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We investigated the association between inflammatory trachoma in children aged 1-5 and environmental and sociodemographic risk factors in a rural Nile Delta hamlet. Inflammatory trachoma clustered in households, emphasising the child-to-child nature of transmission in the hamlet. Multiple logistic regression analysis revealed three factors predicting inflammatory trachoma in children: the absence of a latrine in the household, school-age siblings with inflammatory trachoma, and additional same-age siblings (with or without disease) in the household. In the Egyptian setting the presence of pit latrines in all houses, even when full and unscreened, might result in a reduction in trachoma prevalence in this population from the current 49% to 35%. The construction of pit latrines may offer the simplest and most acceptable environmental method for reducing trachoma in this trachoma endemic area.

Four days after corneal inoculation of mice with herpes simplex (type 1) virus (HSV), infected trigeminal ganglion cells with and without calcitonin gene-related peptide (CGRP) antigenicity were examined by electron microscopy in sections treated with colloidal gold labeled antibodies. Cells that contain CGRP were identified by the dense gold labeling of small vesicles about 100 nm in diameter. Adjacent thin sections were stained using an indirect colloidal gold immunocytochemical technique to reveal HSV-1 antigens. In CGRP-positive neurons, HSV antigens were located over both nuclear and cytoplasmic compartments. HSV label was found over cytoplasmic vesicles that were significantly larger than those labeled with anti-CGRP antisera; the HSV-containing vesicles ranged in profile diameter from less than 170 to greater than 400 nm. There was no overlap in the distribution of the two labels. Thus, for this time period, the organelles involved in transport of the endogenous neuropeptide and HSV appear to remain discrete. Furthermore, there was no significant difference in the distribution of HSV in CGRP-reactive and CGRP-negative trigeminal ganglion cells. Thus, there is no indication of a preferential distribution or limited replication of HSV in CGRP-positive neurons.

Expert Commentary Reports on the Prevalence of Clinical Conditions Are More Convincing When Supported by Objective Evidence Julius Schachter 1 *, Robin Bailey 2 , Chandler R. Dawson 3 , Thomas M. Lietman 3 1 Department of Laboratory Medicine, University of California San Francisco, San Francisco, California, United States of America, 2 Department of Tropical Medicine, London School of Hygiene & Tropical Medicine, London, United Kingdom, 3 Proctor Foundation, University of California San Francisco, San Francisco, California, United States of America A relatively easy way to document the validity of the clinical classifications is to take photographs of the conjunctivae and make these available for external review to ensure that there is no over- grading. Digital photography now offers the ability to generate high-quality records of the initial clinical findings for validation purposes. It is not clear to us why photography is not a routine tool used by programs to monitor their success. A further option would be to document Chlamydia trachomatis infection using current generation nucleic acid amplification tests (NAATs) to detect the causative agent of trachoma. While this may not be the current state-of-the-art for trachoma surveys, and has cost implications, it has proved a useful tool for documenting prevalence rates of chlamydial infection in trachoma-endemic areas, and the positivity prior to treatment correlates well with disease intensity [2]. To reduce costs, a sampling strategy could be developed to use NAAT testing before the program is implemented to estimate a baseline prevalence of infection, and to compare this to results obtained after implementation of the AFE aspects of the Surgery, Antibiotics, Facial hygiene and Environmental improvements (SAFE) strategy [3]. The lower prevalence of infection seen after treatment allows specimen pooling strategies to further reduce costs of NAAT testing. Infection is a more sensitive indicator of the success of antibiotic treatment than is clinical disease, which takes a longer time to resolve. Perhaps resources for NAAT testing were not available, and there were concerns about the use of swabs, and transport of specimens to the laboratory; but certainly in the era of digital photography it is not unreasonable to request documenta- tion of clinical findings for such a report. Having raised this caveat, we must congratulate King and colleagues for performing this survey under extraordinarily difficult conditions. They are working in an area where supplies are difficult to obtain, and where there is civil unrest. They have documented an extremely high prevalence of clinically active The accompanying research report by King and colleagues [1] describes a trachoma survey performed in Ayod County, southern Sudan. They performed a cross-sectional two-stage cluster survey of trachoma status in November 2006 and found levels of disease that rival those in the most hyper-endemic areas: 88% of children between ages 1 and 9 years had clinically active trachoma and the children were actually starting to show trichiasis (approximately 3%). In those over 14 years of age, 59% had clinically active trachoma, 14.6% had trichiasis, and 6.4% had corneal opacity. Trachoma was present in virtually all households; 98% had at least one person having active trachoma, and one-third of households had individuals with trichiasis. Although a number of conditions generally considered to be risk factors for trachoma were commonly found (for example, only 5% of households had latrines and water availability was limited, with journey times to fetch water of more than 30 minutes), these alone could not account for the severity of the disease the authors described. What is certain is that in this extremely impoverished area of Sudan, blinding trachoma is a major public health problem. There has been a major collapse of infrastructure, and rudimentary public health measures have been lacking for many years. However, when faced with reports of such high levels of disease, one must be highly sensitive to the possibility of systematic bias in the clinical grading. The World Health Organization scheme used here has proven invaluable for trachoma programs to assess which areas will require mass (community-wide) treatment. However, the grading scale is subjective, imprecise, and not a particularly good indicator for infection with the ocular strains of chlamydia that cause trachoma. It was developed for, and is best used within programs, but does not have the fine distinctions in grading clinical disease that one would like to see within scientific reports. King et al. report data from within a trachoma elimination program. They have undertaken evaluations and statistical analyses to ensure that the clinical scoring generated by their field workers was consistent and agreed with a standardized set of photos. However, these field workers were relatively inexperienced at dealing with trachoma and were specially trained for this program. The data they have generated will be valuable in the monitoring and evaluation of their trachoma elimination program. There are good self-serving reasons for those performing surveys in the context of control programs to provide the most solid evidence of the validity of their baseline findings. Systematic overscoring of clinical disease at baseline will almost certainly result in a successful outcome for any intervention; it could make the results of ineffective programs appear good, and the results of good programs appear spectacular. It is far better to provide evidence for the baseline levels that either cannot be questioned, or which can be validated. Thus, the unbiased reader would really like to have something besides subjective clinical classifications. www.plosntds.org Citation: Schachter J, Bailey R, Dawson CR, Lietman TM (2008) Reports on the Prevalence of Clinical Conditions Are More Convincing When Supported by Objective Evidence. PLoS Negl Trop Dis 2(9): e302. doi:10.1371/journal. pntd.0000302 Editor: Albert I. Ko, Weill Medical College of Cornell University, United States of America Published September 24, 2008 Copyright: s 2008 Schachter et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: The authors received no specific funding for this article. Competing Interests: The authors have declared that no competing interests exist. * E-mail: Julius.Schachter@ucsf.edu September 2008 | Volume 2 | Issue 9 | e302

Hormonal predictors of labor initiation are of considerable interest but are not clearly elucidated. Current hypotheses suggest a surge in the ratio of estriol to progesterone from b1 to N1 marks the impending onset of labor [1–3]. Little research exists examining relationships between other steroid hormones and parturition in healthy, uncomplicated, late-term pregnancies [4]. The purpose of this study was to assess prospectively associations between salivary progesterone, DHEAS, testosterone, estrone, estradiol, and estriol concentrations and parturition. Twenty-four healthy, medication free, primigravid women were recruited from area childbirth education classes and gave their informed consent to participate. This study was approved by the UNLV institutional review board. Pre-prandial, un-stimulated saliva samples were collected from participants at 9:00 am at 37 weeks +/−2 days of pregnancy. Specimen were mailed via two-day courier to AllVia Diagnostic Lab in Phoenix, AZ for analysis, enzyme immunosorbent assays. Pearson's bivariate correlations were calculated to determine relationships between salivary hormones and length of gestation. Normality was tested using Shapiro–Wilks, pb .05. The mean age of the participants was 29.63, SD 4.16. The average length of gestation was 277 days +/−6.68 days. Participants were tested at 259 days +/−2 days. The mean number of days from test time to delivery was 18 days. All participants began labor naturally without assistance. After labor initiated 11 women required medical intervention either via medication (n=9) or cesarean section (n=2) to deliver. Thirteen women delivered without assistance. All delivered healthy infants. The intraand inter-assay coefficients of variation did not exceed 10% except for inter-day estrone (16.25%). Descriptive hormone data are presented in Table 1. Progesterone was correlated with longer pregnancies (r=.414, pb .05) while estradiol was associated with shorter pregnancies (r= −.519, pb .01). No significant correlations between estriol values or the mean ratio of estriol to progesterone (.57) and delivery was found. No other hormone was correlated with parturition. Researchers have identified a pre-delivery surge of estriol either alone [3] or relative to progesterone [1,2] associated with labor initiation, suggesting that fetal input contributes to the onset of labor and that an estriol surgemarks impending delivery. Our study does not support these findings. Here, progesterone and estradiol, but not estriol either alone or relative to progesterone were associated with parturition in healthy, late

Proteasome inhibition has been shown to be an important strategy for treating many types of cancer. Although proteasome inhibitors are effective at eradicating rapidly proliferating cancer cells, a subset of cancer cells enter quiescence and survive, contributing to tumor recurrence. Using primary human fibroblasts as a model system we have shown that quiescent cells have decreased reactive oxygen species levels and protein aggregates, and undergo apoptosis less frequently than proliferating cells in response to proteasome inhibition. However, the precise mechanism by which quiescent cells become resistant to proteasome inhibition remains largely unknown. Using a GFP-tagged proteasome reporter, we investigated mechanisms protecting quiescent cells from proteasome inhibition-induced apoptosis. We found that, in proliferating cells, proteasome inhibition by MG132 led to high levels of a GFP-tagged proteasome reporter with a visible ubiquitination pattern. In contrast, MG132 treatment of quiescent cells resulted in reduced levels of the ubiquitinated form of this reporter as observed by Western blot analysis. Interestingly, preliminary immunoprecipitation followed by mass-spectrometry analysis revealed none canonical ubiquitin modification on lysine 27 of the reporter in quiescent cells. These findings suggested that quiescent cells may have one or more alternative pathways preventing specific proteasome substrates accumulation in response to proteasome inhibition. Moreover, our data has shown that, upon proteasome inhibition, a GFP-tagged proteasome reporter was secreted into the condition medium. Secretion of cytoplasmic proteins in response to proteasome inhibition is one possible mechanism for reducing protein aggregation and cytotoxicity. Identification of regulatory mechanisms that are activated in quiescent cells in response to proteasome inhibition may help to suggest strategies for improving the effectiveness of proteasome inhibitors in cancer treatment. Citation Format: Gordon-Victor Fon, Chandler R. Keller, David H. Perlman, Aster Legesse-Miller. Investigation of possible cell state dependent differential protein homeostasis mechanism(s). [abstract]. In: Proceedings of the Seventh AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 9-12, 2014; San Antonio, TX. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2015;24(10 Suppl):Abstract nr A81.

PURPOSE OF REVIEW A recently initiated major effort to eliminate blinding trachoma as a public health problem is discussed. RECENT FINDINGS Mass (community-wide) treatment with a short course of oral azithromycin has been shown to be at least as effective as long courses (42 doses over a 6-week period) of topical tetracycline in reducing clinically active trachoma and the prevalence of chlamydial infection. The beneficial effects last for more than a year, in contrast to the short-lived results typically seen after previous control programs that used topical therapy. Azithromycin is a key element in the integrated approach towards eliminating blinding trachoma summarized as the 'SAFE' strategy (surgery for deformed eyelids; antibiotic treatment of whole communities with azithromycin, to control infection; face washing and improved hygiene of young children; and environmental improvements, particularly the provision of water and latrines). The first regional application of this strategy has shown dramatic results, producing a reduction in trachoma activity of more than 70% in Morocco. SUMMARY The goal of eliminating blinding trachoma may be reachable. Further research is needed to determine how best to use azithromycin and which environmental improvements will be most effective. The important questions are as follows: how often antibiotic treatment programs will be required in the endemic areas; how best to evaluate the effects of treatment; and when (and perhaps whom) do we retreat.

We evaluated the validity of clinically determined active trachoma as a surrogate for chlamydial eye infection in 1059 children from the Egyptian arm of the Azithromycin in the Control of Trachoma study. Participants were determined to be "clinically active" if they had >or=5 follicles or intense inflammatory infiltration on the tarsal conjunctiva. Conjunctival swabs were tested using ligase chain reaction (LCR) to detect chlamydial DNA. Of clinically active children aged 1-10 years, 31% did not have infection, as determined by LCR. Conversely, 31% of infected children were not clinically active; 78% of clinically active children aged 1-5 years were infected, versus 17% of those aged 11-15 years. The proportion of clinically active children who were infected decreased from 67% before treatment to 10% 14 months after mass azithromycin treatment. Clinically active trachoma is not always a reliable marker of infection, particularly in teenagers and after treatment.

We determined whether patients with chronic conjunctivitis in whom direct fluorescent antibody (DFA) tests revealed genus-specific chlamydial antigens (but not species-specific Chlamydia trachomatis antigens) were infected with Chlamydia psittaci or Chlamydia pneumoniae. Patients were divided into a case group of possible non-trachomatis chlamydial conjunctivitis and a control group of nonchlamydial conjunctivitis on the basis of examination and DFA testing. Species-specific primers were used to amplify C. trachomatis, C. psittaci, and C. pneumoniae DNA with polymerase chain reaction (PCR). Four (27%) of 15 samples from the case group were positive for C. psittaci or C. pneumoniae DNA, whereas none of 24 control samples were positive. Sequencing revealed a C. pneumoniae, an avian C. psittaci, and two mammalian C. psittaci strains. A short course of oral antibiotic treatment appears to be inadequate for patients with non-trachomatis chlamydial conjunctivitis. Ocular infections due to C. pneumoniae and C. psittaci may be more common than previously recognized and can be identified by DFA and PCR.

Trachoma, an infectious keratoconjunctivitis caused by Chlamydia trachomatis, is a leading cause of preventable blindness in developing countries. In this study we compared oral azithromycin with oxytetracycline/polymyxin eye ointment (once daily for 5 days every 4 weeks; total of six treatment cycles) for the treatment of active endemic trachoma in 168 rural Egyptian children. A suspension of azithromycin was administered to children as a dose of 20 mg/kg by one of three schedules: a single dose, one dose a week for 3 weeks, and one dose every 4 weeks for a total of six doses. The children's clinical status and chlamydial infection rates were evaluated for 1 year. The clinical cure rates were 35% 2 months after initial treatment, 16% at 8 months (during the annual autumn epidemic of purulent conjunctivitis), and 47% at 1 year. The pretreatment chlamydial infection rate of 33% (determined by direct immunofluorescence) decreased to 5% at 2 months and was 9% at 12 months. There were no significant clinical or laboratory differences among the four treatment groups. Thus, 1-6 doses of azithromycin were equivalent to 30 days of topical oxytetracycline/ polymyxin ointment and may offer an effective alternative means of controlling endemic trachoma.

AIMS: Possible risk factors were evaluated for herpes simplex virus (HSV) epithelial keratitis in patients with stromal keratouveitis. METHODS: The study population included 260 patients who had active stromal keratitis and/or iridocyclitis without epithelial disease and who were enrolled in one of three clinical trials of the Herpetic Eye Disease Study. Study treatment involved a 10 week course of topical placebo, topical prednisolone phosphate, or topical prednisolone phosphate with oral acyclovir. All groups received topical trifluridine four times daily for 3 weeks then twice daily for another 7 weeks. Patients were examined for HSV epithelial keratitis for 16 weeks. RESULTS: Dendritic or geographic epithelial keratitis occurred in 12 (4.6%) study patients. Adverse effects attributable to trifluridine prophylaxis were acute allergic blepharoconjunctivitis in 10 (3.8%) study patients and corneal epithelial erosions in 11 (4.2%) study patients. No significant difference in the occurrence of HSV epithelial keratitis was found among the study treatment groups: one (2.0%) of 49 topical placebo treated patients, nine (6.5%) of 138 patients treated with topical corticosteroids without acyclovir, and two (2.7%) of 73 patients treated with topical corticosteroids and oral acyclovir. Univariate exponential models suggested that patients with a history of previous HSV epithelial keratitis and non-white patients were more likely to develop HSV epithelial keratitis during treatment of stromal keratouveitis. CONCLUSION: Individuals with prior HSV epithelial keratitis and certain ethnic groups may have a higher rate of recurrent epithelial keratitis during the acute treatment of HSV stromal keratouveitis.

The TREATMENTof herpes simplex virus (HSV) infections of the eye has been controversial for many years. One unresolved issue involves the use of corticosteroids in the treatment of HSV stromal keratitis. A second issue relates to the use of the potent antiviral, acyclovir, which has been demonstrated to be effective in preventing recurrences of HSV genital infections. 1 Now the results of two placebo-controlled therapeutic trials have addressed these two issues in the management of herpes simplex eye disease. 2,3 TOPICAL CORTICOSTEROIDS FOR HSV STROMAL KERATITIS To evaluate topical corticosteroids, nine clinical centers in the United States recruited 106 patients with active HSV stromal keratitis, no epithelial defect, and no steroid treatment for at least 10 days. 2 Forty-nine patients were randomized to treatment with placebo and 57 patients to topical prednisolone phosphate drops. In a standardized regimen, the prednisolone (and placebo) drops were progressively decreased over a 10-week

Lysozyme is a bacteriolytic enzyme representing approximately 30% of the protein content of human tears.1 Human tear lysozyme production generally parallels aqueous tear secretion and is a good indicator of lacrimal gland function. However, in some instances of ocular pathology, tear lysozyme concentration (HTL) may be decreased before aqueous tear production is reduced.2 Various spectrophotometric, turbidimetric, and immunologic methods for quantitating HTL have been proposed. The most common methods for measuring HTL are based on the ability of lysozyme to cleave the cell wall of Micrococcus lysodeikticus. These techniques suffer from poor standardization, variable results, and the need for specialized personnel to maintain reagents or operate equipment. The purpose of this study was to utilize a known biochemical reaction based on the selective action of lysozyme on N-acetyl-oligosaccharides to develop a rapid, reliable, and sensitive colorimetric methods for the measurement of HTL. The chemical substrate selected for this assay was p-nirrophenyl penta-N-acetyl B-chitopentaoside (PNP).3 The reaction of lysozyme with this substrate releases p-nitrophenyl N-acetyl B-D-glucosaminide, which can be coupled to a reaction with B-N-acetylhexosaminidase (NAHase) to liberate p-nitrophenol. The free p-nitrophenol can then be accurately quantitated with a simple colorimeter.