Prevalence of High-Risk Human Papillomavirus (HR-HPV) Infection among Women with Normal and Abnormal Cervical Cytology in Myanmar

This study aimed to determine the prevalence of normal and abnormal cervical cytology in women who attended the cervical cancer screening clinic of the Department of Medical Research in Lower Myanmar, and to determine the proportion of high-risk (HR) human papillomavirus (HPV) infection and HPV genotypes in women with normal and abnormal cervical cytology. A total of 1,771 women were screened from 2010 to 2011. Among them, 762 women (43.0%) had a normal smear, and 866 (48.9%) and 87 (4.9%) were diagnosed with inflammatory smears and atypical squamous cells of undetermined significance (ASCUS), respectively. Diagnoses of low-grade squamous intraepithelial lesion (LSIL) and high-grade squamous intraepithelial lesion (HSIL) numbered 42 (2.3%) and 11 (0.6%) respectively. Three cases of squamous cell carcinoma (SCC) (0.2%) were detected. Cervical swabs were collected from 96 women with abnormal cervical cytology and 20 with normal cytology. HR-HPV DNA testing was performed by polymerase chain reaction (PCR) with pU1M/pU2R primers. HR-HPV were identified in 35.5% (22/62) of inflammatory smears, 60% (6/10) of ASCUS, 86.7% (13/15) of LSIL, 50% (3/6) of HSIL, 100% (3/3) of SCC and 5% (1/20) of normal cytology. In PCR-positive cases, HPV genotyping was analyzed by the cleaved amplification polymorphism method. The most prevalent HPV genotypes were HPV-16 (60.4%) followed by HPV-31 (14.6%), HPV-18 (12.5%) and HPV-58 (12.5%). Women with abnormal cervical cytology were 10 times more likely to be HR-HPV positive than those with normal cytology (p＝0.0001). This study suggests that the implementation of a cervical cytology screening program and routine vaccination against HPV in preadolescent and adolescent groups are needed to reduce the burden of HPV-associated cervical cancer

Hyperthyroidism, and bone mineral density : dissecting the causal association with Mendelian randomization analysis

IntroductionUntreated hyperthyroidism is associated with accelerated bone turnover, low bone mineral density (BMD) and increased susceptibility to fragility fractures. Although treatment appears to improve or even reverse some of these adverse skeletal effects, there is limited guidance on routine BMD assessment in hyperthyroid patients following treatment. By using Mendelian randomization (MR) analysis, we aimed to assess the causal association of hyperthyroid thyroid states with BMD and fractures using the UK Biobank.MethodsThis MR analysis included data from 473,818 participants (women: 54% of the total sample, the median age of 58.0 years (IQR=50‐63 years), median body mass index (BMI) of 26.70 (IQR+24.11‐29.82 kg/m2) as part of the UK biobank study. The study outcomes were heel BMD assessed by quantitative ultrasound of the heel and self‐reported fractures. Beta‐weighted genetic risk score analysis was performed using 19 Single Nucleotide Polymorphisms (SNPs) for Graves' disease, 9 SNPs for hyperthyroidism and 11 SNPs for autoimmune thyroiditis. Since the unadjusted risk score, MR is equivalent to the inverse‐variance weighted method; the genetic risk score analysis was adjusted for age, gender, and BMI. Sensitivity analyses were conducted using the Mendelian randomization‐Egger (MR‐Egger) and the inverse‐variance weighted estimate methods. Replication analysis was performed using the GEnetic Factors for Osteoporosis (GEFOS) consortium data.ResultsMR analysis using beta‐weighted genetic risk score showed no association of genetic risk for Graves’ disease (Beta = ‐0.01, P‐value=0.10), autoimmune thyroiditis (Beta = ‐0.006 P‐value=0.25) and hyperthyroidism (Beta = ‐0.009, P‐value=0.18) with heel ultrasound BMD. MR Egger and inverse‐variance MR methods in UK Biobank and GEFOS consortium confirmed these findings. The genetic risk for these hyperthyroid conditions was not associated with an increased risk of fractures.ConclusionOur study shows that excess genetic risk for Graves' autoimmune thyroiditis and hyperthyroidism does not increase the risk for low BMD and is not associated fractures in the Caucasian population. Our findings do not support routine screening for osteoporosis following definitive treatment of hyperthyroid states

Trend of Human Papillomavirus Genotypes in Cervical Neoplasia Observed in a Newly Developing Township in Yangon, Myanmar

Persistent infection with oncogenic types of human papillomavirus (HPV) is the most important risk factor associated with cervical cancer. This study detected the oncogenic HPV genotypes in cervical neoplasia in relation to clinicopathological findings using a cross-sectional descriptive method in 2011 and 2012. Cervical swabs and colposcopy-directed cervical biopsy tissues were collected from 108 women (median age 45 years;range 20-78) showing cervical cytological changes at Sanpya General Hospital, Yangon, Myanmar. HPV DNA testing and genotyping were performed by polymerase chain reaction and restriction fragment length polymorphism. HPV was identified in women with cervical intraepithelial neoplasia (CIN) 1 (44.4%), CIN2 (63.2%), CIN3 (70.6%), and squamous cell carcinoma (SCC) (74.1%). The association between cervical neoplasia and HPV positivity was highly significant (p＝0.008). Most patients infected with HPV were between 40-49 years of age, and the youngest were in the 20- to 29-year-old age group. The most common genotype was HPV 16 (65.6%) with the following distribution:70% in CIN1, 41.7% in CIN2, 91.7% in CIN3, and 60% in SCC. HPV-31 was the second-most frequent (21.9%):30% in CIN1, 33.3% in CIN2, 8.3% in CIN3, and 15% in SCC. The third-most frequent-genotype was HPV-18 (7.8%):8.3% in CIN1, and 20% in SCC. Another genotype was HPV-58 (4.7%):16.7% in CIN1 and 5% in SCC. The majority of CIN/SCC cases were associated with HPV genotypes 16, 31, 18, and 58. If oncogenic HPV genotypes are positive, the possibility of cervical neoplasia can be predicted. Knowledge of the HPV genotypes distribution can predict the effectiveness of the currently used HPV vaccine

A Study of Burkholderia pseudomallei in the Environment of Farms in Thanlyin and Hmawbi Townships, Myanmar.

Melioidosis is a tropical infection, first described in Myanmar but now rarely diagnosed there, which is widespread in Southeast Asia. The infection is predominantly acquired by people and animals through contact with soil or water. This study aimed to detect the causative organism, Burkholderia pseudomallei, in environmental samples from farms in Thanlyin and Hmawbi townships near Yangon, Myanmar. One hundred and twenty soil samples and 12 water samples were collected and processed using standard microbiological methods. Burkholderia species were isolated from 50 of the 120 (42%) soil samples but none of the water samples. Arabinose assimilation was tested to differentiate between B. pseudomallei and the nonpathogenic Burkholderia thailandensis, and seven of 50 isolates (14%) were negative. These were all confirmed as B. pseudomallei by a species-specific multiplex polymerase chain reaction (PCR). This is the first study to detect environmental B. pseudomallei in Myanmar and confirms that melioidosis is still endemic in the Yangon area

Increased development of radiographic hip osteoarthritis in individuals with high bone mass: a prospective cohort study.

BACKGROUND: Individuals with high bone mass (HBM) have a greater odds of prevalent radiographic hip osteoarthritis (OA), reflecting an association with bone-forming OA sub-phenotypes (e.g. osteophytosis, subchondral sclerosis). As the role of bone mineral density (BMD) in hip OA progression is unclear, we aimed to determine if individuals with HBM have increased incidence and/or progression of bone-forming OA sub-phenotypes. METHODS: We analysed an adult cohort with and without HBM (L1 and/or total hip BMD Z-score > + 3.2) with pelvic radiographs collected at baseline and 8-year follow-up. Sub-phenotypes were graded using the OARSI atlas. Superior/inferior acetabular/femoral osteophyte and medial/superior joint space narrowing (JSN) grades were summed and Δosteophyte and ΔJSN derived. Pain and functional limitations were quantified using the WOMAC questionnaire. Associations between HBM status and change in OA sub-phenotypes were determined using multivariable linear/logistic regression, adjusting for age, sex, height, total body fat mass, follow-up time and baseline sub-phenotype grade. Generalised estimating equations accounted for individual-level clustering. RESULTS: Of 136 individuals, 62% had HBM at baseline, 72% were female and mean (SD) age was 59 (10) years. HBM was positively associated with both Δosteophytes and ΔJSN (adjusted mean grade differences between individuals with and without HBM βosteophyte = 0.30 [0.01, 0.58], p = 0.019 and βJSN = 0.10 [0.01, 0.18], p = 0.019). Incident subchondral sclerosis was rare. HBM individuals had higher WOMAC hip functional limitation scores (β = 8.3 [0.7, 15.98], p = 0.032). CONCLUSIONS: HBM is associated with the worsening of hip osteophytes and JSN over an average of 8 years, as well as increased hip pain and functional limitation

Self-Regulated Glucose-Sensitive Neoglycoenzyme-Capped Mesoporous Silica Nanoparticles for Insulin Delivery

"This is the peer reviewed version of the following article: Oroval, Mar, Paula Díez, Elena Aznar, Carmen Coll, María Dolores Marcos, Félix Sancenón, Reynaldo Villalonga, and Ramón Martínez-Máñez. 2016. Self-Regulated Glucose-Sensitive Neoglycoenzyme-Capped Mesoporous Silica Nanoparticles for Insulin Delivery. Chemistry - A European Journal 23 (6). Wiley: 1353 60. doi:10.1002/chem.201604104, which has been published in final form at https://doi.org/10.1002/chem.201604104. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving."[EN] We describe herein the preparation of glucose-sensitive capped mesoporous silica nanoparticles for insulin delivery. The new material consists of an expanded-pore nanometric silica support grafted with 1-propyl-1-H-benzimidazole groups, loaded with fluorescein isothiocyanate-labeled insulin (FITC-Ins) and capped by the formation of inclusion complexes between cyclodextrin-modified glucose oxidase (CD-GOx) and the benzimidazole groups grafted on the mesoporous support. Insulin delivery from the gated material in simulated blood plasma was assessed upon addition of glucose. Glucose is transformed by GOx into gluconic acid, which promoted the dethreading of the benzimidazole-CD-GOx inclusion complexes, allowing cargo release. Small quantities of this support would be needed to release the amount of insulin necessary to decrease diabetic blood glucose concentrations to regular levels.The authors thank the Spanish Government (projects CTQ2011-24355, MAT2015-64139-C4-1-R, CTQ2014-58989-P, and AGL2015-70235-C2-2-R (MINECO/FEDER)) and the Generalitat Valenciana (project PROMETEOII/2014/047) for support. M.O. thanks the Universitat Politecnica de Valencia for her FPI grant. P.D. thanks the Ministerio de Economia y Competitividad for her FPI grant (BES-2012-054066). C.C. thanks the Generalitat Valenciana for her postdoctoral contract VALi+D.Oroval, M.; Díez, P.; Aznar, E.; Coll Merino, MC.; Marcos Martínez, MD.; Sancenón Galarza, F.; Villalonga, R.... (2017). Self-Regulated Glucose-Sensitive Neoglycoenzyme-Capped Mesoporous Silica Nanoparticles for Insulin Delivery. Chemistry - A European Journal. 23(6):1353-1360. https://doi.org/10.1002/chem.201604104S13531360236Nicole, L., Laberty-Robert, C., Rozes, L., & Sanchez, C. (2014). Hybrid materials science: a promised land for the integrative design of multifunctional materials. Nanoscale, 6(12), 6267-6292. doi:10.1039/c4nr01788aBeltrán-Osuna, Á. A., & Perilla, J. E. (2015). Colloidal and spherical mesoporous silica particles: synthesis and new technologies for delivery applications. 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Advanced Materials, 15(15), 1262-1266. doi:10.1002/adma.200305165Baeza, A., Guisasola, E., Ruiz-Hernández, E., & Vallet-Regí, M. (2012). Magnetically Triggered Multidrug Release by Hybrid Mesoporous Silica Nanoparticles. Chemistry of Materials, 24(3), 517-524. doi:10.1021/cm203000uHernandez, R., Tseng, H.-R., Wong, J. W., Stoddart, J. F., & Zink, J. I. (2004). An Operational Supramolecular Nanovalve. Journal of the American Chemical Society, 126(11), 3370-3371. doi:10.1021/ja039424uNiedermayer, S., Weiss, V., Herrmann, A., Schmidt, A., Datz, S., Müller, K., … Bräuchle, C. (2015). Multifunctional polymer-capped mesoporous silica nanoparticles for pH-responsive targeted drug delivery. Nanoscale, 7(17), 7953-7964. doi:10.1039/c4nr07245fZhang, X., Li, F., Guo, S., Chen, X., Wang, X., Li, J., & Gan, Y. (2014). Biofunctionalized polymer-lipid supported mesoporous silica nanoparticles for release of chemotherapeutics in multidrug resistant cancer cells. Biomaterials, 35(11), 3650-3665. doi:10.1016/j.biomaterials.2014.01.013Patel, K., Angelos, S., Dichtel, W. R., Coskun, A., Yang, Y.-W., Zink, J. I., & Stoddart, J. F. (2008). Enzyme-Responsive Snap-Top Covered Silica Nanocontainers. Journal of the American Chemical Society, 130(8), 2382-2383. doi:10.1021/ja0772086Bhat, R., Ribes, À., Mas, N., Aznar, E., Sancenón, F., Marcos, M. D., … Martínez-Máñez, R. (2016). Thrombin-Responsive Gated Silica Mesoporous Nanoparticles As Coagulation Regulators. Langmuir, 32(5), 1195-1200. doi:10.1021/acs.langmuir.5b04038Yu, C., Qian, L., Uttamchandani, M., Li, L., & Yao, S. Q. (2015). Single-Vehicular Delivery of Antagomir and Small Molecules to Inhibit miR-122 Function in Hepatocellular Carcinoma Cells by using «Smart» Mesoporous Silica Nanoparticles. Angewandte Chemie International Edition, 54(36), 10574-10578. doi:10.1002/anie.201504913Yu, C., Qian, L., Uttamchandani, M., Li, L., & Yao, S. Q. (2015). Single-Vehicular Delivery of Antagomir and Small Molecules to Inhibit miR-122 Function in Hepatocellular Carcinoma Cells by using «Smart» Mesoporous Silica Nanoparticles. Angewandte Chemie, 127(36), 10720-10724. doi:10.1002/ange.201504913Kavruk, M., Celikbicak, O., Ozalp, V. C., Borsa, B. A., Hernandez, F. J., Bayramoglu, G., … Arica, M. Y. (2015). Antibiotic loaded nanocapsules functionalized with aptamer gates for targeted destruction of pathogens. Chemical Communications, 51(40), 8492-8495. doi:10.1039/c5cc01869bChu, L.-Y. (2005). Controlled release systems for insulin delivery. Expert Opinion on Therapeutic Patents, 15(9), 1147-1155. doi:10.1517/13543776.15.9.1147Suckale, J. (2008). Pancreas islets in metabolic signaling - focus on the beta-cell. Frontiers in Bioscience, Volume(13), 7156. doi:10.2741/3218Diabetes Care 2014 37Pickup, J. C., Hussain, F., Evans, N. D., & Sachedina, N. (2005). In vivo glucose monitoring: the clinical reality and the promise. Biosensors and Bioelectronics, 20(10), 1897-1902. doi:10.1016/j.bios.2004.08.016Farmer, T. G., Edgar, T. F., & Peppas, N. A. (2008). The future of open- and closed-loop insulin delivery systems. Journal of Pharmacy and Pharmacology, 60(1), 1-13. doi:10.1211/jpp.60.1.0001Carino, G. P., & Mathiowitz, E. (1999). Oral insulin delivery1Abbreviations: GI, gastrointestinal; IDDM, insulin-dependent diabetes mellitus; IU, international units; NIDDM, non-insulin-dependent diabetes mellitus; PIN, phase inversion nanoencapsulation; ZOT, zona occludens toxin.1. Advanced Drug Delivery Reviews, 35(2-3), 249-257. doi:10.1016/s0169-409x(98)00075-1Al Rubeaan, K., Rafiullah, M., & Jayavanth, S. (2015). Oral insulin delivery systems using chitosan-based formulation: a review. Expert Opinion on Drug Delivery, 13(2), 223-237. doi:10.1517/17425247.2016.1107543Mo, R., Jiang, T., Di, J., Tai, W., & Gu, Z. (2014). Emerging micro- and nanotechnology based synthetic approaches for insulin delivery. Chemical Society Reviews, 43(10), 3595. doi:10.1039/c3cs60436eSato, K., Imoto, Y., Sugama, J., Seki, S., Inoue, H., Odagiri, T., … Anzai, J. (2005). Sugar-Induced Disintegration of Layer-by-Layer Assemblies Composed of Concanavalin A and Glycogen. Langmuir, 21(2), 797-799. doi:10.1021/la048059xTANNA, S., SAHOTA, T., SAWICKA, K., & TAYLOR, M. (2006). The effect of degree of acrylic derivatisation on dextran and concanavalin A glucose-responsive materials for closed-loop insulin delivery. Biomaterials, 27(25), 4498-4507. doi:10.1016/j.biomaterials.2006.04.007Qi, W., Yan, X., Fei, J., Wang, A., Cui, Y., & Li, J. (2009). Triggered release of insulin from glucose-sensitive enzyme multilayer shells. Biomaterials, 30(14), 2799-2806. doi:10.1016/j.biomaterials.2009.01.027Ishihara, K., Kobayashi, M., Ishimaru, N., & Shinohara, I. (1984). Glucose Induced Permeation Control of Insulin through a Complex Membrane Consisting of Immobilized Glucose Oxidase and a Poly(amine). Polymer Journal, 16(8), 625-631. doi:10.1295/polymj.16.625Wu, Z., Zhang, X., Guo, H., Li, C., & Yu, D. (2012). An injectable and glucose-sensitive nanogel for controlled insulin release. Journal of Materials Chemistry, 22(42), 22788. doi:10.1039/c2jm34082hLiu, P., Luo, Q., Guan, Y., & Zhang, Y. (2010). Drug release kinetics from monolayer films of glucose-sensitive microgel. Polymer, 51(12), 2668-2675. doi:10.1016/j.polymer.2010.04.011Zhang, X., Guan, Y., & Zhang, Y. (2012). Dynamically bonded layer-by-layer films for self-regulated insulin release. Journal of Materials Chemistry, 22(32), 16299. doi:10.1039/c2jm33413eAkhtar, N., El-Safty, S. A., Abdelsalam, M. E., & Kawarada, H. (2015). One-Pot Fabrication of Dendritic NiO@carbon-nitrogen Dot Electrodes for Screening Blood Glucose Level in Diabetes. Advanced Healthcare Materials, 4(14), 2110-2119. doi:10.1002/adhm.201500369Zhao, Y., Trewyn, B. G., Slowing, I. I., & Lin, V. S.-Y. (2009). Mesoporous Silica Nanoparticle-Based Double Drug Delivery System for Glucose-Responsive Controlled Release of Insulin and Cyclic AMP. Journal of the American Chemical Society, 131(24), 8398-8400. doi:10.1021/ja901831uZhao, W., Zhang, H., He, Q., Li, Y., Gu, J., Li, L., … Shi, J. (2011). A glucose-responsive controlled release of insulin system based on enzyme multilayers-coated mesoporous silica particles. Chemical Communications, 47(33), 9459. doi:10.1039/c1cc12740cJain, R. N., Huang, X., Das, S., Silva, R., Ivanova, V., Minko, T., & Asefa, T. (2014). Functionalized Mesoporous Silica Nanoparticles for Glucose- and pH-Stimulated Release of Insulin. Zeitschrift für anorganische und allgemeine Chemie, 640(3-4), 616-623. doi:10.1002/zaac.201300604Pérez-Esteve, É., Fuentes, A., Coll, C., Acosta, C., Bernardos, A., Amorós, P., … Barat, J. M. (2015). Modulation of folic acid bioaccessibility by encapsulation in pH-responsive gated mesoporous silica particles. Microporous and Mesoporous Materials, 202, 124-132. doi:10.1016/j.micromeso.2014.09.049Giménez, C., de la Torre, C., Gorbe, M., Aznar, E., Sancenón, F., Murguía, J. R., … Amorós, P. (2015). Gated Mesoporous Silica Nanoparticles for the Controlled Delivery of Drugs in Cancer Cells. Langmuir, 31(12), 3753-3762. doi:10.1021/acs.langmuir.5b00139De la Torre, C., Casanova, I., Acosta, G., Coll, C., Moreno, M. J., Albericio, F., … Martínez-Máñez, R. (2014). Gated Mesoporous Silica Nanoparticles Using a Double-Role Circular Peptide for the Controlled and Target-Preferential Release of Doxorubicin in CXCR4-Expresing Lymphoma Cells. Advanced Functional Materials, 25(5), 687-695. doi:10.1002/adfm.201403822Aznar, E., Villalonga, R., Giménez, C., Sancenón, F., Marcos, M. D., Martínez-Máñez, R., … Amorós, P. (2013). Glucose-triggered release using enzyme-gated mesoporous silica nanoparticles. Chemical Communications, 49(57), 6391. doi:10.1039/c3cc42210kMizutani, M., Yamada, Y., Nakamura, T., & Yano, K. (2008). Anomalous Pore Expansion of Highly Monodispersed Mesoporous Silica Spheres and Its Application to the Synthesis of Porous Ferromagnetic Composite. Chemistry of Materials, 20(14), 4777-4782. doi:10.1021/cm702792eKim, M.-H., Na, H.-K., Kim, Y.-K., Ryoo, S.-R., Cho, H. S., Lee, K. E., … Min, D.-H. (2011). Facile Synthesis of Monodispersed Mesoporous Silica Nanoparticles with Ultralarge Pores and Their Application in Gene Delivery. ACS Nano, 5(5), 3568-3576. doi:10.1021/nn103130qBarrett, E. P., Joyner, L. G., & Halenda, P. P. (1951). The Determination of Pore Volume and Area Distributions in Porous Substances. I. Computations from Nitrogen Isotherms. Journal of the American Chemical Society, 73(1), 373-380. doi:10.1021/ja01145a126Brunauer, S., Emmett, P. H., & Teller, E. (1938). Adsorption of Gases in Multimolecular Layers. 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Enhanced melioidosis surveillance in patients attending four tertiary hospitals in Yangon, Myanmar.

Abstract To investigate the current epidemiology of melioidosis in Yangon, Myanmar, between June 2017 and May 2019 we conducted enhanced surveillance for melioidosis in four tertiary hospitals in Yangon, where the disease was first discovered in 1911. Oxidase-positive Gram-negative rods were obtained from the microbiology laboratories and further analysed at the Department of Medical Research. Analysis included culture on Ashdown agar, the three disc sensitivity test (gentamicin, colistin and co-amoxiclav), latex agglutination, API 20 NE, antibiotic susceptibility testing, and a subset underwent molecular confirmation with a Burkholderia pseudomallei specific assay. Twenty one of 364 isolates (5.7%) were confirmed as B. pseudomallei and were mostly susceptible to the antibiotics used in standard therapy for melioidosis. Ten patients were from Yangon Region, nine were from Ayeyarwaddy region, and one each was from Kayin and Rakhine States. A history of soil contact was given by seven patients, five had diabetes mellitus and one had renal insufficiency. The patients presented with septicaemia (12 cases), pneumonia (three cases), urinary tract infection (two cases) and wound infection (four cases). Eighteen patients survived to hospital discharge. This study highlights the likelihood that melioidosis may be far more common, but underdiagnosed, in more rural parts of Myanmar as in other countries in SE Asia.</jats:p

The Role of Transporters in the Pharmacokinetics of Orally Administered Drugs

Drug transporters are recognized as key players in the processes of drug absorption, distribution, metabolism, and elimination. The localization of uptake and efflux transporters in organs responsible for drug biotransformation and excretion gives transporter proteins a unique gatekeeper function in controlling drug access to metabolizing enzymes and excretory pathways. This review seeks to discuss the influence intestinal and hepatic drug transporters have on pharmacokinetic parameters, including bioavailability, exposure, clearance, volume of distribution, and half-life, for orally dosed drugs. This review also describes in detail the Biopharmaceutics Drug Disposition Classification System (BDDCS) and explains how many of the effects drug transporters exert on oral drug pharmacokinetic parameters can be predicted by this classification scheme

African Linguistics in Central and Eastern Europe, and in the Nordic Countries

Non peer reviewe

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead