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We measured the radiation tolerance of commercially available diamonds grown by the Chemical Vapor Deposition process by measuring the charge created by a 120 GeV hadron beam in a 50 μm pitch strip detector fabricated on each diamond sample before and after irradiation. We irradiated one group of samples with 70 MeV protons, a second group of samples with fast reactor neutrons (defined as energy greater than 0.1 MeV), and a third group of samples with 200 MeV pions, in steps, to (8.8±0.9) × 1015 protons/cm2, (1.43 ± 0.14) × 1016 neutrons/cm2, and (6.5 ± 1.4) × 1014 pions/cm2, respectively. By observing the charge induced due to the separation of electron–hole pairs created by the passage of the hadron beam through each sample, on an event-by-event basis, as a function of irradiation fluence, we conclude all datasets can be described by a first-order damage equation and independently calculate the damage constant for 70 MeV protons, fast reactor neutrons, and 200 MeV pions. We find the damage constant for diamond irradiated with 70 MeV protons to be 1.62 ± 0.07(stat) ± 0.16(syst) × 10–18 cm2/(p μm), the damage constant for diamond irradiated with fast reactor neutrons to be 2.65 ± 0.13(stat) ± 0.18(syst) × 10–18 cm2/(n μm), and the damage constant for diamond irradiated with 200 MeV pions to be 2.0 ± 0.2(stat) ± 0.5(syst) × 10–18 cm2/(π μm). The damage constants from this measurement were analyzed together with our previously published 24 GeV proton irradiation and 800 MeV proton irradiation damage constant data to derive the first comprehensive set of relative damage constants for Chemical Vapor Deposition diamond. We find 70 MeV protons are 2.60 ± 0.29 times more damaging than 24 GeV protons, fast reactor neutrons are 4.3 ± 0.4 times more damaging than 24 GeV protons, and 200 MeV pions are 3.2 ± 0.8 more damaging than 24 GeV protons. We also observe the measured data can be described by a universal damage curve for all proton, neutron, and pion irradiations we performed of Chemical Vapor Deposition diamond. Finally, we confirm the spatial uniformity of the collected charge increases with fluence for polycrystalline Chemical Vapor Deposition diamond, and this effect can also be described by a universal curve.

We measured the radiation tolerance of commercially available diamonds grown by the Chemical Vapor Deposition process by measuring the charge created by a 120 GeV hadron beam in a 50 μm pitch strip detector fabricated on each diamond sample before and after irradiation. We irradiated one group of samples with 70 MeV protons, a second group of samples with fast reactor neutrons (defined as energy greater than 0.1 MeV), and a third group of samples with 200 MeV pions, in steps, to (8.8±0.9) × 1015 protons/cm2, (1.43±0.14) × 1016 neutrons/cm2, and (6.5±1.4) × 1014 pions/cm2, respectively. By observing the charge induced due to the separation of electron–hole pairs created by the passage of the hadron beam through each sample, on an event-by-event basis, as a function of irradiation fluence, we conclude all datasets can be described by a first-order damage equation and independently calculate the damage constant for 70 MeV protons, fast reactor neutrons, and 200 MeV pions. We find the damage constant for diamond irradiated with 70 MeV protons to be 1.62±0.07(stat)±0.16(syst)× 10−18 cm2/(p μm), the damage constant for diamond irradiated with fast reactor neutrons to be 2.65±0.13(stat)±0.18(syst)× 10−18 cm2/(n μm), and the damage constant for diamond irradiated with 200 MeV pions to be 2.0±0.2(stat)±0.5(syst)× 10−18 cm2/(π μm). The damage constants from this measurement were analyzed together with our previously published 24 GeV proton irradiation and 800 MeV proton irradiation damage constant data to derive the first comprehensive set of relative damage constants for Chemical Vapor Deposition diamond. We find 70 MeV protons are 2.60 ± 0.29 times more damaging than 24 GeV protons, fast reactor neutrons are 4.3 ± 0.4 times more damaging than 24 GeV protons, and 200 MeV pions are 3.2 ± 0.8 more damaging than 24 GeV protons. We also observe the measured data can be described by a universal damage curve for all proton, neutron, and pion irradiations we performed of Chemical Vapor Deposition diamond. Finally, we confirm the spatial uniformity of the collected charge increases with fluence for polycrystalline Chemical Vapor Deposition diamond, and this effect can also be described by a universal curve.

The identification of novel targets for antimicrobial agents is crucial for combating infectious diseases caused by evolving bacterial pathogens. Components of bacterial toxin–antitoxin (TA) systems have been recognized as promising therapeutic targets. These widespread genetic modules are usually composed of two genes that encode a toxic protein targeting an essential cellular process and an antitoxin that counteracts the activity of the toxin. Uncontrolled toxin expression may elicit a bactericidal effect, so they may be considered “intracellular molecular bombs” that can lead to elimination of their host cells. Based on the molecular nature of antitoxins and their mode of interaction with toxins, TA systems have been classified into six groups. The most prevalent are type II TA systems. Due to their ubiquity among clinical isolates of pathogenic bacteria and the essential processes targeted, they are promising candidates for the development of novel antimicrobial strategies. In this review, we describe the distribution of type II TA systems in clinically relevant human pathogens, examine how these systems could be developed as the targets for novel antibacterials, and discuss possible undesirable effects of such therapeutic intervention, such as the induction of persister cells, biofilm formation and toxicity to eukaryotic cells.

Short modified oligonucleotides targeted at bacterial DNA or RNA could serve as antibacterial agents provided that they are efficiently taken up by bacterial cells. However, the uptake of such oligonucleotides is hindered by the bacterial cell wall. To overcome this problem, oligomers have been attached to cell-penetrating peptides, but the efficiency of delivery remains poor. Thus, we have investigated the ability of vitamin B 12 to transport peptide nucleic acid (PNA) oligomers into cells of Escherichia coli and Salmonella Typhimurium. Vitamin B 12 was covalently linked to a PNA oligomer targeted at the mRNA of a reporter gene expressing Red Fluorescent Protein. Cu-catalyzed 1,3-dipolar cycloaddition was employed for the synthesis of PNA-vitamin B 12 conjugates; namely the vitamin B 12 azide was reacted with PNA possessing the terminal alkyne group. Different types of linkers and spacers between vitamin B 12 and PNA were tested, including a disulfide bond. We found that vitamin B 12 transports antisense PNA into E. coli cells more efficiently than the most widely used cell-penetrating peptide (KFF) 3 K. We also determined that the structure of the linker impacts the antisense effect. The results of this study provide the foundation for developing vitamin B 12 as a carrier of PNA oligonucleotides into bacterial cells.

Kinetoplastids are a clade of eukaryotic protozoans that include human parasitic pathogens like trypanosomes and Leishmania species. In these organisms, protein-coding genes are transcribed as polycistronic pre-mRNAs, which need to be processed by the coupled action of trans-splicing and polyadenylation to yield monogenic mature mRNAs. During trans-splicing, a universal RNA sequence, the spliced leader RNA (SL RNA) mini-exon, is added to the 5’-end of each mRNA. The 5’-end of this mini-exon carries a hypermethylated cap structure and is bound by a trypanosomatid-specific cap-binding complex (CBC). The function of three of the kinetoplastid CBC subunits is unknown, but an essential role in cap-binding and trans-splicing has been suggested. Here, we report cryo-EM structures that reveal the molecular architecture of the Trypanosoma brucei CBC ( Tb CBC) complex. We find that Tb CBC interacts with two distinct features of the SL RNA. The Tb CBP20 subunit interacts with the m 7 G cap while Tb CBP66 recognizes double-stranded portions of the SL RNA. Our findings pave the way for future research on mRNA maturation in kinetoplastids. Moreover, the observed structural similarities and differences between Tb CBC and the mammalian cap-binding complex will be crucial for considering the potential of Tb CBC as a target for anti-trypanosomatid drug development. Bernhard et al. reveal the architecture of the tetrameric Trypanosoma brucei nuclear cap-binding complex. Using cryo-electron microscopy and biochemical assays, the researchers characterize its binding to the 5’-cap of the spliced-leader RNA.

The MARIA research reactor is designed and operated as a multipurpose nuclear installation, combining material testing, neutron beam experiments, and medical and industrial radionuclide production, including molybdenum-99 (99Mo). Recently, after fuel conversion to LEU and rejuvenation of the staff while maintaining their experience, MARIA has been used to respond to the increased interest of the scientific community in advanced nuclear power studies, both fission and fusion. In this work, we would like to introduce MARIA’ s capabilities in the irradiation technology field and how it can serve future nuclear research worldwide.

Background/Objectives: Periprocedural blood pressure changes in stroke patients with a large vessel occlusion are a known modifiable risk factor of unfavorable treatment outcomes. We aimed to evaluate the association between pre-revascularization hypotension and the final infarct volume. Methods: In our retrospective analysis, we included 214 consecutive stroke patients with an anterior circulation large vessel occlusion that underwent mechanical thrombectomy under general anesthesia. Noninvasively obtained blood pressure values prior to symptomatic vessel recanalization were analyzed as a predictor of post-treatment infarct size. Linear logistic regression models adjusted for predefined factors were used to investigate the association between blood pressure parameters and the final infarct volume. Results: In our cohort, higher baseline systolic blood pressure (aβ = 8.32, 95% CI 0.93–15.7, p = 0.027), its maximal absolute drop (aβ = 6.98, 95% CI 0.42–13.55, p = 0.037), and >40% mean arterial pressure decrease (aβ = 41.77, CI 95% 1.93–81.61, p = 0.040) were independently associated with higher infarct volumes. Similarly, continuous hypotension measured as intraprocedural cumulative time spent below either 100 mmHg (aβ = 3.50 per 5 min, 95% CI 1.49–5.50, p = 0.001) or 90 mmHg mean arterial pressure (aβ = 2.91 per 5 min, 95% CI 0.74–5.10, p = 0.010) was independently associated with a larger ischemia size. In the subgroup analysis of 151 patients with an M1 middle cerebral artery occlusion, two additional factors were independently associated with a larger ischemia size: systolic blood pressure maximal relative drop and >40% drop from pretreatment value (aβ = 1.36 per 1% lower than baseline, 95% CI 0.04–2.67, p = 0.043, and aβ = 43.01, 95% CI 2.89–83.1, p = 0.036, respectively). No associations between hemodynamic parameters and post-treatment infarct size were observed in the cohort of intracranial internal carotid artery occlusion. Conclusions: In patients with ischemic stroke due to a proximal middle cerebral artery occlusion, higher pre-thrombectomy treatment systolic blood pressure is associated with a larger final infarct size. In patients treated under general anesthesia, hypotension prior to the M1 portion of middle cerebral artery recanalization is independently correlated with the post-treatment infarct volume. In this group, every 5 min spent below the mean arterial pressure threshold of 100 mmHg is associated with a 4 mL increase in ischemia volume on a post-treatment NCCT. No associations between blood pressure and final infarct volume were present in the subgroup of patients with an intracranial internal carotid artery occlusion.

To analyze the patient population diagnosed with transient global amnesia (TGA) concerning their demographic structure, clinical data and results of additional tests performed. Transient global amnesia is a neurological disorder characterized by the sudden onset of temporary memory disturbances, resolving within 24 hours and not accompanied by other focal neurologic symptoms. The pathomechanism of TGA remains unknown. The prognosis is very favorable. Laboratory tests, electroencephalograms or radiologic imaging scans are typically normal. They are usually necessary to exclude alternative diagnoses. The study was a retrospective analysis of 18795 patients hospitalized in the Clinical Provincial Hospital from 1 January 2017 to 30 April 2024. Patients with TGA were identified by searching digital data according to the ICD-10 classification. Each patient met Caplan's criteria (in Walrow and Hodges approach). The analysis considered demographic characteristics: age, gender, comorbidities, preceding factors, the time of illness onset, the results of additional tests [magnetic resonance imaging (MRI) and electroencephalogram (EEG)] and their timing. The study group included 113 patients. Hypertension and lipid disorders were most frequently noted comorbidities. Most common preceding factors were systolic blood pressure above 160 mmHg, (38%), sudden stress-inducing event (13.3%), severe pain (12.4%), physical activity (8.9%). Transient global amnesia episodes occurred most frequently during daytime, between 11 a.m. and 5 p.m. (61 patients, 54%) and 2 patients (1.77%) developed symptoms during nighttime. Magnetic resonance imaging was performed in 83 patients (73.45%). On MRI diffusion weighted imaging (DWI), hippocampal hyperintense areas were found in 15 patients (18.07%). Physical activity and atrial fibrillation were significantly higher in patients with DWI lesions. Electroencephalogram was performed in 102 patients (90.27%). Forty-seven (42%) of them showed abundant and dominant beta rhythm. Approximately one third (n = 39) had no EEG abnormalities. Epileptiform discharges were detected in two cases (1.77%). Abnormal EEG records were significantly higher in patients with present DWI lesions. Transient global amnesia episodes often occur during daily activity, and the main preceding event was an increase in systolic blood pressure above 160 mmHg. Magnetic resonance imaging and EEG tests support the diagnosis. The sensitivity of MRI is higher when performed between 24-96 hours after symptom onset.

INTRODUCTION: Acute ischaemic stroke (AIS) is caused by significant disturbances in the cerebral bloodflow (CBF) that lead to brain ischaemia and eventually result in irreversible brain tissue damage. The main goal of its treatment is to restore bloodflow to the areas at risk of necrosis. Intravenous thrombolysis (IVT) and mechanical thrombectomy (MT) are the mainstay of current therapy, with the latter being widely employed in selected patients with radiologically proven large vessel occlusion (LVO). Despite convincing evidence of its efficacy, up to half of patients undergoing endovascular treatment (EVT) still do not achieve a beneficial functional outcome; this is mainly due to unfavourable brain tissue sequelae. Therefore, factors associated with known adverse brain changes, such as larger infarct size or haemorrhagic and oedematous complications, should be adequately addressed. OBJECTIVE: To review the available literature describing AIS brain tissue outcome assessed by computed tomography (CT) and/ or magnetic resonance imaging (MRI) in patients undergoing MT treatment. Additionally, to evaluate the association of post-MT tissue changes with short- and long-term prognosis. Material and methods. We searched the PubMed, Scopus, EMBASE, and Google Scholar databases according to established criteria. RESULTS: We found a total of 264 articles addressing the most common types of AIS tissue sequelae after EVT (i.e. MT with or without IVT as bridging therapy) by brain CT and MRI. These were: follow-up infarct volume (FIV), cerebral oedema (COD) and haemorrhagic transformation (HT). As the next step, 37 articles evaluating factors associated with defined outcomes were selected. Several non-modifiable factors such as age, comorbidities, pretreatment neurological deficit, and collateral circulation status were found to affect stroke tissue sequelae, to varying degrees. Additionally, some factors including time to treatment initiation, selection of treatment device, and periprocedural systemic blood pressure, the modification of which can potentially reduce the occurrence of an unfavourable tissue outcome, were identified. Some recently revealed biochemical and serological parameters may play a similar role. CONCLUSIONS: The identification of factors that affect post-MT ischaemic area evolution may result in studies assessing the effects of their modification, and potentially improve clinical outcomes. Modifiable parameters, including periprocedural systemic blood pressure and some biochemical factors, may be of particular importance.

Background: Ticks (Acari: Ixodida) pose a serious medical and veterinary threat as vectors of tick-borne pathogens. The wide variety of tick repellents available on the market primarily consist of synthetic preparations that may disrupt the ecological balance and accumulate in the environment, leading to harmful effects on humans and animals. The aim of the study was to develop an ecological preparation based on natural raw materials (biopolymers) with the addition of a mixture of essential oils that act as tick repellents. Methods: The preparations were acquired through the emulsification method, specifically the oil-in-water emulsion technique. The assessment encompassed an analysis of their physicochemical properties, including centrifugal and thermal stability, dynamic viscosity, wetting angle, and conductivity. Additionally, their biodegradation and ecotoxicity profiles were evaluated, as well as their impact on tick behavior. Results: The preparations exhibited stability, rapid biodegradation, and absence of ecotoxicity. Additionally, they had repellent properties against the two tested species of ticks (Ixodes ricinus and Dermacentor reticulatus). Conclusions: Emulsion formulations comprising natural ingredients have significant research potential for combating ticks, thus mitigating the risk of tick-borne diseases in both human and animal populations.