Direct pathway striatal projection neurons (dSPNs) are characterized by the expression of dopamine (DA) class 1 receptors (D1R), as well as cholinergic muscarinic M1 and M4 receptors (M1R, M4R). D1R ...enhances neuronal firing through phosphorylation of voltage‐gate calcium channels (CaV1 Ca2+ channels) activating Gs proteins and protein kinase A (PKA). Concurrently, PKA suppresses phosphatase PP‐1 through DARPP‐32, thus extending this facilitatory modulation. M1R also influences Ca2+ channels in SPNs through Gq proteins and protein kinase C. However, the signaling mechanisms of M4R in dSPNs are less understood. Two pathways are attributed to M4R: an inhibitory one through Gi/o proteins, and a facilitatory one via the cyclin Cdk5. Our study reveals that a previously observed facilitatory modulation via CaV1 Ca2+ channels is linked to the Cdk5 pathway in dSPNs. This result could be significant in treating parkinsonism. Therefore, we questioned whether this effect persists post DA‐depletion in experimental parkinsonism. Our findings indicate that in such conditions, M4R activation leads to a decrease in Ca2+ current and an increased M4R protein level, contrasting with the control response. Nevertheless, parkinsonian and control actions are inhibited by the Cdk5 inhibitor roscovitine, suggesting Cdk5's role in both conditions. Cdk5 may activate PP‐1 via PKA inhibition in DA depletion. Indeed, we found that inhibiting PP‐1 restores control M4R actions, implying that PP‐1 is overly active via M4Rs in DA‐depleted condition. These insights contribute to understanding how DA‐depletion alters modulatory signaling in striatal neurons. Additional working hypotheses are discussed.
Activation of muscarinic M4 receptors in direct striatal projection neurons increases calcium current in control neurons and decreases it in neurons depleted of dopamine. It is proposed that both actions are mediated by Cdk5 because they are both blocked by roscovitine. In control neurons dopamine is present to activate the PKA pathway enhancing calcium current and depressing PP‐1. In dopamine depleted conditions dopamine is not prfesent and there is hypercholinergia with over activation of Cdk5 via M4 receptors. This action further inhibits PKA and disinhibits PP‐1 decreasing calcium current. The inhibition of PP‐1 reverses this action.
Healthcare professionals (HCPs) on the front lines against COVID-19 may face increased workload and stress. Understanding HCPs' risk for burnout is critical to supporting HCPs and maintaining the ...quality of healthcare during the pandemic.
To assess exposure, perceptions, workload, and possible burnout of HCPs during the COVID-19 pandemic we conducted a cross-sectional survey. The main outcomes and measures were HCPs' self-assessment of burnout, indicated by a single item measure of emotional exhaustion, and other experiences and attitudes associated with working during the COVID-19 pandemic.
A total of 2,707 HCPs from 60 countries participated in this study. Fifty-one percent of HCPs reported burnout. Burnout was associated with work impacting household activities (RR = 1·57, 95% CI = 1·39-1·78, P<0·001), feeling pushed beyond training (RR = 1·32, 95% CI = 1·20-1·47, P<0·001), exposure to COVID-19 patients (RR = 1·18, 95% CI = 1·05-1·32, P = 0·005), and making life prioritizing decisions (RR = 1·16, 95% CI = 1·02-1·31, P = 0·03). Adequate personal protective equipment (PPE) was protective against burnout (RR = 0·88, 95% CI = 0·79-0·97, P = 0·01). Burnout was higher in high-income countries (HICs) compared to low- and middle-income countries (LMICs) (RR = 1·18; 95% CI = 1·02-1·36, P = 0·018).
Burnout is present at higher than previously reported rates among HCPs working during the COVID-19 pandemic and is related to high workload, job stress, and time pressure, and limited organizational support. Current and future burnout among HCPs could be mitigated by actions from healthcare institutions and other governmental and non-governmental stakeholders aimed at potentially modifiable factors, including providing additional training, organizational support, and support for family, PPE, and mental health resources.
Cereals (rice, maize, wheat, sorghum and the millets) provide over 50% of the world’s caloric intake, a value that rises to > 80% in developing countries. Since domestication, cereals have been under ...artificial selection, largely directed towards higher yield. Throughout this process, cereals have maintained their capacity to interact with arbuscular mycorrhizal (AM) fungi, beneficial symbionts that associate with the roots of most terrestrial plants. It has been hypothesized that the shift from the wild to cultivation, and above all the last c. 50 years of intensive breeding for high-input farming systems, has reduced the capacity of the major cereal crops to gain full benefit from AM interactions. Recent studies have shed further light on the molecular basis of establishment and functioning of AM symbiosis in cereals, providing insight into where the breeding process might have had an impact. Classic phytohormones, targets of artificial selection during the generation of Green Revolution semi-dwarf varieties, have emerged as important regulators of AM symbiosis. Although there is still much to be learnt about the mechanistic basis of variation in symbiotic outcome, these advances are providing an insight into the role of arbuscular mycorrhiza in agronomic systems.
The prospects of achieving regeneration in the central nervous system (CNS) have changed, as most recent findings indicate that several species, including humans, can produce neurons in adulthood. ...Studies targeting this property may be considered as potential therapeutic strategies to respond to injury or the effects of demyelinating diseases in the CNS. While CNS trauma may interrupt the axonal tracts that connect neurons with their targets, some neurons remain alive, as seen in optic nerve and spinal cord (SC) injuries (SCIs). The devastating consequences of SCIs are due to the immediate and significant disruption of the ascending and descending spinal pathways, which result in varying degrees of motor and sensory impairment. Recent therapeutic studies for SCI have focused on cell transplantation in animal models, using cells capable of inducing axon regeneration like Schwann cells (SchCs), astrocytes, genetically modified fibroblasts and olfactory ensheathing glia cells (OECs). Nevertheless, and despite the improvements in such cell‐based therapeutic strategies, there is still little information regarding the mechanisms underlying the success of transplantation and regarding any secondary effects. Therefore, further studies are needed to clarify these issues. In this review, we highlight the properties of OECs that make them suitable to achieve neuroplasticity/neuroregeneration in SCI. OECs can interact with the glial scar, stimulate angiogenesis, axon outgrowth and remyelination, improving functional outcomes following lesion. Furthermore, we present evidence of the utility of cell therapy with OECs to treat SCI, both from animal models and clinical studies performed on SCI patients, providing promising results for future treatments.
Main Points
OECs ontogeny, physiological, morphological and molecular characteristics.
OECs properties making them suitable for neuroplasticity/neuroregeneration in SCI.
Promising results of OECs cell therapy for SCI (animal models and clinical studies).
•Self-healing is analyzed by permeability and crack closing in concrete specimens.•Self-healing has been compared for two concrete classes healing underwater.•Healing has been evaluated under water ...immersion at 15°C, 30°C and wet/dry cycles.•The results are compared with previous tests, comparing a total of six exposures.
This paper analyzes the self-healing properties of early-age concretes, engineered using a crystalline admixture (4% by the weight of cement), by measuring the permeability of cracked specimens and their crack width. Two concrete classes (C30/37 and C45/55) and three healing exposure conditions have been investigated: water immersion at 15°C, at 30°C and wet/dry cycles. Specimens were pre-cracked at 2days, to values of crack width in the range of 0.10–0.40mm. The results show almost perfect healing capability for specimens healed under water at 30°C, better than for specimens healed under water at 15°C, while insufficient for the wet/dry exposure.
Fluorine, chlorine, bromine, and iodine have been studied in biological samples and other related matrices owing to the need to understand the biochemical effects in living organisms. In this review, ...the works published in last 20 years are covered, and the main topics related to sample preparation methods and analytical techniques commonly used for fluorine, chlorine, bromine, and iodine determination in biological samples, food, drugs, and plants used as food or with medical applications are discussed. The commonest sample preparation methods, as extraction and decomposition using combustion and pyrohydrolysis, are reviewed, as well as spectrometric and electroanalytical techniques, spectrophotometry, total reflection X-ray fluorescence, neutron activation analysis, and separation systems using chromatography and electrophoresis. On this aspect, the main analytical challenges and drawbacks are highlighted. A discussion related to the availability of certified reference materials for evaluation of accuracy is also included, as well as a discussion of the official methods used as references for the determination of halogens in the samples covered in this review.
Figure
Methods commonly used for determination of F, Cl, Br, and I in samples relevant to bioanalytical sciences
Generation Z nursing students have a distinctive combination of attitudes, beliefs, social norms, and behaviors that will modify education and the nursing profession. This cross-sectional research ...study aimed to explore the social media use and characteristics of Generation Z in nursing students and to identify what were the most useful and preferred teaching methods during clinical training. Participants were Generation Z nursing degree students from a Spanish Higher Education Institution. A 41-item survey was developed and validated by an expert panel. The consecutive sample consisted of 120 students. Participants used social media for an average of 1.37 h (SD = 1.15) for clinical learning. They preferred, as teaching methods, linking mentorship learning to clinical experiences (x¯ = 3.51, SD = 0.88), online tutorials or videos (x¯ = 3.22, SD = 0.78), interactive gaming (x¯ = 3.09, SD = 1.14), and virtual learning environments (x¯ = 3, SD = 1.05). Regarding generational characteristics, the majority either strongly agreed or agreed with being high consumers of technology and cravers of the digital world (90.1%,
= 108 and 80%,
= 96). The authors consider it essential to expand our knowledge about the usefulness or possible use of teaching methods during clinical learning, which is essential at this moment because of the rapidly changing situation due to the Covid-19 pandemic.
SARS‐CoV‐2 infection has produced high mortality in kidney transplant (KT) recipients, especially in the elderly. Until December 2020, 1011 KT with COVID‐19 have been prospectively included in the ...Spanish Registry and followed until recovery or death. In multivariable analysis, age, pneumonia, and KT performed ≤6 months before COVID‐19 were predictors of death, whereas gastrointestinal symptoms were protective. Survival analysis showed significant increasing mortality risk in four subgroups according to recipient age and time after KT (age <65 years and posttransplant time >6 months, age <65 and time ≤6, age ≥65 and time >6 and age ≥65 and time ≤6): mortality rates were, respectively, 11.3%, 24.5%, 35.4%, and 54.5% (p < .001). Patients were significantly younger, presented less pneumonia, and received less frequently specific anti‐COVID‐19 treatment in the second wave (July–December) than in the first one (March–June). Overall mortality was lower in the second wave (15.1 vs. 27.4%, p < .001) but similar in critical patients (66.7% vs. 58.1%, p = .29). The interaction between age and time post‐KT should be considered when selecting recipients for transplantation in the COVID‐19 pandemic. Advanced age and a recent KT should foster strict protective measures, including vaccination.
Older recipients diagnosed with COVID‐19 in the first 6 months after transplantation present the highest risk for a fatal outcome during the second wave of the COVID‐19 pandemic.
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