How do meteorological conditions impact the effectiveness of various traffic measures on NOx concentrations in a real hot-spot?

Recently, air quality has become a major concern for policy makers around the world, which has led to the implementation of mitigation measures. In particular, in urban areas most measures affect the road transport sector, as this is one of the main contributors to air pollution in those areas. Recent studies have pointed out the need to determine the importance of external factors such as the meteorological conditions on the net effect on air quality of mitigation strategies. Due to the strong spatial variability of urban air pollution, high spatial resolution modelling is necessary. In this work, the impacts on emissions and nitrogen oxides (NOx) concentrations of several mitigation strategies on a real air pollution hot spot in southern Madrid (Spain) are simulated at microscale under different meteorological conditions. The results show that the meteorological conditions affect local NOx concentrations, and its net changes can be comparable to those due to emission reductions. In particular, meteorological conditions in 2019 induced higher NOx concentrations than in 2016, despite the local emissions were reduced by 50 % from 2016 to 2019. On the other hand, the impact of the implementation of a Low Emissions Zone (LEZ) on NOx concentrations is small and consistent with values found in other LEZs around Europe. However, this impact varies up to 70 % depending on the meteorological conditions. The impacts of a mitigation strategy are largely influenced by the meteorological conditions, and therefore the achievement of the target reduction of concentrations pursued by these measures will depend on the meteorological conditions.

Is chemodenervation with incobotulinumtoxinA an alternative to invasive chronic anal fissure treatments?

BACKGROUND: Botulinum toxin type A is currently strongly recommended for the treatment of anal fissures (AFs). However, there is still no consensus on dosage or injection technique. This study provides further efficacy and safety evidence in a 2-year follow-up. METHOD: Prospective, open-label, single-arm, single-center study carried out in adult patients with AFs non-responsive to previous treatments. Patients were treated with incobotulinumtoxinA (incoBoNT/A) injected in both laterals and posterior intersphincteric groove. Healing rate at 2 years was the primary endpoint. Secondary endpoints included internal anal sphincter pressures, incontinence, and safety. RESULTS: A total of 49 patients were treated with a mean incoBoNT/A dose of 40.5 U (spread across three locations). Healing rate at 2 years was 83.9% with a 24.5% of recurrence throughout the study. Only 7 patients (14.3%) reported adverse events (AEs) that were mild and temporary. Mean reduction in anal resting pressure was -9.1 mmHg at 3 months (p = 0.001). Mean reduction in voluntary squeeze pressure was -27.5 mmHg at 3 months (p < 0.001). Mean pain perception measured with a visual analog scale decreased by -6.5 points at 2 years (p < 0.001). There was an incontinence increase at 1 month of 1.3 points (p = 0.006), but baseline values were restored at 6 months. CONCLUSION: We present results that support the use of incoBoNT/A as a second line for AFs that do not respond to ointment therapy. IncoBoNT/A injection is a less invasive treatment that should be considered before surgery due to its efficacy and its safety which includes no permanent impairment. TRIAL REGISTRATION: ISRCTN90354265; Registered on 16th February 2024. Retrospectively registered.

Comprehensive analysis of ordering in CoCrNi and CrNi2 alloys.

Chemical Short-Range Order (CSRO) has attracted recent attention from many researchers, creating intense debates about its impact on material properties. The challenges lie in confirming and quantifying CSRO, as its detection proves exceptionally demanding, contributing to conflicting data in the literature regarding its true effects on mechanical properties. Our work uses high-precision calorimetric data to unambiguously prove the existence and, coupled with atomistic simulations, quantify the type of CSRO. This methodology allows us to propose a mechanism for its formation and destruction based on the heat evolution during thermal analysis and facilitates a precise identification of local ordering in CoCrNi alloys. Samples of CoCrNi (Co33Cr33Ni33) and CrNi2 (Cr33Ni66) alloys are fabricated in varying ordered states, extensively characterized via synchrotron X-ray diffraction, X-ray absorption spectroscopy, and transmission electron microscopy. Samples with considerably different ordered states are submitted to tensile tests with in-situ synchrotron X-ray diffraction. We demonstrate, despite inducing varied CSRO levels in CoCrNi, no significant alterations in overall mechanical behavior emerge. However, the CrNi2 alloy, which undergoes long-range ordering, experiences significant shifts in yield strength, ultimate tensile stress and ductility.

Insights into the baseline blood pH homeostasis at admission and the risk of in-hospital mortality in COVID-19 patients.

Aim: A laboratory finding in critically ill COVID-19 patients is blood academia (pH <7.35). We investigated its cause in connection with the admission baseline blood pH homeostasis.Patients & methods: We retrospectively monitored the baseline blood pH homeostasis of 1215 COVID-19 patients who were admitted with pneumonia using data-driven knowledge. Two categories of patients were identified: non-survivors (107) and survivors (1108).Results: Non-survivors showed greater levels of lactate and lower blood pH, saturation, and partial pressure of oxygen than survivors. A bivariate Spearman's correlation matrix showed that the [HCO3-]/pCO2 and pCO2 of non-survivors exhibited an unmatched connection, but not in the survivor group. When comparing non-survivors to survivors, the dendrograms derived from the bivariate comparison matrix showed differences in gasometry parameters like blood pH, [HCO3-]/pCO2 ratio, anion gap and pO2.Conclusion: The little variations in the gasometry readings between survivors and non-survivors upon admission suggested abnormal changes in the complementary renal and respiratory systems that bring blood pH back to normal. In advanced COVID-19, modest blood acid-base imbalances could become blood acidemia if these compensatory strategies were overused. Data-driven monitoring of acid-base parameters may help predict abnormal blood pH and the advancement of metabolic acidemia before it is too late.

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Floral resource availability declines and florivory increases along an elevation gradient in a highly biodiverse community.

BACKGROUND AND AIMS: Flower-visitor interactions comprise a continuum of behaviors, from mutualistic partners to antagonistic visitors. Despite being relatively frequent in natural communities, florivory remains unexplored, especially when comprising abiotic factors, spatio-temporal variations and global environmental changes. Here, we addressed the variation of florivory driven by changes in elevation and temporal flower availability. We expect decreased floral resources as elevation increases -due to environmental constraints- which may affect plant-florivore interactions. Yet, if floral resources decrease but florivores remain constant, then we may expect an increase in florivory with increasing elevation in the community. METHODS: The flowering phenology of plant individuals was recorded in the Neotropical campo rupestre vegetation, in southeastern Brazil. Damages by florivores were recorded in plots at elevations ranging from 823 to 1411 m using two response variables as a proxy for florivory: the proportion of attacked flowers per plant and the proportion of petal removal on single flowers. KEY RESULTS: Flower attack increased with elevation and damages were intensified in species with longer flowering periods. Conversely, longer flowering periods resulted in higher levels of petal removal when decreasing elevation. The temporal availability of flowers affected florivory, with the proportion of attacked flowers being more intense when there are less flowered individuals in the community. Petal removal on single flowers was intensified in plots with a larger number of individuals flowering, and with more species co-flowering. CONCLUSIONS: This study brings one of the broadest records of a commonly neglected interaction of insects feeding on floral structures, quantifying the combined effect of floral display and availability along an elevation gradient in a highly biodiverse mountaintop community. These findings contribute to filling in the gap in the understanding of florivory dynamics, focusing on a tropical mountaintop scenario facing imminent environmental changes and excessive natural resource exploitation.

Differential Mitochondrial Bioenergetics in Neurons and Astrocytes Following Ischemia-Reperfusion Injury and Hypothermia.

The close interaction between neurons and astrocytes has been extensively studied. However, the specific behavior of these cells after ischemia-reperfusion injury and hypothermia remains poorly characterized. A growing body of evidence suggests that mitochondria function and putative transference between neurons and astrocytes may play a fundamental role in adaptive and homeostatic responses after systemic insults such as cardiac arrest, which highlights the importance of a better understanding of how neurons and astrocytes behave individually in these settings. Brain injury is one of the most important challenges in post-cardiac arrest syndrome, and therapeutic hypothermia remains the single, gold standard treatment for neuroprotection after cardiac arrest. In our study, we modeled ischemia-reperfusion injury by using in vitro enhanced oxygen-glucose deprivation and reperfusion (eOGD-R) and subsequent hypothermia (HPT) (31.5 °C) to cell lines of neurons (HT-22) and astrocytes (C8-D1A) with/without hypothermia. Using cell lysis (LDH; lactate dehydrogenase) as a measure of membrane integrity and cell viability, we found that neurons were more susceptible to eOGD-R when compared with astrocytes. However, they benefited significantly from HPT, while the HPT effect after eOGD-R on astrocytes was negligible. Similarly, eOGD-R caused a more significant reduction in adenosine triphosphate (ATP) in neurons than astrocytes, and the ATP-enhancing effects from HPT were more prominent in neurons than astrocytes. In both neurons and astrocytes, measurement of reactive oxygen species (ROS) revealed higher ROS output following eOGD-R, with a non-significant trend of differential reduction observed in neurons. HPT after eOGD-R effectively downregulated ROS in both cells; however, the effect was significantly more effective in neurons. Lipid peroxidation was higher after eOGD-R in neurons, while in astrocytes, the increase was not statistically significant. Interestingly, HPT had similar effects on the reduction in lipoperoxidation after eOGD-R with both types of cells. While glutathione (GSH) levels were downregulated after eOGD-R in both cells, HPT enhanced GSH in astrocytes, but worsened GSH in neurons. In conclusion, neuron and astrocyte cultures respond differently to eOGD-R and eOGD-R + HTP treatments. Neurons showed higher sensitivity to ischemia-reperfusion insults than astrocytes; however, they benefited more from HPT therapy. These data suggest that given the differential effects from HPT in neurons and astrocytes, future therapeutic developments could potentially enhance HPT outcomes by means of neuronal and astrocytic targeted therapies.

Healable Supracolloidal Nanocomposite Water-Borne Coatings.

Water-borne coatings often contain nanofillers to enhance their mechanical or optical properties. The aggregation of these fillers may, however, lead to undesired effects such as brittle and opaque coatings, reducing their performance and lifetime. By controlling the distribution and structural arrangement of the nanofillers in the coatings and inserting reversible chemical bonds, both the elasticity and strength of the coatings may be effectively improved, while healing properties, via the reversible chemistry, extend the coating's lifetime. Aqueous dispersions of polymer-core/silica-corona supracolloidal particles were used to prepare water-borne coatings. Polymer and silica nanoparticles were prefunctionalized with thiol/disulfide groups during the supracolloid assembly. Disulfide bridges were further established between a cross-linker and the supracolloids during drying and coating formation. The supracolloidal nanocomposite coatings were submitted to intentional (physical) damages, i.e., blunt and sharp surface scratches or cut through into two pieces, and subsequently UV irradiated to induce the recovery of the damage(s). The viscoelasticity and healing properties of the coatings were examined by dynamic, static, and surface mechanical analyses. The nanocomposite coatings showed a great extent of interfacial restoration of cut damage and surface scratches. The healing properties are strongly related to the coating's viscoelasticity and interfacial (re)activation of the disulfide bridges. Nanocomposite coatings with silica concentrations below their critical volume fraction show higher in situ healing efficiency, as compared to coatings with higher silica concentration. This work provides insights into the control of nanofillers distribution in water-borne coatings and strategies to increase the coating lifetime via mechanical damage recovery.

Rhythms in lipid droplet content driven by a metabolic oscillator are conserved throughout evolution.

The biological clock in eukaryotes controls daily rhythms in physiology and behavior. It displays a complex organization that involves the molecular transcriptional clock and the redox oscillator which may coordinately work to control cellular rhythms. The redox oscillator has emerged very early in evolution in adaptation to the environmental changes in O2 levels and has been shown to regulate daily rhythms in glycerolipid (GL) metabolism in different eukaryotic cells. GLs are key components of lipid droplets (LDs), intracellular storage organelles, present in all living organisms, and essential for energy and lipid homeostasis regulation and survival; however, the cell bioenergetics status is not constant across time and depends on energy demands. Thus, the formation and degradation of LDs may reflect a time-dependent process following energy requirements. This work investigated the presence of metabolic rhythms in LD content along evolution by studying prokaryotic and eukaryotic cells and organisms. We found sustained temporal oscillations in LD content in Pseudomonas aeruginosa bacteria and Caenorhabditis elegans synchronized by temperature cycles, in serum-shock synchronized human embryonic kidney cells (HEK 293 cells) and brain tumor cells (T98G and GL26) after a dexamethasone pulse. Moreover, in synchronized T98G cells, LD oscillations were altered by glycogen synthase kinase-3 (GSK-3) inhibition that affects the cytosolic activity of the metabolic oscillator or by knocking down LIPIN-1, a key GL synthesizing enzyme. Overall, our findings reveal the existence of metabolic oscillations in terms of LD content highly conserved across evolutionary scales notwithstanding variations in complexity, regulation, and cell organization.

Optical projection tomography implemented for accessibility and low cost (OPTImAL).

Optical projection tomography (OPT) is a three-dimensional mesoscopic imaging modality that can use absorption or fluorescence contrast, and is widely applied to fixed and live samples in the mm-cm scale. For fluorescence OPT, we present OPT implemented for accessibility and low cost, an open-source research-grade implementation of modular OPT hardware and software that has been designed to be widely accessible by using low-cost components, including light-emitting diode (LED) excitation and cooled complementary metal-oxide-semiconductor (CMOS) cameras. Both the hardware and software are modular and flexible in their implementation, enabling rapid switching between sample size scales and supporting compressive sensing to reconstruct images from undersampled sparse OPT data, e.g. to facilitate rapid imaging with low photobleaching/phototoxicity. We also explore a simple implementation of focal scanning OPT to achieve higher resolution, which entails the use of a fan-beam geometry reconstruction method to account for variation in magnification. This article is part of the Theo Murphy meeting issue 'Open, reproducible hardware for microscopy'.

Tropical grass digestibility assessed by the mobile bag and in vitro methods in horses.

This study aimed to compare the digestibility of tropical grasses by horses by the in vivo method using mobile nylon bags with the in vitro digestibility method using horse feces as a source of inoculum. Five horses were used in a 2 × 5 factorial design with randomized blocks featuring two methods (in vivo and in vitro) and five grasses: Tifton 85 hay (Cynodon spp.), sixweeks threeawn grass (Aristida adsencionis, Linn), Alexandergrass (Brachiaria plantaginea (Link) Hitchc.), capim-de-raiz (Chloris orthonoton, Doell), and Sabi grass (Urochloa mosambicensis). No difference (P>0.05) was found between the in vivo and in vitro methods regarding nutrient digestibility of Sabi grass and sixweeks threeawn. Tifton 85 was the only grass that showed differences (P<0.05) between the two methods concerning the apparent digestibility of all nutrients. Alexandergrass, Tifton 85, and capim-de-raiz exhibited the best digestibility of dry matter, neutral detergent fiber, acid detergent fiber, and organic matter by the mobile bag method compared to the in vitro method. Tifton 85 and capim-de-raiz had higher crude protein digestibility by the mobile bag method than by the in vitro method. The mean retention time of the mobile bags in the digestive tract of the horses was 43.69 h. The bags with samples of sixweeks threeawn and Sabi grass had shorter retention times than capim-de-raiz and Alexandergrass (P<0.0001). It is concluded that, for sixweeks threeawn and Sabi grass, digestibility in horses can be assessed using the in vitro method in place of the mobile nylon bag method.

Role of Molecular Water Layer State on Freezing Front Propagation Rate and Mode Studied with Thermal Imaging.

In this work, we study the relationship between the molecular water layer (MWL) and frost freezing onset and propagation. The progression of frost has been reported to be governed by various localized icing phenomena, including interdroplet ice bridging, dry zones, and frost halos. Reports studying the state of water on surfaces have revealed the presence of a thin nanometer water layer on a range of surfaces. Regardless of further investigations that show environmental humidity, temperature, and surface energy to affect the thickness of the MWL on surfaces, the influence of the MWL on frost nucleation and propagation has not yet been previously addressed in the literature. To study the effect of the MWL on surface freezing events, a range of surface-functionalized glass substrates were prepared. In situ monitoring of freezing events with thermal imaging allowed studying the effect of surface chemistry and environmental relative humidity (RH) on the thickness and continuity of the MWL. We argue that the observed icing nucleation and propagation kinetics are directly related to the presence and continuity of the MWL, which can be manipulated by controlling the environmental humidity and surface chemistry.

Pharmacological Modulation of the Cytosolic Oscillator Affects Glioblastoma Cell Biology.

The circadian system is a conserved time-keeping machinery that regulates a wide range of processes such as sleep/wake, feeding/fasting, and activity/rest cycles to coordinate behavior and physiology. Circadian disruption can be a contributing factor in the development of metabolic diseases, inflammatory disorders, and higher risk of cancer. Glioblastoma (GBM) is a highly aggressive grade 4 brain tumor that is resistant to conventional therapies and has a poor prognosis after diagnosis, with a median survival of only 12-15 months. GBM cells kept in culture were shown to contain a functional circadian oscillator. In seeking more efficient therapies with lower side effects, we evaluated the pharmacological modulation of the circadian clock by targeting the cytosolic kinases glycogen synthase kinase-3 (GSK-3) and casein kinase 1 ε/δ (CK1ε/δ) with specific inhibitors (CHIR99021 and PF670462, respectively), the cryptochrome protein stabilizer (KL001), or circadian disruption after Per2 knockdown expression in GBM-derived cells. CHIR99021-treated cells had a significant effect on cell viability, clock protein expression, migration, and cell cycle distribution. Moreover, cultures exhibited higher levels of reactive oxygen species and alterations in lipid droplet content after GSK-3 inhibition compared to control cells. The combined treatment of CHIR99021 with temozolomide was found to improve the effect on cell viability compared to temozolomide therapy alone. Per2 disruption affected both GBM migration and cell cycle progression. Overall, our results suggest that pharmacological modulation or molecular clock disruption severely affects GBM cell biology.

Design of Wearable Textile Electrodes for the Monitorization of Patients with Heart Failure.

Heart failure is a severe medical condition with an important worldwide incidence that occurs when the heart is unable to efficiently pump the patient's blood throughout the body. The monitoring of edema in the lower limbs is one of the most efficient ways to control the evolution of the condition. Impedance spectroscopy has been proposed as an efficient technique to monitor body volume in patients with heart failure. It is necessary to research new wearable devices for remote patient monitoring, which can be easily worn by patients in a continuous way. In this work, we design and implement new wearable textile electrodes for the monitoring of edema evolution in patients with heart failure. Impedance spectroscopy measurements were carried out in 5 healthy controls and 2 patients with heart failure using our wearable electrodes for 3 days. The results show the appropriateness of impedance spectroscopy and our wearable electrodes to monitor body volume evolution. Impedance spectroscopy is shown to be an efficient marker of the presence of edema in heart failure patients. Initial patient positive feedback was obtained for the use of the wearable device.

"An app is just available at all times"-the process and outcomes of converting the Georgia Tuberculosis Reference Guide into a mobile application.

BACKGROUND: The physical, paper-based Georgia TB Reference Guide has served as the clinical reference handbook on tuberculosis (TB) diagnostic and treatment guidelines for the state of Georgia in the United States. Supported by the Georgia Department of Public Health, the production of the 112-page palm-sized booklet was previously led by a team of Georgia-based TB experts at Emory University and printed every three-five years with updates to clinical management guidelines and TB consult contact information. However, the costs associated with editorial printing combined with delays in updating a static printed booklet with revised guidance hampered the utility of the tool. Considering the barriers with paper-based production and based on the beneficial use of apps to support the dissemination of clinical management guidance in other settings, the booklet was converted into a mobile application. This paper describes the process of developing a mobile app version of the Georgia TB Reference Guide in an easy-to-update and readily available format. METHODS: We employed a user-centered design approach to develop the app, including a series of qualitative interviews and quantitative surveys. Participants included a mix of state officials and local TB experts. First, initial foundational interviews were conducted to conceptualize current utilization practices of both the paper and PDF versions of the tool. Second, the findings from the initial interviews were organized thematically and informed the design of the app, which was then beta tested by a round of previously unsampled TB experts as well as a re-sample from the initial interviews. Third, the designs were coded into developmental phases and beta tested among users of the current Georgia TB Reference Guide. Fourth, the app was published and downloaded by a pre-selected group of local users who provided answers to a follow-up survey after using the app for one month. Fifth, user growth, self-reported demographics, and app usage between February and July 2022 were recorded through automatic data metrics built into the app. RESULTS: The paper copy Georgia TB Reference Guide usage themes included commonly referenced content, navigation paths, and desired features and content. The themes were converted into features and designs such as prioritizing commonly reviewed topics and guide customization with bookmarks and notes. Iterations of the designs were driven by feedback from TB experts and included home page featured content, improving content readability, and improving the search feature. The follow-up survey revealed a 90% preference for the app over the paper version of the guide. In the six months following the app's release, the app was downloaded by 281 individuals in the United States. The majority of downloads were in Georgia and the app also expanded organically to 19 other states. CONCLUSION: The experience of converting the Georgia TB Reference Guide offers specific and effective steps to converting a medical reference guide into a mobile application tool that is readily available, easy to use, and easy to update. The organic dissemination of the app beyond the state of Georgia's borders within the first six months of app launch underscores desire among TB healthcare professionals for high-quality digital reference content outside the state. This experience offers clear outlines for replication in other contexts and demonstrates the utility of similar mobile medical reference tools.

Incorporating Cardiovascular Risk Assessment into Adolescent Reproductive Health and Primary Care Visits.

STUDY OBJECTIVE: This study aimed to evaluate the usability and feasibility of incorporating a cardiovascular risk assessment tool into adolescent reproductive health and primary care visits. DESIGN, SETTING, AND PARTICIPANTS: We recruited 60 young women ages 13-21 years to complete the HerHeart web-tool in 2 adolescent clinics in Atlanta, GA. MAIN OUTCOME MEASURES: Participants rated the tool's usability via the Website Analysis and Measurement Inventory (WAMMI, range 0-95) and their perceived 10-year and lifetime risk of cardiovascular disease (CVD) on a visual analog scale (range 0-10). Participants' perceived risk, blood pressure, and body mass index were measured at baseline and 3 months after enrollment. Health care providers (HCP, n = 5) completed the WAMMI to determine the usability and feasibility of incorporating the HerHeart tool into clinical practice. RESULTS: Adolescent participants and HCPs rated the tool's usability highly on the WAMMI with a median of 79 (interquartile range [IQR] 65, 84) and 76 (IQR 71, 84). At the baseline visit, participants' median perceived 10-year risk of a heart attack was 1 (IQR 0, 3), and perceived lifetime risk was 2 (IQR 0, 4). Immediately after engaging with the tool, participants' median perceived 10-year risk was 2 (IQR 1, 4.3), and perceived lifetime risk was 3 (IQR 1.8, 6). Thirty-one participants chose to set a behavior change goal, and 12 participants returned for follow-up. Clinical metrics were similar at the baseline and follow-up visits. CONCLUSION: HerHeart is acceptable to young women and demonstrates potential for changing risk perception and improving health habits to reduce risk of CVD. Future research should focus on improving retention in studies to promote cardiovascular health within reproductive health clinics.

An Acute Infection due to Hepatitis E in the Context of a Patient with Rituximab and Methotrexate Therapy.

Background: This report presents the influence of immunosuppression by new rheumatological therapies on hepatitis E virus infection in a 54-year-old male patient with an anti-synthetase syndrome and treatment with methotrexate and rituximab. Case description: The patient arrived at the Emergency Department with epigastric pain, vomiting and dark urine. Initial examination revealed signs of inflammation and hepatic dysfunction. Subsequent laboratory tests and imaging confirmed acute hepatitis E infection in the context of recent initiation of rituximab therapy. Despite initial suspicion of pancreatitis, subsequent investigations ruled out pancreatic involvement. Treatment with ribavirin, along with supportive measures, led to significant clinical improvement with resolution of jaundice, ascites, and oedema. Conclusions: This case underscores the importance of considering hepatitis E in patients with autoimmune conditions, especially when initiating immunosuppressive therapies, a situation that is not well described in scientific literature and is increasingly common, necessitating proper recognition. LEARNING POINTS: Suspect hepatitis E virus infection in the presence of persistent liver failure of unknown cause.Recognise immunosuppression as a cause of increased risk of hepatitis E infection.Take into account the repercussions of immunosuppressive therapy such as rituximab regarding hepatitis E infections in immunocompromised patients.

Investigating ischemia and reperfusion-induced organ damage in severe cardiac arrest: A comprehensive proteomics perspective.

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Molecular docking analysis of chlorpyrifos at the human α7-nAChR and its potential relationship with neurocytoxicity in SH-SY5Y cells.

The organophosphate insecticide chlorpyrifos (CPF), an acetylcholinesterase inhibitor, has raised serious concerns about human safety. Apart from inducing synaptic acetylcholine accumulation, CPF could also act at nicotinic acetylcholine receptors, like the α7-isoform (α7-nAChR), which could potentially be harmful to developing brains. Our aims were to use molecular docking to assess the binding interactions between CPF and α7-nAChR through, to test the neurocytotoxic and oxidative effects of very low concentrations of CPF on SH-SY5Y cells, and to hypothesize about the potential mediation of α7-nAChR. Docking analysis showed a significant binding affinity of CPH for the E fragment of the α7-nAChR (ΔGibbs: -5.63 to -6.85 Kcal/mol). According to the MTT- and Trypan Blue-based viability assays, commercial CPF showed concentration- and time-dependent neurotoxic effects at a concentration range (2.5-20 µM), ten-folds lower than those reported to have crucial effects for sheer CPF. A rise of the production of radical oxygen species (ROS) was seen at even lower concentrations (1-2.5 µM) of CPF after 24h. Notably, our docking analysis supports the antagonistic actions of CPF on α7-nAChR that were recently published. In conclusion, while α7-nAChR is responsible for neuronal survival and neurodevelopmental processes, its activity may also mediate the neurotoxicity of CPF.

Factors associated with referrals for directly observed treatment and unsuccessful treatment.

To describe the characteristics of people indicated for directly observed treatment (DOT) in Spain, and the factors associated with unsuccessful treatment.This was a multicentre observational study based on a prospective follow-up of patients over 18 years old diagnosed with TB between 2006 and 2019 from the registry of the Programa Integrado de Investigación en Tuberculosis (PII-TB). Sociodemographic and clinical variables were collected. Adjusted odds ratios (aORs) were calculated for the indication of DOT and for having an unsuccessful treatment.A total of 7,883 patients were included. The indication of DOT was associated with being homeless (aOR 5.93, 95% CI 3.03-11.59), inactivity status (aOR 2.55, 95% CI 2.02-3.23), alcohol consumption (aOR 1.94, 95% CI 1.51-2.48), parenteral drug use (aOR 1.77, 95% CI 1.06-2.95) and HIV diagnosis (aOR 1.96, 95% CI 1.16-3.29). Unsuccessful treatment was associated with having an HIV diagnosis (aPR 2.31, 95% CI 1.31-4.08), having a worse clinical and radiological evolution (clinical progression: APR 15.59, 95% CI 8.21-29.60; radiological progression: aPR 12.84, 95% CI 6.46-25.52), need for hospitalisation (aPR 1.73, 95% CI 1.10-2.73), unsatisfactory tolerability (aPR 2.82, 95% CI 1.49-5.29), the existence of difficulties in understanding the prescribed treatment (aPR 1.92, 95% CI 1.21-3.06), as well as worse treatment satisfaction (aPR 7.27, 95% CI 4.32-12.24).The prioritisation of vulnerable populations is a key aspect to carry out the new Global Plan to End TB 2023-2030. In these groups DOT indication should be increased to ensure adherence and patient follow-up and outcomes..