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Background. Medicinal products contain excipients that might be associated with toxicity in neonates. The aim of this study was to investigate the administration of medication containing potentially harmful excipients to neonates hospitalized in Kosovo and to identify the possibility of reducing neonatal exposure to these excipients through product substitution. Methods. Data on all medication administered to hospitalized neonates from 1st of February to 1st of August 2018 along with patients` demographic data were collected from medical records for each neonate. Excipients were identified from the Summaries of Product Characteristics. Three stage criteria for product substitution were: (1) same active pharmaceutical ingredient (API) and route of administration; (2) 1 plus same dosage form; (3) 1 and 2 plus same strength. Results. In total, 100 excipients were found in 2388 prescriptions comprising 67 medications and 60 API administered to 294 (183 preterm and 111 term) hospitalized neonates. The excipients of interest (EOI) were present in 409 (17.1%) prescriptions and were administered to 131 (71.6%) preterm and 52 (46.8%) term neonates through a relatively small number of products (n=27; 32.8%). In relation to prescription frequency, the most common EOI was polysorbate 80, found in 229 (56%) of EOI-containing prescriptions. Substitution with EOIfree products was possible for 14 (63.6%), 12 (54.5%) and 5 (22.7%) products, according to the first-, second- and third-stage criteria, respectively. Conclusions. We have provided the first detailed description of neonatal exposure to potentially harmful excipients among neonates admitted to a neonatal intensive care unit in Kosovo. Unnecessary exposure could be reduced by using EOI-free products available in the local medicine market. Collaborative initiative is required to build up the evidence on the use of EOI in neonates and raising awareness among health care professionals on use of products without EOI where possible.

The study evaluates the chemical composition of the volatile constituents of ten plant species traditionally used as herbal tea in the Sharri Mountain regions (Kosovo and North Macedonia). Volatile constituents responsible for the flavour and fragrance of selected species (Crataegus monogyna, Cydonia oblonga, Malus sylvestris, Matricaria chamomilla, Morus alba, Morus nigra, Rosa canina, Sambucus nigra, Tilia cordata, and Vaccinium myrtillus) were separated and then identified using GC-MS, whereas GC-FID is employed for the quantitative analysis. Experimental data revealed different patterns of volatile constituents depending on plant species. Monoterpenes, sesquiterpenes, diterpenes, and norisoprenoids were the most abundant volatile constituents. Principal component analysis (PCA) was deployed for data analysis and resulted in grouping these ten species in four principal clusters. The combination of various volatile constituents present in specific plant species may play an important role in the specific aroma and taste sensation of these species used as recreational teas.

In the present study, eight plant species belonging to Lamiaceae family were identified as ingredients for herbal teas in the region of Sharri Mountains: Thymus serpyllum, Rosmarinus officinalis, Melissa officinalis, Origanum vulgare, Mentha longifolia, Ocimum basilicum, Teucrium chamaedrys, and Sideritis scardica, respectively. Chemical composition of essential oils obtained from these species was analyzed using GC-MS and GC-FID with the aim of examining their volatile compound profiles, responsible for their respective flavors and fragrance. Principal Component Analysis (PCA) was performed with the aim of grouping plant species under study on the basis of their chemical composition. Experimental data revealed the typical volatile constituent pattern for the Lamiaceae family. Monoterpenes and sesquiterpenes, responsible for flavor and medicinal use of these plants, were the most abundant groups of the volatile constituents. PCA data analysis resulted in the grouping of these analyzed species in four principal clusters.

Aspergillus flavus is one of the most important mycotoxigenic species from the genus Aspergillus, due to its ability to synthesize the potent hepatocarcinogen, aflatoxin B1. Moreover, this fungus is capable of producing several other toxic metabolites from the class of indole-tetramates, non-ribosomal peptides, and indole-diterpenoids. Populations of A. flavus are characterized by considerable diversity in terms of morphological, functional and genetic features. Although for many years A. flavus was considered an asexual fungus, researchers have shown evidence that at best these fungi can exhibit a predominantly asexual existence. We now know that A. flavus contains functional genes for mating, uncovering sexuality as potential contributor for its diversification. Based on our results, we reconfirm that A. flavus is a predominant producer of B-type aflatoxins. Moreover, this fungus can decisively produce AFM1 and AFM2. We did not observe any clear relationship between mating-type genes and particular class of metabolites, probably other parameters such as sexual/asexual ratio should be investigated. A dynamic secondary metabolism was found also in strains intended to be used as biocontrol agents. In addition we succeeded to provide mass spectrometry fragmentation spectra for the most important classes of A. flavus metabolites, which will serve as identification cards for future studies. Both, metabolic and phylogenetic analysis proved a high intra-species diversity for A. flavus. These findings contribute to our understanding about the diversity of Aspergillus section Flavi species, raising the necessity for polyphasic approaches (morphological, metabolic, genetic, etc.) when dealing with this type of complex group of species.

The principal aim of this study was to analyze the chemical composition and qualitative and quantitative variability of essential oils obtained from seven naturally grown populations of the Pinus peuce Grisebach, Pinaceae in Kosovo. Plant materials were collected from three populations in the Sharri National Park and from four other populations in the Bjeshkët e Nemuna National Park, in Kosovo. Essential oils were obtained by steam distillation and analyzed by GC-FID (Gas Chromatography-Flame Ionization Detection) and GC-MS (Gas Chromatography-Mass Spectrometry). The results showed that the yield of essential oils (v/w dry weight) varied depending on the origin of population and the plant organs and ranged from 0.7 to 3.3%. In total, 51 compounds were identified. The main compounds were α-pinene (needles: 21.6–34.9%; twigs: 11.0–24%), β-phellandrene (needles: 4.1–27.7; twigs: 29.0–49.8%), and β-pinene (needles: 10.0–16.1; twigs: 6.9–20.7%). HCA (Hierarchical Cluster Analysis) and PCA (Principal Component Analyses) were used to assess geographical variations in essential oil composition. Statistical analysis showed that the analyzed populations are grouped in three main clusters which seem to reflect microclimatic conditions on the chemical composition of the essential oils.

Cyclopiazonic acid (α-cyclopiazonic acid, α-CPA) is an indole-hydrindane-tetramic acid neurotoxin produced by various fungal species, including the notorious food and feed contaminant Aspergillus flavus. Despite its discovery in A. flavus cultures approximately 40 years ago, its contribution to the A. flavus mycotoxin burden is consistently minimized by our focus on the more potent carcinogenic aflatoxins also produced by this fungus. Here, we report the screening and identification of several CPA-type alkaloids not previously found in A. flavus cultures. Our identifications of these CPA-type alkaloids are based on a dereplication strategy involving accurate mass high resolution mass spectrometry data and a careful study of the α-CPA fragmentation pattern. In total, 22 CPA-type alkaloids were identified in extracts from the A. flavus strains examined. Of these metabolites, 13 have been previously reported in other fungi, though this is the first report of their existence in A. flavus. Two of our metabolite discoveries, 11,12-dehydro α-CPA and 3-hydroxy-2-oxo CPA, have never been reported for any organism. The conspicuous presence of CPA and its numerous derivatives in A. flavus cultures raises concerns about the long-term and cumulative toxicological effects of these fungal secondary metabolites and their contributions to the entire A. flavus mycotoxin problem.