Structural and functional models for [NiFe] hydrogenase

The main goal of the research presented in this thesis is the synthesis of suitable structural and functional models for the enzyme [NiFe] hydrogenase, which can reduce protons into dihydrogen. A brief survey of the roles of all the known nickel containing enzymes in biological systems with a focus on the [NiFe] hydrogenases. Structure, function, physicochemical and catalytic properties of the [NiFe] hydrogenase itself and of the reported model complexes are presented. Many new Nickel, [NiFe], [NiRu] and [NiCu] complexes have been synthesized and studied in view of better catalysts for proton electroreduction into dihydrogen.UBL - phd migration 201

Povezanost između novih SNP-a u egzonu 10 gena receptora hormona rasta i pokazatelja rasta u indijskih pasmina ovaca

The growth hormone receptor (GHR) gene encodes the type I cytokine receptor that helps in joining the growth hormone to this receptor, thus promoting receptor-dimerization, leading to up-regulating growth. The ovine GHR gene located on chromosome 16, which consists of 10 exons and 9 introns, along with untranslated regions on either side, comprise a total size of 178.09 kb. However, earlier reports about polymorphism have mainly dealt with exon 10 which is also a larger fragment of this gene comprising 1102 bp. Hence, this study was carried out to detect polymorphism in exon 10 of the GHR gene and its association with growth traits. Genomic DNA was isolated from blood samples of Madras Red and Mecheri sheep breeds from India. Part of exon 10 (895 bp) of the GHR gene was amplified and sent for sequencing. The sequence analysis revealed transition of nucleotide G>A at loci G177624A and G177878A in both sheep breeds. Populations were screened by Tetra-primer ARMS-PCR. The genotype frequencies of GG, GA and AA were 0.276, 0.519 and 0.205 at 177624 G>A, and 0.307, 0.444 and 0.149 at 177878 G>A in Madras Red sheep; whereas in Mecheri they were 0.476, 0.372 and 0.152 at 177624 G>A, and 0.629, 0.314 and 0.057 at 177878 G>A, respectively. Likewise the estimated allele frequencies of G and A were 0.5355 and 0.4645 at 177624 G>A, and 0.5790 and 0.4210 at 177878 G>A in Madras Red sheep; whereas in Mecheri they were 0.6620 and 0.3380 at 177624 G>A, and 0.7860 and 0.2140 at 177878 G>A, respectively. The effect of sex was significant for birth, six and nine month weight; but non-significant for three and 12 month weight in Mecheri sheep. However, in the Madras Red breed the effect of sex was significant for all body weights except weaning weight. The effect of variations on growth traits, viz., birth weight, weight at weaning, and weight at six, nine and twelve months in both breeds were analysed for their association, and they were found non-significant. Since these SNPs are salient findings of GHR gene polymorphism in Indian sheep breeds, further investigation is required into the significant effects of these novel SNPs, which could be useful for genetic improvement based on marker assisted selection.Gen receptora hormona rasta (GHR) kodira tip I citokinskog receptora koji pomaže u vezanju hormona rasta na ovaj receptor, promovirajući dimerizaciju receptora i time regulirajući rast. Ovčji gen GHR, lociran na kromosomu 16, sadržava 10 egzona i 9 introna s netranslatirajućim regijama s obje strane, tvoreći ukupnu veličinu od 178,09 kb. Dosadašnja istraživanja pokazala su da se polimorfizam nalazi većinom u egzonu 10, koji je ujedno veći fragment ovoga gena i sadržava 1102 bp. Ovo je istraživanje provedeno kako bi se otkrio polimorfizam u egzonu 10 gena GHR i njegova povezanost s pokazateljima rasta. Genomska DNA izolirana je iz uzoraka krvi ovaca pasmina Madras Red i Mecheri iz Indije. Dio egzona 10 (895 bp) gena GHR je umnožen i poslan na sekvenciranje koje je u obje pasmine ovaca pokazalo tranziciju nukleotida G > A na lokusima G177624A i G177878A. Probir populacija učinjen je pomoću Tetra-primer ARMS-PCR-a. Učestalost genotipa GG bila je 0,276, genotipa GA 0,519, a genotipa AA 0,205 na 177624 G>A, te 0,307, 0,444 i 0,149 na 177878 G>A u pasmine Madras Red. U pasmine Mecheri učestalost genotipa GG bila je 0,476, učestalost genotipa GA 0,372, a genotipa AA 0,152 na 177624 G > A, te 0,629, 0,314 i 0,057 na 177878 G > A. Učestalost alela G i A, koja je bila 0,5355 i 0,4645 na 177624 G > A, te 0,5790 i 0,4210 na 177878 G>A u ovaca Madras Red, dok je u pasmine Mecheri bila 0,6620 i 0,3380 na 177624 G>A, te 0,7860 i 0,2140 na 177878 G>A. Spol je znakovito utjecao na tjelesnu masu pri janjenju te u dobi od 6 i 9 mjeseci, no nije bilo znakovitog utjecaja u dobi od 3 i 12 mjeseci u pasmine Mecheri. S druge strane, u pasmine Madras Red spol je znakovito utjecao na tjelesnu masu u svim fazama rasta osim pri odbiću. Analizirana je povezanost varijacija s tjelesnom masom pri janjenju, odbiću te u dobi od 6, 9 i 12 mjeseci u obje pasmine, koja nije bila znakovita. Budući da su otkrića ovih SNP-a važna u proučavanju gena GHR u indijskih pasmina ovaca, potrebna su daljnja istraživanja njihova učinka koja bi mogla biti korisna u genetskom poboljšanju populaciju primjenom markerima potpomognute selekcije

Biopharmaceutical Classification System in Invitro/ In-vivo Correlation: Concept and Development Strategies in Drug Delivery

Drug development is a very laborious and expensive process. One of the major reasons for failure during the clinical phases of drug development is inadequate pharmacokinetic data on the drug candidate. Therefore, it would be advantageous if the pharmacokinetic properties of drug candidates be predicted beforehand. One major obstacle in making such  predictions is the inability to appropriately scale the in-vitro data to the in-vivo situation. Results from in-vitro in-vivo correlation (IVIVC) studies have been used to select the appropriate excipients and optimize the manufacturing processes for quality control purposes, and for characterizing the release patterns of newly formulated immediate release, and modified-release products relative to the references. In recent years, the concept and application of the IVIVC for pharmaceutical dosage forms have been a major focus of attention in the pharmaceutical industry, academia and regulatory agencies. Hence, this article highlights the importance of appropriate selection of IVIVC level with respect to the Biopharmaceutical Classification System (BCS) and also covers examples of BCS-based IVIVCs of drugs/products with different types of release profiles.Keywords: In vitro/In vivo correlation, Biopharmaceutical Classification System, Drug Delivery

Transmission of infection among health care personnel performing surgical tracheostomies on COVID-19 patients

Background: Staff and patient safety are of paramount importance while performing a surgical tracheostomy(ST) during the corona virus disease(COVID-19) pandemic. The aim was to assess the incidence of COVID-19 infection among the healthcare personnel(HCP) performing ST on COVID-19 patients. / Methods: One hundred and twenty-two HCP participating in 71 ST procedures performed at our institution between 26th March 2020 and 27th May 2020 were identified. A COVID-19 health questionnaire was distributed among staff with their consent. Data related to the presence of COVID-19 symptoms(new onset continuous cough, fever, loss of taste and/or loss of smell) among HCP involved in ST as well as patient related data were collected. / Results: Of the HCP who responded, eleven(15%,11/72) reported key COVID-19 symptoms and went into self-isolation. Ten members from this group underwent a COVID-19 swab test and three tested positive. Only one HCP attended hospital for symptomatic treatment, none required hospitalisation. Sixty percent(43/72) of the responders had a COVID-19 antibody test with a positive rate of 18.6%(8/43). Among the patients undergoing a ST, 67%(37/55) required a direct intensive care unit(ICU) admission; the mean age was 58 years(29-78) with a male preponderance(65.5%). The median time from intubation to ST was 15 days (range 5-33,IQR=9). The overall mortality was 11%(6/55). / Conclusions: ST can be carried out safely with strict adherence to both, personnel protective equipment and ST protocols which are vital to mitigate the potential transmission of COVID-19 to the HCP

Selective CO₂ capture in metal-organic frameworks with azine-functionalized pores generated by mechanosynthesis

Two new three-dimensional porous Zn(II)-based metal-organic frameworks, containing azine-functionalized pores, have been readily and quickly isolated via mechanosynthesis, by using a nonlinear dicarboxylate and linear N-donor ligands. The use of nonfunctionalized and methyl-functionalized N-donor ligands has led to the formation of frameworks with different topologies and metal-ligand connectivities and therefore different pore sizes and accessible volumes. Despite this, both metal-organic frameworks (MOFs) possess comparable BET surface areas and CO₂ uptakes at 273 and 298 K at 1 bar. The network with narrow and interconnected pores in three dimensions shows greater affinity for CO compared to the network with one-dimensional and relatively large pores-attributable to the more effective interactions with the azine groups

Correction to: Two years later: Is the SARS-CoV-2 pandemic still having an impact on emergency surgery? An international cross-sectional survey among WSES members

Background: The SARS-CoV-2 pandemic is still ongoing and a major challenge for health care services worldwide. In the first WSES COVID-19 emergency surgery survey, a strong negative impact on emergency surgery (ES) had been described already early in the pandemic situation. However, the knowledge is limited about current effects of the pandemic on patient flow through emergency rooms, daily routine and decision making in ES as well as their changes over time during the last two pandemic years. This second WSES COVID-19 emergency surgery survey investigates the impact of the SARS-CoV-2 pandemic on ES during the course of the pandemic. Methods: A web survey had been distributed to medical specialists in ES during a four-week period from January 2022, investigating the impact of the pandemic on patients and septic diseases both requiring ES, structural problems due to the pandemic and time-to-intervention in ES routine. Results: 367 collaborators from 59 countries responded to the survey. The majority indicated that the pandemic still significantly impacts on treatment and outcome of surgical emergency patients (83.1% and 78.5%, respectively). As reasons, the collaborators reported decreased case load in ES (44.7%), but patients presenting with more prolonged and severe diseases, especially concerning perforated appendicitis (62.1%) and diverticulitis (57.5%). Otherwise, approximately 50% of the participants still observe a delay in time-to-intervention in ES compared with the situation before the pandemic. Relevant causes leading to enlarged time-to-intervention in ES during the pandemic are persistent problems with in-hospital logistics, lacks in medical staff as well as operating room and intensive care capacities during the pandemic. This leads not only to the need for triage or transferring of ES patients to other hospitals, reported by 64.0% and 48.8% of the collaborators, respectively, but also to paradigm shifts in treatment modalities to non-operative approaches reported by 67.3% of the participants, especially in uncomplicated appendicitis, cholecystitis and multiple-recurrent diverticulitis. Conclusions: The SARS-CoV-2 pandemic still significantly impacts on care and outcome of patients in ES. Well-known problems with in-hospital logistics are not sufficiently resolved by now; however, medical staff shortages and reduced capacities have been dramatically aggravated over last two pandemic years