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The radionuclides 43 Sc, 44g/mSc, and 47 Sc can be produced cost-effectively in sufficient yield for medical research and applications by irradiating natTi and natV target materials with protons. Maximizing the production yield of the therapeutic 47 Sc in the highest cross section energy range of 24-70 MeV results in the co-production of long-lived, high-γ-ray-energy 46 Sc and 48 Sc contaminants if one does not use enriched target materials. Mass separation can be used to obtain high molar activity and isotopically pure Sc radionuclides from natural target materials; however, suitable operational conditions to obtain relevant activity released from irradiated natTi and natV have not yet been established at CERN-MEDICIS and ISOLDE. The objective of this work was to develop target units for the production, release, and purification of Sc radionuclides by mass separation as well as to investigate target materials for the mass separation that are compatible with high-yield Sc radionuclide production in the 9-70 MeV proton energy range. In this study, the in-target production yield obtained at MEDICIS with 1.4 GeV protons is compared with the production yield that can be reached with commercially available cyclotrons. The thick-target materials were irradiated at MEDICIS and comprised of metallic natTi, natV metallic foils, and natTiC pellets. The produced radionuclides were subsequently released, ionized, and extracted from various target and ion source units and mass separated. Mono-atomic Sc laser and molecule ionization with forced-electron-beam-induced arc-discharge ion sources were investigated. Sc radionuclide production in thick natTi and natV targets at MEDICIS is equivalent to low- to medium-energy cyclotron-irradiated targets at medically relevant yields, furthermore benefiting from the mass separation possibility. A two-step laser resonance ionization scheme was used to obtain mono-atomic Sc ion beams. Sc radionuclide release from irradiated target units most effectively could be promoted by volatile scandium fluoride formation. Thus, isotopically pure 44g/mSc, 46 Sc, and 47 Sc were obtained as mono-atomic and molecular ScF 2+ ion beams and collected for the first time at CERN-MEDICIS. Among all the investigated target materials, natTiC is the most suitable target material for Sc mass separation as molecular halide beams, due to high possible operating temperatures and sustained release.

West Nile virus is widespread in southern Russia, where the fever appears annually. Since Western Kazakhstan borders on southern Russia, we examined mosquitoes in this region for the presence of West Nile virus. Virus was detected in a small proportion of Culex modestus mosquitoes (3/239 pools) and isolates are related to strains from Volgograd, Russia. A screen for West Nile virus IgG was conducted and ~5% of the local human population tested positive., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Nurmakhanov, Sansyzbaev, Atshabar, Berlin, Kobzhasarov, Yeskhojayev, Vilkova, Ayazbayev, Andryuchshenko, Bidashko, Hay and Shvetsov.)

Objectives: To evaluate the employment possibilities of Lithuanian dental hygienists., Methods: The questionnaire asked about the demographics of dental hygienists, characteristics of practice, patient load, career intentions, opinion about dental hygienists workforce and the need of governmental workforce regulation. The study consisted of all licensed dental hygienists in Lithuania in 2018 (N = 1109)., Results: The final response rate was 52.1% (n = 578), 64% (n = 370) of respondents lived in the country's five main cities, and 73.5% (n = 425) worked in these population centres, with 94.3% (n = 545) worked in private sector. Over two-thirds of respondents said there was an excess of dental hygienists in Lithuania. Nearly 80% "always" or "sometimes" reported that they had insufficient patients, which may account for the prevalence of supplementary work (48.4%, n = 280), that is work as a dental assistant (67.9%, n = 190). Data obtained show that dental hygienists with less than ten years' experience were likely to work as a dental assistant (P < .05). Notwithstanding, 73.9% (n = 428) of the dental hygienists reported that they only want to practice their profession. Most (83.4%, n = 483) struggled to find dental hygienist work, and 70.5% (n = 408) wanted regulation of number of dental hygienists at a national level., Conclusions: The respondents suggested there is (a) a lack of dental hygiene patients, (b) available workload for additional preventive dental hygiene services, (c) pressure to search for additional work, usually as a dental assistant. Governmental support to optimally regulate oral health human resources is, according to most dental hygienists, an emphatic wish as a possible solution at national level., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Aim: To map psychological problems amongst undergraduate dental students with a focus on different time points in clinical work in seven Eastern European and Scandinavian countries., Materials and Methods: A total of 1063 3rd- and 5th-year dental students (response rate 70%) participated in this pilot study and completed a pre-tested, structured questionnaire, which collected information on sociodemographic characteristics and self-reported psychological problems. Data were analysed by bivariate and multivariate methods., Results: The majority of participants were female and were younger than male participants. Most participants, though more females than males, agreed that the clinical work of dentistry was psychologically difficult. Almost half of participants felt nervous before working with patients (N = 506, 48%) and experienced a lot of stress whilst working with patients (N = 488, 46%); almost one-third (N = 287, 27%) felt anxious/worried after working with patients. Being a 3rd- and 4th-year student (vs 5th-year) reduced the odds for anxiety after working with patients; being a 3rd-year student (vs 5th-year) increased the odds for stress whilst working with patients. Studying in countries other than Norway reduced the odds for stress whilst working with patients. Less than good self-perceived health, presence of psychological health complaints before starting dental education, female gender and lack of physical activity increased the odds for psychological problems., Conclusion: A high number of undergraduate dental students reported psychological problems in connection with clinical work. It is unlikely that "one size fits all"; therefore, further qualitative investigations on stressors in clinical learning environments should be done in order to design tailor-made supportive strategies., (© 2020 The Authors. European Journal of Dental Education published by John Wiley & Sons Ltd.)

Background: Up to 40% of patients with transvenous implantable cardioverter-defibrillator (ICD) experience lead-associated complications and may suffer from high complication rates when lead extraction is indicated. Subcutaneous ICD may represent a feasible alternative; however, the efficacy of the subcutaneous ICD in the detection and treatment of ventricular arrhythmias in patients with hereditary arrhythmia syndromes has not been fully evaluated., Methods and Results: Patients with primary hereditary arrhythmia syndromes who fulfilled indication for defibrillator placement were eligible for enrollment. Between 2010 and 2016, 62 consecutive patients with primary hereditary arrhythmia syndromes, without indication for antibradycardia therapy, were enrolled in the study. Mean follow-up was 31.0±14.2 months. The study cohort comprised of 24 patients with Brugada syndrome, 17 with idiopathic ventricular fibrillation, 6 with long-QT syndrome, 1 with short-QT syndrome, 3 with catecholaminergic polymorphic ventricular tachycardia, 8 with hypertrophic cardiomyopathy, and 3 with arrhythmogenic right ventricular cardiomyopathy. Thirty-nine patients were implanted for secondary prevention. Twenty-two patients had a previous transvenous ICD implanted, but required revision because of infection or lead defects. A total of 20 spontaneous ventricular tachyarrhythmias requiring shock intervention occurred in 10 patients during follow-up. All episodes were terminated within the first ICD shock delivery with 80 J. Two patients had inappropriate therapies caused by oversensing following an uneventful implantation. No pocket-site infections and no premature revisions have occurred during follow-up., Conclusions: Our study supports the use of the subcutaneous ICD for both secondary and primary prevention of sudden cardiac death as a reliable alternative to the conventional transvenous ICD., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Background and Objective: The requirement for dental specialties and the number of specialists in each country depends on the content and execution of undergraduate dental education, the complex oral health care needs of the society and other factors. The aim of our study was to assess specific treatment procedures of Lithuanian general dentists and their need to refer patients to specialists., Materials and Methods: Census sampling was employed and the data collected by means of a structured questionnaire asking dentists about the frequency of specific treatment procedures they perform and the frequency of referrals they make to different dental specialists. The results are of a self-reported nature., Results: From general dental practice, 76.3% of cases needing orthodontic treatment were referred to orthodontists. About half of patients needing specialized care were referred to periodontists (50.2%), orthopedists (46.9%) and oral surgeons (45.0). More than one-third (39%) of the cases needing specialist care were referred to endodontists. Only one-third of patients were referred to pediatric dentists. In about 60% of cases needing respective care general dentists extracted teeth and roots, made incisions in acute jaw infections and treated young children; in about half of cases general dentists performed complex endodontic manipulations and treatment with fixed and removable prostheses., Conclusions: There is a clear need for Lithuanian dental practitioners to refer patients to all types of dental specialists. Undergraduate dental education program and postgraduate training should be more directed toward the extraction of teeth and roots, treatment of young children and provision of dental prostheses to patients., (Copyright © 2015 Lithuanian University of Health Sciences. Production and hosting by Elsevier Urban & Partner Sp. z o.o. All rights reserved.)

An alanine conjugate of a Candida albicans geranylgeranyl transferase I inhibitor was synthesized to facilitate its uptake into the fungal cell. The antifungal activity of CaGGTase-Ala conjugate is demonstrated. It is also shown that the CaGGTase-Ala conjugate affects prenylation of endogenous Rho1p, but has no effect on prenylation of endogenous Ras1p.

Objectives: To investigate differences in stretching behaviour of hamstring muscles in elite field hockey players and normal subjects., Methods: 16 normal healthy subjects (group A) and 16 elite field hockey players (group B). Stretching of the hamstrings was performed with a knee extension device. Two successive single stretches (1 and 2) until the maximum stretch tolerance was achieved were applied to each subject twice. Simultaneously range of movement (ROM), passive resistance to stretch (PRS) at 36 degrees ROM, and electromyographic (EMG) activity of the biceps femoris and semitendinosus muscles were recorded., Results: ROM (p=0.02 for stretch 1; p=0.04 for stretch 2) and PRS (p=0.04 and p=0.03) were significantly higher in group B, as compared to group A. The EMG activity of the biceps femoris (p=0.02 for stretch 1; p=0.3 for stretch 2) and semitendinosus (p=0.03 and p=0.11) were significantly higher in group B only for stretch 1. From stretch 1 to 2, a significant increase in ROM was observed in both group A (p=0.002) and group B (p=0.0003), as well as a significant decrease of PRS (p=0.0002; p=0.002). EMG activity only showed a significant decrease in group B (biceps p=0.03;semitendinosus p=0.01), but not in group A (p=0.6; p=0.06). The EMG activity sets in when the subjects begin to perceptive pain in the stretched muscles., Conclusions: Significant differences exist. in the stretching behaviour of elite field hockey players and non-athletes. ROM, PRS and EMG activity are higher in athletes. Implications for treatment should be considered, but recommendations cannot be made on the basis of this study yet.

In Saccharomyces cerevisiae, Rho1p plays an important role in cell wall integrity by regulating beta-1,3-glucan synthase, Pkc1p and the actin cytoskeleton. To determine the physiological role of Rho1p in the dimorphic fungus Candida albicans, the major human fungal pathogen, we constructed mutants that conditionally express Rho1p from the glucose-repressible phosphoenolpyruvate carboxykinase promoter (pPCK1). We examined the growth of these cells in a range of conditions. Depletion of Rho1p from yeast cells resulted in cell death, lysis, and aggregation. The Rho1p conditional mutant was inviable on 10% serum indicating that Rho1p was also required for hyphal viability. Furthermore, in a mouse model of systemic candidiasis, strains dependent on pPCK1-driven RHO1 expression failed to colonise the kidneys and establish disease, suggesting that the level of glucose in serum was sufficient to repress the pPCK1 and that Rho1p-depleted strains were inviable within the host. Therefore, Rho1p is essential for the viability of C. albicans in vitro and in vivo.

Rapamycin is a potent immunosuppressant that blocks the G1/S transition in antigen-activated T cells and in yeast. The similar effects of rapamycin in animal cells and yeast suggest that the biochemical steps affected by rapamycin are conserved. Using a two-hybrid system we isolated mammalian clones that interact with the human FK506/rapamycin-binding protein (FKBP12) in the presence of rapamycin. Specific interactors, designated RAPT1, encode overlapping sequences homologous to yeast Tor, a putative novel phosphatidylinositol 3-kinase. A region of 133 amino acids of RAPT1 is sufficient for binding to the FKBP12/rapamycin complex. The corresponding region in yeast Tor contains the serine residue that when mutated to arginine confers resistance to rapamycin. Introduction of this mutation into RAPT1 abolishes its interaction with the FKBP12/rapamycin complex.

The FKB2 gene of Saccharomyces cerevisiae encodes a homolog of mammalian FKBP-13, an FK506/rapamycin-binding protein that localizes to the lumen of the endoplasmic reticulum (ER). We have found that FKB2 mRNA levels increase in response to the accumulation of unfolded precursor proteins in the ER. FKB2 mRNA levels are elevated in cells blocked in N-glycosylation--i.e., in wild-type cells treated with tunicamycin and in the sec53-6 mutant grown at the nonpermissive temperature. Mutations that block other steps in secretion have no effect on FKB2 mRNA levels, indicating that increases in FKB2 mRNA are not the consequence of a general block in secretion. The increase in FKB2 mRNA in response to unfolded proteins in the ER is mediated through a 21-bp unfolded-protein response (UPR) element located in the 5' noncoding region of FKB2. UPR elements present in other ER chaperone genes, such as yeast KAR2 (BiP), mammalian GRP78 (BiP), and GRP94, function in an analogous manner to that in FKB2. As with KAR2, FKB2 mRNA levels are also elevated by heat shock. The similarities in the regulation of FKB2 and other ER chaperone genes suggest that FKBP-13 may play a role in protein trafficking in the ER.

BIK1 function is required for nuclear fusion, chromosome disjunction, and nuclear segregation during mitosis. The BIK1 protein colocalizes with tubulin to the spindle pole body and mitotic spindle. Synthetic lethality observed in double mutant strains containing a mutation in the BIK1 gene and in the gene for alpha- or beta-tubulin is consistent with a physical interaction between BIK1 and tubulin. Furthermore, over- or underexpression of BIK1 causes aberrant microtubule assembly and function, bik1 null mutants are viable but contain very short or undetectable cytoplasmic microtubules. Spindle formation often occurs strictly within the mother cell, probably accounting for the many multinucleate and anucleate bik1 cells. Elevated levels of chromosome loss in bik1 cells are indicative of defective spindle function. Nuclear fusion is blocked in bik1 x bik1 zygotes, which have truncated cytoplasmic microtubules. Cells overexpressing BIK1 initially have abnormally short or nonexistent spindle microtubules and long cytoplasmic microtubules. Subsequently, cells lose all microtubule structures, coincident with the arrest of division. Based on these results, we propose that BIK1 is required stoichiometrically for the formation or stabilization of microtubules during mitosis and for spindle pole body fusion during conjugation.

A method for synchronizing conidiation and isolating large numbers of cells at discrete stages of conidia development is described. Using two-dimensional gel electrophoresis, we analyzed the protein profiles of mycelia, aerial hyphae, and conidia and observed that the concentration of 14 polypeptides increase and 38 decrease during the asexual cycle. Twelve polypeptides were present in extracts of aerial hyphae or conidia, but not mycelia, suggesting that they may be conidiation specific. The protein profiles of mutants defective in conidiation were also analyzed. Differences were detected in the two-dimensional profiles of protein extracts from fluffy and wild-type aerial hyphae. Polyadenylated RNA isolated from wild-type mycelia and conidiating cultures was translated in vitro in a rabbit reticulocyte lysate. Differences were detected in the polypeptide products specified by the two RNA populations, suggesting that changes in steady-state levels of polyadenylated RNAs also occur during conidiation.

The asexual developmental pathway in the life cycle of the filamentous fungus Neurospora crassa culminates in the formation of spores called conidia. Several clones of genomic Neurospora DNA have been isolated that correspond to mRNA species expressed during conidiation and not during mycelial growth (V. Berlin and C. Yanofsky, Mol. Cell. Biol. 5:849-855, 1985). In this paper we describe the characterization of one of these clones, named pCon-10a. This clone contains two genes, con-10 and con-13, which are induced coordinately during the later stages of conidiation. The two genes are separated by 1.4 kilobases of DNA; they are located on linkage group IV and are transcribed from the same strand of DNA. The molecular organization and sequence of one of these genes, con-10, and its flanking regions are presented. Full-length cDNA clones for con-10 also were isolated and sequenced, and transcription-initiation and polyadenylation sites were defined. The con-10 gene contains an open reading frame interrupted by two small introns and encodes an 86-amino-acid residue polypeptide that is both hydrophilic and weakly acidic. Expression of the con-10 gene in various mutants defective at different stages of conidiation indicates that it plays a role after aerial hyphal development. Possible functions, organization, and regulation of conidiation-specific genes are discussed.

A Neurospora crassa genomic DNA library was screened with a cDNA probe enriched in sequences expressed in conidiating cultures. Clones were isolated that preferentially hybridized to this probe versus a second cDNA probe complementary to polyadenylated RNA isolated from mycelia. Twelve clones contained unique sequences that hybridized to 22 transcripts, 19 of which accumulated preferentially in conidiating cultures. Eight transcripts were present in higher levels in conidiating cultures than in mycelia. Eleven transcripts were detected only in conidiating cultures and first appeared at different times during the asexual cycle. We mapped genomic sequences homologous to the 11 clones by conventional crosses using restriction fragment-length polymorphisms as genetic markers. The sequences homologous to genes expressed preferentially in conidiating cultures are distributed on six of the seven chromosomes. Clones that map to the same chromosome are linked. No recombination occurred between genomic sequences homologous to three clones, suggesting that the genes contained in these clones may constitute a gene cluster.