Etiology and Risk Factors for Infectious Keratitis in South Texas

Purpose: To determine the causative organisms and associated risk factors for infectious keratitis in South Texas. Methods: This retrospective study was performed at a tertiary teaching hospital system in South Texas. Medical records of all patients who presented with infectious keratitis from 2012 to 2018 were reviewed. Only patients with culture-proven bacterial, fungal, and Acanthamoeba keratitis were included. Results: In total, 182 eyes of 181 patients had culture-proven bacterial, fungal, or Acanthamoeba keratitis. The age of patients ranged from 3 to 93 years, with a mean of 48.3 ± 20.8 years. The most common etiologic agent was bacteria, with 173 bacterial cultures (95.1%) recovered, followed by 13 fungal cultures (7.1%), and 3 Acanthamoeba cultures (1.6%). Of the 218 bacterial isolates, coagulase-negative Staphylococcus was the most common (25.7%), followed by Pseudomonas aeruginosa (23.4%), Staphylococcus aureus (11.0%), and Moraxella (7.8%). Fusarium was the most common fungal isolate (46.2%). The most common risk factors for infectious keratitis included contact lens wear (32.4%), underlying corneal disease (17.6%), trauma (14.3%), and ocular surface disease (13.7%). Conclusions: Bacteria are the most common cause of infectious keratitis in this patient population, with coagulase-negative Staphylococcus and Pseudomonas as the most common isolates. The prevalence of culture-positive fungal keratitis is significantly lower than that of bacterial keratitis. Contact lens wear is the most common risk factor associated with infectious keratitis in South Texas

Comprehensive Analysis of HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 Loci and Squamous Cell Cervical Cancer Risk

Variation in human major histocompatibility genes may influence the risk of squamous cell cervical cancer (SCC) by altering the efficiency of the T-cell–mediated immune response to human papillomavirus (HPV) antigens. We used high-resolution methods to genotype human leukocyte antigen (HLA) class I (A, B, and Cw) and class II (DRB1 and DQB1) loci in 544 women with SCC and 542 controls. Recognizing that HLA molecules are codominantly expressed, we focused on co-occurring alleles. Among 137 allele combinations present at >5% in the case or control groups, 36 were significantly associated with SCC risk. All but one of the 30 combinations that increased risk included DQB1*0301, and 23 included subsets of A*0201-B*4402-Cw*0501-DRB1*0401-DQB1*0301. Another combination, B*4402-DRB1*1101-DQB1*0301, conferred a strong risk of SCC (odds ratio, 10.0; 95% confidence interval, 3.0–33.3). Among the six combinations that conferred a decreased risk of SCC, four included Cw*0701 or DQB1*02. Most multilocus results were similar for SCC that contained HPV16; a notable exception was A*0101-B*0801-Cw*0701-DRB1*0301-DQB1*0201 and its subsets, which were associated with HPV16-positive SCC (odds ratio, 0.5; 95% confidence interval, 0.3–0.9). The main multilocus associations were replicated in studies of cervical adenocarcinoma and vulvar cancer. These data confirm that T helper and cytotoxic T-cell responses are both important cofactors with HPV in cervical cancer etiology and indicate that co-occurring HLA alleles across loci seem to be more important than individual alleles. Thus, certain co-occurring alleles may be markers of disease risk that have clinical value as biomarkers for targeted screening or development of new therapies

Simple models of the chemical field around swimming plankton

Background. Cervical cancer is the fourth most common cancer in women, and we recently reported human leukocyte antigen (HLA) alleles showing strong associations with cervical neoplasia risk and protection. HLA ligands are recognized by killer immunoglobulin-like receptors (KIRs) expressed on a range of immune cell subsets, governing their proinflammatory activity. We hypothesized that the inheritance of particular HLA-KIR combinations would increase cervical neoplasia risk. Methods. Here, we used HLA and KIR dosages imputed from single-nucleotide polymorphism genotype data from 2143 cervical neoplasia cases and 13 858 healthy controls of European decent. Results. The following 4 novel HLA alleles were identified in association with cervical neoplasia, owing to their linkage disequilibrium with known cervical neoplasia-associated HLA-DRB1 alleles: HLA-DRB3*9901 (odds ratio [OR], 1.24; P = 2.49 × 10−9), HLA-DRB5*0101 (OR, 1.29; P = 2.26 × 10−8), HLA-DRB5*9901 (OR, 0.77; P = 1.90 × 10−9), and HLA-DRB3*0301 (OR, 0.63; P = 4.06 × 10−5). We also found that homozygosity of HLA-C1 group alleles is a protective factor for human papillomavirus type 16 (HPV16)-related cervical neoplasia (C1/C1; OR, 0.79; P = .005). This protective association was restricted to carriers of either KIR2DL2 (OR, 0.67; P = .00045) or KIR2DS2 (OR, 0.69; P = .0006). Conclusions. Our findings suggest that HLA-C1 group alleles play a role in protecting against HPV16-related cervical neoplasia, mainly through a KIR-mediated mechanism

Defining the genetic susceptibility to cervical neoplasia - a genome-wide association study

Funding: MAB was funded by a National Health and Medical Research Council (Australia) Senior Principal Research Fellowship. Support was also received from the Australian Cancer Research Foundation. JL holds a Tier 1 Canada Research Chair in Human Genome Epidemiology. The Seattle study was supported by the following grants: NIH, National Cancer Institute grants P01CA042792 and R01CA112512. Cervical Health Study (from which the NSW component was obtained) was funded by NHMRC Grant 387701, and CCNSW core grant. The Montreal study was funded by the Canadian Institutes of Health Research (grant MOP-42532) and sample processing was funded by the Reseau FRQS SIDA-MI. The Swedish Research Council, the Swedish Foundation for Strategic Research, the ALF/LUA research grant in Gothenburg and Umeå, the Lundberg Foundation, the Torsten and Ragnar Soderberg’s Foundation, the Novo Nordisk Foundation, and the European Commission grant HEALTH-F2-2008-201865-GEFOS, BBMRI.se, the Swedish Society of Medicine, the KempeFoundation (JCK-1021), the Medical Faculty of Umeå University, the County Council of Vasterbotten (Spjutspetsanslag VLL:159:33-2007). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscriptPeer reviewedPublisher PDFPublisher PD

Cervical and Vulvar Cancer Risk in Relation to the Joint Effects of Cigarette Smoking and Genetic Variation in Interleukin 2.

Cigarette smoking is an established cofactor to human papillomavirus (HPV) in the development of cervical and vulvar squamous cell carcinoma (SCC), and may influence risk through an immunosuppressive pathway. Genetic variation in interleukin 2 (IL2), associated in some studies with the inhibition of HPV-targeted immunity, may modify the effect of smoking on the risk of HPV-related anogenital cancers. We conducted a population-based case-only study to measure the departure from a multiplicative joint effect of cigarette smoking and IL2 variation on cervical and vulvar SCC. Genotyping of the four IL2 tagSNPs (rs2069762, rs2069763, rs2069777, and rs2069778) was done in 399 cervical and 486 vulvar SCC cases who had been interviewed regarding their smoking history. Compared with cases carrying the rs2069762 TT genotype, we observed significant departures from multiplicativity for smoking and carriership of the TG or GG genotypes in vulvar SCC risk [interaction odds ratio (IOR), 1.67; 95% confidence interval (CI), 1.16-2.41]. Carriership of one of three diplotypes, together with cigarette smoking, was associated with either a supramultiplicative (TGCT/GGCC; IOR, 2.09; 95% CI, 0.98-4.46) or submultiplicative (TTCC/TGTC; IOR, 0.37; 95% CI, 0.16-0.85 or TGCT/TGCC; IOR, 0.37; 95% CI, 0.15-0.87) joint effect in vulvar cancer risk. For cervical SCC, departure from multiplicativity was observed for smokers homozygous for the rs2069763 variant allele (TT versus GG or GT genotypes; IOR, 1.87; 95% CI, 1.00-3.48), and for carriership of the TTCC/TTCC diplotype (IOR, 2.08; 95% CI, 1.01-4.30). These results suggest that cervical and vulvar SCC risk among cigarette smokers is modified by genetic variation in IL2. (Cancer Epidemiol Biomarkers Prev 2008;17(7):1790-9)

A "novel" reading therapy programme for reading difficulties after a subarachnoid haemorrhage

Background: Although several treatments for acquired reading difficulties exist, few studies have explored the effectiveness of treatment for mild reading difficulties and treatment for reading difficulties associated with cognitive impairment. Aims: This study explored the effectiveness of an individual strategy-based reading treatment of 11 sessions given to a female participant (IW) who had mild reading difficulties following a subarachnoid haemorrhage (SAH). The impact of treatment on reading ability, confidence and emotions associated with reading were investigated. Methods & Procedures: Treatment focussed on the use of strategies to support IW’s memory when reading books, the use of a checklist to select appropriate reading materials, and increasing IW’s confidence in discussing the book she was reading with others. A person-centred approach and personally relevant materials were used throughout the treatment. Reading ability was assessed using the Gray Oral Reading Tests (GORT-4; Lee Wiederholt & Bryant, 2001), and IW’s perspective was obtained using the Reading Confidence and Emotions Questionnaire (RCEQ; see Cocks et al., 2010. Pre-treatment, post-treatment and maintenance (7 weeks post) assessments were undertaken, with an additional exit interview at the final time point. Outcomes & Results: Gains were noted in reading rate, accuracy, comprehension, and confidence, with parallel increased pleasure gained from reading and reduced negative emotions and frustration. Self-reported gains included conversing with others about material read, verbal communication, and re-engagement with the identity of being a reader. Conclusions: Strategy-based treatment resulted in positive gains in reading for pleasure, conversation, and identity, for an individual with mild chronic reading difficulties. Participant self-report and interview reveal the true value of this treatment for the individual. The positive results suggest that further research is warranted that investigates the effectiveness of strategy-based reading therapy approaches for others with acquired reading difficulties

Notch1 is required for maintenance of the reservoir of adult hippocampal stem cells

Notch1 regulates neural stem cell (NSC) number during development, but its role in adult neurogenesis is unclear. We generated nestin-CreER(T2)/R26R-YFP/Notch1(loxP/loxP) [Notch1inducible knock-out (iKO)] mice to allow tamoxifen (TAM)-inducible elimination of Notch1 and concomitant expression of yellow fluorescent protein (YFP) in nestin-expressing Type-1 NSCs and their progeny in the adult hippocampal subgranular zone (SGZ). Consistent with previous research, YFP+ cells in all stages of neurogenesis were evident in the subgranular zone (SGZ) of wild-type (WT) mice (nestin-CreER(T2)/R26R-YFP/Notch1(w/w)) after tamoxifen (post-TAM), producing adult-generated YFP+ dentate gyrus neurons. Compared with WT littermates, Notch1 iKO mice had similar numbers of total SGZ YFP+ cells 13 and 30 d post-TAM but had significantly fewer SGZ YFP+ cells 60 and 90 d post-TAM. Significantly fewer YFP+ Type-1 NSCs and transiently amplifying progenitors (TAPs) resulted in generation of fewer YFP+ granule neurons in Notch1 iKO mice. Strikingly, 30 d of running rescued this deficit, as the total YFP+ cell number in Notch iKO mice was equivalent to WT levels. This was even more notable given the persistent deficits in the Type-1 NSC and TAP reservoirs. Our data show that Notch1 signaling is required to maintain a reservoir of undifferentiated cells and ensure continuity of adult hippocampal neurogenesis, but that alternative Notch- and Type-1 NSC-independent pathways compensate in response to physical activity. These data shed light on the complex relationship between Type-1 NSCs, adult neurogenesis, the neurogenic niche, and environmental stimuli

Seasonal melting and the formation of sedimentary rocks on Mars, with predictions for the Gale Crater mound

A model for the formation and distribution of sedimentary rocks on Mars is proposed. The rate-limiting step is supply of liquid water from seasonal melting of snow or ice. The model is run for a O(10^2) mbar pure CO2 atmosphere, dusty snow, and solar luminosity reduced by 23%. For these conditions snow only melts near the equator, and only when obliquity >40 degrees, eccentricity >0.12, and perihelion occurs near equinox. These requirements for melting are satisfied by 0.01-20% of the probability distribution of Mars' past spin-orbit parameters. Total melt production is sufficient to account for aqueous alteration of the sedimentary rocks. The pattern of seasonal snowmelt is integrated over all spin-orbit parameters and compared to the observed distribution of sedimentary rocks. The global distribution of snowmelt has maxima in Valles Marineris, Meridiani Planum and Gale Crater. These correspond to maxima in the sedimentary-rock distribution. Higher pressures and especially higher temperatures lead to melting over a broader range of spin-orbit parameters. The pattern of sedimentary rocks on Mars is most consistent with a Mars paleoclimate that only rarely produced enough meltwater to precipitate aqueous cements and indurate sediment. The results suggest intermittency of snowmelt and long globally-dry intervals, unfavorable for past life on Mars. This model makes testable predictions for the Mars Science Laboratory rover at Gale Crater. Gale Crater is predicted to be a hemispheric maximum for snowmelt on Mars.Comment: Submitted to Icarus. Minor changes from submitted versio

Atypical processing of gaze cues and faces explains comorbidity between autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD)

This study investigated the neurobiological basis of comorbidity between autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD). We compared children with ASD, ADHD or ADHD+ASD and typically developing controls (CTRL) on behavioural and electrophysiological correlates of gaze cue and face processing. We measured effects of ASD, ADHD and their interaction on the EDAN, an ERP marker of orienting visual attention towards a spatially cued location and the N170, a right-hemisphere lateralised ERP linked to face processing. We identified atypical gaze cue and face processing in children with ASD and ADHD+ASD compared with the ADHD and CTRL groups. The findings indicate a neurobiological basis for the presence of comorbid ASD symptoms in ADHD. Further research using larger samples is needed