University of Prishtina

<b><i>Background/Aims: </i></b>Klotho, a protein mainly produced in the kidney and released into circulating blood, contributes to the negative regulation of 1,25(OH)<sub>2</sub>D<sub>3</sub> formation and is thus a powerful regulator of mineral metabolism. As β-glucuronidase, alpha Klotho protein further regulates the stability of several carriers and channels in the plasma membrane and thus regulates channel and transporter activity. Accordingly, alpha Klotho protein participates in the regulation of diverse functions seemingly unrelated to mineral metabolism including lymphocyte function. The present study explored the impact of alpha Klotho protein on the voltage gated K<sup>+</sup> channel K<sub>v1.3</sub>. <b><i>Methods: </i></b>cRNA encoding K<sub>v1.3</sub> (KCNA3) was injected into <i>Xenopus</i> oocytes and depolarization induced outward current in K<sub>v1.3</sub> expressing <i>Xenopus</i> oocytes determined utilizing dual electrode voltage clamp. Experiments were performed without or with prior treatment with recombinant human Klotho protein (50 ng/ml, 24 hours) in the absence or presence of a β-glucuronidase inhibitor D-saccharic acid-1,4-lactone (DSAL, 10 µM). Moreover, the voltage gated K<sup>+</sup> current was determined in Jcam lymphoma cells by whole cell patch clamp following 24 hours incubation without or with recombinant human Klotho protein (50 ng/ml, 24 hours). K<sub>v1.3</sub> protein abundance in Jcam cells was determined utilising fluorescent antibodies in flow cytometry. <b><i>Results: </i></b>In K<sub>v1.3</sub> expressing <i>Xenopus</i> oocytes the K<sub>v1.3</sub> currents and the protein abundance of K<sub>v1.3</sub> were both significantly enhanced after treatment with recombinant human Klotho protein (50 ng/ml, 24 hours), an effect reversed by presence of DSAL. Moreover, treatment with recombinant human Klotho protein increased K<sub>v</sub> currents and K<sub>v1.3</sub> protein abundance in Jcam cells. <b><i>Conclusion: </i></b>Alpha Klotho protein enhances K<sub>v1.3</sub> channel abundance and K<sub>v1.3</sub> currents in the plasma membrane, an effect depending on its β-glucuronidase activity.

Surface chemistry is the topic of this tutorial review. It describes the electrochemical reduction of aryl diazonium salts on carbon, silicon or metals which leads to the formation of an aromatic organic layer covalently bonded to the surface. The method which permits such a modification is set forth. The proof for the existence of the organic layer is brought forward. The grafting mechanism and the covalent bonding between the surface and the aryl group are discussed. The formation of mono or multilayers depending on the experimental conditions is rationalized. Finally some examples of the possible uses of this reaction are given.

Antimicrobial resistance (AMR) is a serious threat to global public health, but obtaining representative data on AMR for healthy human populations is difficult. Here, we use metagenomic analysis of untreated sewage to characterize the bacterial resistome from 79 sites in 60 countries. We find systematic differences in abundance and diversity of AMR genes between Europe/North-America/Oceania and Africa/Asia/South-America. Antimicrobial use data and bacterial taxonomy only explains a minor part of the AMR variation that we observe. We find no evidence for cross-selection between antimicrobial classes, or for effect of air travel between sites. However, AMR gene abundance strongly correlates with socio-economic, health and environmental factors, which we use to predict AMR gene abundances in all countries in the world. Our findings suggest that global AMR gene diversity and abundance vary by region, and that improving sanitation and health could potentially limit the global burden of AMR. We propose metagenomic analysis of sewage as an ethically acceptable and economically feasible approach for continuous global surveillance and prediction of AMR.

ABSTRACT This paper estimates the value of tax benefits in 76 management buyouts of public companies completed in the period 1980 to 1986. The median value of tax benefits, estimated at the time the buyout company goes private, has a lower bound of 21% and an upper bound of 143% of the premium paid to pre‐buyout shareholders. The estimated value depends on the rate buyout debt is repaid and the tax rate applied to the interest deductions. The paper also presents evidence on the actual taxes paid and debt repayment rates by these companies after the buyout. The results in this paper suggest that tax benefits are an important source of the wealth gains in management buyouts.

Despite the discovery and application of many parenteral (unfractionated and low-molecular-weight heparins) and oral anticoagulant vitamin K antagonist (VKA) drugs, the prevention and treatment of venous and arterial thrombotic phenomena remain major medical challenges. Furthermore, VKAs are the only oral anticoagulants used during the past 60 years. The main objective of this study is to present recent data on non-vitamin K antagonist oral anticoagulants (NOACs) and to analyze their advantages and disadvantages compared with those of VKAs based on a large number of recent studies. NOACs are novel direct-acting medications that are selective for one specific coagulation factor, either thrombin (IIa) or activated factor X (Xa). Several NOACs, such as dabigatran (a direct inhibitor of FIIa) and rivaroxaban, apixaban and edoxaban (direct inhibitors of factor Xa), have been used for at least 5 years but possibly 10 years. Unlike traditional VKAs, which prevent the coagulation process by suppressing the synthesis of vitamin K-dependent factors, NOACs directly inhibit key proteases (factors IIa and Xa). The important indications of these drugs are the prevention and treatment of deep vein thrombosis and pulmonary embolisms, and the prevention of atherothrombotic events in the heart and brain of patients with acute coronary syndrome and atrial fibrillation. They are not fixed, and dose-various strengths are available. Most studies have reported that more advantages than disadvantages for NOACs when compared with VKAs, with the most important advantages of NOACs including safety issues (ie, a lower incidence of major bleeding), convenience of use, minor drug and food interactions, a wide therapeutic window, and no need for laboratory monitoring. Nonetheless, there are some conditions for which VKAs remain the drug of choice. Based on the available data, we can conclude that NOACs have greater advantages and fewer disadvantages compared with VKAs. New studies are required to further assess the efficacy of NOACs.

Cardiovascular diseases (CVDs) are the leading cause of mortality worldwide, reaching 31% of deaths in 2012 [1]. In particular, atherosclerosis and ischemic heart disease (IHD) are the main causes of premature death in Europe and are responsible for 42% of deaths in women and 38% in men under 75 years old [2]. The global economic impact of CVD is estimated to have been US $906 billion in 2015 and is expected to rise by 22% by 2030 [3]. Cardiovascular diseases also represent the major cause of disability in developed countries. It has been estimated that their growing burden could lead to a global increase in loss of disability-adjusted life years (DALYs), from a loss of 85 million DALYs in 1990 to a loss of ~150 million DALYs in 2020, becoming a major non-psychological cause of lost productivity [4]. Several risk factors contribute to the etiology and development of CVD; they are divided into those modifiable through lifestyle changes or by taking a pharmacologic treatment (e.g. for hypertension, smoking, diabetes mellitus, hypercholesterolemia) and those that are not modifiable (age, male gender, and family history) [5]. Elevated total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) blood concentrations are the major modifiable risk factors for coronary heart disease (CHD), whereas high concentrations of plasma high-density lipoprotein cholesterol (HDL-C) in certain conditions are considered protective [6]. Moreover, LDL-C remains a fundamental CV risk factor (and a main target of therapy) even when statins are largely used in the general population [7]. An examination of the data of 18 053 participants aged ≥ 20 years who participated in the National Health and Nutrition Examination Surveys (NHANES) from 1999 to 2006 showed that the unadjusted prevalence of hypercholesterolemia ranged from 53.2% to 56.1% in United States adults [8]. Differences related to gender and race or ethnicity were observed; in particular, a lower rate of control was found among women than men and lower rates of having a cholesterol check and being told about hypercholesterolemia were reported by African Americans and Mexican Americans than whites [8]. A recent report from the American Heart Association confirmed that in the US only 75.7% of children and 46.6% of adults present targeted TC levels (TC < 170 mg/dl for children and < 200 mg/dl for adults, in untreated individuals) [9]. The pattern is similar in other Western countries [10, 11].

In recent years, there has been growing interest in the possible use of nutraceuticals to improve and optimize dyslipidemia control and therapy. Based on the data from available studies, nutraceuticals might help patients obtain theraputic lipid goals and reduce cardiovascular residual risk. Some nutraceuticals have essential lipid-lowering properties confirmed in studies; some might also have possible positive effects on nonlipid cardiovascular risk factors and have been shown to improve early markers of vascular health such as endothelial function and pulse wave velocity. However, the clinical evidence supporting the use of a single lipid-lowering nutraceutical or a combination of them is largely variable and, for many of the nutraceuticals, the evidence is very limited and, therefore, often debatable. The purpose of this position paper is to provide consensus-based recommendations for the optimal use of lipid-lowering nutraceuticals to manage dyslipidemia in patients who are still not on statin therapy, patients who are on statin or combination therapy but have not achieved lipid goals, and patients with statin intolerance. This statement is intended for physicians and other healthcare professionals engaged in the diagnosis and management of patients with lipid disorders, especially in the primary care setting.

Pentaglycidyl ether pentabisphenol A of phosphorus (PGEPBAP) phosphorus polymer was investigated as corrosion inhibition for carbon steel in aggressive solution using potentiodynamic polarization (PDP), electrochemical impedance spectroscopy (EIS), weight loss (WL), scanning electron microscope (SEM), density functional theory (DFT), electrostatic potential (ESP), radial distribution function (RDF), molecular dynamics (MD) and Monte Carlo (MC) simulations. The higher inhibition efficiencies for PDP, EIS and WL studies at 10−3 M concentration of PGEPBA phosphorus polymer are 94.18 %, 91.79 % and 91.3 %, respectively. ΔEcorr (23.7 mV) value of PGEPBAP phosphorus polymer is lower than 85 mV has been assigned to mixed type inhibitor. PGEPBAP formed protective film on carbon steel surface by adsorption according to Langmuir adsorption isotherm. SEM morphology suggested that PGEPBAP could effectively block acid attack by chemisorption on metal surface. To evaluate the polymer inhibitor and potential mechanism were especially realized DFT, ESP, RDF, MD and MC simulations.

Antimicrobial resistance (AMR) is a major threat to global health. Understanding the emergence, evolution, and transmission of individual antibiotic resistance genes (ARGs) is essential to develop sustainable strategies combatting this threat. Here, we use metagenomic sequencing to analyse ARGs in 757 sewage samples from 243 cities in 101 countries, collected from 2016 to 2019. We find regional patterns in resistomes, and these differ between subsets corresponding to drug classes and are partly driven by taxonomic variation. The genetic environments of 49 common ARGs are highly diverse, with most common ARGs carried by multiple distinct genomic contexts globally and sometimes on plasmids. Analysis of flanking sequence revealed ARG-specific patterns of dispersal limitation and global transmission. Our data furthermore suggest certain geographies are more prone to transmission events and should receive additional attention.

This paper analyzes the structures of organic layers that are obtained on metals or carbon by electrochemical reduction of diazonium salts or by simple dipping of the substrate in a diazonium solution. There is a general agreement in the literature on the polyphenylene structure of these layers. But, previous results based on XPS data have indicated the possible presence of azo groups in these layers. IR and TOF-SIMS experiments demonstrate the existence of these azo groups included in the polyphenylene chains. A mechanism is presented that accounts both for the growth of polyphenylene chains and the inclusion of azo bonds in these chains.

BACKGROUND: Sarma - cooked leaves rolled around a filling made from rice and/or minced meat, possibly vegetables and seasoning plants - represents one of the most widespread feasting dishes of the Middle Eastern and South-Eastern European cuisines. Although cabbage and grape vine sarma is well-known worldwide, the use of alternative plant leaves remains largely unexplored. The aim of this research was to document all of the botanical taxa whose leaves are used for preparing sarma in the folk cuisines of Turkey and the Balkans. METHODS: Field studies were conducted during broader ethnobotanical surveys, as well as during ad-hoc investigations between the years 2011 and 2014 that included diverse rural communities in Croatia, Bosnia and Herzegovina, Serbia, Kosovo, Albania, Macedonia, Bulgaria, Romania, and Turkey. Primary ethnobotanical and folkloric literatures in each country were also considered. RESULTS: Eighty-seven botanical taxa, mainly wild, belonging to 50 genera and 27 families, were found to represent the bio-cultural heritage of sarma in Turkey and the Balkans. The greatest plant biodiversity in sarma was found in Turkey and, to less extent, in Bulgaria and Romania. The most commonly used leaves for preparing sarma were those of cabbage (both fresh and lacto-fermented), grape vine, beet, dock, sorrel, horseradish, lime tree, bean, and spinach. In a few cases, the leaves of endemic species (Centaurea haradjianii, Rumex gracilescens, and R. olympicus in Turkey) were recorded. Other uncommon sarma preparations were based on lightly toxic taxa, such as potato leaves in NE Albania, leaves of Arum, Convolvulus, and Smilax species in Turkey, of Phytolacca americana in Macedonia, and of Tussilago farfara in diverse countries. Moreover, the use of leaves of the introduced species Reynoutria japonica in Romania, Colocasia esculenta in Turkey, and Phytolacca americana in Macedonia shows the dynamic nature of folk cuisines. CONCLUSION: The rich ethnobotanical diversity of sarma confirms the urgent need to record folk culinary plant knowledge. The results presented here can be implemented into initiatives aimed at re-evaluating folk cuisines and niche food markets based on local neglected ingredients, and possibly also to foster trajectories of the avant-garde cuisines inspired by ethnobotanical knowledge.

An organic monolayer is obtained on Cu, Au, and SiH by electrografting 3,5-bis-tert-butyl benzenediazonium tetrafluoroborate, as evidenced by cyclic voltammetry, IR-ATR, and ellipsometry. This results from the bulky groups at the 3,5-positions that sterically hinder the growth of the layer.

AIMS: There is good evidence showing that inactivity and walking minimal steps/day increase the risk of cardiovascular (CV) disease and general ill-health. The optimal number of steps and their role in health is, however, still unclear. Therefore, in this meta-analysis, we aimed to evaluate the relationship between step count and all-cause mortality and CV mortality. METHODS AND RESULTS: We systematically searched relevant electronic databases from inception until 12 June 2022. The main endpoints were all-cause mortality and CV mortality. An inverse-variance weighted random-effects model was used to calculate the number of steps/day and mortality. Seventeen cohort studies with a total of 226 889 participants (generally healthy or patients at CV risk) with a median follow-up 7.1 years were included in the meta-analysis. A 1000-step increment was associated with a 15% decreased risk of all-cause mortality [hazard ratio (HR) 0.85; 95% confidence interval (CI) 0.81-0.91; P < 0.001], while a 500-step increment was associated with a 7% decrease in CV mortality (HR 0.93; 95% CI 0.91-0.95; P < 0.001). Compared with the reference quartile with median steps/day 3867 (2500-6675), the Quartile 1 (Q1, median steps: 5537), Quartile 2 (Q2, median steps 7370), and Quartile 3 (Q3, median steps 11 529) were associated with lower risk for all-cause mortality (48, 55, and 67%, respectively; P < 0.05, for all). Similarly, compared with the lowest quartile of steps/day used as reference [median steps 2337, interquartile range 1596-4000), higher quartiles of steps/day (Q1 = 3982, Q2 = 6661, and Q3 = 10 413) were linearly associated with a reduced risk of CV mortality (16, 49, and 77%; P < 0.05, for all). Using a restricted cubic splines model, we observed a nonlinear dose-response association between step count and all-cause and CV mortality (Pnonlineraly < 0.001, for both) with a progressively lower risk of mortality with an increased step count. CONCLUSION: This meta-analysis demonstrates a significant inverse association between daily step count and all-cause mortality and CV mortality with more the better over the cut-off point of 3867 steps/day for all-cause mortality and only 2337 steps for CV mortality.

BACKGROUND: Ethnobotanical studies are crucial in South-Eastern Europe for fostering local development and also for investigating the dynamics of Traditional Environmental Knowledge (TEK) related to plants in one of the most crucial European hotspots for biocultural diversity. The current medico-ethnobotanical survey was conducted in rural alpine communities in Kosovo. The aims of the study were twofold: 1) to document the state of TEK of medicinal plants in these communities; 2) to compare these findings with that of similar field studies previously conducted among local populations inhabiting the Montenegrin and Albanian side of the same Alpine range. METHODS: Field research was conducted in 36 villages on the Kosovar side of the Albanian Alps. Snowball sampling techniques were used to recruit 91 elderly informants (≥ 50 years-old) for participation in semi-structured interviews and structured surveys regarding the use of the local flora for medicinal and food purposes. Standard ethnobotanical methods were employed and prior informed consent was obtained for all study participants. RESULTS AND CONCLUSION: The uses of 98 plants species belonging to 39 families were recorded; the most quoted botanical families were Rosaceae, Asteraceae, and Lamiaceae. Mainly decoctions and infusions were quoted as folk medicinal preparations and the most common uses referred to gastrointestinal and respiratory disorders, as well as illnesses of the uro-genital system. Among the most uncommon medicinal taxa quoted by the informants, Carduus nutans L., Echinops bannaticus Rochel ex Schrad., and Orlaya grandiflora Hoffm. may merit phytochemical and phytopharmacological investigations.Comparison of the data with other ethnobotanical field studies recently conducted on the Albanian and Montenegrin sides of the same Alps has shown a remarkable link between the medical ethnobotany of Montenegrin and Kosovar side of the Albanian Alps. Moreover, folk uses of the most quoted wild medicinal taxa recorded in Kosovo often include those recorded both in Albania and in Montenegro, thus suggesting a hybrid character of the Kosovar local plant knowledge. This may be also explained with the fact that Montenegro and Kosovo, despite their differences in the ethnic composition, have shared a common history during the last Century.

This paper is a review of local plants used in water infusions as aromatic and refreshing hot beverages (recreational tea) consumed in food-related settings in Europe, and not for specific medicinal purposes. The reviewed 29 areas are located across Europe, covering the post-Soviet countries, eastern and Mediterranean Europe. Altogether, 142 taxa belonging to 99 genera and 40 families were reported. The most important families for making herbal tea in all research areas were Lamiaceae and Asteraceae, while Rosaceae was popular only in eastern and central Europe. With regards to botanical genera, the dominant taxa included Mentha, Tilia, Thymus, Origanum, Rubus and Matricaria. The clear favorite was Origanum vulgare L., mentioned in 61% of the regions. Regionally, other important taxa included Rubus idaeus L. in eastern Europe, Chamaemelum nobile (L.) All. in southern Europe and Rosa canina L. in central Europe. Future research on the pharmacological, nutritional and chemical properties of the plants most frequently used in the tea-making process is essential to ensure their safety and appropriateness for daily consumption. Moreover, regional studies dedicated to the study of local plants used for making recreational tea are important to improve our understanding of their selection criteria, cultural importance and perceived properties in Europe and abroad.

This study deals with the importance of applying Management by Objectives (MBO) method, as a method for performance appraisal (PA) in enhancing employees’ effectiveness. A self- administered questionnaire was used, the number of participants included the survey is 172 employees from 13 firms operating in Kosovo. The study aim is to identify the importance of creating objectives, communication objectives, planning goals, setting control points, employees’ commitment to determine objectives, freedom and independence in fulfilling duties, continuous communication, as steps for realizing MBO method in employees’ effectiveness. The questionnaire of the study has been prepared, the responses obtained, the econometric model is constructed in order to test empirically this relationship, passed through the IBM SPSS v.23.0 program has been utilized for the obtained findings. Results and proposals are brought forward by the matched t-test, independent sample t-test, anova, pearson and correlation used as the hypothesis tests. Econometric results suggested that MBO method should be used as a method of performance appraisal as the employees’ effectiveness is enhanced. Also it resulted that the evaluation of individual employees’ performance and a clear definition of results are the hugest parameters from all the other activities of MBO method which we took in the study to raise employees’ effectiveness in organization.

The aim of this review was to highlight the most important complications of arteriovenous fistulas (AVFs) for hemodialysis (HD). The quality of vascular access for HD should be suitable for repeated puncture and allow a high blood flow rate for high-efficiency dialysis with minimal complications. The dialysis staff must be well versed in manipulation of the AVF, and there should be a minimal need for corrective interventions. Construction of an AVF creates conditions for increasing the flow of blood through the venous system. Fulfillment of these conditions reduces the risk of turbulence and endothelium injury, which, in turn, minimizes the potential for stenosis. An AVF is closest to the ideal model of vascular access. The most important complications of fistulae for HD are lymphedema, infection, aneurysm, stenosis, congestive heart failure, steal syndrome, ischemic neuropathy and thrombosis. In HD patients, the most common cause of vascular access failure is neointimal hyperplasia. It is important to gain information about early clinical symptoms of AVF dysfunction in order to prevent and adequately treat potential complications.

Grafting of aryl layers derived from aryl diazonium salts onto glassy carbon electrodes is observed by time-of-flight secondary ion mass spectroscopy (ToF-SIMS). The grafting occurs spontaneously when a glassy carbon plate is immersed into a solution of aryl diazonium salt and can be enhanced by biasing the carbon plate at a potential a little more negative than the diazonium salt reduction. C-C and C-O covalent bonding are believed to be responsible for the strong attachment of these layers onto the carbon substrate. Fragments containing aryl dimers, trimers, or tetramers are also observed. A mechanism is proposed to account for the formation of these polymeric chains.

It is possible to form micrometer thick polyphenylene (PP) films by electrochemical reduction of benzenediazonium tetrafluoroborate on metals in acetonitrile. The electrochemical behavior of the PP film is characterized by different electrochemical transient methods and is surprisingly different from that observed with other diazonium salts. The films are analyzed by IR and time-of-flight secondary ion mass spectroscopies; their thickness and conductivity are also characterized. Because they are conductive, these micrometer thick films can be further derivatized by electrochemical reduction of other diazonium salts, for example, nitrophenyl or bromophenyl diazonium salts. Copper can also be deposited on the top of the PP film. The behavior of redox probes on PP films is discussed as well as the origin of this increased conductivity. A simple model for the reaction kinetics of electrografting is presented.

A cross-sectional cluster sample survey was conducted in June 2000 in Kosovo to assess the prevalence of mental health problems associated with traumatic experiences, feelings of hatred and revenge, and the level of social functioning among Kosovar Albanians approximately 1 year after the end of the war. Findings of the second cross-sectional survey were compared with those from our 1999 mental health survey in Kosovo. Included in the survey were 1399 Kosovar Albanians aged 15 years or older living in 593 randomly selected households across Kosovo. Twenty-five percent of respondents reported PTSD symptoms, compared with 17.1% in 1999. The MOS-20 social functioning score improved to 69.8 from 29.5 in 1999. In the 2000 survey 54% of men felt hatred toward the Serbs, compared with 88.7% in 1999.