This study presents an exploration of the chemical space around derivatives of 3-benzamidopyrazine-2-carboxamides, previously identified as potent antimycobacterial compounds with predicted binding to mycobacterial prolyl-transfer RNA synthetase. New urea derivatives (Series-1) were generally inactive, probably due to their preference for cis-trans conformation (confirmed by density functional theory calculations and experimentally by nuclear overhauser effect spectroscopy NMR). Series-2 (3-benzamidopyrazine-2-carboxamides with disubstituted benzene ring) demonstrated that substituents larger than fluorine are not tolerated in the ortho position of the benzene ring. This series brought two new compounds (21: R = 2-F, 4-Cl and 22: R = 2-F, 4-Br) with in vitro activity against Mycobacterium tuberculosis H37Rv as well as multidrug-resistant clinical isolates, with minimum inhibitory concentration ranging from 6.25 to 25 μg/mL. The lactone-type derivatives 4H-pyrazino[2,3-d][1,3]oxazin-4-ones (Series-3) were inactive, but solvent stability studies of compound 29 indicated that they might be developed to usable lactone prodrugs of inhibitors of mycobacterial aspartate decarboxylase (PanD).
- MeSH
- aminoacyl-tRNA-synthetasy antagonisté a inhibitory metabolismus MeSH
- antituberkulotika * farmakologie chemie chemická syntéza MeSH
- inhibitory enzymů farmakologie chemie chemická syntéza MeSH
- mikrobiální testy citlivosti * MeSH
- molekulární struktura MeSH
- Mycobacterium tuberculosis * účinky léků enzymologie MeSH
- pyraziny farmakologie chemie chemická syntéza MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: The escalating global prevalence of type 2 diabetes and prediabetes presents a major public health challenge. Physical activity plays a critical role in managing (pre)diabetes; however, adherence to physical activity recommendations remains low. The ENERGISED trial was designed to address these challenges by integrating mHealth tools into the routine practice of general practitioners, aiming for a significant, scalable impact in (pre)diabetes patient care through increased physical activity and reduced sedentary behaviour. METHODS: The mHealth intervention for the ENERGISED trial was developed according to the mHealth development and evaluation framework, which includes the active participation of (pre)diabetes patients. This iterative process encompasses four sequential phases: (a) conceptualisation to identify key aspects of the intervention; (b) formative research including two focus groups with (pre)diabetes patients (n = 14) to tailor the intervention to the needs and preferences of the target population; (c) pre-testing using think-aloud patient interviews (n = 7) to optimise the intervention components; and (d) piloting (n = 10) to refine the intervention to its final form. RESULTS: The final intervention comprises six types of text messages, each embodying different behaviour change techniques. Some of the messages, such as those providing interim reviews of the patients' weekly step goal or feedback on their weekly performance, are delivered at fixed times of the week. Others are triggered just in time by specific physical behaviour events as detected by the Fitbit activity tracker: for example, prompts to increase walking pace are triggered after 5 min of continuous walking; and prompts to interrupt sitting following 30 min of uninterrupted sitting. For patients without a smartphone or reliable internet connection, the intervention is adapted to ensure inclusivity. Patients receive on average three to six messages per week for 12 months. During the first six months, the text messaging is supplemented with monthly phone counselling to enable personalisation of the intervention, assistance with technical issues, and enhancement of adherence. CONCLUSIONS: The participatory development of the ENERGISED mHealth intervention, incorporating just-in-time prompts, has the potential to significantly enhance the capacity of general practitioners for personalised behavioural counselling on physical activity in (pre)diabetes patients, with implications for broader applications in primary care.
Non-thermal plasma (NTP) is a well-known decontamination tool applicable for a wide range of microorganisms and viruses. Since the recent COVID-19 pandemic highlighted the need to decontaminate all daily used items, it is highly desirable to address the applicability of NTP, including its possible harmful effects. To the best of our knowledge, a comprehensive characterization of NTP effects on sensitive materials is still lacking. We investigated the potential damage to common materials of daily use inflicted by air atmospheric NTP generated in Plasmatico v1.0. The materials tested were paper, various metals, and passive and active electronic components modelling sensitive parts of commonly used small electronic devices. The NTP-exposed paper remained fully usable with only slight changes in its properties, such as whitening, pH change, and degree of polymerization. NTP caused mild oxidation of copper, tinned copper, brass, and a very mild oxidation of stainless steel. However, these changes do not affect the normal functionality of these materials. No significant changes were observed for passive electronic components; active components displayed a very slight shift of the measured values observed for the humidity sensor. In conclusion, NTP can be considered a gentle tool suitable for decontamination of various sensitive materials.
- MeSH
- COVID-19 * prevence a kontrola MeSH
- elektronika MeSH
- lidé MeSH
- měď MeSH
- pandemie MeSH
- plazmové plyny * MeSH
- potřeby pro domácnost * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Ants are key ecosystem service providers and can serve as important biological control agents in pest management. However, the effects of insecticides on common farmland ant species are poorly understood. We tested the effects of three commonly used insecticides on ants (Hymenoptera, Formicidae). The tested insecticides were acetamiprid (neonicotinoid; formulated as Mospilan 20 SP), deltamethrin (pyrethroid; formulated as Sanium Ultra), and sulfoxaflor (sulfilimine; formulated as Gondola). We tested two ant (Hymenoptera: Formicidae) species with different colony founding strategies, Lasius niger (Linnaeus, 1758) and Myrmica rubra (Linnaeus, 1758). We sprayed their queens with insecticides at concentrations recommended for use in foliar applications in agriculture, i.e., at 1.25 g L-1 (acetamiprid), 0.6 g L-1 (sulfoxaflor), and 0.875 g L-1 (deltamethrin). Further, we diluted the compounds in distilled water and tested them at 10%, 1%, and 0.1% of the field-recommended concentrations, and used distilled water as a control. We monitored the survival of the queens and the number of eggs laid. All three tested insecticides caused severe lethal and sublethal concentration-dependent effects. Even at concentrations three orders of magnitudes lower than recommended for field applications, significantly lower numbers of eggs were found in the queens' nests. The extent of the sublethal effects of acetamiprid and sulfoxaflor was concentration-dependent and differed between the two ant species. Besides bees and bumblebees, ants represent an important group of hymenopterans that are severely affected even by low concentrations of the tested compounds and therefore should be included in risk assessment schemes.
- MeSH
- ekosystém MeSH
- Formicidae * MeSH
- insekticidy * toxicita MeSH
- neonikotinoidy toxicita MeSH
- včely MeSH
- voda MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: The growing number of patients with type 2 diabetes and prediabetes is a major public health concern. Physical activity is a cornerstone of diabetes management and may prevent its onset in prediabetes patients. Despite this, many patients with (pre)diabetes remain physically inactive. Primary care physicians are well-situated to deliver interventions to increase their patients' physical activity levels. However, effective and sustainable physical activity interventions for (pre)diabetes patients that can be translated into routine primary care are lacking. METHODS: We describe the rationale and protocol for a 12-month pragmatic, multicentre, randomised, controlled trial assessing the effectiveness of an mHealth intervention delivered in general practice to increase physical activity and reduce sedentary behaviour of patients with prediabetes and type 2 diabetes (ENERGISED). Twenty-one general practices will recruit 340 patients with (pre)diabetes during routine health check-ups. Patients allocated to the active control arm will receive a Fitbit activity tracker to self-monitor their daily steps and try to achieve the recommended step goal. Patients allocated to the intervention arm will additionally receive the mHealth intervention, including the delivery of several text messages per week, with some of them delivered just in time, based on data continuously collected by the Fitbit tracker. The trial consists of two phases, each lasting six months: the lead-in phase, when the mHealth intervention will be supported with human phone counselling, and the maintenance phase, when the intervention will be fully automated. The primary outcome, average ambulatory activity (steps/day) measured by a wrist-worn accelerometer, will be assessed at the end of the maintenance phase at 12 months. DISCUSSION: The trial has several strengths, such as the choice of active control to isolate the net effect of the intervention beyond simple self-monitoring with an activity tracker, broad eligibility criteria allowing for the inclusion of patients without a smartphone, procedures to minimise selection bias, and involvement of a relatively large number of general practices. These design choices contribute to the trial's pragmatic character and ensure that the intervention, if effective, can be translated into routine primary care practice, allowing important public health benefits. TRIAL REGISTRATION: ClinicalTrials.gov (NCT05351359, 28/04/2022).
- MeSH
- cvičení MeSH
- diabetes mellitus 2. typu * prevence a kontrola MeSH
- lidé MeSH
- multicentrické studie jako téma MeSH
- pragmatické klinické studie jako téma MeSH
- praktické lékařství * MeSH
- prediabetes * terapie MeSH
- randomizované kontrolované studie jako téma MeSH
- sedavý životní styl MeSH
- telemedicína * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- protokol klinické studie MeSH
Anthropogenic habitats that are contaminated by toxic elements were recently shown to host abundant and diverse assemblages of bees and wasps (Hymenoptera: Aculeata), including numerous threatened species. However, toxic elements adversely affect insect fitness. We address the effects of toxic elements on aculeate inquilines that occupy Lipara lucens-induced galls on the common reed, Phragmites australis. We hypothesized that contamination of potential nesting and feeding habitats is associated with adverse changes in bee and wasp populations that are attracted in these environments. To address this hypothesis, we analyzed the contents of As, Cd, Cu, Pb, Zn, Fe, and S in site-matched samples of soil, reed galls, and crabronid wasp bodies and correlated them with abundance and species richness of aculeate hymenopterans in reed galls and with the number of larvae in nests of the eudominant hymenopteran, Pemphredon fabricii. The common reed was present at all the examined sites, and L. lucens-induced galls were present at all but one sampling site; the single exception was the sampling site with the highest contents of four of the seven analyzed elements. The alpha diversity of gall-associated aculeate inquilines, abundance of P. fabricii, and number of prepupae per nest of P. fabricii were not correlated with the contents of any of the seven analyzed toxic elements. We found P. fabricii to be abundantly present in habitats with extreme concentrations of toxic elements. Exposed P. fabricii accumulated Cd, Cu, and Pb, while they eliminated Fe and Zn. The obtained data did not support the hypothesis that heavy metal contamination of anthropogenic sites affects P. fabricii and other reed gall-associated aculeates.
Azole fungicides have been essential pillars of global food security since the commercialization of triadimefon. However, the potential for fungicides to induce sublethal effects on larval development and emergence from overwintering is underresearched. We hypothesized that contact exposure to field-realistic concentrations of a broad spectrum of triazole fungicides alters the pupation and metamorphosis of crabronid wasps. Therefore, triazole fungicides shape the hymenopteran communities in agrocenoses. We applied field-realistic concentrations of three triazole fungicides, difenoconazole, penconazole, and tebuconazole, to the defecated prepupae of Pemphredon fabricii (Hymenoptera: Crabronidae). We monitored their survival, pupation, and metamorphosis into adults, including the timing of these events. All three tested triazole fungicides altered the time to the metamorphosis into adults of P. fabricii prepupae compared to the vehicle-treated controls. This effect was concentration-independent within the recommended concentration ranges for foliar applications. However, the three triazole fungicides were not associated with any significant declines in overall survival. Thus, the commonly used triazole fungicides affect the synchronization of the metamorphosis into adults with the availability of food and nesting resources of the study species. The study compounds did not affect the survival, which agrees with previous studies of other azole fungicides, which revealed effects on survival only when used in combination with other compounds. Further research should address the multiplicative effects of the triazole fungicides with other agrochemicals on the timing of the metamorphosis of bees and wasps.
- MeSH
- azoly farmakologie MeSH
- biologická proměna MeSH
- fungicidy průmyslové * chemie MeSH
- Hymenoptera * MeSH
- sršňovití * MeSH
- triazoly chemie toxicita MeSH
- včely MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
The current pandemic resulted in a rapidly increasing demand for personal protective equipment (PPE) initially leading to severe shortages of these items. Hence, during an unexpected and fast virus spread, the possibility of reusing highly efficient protective equipment could provide a viable solution for keeping both healthcare professionals and the general public equipped and protected. This requires an efficient decontamination technique that preserves functionality of the sensitive materials used for PPE production. Non-thermal plasma (NTP) is a decontamination technique with documented efficiency against select bacterial and fungal pathogens combined with low damage to exposed materials. We have investigated NTP for decontamination of high-efficiency P3 R filters from viral respiratory pathogens in comparison to other commonly used techniques. We show that NTP treatment completely inactivates SARS-CoV-2 and three other common human respiratory viruses including Influenza A, Rhinovirus and Adenovirus, revealing an efficiency comparable to 90°C dry heat or UVC light. Unlike some of the tested techniques (e.g., autoclaving), NTP neither influenced the filtering efficiency nor the microstructure of the filter. We demonstrate that NTP is a powerful and economic technology for efficient decontamination of protective filters and other sensitive materials from different respiratory pathogens.
- Publikační typ
- časopisecké články MeSH
AIMS: A reduction of habitual physical activity due to prolonged COVID-19 quarantine can have serious consequences for patients with cardiovascular diseases, such as heart failure. This study aimed to explore the effect of COVID-19 nationwide quarantine on accelerometer-assessed physical activity of heart failure patients. METHODS AND RESULTS: We analysed the daily number of steps in 26 heart failure patients during a 6-week period that included 3 weeks immediately preceding the onset of the quarantine and the first 3 weeks of the quarantine. The daily number of steps was assessed using a wrist-worn accelerometer worn by the patients as part of an ongoing randomized controlled trial. Multilevel modelling was used to explore the effect of the quarantine on the daily step count adjusted for weather conditions. As compared with the 3 weeks before the onset of the quarantine, the step count was significantly lower during each of the first 3 weeks of the quarantine (P < 0.05). When the daily step count was averaged across the 3 weeks before and during the quarantine, the decrease amounted to 1134 (SE 189) steps per day (P < 0.001), which translated to a 16.2% decrease. CONCLUSIONS: The introduction of the nationwide quarantine due to COVID-19 had a detrimental effect on the level of habitual physical activity in heart failure patients, leading to an abrupt decrease of daily step count that lasted for at least the 3-week study period. Staying active and maintaining sufficient levels of physical activity during the COVID-19 pandemic are essential despite the unfavourable circumstances of quarantine.
- MeSH
- akcelerometrie metody MeSH
- časové faktory MeSH
- COVID-19 MeSH
- cvičení fyziologie MeSH
- dospělí MeSH
- hodnocení rizik MeSH
- karanténa * MeSH
- kohortové studie MeSH
- koronavirové infekce epidemiologie prevence a kontrola MeSH
- lidé středního věku MeSH
- lidé MeSH
- pandemie prevence a kontrola statistika a číselné údaje MeSH
- prognóza MeSH
- retrospektivní studie MeSH
- senioři MeSH
- srdeční selhání patofyziologie rehabilitace MeSH
- tělesná výkonnost fyziologie MeSH
- test chůzí statistika a číselné údaje MeSH
- virová pneumonie epidemiologie prevence a kontrola MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
It is known that tetraspanin proteins are involved in many physiological somatic cell mechanisms. Additionally, research has indicated they also have a role in various infectious diseases and cancers. This review focuses on the molecular interactions underlying the tetraspanin web formation in gametes. Primarily, tetraspanins act in the reproductive tract as organizers of membrane complexes, which include the proteins involved in the contact and association of sperm and oocyte membranes. In addition, recent data shows that tetraspanins are likely to be involved in these processes in a complex way. In mammalian fertilization, an important role is attributed to CD molecules belonging to the tetraspanin superfamily, particularly CD9, CD81, CD151, and also CD63; mostly as part of extracellular vesicles, the significance of which and their potential in reproduction is being intensively investigated. In this article, we reviewed the existing knowledge regarding the expression of tetraspanins CD9, CD81, CD151, and CD63 in mammalian spermatozoa, oocytes, and embryos and their involvement in reproductive processes, including pathological events.
- MeSH
- embryonální vývoj MeSH
- lidé MeSH
- oocyty fyziologie MeSH
- rozmnožování * MeSH
- savci fyziologie MeSH
- spermie fyziologie MeSH
- tetraspaniny fyziologie MeSH
- zvířata MeSH
- zygota fyziologie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
