Rhodamine 6G and 800 intermolecular heteroaggregates embedded in PMMA for near-infrared wavelength shifting

The opto-electronic properties of small-molecules and functional dyes usually differ when incorporated into solid matrices with respect to their isolated form due to an aggregation phenomenon that alters their optical and fluorescent properties. These spectroscopic modifications are studied in the framework of the exciton theory of aggregates, which has been extensively applied in the literature for the study of molecular aggregates of the same type of molecules (homoaggregation). Despite the demonstrated potential of the control of the heteroaggregation process (aggregation of different types of molecules), most of the reported works are devoted to intramolecular aggregates, complex molecules formed by several chromophores attached by organic linkers. The intramolecular aggregates are specifically designed to hold a certain molecular structure that, on the basis of the exciton theory, modifies their optical and fluorescent properties with respect to the isolated chromophores that form the molecule. The present article describes in detail the incorporation of Rhodamine 6G (Rh6G) and 800 (Rh800) into polymeric matrices of poly-(methyl methacrylate), PMMA. The simultaneous incorporation of both dyes results in an enhanced fluorescent emission in the near-infrared (NIR), originating from the formation of ground-state Rh6G–Rh800 intermolecular heteroaggregates. The systematic control of the concentration of both rhodamines provides a model system for the elucidation of the heteroaggregate formation. The efficient energy transfer between Rh6G and Rh800 molecules can be used as wavelength shifters to convert effectively the light from visible to NIR, a very convenient wavelength range for many practical applications which make use of inexpensive commercial detectors and systems

Cardiovascular Screening Practices and Statin Prescription Habits in Patients with Psoriasis among Dermatologists, Rheumatologists and Primary Care Physicians

Patients with psoriasis have a higher prevalence of cardiovascular risk factors. This study evaluated cardio-vascular screening practices and statin prescribing habits among dermatologists, rheumatologists and primary care physicians (PCPs) through an online questionnaire, which was distributed through the Spanish scientific societies of the above-mentioned specialties. A total of 299 physicians (103 dermatologists, 94 rheumatologists and 102 PCPs) responded to the questionnaire. Of these, 74.6% reported screening for smoking, 37.8% for hypertension, 80.3% for dyslipidaemia, and 79.6% for diabetes mellitus. Notably, only 28.4% performed global screening, defined as screening for smoking, hypertension, dyslipidaemia, and diabetes mellitus by the same physician, and 24.4% reported calculating 10-year cardiovascular disease (CVD) risk, probably reflecting a lack of comprehensive cardiovascular risk assessment in these patients. This study also identified unmet needs for awareness of cardiovascular comorbidities in psoriasis and corresponding screening and treatment recommendations among PCPs. Of PCPs, 61.2% reported not being aware of the association between psoriasis and CVD and/or not being aware of its screening recommendations, and 67.6% did not consider psoriasis as a risk-enhancing factor when deciding on statin prescription. Thirteen dermatologists (12.6%) and 35 rheumatologists (37.2%) reported prescribing statins. Among those who do not prescribe, 49.7% would be willing to start their prescription

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Spatiotemporal Characteristics of the Largest HIV-1 CRF02_AG Outbreak in Spain: Evidence for Onward Transmissions

Background and Aim: The circulating recombinant form 02_AG (CRF02_AG) is the predominant clade among the human immunodeficiency virus type-1 (HIV-1) non-Bs with a prevalence of 5.97% (95% Confidence Interval-CI: 5.41–6.57%) across Spain. Our aim was to estimate the levels of regional clustering for CRF02_AG and the spatiotemporal characteristics of the largest CRF02_AG subepidemic in Spain.Methods: We studied 396 CRF02_AG sequences obtained from HIV-1 diagnosed patients during 2000–2014 from 10 autonomous communities of Spain. Phylogenetic analysis was performed on the 391 CRF02_AG sequences along with all globally sampled CRF02_AG sequences (N = 3,302) as references. Phylodynamic and phylogeographic analysis was performed to the largest CRF02_AG monophyletic cluster by a Bayesian method in BEAST v1.8.0 and by reconstructing ancestral states using the criterion of parsimony in Mesquite v3.4, respectively.Results: The HIV-1 CRF02_AG prevalence differed across Spanish autonomous communities we sampled from (p < 0.001). Phylogenetic analysis revealed that 52.7% of the CRF02_AG sequences formed 56 monophyletic clusters, with a range of 2–79 sequences. The CRF02_AG regional dispersal differed across Spain (p = 0.003), as suggested by monophyletic clustering. For the largest monophyletic cluster (subepidemic) (N = 79), 49.4% of the clustered sequences originated from Madrid, while most sequences (51.9%) had been obtained from men having sex with men (MSM). Molecular clock analysis suggested that the origin (tMRCA) of the CRF02_AG subepidemic was in 2002 (median estimate; 95% Highest Posterior Density-HPD interval: 1999–2004). Additionally, we found significant clustering within the CRF02_AG subepidemic according to the ethnic origin.Conclusion: CRF02_AG has been introduced as a result of multiple introductions in Spain, following regional dispersal in several cases. We showed that CRF02_AG transmissions were mostly due to regional dispersal in Spain. The hot-spot for the largest CRF02_AG regional subepidemic in Spain was in Madrid associated with MSM transmission risk group. The existence of subepidemics suggest that several spillovers occurred from Madrid to other areas. CRF02_AG sequences from Hispanics were clustered in a separate subclade suggesting no linkage between the local and Hispanic subepidemics

Treatment of Refractory Uveitis with Adalimumab: A Prospective Multicenter Study of 131 Patients

Objective: To evaluate adalimumab therapy in refractory uveitis. Design: Prospective case series. Participants: A total of 131 patients with refractory uveitis and intolerance or failure to respond to prednisone and at least 1 other systemic immunosuppressive drug participated. Intervention: Patients received a 40 mg adalimumab subcutaneous injection every other week for 6 months. The associated immunosuppressants were tapered after administering 3 adalimumab injections (week 6). Main outcome measures: Degree of anterior and posterior chamber inflammation (Standardization of Uveitis Nomenclature Working Group criteria), immunosuppression load (as defined by Nussenblatt et al), visual acuity (logarithm of the minimal angle of resolution [logMAR]), and macular thickness (optical coherence tomography). Results: There were 61 men and 70 women (mean age, 27.3 years). The most common causes were juvenile idiopathic arthritis in 39 patients, pars planitis in 16 patients, and Behçet's disease in 13 patients. Twenty-seven patients had uveitis of idiopathic origin. Inflammation in the anterior chamber was present in 82% of patients and in the vitreous cavity in 59% of patients. Anterior chamber inflammation and vitreous inflammation decreased significantly (P < 0.001) from a mean of 1.51 and 1.03 at baseline to 0.25 and 0.14, respectively, at 6 months. Macular thickness was 296 (102) μ at baseline versus 240 (36) μ at the 6-month visit (P < 0.001). Visual acuity improved by -0.3 logMAR in 32 of 150 eyes (21.3%) and worsened by +0.3 logMAR (-15 letters) in 5 eyes (3.3%). The dose of corticosteroids also decreased from 0.74 (3.50) to 0.20 (0.57) mg/kg/day (P < 0.001). Cystoid macular edema, which was present in 40 eyes at baseline, showed complete resolution in 28 eyes at 6 months. The mean suppression load decreased significantly (8.81 [5.05] vs 5.40 [4.43]; P < 0.001). Six months after the initiation of the study, 111 patients (85%) were able to reduce at least 50% of their baseline immunosuppression load. Only 9 patients (6.9%) had severe relapses during the 6 months of follow-up. Conclusions: Adalimumab seems to be well tolerated and helpful in decreasing inflammatory activity in refractory uveitis and may reduce steroid requirement. Further controlled studies of adalimumab for uveitis are warranted.Medicin

ICU-Acquired Pneumonia Is Associated with Poor HealthPost-COVID-19 Syndrome

Background. Some patients previously presenting with COVID-19 have been reported to develop persistent COVID-19 symptoms. While this information has been adequately recognised and extensively published with respect to non-critically ill patients, less is known about the incidence and factors associated with the characteristics of persistent COVID-19. On the other hand, these patients very often have intensive care unit-acquired pneumonia (ICUAP). A second infectious hit after COVID increases the length of ICU stay and mechanical ventilation and could have an influence on poor health post-COVID 19 syndrome in ICU-discharged patients. Methods: This prospective, multicentre, and observational study was carrid out across 40 selected ICUs in Spain. Consecutive patients with COVID-19 requiring ICU admission were recruited and evaluated three months after hospital discharge. Results: A total of 1255 ICU patients were scheduled to be followed up at 3 months; however, the final cohort comprised 991 (78.9%) patients. A total of 315 patients developed ICUAP (97% of them had ventilated ICUAP). Patients requiring invasive mechanical ventilation had more persistent post-COVID-19 symptoms than those who did not require mechanical ventilation. Female sex, duration of ICU stay, development of ICUAP, and ARDS were independent factors for persistent poor health post-COVID-19. Conclusions: Persistent post-COVID-19 symptoms occurred in more than two-thirds of patients. Female sex, duration of ICU stay, development of ICUAP, and ARDS all comprised independent factors for persistent poor health post-COVID-19. Prevention of ICUAP could have beneficial effects in poor health post-COVID-1

Comparative Study of Infliximab Versus Adalimumab in Refractory Uveitis due to Behçet's Disease: National Multicenter Study of 177 Cases.

To compare the efficacy of infliximab (IFX) versus adalimumab (ADA) as a first-line biologic drug over 1 year of treatment in a large series of patients with refractory uveitis due to Behçet's disease (BD). We conducted an open-label multicenter study of IFX versus ADA for BD-related uveitis refractory to conventional nonbiologic treatment. IFX or ADA was chosen as the first-line biologic agent based on physician and patient agreement. Patients received 3-5 mg/kg intravenous IFX at 0, 2, and 6 weeks and every 4-8 weeks thereafter, or 40 mg subcutaneous ADA every other week without a loading dose. Ocular parameters were compared between the 2 groups. The study included 177 patients (316 affected eyes), of whom 103 received IFX and 74 received ADA. There were no significant baseline differences between treatment groups in main demographic features, previous therapy, or ocular sign severity. After 1 year of therapy, we observed an improvement in all ocular parameters in both groups. However, patients receiving ADA had significantly better outcomes in some parameters, including improvement in anterior chamber inflammation (92.31% versus 78.18% for IFX; P = 0.06), improvement in vitritis (93.33% versus 78.95% for IFX; P = 0.04), and best-corrected visual acuity (mean ± SD 0.81 ± 0.26 versus 0.67 ± 0.34 for IFX; P = 0.001). A nonsignificant difference was seen for macular thickness (mean ± SD 250.62 ± 36.85 for ADA versus 264.89 ± 59.74 for IFX; P = 0.15), and improvement in retinal vasculitis was similar between the 2 groups (95% for ADA versus 97% for IFX; P = 0.28). The drug retention rate was higher in the ADA group (95.24% versus 84.95% for IFX; P = 0.042). Although both IFX and ADA are efficacious in refractory BD-related uveitis, ADA appears to be associated with better outcomes than IFX after 1 year of follow-up

New insights into the genetic etiology of Alzheimer’s disease and related dementias

Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele