Creatine supplementation combined with breathing exercises reduces respiratory discomfort and improves creatine status in patients with long-COVID.

ABSTRACT: Eight long-COVID patients with moderate fatigue that had lasted for ≥3 months were recruited. All patients were allocated in a double-blind parallel-group design to receive either 4 g of creatine per day plus breathing exercises (study group) or breathing exercises only (control group) for 3 months. Creatine induced a significant increase in tissue total creatine levels for all 14 locations evaluated in the present study ( P < 0.05), while its levels significantly dropped in the right frontal gray matter and left parietal mesial gray matter at follow-up in the control group ( P < 0.05). No change in time to exhaustion was demonstrated in the control group (P > 0.05), while the mean time to exhaustion was significantly improved for 54 s in the study group post-administration (P = 0.05). These preliminary findings suggest that creatine is as an effective adjuvant therapeutic to breathing exercises for tackling the clinical features in long-COVID.

Reduced tissue creatine levels in patients with long COVID-19: A cross-sectional study.

Total creatine concentration in the skeletal muscle and brain of long COVID patients were significantly lower when compared to the reference values for the general population, as measured with proton magnetic resonance spectroscopy at 1.5-T in vastus medialis muscle, thalamus, and three bilateral cerebral locations across the white and gray matter.

Comparison of formulation characteristics of drugs and dietary supplements containing alpha-lipoic acid relevant to therapeutic efficacy.

OBJECTIVE: Healthcare professionals lack the knowledge about the impact of formulations on treatment effectiveness. This is further complicated by the existence of dietary supplements containing the same active pharmaceutical ingredients (API) as drug formulations [e.g., alpha-lipoic acid (ALA)], to which the strict formulation testing requirements do not apply. This research aimed to compare ALA-containing drugs and dietary supplements through the determination of uniformity of content, disintegration time and dissolution rates. MATERIALS AND METHODS: A total of seven different ALA formulations (5 dietary supplements, 2 drugs) were tested for uniformity of content, disintegration time and dissolution rates. All tests were performed in accordance with the 10th European Pharmacopoeia. ALA was determined spectrophotometrically. RESULTS: Uniformity of content testing revealed larger variations of ALA content in three formulations of dietary supplements. Dissolution curves generated at 50 and 100 rpm differed significantly. Testing requirements were met only by one dietary supplement at 50 rpm, and one drug and two dietary supplements at 100 rpm. Disintegration testing showed limited impact on the release kinetic of ALA, as opposed to formulation type. CONCLUSIONS: Considering the lack of regulation on dietary supplement formulations and the variable success of them conforming to pharmacopoeial requirements, it is an imperative for stricter regulations on the dietary supplements' formulations to be imposed globally.

The COVID-19 pandemic - related psychological distress and job burnout among Serbian pharmacy practitioners: a cross-sectional online study.

OBJECTIVE: The current COVID-19 pandemic has increased occupational stress for all healthcare providers, making job burnout one of the most common and largely unrecognized mental health issues among healthcare professionals. Besides physicians and nurses, pharmacy practitioners were "front-line" healthcare professionals with a critical and unique role in the public health crisis. Considering this, the aim of this study was to examine distress levels and the prevalence of job burnout among Serbian pharmacy practitioners in relation to the COVID-19 pandemic. SUBJECTS AND METHODS: This cross-sectional online study was conducted in April and May of 2020. A total of 176 pharmacy practitioners anonymously and voluntarily completed the two-section questionnaire, consisting of Copenhagen burnout inventory, CBI and 4DSQ Distress subscale. The two-section questionnaire was distributed online, among various social-media groups of pharmacy practitioners, as well as by personal contacts following the "snowball" sampling method. RESULTS: Results revealed moderately high burnout scores in our sample. The majority of the participants showed signs of personal-related job burnout, followed by work-related and client-related burnout. A strongly elevated distress level was obtained in almost two-thirds of study respondents. In addition, a significant and high correlation of all CBI subscales with distress was found, as well as medium correlations with sleep duration shortening as a mediator between distress and job burnout. CONCLUSIONS: Results of our study showed that job burnout significantly increased among pharmacy practitioners during the COVID-19 pandemic. Furthermore, we discovered that stress has an indirect impact on study participants' burnout via insufficient sleep.

Estimation of absorbed gamma dose rate from granite by Monte Carlo simulation approach.

Apart from the continuous exposure of humans to background ionising radiation, an increased level of radiation may also originate from the use of building materials with an enhanced level of radioactivity. Thus, it is necessary to examine the content of radionuclides present in building materials, as well as the corresponding dose which may be received by residents from these materials. In this paper, particular attention was dedicated to finding the absorbed dose rate and annual effective dose caused by the presence of naturally occurring radioisotopes 226Ra, 232Th, and 40K in granite, a widely used building material, by means of Monte Carlo simulations. In addition, the obtained dose rate simulation results were compared with values estimated from commonly used simple equations, relating to the dose rate emitted by granite plates, covering the interior of a standard room. In the simulation, a room was constructed with standard dimensions (4 m × 5 m × 2.8 m), and with floor and walls covered with 3 cm thick granite. A water cylinder (approximate mass 65 kg) was positioned in the center of the room, representing a human body. The emission of the most intense gamma rays from 226Ra and 232Th progenies, as well as from 40K, emanating from the granite matrix, was simulated. The number of generated photons in each simulation (typically it was an order of magnitude of ~106) precisely represented actual activity concentrations of 226Ra, 232Th, and 40K in granite samples. All processes playing a role in the interactions of gamma photons with the granite matrix itself, the outer concrete shell, the air within the room, and the water cylinder, were taken into account by GEANT4 simulation software, after which the spectra of deposited energy inside of the water cylinder were obtained. Based on the deposited energy, the absorbed dose rate and annual effective dose were calculated for 6 analysed granite samples, each with different 226Ra, 232Th, and 40K contents. Furthermore, the effect of the position of the water cylinder in the simulated room on the absorbed dose rate was considered, as well as the distribution of the deposited energy within the water cylinder. The absorbed dose rates, and consequently annual effective dose, obtained in the simulations were found to be 30%-40% higher than the values obtained from using a standard formula.

Production of levan by Bacillus licheniformis NS032 in sugar beet molasses-based medium.

The production of levan by Bacillus licheniformis NS032 in a medium based on sugar beet molasses was studied. High polysaccharide yields were produced by using diluted molasses (100-140 g/L of total sugars) with the addition of commercial sucrose up to 200 g/L of total sugars, as well as K2HPO4. A levan yield of 53.2 g/L was obtained on a medium optimized by response surface methodology, containing 62.6% of sugar originating from molasses, and 4.66 g/L of phosphate, with initial pH value of 7.2. In comparison to the media with 200 and 400 g/L sucrose, in the molasses optimized medium, the observed bacterial growth was faster, while the maximum production of polysaccharide was achieved over a shorter time interval (48 h). The polysaccharide produced in molasses medium had a weight average molecular weight of 5.82 × 106 Da, degree of branching 12.68%, viscosity of 0.24 dL/g, and based on methylation analysis and NMR data, it did not significantly differ from levan obtained in the medium with 200 g/L sucrose.

Radiation exposure to nuclear medicine staff involved in PET/CT practice in Serbia.

The purpose of this work is to evaluate the radiation exposure to nuclear medicine (NM) staff in the two positron emission tomography-computed tomography centres in Serbia and to investigate the possibilities for dose reduction. Dose levels in terms of Hp(10) for whole body and Hp(0.07) for hands of NM staff were assessed using thermoluminescence and electronic personal dosemeters. The assessed doses per procedure in terms of Hp(10) were 4.2-7 and 5-6 µSv, in two centres, respectively, whereas the extremity doses in terms of Hp(0.07) in one of the centres was 34-126 µSv procedure(-1). The whole-body doses per unit activity were 17-19 and 21-26 µSv GBq(-1) in two centres, respectively, and the normalised finger dose in one centre was 170-680 µSv GBq(-1). The maximal estimated annual whole-body doses in two centres were 3.4 and 2.0 mSv, while the corresponding extremity dose in the later one was 45 mSv. Improvements as introduction of automatic dispensing system and injection and optimisation of working practice resulted in dose reduction ranging from 12 up to 67 %.

Indoor radon in rural dwellings of the South-Pannonian region.

The results of indoor radon survey in the South-Pannonian Province Vojvodina (Serbia and Montenegro) are presented. The sampling strategy was oriented towards suburban and urban regions in the Province. For the dwellings typical for such regions the geometric mean annual radon activity concentration of 76.1 Bq m(-3) is measured (1000 measurements). This result leads to the annual dose estimate of 4.3 mSv y(-1), which is above the recommended action limit of ICRP. For urban dwellings in Novi Sad (the Province capital), the annual mean value of 54 Bq m(-3) (220 measurements) is obtained. By comparison of these two results it is concluded that radon surveys based on measurements in urban environment may seriously underestimate the radon-related health risk. The elevated radon levels could not be explained by elevated uranium levels of surface soil.

Radioactivity of the Bega sediment-case study of a contaminated canal.

The Bega canal is one among many heavily polluted canals in Vojvodina (the northern province of Serbia and Montenegro). In the framework of the revitalization of this canal, the radionuclide content of the sediment was investigated in order to support the safe deposition after excavation. It was found that, in comparison with the Danube sediment and Vojvodina soil, the Bega sediment is contaminated with (238)U and (137)Cs. The origin of this contamination is discussed. No traces of contamination by nuclear power plants in the region were found, while the presence of technologically enhanced, natural occurring radioactive materials (TENORM) was proved.

Radioactivity of the soil in Vojvodina (northern province of Serbia and Montenegro).

The widespread public belief that during the bombardment of Vojvodina (Yugoslavia) this region was contaminated by depleted uranium has recently raised public concern with respect to the potential contamination of agricultural products due to soil radioactivity. Based on the gamma-spectrometric analysis of 50 soil samples taken from the region of Vojvodina we concluded that there is no increase of radioactivity that could endanger the food production. Taking into account the transfer factors of 137Cs to plants, the measured activity concentrations of this isotope should not endanger the health safety of the produced food. No traces of depleted uranium have been found. The natural radioactivity levels are compared with the results form other countries.

Differential effects of NMDA and AMPA/kainate receptor antagonists on superoxide production and MnSOD activity in rat brain following intrahippocampal injection.

The involvement of NMDA and AMPA/kainate receptors in the induction of superoxide radical production in the rat brain was examined after injection of kainate, non-NMDA receptor agonist, kainate plus 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), selective AMPA/kainate receptor antagonist, or kainate plus 2-amino-5-phosphonopentanoic acid (APV), selective NMDA receptor antagonist. Competitive glutamate receptor antagonists were injected with kainate unilaterally into the CA3 region of the rat hippocampus. We investigated superoxide production and mitochondrial MnSOD activity after injection. The measurements took place at different times (5, 15 min, 2, 48 h and 7 days) in the ipsi- and contralateral hippocampus, forebrain cortex, striatum, and cerebellum homogenates. Used glutamate antagonists APV and CNQX both expressed sufficient neuroprotection in sense of decreasing superoxide production and increasing MnSOD levels, but with differential effect in mechanisms and time dynamics. Our findings suggest that NMDA and AMPA/kainate receptors are differentially involved in superoxide production. Following intrahippocampal antagonists injection they, also, interpose different neuroprotection effect on the induction of MnSOD activity in distinct brain regions affected by the injury, which are functionally connected via afferents and efferents. It suggests that MnSOD protects the cells in these regions from superoxide-induced damage and therefore may limit the retrograde and anterograde spread of neurotoxicity.

Distribution and regulation of expression of serum- and glucocorticoid-induced kinase-1 in the rat kidney.

The serum- and glucocorticoid-induced kinase-1 (sgk1) increases the activity of a number of epithelial ion channels and transporters. The present study examines the distribution and subcellular localization of sgk1 protein in the rat kidney and the regulation of levels of expression induced by steroids. The results indicate that the kidney expresses predominantly the sgk1 isoform with a distribution restricted to the thick ascending limb of Henle, distal convoluted, connecting and cortical collecting tubules. Within cells, sgk1 strongly associates with the microsomal fraction of homogenates and it colocalizes with the Na+,K+-ATPase to the basolateral membrane. Analysis of the levels of expression of sgk1 by Western blotting and immunohistochemistry indicates constitutive high expression under basal conditions. Approximately half of the basal level is maintained by glucocorticoids whereas physiological fluctuations of aldosterone produce minor changes in sgk1 abundance in adrenal-intact animals. These results do not support the notion that physiological changes of aldosterone concentration turn the expression of sgk1 'on and off' in the mammalian kidney. Additionally, localization of sgk1 to the basolateral membrane indicates that the effects mediated by sgk1 do not require a direct interaction with the ion channels and transporters whose activity is modulated, since most of these proteins are located in the apical membrane of renal epithelial cells.

Mixed cobalt(III) complexes with aromatic amino acids and diamine. Part IV. Influence of noncovalent intra-and interligand interactions on rotamer population of the S-phenylalaninato and S-tyrosinato side groups in (1,2-diaminoethane)bis-(S-aminocarboxylato)cobalt(III) complexes.

Rotamer population of S-tyrosinato and S-phenylalaninato ligands side groups in diastereomers of (1,2-diaminoethane)bis-(S-aminocarboxylato)cobalt(III) complexes is calculated by vicinal alpha and beta proton coupling constant analysis. The effect of noncovalent intra- and interligand interactions on the population of rotamers in D20 solution is discussed. It has been established that in all the complexes investigated the most abundant is rotamer t, in which aromatic voluminous moiety and carboxylic group are in an anti position. In almost all complexes the lowest content is of rotamer g, in which these two groups are in the nearest position. Relatively high population of rotamer h in complex 5 tyr, in spite of high steric hindrances, is due to intra- and interligand NH...pi interactions.

Further sesquiterpene lactones from Anthemis carpatica.

A new germacranolide, (E)-1alpha, 10beta-epoxy-3beta-acetoxy-6alpha-hydroxygermacra-4,11 (13)-dien-12,8alpha-olide, together with nine new highly oxygenated guaiadien-12,6alpha-olides of anthemolide, and cumambrin type were identified in the repeated examination of the aerial parts of the flowering Anthemis carpatica. In addition, six known guaianolides belonging to the same groups, also isolated previously from A. carpatica, along with two guaianolides, 2beta-hydroxyepiligustrin and cumambrin B, not found before in this species, were isolated this time.

Guaianolides from Centaurea nicolai: antifungal activity.

A new guaianolide, 3-deacetyl-9-O-acetylsalograviolide A, along with four known closely related lactones, salograviolide A, 9-O-acetylsalograviolide A, kandavanolide and salograviolide B were detected in the aerial parts of the flowering plant Centaurea nicolai. Antifungal tests performed on salograviolide A and its 9-O-acetyl and 3-O-deacetyl-9-O-acetyl derivatives revealed inhibitory activity against Aspergillus niger, A. ochraceus, Penicillium ochrochloron, Cladosporium cladosporoides, Fusarium tricinctum and Phomopsis helianthi. Neither of them was active against Trichoderma viride.

Steroidal geminal dihydroperoxides and 1,2,4,5-tetraoxanes: structure determination and their antimalarial activity.

Cholestane-derived gem-dihydroperoxides and tetraoxanes were synthesized starting from 5 alpha- and 5 beta-cholestan-3-ones by acid-catalyzed addition of hydrogen peroxide to the ketone. They were characterized by IR, NMR, and mass spectroscopy analysis aided by molecular mechanics calculations, and, in the instance of 5 beta-cholestane-3 alpha,3 beta-dihydroperoxide (6), by x-ray analysis. The synthesized compounds were tested in vitro against Plasmodium falciparum Sierra Leone (D6) and Indochina (W2) malaria clones. All compounds were inactive to both clones, with the exception of tetraoxane 7a, which exhibited modest activity toward D6 clone with IC50 = 155 nM.