"It wasn't me, check the cameras!" Suspects' apparent verifiable responses might not indicate innocence.

The verifiability of a suspect's alibi is often interpreted as a sign of innocence. Because the police resources are limited, verifiability could be used to dismiss suspects of minor offenses. We examined whether alibi verifiability actually indicates innocence for minor crimes. In Experiment 1, participants imagined they were guilty or innocent suspects of minor crimes and selected a response to convince the police of their innocence. Compared to innocent suspects, guilty suspects were more likely to select pseudo-verifiable responses (which seemed verifiable but were not) rather than non-verifiable responses. Experiment 2 revealed that pseudo-verifiable responses increased observers' perceptions of innocence (rather than guilt). Experiment 3 suggested that people infer the police will not verify alibis of minor crimes, which may lead people to invent pseudo-verifiable responses. These results indicate that apparent verifiability does not necessarily indicate innocence. The police should systematically test alternative hypotheses whenever they encounter apparent verifiable responses.

Diagnostic accuracy of imaging compared to histology in congenital lung malformations.

INTRODUCTION: The aim of this study was to evaluate the accuracy of imaging tests (prenatal ultrasound [US] and postnatal computed tomography [CT]) in comparison to histology for diagnosis of congenital lung malformations (CLMs). MATERIAL AND METHODS: Retrospective study of patients with a prenatal diagnosis of CLM whose postnatal follow-up included thoracic CT scan and histological examination of the lesion. We collected data on demographic variables, gestational age at diagnosis, US findings and the history of multiple gestation. We used the kappa coefficient to determine the level of agreement between the findings of prenatal US and postnatal tests (CT and histology).We analysed paired data on the size of the lesion, its location and the presence or absence of systemic arterial vascularization. RESULTS: The sample included 56 patients with 57 lesions. The mean gestational age at diagnosis was 22.42 weeks (SD, 3.94) and 57% were male. Malformations most frequently involved the left lung and the lower lobes. The agreement between CT and histology in the detection of cystic lesions was moderate (κ = 0.55) but stronger compared to the agreement between US and histology (κ = 0.10). The agreement between CT and histology was substantial (κ = 0.66) in the detection of systemic vascularization of the lesion and stronger compared to the agreement between US and histology. Both imaging methods were highly accurate in the identification of the location of the pulmonary lesions. CONCLUSIONS: postnatal CT offers a substantial concordance with histological findings, especially in the detection of systemic vascularization, and an accurate prediction of the anatomy of the lesion.

EN-DALBACEN 2.0 Cohort: real-life study of dalbavancin as sequential/consolidation therapy in patients with infective endocarditis due to Gram-positive cocci.

OBJECTIVES: Infective endocarditis (IE) has high mortality and morbidity and requires long hospital stays to deliver the antibiotic treatment recommended in clinical practice guidelines. We aimed to analyse the health outcomes of the use of dalbavancin (DBV) in the consolidation treatment of IEs caused by Gram-positive cocci and to perform a pharmacoeconomic study. MATERIALS AND METHODS: This observational, retrospective, Spanish multicentre study in patients with IE who received DBV as part of antibiotic treatment in consolidation phase were followed for at least 12 months. The study was approved by the Provincial Committee of the coordinating centre. RESULTS: The study included 124 subjects, 70.2% male, with a mean age of 67.4 years and median Charlson index of 4 (interquartile range: 2.5-6). Criteria for definite IE were met by 91.1%. Coagulase-negative staphylococci (38.8%), Staphylococcus aureus (22.6%), Enterococcus faecalis (19.4%), and Streptococcus Spp. (9.7%) were isolated more frequently, all susceptible to vancomycin. Before DVB administration, 91.2% had undergone surgery; 60.5% had received a second regimen for 24.5 d (16.6-56); and 20.2% had received a third regimen for 14.5 d (12-19.5). DBV was administered to facilitate discharge in 95.2% of cases. At 12 months, the effectiveness was of 95.9%, and there was 0.8% loss to follow-up, 0.8% IE-related death, and 3.2% relapse. Adverse events were recorded in 3.2%. The hospital stay was reduced by 14 d, and there was a mean savings of 5548.57 €/patient vs. conventional treatments. CONCLUSION: DBV is highly effective, safe, and cost-effective as consolidation therapy in patients with IE by Gram-positive cocci, with few adverse events.

Universal evaluation of MLC models in treatment planning systems based on a common set of dynamic tests.

PURPOSE: To demonstrate the feasibility of characterising MLCs and MLC models implemented in TPSs using a common set of dynamic beams. MATERIALS AND METHODS: A set of tests containing synchronous (SG) and asynchronous sweeping gaps (aSG) was distributed among twenty-five participating centres. Doses were measured with a Farmer-type ion chamber and computed in TPSs, which provided a dosimetric characterisation of the leaf tip, tongue-and-groove, and MLC transmission of each MLC, as well as an assessment of the MLC model in each TPS. Five MLC types and four TPSs were evaluated, covering the most frequent combinations used in radiotherapy departments. RESULTS: Measured differences within each MLC type were minimal, while large differences were found between MLC models implemented in clinical TPSs. This resulted in some concerning discrepancies, especially for the HD120 and Agility MLCs, for which differences between measured and calculated doses for some MLC-TPS combinations exceeded 10%. These large differences were particularly evident for small gap sizes (5 and 10 mm), as well as for larger gaps in the presence of tongue-and-groove effects. A much better agreement was found for the Millennium120 and Halcyon MLCs, differences being within ± 5% and ± 2.5%, respectively. CONCLUSIONS: The feasibility of using a common set of tests to assess MLC models in TPSs was demonstrated. Measurements within MLC types were very similar, but TPS dose calculations showed large variations. Standardisation of the MLC configuration in TPSs is necessary. The proposed procedure can be readily applied in radiotherapy departments and can be a valuable tool in IMRT and credentialing audits.

Obesity-Related Single-Nucleotide Polymorphisms and Weight Gain Following First-Line Antiretroviral Therapy.

BACKGROUND: We studied the association of obesity-related single-nucleotide polymorphisms (OR-SNPs) with weight gain after antiretroviral therapy (ART) in people with human immunodeficiency virus (HIV; PWH). METHODS: Participants were ART-naive PWH from the Spanish HIV Research Cohort who started ART from 2014 onward and had blood/DNA deposited in the cohort Biobank. The primary outcome was change in weight at 96 weeks after starting ART. We genotyped 14 OR-SNPs from a meta-analysis of genome-wide association studies of body mass index (BMI) loci. Changes over time in weight and BMI were studied using adjusted linear mixed models. RESULTS: A total of 1021 PWH were included. The mean weight gain over 96 weeks was 2.90 (95% confidence interval, 2.54-3.26) kg. Factors associated with higher weight gain were female sex, birth in sub-Saharan Africa, prior AIDS, CD4+ <200 cells/µL, HIV-RNA >100 000 copies/mL, negative hepatitis C virus serology, and use of tenofovir alafenamide. A significant association was found between ZC3H4 rs3810291 GG genotype and BCDIN3D/FAIM2 rs7138803 GG genotype polymorphisms and weight and BMI increase. The estimated adjusted mean (standard error [SE]) of weight gain was 4.26 (0.56) kg in ZC3H4 rs3810291 GG carriers and 2.66 (0.19) kg in AA/AG carriers (P = .007). Likewise the estimated weight gain at 96 weeks was 3.35 (0.29) kg in BCDIN3D/FAIM2 rs7138803 GG carriers and 2.51 (0.24) kg in AG/AA carriers (P = .020). CONCLUSIONS: Genetic factors may play a role in weight gain after ART initiation. Further work is needed to replicate our findings and understand how the identified SNPs lead to higher weight gain in this context.

Seven years of pig slurry fertilization: impacts on soil chemical properties and the element content of winter barley plants.

Intensive pig farming produces large amounts of slurry, which is applied to agricultural soils as fertilizer. A 7-year field study was performed to check the effect of pig slurry on soil properties and on the accumulation of some essential nutrients and heavy metals in a calcareous silty-loam soil (0-0.3 m) and in barley (Hordeum vulgare L.) plants in two cropping seasons with contrasting amounts of rainfall. Five fertilization treatments, control (no N applied), mineral fertilizer (90 kg N ha-1), and different N doses of pig slurry (146, 281, 534 kg N ha-1), were applied at sowing of a barley crop. Organic carbon, available P and K, and total P in soil increased with slurry dose. No differences were found in Co, Cr, Fe, Mn, Ni, and Pb soil concentrations. Slurries increased Cu, Mn, and Zn extractions and plant concentrations of P in straw and Zn in grain. However, the lowest slurry rate was able to maintain the highest grain yields while improving fertility. The results of this research study support the sustainability of pig slurry fertilization at appropriate rates in relation to soil chemical quality.

Estimation of gestational age in neonates using clavicular-pubis length on routine chest-abdomen radiographs.

BACKGROUND: Neonatal diseases differ depending on gestational age and weight. In the setting of an emergency in the neonatal intensive care unit (NICU), relevant clinical information is often not available when the first neonatal radiograph is obtained. When reading an initial chest-abdomen radiograph, the paediatric radiologist needs gestational age data for best radiologic practice. A transverse diameter of the chest has been previously described to estimate gestational age (GA). OBJECTIVES: To determine the strength of the correlation between GA/weight and clavicular-pubis length (CPL) on admission radiographs; to obtain a quadratic formula based on the correlation of CPL with GA and to demonstrate if a more simplified formula used by our group works as efficiently as the formula provided by the regression analysis. MATERIALS AND METHODS: A retrospective study was approved by the institutional review board and informed consent was waived. The length from the medial aspect of the clavicle to the pubic bone was measured on the initial portable chest-abdomen radiographs of 260 patients admitted to the NICU in 2016. Regression analysis was performed to investigate the association between CPL and GA/birth weight. RESULTS: One hundred eleven females and 149 males with GA between 23 and 42 weeks were evaluated. CPL was statistically associated with both GA (P<0,01) and birth weight. The estimation can be expressed with an equation of the model: GA (weeks) = (CPL in cm - 1.98)/0.42. A simplified formula: GA (weeks) = (CPL in cm) ×2+2, strongly correlates with the equation model. CONCLUSION: In patients in whom it is not known, GA can be estimated by measuring the length between medial clavicle and symphysis pubis using the formulae we propose.

A 6-mRNA host response classifier in whole blood predicts outcomes in COVID-19 and other acute viral infections.

Predicting the severity of COVID-19 remains an unmet medical need. Our objective was to develop a blood-based host-gene-expression classifier for the severity of viral infections and validate it in independent data, including COVID-19. We developed a logistic regression-based classifier for the severity of viral infections and validated it in multiple viral infection settings including COVID-19. We used training data (N = 705) from 21 retrospective transcriptomic clinical studies of influenza and other viral illnesses looking at a preselected panel of host immune response messenger RNAs. We selected 6 host RNAs and trained logistic regression classifier with a cross-validation area under curve of 0.90 for predicting 30-day mortality in viral illnesses. Next, in 1417 samples across 21 independent retrospective cohorts the locked 6-RNA classifier had an area under curve of 0.94 for discriminating patients with severe vs. non-severe infection. Next, in independent cohorts of prospectively (N = 97) and retrospectively (N = 100) enrolled patients with confirmed COVID-19, the classifier had an area under curve of 0.89 and 0.87, respectively, for identifying patients with severe respiratory failure or 30-day mortality. Finally, we developed a loop-mediated isothermal gene expression assay for the 6-messenger-RNA panel to facilitate implementation as a rapid assay. With further study, the classifier could assist in the risk assessment of COVID-19 and other acute viral infections patients to determine severity and level of care, thereby improving patient management and reducing healthcare burden.

Dealing with categorical data in a multidimensional context: The multidimensional balanced worth.

This paper presents an evaluation protocol that permits evaluating the relative performance of a set of populations in a multidimensional context when outcomes are measured in terms of categorical variables. This problem appears in many different fields, such as Medicine, Social Sciences, or Engineering. The key ingredient for this evaluation is comparing the likelihood of achieving higher performance levels in the different dimensions. This way of addressing this family of problems derives from extending the balanced worth (Herrero and Villar, 2018) to a multidimensional setting. This evaluation protocol is illustrated by means of two empirical applications regarding life satisfaction in Europe and multidimensional poverty measurement in Spain.

A synthetic indicator on the impact of COVID-19 on the community's health.

The expansion of Covid-19 has severely hit the community's health all over the world, killing hundreds of thousands of people, subjecting health systems to an enormous stress (besides derailing economic activities and altering personal and social behavior). Two elements are essential to monitor the evolution of the pandemic as well as to analyze the effectiveness of the response measures: reliable data and useful indicators. We present an indicator that helps to assess the impact of Covid-19 on the community's health, combining two different components: the extent of the pandemics (i.e. the share of the population affected) and its severity (the intensity of the disease on those affected). The severity measure derives from the application of an evaluation protocol that allows comparing population distributions based on the proportions of those affected with different health conditions. We illustrate the functioning of this indicator over a case study regarding the situation of the Italian regions on March 9 (the beginning of the confinement) and April 8, 2020, one month later.

DALBACEN cohort: dalbavancin as consolidation therapy in patients with endocarditis and/or bloodstream infection produced by gram-positive cocci.

OBJECTIVES: To analyse the effectiveness of dalbavancin (DBV) in clinical practice as consolidation therapy in patients with bloodstream infection (BSI) and/or infective endocarditis (IE) produced by gram-positive cocci (GPC), as well as its safety and pharmacoeconomic impact. METHODS: A multicentre, observational and retrospective study was conducted of hospitalised patients with IE and/or BSI produced by GPC who received at least one dose of DBV. Clinical response was assessed during hospitalization, at 3 months and at 1 year. RESULTS: Eighty-three patients with median age of 73 years were enrolled; 73.5% were male; 59.04% had BSI and 49.04% IE (44.04% prosthetic valve IE, 32.4% native IE, 23.5% pacemaker lead). The most frequently isolated microorganism was Staphylococcus aureus in BSI (49%) and coagulase-negative staphylococci in IE (44.1%). All patients with IE were clinically cured in hospital; at 12 months, there was 2.9% loss to follow-up, 8.8% mortality unrelated to IE, and 2.9% therapeutic failure rate. The percentage effectiveness of DBV to treat IE was 96.7%. The clinical cure rate for BSI was 100% during hospital stay and at 3 months; there were no recurrences or deaths during the follow-up. No patient discontinued treatment for adverse events. The saving in hospital stay was 636 days for BSI (315,424.20€) and 557 days for IE (283,187.45€). CONCLUSIONS: DBV is an effective consolidation antibiotic therapy in clinically stabilized patients with IE and/or BSI. It proved to be a cost-effective treatment, reducing the hospital stay, thanks to the pharmacokinetic/pharmacodynamic profile of this drug.

Agricultural soil organic carbon stocks in the north-eastern Iberian Peninsula: Drivers and spatial variability.

Estimating soil organic carbon (SOC) stocks under agriculture, assessing the importance of their drivers and understanding the spatial distribution of SOC stocks are crucial to predicting possible future SOC stocks scenarios under climate change conditions and to designing appropriate mitigation and adaptation strategies. This study characterized and modelled SOC stocks at two soil depth intervals, topsoil (0-30 cm) and subsoil (30-100 cm), based on both legacy and recent data from 7245 agricultural soil profiles and using environmental drivers (climate, agricultural practices and soil properties) for agricultural soils in Catalonia (NE Spain). Generalized Least Square (GLS) and Geographical Weighted Regression (GWR) were used as modelling approaches to: (i) assess the main SOC stock drivers and their effects on SOC stocks; (ii) analyse spatial variability of SOC stocks and their relationships with the main drivers; and (iii) predict and map SOC stocks at the regional scale. While topsoil variation of SOC stocks depended mainly on climate, soil texture and agricultural variables, subsoil SOC stocks changes depended mainly on soil attributes such us soil texture, clay content, soil type or depth to bedrock. The GWR model revealed that the relationship between SOC stocks and drivers varied spatially. Finally, the study was only able to predict and map topsoil SOC stocks at the regional scale, because controlling factors of SOC stocks at the subsoil level were largely unavailable for digital mapping. According to the resulting map, the mean SOC stock value for Catalan agriculture at the topsoil level was 4.88 ±â€¯0.89 kg/m2 and the total magnitude of the carbon pool in agricultural soils of Catalonia up to 30 cm reached 47.9 Tg. The present study findings are useful for defining carbon sequestration strategies at the regional scale related with agricultural land use changes and agricultural management practices in a context of climate change.

Dataset on the TIC-MOC cruise onboard the R/V Hespérides, March 2015, Brazil-Malvinas Confluence.

This oceanographic dataset was gathered during the TIC-MOC cruise, which was designed to characterize the dynamics of the Brazil-Malvinas Confluence. The cruise was carried on board the R/V Hespérides, with departure from Ushuaia and arrival to Salvador de Bahía. A total of 66 conductivity-temperature-depth (CTD) stations were completed between 8 and 22 March 2015, offshore from the continental platform and within 45°S-35°S and 61°W-50°W. At each station, water samples were collected, which were used to calibrate the CTD salinity-oxygen sensors and to determine inorganic nutrient concentrations, and the horizontal current was measured. Along its track, the vessel recorded surface temperature and salinity, as well as the horizontal flow down to about 700 m. Lastly, eight position-transmitting drifters were launched and two profiling floats were deployed and later recovered.

Microthrombotic Renal Vascular Lesions Are Associated to Increased Renal Inflammatory Infiltration in Murine Lupus Nephritis.

Background: Vascular microthrombotic lesions in lupus nephritis with or without antiphospholipid antibodies may relate to worse renal outcomes. Whether microthrombotic lesions are a consequence of renal inflammation or independently contribute to renal damage is unclear. Our aim was to investigate the relationship between microthrombotic renal vascular lesions and nephritis progression in MRL/lpr mice. Methods: MRL/lpr mice were analyzed for the presence of renal microvascular, glomerular and tubulointerstitial lesions and the effect of anti-aggregation (aspirin or clopidogrel) and dexamethasone on renal clinical and pathological manifestations was evaluated. Intravascular platelet aggregates (CD41), peri- (F4/80), and intraglomerular (Mac-2) macrophage infiltration, and C3 deposition were quantified by immunohistochemistry. Renal function was assessed by measuring proteinuria, and serum levels of creatinine and albumin. Anti-dsDNA and anti-cardiolipin antibodies, and thromboxane B2 levels were quantified by ELISA. Results: Frequency of microthrombotic renal lesions in MRL/lpr mice was high and was associated with immune-mediated renal damage. Proteinuria positively correlated with glomerular macrophage infiltration and was higher in mice with proliferative glomerular lesions. All mice had detectable anti-dsDNA and anti-cardiolipin IgG, regardless the presence of microthrombosis. Proteinuria and glomerular macrophage infiltration were significantly reduced in all treatment groups. Dexamethasone and platelet anti-aggregation similarly reduced glomerular damage and inflammation, but only platelet anti-aggregation significantly reduced anti-cardiolipin antibodies, renal complement deposition and thromboxane B2 levels. Conclusions: Platelet anti-aggregation reduced renal inflammatory damage, renal complement deposition, anti-cardiolipin antibodies, and thromboxane B2 levels and in MRL/lpr mice, suggesting that platelet activation has a pathogenic effect on immune-mediated nephritis. Our results point to MRL/lpr mice with lupus nephritis as an appropriate model to analyze the potential impact of anti-thrombotic intervention on renal inflammation.

Functional characterization of MODY2 mutations in the nuclear export signal of glucokinase.

Glucokinase (GCK) plays a key role in glucose homeostasis. Heterozygous inactivating mutations in the GCK gene cause the familial, mild fasting hyperglycaemia named MODY2. Besides its particular kinetic characteristics, glucokinase is regulated by subcellular compartmentation in hepatocytes. Glucokinase regulatory protein (GKRP) binds to GCK, leading to enzyme inhibition and import into the nucleus at fasting. When glucose concentration increases, GCK-GKRP dissociates and GCK is exported to the cytosol due to a nuclear export signal (NES). With the aim to characterize the GCK-NES, we have functionally analysed nine MODY2 mutations located within the NES sequence. Recombinant GCK mutants showed reduced catalytic activity and, in most cases, protein instability. Most of the mutants interact normally with GKRP, although mutations L306R and L309P impair GCK nuclear import in cotransfected cells. We demonstrated that GCK-NES function depends on exportin 1. We further showed that none of the mutations fully inactivate the NES, with the exception of mutation L304P, which likely destabilizes its α-helicoidal structure. Finally, we found that residue Glu300 negatively modulates the NES activity, whereas other residues have the opposite effect, thus suggesting that some of the NES spacer residues contribute to the low affinity of the NES for exportin 1, which is required for its proper functioning. In conclusion, our results have provided functional and structural insights regarding the GCK-NES and contributed to a better knowledge of the molecular mechanisms involved in the nucleo-cytoplasmic shuttling of glucokinase. Impairment of this regulatory mechanism by some MODY2 mutations might contribute to the hyperglycaemia in the patients.

Examining police officers' response bias in judging veracity.

BACKGROUND: Deception detection research has shown that, in judging veracity, police officers are less truth biased than non-officers. However, previous researchers have normally used videotaped statements where an unknown (but presumably large) number of stereotypical or real deception cues are displayed by the senders. We examined non-officers, novice officers, and experienced officers’ response tendencies in a more controlled situation where cue availability was severely restricted. METHOD: We used written vignettes describing either police-related or police-unrelated scenarios where the protagonist denied having committed a misdeed. Each vignette contained only two pieces of relevant information, one suggesting that the protagonist was lying and one suggesting that she or he was telling the truth. RESULTS: Officers made fewer truth judgments than non-officers in judging police-relevant vignettes, but not in judging police-irrelevant vignettes. Both novice and experienced officers had greater judgmental confidence than non-officers. CONCLUSIONS: The findings are consistent with the Adaptive Lie Detection Theory (ALIED). Future research should continue to explore how the police relevance of the situation or task at hand influences novice and experienced officers’ veracity judgments.

Epidemiology and pathophysiology of pregnancy-associated breast cancer: A review.

The interactions between pregnancy and breast cancer (BC) are complex. Overall, parity is associated with long-term protective effects against BC, however in a small group of susceptible patients, pregnancy can lead to the development of a form of BC with a particularly poor prognosis. Pregnancy-associated breast cancer (PABC) remains an under-studied but important and growing clinical problem worldwide. Several aspects of PABC, including risk factors and mechanisms involved in its occurrence and aggressiveness, are incompletely understood. This review aims to summarize the epidemiology, biology, patho-physiology and clinical characteristics of PABC. We emphasize that age at first pregnancy, absence of breastfeeding and family history stand out as possible risk factors for developing PABC that ought to be incorporated into clinical tools for assessing a woman's risk of developing PABC. Also, improved methods for identifying women at risk of developing PABC in the general population are needed.

Endoplasmic Reticulum Stress Sensor IRE1α Enhances IL-23 Expression by Human Dendritic Cells.

Human monocyte-derived dendritic cells (DCs) exposed to pathogen-associated molecular patterns (PAMPs) undergo bioenergetic changes that influence the immune response. We found that stimulation with PAMPs enhanced glycolysis in DCs, whereas oxidative phosphorylation remained unaltered. Glucose starvation and the hexokinase inhibitor 2-deoxy-d-glucose (2-DG) modulated cytokine expression in stimulated DCs. Strikingly, IL23A was markedly induced upon 2-DG treatment, but not during glucose deprivation. Since 2-DG can also rapidly inhibit protein N-glycosylation, we postulated that this compound could induce IL-23 in DCs via activation of the endoplasmic reticulum (ER) stress response. Indeed, stimulation of DCs with PAMPs in the presence of 2-DG robustly activated inositol-requiring protein 1α (IRE1α) signaling and to a lesser extent the PERK arm of the unfolded protein response. Additional ER stressors such as tunicamycin and thapsigargin also promoted IL-23 expression by PAMP-stimulated DCs. Pharmacological, biochemical, and genetic analyses using conditional knockout mice revealed that IL-23 induction in ER stressed DCs stimulated with PAMPs was IRE1α/X-box binding protein 1-dependent upon zymosan stimulation. Interestingly, we further evidenced PERK-mediated and CAAT/enhancer-binding protein ß-dependent trans-activation of IL23A upon lipopolysaccharide treatment. Our findings uncover that the ER stress response can potently modulate cytokine expression in PAMP-stimulated human DCs.

Hif-1α Knockdown Reduces Glycolytic Metabolism and Induces Cell Death of Human Synovial Fibroblasts Under Normoxic Conditions.

Increased glycolysis and HIF-1α activity are characteristics of cells under hypoxic or inflammatory conditions. Besides, in normal O2 environments, elevated rates of glycolysis support critical cellular mechanisms such as cell survival. The purpose of this study was to analyze the contribution of HIF-1α to the energy metabolism and survival of human synovial fibroblasts (SF) under normoxic conditions. HIF-1α was silenced using lentiviral vectors or small-interfering RNA (siRNA) duplexes. Expression analysis by qRT-PCR and western blot of known HIF-1α target genes in hypoxia demonstrated the presence of functional HIF-1α in normoxic SF and confirmed the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as a HIF-1α target even in normoxia. HIF-1α silencing induced apoptotic cell death in cultured SF and, similarly, treatment with glycolytic, but not with OXPHOS inhibitors, induced SF death. Finally, in vivo HIF-1α targeting by siRNA showed a significant reduction in the viability of human SF engrafted into a murine air pouch. Our results demonstrate that SF are highly dependent on glycolytic metabolism and that HIF-1α plays a regulatory role in glycolysis even under aerobic conditions. Local targeting of HIF-1α provides a feasible strategy to reduce SF hyperplasia in chronic arthritic diseases.