Association between sleep microarchitecture and cognition in obstructive sleep apnea.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) increases the risk of cognitive impairment. Measures of sleep microarchitecture from EEG may help identify patients at risk of this complication. METHODS: Participants with suspected OSA (n=1142) underwent in-laboratory polysomnography and completed sleep and medical history questionnaires, and tests of global cognition (Montreal Cognitive Assessment, MoCA), memory (Rey Auditory Verbal Learning Test, RAVLT) and information processing speed (Digit-Symbol Coding, DSC). Associations between cognitive scores and stage 2 NREM sleep spindle density, power, frequency and %-fast (12-16Hz), odds-ratio product (ORP), normalized EEG power (EEGNP) and the delta:alpha ratio were assessed using multivariable linear regression (MLR) adjusted for age, sex, education, and total sleep time. Mediation analyses were performed to determine if sleep microarchitecture indices mediate the negative effect of OSA on cognition. RESULTS: All spindle characteristics were lower in participants with moderate and severe OSA (p≤0.001, versus no/mild OSA) and positively associated with MoCA, RAVLT and DSC scores (false discovery rate corrected p-value, q≤0.026), except spindle power which was not associated with RAVLT (q=0.185). ORP during NREM sleep (ORPNREM) was highest in severe OSA participants (p≤0.001) but neither ORPNREM (q≥0.230) nor the delta:alpha ratio were associated with cognitive scores in MLR analyses (q≥0.166). In mediation analyses, spindle density and EEGNP (p≥0.048) mediated moderate-to-severe OSA's negative effect on MoCA scores while ORPNREM, spindle power and %-fast spindles mediated OSA's negative effect on DSC scores (p≤0.018). CONCLUSION: Altered spindle activity, ORP and normalized EEG power may be important contributors to cognitive deficits in patients with OSA.

Scott-Taor Syndrome: A Clinical Case Report.

Scott-Taor syndrome is a benign bone dysplasia with less than 50 cases reported. The latter is an autosomal dominant disease characterized mainly by patellar a/hypoplasia and bilateral malunion ossification of the ischiopubic junction, a wide gap between the first and second toes. The diagnosis is clinical and radiographical. Here, we present a 17-year-old female patient with this rare syndrome. Considering this diagnosis is crucial for a better understanding of the pathology and to effectively contextualize the patient's clinical findings.

Deciphering plant health status: The link between secondary metabolites, fungal community and disease incidence in olive tree.

Plant-associated microorganisms are increasingly recognized to play key roles in host health. Among several strategies, associated microorganisms can promote the production of specific metabolites by their hosts. However, there is still a huge gap in the understanding of such mechanisms in plant-microorganism interaction. Here, we want to determine whether different levels of olive leaf spot (OLS) disease incidence were related to differences in the composition of fungal and secondary metabolites (i.e. phenolic and volatile compounds) in leaves from olive tree cultivars with contrasting OLS susceptibilities (ranging from tolerant to highly susceptible). Accordingly, leaves with three levels of OLS incidence from both cultivars were used to assess epiphytic and endophytic fungal communities, by barcoding of cultivable isolates, as well as to evaluate leaf phenolic and volatile composition. Fungal and metabolite compositions variations were detected according to the level of disease incidence. Changes were particularly noticed for OLS-tolerant cultivars, opposing to OLS-susceptible cultivars, suggesting that disease development is linked, not only to leaf fungal and metabolite composition, but also to host genotype. A set of metabolites/fungi that can act as predictive biomarkers of plant tolerance/susceptibility to OLS disease were identified. The metabolites α-farnesene and p-cymene, and the fungi Fusarium sp. and Alternaria sp. were more related to disease incidence, while Pyronema domesticum was related to the absence of disease symptoms. Cultivar susceptibility to OLS disease is then suggested to be driven by fungi, volatile and phenolic host leaves composition, and above all to plant-fungus interaction. A deeper understanding of these complex interactions may unravel plant defensive responses.

Associations between sleep-related symptoms, obesity, cardiometabolic conditions, brain structural alterations and cognition in the UK biobank.

OBJECTIVES: Sleep disturbances are increasingly recognized as adversely affecting brain health in aging. Our aim was to investigate interrelations between subjective sleep-related symptoms, obesity, cardiometabolic disorders, brain structure and cognitive decline in a population-based aging sample. METHODS: Data were extracted from the UK Biobank for anthropometric and demographic information, self-reported sleep behaviours, cardiometabolic measures, structural brain magnetic resonance imaging and cognitive test scores. "Sleep-related symptoms" (SRS) were measured using four questionnaire items: loud snoring, daytime sleepiness, likelihood to nap and difficulty getting up in the morning. Associations were tested using a structural equation model (SEM), adjusted for confounders. Further, multiple regression analysis was used to test for direct relationships between SRS and specific cognitive domains. RESULTS: Among 36,468 participants with an average age of 63.6 (SD 7.5) years and 46.7% male, we found that SRS were associated with obesity and several pre-existing cardiometabolic disturbances. In turn, cardiometabolic disorders were associated with increased white matter hyperintensities and cortical thinning, which were related to cognitive dysfunction. SRS were also directly related to several structural brain changes and to cognitive dysfunction. Regression analyses showed that SRS were directly associated with slower reaction times, and lower scores in fluid intelligence, working memory and executive function. CONCLUSIONS: Self-reported sleep-related symptoms were associated with cognitive dysfunction directly and through pre-existing cardiometabolic disorders and brain structural alterations. These findings provide evidence that symptoms of sleep disturbances, here defined primarily by hypersomnolence and snoring, are important risk factors or markers for cognitive dysfunction in an aging population.

Validation of STOP, STOP-BANG, STOP-BAG, STOP-B28, and GOAL screening tools for identification of obstructive sleep apnea in patients with Parkinson disease.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is common in Parkinson disease (PD). Questionnaires can be used as screening tools and have been used as a surrogate definition of OSA in large-scale research. This study aimed to validate the performance of STOP, STOP-BANG, STOP-BAG, STOP-B28, and GOAL and OSA predictors as tools to identify OSA in PD. METHODS: Data were analyzed from a PD cohort study in which OSA was diagnosed using laboratory polysomnography. We calculated sensitivity and specificity of each questionnaire for OSA using different definitions and performed receiver operating characteristics curve analysis. Linear regression was used to assess adjusted associations between questionnaires and outcomes: Montreal Cognitive Assessment, Epworth Sleepiness Scale, and Movement Disorder Society revision of the Unified Parkinson Disease Rating Scale. RESULTS: Questionnaire data were available for 68 PD patients (61.8% male, mean age 64.5 [standard deviation 9.9] years, and Hoehn and Yahr score 2.1 [0.8]). OSA (apnea-hypopnea index ≥ 15 events/h) occurred in 69.4% of participants. STOP-B28 ≥ 2 presented a higher sensitivity for OSA than STOP ≥ 2 (0.76 vs 0.65, respectively) and slightly lower specificity (0.65 vs 0.70, respectively). GOAL ≥ 2 had the highest sensitivity but poor specificity. Loud snoring had sensitivity 0.63 and specificity 0.65. STOP and snoring were significantly associated with Montreal Cognitive Assessment, Epworth Sleepiness Scale, and Movement Disorder Society revision of the Unified Parkinson Disease Rating Scale (total, motor, and nonmotor); STOP-BANG, STOP-BAG, and STOP-B28 showed associations with most outcomes, but the GOAL showed none. CONCLUSIONS: The STOP-B28 followed by STOP and presence of loud snoring alone seem to have the best overall properties to identify PD patients with OSA, whose clinical characteristics differ from the general population with OSA. CITATION: Gomes T, Benedetti A, Lafontaine A-L, Kimoff RJ Robinson A, Kaminska M. Validation of STOP, STOP-BANG, STOP-BAG, STOP-B28, and GOAL screening tools for identification of obstructive sleep apnea in patients with Parkinson disease. J Clin Sleep Med. 2023;19(1):45-54.

Moderate sedation with dexmedetomidine-remifentanil is safer than deep sedation with propofol-remifentanil for endobronchial ultrasound while providing comparable quality: a randomized double-blind trial.

OBJECTIVE: We compared dexmedetomidine-remifentanil vs. propofol-remifentanil in terms of safety and quality during sedation for Endobronchial ultrasonography (EBUS). METHODS: A randomized, double-blind trial. Outpatients undergoing EBUS randomly received 1 µg/kg/hour dexmedetomidine or a target concentration of 2.5 µg/mL propofol, both combined with remifentanil initially targeted at 1.5 ng/mL and subsequently titrated. Additional sedatives were restricted. The primary outcome was the need for airway rescue interventions to treat oxygen desaturation. RESULTS: Twenty-eight patients received dexmedetomidine-remifentanil and 27 received propofol-remifentanil. Airway rescue interventions were fewer in the dexmedetomidine group vs. the propofol one (23 vs. 76% patients, relative risk 3.21 (95% CI 1.55-6.64, P < 0.002)). Desaturation in the dexmedetomidine group was always resolved by increasing nasal oxygen flow, whereas additional interventions were needed in 60% of patients receiving propofol. Hypotension was more frequent in the propofol group, while hypertension, bradycardia and coughing were similar in both. Bronchoscopists' and patients' satisfaction were similar, although in the dexmedetomidine group two patients needed additional sedatives and two patients would not repeat the sedation technique. CONCLUSION: Moderate sedation with dexmedetomidine-remifentanil for EBUS is safer than deep sedation with propofol-remifentanil but it would occasionally need additional sedatives to ensure patient satisfaction.

Association of insomnia and short sleep duration, alone or with comorbid obstructive sleep apnea, and the risk of chronic kidney disease.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA), sleep fragmentation, and short sleep duration (SD) have been associated with chronic kidney disease (CKD). However, these potential mechanisms for CKD have not been compared in the same cohort. This study investigated the independent and combined impact of OSA and insomnia with short sleep duration on the risk of CKD progression in a sleep clinic population. METHODS: In a cross-sectional study design, adults with suspected OSA completed an overnight sleep study and a questionnaire that included the Insomnia Severity Index (ISI) and Pittsburgh Sleep Quality Index (PSQI). They also provided blood and urine samples for measurement of the glomerular filtration rate and urine albumin:creatinine ratio, from which the risk of CKD progression was determined. RESULTS: Participants (n = 732, 41% female, 55 ± 13 years) were categorized into four groups: no/mild OSA without insomnia (NM-OSA, n = 203), insomnia with SD without OSA (Insomnia-SD, n = 104), moderate-to-severe OSA without insomnia (MS-OSA, n = 242), and comorbid insomnia and OSA with SD (COMISA-SD, n = 183). After stratification, 12.8% of NM-OSA, 15.4% of Insomnia-SD, 28.9% of MS-OSA, and 31.7% of the COMISA-SD participants had an increased risk of CKD progression. Compared to NM-OSA, the odds ratio (OR) for an increased risk of CKD progression was not increased in Insomnia-SD (OR 0.95, confidence interval [CI]: 0.45-1.99) and was increased to the same degree in MS-OSA (OR 2.79, CI: 1.60-4.85) and COMISA-SD (OR 3.04, CI: 1.69-5.47). However, the ORs were similar between the MS-OSA and COMISA-SD groups across all statistical models (p ≥ .883). CONCLUSIONS: In a sleep clinic population, insomnia with short sleep duration does not increase the risk of CKD progression; nor does it further increase the risk of CKD progression associated with moderate-to-severe OSA.

Risk of chronic kidney disease in patients with obstructive sleep apnea.

STUDY OBJECTIVES: Chronic kidney disease (CKD) is a global health concern and a major risk factor for cardiovascular morbidity and mortality. Obstructive sleep apnea (OSA) may exacerbate this risk by contributing to the development of CKD. This study investigated the prevalence and patient awareness of the risk of CKD progression in individuals with OSA. METHODS: Adults referred to five Canadian academic sleep centers for suspected OSA completed a questionnaire, a home sleep apnea test or in-lab polysomnography and provided blood and urine samples for measurement of estimated glomerular filtration rate (eGFR) and the albumin:creatinine ratio (ACR), respectively. The risk of CKD progression was estimated from a heat map incorporating both eGFR and ACR. RESULTS: 1295 adults (42% female, 54 ± 13 years) were categorized based on the oxygen desaturation index (4% desaturation): <15 (no/mild OSA, n = 552), 15-30 (moderate OSA, n = 322), and >30 (severe OSA, n = 421). After stratification, 13.6% of the no/mild OSA group, 28.9% of the moderate OSA group, and 30.9% of the severe OSA group had a moderate-to-very high risk of CKD progression (p < .001), which was defined as an eGFR <60 mL/min/1.73 m2, an ACR ≥3 mg/mmol, or both. Compared to those with no/mild OSA, the odds ratio for moderate-to-very high risk of CKD progression was 2.63 (95% CI: 1.79-3.85) for moderate OSA and 2.96 (2.04-4.30) for severe OSA after adjustment for CKD risk factors. Among patients at increased risk of CKD progression, 73% were unaware they had abnormal kidney function. CONCLUSION: Patients with moderate and severe OSA have an increased risk of CKD progression independent of other CKD risk factors; most patients are unaware of this increased risk.

theLiTE™: A Screening Platform to Identify Compounds that Reinforce Tight Junctions.

Tight junctions (TJ) are formed by transmembrane and intracellular proteins that seal the intercellular space and control selective permeability of epithelia. Integrity of the epithelial barrier is central to tissue homeostasis and barrier dysfunction has been linked to many pathological conditions. TJ support the maintenance of cell polarity through interactions with the Par complex (Cdc42-Par-6-Par-3-aPKC) in which Par-6 is an adaptor and links the proteins of the complex together. Studies have shown that Par-6 overexpression delays the assembly of TJ proteins suggesting that Par-6 negatively regulates TJ assembly. Because restoring barrier integrity is of key therapeutic and prophylactic value, we focus on finding compounds that have epithelial barrier reinforcement properties; we developed a screening platform (theLiTE™) to identify compounds that modulate Par-6 expression in follicular epithelial cells from Par-6-GFP Drosophila melanogaster egg chambers. Hits identified were then tested whether they improve epithelial barrier function, using measurements of transepithelial electrical resistance (TEER) or dye efflux to evaluate paracellular permeability. We tested 2,400 compounds, found in total 10 hits. Here we present data on six of them: the first four hits allowed us to sequentially build confidence in theLiTE™ and two compounds that were shortlisted for further development (myricetin and quercetin). We selected quercetin due to its clinical and scientific validation as a compound that regulates TJ; food supplement formulated on the basis of this discovery is currently undergoing clinical evaluation in gastroesophageal reflux disease (GERD) sufferers.

Bacterial disease induced changes in fungal communities of olive tree twigs depend on host genotype.

In nature, pathogens live and interact with other microorganisms on plant tissues. Yet, the research area exploring interactions between bacteria-fungi and microbiota-plants, within the context of a pathobiome, is still scarce. In this study, the impact of olive knot (OK) disease caused by the bacteria Pseudomonas savastanoi pv. savastanoi (Psv) on the epiphytic and endophytic fungal communities of olive tree twigs from three different cultivars, was investigated in field conditions. The ITS-DNA sequencing of cultivable fungi, showed that OK disease disturbs the resident fungal communities, which may reflect changes in the habitat caused by Psv. In particular, a reduction on epiphyte abundance and diversity, and changes on their composition were observed. Compared to epiphytes, endophytes were less sensitive to OK, but their abundance, in particular of potential pathogens, was increased in plants with OK disease. Host genotype, at cultivar level, contributed to plant fungal assembly particularly upon disease establishment. Therefore, besides fungi - Psv interactions, the combination of cultivar - Psv also appeared to be critical for the composition of fungal communities in olive knots. Specific fungal OTUs were associated to the presence and absence of disease, and their role in the promotion or suppression of OK disease should be studied in the future.

Modeling the interactions among phythopatogens and phyllosphere microorganisms for the biological disease control of Olea europaea L.

In this paper we formulate a model for assessing the interaction between the phytopathogen Spilocaea oleaginea and the phyllosphere microorganisms that are present in the olive tree leaves. The model describes the evolution in time of the foliage of the olive tree and the two different microorganisms, the phytopathogen fungi, that negatively affect the plant causing spots in the leaves, and the beneficial phyllosphere microorganisms, that help in keeping in check the invasion of the former. The system possesses five equilibria that are suitably analysed for feasibility and stability. The model shows interesting features: a bistable behavior, exhibited by three different pairs of equilibria. The separatrix surface of the basins of attraction of one such pair is computed. This allows the possible assessment of human intervention for control of the disease. Persistent oscillations via Hopf bifurcation are also discovered.

Diffuse alveolar hemorrhage: how relevant is etiology?

BACKGROUND: Diffuse Alveolar Hemorrhage (DAH) is a rare and potentially life-threatening clinical syndrome whose early recognition is essential. OBJECTIVES: Characterization of patients with DAH and comparison of presentation and evolution of the disease according to etiology. METHODS: We retrospectively reviewed the clinical records of patients admitted to our hospital over a 7-year period with DAH. Criteria for DAH (1+2): 1 - hemoptysis and/or pulmonary infiltrates and/or anemia (DAH triad); 2 - hemorrhagic bronchoalveolar lavage (BAL) or siderophagic alveolitis. DAH was grouped in immune and nonimmune and the course of disease was compared. RESULTS: We included 24 patients admitted with DAH, of which 11 had an immune cause: p-ANCA vasculitis (n=7), Systemic Lupus Erythematosus (n=2), c-ANCA vasculitis (n=1), Rheumatoid Arthritis (n=1) and 13 had a nonimmune cause: heart disease (n=6), amiodarone toxicity (n=2), clotting disorder (n=2), cannabis toxicity (n=1), S. aureus infection (n=1) and idiopathic (n=1). Patients with nonimmune DAH were significantly older than those with immune DAH (67.9±18.1 vs 56.6±18.8 years, p=0.042). DAH triad was observed in 54% of all patients, hemoptysis in 67%, anemia in 79%, and pulmonary infiltrates in all cases. Patients with immune DAH had more frequently pulmonary-renal syndrome (p<0.001), kidney failure (p=0.048), shock (p=0.049) and needed more frequently admition in ICU (p=0.039) and blood transfusion (p=0.043). Hospital length of stay was superior in immune group (29.5±20.0 vs 19.5±14.3 days, p=0.047). In-hospital mortality was exclusive to immune DAH (12.5%). CONCLUSIONS: Patients with DAH due to immune causes were significantly younger, had more severe presentations of the disease and worst outcomes.

XEN® implant and trabeculectomy medium-term quality of life assessment and comparison of results.

AIM: To evaluate and compare the quality of life of patients submitted to XEN® implant or trabeculectomy and the relationship with potentially involved variables. METHODS: A cross-sectional study of patients with advanced open-angle glaucoma who underwent implantation of XEN® (group 1) and trabeculectomy (group 2) between October 2015 and February 2017. The studied variables were: age, gender, follow-up time, need of topical anti-hypertensive therapy, visual acuity and intraocular pressure (IOP). The quantification of the quality of life was attained through the Glaucoma Symptom Scale (GSS) questionnaire. RESULTS: Totally 34 eyes (34 patients) were included, 17 in each group. The mean GSS scores for group 1 were 42.6±6.8 (median, 47; p25, 36.5; p75, 48.5) and for group 2 it was 41.6±7.0 (median, 43; p25, 36.5; p75, 47.0; P=0.34). There was a strong negative correlation between the need for topical anti-hypertensive drugs and the GSS result in both groups (r=-0.88, P<0.01, r=-0.59, P=0.01, respectively) and a moderate negative correlation with IOP in group 1 (r=-0.50, P=0.03). CONCLUSION: The analysis demonstrates the non-inferiority of medium-term quality of life of one group in relation to the other (XEN® implant and trabeculectomy). The number of topical anti-hypertensive drugs and IOP negatively influenced the quality of life.

Endophytic and Epiphytic Phyllosphere Fungal Communities Are Shaped by Different Environmental Factors in a Mediterranean Ecosystem.

The diversity and factors influencing fungal assemblages in phyllosphere of Mediterranean tree species have been barely studied, especially when endophytic and epiphytic communities are simultaneously considered. In this work, the endophytic and epiphytic fungal communities from olive tree phyllosphere were studied. This tree species is natural from the Mediterranean region and adapted to grow under adverse climatic conditions. The main objectives were to determine whether there are differences between both fungal communities and to examine whether different abiotic (climate-related) and biotic (plant organs) factors play a pivotal role in structuring these communities. Both communities differed in size and composition, with epiphytic community being richer and more abundant, displaying also a dominance of melanized fungi. Season was the major driver of community composition, especially of epiphytes. Other drivers shaping epiphytes were wind speed and temperature, while plant organ, rainfall, and temperature were the major drivers for endophytic composition. In contrast, canopy orientation caused slight variations in community composition of fungi, but with distinct effects in spring and autumn seasons. In conclusion, epiphytic and endophytic communities are not driven by the same factors. Several sources of variation undergo complex interactions to form and maintain phyllosphere fungal community in Mediterranean climates. Climatic parameters have influence on these fungal communities, suggesting that they are likely to be affected by climate changes in a near future.

A Case of Tracheomalacia in Chronic Obstructive Pulmonary Disease: What Went Wrong?

Tracheobronchomalacia is defined as loss of the structural integrity of airway wall cartilaginous structures with hyperdynamic airway collapse during respiration. It is a common finding in chronic obstructive pulmonary disease (COPD) but is not always symptomatic, especially if airway narrowing is mild. Symptoms and signs develop as the severity of airway narrowing progresses. When a patient is symptomatic, a prompt study with computerized tomography and flexible bronchoscopy is mandatory for future management. We present a case of tracheobronchomalacia in a patient with COPD whose diagnosis and treatment were challenging. LEARNING POINTS: Tracheobroncomalacia is a common finding in chronic obstructive pulmonary disease patients; management of the obstructive disorder is the first treatment step.When patients remain symptomatic, non-invasive positive pressure ventilation can be applied; if there is no response, a stent trial or surgical procedure should be considered.It is a challenge to identify which patients should undergo invasive intervention or surgical management.

Impact of a natural soil salinity gradient on fungal endophytes in wild barley (Hordeum maritimum With.).

Occurrence and distribution pattern of fungal endophytes in different tissues of halophytic plants across saline depressions are poorly studied. We investigated the endophytic fungal communities inhabiting roots, stems and leaves of Hordeum maritimum collected in a soil salinity gradient, i.e. non-saline, slightly saline and saline, using a culture-dependent approach. A total of 20 taxa belonging to Ascomycota phylum were identified by ITS rRNA gene sequence. Pyronema domesticum and Alternaria spp. were the most frequently isolated. Roots host higher diversity and were more frequently colonized by endophytes than aboveground organs. Endophytic composition of all organs surveyed differed according to salinity gradient. Contrary to expectations, the colonization rate of roots increased with soil salinity, indicating that under salt stress the endophyte-plant association is promoted. All the isolates exhibited in vitro saline tolerance, especially those belonging to genera Xylaria, Chalastospora, Alternaria and Pyronema. Fungal tolerance to NaCl under in vitro conditions appears to be more dependent on the isolates than on the sites of their isolation, suggesting that under natural conditions other factors, beyond soil salinity, should be taken into account. These findings highlight the importance of fungal endophytes in the protection and/or adaptation of both interacting species (plant-fungus) to salt stress under natural conditions.

Transcriptomic and metabolomic profiling of ionic liquid stimuli unveils enhanced secondary metabolism in Aspergillus nidulans.

BACKGROUND: The inherent potential of filamentous fungi, especially of Ascomycota, for producing diverse bioactive metabolites remains largely silent under standard laboratory culture conditions. Innumerable strategies have been described to trigger their production, one of the simplest being manipulation of the growth media composition. Supplementing media with ionic liquids surprisingly enhanced the diversity of extracellular metabolites generated by penicillia. This finding led us to evaluate the impact of ionic liquids' stimuli on the fungal metabolism in Aspergillus nidulans and how it reflects on the biosynthesis of secondary metabolites (SMs). RESULTS: Whole transcriptional profiling showed that exposure to 0.7 M cholinium chloride or 1-ethyl-3-methylimidazolium chloride dramatically affected expression of genes encoding both primary and secondary metabolism. Both ionic liquids apparently induced stress responses and detoxification mechanisms but response profiles to each stimulus were unique. Primary metabolism was up-regulated by choline, but down-regulated by 1-ethyl-3-methylimidazolium chloride; both stimulated production of acetyl-CoA (key precursor to numerous SMs) and non proteinogenic amino acids (building blocks of bioactive classes of SMs). In total, twenty one of the sixty six described backbone genes underwent up-regulation. Accordingly, differential analysis of the fungal metabolome showed that supplementing growth media with ionic liquids resulted in ca. 40 differentially accumulated ion masses compared to control conditions. In particular, it stimulated production of monodictyphenone and orsellinic acid, otherwise cryptic. Expression levels of genes encoding corresponding polyketide biosynthetic enzymes (i.e. backbone genes) increased compared to control conditions. The corresponding metabolite extracts showed increased cell polarity modulation potential in an ex vivo whole tissue assay (The lial Live Targeted Epithelia; theLiTE™). CONCLUSIONS: Ionic liquids, a diverse class of chemicals composed solely of ions, can provide an unexpected means to further resolve the diversity of natural compounds, guiding discovery of fungal metabolites with clinical potential.

Tuberculosis DALY-Gap: Spatial and Quantitative Comparison of Disease Burden Across Urban Slum and Non-slum Census Tracts.

To quantitatively assess disease burden due to tuberculosis between populations residing in and outside of urban informal settlements in Rio de Janeiro, Brazil, we compared disability-adjusted life years (DALYs), or "DALY-gap." Using the 2010 Brazilian census definition of informal settlements as aglomerados subnormais (AGSN), we allocated tuberculosis (TB) DALYs to AGSN vs non-AGSN census tracts based on geocoded addresses of TB cases reported to the Brazilian Information System for Notifiable Diseases in 2005 and 2010. DALYs were calculated based on the 2010 Global Burden of Disease methodology. DALY-gap was calculated as the difference between age-adjusted DALYs/100,000 population between AGSN and non-AGSN. Total TB DALY in Rio in 2010 was 16,731 (266 DALYs/100,000). DALYs were higher in AGSN census tracts (306 vs 236 DALYs/100,000), yielding a DALY-gap of 70 DALYs/100,000. Attributable DALY fraction for living in an AGSN was 25.4%. DALY-gap was highest for males 40-59 years of age (501 DALYs/100,000) and in census tracts with <60% electricity (12,327 DALYs/100,000). DALY-gap comparison revealed spatial and quantitative differences in TB burden between slum vs non-slum census tracts that were not apparent using traditional measures of incidence and mortality. This metric could be applied to compare TB burden or burden for other diseases in mega-cities with large informal settlements for more targeted resource allocation and evaluation of intervention programs.

Intraocular Pressure in Eyes Receiving Intravitreal Antivascular Endothelial Growth Factor Injections.

PURPOSE: The aim of the this study was to determine the effect of intravitreal antivascular endothelial growth factor injections on intraocular pressure (IOP) and identify possible risk factors for the development of increased IOP. MATERIALS AND METHODS: This prospective study included a total of 106 eyes receiving intravitreal injection of bevacizumab as treatment for macular edema or active choroidal neovascularization. IOP was measured by Goldmann applanation tonometry immediately before the intravitreal injection and 5 min, 1 h and 15 days after the procedure. The records of the study patients were reviewed for age, gender, history of glaucoma, diabetes mellitus, phakic status, systemic and topical medication and number of previous injections. Subconjunctival reflux was registered. IOP elevation was defined as IOP ≥21 mm Hg and/or a change from baseline of ≥5 mm Hg recorded at least on two or more measurements on the same visit. RESULTS: Mean preoperative IOP was 15.31 ± 3.90 mm Hg and postoperative IOP values were 27.27 ± 11.87 mm Hg (after 5 min), 17.59 ± 6.24 mm Hg (after 1 h) and 16.86 ± 3.62 mm Hg (after 15 days). The IOP variation was statistically significant between pre- and postoperative measurements (p < 0.05). Subconjunctival reflux was recorded in 11.3%, and in this subgroup the IOP at 5 min and at 1 h was lower than preoperative IOP (p < 0.05). CONCLUSIONS: More than one third of the eyes achieved IOPs >30 mm Hg 5 min after injection. Subconjunctival reflux contributed to a lower mean postoperative IOP (p < 0.05). Considerations for the management include prophylactic IOP lowering with medical therapy and/or preinjection ocular decompression for patients with a history of glaucoma or ocular hypertension and switching to an as-needed injection protocol in patients suffering a marked IOP rise in previous injections.