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Purpose: This study aimed to develop and validate a comprehensive polygenic risk score (PRS) for keratoconus, enhancing the predictive accuracy for identifying individuals at increased risk, which is crucial for preventing keratoconus-associated visual impairment such as post-Laser-assisted in situ keratomileusis (LASIK) ectasia., Methods: We applied a multi-trait analysis approach (MTAG) to genome-wide association study data on keratoconus and quantitative keratoconus-related traits and used this to construct PRS models for keratoconus risk using several PRS methodologies. We evaluated the predictive performance of the PRSs in two biobanks: Estonian Biobank (EstBB; 375 keratoconus cases and 17 902 controls) and UK Biobank (UKB: 34 keratoconus cases and 1000 controls). Scores were compared using the area under the curve (AUC) and odds ratios (ORs) for various PRS models., Results: The PRS models demonstrated significant predictive capabilities in EstBB, with the SBayesRC model achieving the highest OR of 2.28 per standard deviation increase in PRS, with a model containing age, sex and PRS showing good predictive accuracy (AUC = 0.72). In UKB, we found that adding the best-performing PRS to a model containing corneal measurements increased the AUC from 0.84 to 0.88 (P = 0.012 for difference), with an OR of 4.26 per standard deviation increase in the PRS. These models showed improved predictive capability compared to previous keratoconus PRS., Conclusion: The PRS models enhanced prediction of keratoconus risk, even with corneal measurements, showing potential for clinical use to identify individuals at high risk of keratoconus, and potentially help reduce the risk of post-LASIK ectasia., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Purpose: To assess the association between physical activity and spectral-domain optical coherence tomography (SD-OCT)-measured rates of macular thinning in an adult population with primary open-angle glaucoma., Methods: The correlation between accelerometer-measured physical activity and rates of macular ganglion cell-inner plexiform layer (GCIPL) thinning was measured in 735 eyes from 388 participants of the Progression Risk of Glaucoma: RElevant SNPs with Significant Association (PROGRESSA) study. The association between accelerometer-measured physical activity and cross-sectional SD-OCT macular thickness was then assessed in 8862 eyes from 6152 participants available for analysis in the UK Biobank who had SD-OCT, ophthalmic, comorbidity, and demographic data., Results: Greater physical activity was associated with slower rates of macular GCIPL thinning in the PROGRESSA study (beta = 0.07 µm/y/SD; 95% confidence interval [CI], 0.03-0.13; P = 0.003) after adjustment for ophthalmic, demographic and systemic predictors of macular thinning. This association persisted in subanalyses of participants characterized as glaucoma suspects (beta = 0.09 µm/y/SD; 95% CI, 0.03-0.15; P = 0.005). Participants in the upper tertile (greater than 10,524 steps/d) exhibited a 0.22-µm/y slower rate of macular GCIPL thinning than participants in the lower tertile (fewer than 6925 steps/d): -0.40 ± 0.46 µm/y versus -0.62 ± 0.55 µm/y (P = 0.003). Both time spent doing moderate/vigorous activity and mean daily active calories were positively correlated with rate of macular GCIPL thinning (moderate/vigorous activity: beta = 0.06 µm/y/SD; 95% CI, 0.01-0.105; P = 0.018; active calories: beta = 0.06 µm/y/SD; 95% CI, 0.006-0.114; P = 0.032). Analysis among 8862 eyes from the UK Biobank revealed a positive association between physical activity and cross-sectional total macular thickness (beta = 0.8 µm/SD; 95% CI, 0.47-1.14; P < 0.001)., Conclusions: These results highlight the potential neuroprotective benefits of exercise on the human retina.

Purpose: To evaluate the relationship between body mass index (BMI) and glaucoma progression., Design: Multicohort observational study., Methods: This study combined a retrospective longitudinal analysis of suspect and early manifest primary open angle glaucoma cases from the Progression Risk of Glaucoma: RElevant SNPs with Significant Association (PROGRESSA) study with 2 replication cohorts from the UK Biobank and the Canadian Longitudinal Study of Ageing (CLSA). In the PROGRESSA study, multivariate analysis correlated BMI with longitudinal visual field progression in 471 participants. The BMI was then associated with glaucoma diagnosis and cross-sectional vertical cup-disc ratio (VCDR) measurements in the UK Biobank, and finally prospectively associated with longitudinal change in VCDR in the CLSA study., Results: In the PROGRESSA study, a lower BMI conferred a faster rate of visual field progression (mean duration of monitoring (5.28 ± 1.80 years (10.6 ± 3.59 visits) (β 0.04 dB/year/SD95% CI [0.005, 0.069]; P = .013). In the UK Biobank, a 1 standard deviation lower BMI was associated with a worse cross-sectional VCDR (β -0.048/SD 95% CI [-0.056, 0.96]; P < .001) and a 10% greater likelihood of glaucoma diagnosis, as per specialist grading of retinal fundus imaging (OR 0.90 95% CI [0.84, 0.98]; P = .011). Similarly, a lower BMI was associated with a greater risk of glaucoma diagnosis as per International Classification of Disease data (OR 0.94/SD; 95% CI [0.91, 0.98]; P = .002). Body mass index was also positively correlated with intraocular pressure (β 0.11/SD; 95% CI [0.06, 0.15]; P < .001). Finally, a lower BMI was then associated with greater VCDR change in the CLSA (β -0.007/SD; 95% CI [-0.01, -0.001]; P = .023)., Conclusions: Body mass index correlated with longitudinal and cross-sectional glaucomatous outcomes. This supports previous work illustrating a correlation between BMI and glaucoma., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Bouvardia ternifolia is a medicinal plant considered a source of therapeutic compounds, like the antitumoral cyclohexapeptide bouvardin. It is known that large number of secondary metabolites produced by plants results from the interaction of the host and adjacent or embedded microorganisms. Using high-throughput DNA sequencing of V3-16S and V5-18S ribosomal gene libraries, we characterized the endophytic, endophytic + epiphyte bacterial, and fungal communities associated to flowers, leaves, stems, and roots, as well as the rhizosphere. The Proteobacteria (average 80.7%) and Actinobacteria (average 14.7%) were the most abundant bacterial phyla, while Leotiomycetes (average 54.8%) and Dothideomycetes (average 27.4%) were the most abundant fungal classes. Differential abundance for the bacterial endophyte group showed a predominance of Erwinia, Propionibacterium, and Microbacterium genera, while Sclerotinia, Coccomyces, and Calycina genera predominated for fungi. The predictive metagenome analysis for bacteria showed significative abundance of pathways for secondary metabolite production, while a FUNguild analysis revealed the presence of pathotroph, symbiotroph, and saprotrophs in the fungal community. Intra and inter copresence and mutual exclusion interactions were identified for bacterial and fungal kingdoms in the endophyte communities. This work provides a description of the diversity and composition of bacterial and fungal microorganisms living in flowers, leaves, stems, roots, and the rhizosphere of this medicinal plant; thus, it paves the way towards an integral understanding in the production of therapeutic metabolites., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Community-acquired bacterial meningitis (CABM) morbidity and mortality remains high in those infected. Rapid diagnosis and treatment is paramount to reducing mortality and improving outcome. This retrospective cohort study aims to assess the time from presentation to diagnosis and treatment of vaccine preventable CABM as well as identify possible factors associated with delays in diagnosis and antibiotic administration. A retrospective chart review was conducted of individuals who presented to Columbia University Irving Medical Center (CUIMC), Children's Hospital of New York (CHONY), Mount Sinai Medical Center, and Weill Cornell Medical Center with BM due to Haemophilus influenzae type B, Streptococcus pneumoniae, and Neisseria meningitidis between January 1, 2012 and December 31, 2017. Diagnosis was delayed by more than 8 hours in 13 patients (36.1%) and 5 individuals (13.9%) had a delay of 4 hours or more from presentation to the administration of antibiotics with appropriate CNS coverage. All of these patients were also initially misdiagnosed at an outpatient clinic, outside hospital, or emergency department. This retrospective study identified febrile and/or viral infections not otherwise specified and otitis media as the most common misdiagnoses underlying delays from presentation to diagnosis and to antibiotic treatment in those with BM., Competing Interests: Declaration of Conflicting Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

Enteroviruses (EV) are responsible for a large number of meningoencephalitis cases, especially in children. The objective of this study was to identify modes of diagnosis including the significance of respiratory and cerebrospinal fluid samples, associated clinical characteristics, inpatient management, and outcome of individuals with EV infections of the central nervous system (CNS). Electronic medical records of individuals with enterovirus infections of the CNS who presented to the Columbia University Irving Medical Center and Children's Hospital of New York between January 1, 2012 and December 31, 2017 were reviewed retrospectively for demographic, epidemiological, and clinical data. The median age overall was 1.7 months (interquartile range 14 years) and most (62.4%) were male. The majority of CNS infections presented as meningitis (95.7%) and occurred in the summer (45.2%) and fall seasons (37.6%). Eighty-five cases (91.4%) demonstrated EV positivity in cerebrospinal fluid, thirty cases (32.3%) exhibited both cerebrospinal fluid and respiratory positivity, and eight cases (8.6%) exhibited respiratory positivity with coinciding neurological findings. Eighty-nine individuals overall (95.7%) received antibiotics and 37 (39.8%) received antiviral treatment. All surviving individuals had favorable Modified Rankin Scores (MRS) within the zero to two ranges upon discharge. Testing respiratory samples in addition to cerebrospinal fluid was found to be an important diagnostic tool in EV-associated cases. While clinical outcomes were favorable for an overwhelming majority of cases, etiological understanding of CNS infections is essential for identifying ongoing and changing epidemiological patterns and aid in improving the diagnosis and treatment.

Background: Socioeconomic factors have been consistently linked with the structure of children's hippocampus and anterior cingulate cortex (ACC). Chronic stress-as indexed by hair cortisol concentration-may represent an important mechanism underlying these associations. Here, we examined associations between hair cortisol and children's hippocampal and ACC structure, including across hippocampal subfields, and whether hair cortisol mediated associations between socioeconomic background (family income-to-needs ratio, parental education) and the structure of these brain regions., Methods: Participants were 5- to 9-year-old children (N = 94; 61% female) from socioeconomically diverse families. Parents and children provided hair samples that were assayed for cortisol. High-resolution, T1-weighted magnetic resonance imaging scans were acquired, and FreeSurfer 6.0 was used to compute hippocampal volume and rostral and caudal ACC thickness and surface area (n = 37 with both child hair cortisol and magnetic resonance imaging data; n = 41 with both parent hair cortisol and magnetic resonance imaging data)., Results: Higher hair cortisol concentration was significantly associated with smaller CA3 and dentate gyrus hippocampal subfield volumes but not with CA1 or subiculum volume. Higher hair cortisol was also associated with greater caudal ACC thickness. Hair cortisol significantly mediated associations between parental education level and CA3 and dentate gyrus volumes; lower parental education level was associated with higher hair cortisol, which in turn was associated with smaller volume in these subfields., Conclusions: These findings point to chronic physiologic stress as a potential mechanism through which lower parental education level leads to reduced hippocampal volume. Hair cortisol concentration may be an informative biomarker leading to more effective prevention and intervention strategies aimed at childhood socioeconomic disadvantage., (Copyright © 2019 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: Mosquito-borne pathogens pose major public health challenges worldwide. With vaccines or effective drugs still unavailable for most such pathogens, disease prevention heavily relies on vector control. To date, however, mosquito control has proven difficult, with low breeding-site coverage during control campaigns identified as a major drawback. A novel tactic exploits the egg-laying behavior of mosquitoes to have them disseminate tiny particles of a potent larvicide, pyriproxyfen (PPF), from resting to breeding sites, thus improving coverage. This approach has yielded promising results at small spatial scales, but its wider applicability remains unclear., Methodology/principal Findings: We conducted a four-month trial within a 20-month study to investigate mosquito-driven dissemination of PPF dust-particles from 100 'dissemination stations' (DSs) deployed in a 7-ha sub-area to surveillance dwellings and sentinel breeding sites (SBSs) distributed over an urban neighborhood of about 50 ha. We assessed the impact of the trial by measuring juvenile mosquito mortality and adult mosquito emergence in each SBS-month. Using data from 1,075 dwelling-months, 2,988 SBS-months, and 29,922 individual mosquitoes, we show that mosquito-disseminated PPF yielded high coverage of dwellings (up to 100%) and SBSs (up to 94.3%). Juvenile mosquito mortality in SBSs (about 4% at baseline) increased by over one order of magnitude during PPF dissemination (about 75%). This led to a >10-fold decrease of adult mosquito emergence from SBSs, from approximately 1,000-3,000 adults/month before to about 100 adults/month during PPF dissemination., Conclusions/significance: By expanding breeding-site coverage and boosting juvenile mosquito mortality, a strategy based on mosquito-disseminated PPF has potential to substantially enhance mosquito control. Sharp declines in adult mosquito emergence can lower vector/host ratios, reducing the risk of disease outbreaks. This approach is a very promising complement to current and novel mosquito control strategies; it will probably be especially relevant for the control of urban disease vectors, such as Aedes and Culex species, that often cause large epidemics.

Aedes aegypti and Ae. albopictus are the vectors of dengue, the most important arboviral disease of humans. To date, Aedes ecology studies have assumed that the vectors are truly absent from sites where they are not detected; since no perfect detection method exists, this assumption is questionable. Imperfect detection may bias estimates of key vector surveillance/control parameters, including site-occupancy (infestation) rates and control intervention effects. We used a modeling approach that explicitly accounts for imperfect detection and a 38-month, 55-site detection/non-detection dataset to quantify the effects of municipality/state control interventions on Aedes site-occupancy dynamics, considering meteorological and dwelling-level covariates. Ae. aegypti site-occupancy estimates (mean 0.91; range 0.79-0.97) were much higher than reported by routine surveillance based on 'rapid larval surveys' (0.03; 0.02-0.11) and moderately higher than directly ascertained with oviposition traps (0.68; 0.50-0.91). Regular control campaigns based on breeding-site elimination had no measurable effects on the probabilities of dwelling infestation by dengue vectors. Site-occupancy fluctuated seasonally, mainly due to the negative effects of high maximum (Ae. aegypti) and minimum (Ae. albopictus) summer temperatures (June-September). Rainfall and dwelling-level covariates were poor predictors of occupancy. The marked contrast between our estimates of adult vector presence and the results from 'rapid larval surveys' suggests, together with the lack of effect of local control campaigns on infestation, that many Aedes breeding sites were overlooked by vector control agents in our study setting. Better sampling strategies are urgently needed, particularly for the reliable assessment of infestation rates in the context of control program management. The approach we present here, combining oviposition traps and site-occupancy models, could greatly contribute to that crucial aim.

Introduction: Rheumatoid arthritis (RA) is a common autoimmune disease with a complex genetic background. The PTPN22 gene encodes lymphoid tyrosine phosphatase LYP, a potent negative regulator of T cell activation. Polymorphic variants of this gene have previously been associated with various autoimmune disorders. The +1858C/T single-nucleotide polymorphism (SNP) (rs2476601), in the exon 14 of the PTPN22 gene has been associated with susceptibility to RA in several population., Objective: The aim of this work was to investigate whether the +1858C/T of the PTPN22 gene is associated with susceptibility to RA in Western Mexico population., Methods: A total of 309 unrelated RA patients, classified according to American College of Rheumatology (ACR) 1987 criteria, as well as 347 controls residents from Western Mexico were recruited for this study. The DNA samples were genotyped for +1858C/T PTPN22 gene SNP using the PCR-RFLP technique. Antibodies to cyclic citrullinated peptides (anti-CCP) were measured by enzyme-linked immunosorbent assay (ELISA)., Results: The frequency of +1858T risk allele was significantly increased in patients with RA compared with controls (p=0.001, OR=2.83, 95%CI=1.50-5.32). To confirm this results we established a comparison between subjects carrying of CT+TT genotypes versus those carrying CC genotype, between both groups (p=0.004, OR=2.65, 95%CI=1.33-5.36). Nevertheless, we not observed association of the +1858C/T PTPN22 gene SNP with clinical activity and functional disability in RA patients. Likewise, the +1858T variant in RA patients seropositive for anti-CCP antibodies, increased the risk for RA (p=0.008, OR=2.5, 95%CI=1.3-5.0) when we compared with controls; however, in the group of seronegative patients, no was found significant difference (p=0.1, OR=2.5, 95%CI=0.9-7.2)., Conclusions: Our results support the association of the +1858T risk allele of the +1858C/T PTPN22 polymorphism with susceptibility to RA and confirm that, in combination with anti-CCP antibodies, this SNP influence the autoimmune processes towards a development of RA in Mexican population., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Objective: Rheumatoid arthritis (RA) is an autoimmune disease of unknown etiology in which inflammatory pathology involves T cell activation and the CD28 costimulatory molecule involved in T cell presentation. The gene includes the CD28 IVS3 +17T/C polymorphism that could be associated with susceptibility to RA whereas the soluble concentrations of CD28 (sCD28) could be related to clinical activity., Methods: We investigated the CD28 IVS3 +17T/C polymorphism in 200 RA patients and 200 healthy subjects (HS). Furthermore, we quantified the sCD28 concentrations in 77 samples of each group. We applied indexes focused to determine the activity and disability (DAS28 and Spanish HAQ-DI, respectively) in RA patients., Results: RA patients had significantly higher frequencies of the CD28 T allele compared to HS (p = 0.032 OR = 1.59, C.I. 1.02-2.49). In addition, the IVS3 +17 T/T genotype frequency was also increased in RA vs. HS (p = 0.026). The RA patients showed higher sCD28 serum levels than HS (p = 0.001). Carriers of the T/T genotype in RA patients showed higher sCD28 levels than C/C carriers (p =0.047). In addition, a correlation between sCD28 and Spanish HAQ-DI (correlation, 0.272; p =0.016), was found., Conclusion: The T allele in CD28 IVS3 +17T/C polymorphism is associated with a susceptibility to RA in Western Mexico. In addition, increased sCD28 levels are related to T/T genotype in RA patients.