The increasing occurrence of antibiotic-resistant bacteria and the dwindling antibiotic research and development pipeline have created a pressing global health crisis. Here, we report the discovery ...of a distinctive antibacterial therapy that uses visible (405 nanometers) light-activated synthetic molecular machines (MMs) to kill Gram-negative and Gram-positive bacteria, including methicillin-resistant
, in minutes, vastly outpacing conventional antibiotics. MMs also rapidly eliminate persister cells and established bacterial biofilms. The antibacterial mode of action of MMs involves physical disruption of the membrane. In addition, by permeabilizing the membrane, MMs at sublethal doses potentiate the action of conventional antibiotics. Repeated exposure to antibacterial MMs is not accompanied by resistance development. Finally, therapeutic doses of MMs mitigate mortality associated with bacterial infection in an in vivo model of burn wound infection. Visible light-activated MMs represent an unconventional antibacterial mode of action by mechanical disruption at the molecular scale, not existent in nature and to which resistance development is unlikely.
Increases brain size has been hypothesized to be inversely associated with the expression of behavioral and brain asymmetries within and between species. We tested this hypothesis by analyzing the ...relation between asymmetries in the planum temporale (PT) and different measures of the corpus callosum (CC) including surface area, streamline count as measured from diffusion tensor imaging, fractional anisotropy values and the ratio in the number of fibers to surface area in a sample of chimpanzees. We found that chimpanzees with larger PT asymmetries in absolute terms had smaller CC surface areas, fewer streamlines and a smaller ratio of fibers to surface area. These results were largely specific to male but not female chimpanzees. Our results partially support the hypothesis that brain asymmetries are linked to variation in corpus callosum morphology, although these associations may be sex-dependent.
The penetration of the toxic substances into mother's organism leads to the cumulative xenobiotic burden of different degree with the following induction of removal reactions and developing of ...obstetric complications, and may cause the metabolic form of fetoplacental insufficiency. The pathogenesis of the fetoplacental insufficiency is determined by morphological changes and disturbances of placenta functioning. The purposes of this work were to study influence of further consequences of experimental fetoplacental insufficiency in mothers of young and mature reproductive age on the females-offspring fertility and to investigate the protective properties of original pharmaceutical composition.Materials and methods. The healthy, Vistar mature rat's females of young (3 months) and mature (10 months) reproductive age have been used in the experiment. 8 groups for 7 pregnant females in each have been formed: groups 1 and 2 — intact animals of young and mature reproductive age; groups 3 and 4 — females with experimental fetoplacental insufficiency of young and mature reproductive age accordingly; groups 5 and 6 — young and mature animals with experimental fetoplacental insufficiency treated by pharmaceutical composition from 11 to 19 day of pregnancy. Groups 7 and 8 — young and mature animals with experimental fetoplacental insufficiency treated by drug of comparison – Dipyridamole. The modeling of fetoplacental insufficiency has been fulfilled by daily subcutaneous introduction of 50% tetrachloromethane oil solution in dose of 2 ml/kg of body mass from 12 to 18 day of pregnancy. The fertility of females has been determined according to the results of mating with intact healthy males. The blood serum samples have been obtained for Estradiol and Testosterone levels determination.Results. Fetoplacental insufficiency influences the fertility of females-offspring born to mothers of young and mature reproductive age. Аll the groups of females-offspring born to mothers with fetoplacental insufficiency have significantly lowered pregnancy index and integral fecundity. Only in offspring born to mothers of young reproductive age with fetoplacental insufficiency the decreased number of pregnancy corpus luteum, implantation sites and fetuses has been observed. The introduction of pharmaceutical composition to pregnant females has lead to female birth with normalized levels of sex hormones, nevertheless, animals has demonstrated decreased fecundity.
The aim of this scientific work was to determine the influence of the experimental fetoplacental insufficiency on the both sex offspring oxidative status during puberty and to estimate the efficiency ...of base and complextherapy during pregnancy.Materials. The healthy, Vistar mature rat’s females of young (3–4 months) and mature (8–10 months)reproductive age have been used for both sex offspring obtaining. 8 groups for 7 pregnant females in eachhave been formed: Groups I and II — intact animals of young and mature reproductive age; Group III andIV — females with experimental Fetoplacental insufficiency (FPI) of young and mature reproductive age accordingly; Groups V and VI — young and mature animals with experimental FPI treated by pharmaceuticalcomposition which contains nontoxic active pharmaceutical ingredients of FPI basic therapeutic group — aminoacid (L-arginine), dicarbonic acid (succinic acid), vitamins (folic acid) and vasoactive drug (dipyridamole).Experimental animals have received treatment from 11 to 19 day of pregnancy. Groups VII and VIII — youngand mature animals with experimental FPI treated by drug of comparison — dipyridamole. The modeling ofFPI has been carried out by daily subcutaneous introduction of 50 % tetrachlormethane oil solution in dose of2 ml/kg of body weight from 12 to 18 day of pregnancy. Animals — offspring have been killed on the 50th day oflife (puberty period) by quick decapitation without general anesthesia to avoid negative effects on sex hormoneslevel and antioxidant enzymes systems.Results. The effect of experimental fetoplacental insufficiency in rats of young and mature reproductiveage on the oxidative status formation in offspring of both sexes during puberty was determined and the effectsof basic and complex therapy during pregnancy were evaluated. It was revealed that fetoplacental insufficiencyin the second half of pregnancy leads to the formation in offspring of both sexes, but more pronounced in maleoffspring, during the puberty, an altered pattern of the antioxidant system enzymatic activity, which is realizedin increased levels of both primary and final products of lipoperoxidation and may be the basis for further development of chronic diseases. More pronounced disorders were observed in the offspring of mothers of maturereproductive age, which may be due to the additional influence of involutive processes in the placenta. The useof a vasodilator drug alone and, more effectively in combination, significantly restored the studied parameters
The paper presents different techniques for digitizing grinding pins and discusses the use of digitalized pins and the results of measurements in technological process planning (TPP), focusing on the ...challenges of the digital era. It describes the potential of different measuring devices, taking into account the digitization of a real tool shape into virtual 2D and 3D models. The following methods for measuring grinding pins are presented in the study: contact and non-contact coordinate measurements – performed on coordinate measuring machines (CMM); optical measurements on microscopes (i.e. focus-variation technique); optical measurements using tool presetters; optical measurements with measuring arm; laser micrometer measurements; and laser triangulation sensor measurements. Moreover, the use of testers which are applied in contour measurements is analyzed. On the basis of the presented methods, taking into account their possibilities and limitations, we discuss how the obtained digital data can be used in the planning of technological processes.
The aim of this study was to evaluate the impact of GSTM1, GSTT1, and GSTP1 gene polymorphism on urinary excretion of unchanged ifosfamide, 2-dechloroethylifosfamide (2DCIF), and ...3-dechloroethylifosfamide (3DCIF) with regard to the incidence of ifosfamide-related nephrotoxicity and neurotoxicity in children. The study comprised 76 children (38 girls, 38 boys) ages 9.84 to 210 months who were being treated for various malignant diseases with ifosfamide. The children were enrolled after identification of genotype coding for three classes of glutathione S-transferases (GSTM1, GSTT1, and GSTP1) at the initial stage of diagnosis. (P) nuclear magnetic resonance spectroscopy was used to analyze the urinary excretion of unchanged ifosfamide, 2DCIF, and 3DCIF metabolites on consecutive days after the end of the 3-hour infusion of ifosfamide. In children with polymorphic locus of the GSTP1 gene compared with children with homozygous wild alleles, increased urinary excretion of 3DCIF (P=0.029) and decreased creatinine clearance was found (Mann-Whitney P=0.03; median 81.1 mL/min/1.73 m vs. 105.0 mL/min/1.73 m, respectively). The authors' multidimensional analysis model revealed that besides the total ifosfamide dose and co-administration of other toxic drugs, polymorphic locus of GSTP1 gene may be one of the factors determining a higher toxicity of the cytostatic agent. The model was construed at P=0.029. Moreover, no correlation was found between the GSTM1 or GSTT1 genotype and ifosfamide toxicity and the urinary excretion of its metabolites. The results of this analysis indicate that individual reactions to ifosfamide can depend on inherited genetic polymorphisms, especially associated with the GSTP1 gene coding detoxifying enzyme.
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