Lymph node regression after neoadjuvant chemoradiotherapy in rectal cancer.

AIMS: Lymph node metastases (LNM) are one of the most important prognostic indicators in solid tumours and a major component of cancer staging. Neoadjuvant therapy might influence nodal status by induction of regression. Our aim is to determine the prevalence and role of regression of LNM on outcomes in patients with rectal cancer. METHODS AND RESULTS: Four independent study populations of rectal cancer patients treated with similar regimens of chemoradiotherapy were pooled together to obtain a total cohort of 469 patients. Post-treatment nodal status (ypN) and signs of tumour regression (Reg) were incorporated to form three-tiered (ypN- Reg+, ypN- Reg- and ypN+) and four-tiered (ypN- Reg+, ypN- Reg-, ypN+ Reg+ and ypN+ Reg-) classifications. In our cohort, 31% of patients presented with ypN+ rectal cancer. As expected, we found significantly worse overall survival (OS) in ypN+ patients compared to ypN- patients (P = 0.002). The percentage of ypN- patients with lymph nodes with complete regression was 20% in our cohort. While node-negative patients with and without regression had similar OS (P = 0.09), disease-free survival (DFS) was significantly better in node-negative patients with regression (P = 0.009). CONCLUSIONS: Regression in lymph nodes is frequent, and node-negative patients with evidence of lymph node regression have better DFS compared to node-negative patients without such evidence.

Predictive value of functional disability scales among stroke survivors: A long-term mortality evaluation in a Brazilian stroke cohort.

OBJECTIVE: To assess the influence of two functional scales- Modified Rankin Scale (m-RS) and Modified Katz Index (m-Katz Index) on long-term mortality in a stroke cohort. MATERIAL AND METHODS: Among 760 stroke survivors (median age: 66 (IQR:56-75), 56.4 % women) m-Katz Index and m-RS scales applied at 1 and 6 months after stroke, were investigated in relation to 12-years of all-cause mortality. Kaplan-Meier survival curves were computed, and time-varying covariate Cox regression models were fitted to calculate hazard ratios (HRs) with 95 % confidence intervals (CIs) in all sample and by sex. The prognostic ability of the fitted models was computed for each model by six different measures. RESULTS: After 12 years of follow-up (median survival time: 7.3 years), 311 participants died. Overall survival curves show lower survival rates among those with the highest levels of disability/dependence (all log-rank p-values <0.0001). These findings were confirmed in all regression models for both sexes, particularly in men who had higher levels of dependence on Activities of Daily Living (ADLs) by m-Katz Index and severe disability by m-RS and presented the highest HR of dying (HR: 3.34 (95 %CI: 2.27-4.92) and HR: 4.94 (95 % CI: 3.15-7.75), respectively). CONCLUSIONS: Both the m-Katz Index and the m-RS scale were good predictors of long-term mortality, which is of importance for guiding the functional rehabilitation of stroke patients. Besides, high levels of disability and dependence were implicated with high mortality risks, regardless of sex.

Fire suppression and land-use strategies drive future dynamics of an invasive plant in a fire-prone mountain area under climate change.

Woody invasive alien species can have profound impacts on ecosystem processes and functions, including fire regulation, which can significantly affect landscape resilience. Acacia dealbata, a widespread invasive alien plant in the Iberian Peninsula, holds well-known fire-adaptation traits (e.g., massive soil seed banks and heat-stimulated seed germination). In this study, we assess to what extent fire suppression and land-use strategies could affect the potential distribution of A. dealbata in a fire-prone transboundary protected mountain area of Portugal and Spain, using Habitat Suitability Models. Specifically, we predicted changes in habitat suitability for A. dealbata between years 2010 and 2050. We explored the potential impacts of two land-use strategies ('Business-as-usual' or 'High Nature Value farmlands') combined with three levels of fire suppression effectiveness using the biomod2 package in R. We also considered the potential effects of two climate change scenarios (RCP4.5 and RCP8.5). Our modeling approach demonstrated a strong capacity to predict habitat suitability using either climate or land-cover information alone (AUC climate = 0.947; AUC LC = 0.957). According to climate-based models, A. dealbata thrives under conditions characterized by higher precipitation seasonality, higher precipitation in the warmest month, and higher minimum temperature in the coldest month. Regarding land cover, A. dealbata thrives mainly in landscapes dominated by urban areas and evergreen forest plantations. Our models forecasted that habitat suitability by 2050 could either increase or decrease depending on the specific combinations of fire suppression, land-use, and climate scenarios. Thus, a combination of business-as-usual and fire-exclusion strategies would enhance habitat suitability for the species. Conversely, management promoting High Nature Value farmlands would decrease the available suitable habitat, particularly under low fire suppression efforts. These findings suggest that promoting sustainable farming activities could impede the spread of A. dealbata by reducing habitat availability, while strategies aiming at fire-exclusion could facilitate its expansion, likely by enabling establishment and large seed production. This study highlights the complex interplay between fire-prone invasive species, fire and land-use strategies, and climate change; and thus the need to consider the interactions between land-use and fire management to promote invasive species control and landscape resilience.

Patterns of antibiotic use, pathogens, and prediction of mortality in hospitalized neonates and young infants with sepsis: A global neonatal sepsis observational cohort study (NeoOBS).

BACKGROUND: There is limited data on antibiotic treatment in hospitalized neonates in low- and middle-income countries (LMICs). We aimed to describe patterns of antibiotic use, pathogens, and clinical outcomes, and to develop a severity score predicting mortality in neonatal sepsis to inform future clinical trial design. METHODS AND FINDINGS: Hospitalized infants <60 days with clinical sepsis were enrolled during 2018 to 2020 by 19 sites in 11 countries (mainly Asia and Africa). Prospective daily observational data was collected on clinical signs, supportive care, antibiotic treatment, microbiology, and 28-day mortality. Two prediction models were developed for (1) 28-day mortality from baseline variables (baseline NeoSep Severity Score); and (2) daily risk of death on IV antibiotics from daily updated assessments (NeoSep Recovery Score). Multivariable Cox regression models included a randomly selected 85% of infants, with 15% for validation. A total of 3,204 infants were enrolled, with median birth weight of 2,500 g (IQR 1,400 to 3,000) and postnatal age of 5 days (IQR 1 to 15). 206 different empiric antibiotic combinations were started in 3,141 infants, which were structured into 5 groups based on the World Health Organization (WHO) AWaRe classification. Approximately 25.9% (n = 814) of infants started WHO first line regimens (Group 1-Access) and 13.8% (n = 432) started WHO second-line cephalosporins (cefotaxime/ceftriaxone) (Group 2-"Low" Watch). The largest group (34.0%, n = 1,068) started a regimen providing partial extended-spectrum beta-lactamase (ESBL)/pseudomonal coverage (piperacillin-tazobactam, ceftazidime, or fluoroquinolone-based) (Group 3-"Medium" Watch), 18.0% (n = 566) started a carbapenem (Group 4-"High" Watch), and 1.8% (n = 57) a Reserve antibiotic (Group 5, largely colistin-based), and 728/2,880 (25.3%) of initial regimens in Groups 1 to 4 were escalated, mainly to carbapenems, usually for clinical deterioration (n = 480; 65.9%). A total of 564/3,195 infants (17.7%) were blood culture pathogen positive, of whom 62.9% (n = 355) had a gram-negative organism, predominantly Klebsiella pneumoniae (n = 132) or Acinetobacter spp. (n = 72). Both were commonly resistant to WHO-recommended regimens and to carbapenems in 43 (32.6%) and 50 (71.4%) of cases, respectively. MRSA accounted for 33 (61.1%) of 54 Staphylococcus aureus isolates. Overall, 350/3,204 infants died (11.3%; 95% CI 10.2% to 12.5%), 17.7% if blood cultures were positive for pathogens (95% CI 14.7% to 21.1%, n = 99/564). A baseline NeoSep Severity Score had a C-index of 0.76 (0.69 to 0.82) in the validation sample, with mortality of 1.6% (3/189; 95% CI: 0.5% to 4.6%), 11.0% (27/245; 7.7% to 15.6%), and 27.3% (12/44; 16.3% to 41.8%) in low (score 0 to 4), medium (5 to 8), and high (9 to 16) risk groups, respectively, with similar performance across subgroups. A related NeoSep Recovery Score had an area under the receiver operating curve for predicting death the next day between 0.8 and 0.9 over the first week. There was significant variation in outcomes between sites and external validation would strengthen score applicability. CONCLUSION: Antibiotic regimens used in neonatal sepsis commonly diverge from WHO guidelines, and trials of novel empiric regimens are urgently needed in the context of increasing antimicrobial resistance (AMR). The baseline NeoSep Severity Score identifies high mortality risk criteria for trial entry, while the NeoSep Recovery Score can help guide decisions on regimen change. NeoOBS data informed the NeoSep1 antibiotic trial (ISRCTN48721236), which aims to identify novel first- and second-line empiric antibiotic regimens for neonatal sepsis. TRIAL REGISTRATION: ClinicalTrials.gov, (NCT03721302).

Neonatal invasive candidiasis in low- and middle-income countries: Data from the NeoOBS study.

Neonatal invasive candidiasis (NIC) has significant morbidity and mortality. Reports have shown a different profile of those neonates affected with NIC and of fluconazole-resistant Candida spp. isolates in low- and middle-income countries (LMICs) compared to high-income countries (HICs). We describe the epidemiology, Candida spp. distribution, treatment, and outcomes of neonates with NIC from LMICs enrolled in a global, prospective, longitudinal, observational cohort study (NeoOBS) of hospitalized infants <60 days postnatal age with sepsis (August 2018-February 2021). A total of 127 neonates from 14 hospitals in 8 countries with Candida spp. isolated from blood culture were included. Median gestational age of affected neonates was 30 weeks (IQR: 28-34), and median birth weight was 1270 gr (interquartile range [IQR]: 990-1692). Only a minority had high-risk criteria, such as being born <28 weeks, 19% (24/127), or birth weight <1000 gr, 27% (34/127). The most common Candida species were C. albicans (n = 45, 35%), C. parapsilosis (n = 38, 30%), and Candida auris (n = 18, 14%). The majority of C. albicans isolates were fluconazole susceptible, whereas 59% of C. parapsilosis isolates were fluconazole-resistant. Amphotericin B was the most common antifungal used [74% (78/105)], followed by fluconazole [22% (23/105)]. Death by day 28 post-enrollment was 22% (28/127). To our knowledge, this is the largest multi-country cohort of NIC in LMICs. Most of the neonates would not have been considered at high risk for NIC in HICs. A substantial proportion of isolates was resistant to first choice fluconazole. Understanding the burden of NIC in LMIC is essential to guide future research and treatment guidelines.

Our study describes neonates from low- and middle-income countries with neonatal invasive candidiasis (NIC). Most of them were outside the groups considered at high risk for NIC described in high-income countries. Candida spp. epidemiology was also different. The mortality was high (22%). Further research in these settings is required.

Reversible Single-Electron-Transfer to Oxygen in a Stable N-Heterocyclic Carbene Palladium(I) Metalloradical.

The chemical and electrochemical one-electron oxidation of [Pd(IPr)2] (1) leads to the formation of mononuclear palladium(I) complex [Pd(IPr)2][PF6] (2). This bench-stable metalloradical has been fully characterized and its structure confirmed by X-ray diffraction analysis. EPR and DFT studies confirm the localization of the unpaired electron onto the metal center. Low temperature NMR and EPR measurements reveal the ability of complex 2 to reversibly coordinate and reduce the dioxygen molecule, leading to the formation of a three-coordinate complex, [PdII(IPr)2(η1-O2)]+ (4), in which the unpaired electron has been transferred to the superoxido ligand.

Effects of prenatal alcohol and delta-9-tetrahydrocannabinol exposure via electronic cigarettes on motor development.

BACKGROUND: Prenatal alcohol exposure can lead to a wide range of neurological and behavioral deficits, including alterations in motor domains. However, much less is known about the effects of prenatal cannabis exposure on motor development, despite cannabis being the most consumed illicit drug among women. Cannabis use among pregnant women has become increasingly popular given the widespread perception that consumption is safe during pregnancy. Moreover, alcohol and cannabis are commonly used together, even among pregnant women. Yet few studies have explored the potential consequences of combined prenatal exposure on behavioral domains. METHODS: Using our previously established model, during gestational days 5 to 20, four groups of pregnant Sprague-Dawley rats were exposed to vaporized alcohol, delta-9-Tetrahydrocannabinol (THC) via electronic (e-) cigarettes, the combination of alcohol and THC, or a vehicle. Following birth, offspring were tested on early sensorimotor development, adolescent motor coordination, and adolescent activity levels. RESULTS: Prenatal THC e-cigarette exposure delayed sensorimotor development early in life and impaired motor coordination later in early adolescence; combined prenatal alcohol and THC exposure did not have additive effects on sensorimotor development. However, combined prenatal exposure produced hyperactivity among male offspring. CONCLUSIONS: Prenatal cannabis exposure may lead to impaired motor skills throughout early development and combined exposure with alcohol during gestation may lead to hyperactivity in early adolescence. These findings have important implications for informing pregnant women of the risks to the fetus associated with prenatal cannabis exposure, with and without alcohol, and could influence public policy.

Explicit Instruction of Scientific Uncertainty in an Undergraduate Geoscience Field-Based Course.

Understanding and communicating uncertainty is a key skill needed in the practice of science. However, there has been little research on the instruction of uncertainty in undergraduate science education. Our team designed a module within an online geoscience field course which focused on explicit instruction around uncertainty and provided students with an uncertainty rating scale to record and communicate their uncertainty with a common language. Students then explored a complex, real-world geological problem about which expert scientists had previously made competing claims through geologic maps. Provided with data, expert uncertainty ratings, and the previous claims, students made new geologic maps of their own and presented arguments about their claims in written form. We analyzed these reports along with assessments of uncertainty. Most students explicitly requested geologists' uncertainty judgments in a post-course assessment when asked why scientists might differ in their conclusions and/or utilized the rating scale unprompted in their written arguments. Through the examination of both pre- and post-course assessments of uncertainty and students' course-based assessments, we argue that explicit instruction around uncertainty can be introduced during undergraduate coursework and could facilitate geoscience novices developing into practicing geoscientists.

Prevalence and correlates of cancer-related fatigue in breast cancer survivors.

PURPOSE: To identify potential correlates of cancer-related fatigue (CRF) after curative breast cancer (BC) treatment. The hypothesis was that fatigue would be more severe among women treated with cardiotoxic drugs, with poor physical condition and those who exercised less. METHODS: Observational cross-sectional design. Fatigue was evaluated through PERFORM Questionnaire (multi-item, multi-dimensional). Patient-reported assessments and objective information regarding clinical data, physical activity (PA) and physical condition were analysed as potential correlates of CRF. RESULTS: One hundred eighty women who remained free of disease were recruited. The prevalence of fatigue interfering with quality of life was 43%. Weight, resting and recovery heart rate were positively associated with fatigue. Age and time from diagnosis were negatively associated. Previous therapies, objectively assessed weekly PA, cardiorespiratory condition, muscular strength and adherence to Mediterranean diet were not associated with CRF. CONCLUSIONS: CRF is a prevalent problem after BC treatment. Objectively assessed PA, cardiorespiratory fitness and muscular strength did not predict CRF. The association of heart rate and fatigue deserves a further insight. Future research should include longitudinal studies and determination of biomarkers. IMPLICATIONS FOR CANCER SURVIVORS: BC survivors, especially younger and overweight women, should be informed about fatigue as a potential persistent symptom through all stages of the cancer trajectory and into survivorship. They also should be routinely screened for CRF.

Fragmentation in the future of work: A horizon scan examining the impact of the changing nature of work on workers experiencing vulnerability.

INTRODUCTION: The future of work is characterized by changes that could disrupt all aspects of the nature and availability of work. Our study aims to understand how the future of work could result in conditions, which contribute to vulnerability for different groups of workers. METHODS: A horizon scan was conducted to systematically identify and synthesize diverse sources of evidence, including academic and gray literature and resources shared over social media. Evidence was synthesized, and trend categories were developed through iterative discussions among the research team. RESULTS: Nine trend categories were uncovered, which included the digital transformation of the economy, artificial intelligence (AI)/machine learning-enhanced automation, AI-enabled human resource management systems, skill requirements for the future of work; globalization 4.0, climate change and the green economy, Gen Zs and the work environment; populism and the future of work, and external shocks to accelerate the changing nature of work. The scan highlighted that some groups of workers may be more likely to experience conditions that contribute to vulnerability, including greater exposure to job displacement or wage depression. The future of work could also create opportunities for labor market engagement. CONCLUSION: The future of work represents an emerging public health concern. Exclusion from the future of work has the potential to widen existing social and health inequities. Thus, tailored supports that are resilient to changes in the nature and availability of work are required for workers facing vulnerability.

Assessing planning implementation using the conformance and performance approach: The case of Romania's local environmental action plans.

Many of the outcomes of environmental plans are difficult to measure. Therefore, little is known as to whether such plans achieve their goals, whether outcomes are reached and lessons learned to influence future plans. Our study aims to address this gap by systematically evaluating the implementation of Local Environmental Action Plans (LEAPs) of 29 counties in Romania and the factors affecting it. We draw on both quantitative (official statistical data) and qualitative (planners' assessments) evaluation methods and two conceptions of plan implementation success (conformance and performance based) to assess LEAP implementation. Our findings indicate mixed levels of conformance and performance. While the implementation of LEAPs conforms with the plans from the perspective of progress of overall policy implementation, this does not conform with the plans in terms of positive changes on the ground. LEAPs perform well in mitigating local environmental problems and coordinating with other planning initiatives but badly in terms of their usefulness in the decision-making process, having little influence on lower-level plans. Furthermore, the quality of LEAPs may not be important in relation to their implementation, while investments in the capacity of planning agencies, as well as local political support and participatory approaches, may improve the implementation of LEAPs in the future. The results of our study may assist the devising bodies in enhancing the implementation of future versions of LEAPs by revealing the main opportunities and constraints influencing implementation.

Copper Complexes with 1,10-Phenanthroline Derivatives: Underlying Factors Affecting Their Cytotoxicity.

The interpretation of in vitro cytotoxicity data of Cu(II)-1,10-phenanthroline (phen) complexes normally does not take into account the speciation that complexes undergo in cell incubation media and its implications in cellular uptake and mechanisms of action. We synthesize and test the activity of several distinct Cu(II)-phen compounds; up to 24 h of incubation, the cytotoxic activity differs for the Cu complexes and the corresponding free ligands, but for longer incubation times (e.g., 72 h), all compounds display similar activity. Combining the use of several spectroscopic, spectrometric, and electrochemical techniques, the speciation of Cu-phen compounds in cell incubation media is evaluated, indicating that the originally added complex almost totally decomposed and that Cu(II) and phen are mainly bound to bovine serum albumin. Several methods are used to disclose relationships between structure, activity, speciation in incubation media, cellular uptake, distribution of Cu in cells, and cytotoxicity. Contrary to what is reported in most studies, we conclude that interaction with cell components and cell death involves the separate action of Cu ions and phen molecules, not [Cu(phen)n] species. This conclusion should similarly apply to many other Cu-ligand systems reported to date.

Recapitulating the Bayesian framework for neurosurgical outpatient care and a cost-benefit analysis of telemedicine for socioeconomically disadvantaged patients in the Philippines during the pandemic.

OBJECTIVE: In the Philippines during recent months, a neurosurgical center that caters primarily to socioeconomically disadvantaged patients has encountered unprecedented changes in practice patterns brought about by the COVID-19 pandemic. In particular, the usual task of outpatient care has shifted to the telemedicine format, bringing along all of its attendant advantages and gargantuan challenges. The authors sought to determine the responsiveness of this telemedicine setup to the needs of their disadvantaged patients and explored the application of Bayesian inference to enhance the use of teleconsultation in daily clinical decision-making. METHODS: The authors used the following methods to assess the telemedicine setup used in a low-resource setting during the pandemic: 1) a cross-sectional survey of patients who participated in a medical consultation via telemedicine during the 16-week period from March 16, 2020, to July 15, 2020; 2) a cost-benefit analysis of the use of telemedicine by patients; and 3) a case illustration of a Bayesian approach application unique to the teleconsultation scenario. RESULTS: Of the 272 patient beneficiaries of telemedicine in a 16-week period, 57 responded to the survey. The survey responses regarding neurosurgical outpatient care through telemedicine yielded high ratings of utility for the patients and their caregivers. According to 64% of respondents, the affordability of the telemedicine setup also prevented them from borrowing money from others, among other adverse life events prevented. There were realized financial gains on the part of the patients in terms of cost savings and protection from further impoverishment. The benefit-cost ratio was 3.51 for the patients, signifying that the benefits outweighed the costs. An actual teleconsultation case vignette was reported that is meant to be instructive and contributory to the preparedness of the neurosurgeon on the provider end of the service delivery. CONCLUSIONS: Telemedicine holds promise as a viable and safe method for health service delivery during the pandemic. In the setting of a health system that is continually challenged by shortages of resources, this study shows that an effective telemedicine setup can come with high benefit-cost ratios and quality of care, along with the assurance of patient satisfaction. The potential for high-quality care can be enhanced by the inclusion of the Bayesian framework to the basic toolkit of remote clinical assessment. When confronted with choices in terms of differential diagnosis and tests, the rigor of a simple application of the Bayesian framework can minimize costs arising from uncertainties.

Antiparasitic and anti-inflammatory activities of ß-lapachone-derived naphthoimidazoles in experimental acute Trypanosoma cruzi infection.

BACKGROUND: Chagas disease, which is caused by the protozoan Trypanosoma cruzi, is endemic to Latin America and mainly affects low-income populations. Chemotherapy is based on two nitrocompounds, but their reduced efficacy encourages the continuous search for alternative drugs. Our group has characterised the trypanocidal effect of naphthoquinones and their derivatives, with naphthoimidazoles derived from ß-lapachone (N1, N2 and N3) being the most active in vitro. OBJECTIVES: In the present work, the effects of N1, N2 and N3 on acutely infected mice were investigated. METHODS: in vivo activity of the compounds was assessed by parasitological, biochemical, histopathological, immunophenotypical, electrocardiographic (ECG) and behavioral analyses. FINDINGS: Naphthoimidazoles led to a decrease in parasitaemia (8 dpi) by reducing the number of bloodstream trypomastigotes by 25-50% but not by reducing mortality. N1 protected mice from heart injury (15 dpi) by decreasing inflammation. Bradycardia was also partially reversed after treatment with N1 and N2. Furthermore, the three compounds did not reverse hepatic and renal lesions or promote the improvement of other evaluated parameters. MAIN CONCLUSION: N1 showed moderate trypanocidal and promising immunomodulatory activities, and its use in combination with benznidazole and/or anti-arrhythmic drugs as well as the efficacy of its alternative formulations must be investigated in the near future.

An evaluation of environmental plans quality: Addressing the rational and communicative perspectives.

Environmental action plans are important instruments intended to provide sustainable solutions for the most pressing environmental issues. As they should be updated regularly, efforts to evaluate their quality are essential for enabling incremental improvements in upcoming versions. The aim of our study was to systematically evaluate the quality of Romania's Local Environmental Action Plans (LEAPs) by following a theoretical framework that includes principles from both rational and communicative approaches to assessing plan quality. We selected 32 LEAPs and applied an evaluation protocol that enabled a comprehensive assessment of the plans. Our results showed an overall moderate quality of the LEAPs. Although most plans identify many environmental problems in need of solutions, in reality additional urgent environmental problems often exist. Furthermore, LEAPs perform only moderately in identifying tools for implementation provisions and ensuring the participation of the public in the planning process, and they are even weaker in establishing goals and achieving coordination across different governmental levels. Overall the assessment reveals that plans are rarely able to craft an appealing policy message. Our findings could be used as guidance for LEAP coordinating agencies to improve the plans in the upcoming updating processes, as they identify plan weaknesses and suggest ways to achieve high quality environmental plans. Furthermore, our novel plan assessment method based on rational comprehensive and communicative approaches to plan quality evaluation can be adapted easily to other studies.

Organophosphorus Pesticides Induce Cytokine Release from Differentiated Human THP1 Cells.

Epidemiologic studies link organophosphorus pesticides (OPs) to increased incidence of asthma. In guinea pigs, OP-induced airway hyperreactivity requires macrophages and TNF-α. Here, we determined whether OPs interact directly with macrophages to alter cytokine expression or release. Human THP1 cells were differentiated into macrophages and then exposed to parathion, chlorpyrifos, or diazinon, or their oxon, phosphate, or phosphorothioate metabolites for 24 hours in the absence or presence of reagents that block cholinergic receptors. TNF-α, IL-1ß, platelet-derived growth factor, and transforming growth factor-ß mRNA and protein were quantified by qPCR and ELISA, respectively. The effects of OPs on NF-κB, acetylcholinesterase, and intracellular calcium were also measured. Parent OPs and their oxon metabolites upregulated cytokine mRNA and stimulated cytokine release. TNF-α release, which was the most robust response, was triggered by parent, but not oxon, compounds. Cytokine expression was also increased by diethyl dithiophosphate but not diethyl thiophosphate or diethyl phosphate metabolites. Parent OPs, but not oxon metabolites, activated NF-κB. Parent and oxon metabolites decreased acetylcholinesterase activity, but comparable acetylcholinesterase inhibition by eserine did not mimic OP effects on cytokines. Consistent with the noncholinergic mechanisms of OP effects on macrophages, pharmacologic antagonism of muscarinic or nicotinic receptors did not prevent OP-induced cytokine expression or release. These data indicate that phosphorothioate OP compounds directly stimulate macrophages to release TNF-α, potentially via activation of NF-κB, and suggest that therapies that target NF-κB may prevent OP-induced airway hyperreactivity.

Successful aging in Spanish older adults: the role of psychosocial resources.

ABSTRACTBackground:Psychological and social resources such as extraversion, optimism, social support, or social networks contribute to adaptation and to successful aging. Building on assumptions derived from successful aging and from the developmental adaptation models, this study aims to analyze the joint impact of different psychosocial resources, such as personality, social relations, health, and socio-demographic characteristics on life satisfaction in a group of people aged 65 years-old and older from Spain. METHOD: A cross-sectional survey using non-proportional quota sampling was carried out. The sample comprised 406 community-dwelling older adults (M = 74.88, SD = 6.75). In order to collect the data, face-to-face interviews were individually conducted. A structural equation model (SEM) was carried out using the PLS software. RESULTS: The results of the SEM model showed that, within this sample, psychosocial variables explain 47.4% of the variance in life satisfaction. Social relations and personality, specifically optimism, were strongly related with life satisfaction, while health status and socio-demographic characteristics were modestly associated with life satisfaction. CONCLUSIONS: Findings support the view that psychosocial resources are important for successful aging and therefore should be included in successful aging models. Furthermore, interventions aimed at fostering successful aging should take into account the role of psychosocial variables.

Construction and validation of an questionnaire for evaluating self-medication practised by patients with temporomandibular disorders.

AIMS: Despite the fact that self-medication associated with temporomandibular disorders is clinically quite common and is considerably harmful, there is no instrument in the literature to assess this practice. The aim of this study was to construct and validate a questionnaire to study this important issue specifically. METHODS: After completing the literature review, semi-structured interviews, focus group and pretest, the first version of the instrument resulted in 62 questions. After face validity testing, pretest and the necessary corrections and changes, the instrument had 41 questions and was administered for validation to a sample of 110 patients diagnosed with TMD according to the RDC/TMD (1992) criteria. RESULTS: According to factor analysis, seven questions with loadings below 0.30 were removed, with the final version consisting of 34 questions. The analysis of internal consistency and temporal stability showed values of 0.844 for Cronbach's alpha coefficient and a Kappa coefficient of 0.810, respectively, indicating that the instrument presents sufficient reliability and reproducibility for its proposed objective. After validation, with the ultimate goal of classifying patients according to the degree/intensity of self-medication, a classification was proposed that allowed the discrimination of results into three distinct groups regarding self-medication exposure: mild, moderate or severe, based on the self-medication raw point score. CONCLUSION: The results of the instrument validation process showed that it has suitable properties for evaluating the practice of self-medication in patients with TMD.

Coping strategies in Spanish older adults: a MIMIC model of socio-demographic characteristics and activity level.

OBJECTIVES: The aim of this study was to analyze the combined effect of socio-demographic characteristics and activity level on coping strategies and to test which of these variables has a greater impact on coping. METHOD: A sample of 243 men and women aged 55-99 years old was selected from different elderly activity centers in Granada, Spain, using a convenience sampling. Associations between eight coping strategies measured by Coping Strategies Inventory and the above mentioned variables were examined using a Multiple Indicator and Multiple Causes model. RESULTS: Age was negatively related with problem solving, express emotions and social support. Activity level was positively related with problem solving, cognitive restructuring, express emotions and social support and it was negatively associated with social withdrawal. Gender only predicted the scores in self-criticism and living alone was related with higher emotional expression. Participation in creative activities, attending University for the third age and practicing physical exercise were related with differences in the use of several coping strategies. CONCLUSIONS: There is a complex relationship between socio-demographic characteristics, activity level and the coping strategies used by the elderly. It is important to understand this relationship in order to identify older adults who use ineffective coping, and to subsequently include them in intervention programs to improve their coping abilities.

Extroversion, social support and life satisfaction in old age: a mediation model.

OBJECTIVES: The aim of this study was twofold: on the one hand to analyze whether extroversion predicts social support in older people, and on the other hand to determine if different types of social support mediate the effect that extroversion has on older people's life satisfaction. METHOD: The sample comprised 406 community-dwelling older adults (M = 74.88, SD = 6.75) from urban areas of Granada, southern Spain. RESULTS: Extroversion was positively correlated with emotional (r = .23) and with affectionate support (r = .30). Extroversion and all types of social support also positively correlated with life satisfaction. The multiple mediation analysis revealed that when age, gender, marital status and loneliness were controlled, extroversion predicted emotional (B = .008, p < .01) and affectionate support (B = .015, p < .01) and emotional and affectionate support mediated the association between extroversion and life satisfaction (total effect: B = .034, SE = .0024, p < .001, r2 = .295). Results from this study highlight the fact supportive social relations are crucial for older people's life satisfaction. Also emotional and affectionate support constitutes important explanatory mechanisms of the indirect effect of extroversion on life satisfaction. CONCLUSION: Personality traits should be considered when interventions aimed at promoting life satisfaction in old age and successful aging are designed.