The Role of Nicotinic Receptors on Ca2+ Signaling in Bovine Chromaffin Cells.

Chromaffin cells have been used as a physiological model to understand neurosecretion in mammals for many years. Nicotinic receptors located in the cells' membrane are stimulated by acetylcholine, and they participate in the exocytosis of chromaffin granules, releasing catecholamines in response to stress. In this work, we discuss how the participation of nicotinic receptors and the localization of active zones in the borders of the cytoskeleton can generate local calcium signals leading to secretion. We use a computational model of a cytoskeleton cage to simulate Ca2+ levels in response to voltage and acetylcholine pulses. We find that nicotinic receptors are able to enhance the differences between local and average calcium values, as well as the heterogeneous distributions around the active zones, producing a non-linear, highly localized Ca2+ entry that, although consisting of a few ions, is able to improve secretion responses in chromaffin cells. Our findings emphasize the intricate interplay among nicotinic receptors, the cytoskeleton, and active zones within chromaffin cells as an example of Ca2+-dependent neurosecretion in mammals.

Pan American League of Associations for Rheumatology Recommendations for the Treatment of Psoriatic Arthritis.

OBJECTIVE: Psoriatic arthritis (PsA) is chronic disease that compromises multiple domains and might be associated with progressive joint damage, increased mortality, functional limitation, and considerably impaired quality of life. Our objective was to generate evidence-based recommendations on the management of PsA in Pan American League of Associations for Rheumatology (PANLAR) countries. METHODS: We used the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE)-ADOLOPMENT approach to adapt the 2019 recommendations of the European Alliance of Associations for Rheumatology. A working group consisting of rheumatologists from various countries in Latin America identified relevant topics for the treatment of PsA in the region. The methodology team updated the evidence and synthesized the information used to generate the final recommendations. These were then discussed and defined by a panel of 31 rheumatologists from 15 countries. RESULTS: Theses guidelines report 15 recommendations addressing therapeutic targets, use of antiinflammatory agents and corticosteroids, treatment with disease-modifying antirheumatic drugs (conventional synthetic, biologic, and targeted synthetic), therapeutic failure, optimization of biologic therapy, nonpharmacological interventions, assessment tools, and follow-up of patients with PsA. CONCLUSION: Here we present a set of recommendations to guide decision making in the treatment of PsA in Latin America, based on the best evidence available, considering resources, medical expertise, and the patient's values and preferences. The successful implementation of these recommendations should be based on clinical practice conditions, healthcare settings in each country, and a tailored evaluation of patients.

Blood salvage and autotransfusion during orthotopic liver transplantation for hepatocellular carcinoma: A systematic review and meta-analysis.

BACKGROUND: Hepatocellular carcinoma (HCC) is a significant cause of oncologic mortality worldwide. Liver transplantation represents a curative option for patients with significant liver dysfunction and absence of metastases. However, this therapeutic option is associated with significant blood loss and frequently requires various transfusions and intraoperative blood salvage for autotransfusion (IBS-AT) with or without a leukocyte reduction filter. This study aimed to analyze available evidence on long-term oncologic outcomes of patients undergoing liver transplantation for HCC with and without IBS-AT. METHODS: Per PRISMA guidelines, a systematic review of keywords "Blood Salvage," "Auto-transfusion," "Hepatocellular carcinoma," and "Liver-transplant" was conducted in PubMed, EMBASE, and SCOPUS. Studies comparing operative and postoperative outcomes were screened and analyzed for review. RESULTS: Twelve studies totaling 1704 participants were included for analysis. Length of stay, recurrence rates, and overall survival were not different between IBS-AT group and non IBS-AT group. CONCLUSION: IBS-AT use is not associated with increased risk of recurrence in liver transplant for HCC even without leukocyte filtration. Both operative and postoperative outcomes are similar between groups. Comparison of analyzed studies suggest that IBS-AT is safe for use during liver transplant for HCC.

Crossed-reflex in antiphospholipid chorea.

Chorea is a hyperkinetic movement disorder associated with various underlyingconditions, including autoimmune diseases such as antiphospholipid syndrome (APS). APS can manifest with a wide range of neurological symptoms, including chorea. We present a case of a 77-year-old man with subacute generalized chorea secondary to primary APS. Notably, the patient exhibited a left patellar crossed-reflex, a phenomenon rarely documented in chorea cases, the pathophysiology of which has not yet been elucidated. In summary, this case challenges the traditional demographics of antiphospholipid syndrome (APS) by suggesting a potential link between APS and late-age patients. It emphasizes the importance of considering APS in late-onset chorea cases.

Lessons Learned From Ocular Graft versus Host Disease: An Ocular Surface Inflammatory Disease of Known Time of Onset.

ABSTRACT: The ocular surface inflammatory disorders (OSIDs) comprise a group of conditions characterized by persistent inflammation of the ocular surface and adnexal tissues. Systemic autoimmune diseases and hypersensitivity reactions cause them, and, if left untreated, can result in severe inflammatory dry eye, corneal damage, and vision loss. Ocular graft-versus-host disease (oGVHD) forms part of the ocular surface inflammatory disease umbrella. It is a condition occurring after allogeneic hematopoietic stem cell or bone marrow transplantation, usually in chronic graft-versus-host disease. oGVHD can virtually affect any ocular adnexal tissue, especially the meibomian glands, and cause persistent inflammation, tissue fibrosis, and subsequent chronic, severe dry eye disease. Among the OSIDs, oGVHD has the particularity that it has a "time zero," meaning we know when the disease started. As such, preclinical models have leveraged this to investigate the molecular mechanisms involved in the damage oGVHD causes to the ocular surface. In oGVHD, establishing a "time zero" allows for predicting the clinical course and establishing adequate treatment. This is also possible because the inflammatory infiltration occurs in ocular surface tissues, which are readily accessible. Using oGVHD, we might be able to understand the immune response mechanisms in other OSIDs better (i.e., Sjögren syndrome, Stevens-Johnson syndrome, among others). This review presents an up-to-date overview of the pathogenesis, clinical presentation, and treatment of oGVHD. In addition, we will discuss the value of the "time zero" concept in the study of oGVHD.

Understanding antibiotic knowledge, attitudes, and practices: a cross-sectional study in physicians from a Colombian region, 2023.

BACKGROUND: Antibiotic resistance has been identified as a global health threat. Knowledge, attitudes, and inappropriate prescription practices of antibiotics by physicians play a crucial role in this problem. In Colombia, research addressing this issue is scarce. METHODS: A cross-sectional study involving 258 physicians was conducted. A scale with questions on sociodemographic aspects, level of education, satisfaction with antibiotic education received, and knowledge, attitudes, and practices was administered. The scale was designed for each item to be analyzed individually or as a total score ranging from 0 to 100 (0 being the lowest and 100 the highest). RESULTS: 31.5% of physicians rated the education received on antibiotics as fair to poor. The knowledge score was 80.1 (IQR 70.5-87.5); however, 25.2% agreed to some extent that amoxicillin is useful in treating most respiratory infections, and 15% agreed that antibiotics are effective in treating upper respiratory infections. Attitudes scored 80.2 (IQR 75.0-86.5), with 99% stating that bacterial resistance is a public health problem in Colombia, but only 56.9% considering it a problem affecting their daily practice. Practices scored 75.5 (IQR 68.8-81.2), and 71.7% affirmed that if they refuse to prescribe antibiotics to a patient who does not need them, the patient can easily obtain them from another physician. General practitioners were found to have lower scores in all three indices evaluated. CONCLUSION: The study reveals enduring misconceptions and concerning practices in antibiotic prescription, particularly among general practitioners. Enhancing knowledge necessitates the implementation of continuous medical education programs that focus on updated antibiotic guidelines, and resistance patterns. Fostering positive attitudes requires a culture of trust and collaboration among healthcare professionals. Practical enhancements can be realized through the establishment of evidence-based prescribing guidelines and the integration of regular feedback mechanisms. Moreover, advocating for the inclusion of antimicrobial stewardship principles in medical curricula is crucial, emphasizing the significance of responsible antibiotic use early in medical education.

Effects of Vape Use on Oral Health: A Review of the Literature.

Background and Objectives: The widespread use of tobacco has evolved with the popularity of vapes, especially among young people, despite the lack of clarity in warnings about their risks. Studies indicate the need for more effective communication about the oral risks of vaping. In addition to systemic, respiratory, and cardiovascular effects, vaping is associated with an increased risk of gingivitis and periodontal disease as well as reduced antioxidant capacity of saliva. The objectives of this narrative review are to summarize the existing information in the literature on the effects of vaping at the oral level and to bring together knowledge about the mechanism of action of vaping in oral tissues. Materials and Methods: In the present study, articles were searched in PubMed, Elsevier Scopus, and Web of Science using the keywords "oral health", "vaping", and "vape". Studies published in the last 6 years that addressed the effects of oral vaping were selected, including comparisons among vape users, smokers, and non-smokers. Repeated articles, prior to 2017 and in languages other than English, were excluded. Two review authors (A.M.I and M.F.E.M) independently selected the papers based on titles and abstracts and conducted a full review of the remaining papers. In cases of disagreement, a third reviewer was used. Results: A total of 113 results were obtained, distributed as 16 from PubMed, 35 from Web of Science, and 62 from Elsevier Scopus. After removing duplicates, 67 articles were filtered by reviewing titles and abstracts, and finally, 22 articles were selected for comprehensive reading. Subsequently, eight of these articles were chosen for qualitative synthesis and are presented in standardized tables. The sample size of all included studies was composed of 31,647 participants, (14,477 male and 17,170 female) with a mean of 35.016 ± 7.57 years of age. Conclusions: This review indicates that the use of vapes is associated with an increased risk of periodontitis and caries. Although users experience more oral problems than non-smokers, these are less severe than those of traditional smokers. The widespread prevalence, especially among young people, highlights the urgency of awareness campaigns to warn of risks and understand potential harm.

Outcomes of accelerated corneal cross-linking for pediatric and adult keratoconus: a comparative study.

PURPOSE: To compare the visual, refractive, and topographic outcomes of a high irradiance accelerated corneal crosslinking (ACXL) protocol after a 12-month follow-up between pediatric and adult patients with progressive keratoconus (KC). METHODS: Retrospective, comparative, cohort study. Patients with KC were divided into two groups: pediatric (≤ 18 years) and adult (> 18 years). All of them were managed with epi-OFF ACXL (30 mW/cm2, 8 min, pulsed 1:1 on and off = 7.2 J/cm2). Visual, refractive, and topographic values were measured preoperatively and at 1, 3, 6, and 12 months postoperative. KC progression, defined as a Kmax increase of ≥ 1D during follow-up, was recorded. RESULTS: Eighty-nine eyes (53 patients) were included for analysis; 45 (50.6%) eyes were from pediatric patients and 44 (49.4%) from adults. At one-year follow-up, pediatric patients experienced significantly higher rates of progression (22.2% vs. 4.5%, p = .014). Contrariwise, female gender (Beta = - 3.62, p = .018), a baseline uncorrected visual acuity of Snellen ≥ 20/60 (Beta = - 5.96, p = .007), and being ≥ 15 years at ACXL treatment (Beta = - 0.31, p = .021) were associated with non-progressive disease. A significant improvement in best-corrected visual acuity, Kmin, Km, and Kmax was recorded in both groups. Overall, 86.5% of eyes from both groups showed Kmax stabilization or improvement. CONCLUSIONS: Despite the similarity in visual, refractive, and topographic outcomes in both groups, younger age was associated with KC progression after ACXL at one year of follow-up.

Multiple nutrient transporters enable cells to mitigate a rate-affinity tradeoff.

Eukaryotic genomes often encode multiple transporters for the same nutrient. For example, budding yeast has 17 hexose transporters (HXTs), all of which potentially transport glucose. Using mathematical modelling, we show that transporters that use either facilitated diffusion or symport can have a rate-affinity tradeoff, where an increase in the maximal rate of transport decreases the transporter's apparent affinity. These changes affect the import flux non-monotonically, and for a given concentration of extracellular nutrient there is one transporter, characterised by its affinity, that has a higher import flux than any other. Through encoding multiple transporters, cells can therefore mitigate the tradeoff by expressing those transporters with higher affinities in lower concentrations of nutrients. We verify our predictions using fluorescent tagging of seven HXT genes in budding yeast and follow their expression over time in batch culture. Using the known affinities of the corresponding transporters, we show that their regulation in glucose is broadly consistent with a rate-affinity tradeoff: as glucose falls, the levels of the different transporters peak in an order that mostly follows their affinity for glucose. More generally, evolution is constrained by tradeoffs. Our findings indicate that one such tradeoff often occurs in the cellular transport of nutrients.

Analysing and meta-analysing time-series data of microbial growth and gene expression from plate readers.

Responding to change is a fundamental property of life, making time-series data invaluable in biology. For microbes, plate readers are a popular, convenient means to measure growth and also gene expression using fluorescent reporters. Nevertheless, the difficulties of analysing the resulting data can be a bottleneck, particularly when combining measurements from different wells and plates. Here we present omniplate, a Python module that corrects and normalises plate-reader data, estimates growth rates and fluorescence per cell as functions of time, calculates errors, exports in different formats, and enables meta-analysis of multiple plates. The software corrects for autofluorescence, the optical density's non-linear dependence on the number of cells, and the effects of the media. We use omniplate to measure the Monod relationship for the growth of budding yeast in raffinose, showing that raffinose is a convenient carbon source for controlling growth rates. Using fluorescent tagging, we study yeast's glucose transport. Our results are consistent with the regulation of the hexose transporter (HXT) genes being approximately bipartite: the medium and high affinity transporters are predominately regulated by both the high affinity glucose sensor Snf3 and the kinase complex SNF1 via the repressors Mth1, Mig1, and Mig2; the low affinity transporters are predominately regulated by the low affinity sensor Rgt2 via the co-repressor Std1. We thus demonstrate that omniplate is a powerful tool for exploiting the advantages offered by time-series data in revealing biological regulation.

Social determination of malaria in pregnancy in Colombia: a critical ethnographic study.

BACKGROUND: The meanings and experiences related to malaria in pregnancy (MiP) and its processes of social determination of health (PSDH) have not been reported in the world scientific literature. The objective was to understand the meanings and experiences of MiP, and to explain their PSDH in an endemic area from Colombia, 2022. METHODS: Critical ethnography with 46 pregnant women and 31 healthcare workers. In-depth and semi-structured interviews, focus group discussions, participant and non-participant observations, and field diaries were applied. A phenomenological-hermeneutic analysis, saturation and triangulation was carried out. The methodological rigor criteria were reflexivity, credibility, auditability, and transferability. RESULTS: At the singular level, participants indicated different problems in antenatal care and malaria control programmes, pregnant women were lacking knowledge about MiP, and malaria care was restricted to cases with high obstetric risk. Three additional levels that explain the PSDH of MiP were identified: (i) limitations of malaria control policies, and health-system, geographic, cultural and economic barriers by MiP diagnosis and treatment; (ii) problems of public health programmes and antenatal care; (iii) structural problems such as monetary poverty, scarcity of resources for public health and inefficiency in their use, lacking community commitment to preventive actions, and breach of institutional responsibilities of health promoter entity, municipalities and health services provider institutions. CONCLUSION: Initiatives for MiP control are concentrated at the singular level, PDSH identified in this research show the need to broaden the field of action, increase health resources, and improve public health programmes and antenatal care. It is also necessary to impact the reciprocal relationships of MiP with economic and cultural dimensions, although these aspects are increasingly diminished with the predominance and naturalization of neoliberal logic in health.

High tumor burden in patients with non-small-cell lung cancer: a Delphi survey among Spanish oncologists.

Aim: To define high tumor burden (HTB) in non-small-cell lung cancer. Methods: A total of five oncologists initiated the project, selecting 66 participants, and elaborated a questionnaire with 26 statements using the Delphi method with a 9-point Likert scale of agreement. Results: Factors with moderate strength of consensus were identified, including a sum of the longest diameter of lesions ≥10 cm, elevated Lactate dehydrogenase, hepatic involvement, lymphangitis carcinomatosis, brain involvement unapproachable with local techniques and pericardial effusion. There was a consensus against increases in tumor markers and asymptomatic brain involvement being related to HTB. HTB was considered a relevant factor for treatment selection supporting the choice of combination regimens versus immunotherapy only. Conclusion: In this Delphi study, experts defined several factors associated with HTB in non-small cell lung cancer.

Clinical and economic impact of 'ROS1-testing' strategy compared to a 'no-ROS1-testing' strategy in advanced NSCLC in Spain.

BACKGROUND: Detection of the ROS1 rearrangement is mandatory in patients with advanced or metastatic non-small cell lung cancer (NSCLC) to allow targeted therapy with specific inhibitors. However, in Spanish clinical practice ROS1 determination is not yet fully widespread. The aim of this study is to determine the clinical and economic impact of sequentially testing ROS1 in addition to EGFR and ALK in Spain. METHODS: A joint model (decision-tree and Markov model) was developed to determine the cost-effectiveness of testing ROS1 strategy versus a no-ROS1 testing strategy in Spain. Distribution of ROS1 techniques, rates of testing, positivity, and invalidity of biomarkers included in the analysis (EGFR, ALK, ROS1 and PD-L1) were based on expert opinion and Lungpath real-world database. Treatment allocation depending on the molecular testing results was defined by expert opinion. For each treatment, a 3-states Markov model was developed, where progression-free survival (PFS) and overall survival (OS) curves were parameterized using exponential extrapolations to model transition of patients among health states. Only medical direct costs were included (€ 2021). A lifetime horizon was considered and a discount rate of 3% was applied for both costs and effects. Both deterministic and probabilistic sensitivity analyses were performed to address uncertainty. RESULTS: A target population of 8755 patients with advanced NSCLC (non-squamous or never smokers squamous) entered the model. Over a lifetime horizon, the ROS1 testing scenario produced additional 157.5 life years and 121.3 quality-adjusted life years (QALYs) compared with no-ROS1 testing scenario. Total direct costs were increased up to € 2,244,737 for ROS1 testing scenario. The incremental cost-utility ratio (ICUR) was 18,514 €/QALY. Robustness of the base-case results were confirmed by the sensitivity analysis. CONCLUSIONS: Our study shows that ROS1 testing in addition to EGFR and ALK is a cost-effective strategy compared to no-ROS1 testing, and it generates more than 120 QALYs in Spain over a lifetime horizon. Despite the low prevalence of ROS1 rearrangements in NSCLC patients, the clinical and economic consequences of ROS1 testing should encourage centers to test all advanced or metastatic NSCLC (non-squamous and never-smoker squamous) patients.

Endovascular Treatment of Transplant Renal Artery Stenosis: A Systematic Review and Meta-analysis.

OBJECTIVE: Endovascular treatment through either percutaneous transluminal angioplasty (PTA) alone or stenting has been previously used as a treatment for transplant renal artery stenosis (TRAS). This review aimed to investigate the results of endovascular treatment for renal artery stenosis in transplanted kidneys as compared with the outcomes of interventions, medical management, and graft survival in non-TRAS patients. METHODS: A systematic review of PubMed, Google Scholar, Cochrane, and Scopus was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines in which studies that reported outcomes of the treatment of TRAS via the endoluminal approach were identified, and their results were meta-analyzed. RESULTS: Fifty-four studies with a total of 1522 patients were included. A significant reduction of serum creatinine level was found, favoring the stenting group, with a mean difference of 0.68 mg/dL (95% confidence interval (CI), 0.17-1.19; Z=2.60, p=0.0009). Comparison of pre- and post-intervention values of any intervention revealed a significant decrease in overall serum creatinine level (0.65 mg/dL; 95% CI, 0.40-0.90; Z=5.09, p=0.00001), overall blood pressure, with a mean difference of 11.12 mmHg (95% CI, 7.29-14.95; Z=5.59, p=0.00001), mean difference in the use of medications (0.77; 95% CI, 0.29-1.24; p=0.002), and peak systolic velocity (190.05; 95% CI, 128.41-251.69; p<0.00001). The comparison of serum creatinine level between endovascular interventions and best medical therapy favored endovascular intervention, with a mean difference of 0.23 mg/dL (95% CI, 0.14-0.32; Z=5.07, p<0.00001). Graft survival was similar between the treated patients and those without TRAS (hazard ratio, 0.98; 95% CI, 0.75-1.28; p=0.091). The overall pooled success rate was 89%, and the overall complication rate was 10.4%, with the most prevalent complication being arterial dissection. CONCLUSION: The endovascular treatment of TRAS improves graft preservation and renal function and hemodynamic parameters. PTA + stenting appears to be a more effective option to PTA alone in the stabilization of renal function, with additional benefits from decreased restenosis rates. Further high-quality studies could expand on these findings.

Harmonized D-dimer levels upon admission for prognosis of COVID-19 severity: Results from a Spanish multicenter registry (BIOCOVID-Spain study).

Coagulopathy is a key feature of COVID-19 and D-dimer has been reported as a predictor of severity. However, because D-dimer test results vary considerably among assays, resolving harmonization issues is fundamental to translate findings into clinical practice. In this retrospective multicenter study (BIOCOVID study), we aimed to analyze the value of harmonized D-dimer levels upon admission for the prediction of in-hospital mortality in COVID-19 patients. All-cause in-hospital mortality was defined as endpoint. For harmonization of D-dimer levels, we designed a model based on the transformation of method-specific regression lines to a reference regression line. The ability of D-dimer for prediction of death was explored by receiver operating characteristic curves analysis and the association with the endpoint by Cox regression analysis. Study population included 2663 patients. In-hospital mortality rate was 14.3%. Harmonized D-dimer upon admission yielded an area under the curve of 0.66, with an optimal cut-off value of 0.945 mg/L FEU. Patients with harmonized D-dimer ≥ 0.945 mg/L FEU had a higher mortality rate (22.4% vs. 9.2%; p < 0.001). D-dimer was an independent predictor of in-hospital mortality, with an adjusted hazard ratio of 1.709. This is the first study in which a harmonization approach was performed to assure comparability of D-dimer levels measured by different assays. Elevated D-dimer levels upon admission were associated with a greater risk of in-hospital mortality among COVID-19 patients, but had limited performance as prognostic test.

Headache related to personal protective equipment in healthcare workers during COVID-19 pandemic in Mexico: baseline and 6-month follow-up.

BACKGROUND AND AIM: Headaches related to the use of personal protective equipment (PPE) could affect performance at work in healthcare personnel. Our aim was to describe the prevalence and risk factors for headaches related to PPE, in the personnel of a specialized coronavirus disease 2019 (COVID-19) tertiary hospital. METHODS: In this cross-sectional survey study, we invited healthcare workers from COVID-19 referral center in Mexico (May 22-June 19, 2020) to answer a standardized structure questionnaire on characteristics of new-onset PPE-related headache or exacerbation of primary headache disorder. Participants were invited regardless of whether they had a current headache to avoid selection bias. This is the primary analysis of these data. RESULTS: Two hundred and sixty-eight subjects were analyzed, 181/268 (67.5%) women, 177/268 (66%) nurses, mean age 28 years. The prevalence of PPE-related headache was 210/268 (78.4%). Independent risk factors were occupation other than physician (OR 1.59, 95% CI 1.20-2.10), age > 30 years (OR 2.54, 95% CI 1.25-5.14), and female sex (OR 3.58, 95% CI 1.86-6.87). In the 6-month follow-up, 13.1% of subjects evolve to chronic headache, with stress as predictive risk factor. CONCLUSION: The frequency of PPE-associated headache is high, and a subgroup could evolve to chronic headache. More studies are necessary to improve the knowledge about this condition.

Vesicle Fusion as a Target Process for the Action of Sphingosine and Its Derived Drugs.

The fusion of membranes is a central part of the physiological processes involving the intracellular transport and maturation of vesicles and the final release of their contents, such as neurotransmitters and hormones, by exocytosis. Traditionally, in this process, proteins, such SNAREs have been considered the essential components of the fusion molecular machinery, while lipids have been seen as merely structural elements. Nevertheless, sphingosine, an intracellular signalling lipid, greatly increases the release of neurotransmitters in neuronal and neuroendocrine cells, affecting the exocytotic fusion mode through the direct interaction with SNAREs. Moreover, recent studies suggest that FTY-720 (Fingolimod), a sphingosine structural analogue used in the treatment of multiple sclerosis, simulates sphingosine in the promotion of exocytosis. Furthermore, this drug also induces the intracellular fusion of organelles such as dense vesicles and mitochondria causing cell death in neuroendocrine cells. Therefore, the effect of sphingosine and synthetic derivatives on the heterologous and homologous fusion of organelles can be considered as a new mechanism of action of sphingolipids influencing important physiological processes, which could underlie therapeutic uses of sphingosine derived lipids in the treatment of neurodegenerative disorders and cancers of neuronal origin such neuroblastoma.

α3ß4 Acetylcholine Nicotinic Receptors Are Components of the Secretory Machinery Clusters in Chromaffin Cells.

The heteromeric assembly of α3 and ß4 subunits of acetylcholine nicotinic receptors (nAChRs) seems to mediate the secretory response in bovine chromaffin cells. However, there is no information about the localization of these nAChRs in relationship with the secretory active zones in this cellular model. The present work presents the first evidence that, in fact, a population of these receptors is associated through the F-actin cytoskeleton with exocytotic machinery components, as detected by SNAP-25 labeling. Furthermore, we also prove that, upon stimulation, the probability to find α3ß4 nAChRs very close to exocytotic events increases with randomized distributions, thus substantiating the clear dynamic behavior of these receptors during the secretory process. Modeling on secretory dynamics and secretory component distributions supports the idea that α3ß4 nAChR cluster mobility could help with improving the efficiency of the secretory response of chromaffin cells. Our study is limited by the use of conventional confocal microscopy; in this sense, a strengthening to our conclusions could come from the use of super-resolution microscopy techniques in the near future.

Characterizing regional radon-in-air levels in rocks of the Canary Islands (Spain): new data and results.

In this work, a regional-scale strategy to characterize the radon activity levels in the Canary Islands (Spain) is described. The main objectives of this strategy consisted of (1) studying the likely relationship between radon concentration and lithology of the rock matrix through the lithological data of 247 samples from volcanic rocks of the Canary Islands and (2) implementing a series of monitoring sites in the form of boreholes and wells to study the evolution of radon-in-air activity on a daily to yearly timescale.

Posttraumatic Stress Disorder Risk and Benzodiazepine Dependence in Older Veterans with Insomnia Symptoms.

OBJECTIVES: To measure the rate of benzodiazepine receptor agonist (BZA) dependence in older veterans with insomnia symptoms chronically using BZAs and to assess for associations between high posttraumatic stress disorder (PTSD) risk and BZA dependence. METHODS: A cross-sectional study was conducted among veterans aged 55 years and older with insomnia symptoms (current or historical) and chronic use of BZAs (≥3 months). Measurements included the Primary Care-PTSD screen (score >2 indicates high PTSD risk) and Benzodiazepine Dependence Questionnaire. Logistic regression was used to test for associations between PTSD risk and BZA dependence. RESULTS: A high PTSD risk was observed in 40% of the participants (N = 33). One-fifth (21.7%, N = 18) of participants met the criteria for benzodiazepine dependence (score ≥23 on Benzodiazepine Dependence Questionnaire). Veterans with high PTSD risk were significantly more likely to have BZA dependence (odds ratio 10.09, 95% CI [2.39, 42.54], p = .002). CONCLUSIONS: In older veterans with insomnia symptoms and chronic use of BZAs, high PTSD risk is associated with elevated risk for BZA dependence, which may make discontinuation of these medications difficult. CLINICAL IMPLICATIONS: Clinicians should consider the strong association between PTSD symptoms and benzodiazepine dependence when developing plans to taper a BZA in veterans with these symptoms.