Pandemic diplomacy and patron-client relations in Sino-Serbian cooperation.

Since the outbreak of the COVID-19 pandemic, the authorities of Serbia have undertaken a concerted effort to secure China's support in containing the coronavirus. This asymmetrical cooperation, apart from aspects concerning health security, has allowed both sides to obtain considerable political and economic benefits. This article examines how China and Serbia utilize pandemic cooperation to pursue and realize their wider foreign and internal policy goals through patron-client ties, as well as highlighting the pitfalls of this kind of relationship. Although the outbreak of the pandemic and the medical cooperation that followed do not constitute a turning point in the well-established relations between the two countries, the article argues that pandemic cooperation has considerably strengthened relations. In many ways, the pattern observed by the authors resembles China's pandemic exchanges with other countries, especially smaller states with authoritarian inclinations.

Phosphoglucose Isomerase Is Important for Aspergillus fumigatus Cell Wall Biogenesis.

Aspergillus fumigatus is a devastating opportunistic fungal pathogen causing hundreds of thousands of deaths every year. Phosphoglucose isomerase (PGI) is a glycolytic enzyme that converts glucose-6-phosphate to fructose-6-phosphate, a key precursor of fungal cell wall biosynthesis. Here, we demonstrate that the growth of A. fumigatus is repressed by the deletion of pgi, which can be rescued by glucose and fructose supplementation in a 1:10 ratio. Even under these optimized growth conditions, the Δpgi mutant exhibits severe cell wall defects, retarded development, and attenuated virulence in Caenorhabditis elegans and Galleria mellonella infection models. To facilitate exploitation of A. fumigatus PGI as an antifungal target, we determined its crystal structure, revealing potential avenues for developing inhibitors, which could potentially be used as adjunctive therapy in combination with other systemic antifungals. IMPORTANCE Aspergillus fumigatus is an opportunistic fungal pathogen causing deadly infections in immunocompromised patients. Enzymes essential for fungal survival and cell wall biosynthesis are considered potential drug targets against A. fumigatus. PGI catalyzes the second step of the glycolysis pathway, linking glycolysis and the pentose phosphate pathway. As such, PGI has been widely considered as a target for metabolic regulation and therefore a therapeutic target against hypoxia-related diseases. Our study here reveals that PGI is important for A. fumigatus survival and exhibit pleiotropic functions, including development, cell wall glucan biosynthesis, and virulence. We also solved the crystal structure of PGI, thus providing the genetic and structural groundwork for the exploitation of PGI as a potential antifungal target.

Genetic validation of Aspergillus fumigatus phosphoglucomutase as a viable therapeutic target in invasive aspergillosis.

Aspergillus fumigatus is the causative agent of invasive aspergillosis, an infection with mortality rates of up to 50%. The glucan-rich cell wall of A. fumigatus is a protective structure that is absent from human cells and is a potential target for antifungal treatments. Glucan is synthesized from the donor uridine diphosphate glucose, with the conversion of glucose-6-phosphate to glucose-1-phosphate by the enzyme phosphoglucomutase (PGM) representing a key step in its biosynthesis. Here, we explore the possibility of selectively targeting A. fumigatus PGM (AfPGM) as an antifungal treatment strategy. Using a promoter replacement strategy, we constructed a conditional pgm mutant and revealed that pgm is required for A. fumigatus growth and cell wall integrity. In addition, using a fragment screen, we identified the thiol-reactive compound isothiazolone fragment of PGM as targeting a cysteine residue not conserved in the human ortholog. Furthermore, through scaffold exploration, we synthesized a para-aryl derivative (ISFP10) and demonstrated that it inhibits AfPGM with an IC50 of 2 µM and exhibits 50-fold selectivity over the human enzyme. Taken together, our data provide genetic validation of PGM as a therapeutic target and suggest new avenues for inhibiting AfPGM using covalent inhibitors that could serve as tools for chemical validation.

Clinical Evaluation of Magnesium Alloy Osteosynthesis in the Mandibular Head.

Titanium alloys are used in skeletal surgery. However, once bone union is complete, such fixation material becomes unnecessary or even harmful. Resorbable magnesium materials have been available for several years (WE43 alloy). The aim of this study was to clinically compare magnesium versus titanium open reduction and rigid fixations in mandible condylar heads. Ten patients were treated for fractures of the mandibular head with magnesium headless compression screws (2.3 mm in diameter), and 11 patients were included as a reference group with titanium screws (1.8 mm in diameter) with similar construction. The fixation characteristics (delay, time, and number of screws), distant anatomical results (mandibular ramus height loss, monthly loss rate, and relative loss of reconstructed ramus height), basic functional data (mandibular movements, facial nerve function, and cutaneous perception) and the influence of the effects of the injury (fracture type, fragmentation, occlusion, additional fractures, and associated diseases) on the outcome were evaluated. The long-term results of treatment were evaluated after 18 months. Treatment results similar to those of traditional titanium fixation were found with magnesium screws. Conclusions: Resorbable metal screws can be a favored option for osteosynthesis because surgical reentry can be avoided. These materials provide proper and stable treatment results.

Assessment of Differences in the Dimensions of Mandible Condyle Models in Fan- versus Cone-Beam Computer Tomography Acquisition.

Modern treatment in the field of head and neck surgery aims for the least invasive therapy and places great emphasis on restorative treatment, especially in the case of injury and deformation corrective surgery. More and more often, surgeons use CAD/CAM (Computer-Aided Design and Computer-Aided Manufacturing) tools in their daily practice in the form of models, templates, and computer simulations of planning. These tools are based on DICOM (Digital Imaging and Communications in Medicine) files derived from computed tomography. They can be obtained from both fan-beam (FBCT) and cone-beam tomography (CBCT) acquisitions, which are subsequently segmented in order to transform them into a 1-bit 3D model, which is the basis for further CAD processes. AIM: Evaluation of differences in the dimensions of mandible condyle models in fan- versus cone-beam computer tomography for surgical treatment purposes. METHODS: 499 healthy condyles were examined in CT-based 3D models of Caucasians aged 8-88 years old. Datasets were obtained from 66 CBCT and 184 FBCT axial image series (in each case, imaging both mandible condyles resulted in the acquisition of 132 condyles from CBCT and 368 condyles from FBCT) and were transformed into three-dimensional models by digital segmentation. Eleven different measurements were performed to obtain information whether there were any differences between FBCT and CBCT models of the same anatomical region. RESULTS: 7 of 11 dimensions were significantly higher in FBCT versus lower in CBCT (p < 0.05).

Clinico-anatomical classification of the processus condylaris mandibulae for traumatological purposes.

Mandible condyle fracture has been reported to constitute 9-45 % (Asprino and Consani, 2006), 14.1 % (Bataineh, 1998), 25-50 % (Silvennoinen, Iizuka, 1992), 32 % (Chrcanovic et al., 2004), and 38 % (Brasileiro and Passeri, 2006) of all mandible fractures (Kozakiewicz and Swiniarski, 2013). Small bone segments, limited available space for application of the fixation material and limited visibility of the operative field are common difficulties. To guarantee satisfactory treatment effects, anatomical reduction and proper fracture stability are necessary. The use of 3-4 screws in the upper section (proximal segment) provides adequate immobilization, which can be easily achieved when the condyle is low and wide. However, if the condyle is slender, it is not technically possible to fix 2 plates and 4 screws for osteosynthesis. Selection of the appropriate fixative material that will provide adequate rigidity during the healing period while simultaneously allowing proper construction of the lateral silhouette of the processus condylaris mandibulae to fix the plate remains a key consideration. The aim of this study was to evaluate clinico-anatomical classification of the condyle of mandible posture for traumatological purposes. Five hundred computer tomography virtual models were created, from which 11 measurements were made, and 2 indexes were calculated. Assessment of types based on the ratio of the condyle height index revealed a dichotomous division into high and short condyles. Statistically associated with the division, the Width_neck_basal (the width of the bone at the level of semilunar notch measured by a frontal projection perpendicular to line "A", as described by Neff (Neff et al., 2014)) measurement allowed the creation of the following clinico-anatomical classification: -slender-type condyles have a Width_neck_basal in the range of 4-8.5mm; -squad-type condyles have a Width_neck_basal in the range of 11.5-19.5mm. Patients with a Width_neck_basal value in the 8.5-11.5mm range cannot be classified using this method, and a different method to assess the lateral condylar silhouette must be used. The proposed clinic-anatomical classification method avoids the problems associated with incorrect osteosynthesis plate selection. Assignment to a group can be obtained by making one measurement (the Width_neck_basal). In that way, the optimal fixing material can be selected by the surgeon before the operation commences, with great intraoperation time savings.

Flavonoids enantiomer distribution in different parts of goldenrod (Solidago virgaurea L.), lucerne (Medicago sativa L.) and phacelia (Phacelia tanacetifolia Benth.).

Plant material is a rich source of valuable compounds such as flavanones. Their different forms influence bioavailability and biological activity, causing problems with the selection of plant material for specific purposes. The purpose of this research was to determine selected flavanone (eriodictyol, naringenin, liquiritigenin, and hesperetin) enantiomer contents in free form and bonded to glycosides by an RP-UHPLC-ESI-MS/MS method. Different parts (stems, leaves, and flowers) of goldenrod (Solidago virgaurea L.), lucerne (Medicago sativa L.), and phacelia (Phacelia tanacetifolia Benth.) were used. The highest content of eriodictyol was found in goldenrod flowers (13.1 µg/g), where it occurred mainly as the (S)-enantiomer, and the greatest proportion of the total amount was bonded to glycosides. The richest source of naringenin was found to be lucerne leaves (4.7 µg/g), where it was mainly bonded to glycosides and with the (S)-enantiomer as the dominant form. Liquiritigenin was determined only in lucerne, where the flowers contained the highest amount (1.2 µg/g), with the (R)-enantiomer as dominant aglycone form and the (S)-enantiomer as the dominant glycosylated form. The highest hesperetin content was determined in phacelia leaves (0.38 µg/g), where it was present in the form of a glycoside and only as the (S)-enantiomer. A comparison of the different analyte forms occurring in different plant parts was performed for the first time.

Ethylene glycol dimethacrylate and diethylene glycol dimethacrylate exhibits cytotoxic and genotoxic effect on human gingival fibroblasts via induction of reactive oxygen species.

Although methacrylic acid derivatives in their polymeric form are considered to be safe, insufficient polymerization and the release of monomers due to either mechanical or enzymatical factors can lead to their reaching millimolar concentrations in local tissue. The present study evaluates the effect of two methacrylate monomers - ethylene glycol dimethacrylate (EGDMA) and diethylene glycol dimethacrylate (DEGDMA) - on human gingival fibroblasts (HGFs). Both monomers were found to reduce cells viability in MTT assay, increase apoptosis and cause cell cycle arrest in G1/G0 phase. They also increased intracellular reactive oxygen species (ROS) production as measured by DCFH-DA and DHE probes and increased expression of GPx4 and SOD2. Both monomers increased DNA damage in comet assay. Moreover, HGFs were not able to repair those lesions within 120min of repair incubation. However, the monomers were not found to have any effect on the integrity of isolated plasmids. We postulate that EGDMA and DEGDMA exhibit their cytotoxic and genotoxic properties via increased production of ROS, which cause DNA damage, affect apoptosis, viability and cell cycle. Further studies are needed to better understand the properties of methacrylic acid monomers and to evaluate the risk that they cause for patients, dentists and dental technicians.

The Simultaneous Determination of Six Flame Retardants in Water Samples Using SPE Pre-concentration and UHPLC-UV Method.

Analytical method for the determination of six flame retardants (FRs) from two groups was proposed. These groups included the brominated flame retardants (BFRs) 3,3',5,5'-tetrabromobisphenol A (TBBPA), 1,2,5,6,9,10-hexabromocyclododecane (HBCD) and tetrabromophthalic anhydride (TBPA) and triester organophosphate flame retardants (OPFRs) tris(2,3-dibromopropyl) phosphate (TBPP), ethylhexyl diphenyl phosphate (EHDP) and triphenyl phosphate (TPhP). Reversed phase ultrahigh-performance liquid chromatography (UHPLC) with a UV detector, different chromatographic columns, different mobile phases and gradient elution programmes were used to obtain the best separations within the shortest possible time. Solid-phase extraction (SPE) was examined as a pre-concentration step from distilled water. The column with the highest recoveries (the Bond Elut ENV column gave recoveries over 70 % for all compounds) was then tested on 1-L blank surface water samples. The proposed analytical procedure was applied for the determination of FRs in surface water samples. The concentrations of FRs found in water samples ranged from 0.03 (TPhP) to 3.10 µg L-1 (HBCD). Method detection limits (MDLs) ranged from 0.008 to 0.518 µg L-1, and method quantification limits (MQLs) ranged from 0.023 to 1.555 µg L-1 for all compounds.

Usefulness of electrosurgical techniques in thyroid gland surgery.

UNLABELLED: Wide propagation of new generation of electrosurgical devices such as bipolar vessel sealing systems (eg. Thermostapler® by EMED) enabled seamless closing of blood vessels with a diameter up to 7 mm while maintaining the necessary safety margin, as well as reducing the duration of the operation. We decided to verify these reports in our material. AIM OF THE STUDY was comparison of thyroid surgery performed with the electrocautery tool - Thermostapler ® by EMED with surgery using classic hemostasis technique to evaluate the operative time and complications in the form of bleeding, recurrent laryngeal nerve paralysis, symptoms of hypoparathyroidism, and wound infection. MATERIAL AND METHODS: We retrospectively analyzed 256 patients operated in the Department of General and Proctological Surgery Solec Hospital in Warsaw due to inert thyroid goitre. All patients underwent total thyroidectomy. Patients were divided into two groups. The first group consisted of 126 patients operated in 2000, using classic techniques of hemostasis. While the second group consisted of 130 patients operated in 2007-2008 with Thermostapler®. We compared duration of surgery and the incidence of postoperative complications. RESULTS: The operative time was significantly shorter (average 18 minutes) in the second group of patients. We also recorded a statistically significant decrease in the incidence of complications in the group operated with Thermostapler. CONCLUSIONS: Use of bipolar vessel sealing system in a decisive manner shortens the duration of operation. Use of bipolar vessel sealing system also enables a radical reduction in the incidence of complications rate such as bleeding, recurrent laryngeal nerve paralysis, symptoms of hypoparathyroidism, and wound infection. In the future, similar studies should be performed to assess the real costs resulting from the use Thermostapler®.

A rapid UHPLC method for the simultaneous determination of drugs from different therapeutic groups in surface water and wastewater.

A SPE-UHPLC-UV method for the determination of 13 pharmaceuticals from different therapeutic groups in surface water and wastewater samples was proposed. The following three solid-phase-extraction (SPE) columns with polymeric sorbents were used as a pre-concentration step: the Oasis HLB (average recoveries 93.8 %), the Nexus (84.0 %) and the Bond Elut ENV (88.3 %). A reverse-phase UHPLC with a C(18e) monolithic column and gradient elution program was used to obtain the best separations for all 13 drugs in short analysis time (3.4 min). The LOD range for determined drugs was 0.02-0.18 µg L(-1), and the concentration range for drugs found in water samples was 0.06-0.90 µg L(-1). The proposed method was used to analyze different water samples, mostly from rivers, and can be used as a monitoring tool for environmental pollution.

Somatic mutations affecting the selectivity filter of KCNJ5 are frequent in 2 large unselected collections of adrenal aldosteronomas.

Primary hyperaldosteronism, one cause of which is aldosterone-producing adenomas (APAs), may account for ≤5% to 10% of cases of essential hypertension. Germline mutations have been identified in 2 rare familial forms of primary hyperaldosteronism, but it has been reported recently that somatic mutations of the KCNJ5 gene, which encodes a potassium channel, are present in some sporadic nonsyndromic APAs. To address this further we screened 2 large collections of sporadic APAs from the United Kingdom and Australia (totalling 73) and found somatic mutations in the selectivity filter of KCNJ5 in 41% (95% CI: 31% to 53%) of the APAs (30 of 73). These included the previously noted nonsynonymous mutations, G151R and L158R, and an unreported 3-base deletion, delI157, in the region of the selectivity filter. APAs containing a somatic KCNJ5 mutation were significantly larger than those without (1.61 cm [95% CI: 1.39-1.83 cm] versus 1.04 cm [95% CI: 0.91-1.17 cm]; P<0.0001) but with substantial overlap in size between genotypes. The APAs carrying a mutation, but not those without, also consistently lacked a postural aldosterone response, suggesting a physiologically distinct subtype. Hence, somatic KCNJ5 mutations are not restricted to large APAs (>2 cm), and their frequency in our unselected series suggests they are common and could be important in the molecular pathogenesis of many sporadic cases of APA.

Missense mutations in the copper transporter gene ATP7A cause X-linked distal hereditary motor neuropathy.

Distal hereditary motor neuropathies comprise a clinically and genetically heterogeneous group of disorders. We recently mapped an X-linked form of this condition to chromosome Xq13.1-q21 in two large unrelated families. The region of genetic linkage included ATP7A, which encodes a copper-transporting P-type ATPase mutated in patients with Menkes disease, a severe infantile-onset neurodegenerative condition. We identified two unique ATP7A missense mutations (p.P1386S and p.T994I) in males with distal motor neuropathy in two families. These molecular alterations impact highly conserved amino acids in the carboxyl half of ATP7A and do not directly involve the copper transporter's known critical functional domains. Studies of p.P1386S revealed normal ATP7A mRNA and protein levels, a defect in ATP7A trafficking, and partial rescue of a S. cerevisiae copper transport knockout. Although ATP7A mutations are typically associated with severe Menkes disease or its milder allelic variant, occipital horn syndrome, we demonstrate here that certain missense mutations at this locus can cause a syndrome restricted to progressive distal motor neuropathy without overt signs of systemic copper deficiency. This previously unrecognized genotype-phenotype correlation suggests an important role of the ATP7A copper transporter in motor-neuron maintenance and function.

An analytical procedure for the determination of different therapeutic drugs in surface waters.

An analytical procedure for the determination of 10 drugs belonging to three different therapeutic groups was analysed. Several compounds were investigated which comprise of beta-blockers: sotalol (SOT), metoprolol (MET), propranolol (PRO), carvedilol (CAR); corticosteroids: prednisolone (PRE), dexamethasone (DEX); analgesic, non-steroidal anti-inflammatory (NSAID): paracetamol (PAR), metamizole (MTZ), aspirin (ASP) and ketoprofen (KET). Reversed-phase liquid chromatography with gradient elution, fluorescence (FL) and diode array detectors (DAD) was applied for the selective investigation of the drugs. Three solvents were used as the mobile phase: methanol, 0.05% trifluoroacetic acid (TFA) in water and acetonitrile. The solid phase extraction (SPE) method using the Oasis HLB column was proposed for the preconcentration step. The recovery level for most of the drugs was above 80%. The low values of limits of detection (LOD) for PAR, SOT, MTZ, MET, SAL, PRO, PRE, CAR, DEX and KET were achieved: 106 ng L(-1), 1,048 ng L(-1), 2.48 ng L(-1), 2.17 ng L(-1), 16.5 ng L(-1), 1.10 ng L(-1), 160 ng L(-1), 6.62 ng L(-1), 76.5 ng L(-1) and 45.2 ng L(-1), respectively. The suggested method was used for the determination of drugs in spiked surface water.