Outcomes of Cerebral Venous Thrombosis due to Vaccine-Induced Immune Thrombotic Thrombocytopenia After the Acute Phase.

BACKGROUND: Cerebral venous thrombosis (CVT) due to vaccine-induced immune thrombotic thrombocytopenia (VITT) is a severe condition, with high in-hospital mortality rates. Here, we report clinical outcomes of patients with CVT-VITT after SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) vaccination who survived initial hospitalization. METHODS: We used data from an international registry of patients who developed CVT within 28 days of SARS-CoV-2 vaccination, collected until February 10, 2022. VITT diagnosis was classified based on the Pavord criteria. Outcomes were mortality, functional independence (modified Rankin Scale score 0-2), VITT relapse, new thrombosis, and bleeding events (all after discharge from initial hospitalization). RESULTS: Of 107 CVT-VITT cases, 43 (40%) died during initial hospitalization. Of the remaining 64 patients, follow-up data were available for 60 (94%) patients (37 definite VITT, 9 probable VITT, and 14 possible VITT). Median age was 40 years and 45/60 (75%) patients were women. Median follow-up time was 150 days (interquartile range, 94-194). Two patients died during follow-up (3% [95% CI, 1%-11%). Functional independence was achieved by 53/60 (88% [95% CI, 78%-94%]) patients. No new venous or arterial thrombotic events were reported. One patient developed a major bleeding during follow-up (fatal intracerebral bleed). CONCLUSIONS: In contrast to the high mortality of CVT-VITT in the acute phase, mortality among patients who survived the initial hospitalization was low, new thrombotic events did not occur, and bleeding events were rare. Approximately 9 out of 10 CVT-VITT patients who survived the acute phase were functionally independent at follow-up.

Linear and non-linear relationships among the dimensions representing the cognitive structure of emotion.

While dimensional models play a key role in emotion psychology, no consensus has been reached about their number and nature. The current study sheds a new light on this central issue by examining linear and non-linear relationships among the dimensions in the cognitive emotion structure. The meaning of 80 emotion terms was evaluated on 68 features representing appraisals, action tendencies, bodily reactions, expressions, and subjective experiences by 213 English-speaking US, 156 French-speaking Swiss, and 194 Indonesian-speaking Indonesian students. In a two-dimensional valence and arousal representation, neither linear nor non-linear relationships were observed. In a four-dimensional valence, power, arousal, and novelty representation, both linear (e.g. a positive relationship between valence and power) and non-linear (e.g. a strong positive correlation between valence and power found only for positively valenced emotion terms) relationships were observed. Joy- and sadness-related emotion terms where about as well represented by the two- than by the four-dimensional representation. However, especially anger- and surprise-related terms were only adequately represented by the four-dimensional representation. These findings were generalisable across the three languages. Even though a two-dimensional structure fits the data well in general, four dimensions are needed to sufficiently represent the cognitive structure of the whole gamut of human emotions.

Collaborative agroforestry to mitigate wildfires in Extremadura, Spain: land manager motivations and perceptions of outcomes, benefits, and policy needs.

Wildfires are increasing in severity, and magnitude in the Mediterranean Basin in recent years, reaching a yearly average of 450 000 ha over the last decade. Drivers include climate change, land-use change, and land abandonment. Wildfire mitigation requires landscape-level action as impact to each parcel is affected by the conditions of the others. We conducted a case study of a regional-level initiative that develops community efforts to mitigate wildfires through silvo-pastoral agroforestry systems, using an integrated landscape management approach. This approach involves collaboration among stakeholders to achieve multiple objectives. In order to derive insights into its potential, we asked participating land managers: (1) What motivates their participation?, (2) How do they perceive initiative outcomes?, and as urban outmigrants with non-traditional goals are increasing in rural areas, (3) Do responses differ between rural and neo-rural participants? Our results show that managers feel highly affected by wildfires and are strongly motivated to reduce wildfire risk. Land abandonment and inappropriate policy were major concerns. The initiative was seen to have positive outcomes for individual participants as well as the region, and to stimulate community connectedness. We conclude that fit to local contexts, integrated landscape management can be a well-received approach to reducing wildfire risk. Agroforestry systems in Extremadura can act as "productive fuelbreaks" that reduce fire risk over extensive areas, while restoring traditional landscapes. We suggest that programs to reduce wildfire risk can also be used as a leverage point for financing rural revival and provision of multiple ecosystem services. Supplementary Information: The online version contains supplementary material available at 10.1007/s10457-022-00771-6.

Bronchial Infection and Temporal Evolution of Bronchiectasis in Patients With Chronic Obstructive Pulmonary Disease.

BACKGROUND: Bronchiectasis (BE) impact the clinical course and prognosis of patients with chronic obstructive pulmonary disease (COPD). Yet, the temporal evolution of BE in these patients is unknown. This study seeks to assess the temporal evolution of BE in persons with COPD. METHODS: 201 moderate-to-severe patients were recruited between 2004 and 2007 and followed up at least every 6 monts (median of 102 months). To investigate the temporal evolution of BE, in 2015 a second high-resolution computed tomography scan (HRCT) was obtained in survivors and compared with the one obtained at recruitment. RESULTS: 99 (49.3%) died during follow-up. The second HRCT could be obtained in 77 patients and showed that (1) in 27.3% of patients BE never developed, in 36.4% they remained stable, in 16.9% they increased in size and/or extension, and in 19.5% new BE emerged; and that (2) the presence of chronic purulent sputum (hazard ratio [HR], 2.8 [95% confidence interval {CI}, 1.3-5.8]), number of hospitalizations due to exacerbatons (HR, 1.2 [95% CI, 1.1-1.5]), and number of pathogenic microorganism (PPM) isolations (HR, 1.1 [95% CI, 1.02-1.3]) were independent risk factors for the progression or development of BE. CONCLUSIONS: The presence of chronic purulent sputum production, number of PPMs isolated in sputum, and number of hospitalizations due to exacerbations of COPD are independent risk factors of BE progression in patients with COPD.

Mercury consumption and human health: Linking pollution and social risk perception in the southeastern United States.

The study of the relationships between freshwater organisms, pollution and public awareness has been little researched. The public's perception of risk from pollution is a fundamental component in determining consumer behavior and promoting healthy habits. For instance, understanding how consumers perceive the risks associated with pollution can help with adoption of safe behaviors to reduce the health hazard associated with pollutant exposure. This study focused on the southeastern United States, a region predicted to be exposed to high mercury stress by increasing mercury deposition and methylation. First, we placed our study region in the world map of regions more prone to suffer from increasing mercury stress in a climate change scenario. Second, mercury levels in fish tissues was quantified by direct mercury analyzer (DMA). Third, we explored human fish consumption habits and risk social perception, including willingness to adapt fish consumption based on two future hypothetical scenarios of mercury stress. From a global perspective, our analysis demonstrates that the southern US is one of five world areas of greatest conservation concern for mercury stress. In this region, the average mono-methyl mercury concentration in fish tissues exceeded the limits considered safe for human consumption. Even though many in the local population were aware of the health hazards associated with fish consumption, only women of reproductive age were willing to adopt safe consumption habits. Altogether, these results show how bringing together field data, social perceptions, and consumption habits can help in designing an adaptive strategy to confront mercury pollution. Although our results are for the United States, other world regions prone to suffer increasing mercury stress have been identified and should be the focus of future studies and prescriptions.

Are concepts of achievement-related emotions universal across cultures? A semantic profiling approach.

Verifying that conceptualisations of emotions are consistent across languages and cultures is a critical precondition for meaningful cross-cultural research on emotional experience. For achievement-related emotions tied to successes or failures, such evidence is virtually non-existent. To address this gap, we compared Canadian, German, Colombian, and Chinese university students' (NTotal = 126) perceptions of affective, cognitive, motivational, physiological, and expressive characteristics of 16 achievement-related emotions using a psycholinguistic tool for profiling emotion concepts (Achievement Emotions CoreGRID). Cross-cultural similarity of emotion concepts quantified through double-entry intraclass correlations was generally high, and highest for their affective, cognitive, and motivational components. However, results also point to cultural variation, particularly for physiological and expressive components. Variation in perceived physiological characteristics was most pronounced for boredom, and for comparisons of Canada, Germany, and Colombia with China. Implications for theoretical propositions of universality of emotion concepts and future research on achievement-related emotions are discussed.

Increased Incidence of Stroke, but Not Coronary Heart Disease, in Elderly Patients With Sleep Apnea.

Background and Purpose- The influence of age on the relationship between obstructive sleep apnea (OSA) and the incidence of hard cardiovascular events remains controversial. We sought to analyze the relationship between OSA and the incidence of stroke and coronary heart disease in a large cohort of elderly patients, as well as to investigate the role of continuous positive airway pressure (CPAP) treatment in these associations. Methods- Post hoc analysis of a prospective observational study of consecutive patients ≥65 years studied for OSA suspicion at 2 Spanish University Hospitals. Patients with an apnea-hypopnea index (AHI) <15 were the reference group. OSA was defined by an AHI ≥15 and classified as untreated (CPAP not prescribed or compliance <4 hours/day), mild-moderate (AHI 15-29), untreated severe (AHI ≥30), and CPAP-treated (AHI ≥15 and CPAP compliance ≥4 hours/day). Results- 859 and 794 elderly patients were included in the stroke and coronary heart disease analyses, respectively. The median (interquartile range) follow-up was 72 (50-88.5) and 71 (51.5-89) months, respectively. Compared with the reference group, the fully adjusted hazard ratios for the incidence of stroke were 3.42 (95% CI, 1.37-8.52), 1.02 (95% CI, 0.41-2.56), and 1.76 (95% CI, 0.62-4.97) for the untreated severe OSA group, CPAP-treated group, and untreated mild-moderate OSA group, respectively. No associations were shown between any of the different OSA groups and coronary heart disease incidence. Conclusions- The incidence of stroke, but not coronary heart disease, is increased in elderly patients with untreated severe OSA. Adequate CPAP treatment may reduce this risk.

Good long-term adherence to continuous positive airway pressure therapy in patients with resistant hypertension and sleep apnea.

Although adequate adherence is paramount in achieving the beneficial effects of continuous positive airway pressure therapy in patients with obstructive sleep apnea, long-term adherence and the variables involved in continuous positive airway pressure compliance in patients with resistant hypertension and obstructive sleep apnea are yet unknown. We conducted a prospective, multicentre, observational study in 177 patients recruited from hypertensive units with resistant hypertension confirmed by means of 24-hr blood pressure monitoring (blood pressure ≥ 130 and/or ≥ 80 mmHg, despite taking at least three antihypertensive drugs or < 130/80 mmHg with > 3 drugs) and obstructive sleep apnea (apnea-hypopnea index ≥ 5 in a respiratory polygraph) who were prescribed continuous positive airway pressure treatment. Good adherence was defined as an average cumulative continuous positive airway pressure use of ≥ 4 hr per night at the end of the follow-up. A multivariate Cox regression analysis was performed to identify independent predictors of continuous positive airway pressure adherence. Patients were followed for a median of 57.6 (42-72) months after initiating continuous positive airway pressure therapy. At the end of the follow-up, the median continuous positive airway pressure use was 5.7 (inter-quartile range 3.9-6.6) hr per night, and 132 patients (74.5%) showed good continuous positive airway pressure adherence. The only baseline variable associated with poor adherence was the presence of previous stroke (hazard ratio 4.00, 95% confidence interval 1.92-8.31). Adequate adherence at 1 month also predicted good adherence at the end of the follow-up (hazard ratio 14.4, 95% confidence interval 4.94-56). Both variables also predicted adherence at a threshold of 6 hr per night. Our results show that good continuous positive airway pressure adherence is an achievable and feasible goal in patients with resistant hypertension and obstructive sleep apnea. Previous stroke and short-term adherence predicted long-term adherence.

Urinary levels of sirtuin-1 associated with disease activity in lupus nephritis.

Identifying new markers of disease flares in lupus nephritis (LN) that facilitate patient stratification and prognosis is important. Therefore, the aim of the present study was to analyze whether urinary SIRT1 expression was altered in LN and whether SIRT1 values in urine could be valuable biomarker of disease activity. In a cohort study, urinary pellets from 40 patients diagnosed with systemic lupus erythematosus (SLE) were analyzed. Clinical measures of lupus activity were assessed. The expression of SIRT1 was quantified by quantitative PCR (qRT-PCR) and immunoblot, then compared between patients with active lupus nephritis, in remission and healthy controls. Association with lupus activity and renal histological features was also analyzed. A significant increase in SIRT1 mRNA levels in patients with active LN was observed compared with those in remission (P=0.02) or healthy controls (P=0.009). In addition, SIRT-1 protein levels were also augmented in LN group than remission (P=0.029) and controls (P=0.001). A strong association was found between SIRT1 expression with anti-dsDNA in SLE and in patients with LN. In addition, histological features in LN biopsies were related with SIRT1, increasing its expression in proliferative forms. Finally, SIRT1 expression values showed a strong discriminatory power of renal injury in SLE. Our study demonstrated an altered urinary expression of SIRT1 and a strong association with disease activity in LN patients, being a valuable marker of renal injury. These results showed the role of the SIRT1 pathway in the SLE pathogenesis.

Effects of achievement contexts on the meaning structure of emotion words.

Little is known about the impact of context on the meaning of emotion words. In the present study, we used a semantic profiling instrument (GRID) to investigate features representing five emotion components (appraisal, bodily reaction, expression, action tendencies, and feeling) of 11 emotion words in situational contexts involving success or failure. We compared these to the data from an earlier study in which participants evaluated the typicality of features out of context. Profile analyses identified features for which typicality changed as a function of context for all emotion words, except contentment, with appraisal features being most frequently affected. Those context effects occurred for both hypothesised basic and non-basic emotion words. Moreover, both data sets revealed a four-dimensional structure. The four dimensions were largely similar (valence, power, arousal, and novelty). The results suggest that context may not change the underlying dimensionality but affects facets of the meaning of emotion words.

Can dry rivers provide a good quality of life? Integrating beneficial and detrimental nature's contributions to people over time.

Although dry rivers only flow after heavy rainfall, recent studies have evidenced that they provide benefits to people. However, part of society undervalues these benefits, raising the question of whether they contribute to a good quality of life (GQL). We hypothesised that the benefits of dry rivers contribute to GQL of local communities as long as these benefits are not altered by human disturbance. Local communities closely associated with three dry rivers in Murcia (Spain) were interviewed. The relationships between benefits and GQL, and between detriments and GQL were described. Different benefits and detriments have different impacts on GQL dimensions. Social perceptions of the contribution of benefits and detriments to GQL vary between communities and individuals, and change over time. This implies the development of social studies to ensure inclusive management. Incorporating detriment co-production into research can raise people's awareness of the role that human activities play in maintaining GQL.

Gender Disparities in Adverse Events Resulting From Low-Value Practices in Family Practice in Spain: A Retrospective Cohort Study.

Objectives: This study aimed to evaluate gender-based disparities in preventable adverse events due to low-value practices (LVPs) in primary care. Methods: A retrospective cohort study in Alicante, Spain. Results: A total of 1,516 patient records were examined, finding that older individuals and women experienced more LVP-related events. Female patients faced a higher volume of such events than males with the same health issue. Interaction analysis revealed patients treated by male physicians had more severe events, while those attended by females experienced milder ones. Adverse events were more frequent in LVPs associated with gender-based reasons. Conclusion: These results highlight the need for tailored healthcare professional awareness programs on overuse's impact on safety. Addressing outcome differences between male and female patients should inform awareness campaigns.

Landscape products for sustainable agricultural landscapes.

Landscape products link to low-input practices and traditional ecological knowledge, and have multiple functions supporting human well-being and sustainability. Here we explore seven landscape products worldwide to identify these multiple functions in the context of food commodification and landscape sustainability. We show that a landscape products lens can improve food systems by fostering sustainability strategies and standards that are place-sensitive, and as such can mitigate conflicts related to food production, social justice and the environment. Co-management strategies and information policies, such as certification, labelling, product information and raising of awareness could accelerate, incentivize and catalyse actions to support landscape products in the context of sustainability strategies.

An interdisciplinary assessment of private conservation areas in the Western United States.

Conservation easements are the fastest growing private conservation strategy in the United States. However, mechanisms to assess private land conservation as well as their support by the general public are not well understood. This study uses the ecosystem services framework for assessing existing private lands in Idaho and identifies areas for future conservation easements. Using conservation targets of the land trust as a guide for selecting ecosystem services, we (a) mapped the spatial delivery of conservation targets across public and private lands, (b) explored public awareness in terms of social importance and vulnerability, and (c) mapped future priority areas by characterizing conservation bundles. We found that public lands provided the highest levels of conservation targets, and we found no difference in conservation target provision between private areas and conservation easements. The spatial characterization of conservation target bundles identified potential future priority areas for conservation easements, which can guide planning of land trust conservation efforts.

Long-term Effect of CPAP Treatment on Cardiovascular Events in Patients With Resistant Hypertension and Sleep Apnea. Data From the HIPARCO-2 Study.

BACKGROUND: There is some controversy about the effect of continuous positive airway pressure (CPAP) on the incidence of cardiovascular events (CVE). However, the incidence of CVE among patients with both obstructive sleep apnea (OSA) ans resistant hypertension (HR) has not been evaluated. Our objective was to analyze the long-term effect of CPAP treatment in patients with RH and OSA on the incidence of CVE. METHODS: Multi-center, observational and prospective study of patients with moderate-severe OSA and RH. All the patients were followed up every 3-6 months and the CVE incidence was measured. Patients adherent to CPAP (at least 4h/day) were compared with those with not adherent or those who had not been prescribed CPAP. RESULTS: Valid data were obtained from 163 patients with 64 CVE incidents. Treatment with CPAP was offered to 82%. After 58 months of follow-up, 58.3% of patients were adherent to CPAP. Patients not adherent to CPAP presented a non-significant increase in the total CVE incidence (HR:1.6; 95%CI: 0.96-2.7; p=0.07). A sensitivity analysis showed that patients not adherent to CPAP had a significant increase in the incidence of cerebrovascular events (HR: 3.1; CI95%: 1.07-15.1; p=0.041) and hypertensive crises (HR: 5.1; CI95%: 2.2-11.6; p=0.006), but the trend went in the opposite direction with respect to coronary events (HR: 0.22; CI95%: 0.05-1.02; p=0.053). CONCLUSIONS: In patients with RH and moderate-severe OSA, an uneffective treatment with CPAP showed a trend toward an increase in the incidence of CVE (particularly neurovascular events and hypertensive crises) without any changes with respect to coronary events.

The HIPARCO-2 study: long-term effect of continuous positive airway pressure on blood pressure in patients with resistant hypertension: a multicenter prospective study.

INTRODUCTION: Short-term treatment with continuous positive airway pressure (CPAP) produces a clinically significant reduction in blood pressure (BP) in patients with obstructive sleep apnea (OSA) and resistant hypertension. However, it is unknown whether this effect continues over the long-term. Our objective was to assess the effect of long-term CPAP on BP in patients with OSA and resistant hypertension. METHODS: The study included 161 patients diagnosed with both OSA [apnea--hypopnea index (AHI) ≥15] and resistant hypertension diagnosed via 24-hour ambulatory BP measurement (24-h ABPM), in whom a second analysis via 24-h ABPM was performed at the end of the follow-up. RESULTS: Patients were followed up within 59 months [interquartile range (IQR): 44-70]. CPAP treatment was prescribed to 82% of the patients (70% with good adherence to CPAP defined as use of CPAP at least 4 h/night). A comparison between the adherent group and nonadherent group (including those with CPAP not prescribed) showed that CPAP adherents had a significant drop in the 24-h BP, both systolic [-3.9 mmHg; 95% confidence interval (CI): -8.1 to 0.3] and diastolic pressure (-3.5 mmHg [95% [CI]: -6.4-0.5]), with a higher magnitude during the night (-5.5 and -4.9 mmHg, respectively). The CPAP adherent group needed a mean of 1.1 less antihypertensive drugs (particularly spironolactone). Finally, there was a positive correlation between the drop in 24-h SBP and the hours of CPAP use (r = 0.24; P = 0.01). CONCLUSION: Good adherence to long-term CPAP treatment largely succeeded in significantly reducing BP in those patients with OSA and resistant hypertension, despite the use of a lower number of antihypertensive drugs.

Effect of continuous positive airway pressure in patients with true refractory hypertension and sleep apnea: a post-hoc intention-to-treat analysis of the HIPARCO randomized clinical trial.

RATIONALE: Continuous positive airway pressure (CPAP) can significantly reduce blood pressure (BP) levels in patients with resistant hypertension and sleep apnea (OSA); however, the effect on patients with refractory hypertension (RfH) is not known. This study seeks to evaluate the effect of CPAP treatment on BP levels in patients with OSA and RfH, compared with those with OSA and resistant hypertension. METHODS: Post-hoc analysis of the HIPARCO randomized clinical trial on the effect of CPAP treatment on BP levels in patients with resistant hypertension. Those patients with uncontrolled 24-h ambulatory BP monitoring readings (>130 and/or >80 mmHg) in SBP or DBP were considered to have resistant hypertension (if they were taking three or four antihypertensive drugs) or RfH (if they were taking at least five drugs). OSA patients were randomized to receive CPAP or usual care for 3 months. They underwent a second 24-h ambulatory BP monitoring study to establish the effect of CPAP treatment on BP levels in both groups. RESULTS: A total of 98 patients were randomized to CPAP (19 RfH/79 resistant hypertension) and 96 to usual care (21 RfH/75 resistant hypertension). BP readings dropped more marked in patients with RfH than resistant hypertension, in both 24-h SBP (-9 vs. -1.6 mmHg, P = 0.021) and 24-h DBP (-7.3 vs. -2.3 mmHg, P = 0.074), especially at night (-11.3 vs. -3.8, P = 0.121 and -8.8 vs. -2.2, P = 0.054) respectively. Adjusted difference between groups was statistically significant in 24-h SBP levels (-7.4 mmHg, P = 0.021). CONCLUSION: CPAP lowers BP levels in both resistant hypertension and RfH patients although the degree of this reduction is higher in those with RfH especially during the night.

Factors associated with the changes from a resistant to a refractory phenotype in hypertensive patients: a Pragmatic Longitudinal Study.

Refractory hypertension (RfH) is defined as a lack of blood pressure control despite the administration of at least 5 anti-hypertensive drugs. The factors associated with its natural history are unknown. This study aimed to evaluate both the incidence of RfH in an cohort of patients with resistant hypertension (RH) and the factors involved in that progression. This was an observational prospective multicenter study (24 centers) with 172 patients with confirmed RH (24-h ABPM) who underwent a further 24 h ABPM study at the end of the follow-up. Prospective information was obtained from all patients in their corresponding Hypertension Units via a standard clinical protocol, and they all underwent a sleep study. Thirty patients were diagnosed with RfH (17.4%) after a mean follow-up of 57 months, despite the prescription of a greater number of long-acting thiazide-like diuretics and mineralocorticoid receptor antagonists. The factors associated with progression to RfH were: a longer period since the diagnosis of RH (OR: 1.06, 95% CI: 1.01-1.1, p = 0.007); the HbA1c concentration (OR: 1.42, 95% CI: 1.42-1.8; p = 0.005); the initial heart rate (OR: 1.05, 95% CI: 1.01-1.09, p = 0.004); and poor adherence to continuous positive airway pressure (CPAP) in cases of obstructive sleep apnea (OR: 3.36, 95% CI: 1.47-7.7, p = 0.004). In conclusion, a considerable percentage of patients evolved from the RH to the RfH phenotype despite changes in their treatment. Some easily measurable variables, such as heart rate, the time since the diagnosis, the HbA1c level, and the presence of untreated obstructive sleep apnea (or poor adherence to CPAP) have been demonstrated to be prognostic factors in the progression to RfH.

Beyond Resistant Hypertension.

Obstructive sleep apnea (OSA) is an independent cause of resistant hypertension (RH) but its association with refractory hypertension (RfH), a recently described form of severe hypertension, has not yet been investigated. This study seeks to analyze the association between the presence and severity of OSA/OSA syndrome with RfH and to compare it with a group of patients with OSA/OSA syndrome and RH. We conducted a multicenter, cross-sectional study of consecutive patients diagnosed with RH by means of 24-hour ambulatory blood pressure monitoring. Those patients with blood pressure levels ≥130/80 mm Hg, despite taking at least 5 antihypertensive drugs, were considered to have true RfH. All patients underwent a sleep study and completed a detailed clinical history related to OSA, current medication, and cardiovascular diseases. Overall, 229 patients were included (mean age, 58.3 years; 63% male), of whom 42 (18.3%) satisfied the criteria for RfH. Compared with those with RH, patients with RfH had a higher cardiovascular risk profile, higher blood pressure measurements, and a 2-fold greater risk of having both severe OSA (odds ratio, 2.1, with a prevalence of apnea-hypopnea index ≥15, 95.2% and apnea-hypopnea index ≥30, 64.3%) and OSA syndrome (apnea-hypopnea index ≥5+Epworth Sleepiness Scale >10; odds ratio, 1.9; 52.4% versus 37.3%; P=0.023), as well as higher OSA severity (apnea-hypopnea index, 41.8 versus 33.8 events/h; P=0.026). Patients with RfH had an even greater prevalence and severity of OSA and OSA syndrome than RH patients, highlighting the need to identify these patients to refer them to sleep units on a preferential basis.

Are IL18RAP gene polymorphisms associated with body mass regulation? A cross-sectional study.

OBJECTIVES: To investigate the association between IL18RAP and body mass index (BMI) and obesity and to verify the effect of a polymorphism in the microRNA136 (MIR136) IL18RAP binding region. DESIGN: We analysed samples from two Spanish cross-sectional studies, VALCAR (Spanish Mediterranean coast) and Hortega (Spanish centre). These studies aimed at analysing cardiovascular risk and development of cardiovascular disease in the general population. Both populations correspond to regions with different characteristics. SETTING: Five IL18RAP single nucleotide polymorphisms were selected using the SYSNPs web tool and analysed by oligonucleotide ligation assay (SNPlex). For the MIR136 functional study, cells were transfected with plasmids containing different rs7559479 polymorphism alleles and analysed by luciferase reporter assays. PARTICIPANTS: 1970 individuals (Caucasian, both genders): VALCAR (468) and Hortega (1502). RESULTS: rs2293225, rs2272127 and rs7559479 showed the following associations: rs7559479 G allele correlated with a higher obesity risk (P=0.01; OR=1.82; 95% CI 1.15 to 2.87 for the VALCAR group; P=0.033; OR=1.35; 95% CI 1.03 to 1.79 for the Hortega population) and higher body mass index (BMI) values (P=0.0045; P=0.1 for VALCAR and Hortega, respectively); a significant association with obesity (P=0.0024, OR=1.44, 95% CI 1.14 to 1.82) and increased BMI values (P=0.008) was found when considering both populations together. rs2293225 T allele was associated with lower obesity risk (P=0.036; OR=0.60; 95% CI 0.35 to 0.96) and lower BMI values (P=0.0038; OR=1.41) while the rs2272127 G allele was associated with lower obesity risk (P=0.028; OR=0.66; 95% CI 0.44 to 0.97) only in the VALCAR population. A reporter assay showed that the presence of the A allele in rs7559479 was associated with increased MIR136 binding to IL18RAP. CONCLUSIONS: Our results suggest that polymorphisms in IL18RAP influence susceptibility to obesity. We demonstrated that the A allele in rs7559479 increases MIR136 binding, which regulates IL-18 system activity.