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This community-based study was carried out to estimate the prevalence and identify the determinants of glaucoma in the Omani population in 2005-06. Residents of 75 randomly selected houses in 25 clusters participated in the survey. We interviewed and examined 3324 individuals aged > or = 30 years in their homes and in eye clinics to note personal details, glaucoma status and presence of selected risk factors: 180 were diagnosed as having glaucoma. Projected prevalence of glaucoma among the Omani population > or = 30 years was 4.75%. Open angle and angle closure types of glaucoma contributed 40.6% and 37.8% respectively. History of hypertension was negatively, and older age and family history of glaucoma were positively, associated with glaucoma. [ABSTRACT FROM AUTHOR]

Most health care providers in developing countries know that oral rehydration salts (ORS) are a lifesaving and inexpensive treatment for child diarrhea, yet few prescribe it. This know-do gap has puzzled experts for decades. Using randomized experiments in India, we estimated the extent to which ORS underprescription is driven by perceptions that patients do not want ORS, provider's financial incentives, and ORS stock-outs (out-of-stock events). Patients expressing a preference for ORS increased ORS prescribing by 27 percentage points. Eliminating stock-outs increased ORS provision by 7 percentage points. Removing financial incentives did not affect ORS prescribing on average but did increase ORS prescribing at pharmacies. We estimate that perceptions that patients do not want ORS explain 42% of underprescribing, whereas stock-outs and financial incentives explain only 6 and 5%, respectively.

Plasmodium kinases are increasingly recognized as potential novel antiplasmodial targets for the treatment of malaria, but only a small subset of these kinases have had structure-activity relationship (SAR) campaigns reported. Herein we report the discovery of CZC-54252 ( 1 ) as an inhibitor of five P. falciparum kinases PfARK1, PfARK3, PfNEK3, PfPK9, and PfPKB. 39 analogues were evaluated against all five kinases to establish SAR at three regions of the kinase active site. Nanomolar inhibitors of each kinase were discovered. We identified common and divergent SAR trends across all five kinases, highlighting substituents in each region that improve potency and selectivity for each kinase. Potent analogues were evaluated against the P. falciparum blood stage. Eight submicromolar inhibitors were discovered, of which 37 demonstrated potent antiplasmodial activity (EC 50 = 0.16 μM). Our results provide an understanding of features needed to inhibit each individual kinase and lay groundwork for future optimization efforts toward novel antimalarials., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Malaria is a devastating disease that causes significant global morbidity and mortality. The rise of drug resistance against artemisinin-based combination therapy demonstrates the necessity to develop alternative antimalarials with novel mechanisms of action. We report the discovery of Ki8751 as an inhibitor of essential kinase PfPK6. 79 derivatives were designed, synthesized and evaluated for PfPK6 inhibition and antiplasmodial activity. Using group efficiency analyses, we established the importance of key groups on the scaffold consistent with a type II inhibitor pharmacophore. We highlight modifications on the tail group that contribute to antiplasmodial activity, cumulating in the discovery of compound 67, a PfPK6 inhibitor (IC 50  = 13 nM) active against the P. falciparum blood stage (EC 50  = 160 nM), and compound 79, a PfPK6 inhibitor (IC 50  < 5 nM) with dual-stage antiplasmodial activity against P. falciparum blood stage (EC 50  = 39 nM) and against P. berghei liver stage (EC 50  = 220 nM)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Small molecule modulators are important tools to study both basic biology and the complex signaling of protein kinases. The cdc2-like kinases (CLK) are a family of four kinases that have garnered recent interest for their involvement in a diverse set of diseases such as neurodegeneration, autoimmunity, and many cancers. Targeted medicinal chemistry around a CLK inhibitor hit identified through screening of a kinase inhibitor set against a large panel of kinases allowed us to identify a potent and selective inhibitor of CLK1, 2, and 4. Here, we present the synthesis, selectivity, and preliminary biological characterization of this compound - SGC-CLK-1 (CAF-170). We further show CLK2 has the highest binding affinity, and high CLK2 expression correlates with a lower IC 50 in a screen of multiple cancer cell lines. Finally, we show that SGC-CLK-1 not only reduces serine arginine-rich (SR) protein phosphorylation but also alters SR protein and CLK2 subcellular localization in a reversible way. Therefore, we anticipate that this compound will be a valuable tool for increasing our understanding of CLKs and their targets, SR proteins, at the level of phosphorylation and subcellular localization.

Despite a number of public health and policy-based initiatives, Ireland's national breastfeeding rates are among the lowest globally. Regionally, the Mid-West of Ireland has historically had low breastfeeding initiation rates, and parts of its major urban area such as Limerick City suffer the highest levels of economic deprivation in the country. In that context, this repeated cross-sectional study analysed breastfeeding initiation trends in the Mid-West of Ireland for two decades, from 2001 to 2020 inclusively. Statistical analysis revealed persistently low percentages of women initiating breastfeeding in the region. Time series analyses of the data demonstrated that overall breastfeeding rates are increasing, but continue to be lower than Irish national averages. From these findings and a narrative review of published research, we determined 10 plausible reasons for these consistently low breastfeeding rates. Arising from these, we propose '10 Priorities' to increase the breastfeeding initiation rates in Ireland., (© 2022 The Authors. Maternal & Child Nutrition published by John Wiley & Sons Ltd.)

Essential plasmodial kinases Pf GSK3 and Pf PK6 are considered novel drug targets to combat rising resistance to traditional antimalarial therapy. Herein, we report the discovery of IKK16 as a dual Pf GSK3/ Pf PK6 inhibitor active against blood stage Pf 3D7 parasites. To establish structure-activity relationships for Pf PK6 and Pf GSK3, 52 analogues were synthesized and assessed for the inhibition of Pf GSK3 and Pf PK6, with potent inhibitors further assessed for activity against blood and liver stage parasites. This culminated in the discovery of dual Pf GSK3/ Pf PK6 inhibitors 23d ( Pf GSK3/ Pf PK6 IC 50 = 172/11 nM) and 23e ( Pf GSK3/ Pf PK6 IC 50 = 97/8 nM) with antiplasmodial activity ( 23d Pf 3D7 EC 50 = 552 ± 37 nM and 23e Pf 3D7 EC 50 = 1400 ± 13 nM). However, both compounds exhibited significant promiscuity when tested in a panel of human kinase targets. Our results demonstrate that dual Pf PK6/ Pf GSK3 inhibitors with antiplasmodial activity can be identified and can set the stage for further optimization efforts.

Deep annotation of a library of 4-anilinoquin(az)olines led to the identification of 7-iodo-N-(3,4,5-trimethoxyphenyl)quinolin-4-amine 16 as a potent inhibitor (IC 50 =14 nM) of Protein Kinase Novel 3 (PKN3) with micromolar activity in cells. Compound 16 is a potential tool compound to study the cell biology of PKN3 and its role in pancreatic and prostate cancer and T-cell acute lymphoblastic leukemia. These 4-anilinoquin(az)olines may also be useful tools to uncover the therapeutic potential of PKN3 inhibition in a broad range of diseases., (© 2022 Wiley-VCH GmbH.)

Community health workers (CHWs) are a vital part of the health infrastructure in Uganda and in many other low- and middle-income countries. While the need for CHWs is clear, it is less clear how they should dispense health products to maximize the health benefits to their community. In this study, we assess the cost-effectiveness of several competing CHW distribution strategies in the context of treatment for child diarrhoea. We used data from a four-armed cluster-randomized controlled trial to assess the cost-effectiveness of (1) free distribution of oral rehydration salts (ORS) via home deliveries prior to diarrhoea onset (free delivery arm), (2) free distribution via vouchers where households retrieved the treatment from a central location (voucher arm), (3) a door-to-door sales model (home sales arm) and (4) a control arm where CHWs carried out their activities as normal. We assessed the cost-effectiveness from the implementor's perspective and a societal perspective in terms of cost per case treated with ORS and cost per disability-adjusted life year (DALY) averted. Free delivery was the most effective strategy and the cheapest from a societal perspective. Although implementor costs were highest in this arm, cost savings comes from households using fewer resources to seek treatment outside the home (transport, doctor fees and treatment costs). From the implementors' perspective, free delivery costs $2.19 per additional case treated and $56 per DALY averted relative to the control. Free delivery was also extremely cost-effective relative to home sales and vouchers, but there was a large degree of uncertainty around the comparison with vouchers. Free distribution of ORS by CHWs prior to diarrhoea onset is extremely cost-effective compared to other CHW distribution models. Implementers of CHW programmes should consider free home delivery of ORS., (© The Author(s) 2021. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Alcohol consumption has been associated with increased risk for sexual violence victimization and perpetration. Pregaming, a popular activity among college students that involves heavy and quick drinking prior to going out for the night and often results in high blood alcohol levels (BALs), may convey increased risk for sexual violence-potentially due to greater likelihood of contact with intoxicated perpetrators and significantly impaired victim ability to consent or resist. Yet no published work has evaluated whether there is increased risk for victimization on drinking days that involve pregaming. Using a sample of 390 college student drinkers who completed a past 30-day Timeline Followback, we examined heavy drinking behavior, estimated BALs, and experience of sexual violence victimization during 1,899 drinking days, of which 30% involved pregaming. After controlling for demographics, we found that participants drank approximately two more drinks and reached significantly higher BALs on drinking days where they pregamed as compared to drinking days where they did not pregame. Nearly 6% of drinking days that included pregaming involved sexual violence victimization, compared to about 2% of drinking days where pregaming did not occur. Participants were at 2.71 times the odds of experiencing sexual violence, primarily unwelcomed comments and nonconsensual sexual touching, during drinking days with pregaming. This study represents a first step toward greater understanding of the sexual violence and pregaming link, but future research assessing perpetrator behavior and context-specific factors (e.g., amount consumed by victims and perpetrators, location of sexual violent events and peers present) are needed.

Introduction: Cigarette smoking and associated high-risk behaviors are prevalent among youth experiencing homelessness (YEH), making appropriately tailored interventions targeting smoking behavior important for this group. We pilot tested a brief text-messaging intervention (TMI) as an adjunct to standard care for YEH who smoke and found promising preliminary effects of the intervention on smoking cessation. The purpose of the present study was to test the TMI's effect on the secondary outcomes of other substance use (including use of other tobacco/nicotine devices) and mental health symptoms., Methods: A total of 77 participants completed the pilot randomized controlled trial, with 40 receiving the TMI (174 automated text messages plus a group smoking counseling session and provision of nicotine patches). They completed an assessment at baseline and another three months later that evaluated use of other tobacco/nicotine devices, alcohol, marijuana, and anxiety and depression symptoms., Results: We found that the TMI helped to reduce secondary substance use behaviors and mental health symptoms among the participants; mainly there were medium effects of the intervention on changes in other tobacco/nicotine use, drinking, and anxiety and depression symptoms. The intervention did not have an effect on number of marijuana use days in the past month; however, past 30-day marijuana users who received the intervention benefited by reducing the number of times they used marijuana per day., Conclusions: In addition to helping reduce cigarette smoking, we found that a TMI for YEH was helpful in improving secondary outcomes, suggesting the promise of the TMI on benefiting YEH even beyond targeted smoking behavior., Implications: This pilot study demonstrates that by targeting cigarette smoking using a text message-based intervention among youth experiencing homelessness, effects may be seen in other areas of functioning such as other substance use and mental health., Trial Registration: ClinicalTrials.gov Identifier NCT03874585. Registered March 14, 2019, https://clinicaltrials.gov/ct2/show/record/NCT03874585., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: The aim of this study was to estimate long-term impacts of health education interventions on cardiometabolic health disparities., Methods: The model simulates how health education implemented in the United States throughout 2019 to 2049 would lead to changes in adult BMI and consequent hypertension and type 2 diabetes. Health outcome changes by sex, racial/ethnic (non-Hispanic White, non-Hispanic Black, and Hispanic), and weight status (normal: 18.5 ≤ BMI < 25; overweight: 25 ≤ BMI < 30; and obesity: 30 ≤ BMI) subpopulations were compared under a scenario with and one without health education., Results: By 2049, the intervention would reduce average BMI of women with obesity to 27.7 kg/m 2 (CI: 27.4-27.9), which would be 2.9 kg/m 2 lower than the expected average BMI without an intervention. Education campaigns would reduce type 2 diabetes prevalence, but it would remain highest among women with obesity at 27.7% (CI: 26.2%-29.2%). The intervention would reduce hypertension prevalence among White women by 4.7 percentage points to 38.0% (CI: 36.4%-39.7%). For Black women in the intervention, the 2049 hypertension prevalence would be 52.6% (CI: 50.7%-54.5%). Results for men and women were similar., Conclusions: Long-term health education campaigns can reduce obesity-related disease. All population groups benefit, but they would not substantially narrow cardiometabolic health disparities., (© 2021 The Obesity Society.)

Introduction: Smoking rates are alarmingly high among young people experiencing homelessness (YEH), yet there are no evidence-based cessation programs for this population. This paper presents results from a pilot evaluation of a text messaging-based smoking cessation treatment, as an adjunct to brief group cessation counseling, to improve abstinence rates among 18-25-year-old smokers experiencing homelessness. The goal of this study was to estimate effect sizes for a larger trial and it was not powered to detect group differences., Aims and Methods: YEH smokers who had a working cell phone with them at recruitment were randomized to receive a group counseling session, nicotine patches, and written material on quitting (n = 37) or a similar program that also included a 6-week automated text messaging intervention (TMI) to provide ongoing support for quitting (n = 40). Smoking outcomes were evaluated through a 90-day follow-up., Results: Seven-day point prevalence abstinence at 90-day follow-up was higher in the TMI condition than standard condition (17.50% vs. 8.11%, respectively; Cohen's h = .37); however, the 90-day continuous abstinence rate was not statistically different from zero in either condition. Reductions in the number of days smoked in the past 30 days from baseline to follow-up were greater in the TMI condition than the standard condition (-14.24 vs. -8.62, respectively; Cohen's d = .49)., Conclusions: Adding a 6-week TMI support to a brief group counseling and pharmacotherapy protocol holds promise for smoking reduction and abstinence among YEH smokers. Results indicate that further development and evaluation of the TMI in this population is warranted., Trial Registration: ClinicalTrials.gov Identifier NCT03874585. Registered March 14, 2019, https://clinicaltrials.gov/ct2/show/record/NCT03874585., Implications: This is the first study to evaluate the feasibility of using a text messaging-based intervention (TMI) for behavior change with 18-25 year olds experiencing homelessness, and more specifically, the first to test a TMI to provide ongoing support for smoking cessation. Small to medium effect sizes for the TMI are promising in terms of implementing a TMI using participants' own cell phones, as well as the efficacy of this approach as an adjunct to standard care (brief group counseling and pharmacotherapy) for smoking cessation among YEH., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Smoking rates are significantly higher among young people experiencing homelessness than in the general population. Despite a willingness to quit, homeless youth have little success in doing so on their own, and existing cessation resources tailored to this population are lacking. Homeless youth generally enjoy the camaraderie and peer support that group-based programs offer, but continuous in-person support during a quit attempt can be prohibitively expensive., Objective: This study aimed to assess the feasibility and acceptability of an automated text messaging intervention (TMI) as an adjunct to group-based cessation counseling and provision of nicotine patches to help homeless youth quit smoking. This paper outlines the lessons learned from the implementation of the TMI intervention., Methods: Homeless youth smokers aged 18 to 25 years who were interested in quitting (n=77) were recruited from drop-in centers serving homeless youth in the Los Angeles area. In this pilot randomized controlled trial, all participants received a group-based cessation counseling session and nicotine patches, with 52% (40/77) randomly assigned to receive 6 weeks of text messages to provide additional support for their quit attempt. Participants received text messages on their own phone rather than receiving a study-issued phone for the TMI. We analyzed baseline and follow-up survey data as well as back-end data from the messaging platform to gauge the acceptability and feasibility of the TMI among the 40 participants who received it., Results: Participants had widespread (smart)phone ownership-16.4% (36/219) were ineligible for study participation because they did not have a phone that could receive text messages. Participants experienced interruptions in their phone use (eg, 44% [16/36] changed phone numbers during the follow-up period) but reported being able to receive the majority of messages. These survey results were corroborated by back-end data (from the program used to administer the TMI) showing a message delivery rate of about 95%. Participant feedback points to the importance of carefully crafting text messages, which led to high (typically above 70%) approval of most text messaging components of the intervention. Qualitative feedback indicated that participants enjoyed the group counseling session that preceded the TMI and suggested including more such group elements into the intervention., Conclusions: The TMI was well accepted and feasible to support smoking cessation among homeless youth. Given high rates of smartphone ownership, the next generation of phone-based smoking cessation interventions for this population should consider using approaches beyond text messages and focus on finding ways to develop effective approaches to include group interaction using remote implementation. Given overall resource constraints and in particular the exigencies of the currently ongoing COVID-19 epidemic, phone-based interventions are a promising approach to support homeless youth, a population urgently in need of effective smoking cessation interventions., Trial Registration: ClinicalTrials.gov NCT03874585; https://clinicaltrials.gov/ct2/show/NCT03874585., International Registered Report Identifier (irrid): RR2-10.1186/s13722-020-00187-6., (©Sebastian Linnemayr, Rushil Zutshi, William Shadel, Eric Pedersen, Maria DeYoreo, Joan Tucker. Originally published in JMIR mHealth and uHealth (http://mhealth.jmir.org), 01.04.2021.)

STK17B is a member of the death-associated protein kinase family and has been genetically linked to the development of diverse diseases. However, the role of STK17B in normal and disease pathology is poorly defined. Here, we present the discovery of thieno[3,2-d] pyrimidine SGC-STK17B-1 ( 11s ), a high-quality chemical probe for this understudied "dark" kinase. 11s is an ATP-competitive inhibitor that showed remarkable selectivity over other kinases including the closely related STK17A. X-ray crystallography of 11s and related thieno[3,2-d]pyrimidines bound to STK17B revealed a unique P-loop conformation characterized by a salt bridge between R41 and the carboxylic acid of the inhibitor. Molecular dynamic simulations of STK17B revealed the flexibility of the P-loop and a wide range of R41 conformations available to the apo-protein. The isomeric thieno[2,3-d]pyrimidine SGC-STK17B-1N ( 19g ) was identified as a negative control compound. The >100-fold lower activity of 19g on STK17B was attributed to the reduced basicity of its pyrimidine N1.

Background: Cigarette smoking is much more prevalent among young people experiencing homelessness than in the general population of adolescents and young adults. Although many young homeless smokers are motivated to quit, there are no empirically-evaluated smoking cessation programs for this population. It is important that any such program address the factors known to be associated with quitting-related outcomes among homeless young people, to provide ongoing support in a way that accommodates the mobility of this population, and does not rely on scarce service provider resources for its delivery. The objective of this project is to develop and pilot test a text messaging-based intervention (TMI), as an adjunct to brief cessation counseling and provision of nicotine patches, to help homeless young people who want to quit smoking., Methods/design: This pilot study will utilize a cluster cross-over randomized controlled design with up to 80 current smokers who desire to quit and are recruited from three drop-in centers serving young people experiencing homelessness in the Los Angeles area. All participants will be provided with a minimum standard of care: a 30-min group-based smoking cessation counseling session and free nicotine replacement. Half of these smokers will then also receive the TMI, as an adjunct to this standard care, which will provide 6 weeks of ongoing support for quitting. This support includes continued and more intensive education regarding nicotine dependence, quitting smoking, and relapse; does not require additional agency resources; can be available "on demand" to users; and includes features to personalize the quitting experience. This study will investigate whether receiving the TMI adjunct to standard smoking cessation care results in greater reductions in cigarette smoking compared to standard care alone over a 3-month period., Discussion: This study has the potential to address an important gap in the clinical research literature on cigarette smoking cessation and provide empirical support for using a TMI to provide ongoing assistance and support for quitting among young smokers experiencing homelessness. Trial registration ClinicalTrials.gov Identifier NCT03874585. Registered March 14, 2019, https://clinicaltrials.gov/ct2/show/record/NCT03874585.

Objective: Ductal carcinoma in situ (DCIS) has the potential to progress to invasive carcinoma. The optimal management of DCIS and methods for individualizing treatment of DCIS are still being determined. This evidence map depicts the robustness and topical span of research on DCIS management choice on patient-centered and clinical outcomes., Methods: We searched PubMed, EMBASE, PsycINFO, PubMed Health, PROSPERO, and clinical practice guideline sites to identify systematic reviews of DCIS management options and consulted with topic experts. A bubble plot visualizes the literature volume and research content for patient-centered outcomes. An online decision tree facilitates discussions with patients and guides through the available evidence., Results: In total, 40 systematic reviews met inclusion criteria. The research syntheses addressed DCIS management options, including the role of magnetic resonance imaging, axillary surgery/sentinel lymph node biopsy, and excisional biopsy. The map shows existing evidence for mutually exclusive treatment options including active surveillance, breast-conserving surgery, nipple sparing mastectomy, and simple mastectomy. Research findings for intraoperative radiation, adjuvant radiation therapy, adjuvant hormone therapy, hypofractionation radiotherapy, accelerated partial breast irradiation, radiation therapy plus boost, and combined radiation and hormone therapy, as well as for breast reconstruction after mastectomy and surveillance mammography postsurgery are also displayed. The evidence map highlights a scarcity of robust evidence on patient-centered outcomes., Conclusions: The evidence map provides an overview of DCIS research showing the range of management options and remaining decisional dilemmas that follow a diagnosis of DCIS. It maps the evidence in accessible tools to guide practice and future research. : Video Summary:http://links.lww.com/MENO/A448.

Inhibitors based on a 3-acylaminoindazole scaffold were synthesized to yield potent dual AAK1/BMP2K inhibitors. Optimization furnished a small molecule chemical probe (SGC-AAK1-1, 25 ) that is potent and selective for AAK1/BMP2K over other NAK family members, demonstrates narrow activity in a kinome-wide screen, and is functionally active in cells. This inhibitor represents one of the best available small molecule tools to study the functions of AAK1 and BMP2K., Competing Interests: The authors declare no competing financial interest., (Copyright © 2019 American Chemical Society.)

Background: We present outcomes of Ahmed Glaucoma Valve (AGV) implantation in treating refractory glaucoma in a tertiary hospital in Oman. Refractory glaucoma was defined as previously failed conventional glaucoma surgery and an uncontrolled intraocular pressure (IOP) of more than 21 mm Hg despite treatment with three topical and/or oral therapy., Materials and Methods: This historical cohort study was conducted in 2010. Details of medical and surgical treatment were recorded. Ophthalmologists examined eyes and performed glaucoma surgeries using AGV. The best corrected distant vision, IOP, and glaucoma medications were prospectively reviewed on 1(st) day, 1(st), 6(th), 12(th) week postoperatively, and at the last follow up., Result: Glaucoma specialists examined and treated 40 eyes with refractory glaucoma of 39 patients (20 males + 19 females). Neo-vascular glaucoma was present in 23 eyes. Vision before surgery was <3/60 in 21 eyes. At 12 weeks, one eye had vision better than 6/12, seven eyes had vision 6/18 to 6/60, and eight eyes had vision 6/60 to 3/60. Mean IOP was reduced from 42.9 (SD 16) to 14.2 (SD 8) and 19.1 (SD 7.8) mmHg at one and 12 weeks after surgery, respectively. At 12 weeks, five (12.5%) eyes had IOP controlled without medication. In 33 (77.5%) eyes, pressure was controlled by using one or two eye drops. The mean number of preoperative anti-glaucoma medications (2.38; SD 1.1) was reduced compared to the mean number of postoperative medications (1.92; SD 0.9) at 12 weeks., Conclusion: We succeeded in reducing visual disabilities and the number of anti-glaucoma medications used to treat refractory glaucoma by AGV surgery.

Background: A hospital-based study was conducted in 2007 in Oman to determine the validity of frequency doubling perimetry (FDP). The authors have compared the ability of FDP to detect glaucoma among patients with and without diabetes., Methods: This was a validity study of the screening procedure. An ophthalmologist and an optometrist examined Omani persons >30 years of age with and without diabetes. They determined glaucomatous field changes by using FDP. The glaucoma specialist labeled the eye and the person as suffering from glaucoma if two criteria were present: (1) optic cup disc and other retinal changes suggestive of glaucoma and (2) field changes on automated perimeter suggestive of glaucoma. Ocular pressure was measured with a Tono-Pen (Medtronic Ophthalmics, Jacksonville, FL). We calculated the validity of glaucoma screening by FDP among persons both with diabetes and without diabetes., Results: We examined 111 eyes of 56 Omani patients (55 eyes of 28 patients with diabetes and 56 eyes of 28 persons without diabetes). Two persons had a history of glaucoma in both eyes. Glaucoma screening by FDP detected five eyes (two eyes of patients with diabetes and three eyes of persons without diabetes) with glaucoma. The specificity of glaucoma screening among those with and without diabetes was 97.4% and 97.3%, respectively. The sensitivity was 6% and 11%, respectively, in these two groups., Conclusions: Validity of glaucoma screening by FDP is not different among those with and without diabetes. In countries with high rates of diabetes, FDP could be used as a first-level screening tool for glaucoma.

Lipid-coated perfluorocarbon nanodroplets are submicrometer-diameter liquid-filled droplets with proposed applications in molecularly targeted therapeutics and ultrasound (US) imaging. Ultrasonic molecular imaging is unique in that the optimal application of these agents depends not only on the surface chemistry, but also on the applied US field, which can increase receptor-ligand binding and membrane fusion. Theory and experiments are combined to demonstrate the displacement of perfluorocarbon nanoparticles in the direction of US propagation, where a traveling US wave with a peak pressure on the order of megapascals and frequency in the megahertz range produces a particle translational velocity that is proportional to acoustic intensity and increases with increasing center frequency. Within a vessel with a diameter on the order of hundreds of micrometers or larger, particle velocity on the order of hundreds of micrometers per second is produced and the dominant mechanism for droplet displacement is shown to be bulk fluid streaming. A model for radiation force displacement of particles is developed and demonstrates that effective particle displacement should be feasible in the microvasculature. In a flowing system, acoustic manipulation of targeted droplets increases droplet retention. Additionally, we demonstrate the feasibility of US-enhanced particle internalization and therapeutic delivery.

Purpose: Glaucoma is one of the priority eye diseases in Oman in its VISION 2020 Plan. A review of available data is presented on the basis of situation analysis carried out in 2002., Methods: The General demography, morbidity and management of eye diseases reported by different eye institutions. Predefined parameters and definitions were used to calculate incidence and coverage of glaucoma., Results: The rate of glaucoma cases reported by ophthalmologists was 1.14/1000. 11.5% of estimated blindness in Oman in 1997 was due to glaucoma. Primary Open angle glaucoma constituted 63.5% of the total glaucoma cases. In spite of free and easy access to the eye treatment, coverage of glaucoma surgery was 25% of the reported cases. Evidence based information on glaucoma in the community is needed in Oman. The health facilities for eye care of glaucoma cases are available in different health regions of Oman., Conclusions: Glaucoma should be addressed through a program approach both to reduce/delay visual disabilities and improve quality of life of glaucoma patients.

This is a prospective, non-randomized study to evaluate and compare the results, morbidity and surgical time for endonasal carbon-dioxide laser assisted dacryocystorhinostomy and external dacryocystorhinostomy. 70 consecutive patients of chronic dacryocystitis with nasolacrimal duct obstruction were selected for the study. 36 patients under went endonasal CO2 laser assisted dacryocystorhinostomy and 34 had external dacryocystorhinostomy. Selection of the type of operation was left to the patient's choice. All the patients had preoperative counseling and both the procedures were explained in detail with their advantages and disadvantages. Patients not willing for the external incision were selected for endonasal laser assisted dacryocystorhinostomy and others were operated via external approach. Silicone tubes were put in all the patients for three months after surgery. The final follow up was 12 months after the removal of silicone tubes. The patency of the lacrimal passage was confirmed by irrigation, and patients were questioned about their symptoms.The success rates, 12 months after removal of silicone tubes were 100% in endonasal CO2 laser assisted dacryocystorhinostomy and 88.24% in external dacryocystorhinostomy. The surgical time of endonasal laser assisted dacryocystorhinostomy was 38 minutes as compared to 62 in external dacryocystorhinostomy. Complication rate in both groups was almost equal.Thus, we came to the conclusion that Endonasal CO2 laser assisted dacryocystorhinostomy is a better surgical option to external dacryocystorhinostomy in cases of chronic dacryocystitis with nasolacrimal duct obstruction, with shorter surgical time.

Lipid-coated microbubbles represent a new class of agents with both diagnostic and therapeutic applications. Microbubbles have low density. Stabilization of microbubbles by lipid coatings creates low-density particles with unusual properties for diagnostic imaging and drug delivery. Perfluorocarbon (PFC) gases entrapped within lipid coatings make microbubbles that are sufficiently stable for circulation in the vasculature as blood pool agents. Microbubbles can be cavitated with ultrasound energy for site-specific local delivery of bioactive materials and for treatment of vascular thrombosis. The blood-brain barrier (BBB) can be reversibly opened without damaging the neurons using ultrasound applied across the intact skull to cavitate microbubbles within the cerebral microvasculature for delivery of both low and high molecular weight therapeutic compounds to the brain. The first lipid-coated PFC microbubble product is currently marketed for diagnostic ultrasound imaging. Clinical trials are currently in process for treatment of vascular thrombosis with ultrasound and lipid-coated PFC microbubbles (SonoLysis Therapy). Targeted microbubbles and acoustically active PFC nanoemulsions with specific ligands can be developed for detecting disease at the molecular level and targeted drug and gene delivery. Bioactive compounds can be incorporated into these carriers for site-specific delivery. Our aim is to cover the therapeutic applications of lipid-coated microbubbles and PFC emulsions in this review.

The goal of targeted ultrasound contrast agents is to significantly and selectively enhance the detection of a targeted vascular site. In this manuscript, three distinct contrast agents targeted to the alphavbeta3 integrin are examined. The alphavbeta3 integrin has been shown to be highly expressed on metastatic tumors and endothelial cells during neovascularization, and its expression has been shown to correlate with tumor grade. Specific adhesion of these contrast agents to alphavbeta3-expressing cell monolayers is demonstrated in vitro, and compared with that of nontargeted agents. Acoustic studies illustrate a backscatter amplitude increase from monolayers exposed to the targeted contrast agents of up to 13-fold (22 dB) relative to enhancement due to control bubbles. A linear dependence between the echo amplitude and bubble concentration was observed for bound agents. The decorrelation of the echo from adherent targeted agents is observed over successive pulses as a function of acoustic pressure and bubble density. Frequency-domain analysis demonstrates that adherent targeted bubbles exhibit high-amplitude narrowband echo components, in contrast to the primarily wideband response from free microbubbles. Results suggest that adherent targeted contrast agents are differentiable from free-floating microbubbles, that targeted contrast agents provide higher sensitivity in the detection of angiogenesis, and that conventional ultrasound imaging techniques such as signal subtraction or decorrelation detection can be used to detect integrin-expressing vasculature with sufficient signal-to-noise.

Self-replication has been demonstrated in synthetic chemical systems based on oligonucleotides, peptides and complementary molecules without natural analogues. However, within a living cell virtually no molecule catalyses its own formation, and the search for chemical systems in which both auto- and cross-catalysis can occur has therefore attracted wide interest. One such system, consisting of two self-replicating peptides that catalyse each other's production, has been reported. Here we describe a four-component peptide system that is capable of auto- and cross-catalysis and allows for the selective amplification of one or more of the products by changing the reaction conditions. The ability of this system selectively to amplify one or more molecules in response to changes in environmental conditions such as pH or salt concentration supports the suggestions that self-replicating peptides may have played a role in the origin of life.

The chemical coupling of two peptide fragments to give the peptide K1 K2 (shown in the helical wheel diagram on the right) is autocatalytic at high NaClO 4 concentrations (1 M). Under these conditions K1 K2 assumes a coiled-coil conformation, which can function as a template for the coupling. Autocatalysis is not observed under conditions that prevent formation of the coiled-coil conformation., (© 1998 WILEY-VCH Verlag GmbH, Weinheim, Fed. Rep. of Germany.)