnicy rurki. Początek rurki jest najczęściej nie zachowany. Koniec adapikalny jednego okazu jest zamknięty i nieco rozdęty ; być może, że rozszerzenie to odpowiada prolokulusowi, chociaż nie jest ono wyraźnie odgraniczone. Ściany zbudowane są z bardzo drobnych ziarnek kwarcu i spoiwa krzemionkowego . Ammodiscus similis n.sp . (fig.2) Skorupka zlepieńcowata okrągła, plaska, pośrodku nieco wklęsła, utworzona przez rurkę zwiniętą planispiralnie, tworzącą 5-7 skrętów. Przy prolokulusie skręty są węższe, przy ujściu zlekka się rozszerzają i trochę zachodzą na siebie. Ujście zaokrąglone. Ścianki zabudowane są z drobnych ziarnek kwarcu i lepiszcza krzemionkowego. Reophax wydryszowiensis n. sp. (fig.3 i pl. I) Skorupka zlepieńcowata, jednoseryjna, dwu- lub trójkomorowa. Ścianka zbudowana z dużych kanciastych ziarnek kwarcu bez śladów obtoczenia. Lepiszcze krzemionkowe, przekrystalizowane, mikrokrystaliczne, niezbyt obfite. Badania szlifów wykazały, że grubość ścianek skorupki równa jest grubości pojedynczego ziarna kwarcu. Wielkość poszczególnych ziaren jest rożna , waha się w granicach od 6 do 78, a długość - od 24 do 47u. Ziarna kwarcu położone są względem siebie mniej lub więcej równolegle. Powierzchnia wewnętrzna i zewnętrzna ścianki jest chropowata. Prolokulus kulisty, o średnicy 0,03-0,34 mm. Komory są zaokrąglone , o wzrastającej w kierunku ujścia objętości. Poszczególne komory stykają się bezpośrednio ze sobą, łącząc się głębokim szwem. Ostatnia komora ma kształt gruszkowaty i szyjkę z terminalnym zaokrąglonym ujściem. Pseudopalmula polonica n.sp . (fig.7) Skorupka trójkątna o zaokrąglonych narożach, dwuseryjna, spłaszczona, złożona z 8-11 komór mocno wydłużonych, trochę wygiętych. Każda komora jest podzielona poprzecznymi przegrodami na szereg wtórnych komórek. Szerokość poszczególnej komórki jest prawie równa grubości przegrody poprzecznej. Zewnętrzna powierzchnia skorupki jest wyraźnie poprzecznie prążkowana. Komory przy prolokulusie są krótkie, w. kierunku ujścia wydłużają się. Szwy nieco wgłębione. Prolokulus okrągły, duży, o średnicy 0,11 do 0,07 mm. Ujście na końcu ostatniej komory, niezbyt widoczne. Ścianki zbudowane są z kryptokrystalicznego kalcytu

Foraminifery srednego debona Sventokrzhiskikh Gor

Description is given of three species of Devonian (Givetian) foraminifers , never before collected in Poland. These specimens represent forms with a wide geographical and stratigraphic range. Identical or similar forms have been yielded by rocks from the Middle and Upper Devonian of Europe and from the Upper Devonian of North America.Autorka opisuje trzy gatunki otwornic, znalezione przez mgra F. Adamczaka w miejscowości Skały w Górach Świętokrzyskich. Występują tam one w tzw. łupkach brachiopodowych wieku żywieckiego. Są to następujące gatunki : Moravammina segmentata Pokorny Semitextularia thomasi Miller & Carmer Textularia? proboscidea Cushman & Stainbrook. Pierwszy z nich znany jest z dewonu środkowego Czechosłowacji, drugi zaś i trzeci występują w dewonie górnym Ameryki Północnej . Poza tym, formy zbliżone do Semitextularia thomasi i do Textularia? proboscidea opisane zostały przez E. W. Bykowa z dewonu środkowego i górnego Platformy Rosyjskiej . Zbadanie kilkuset okazów S. thomasi z Gór Świętokrzyskich dało autorce możność stwierdzenia dużej zmienności i różnych cech tego gatunku, Na podstawie tych obserwacji stało się wielce prawdopodobne, że formy, opisane przez E. W. Bykowa i zaliczone przez nią aż do ośmiu gatunków rodzaju Semitextularia, są w rzeczywistości wariantami jednego lub najwyżej paru gatunków