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Phenotypic screening of an in-house library of small molecule purine derivatives against Mycobacterium tuberculosis (Mtb) led to the identification of 2-morpholino-7-(naphthalen-2-ylmethyl)-1,7-dihydro-6H-purin-6-one 10 as a potent antimycobacterial agent with MIC 99 of 4 μM. Thorough structure-activity relationship studies revealed the importance of 7-(naphthalen-2-ylmethyl) substitution for antimycobacterial activity, yet opened the possibility of structural modifications at positions 2 and 6 of the purine core. As the result, optimized analogues with 6-amino or ethylamino substitution 56 and 64, respectively, were developed. These compounds showed strong in vitro antimycobacterial activity with MIC of 1 μM against Mtb H 37 Rv and against several clinically isolated drug-resistant strains, had limited toxicity to mammalian cell lines, medium clearance with respect to phase I metabolic deactivation (27 and 16.8 μL/min/mg), sufficient aqueous solubility (>90 μM) and high plasma stability. Interestingly, investigated purines, including compounds 56 and 64, lacked activity against a panel of Gram-negative and Gram-positive bacterial strains, indicating a specific mycobacterial molecular target. To investigate the mechanism of action, Mtb mutants resistant to hit compound 10 were isolated and their genomes were sequenced. Mutations were found in dprE1 (Rv3790), which encodes decaprenylphosphoryl-β-d-ribose oxidase DprE1, enzyme essential for the biosynthesis of arabinose, a vital component of the mycobacterial cell wall. Inhibition of DprE1 by 2,6-disubstituted 7-(naphthalen-2-ylmethyl)-7H-purines was proved using radiolabelling experiments in Mtb H 37 Rv in vitro. Finally, structure-binding relationships between selected purines and DprE1 using molecular modeling studies in tandem with molecular dynamic simulations revealed the key structural features for effective drug-target interaction., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Aldose reductase, the first enzyme of the polyol pathway represents a key drug target in therapy of diabetic complications. In this study a series of six novel rhodanine based inhibitors of aldose reductase was designed, synthesized, and tested for their ability to inhibit aldose reductase and for selectivity relative to structurally related aldehyde reductase. Aldose reductase inhibitory activities of the compounds were characterized by the IC 50 values ranging from 2000 nM to 20 nM. The values of selectivity factors relative to aldehyde reductase were decreasing in the same array from 24 to 5. In silico docking into the inhibitor binding site of aldose reductase revealed a specific binding pattern of the compounds comprising interaction of the deprotonated 4-hydroxybenzylidene group with the anion-binding sub-pocket of aldose reductase, creating a strong H-bond and charge interactions. Predicted pH-distribution profiles of the novel compounds into octanol, supported by experimentally determined distribution ratios, favour drug uptake at the physiological pH, as a result of the presence of the low-acidic phenolic group, instead of the more acidic carboxymethyl functional group., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

The fight against unmanned vehicles is nothing new; however, especially with the arrival of new technologies that are easily accessible for the wider population, new problems are arising. The deployment of small unmanned aerial vehicles (UAVs) by paramilitary organizations during conflicts around the world has become a reality, non-lethal "paparazzi" actions have become a common practice, and it is only a matter of time until the population faces lethal attacks. The basic prerequisite for direct defense against attacking UAVs is their detection. The authors of this paper analysed the possibility of detecting flying aircraft in several different electro-magnetic spectrum bands. Firstly, methods based on calculations and simulations were chosen, and experiments in laboratories and measurements of the exterior were subsequently performed. As a result, values of the radar cross section (RCS), the noise level, the surface temperature, and optical as well as acoustic traces of tested devices were quantified. The outputs obtained from calculated, simulated, and experimentally detected values were found via UAV detection distances using specific sensors working in corresponding parts of the frequency spectrum., Competing Interests: The authors declare no conflict of interest. The founding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

The case history of a 15 1/2-year-old boy is presented who suffers from screaming fits during the night and epilepsia. The problem has existed since he was eight. He lives alone with his mother in a "partner-like" relationship. The previous diagnosis, namely epilepsy, has masked any possible psychodynamic element. Our diagnostic instruments were: 1. Standardized diagnostics with DSM III-R; 2. psychoanalytically oriented psychodiagnostics; 3. long term EEG-video-monitoring, which eventually succeeded in differentiating his multiple symptoms. Using these methods we were able to differentiate a sleep disorder (somnambulism) from his grandmal epilepsy. We changed his anticonvulsive pharmacological therapy and introduced an individual psychotherapy ("Katathymes Bilderleben"). This kind of psychotherapy is applied for the first time as a therapy for somnambulism. By using this therapeutic concept we cured our patient from his symptoms.

We present the second description of an early diagnosed state of Hallervorden-Spatz disease (HSD) verified clinically and by means of magnet resonance imaging. Since the magnet resonance shows HSD specific transformations brain biopsy can be relinquished. In our case the early confirmation of a neurodegenerative disease (versus the presumption of a severe adjustment disorder as the case was presented) brought much relief in respect of the feelings of guilt to the family, although the long term prognosis is poor. The distinction between neurodegenerative diseases, demyelinisating diseases and HSD was possible considering the clinical signs and using the magnet resonance, which showed various pigments within the globus pallidum.

Early morbidity and neurological development in 40 term infants with UApH less than or equal to 7,00 (6,60-7,00) were investigated. Group 1: 18 infants (45%) responded well to the measures of primary resuscitation--they never revealed any neurological symptoms and their growth and development were normal. Group 2: 15 infants (37,5%) who responded less well to primary resuscitation initially had mild to moderate neurological symptoms subsiding during the first few days of life. There were 2 cases of necrotizing enterocolitis and 4 cases of moderate meconium aspiration syndrome. Apgar scores, pH and blood-gases were worse than in group 1. At discharge and on follow-up all children appeared clinically normal. Group 3: 7 infants (17,5%) with severe neurological signs were not responding well to resuscitation. They were referred to the intensive care nursery and treated for cerebral edema (hyperventilation, pentobarbital, steroids). 2 infants with severe meconium aspiration syndrome recovered entirely. Two children had evidence of cerebral involvement as demonstrated by means of computerized tomography of the head, but were normal on follow-up. Three children with distinct signs of cerebral palsy developed cerebral atrophy and microcephaly, presumably due to hypoxic-ischemic encephalopathy. Early morbidity, comprising all 22 infants from group 2 and 3 amounts to 55%, morbidity up to an average age of 14,7 month includes 5 infants from group 3 (suspected cerebral lesions in 2, microcephalus in 3) and thus comes to 12,5% of the total.

Trifluralin, a widely used herbicide, added to the diet before the p.o. administration of benzo(a)pyrene (BP) and fed continuously, significantly inhibited the induction of lung and forestomach tumors in female A/J mice. Dietary intake of trifluralin before the administration of BP resulted in a significant increase in glutathione in lung and forestomach but not in liver and glandular stomach. Trifluralin treatment also inhibited the binding of [3H]BP to liver and lung DNA, as well as to protein in the liver. Under these conditions, the protection against BP-induced lung tumors and perhaps forestomach tumors may be due to an elevation of tissue glutathione, resulting in a decreased binding of reactive metabolites of BP to macromolecules at these sites. The results indicate that trifluralin has a "blocking" effect in its inhibition of BP-induced tumors. Our studies show that trifluralin also inhibits chemical carcinogenesis in lung and forestomach when started in the diet 1 day after the administration of BP and fed continuously thereafter. In the case of lung, although maximum inhibition of tumors occurred when trifluralin was started 1 day after BP, there was significant protection at all time intervals (0 to 7 days) against lung tumors. The finding that trifluralin protects against BP tumorigenesis when started in the diet after the administration of the carcinogen clearly demonstrates that trifluralin also has a "suppressive" effect against BP-induced tumors.

37 children (aged 4 1/2-15 1/2 years) with encopresis were seen at the psychosomatic outpatient unit of the university children's hospital of Graz in the course of two years, comprising 1.8% of all our outpatients of that time (n = 2037). They had been referred to us by pediatricians general practitioners, welfare institutions and the local children's surgical hospital. Based an our observations and data-analysis of this heterogenic group we would like to suggest a subdivision of the new classification group of "elimination disorders" (307.70/307.60 DSM III-R) into three main subgroups; according to the use of the fifth digit in the DSM III-R (e.g. mood disorders 296.xx) we define: 307.71: primary infantile encopresis (group I); 307.72: primary reactive encopresis (group II a); 307.73: secondary reactive encopresis (group II b); 307.74: late "neurotic" encopresis (group III); 307.70: not otherwise specified NOS. Moreover, we hope to draw attention to the specific psychodynamics of this functional disorder, since we believe this to be a fundamental prerequisite for any successful therapeutic intervention.

We present outcome data of 171 children with psychosomatic and child-psychiatric disorders and discuss the pros and cons of two standardized multiaxial diagnostic systems (DSM III and the Multiaxial System of Rutter 1975). Results and arguments were considered until a clearcut choice fell for the DSM-III. As a major conclusion we introduce the BAT-Index, a factor derived by comparing the psychosocial stressors (Axis 4 DSM III) to the highest level to adaptive functioning past year (Axis 5 DSM III) which can be helpful in estimating the to be expected changes and complications in therapeutic settings and gives us a good prognostic assessment of the patient.

A 10 5/12 year old boy was presented with seizures of uncertain origin on to the psychosomatic ward of our University Children's Hospital. The question and problem was the distinction of psychogenic versus epileptogenic origin (repeatedly performed EEG's had shown normal findings, the seizures did not response to anticonvulsive therapy). The exploration of a psychodynamic causes of the presenting problem was excluded by family therapeutic and psychoanalytical case history and psychodynamic interview. The first pathological finding was seen with registration of a long term EEG with typical findings of temporal central spikes and waves as seen in the benign rolandic-epilepsia. The following diagnostic considerations were discussed and differentiated. a) benign rolandi epilepsia b) malign rolandi epilepsia c) psychomotoric seizures d) rolandic spikes as symptomatic finding of a brain tumor. The definite diagnosis was finally confirmed by a cerebral computer-tomography which showed a large expensive process in the interferior right regio temporalis, which was identified histologically after operation as a oligodendrogliom grad-I. The tumor was removed successfully as a whole without any neurological defects.