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In Paraguay, incomplete surveillance data resulted in the burden of congenital syphilis being underestimated, which, in turn, led to missed opportunities for infant diagnosis and treatment.The prevalence of congenital syphilis, as defined by the World Health Organization (WHO), was estimated for Paraguay using the WHO congenital syphilis estimation tool. This tool was also used to monitor progress towards the elimination of mother-to-child transmission of syphilis.The burden of syphilis in Paraguay has historically been high: its prevalence in pregnant women was estimated to be 3% in 2018.The incidence rate of congenital syphilis estimated using the WHO tool was around nine times the reported prevalence. Subsequently, Paraguay: (i) provided training to improve diagnosis and case reporting; (ii) strengthened information systems for case monitoring and reporting; and (iii) procured additional rapid dual HIV-syphilis and rapid plasma reagin tests to increase syphilis testing capacity. In addition, the Ministry of Health prepared a new national plan for eliminating mother-to-child transmission of syphilis, with clear monitoring milestones.Health-care providers' reporting and surveillance procedures for congenital syphilis may not adequately reflect national and international case definitions. Use of the WHO congenital syphilis estimation tool in Paraguay drew attention to congenital syphilis as a national public health problem and highlighted the importance of comprehensive national surveillance systems and accurate data. Ongoing use of the WHO tool can track progress towards the elimination of mother-to-child transmission of syphilis by helping improve syphilis service coverage and national surveillance.Au Paraguay, l'insuffisance de données de surveillance entraîne une sous-estimation du fardeau causé par la syphilis congénitale, ce qui aboutit à des occasions manquées de diagnostiquer et traiter les nourrissons.Le taux d'incidence de la syphilis congénitale, telle que définie par l'Organisation mondiale de la Santé (OMS), a été calculée au Paraguay à l'aide de l'outil d'évaluation de l'OMS. Cet outil a également servi à suivre les progrès dans l'élimination de la transmission de la syphilis de la mère à l'enfant.Le fardeau de la syphilis au Paraguay a toujours été lourd: la prévalence de la maladie chez les femmes enceintes était estimée à 3% en 2018.Le taux de prévalence de la syphilis congénitale calculé avec l'outil de l'OMS était environ neuf fois plus élevé que celui enregistré. Par conséquent, le Paraguay a: (i) proposé des formations afin d'améliorer le diagnostic et le signalement des cas; (ii) renforcé les systèmes d'information pour le suivi et la notification des cas; et enfin, (iii) fourni des doubles tests rapides VIH/syphilis et des tests rapides de la réagine plasmatique supplémentaires en vue d'accroître les capacités de dépistage de la syphilis. En outre, le ministère de la Santé a élaboré un nouveau plan national destiné à éliminer la transmission de la syphilis de la mère à l'enfant, comprenant une série d'étapes de suivi.Les procédures des prestataires de soins de santé en matière de notification et de surveillance de la syphilis congénitale pourraient différer de la définition des cas aux niveaux national et international. L'utilisation de l'outil d'évaluation mis au point par l'OMS pour la syphilis congénitale au Paraguay a attiré l'attention sur cette maladie qui représente un problème de santé publique nationale, et souligné l'importance des systèmes de surveillance complets et des données précises. Continuer à employer cet outil peut permettre de mesurer les progrès accomplis dans l'élimination de la transmission de la syphilis de la mère à l'enfant, en contribuant à améliorer la couverture des services et la surveillance nationale.En Paraguay, los datos de vigilancia incompletos ocasionaron que se subestimara la carga de sífilis congénita, lo que, a su vez, hizo que se perdieran las oportunidades de diagnóstico y tratamiento de los lactantes.La prevalencia de la sífilis congénita, según la definición de la Organización Mundial de la Salud (OMS), se estimó para Paraguay utilizando la herramienta de estimación de la sífilis congénita de la OMS. Esta herramienta también se utilizó para monitorear el progreso hacia la eliminación de la transmisión maternofilial de la sífilis.La carga de sífilis en Paraguay ha sido históricamente alta: su prevalencia en embarazadas se estimó en un 3 % en 2018.La tasa de incidencia de sífilis congénita estimada con la herramienta de la OMS era aproximadamente nueve veces superior a la notificada. En consecuencia, Paraguay: i) impartió formación para mejorar el diagnóstico y la notificación de los casos; ii) reforzó los sistemas de información para el monitoreo y la notificación de los casos; y iii) adquirió más pruebas rápidas duales de VIH-sífilis y de inmunoglobulina E plasmática rápida para aumentar la capacidad de realizar pruebas de sífilis. Además, el Ministerio de Salud Pública preparó un nuevo plan nacional para eliminar la transmisión maternofilial de la sífilis, con claros hitos de monitoreo.Es posible que los procedimientos de notificación y vigilancia de la sífilis congénita que aplican los profesionales sanitarios no reflejen de manera adecuada las definiciones nacionales e internacionales de los casos. El uso de la herramienta de estimación de la sífilis congénita de la OMS en Paraguay llamó la atención sobre la sífilis congénita como un problema nacional de salud pública y destacó la importancia de contar con sistemas nacionales de vigilancia integrales y datos precisos. El uso constante de la herramienta de la OMS puede hacer un seguimiento de los avances hacia la eliminación de la transmisión maternofilial de la sífilis al ayudar a mejorar la cobertura de los servicios relacionados con la sífilis y la vigilancia nacional.أدت بيانات المراقبة غير المكتملة في باراغواي إلى الحد من عبء تقييم الزهري الخلقي، مما أدى بدوره إلى ضياع فرص تشخيص الرضع وعلاجهم.تم تقييم انتشار مرض الزهري الخلقي، وفقًا لتعريف منظمة الصحة العالمية (WHO)، في باراغواي باستخدام أداة تقييم الزهري الخلقي التابعة لمنظمة الصحة العالمية. تم استخدام هذه الأداة أيضًا لرصد التقدم نحو القضاء على انتقال مرض الزهري من الأم إلى الطفل.كان عبء مرض الزهري في باراغواي مرتفعًا على مدى تاريخها، فقد تم تقدير انتشاره بين النساء الحوامل بنسبة 3% في عام 2018.在巴拉圭，不完整的监测数据导致先天性梅毒的负担被低估，由此导致错过婴儿诊断和治疗的机会。.根据世界卫生组织的 (WHO) 定义，采用世界卫生组织先天性梅毒评估工具来估算先天性梅毒的患病率。该工具还可用来监测梅毒母婴传播评估领域的进展情况。.巴拉圭的梅毒负担历来很高：2018 年的孕妇患病率估计占到 3%。.使用世界卫生组织工具评估的先天性梅毒患病率大约是所报告的患病率的九倍。随后，巴拉圭：(I) 开展了培训以提升诊断和病例报告；(ii) 加强了病例监测和报告的信息系统，并且 (iii) 采购了额外的快速双重 HIV-梅毒检测和快速血浆反应素试验以增强梅毒检测能力。除此以外，卫生部还制定了一项新的全国性计划，通过明确的监测里程碑来评估梅毒的母婴传播。.医疗护理机构的先天性梅毒报告和监测程序可能无法充分反映全国性和国际性的病例定义。在巴拉圭采用世界卫生组织先天性梅毒评估工具提高了对先天性梅毒作为全国性公共卫生问题的关注度，强调了综合的全国性监测系统和准确数据的重要性。持续使用世界卫生组织工具可以有助于提高梅毒卫生服务覆盖面和全国性监测的普及，从而追赶梅毒母婴传播评估领域的进展。.В Парагвае неполные данные наблюдений привели к недооценке бремени врожденного сифилиса, что в свою очередь привело к упущенным возможностям в диагностике и лечении младенцев.В Парагвае распространенность врожденного сифилиса, по определению Всемирной организации здравоохранения (ВОЗ), оценивалась с использованием инструмента ВОЗ для оценки врожденного сифилиса. Этот инструмент также использовали для мониторинга прогресса в борьбе с передачей сифилиса от матери к ребенку.В Парагвае бремя сифилиса достигло рекордных показателей: его распространенность среди беременных женщин в 2018 году составила 3%.Распространенность врожденного сифилиса, оцененная с помощью инструмента ВОЗ, примерно в девять раз превышала зарегистрированную распространенность. В результате Парагвай: (i) организовал обучение для улучшения диагностики и отчетности о случаях заболевания; (ii) укрепил информационные системы для мониторинга случаев заболевания и отчетности; (iii) закупил дополнительные двойные экспресс-тесты на ВИЧ/сифилис и реакцию быстрого определения реагинов плазмы, чтобы расширить возможности тестирования на сифилис. Кроме того, Министерство здравоохранения подготовило новый национальный план по борьбе с передачей сифилиса от матери к ребенку с четкими этапами мониторинга.Процедуры отчетности и наблюдения медицинских работников за врожденным сифилисом могут неадекватно отражать определения случаев заболевания на национальном и международном уровне. Использование инструмента ВОЗ для оценки врожденного сифилиса в Парагвае привлекло внимание к врожденному сифилису как национальной проблеме в сфере общественного здравоохранения и подчеркнуло важность комплексных национальных систем наблюдения и точных данных. Постоянное использование инструмента ВОЗ поможет отслеживать прогресс в борьбе с передачей сифилиса от матери к ребенку, способствуя большему охвату услугами по борьбе с сифилисом и наблюдению на национальном уровне.

In 2016, Asia and Pacific countries endorsed action plans for reaching viral hepatitis elimination targets set in the Global Health Sector Strategy (GHSS) for Viral Hepatitis 2016-2021. We examine the region's progress by modelling disease burden and constructing the cascade of care. Between 2015 and 2020, chronic HBV prevalence declined from 4.69% to 4.30%, and HCV prevalence declined from 0.64% to 0.58%. The region achieved the 2020 target of 30% incidence reduction for HBV, whereas HCV incidence declined by 6%. Hepatocellular carcinoma incidence for HBV and HCV increased by 9% and 7%, respectively. Liver-related deaths from HBV rose by 8%, and mortality attributable to HCV plateaued. Large testing and treatment gaps remained in 2019: only 13% of chronic HBV infections were diagnosed and 25% treated; 21% of chronic HCV infection were diagnosed and 11% treated. Viral hepatitis must become national priority with adequate funding to reach elimination goals by 2030.

Chronic hepatitis C (HCV) infection is a major global public health threat and in 2019 there were an estimated 58 million infected globally and 290,000 deaths. Elimination of viral hepatitis B/C as a public health threat by 2030 is defined as a 90% incidence reduction and a 65% mortality reduction. The Western Pacific region is one of the most affected regions with 10 million people living with HCV, one-fifth of the global burden. We review progress towards HCV elimination in the Western Pacific region since 2015. Key developments in the region, which comprises of 37 high-and-middle-income countries, include the following: 20 countries have national hepatitis action plans, 19 have conducted recent disease burden and investment cases, 10 have scaled-up hepatitis services at primary health care level, and in 11 countries, domestic financing including social health insurance support DAA costs. We highlight six countries' experience in navigating the path towards HCV elimination: Cambodia, China, Malaysia, Mongolia, Philippines, and Viet Nam. Future initiatives to accelerate elimination are expanding access to community-based testing using HCV point-of-care tests among at-risk and general populations; adopting decentralized and integrated HCV one-stop services at harm reduction sites, detention settings and primary care; expanding treatment to include children and adolescents; address stigma and discrimination; and ensuring sustainable financing through domestic resources to scale-up testing, treatment and prevention. The COVID-19 pandemic has a significant impact on hepatitis response across the region on community and facility-based testing, treatment initiation, monitoring and cancer screening, which is projected to delay elimination goals.

Pregnant women in Vietnam have a high prevalence of hepatitis B virus (HBV) and low prevalence of human immunodeficiency virus (HIV) and syphilis. This study aims to assess the feasibility and benefit of universal testing for HIV, HBV and syphilis in antenatal care (ANC) services. A pilot project was conducted in the Thai Nguyen province of Vietnam between 2012 and 2014. HIV, HBV and syphilis testing were offered to pregnant women. Interventions to eliminate mother-to child-transmission (MTCT) of the three pathogens were provided to infected mothers and their infants. Descriptive analysis was conducted, and the number of infections averted from integrating hepatitis B tests into ANC was estimated. Testing coverage for HIV, HBV and syphilis for the cohort of pregnant women during the pilot project was 98%. Prevalence of HIV, HBV and syphilis infections in this cohort was 0.14%, 7.8%, and 0.03%, respectively. No infant was infected with HIV or syphilis, while HBV infection was diagnosed in 27 infants (13.9%). An estimated 23 mother to child HBV infections were prevented by integrated interventions. The triple prevention of mother-to-child transmission of HIV, HBV and syphilis is feasible. Investment in the expansion of the integrated approach is required to achieve the goal of eliminating MTCT.

Ending AIDS in Asia Pacific by 2030 requires countries to give higher priority to financing community-based and key population-led service delivery. Mechanisms must be developed for civil society organisations to deliver health and HIV/AIDS services for key populations, especially men who have sex with men, and transgender people, within national health policy frameworks. Current investments in the HIV response in the Asia Pacific region reflect inadequate HIV financing for key populations, particularly for civil society and key population-led organisations that are optimally positioned to advance HIV epidemic control. These organisations are typically supported by international agencies whose investments are starting to decline. Domestic investments in key population-led organisations are often hampered by punitive laws against their communities, pervasive stigma and discrimination by policy makers, an insufficient understanding of the most effective HIV epidemic control strategies, and financing systems that limit access to funding for these organisations from the national budget. Countries in the Asia Pacific region are evolving their community-based and key population policies and programmes. We need accessible, disaggregated financial data and in-depth case studies that showcase effective key population-led programmes, to enable countries to learn from each other.

Background and AimsContrasting life-history traits can evolve through generations of dwarf plant ecotypes, yet such phenotypic changes often involve decreased plant size and reproductive allocation, which can configure seed dispersal patterns and, subsequently, population demography. Therefore, evolutionary transitions to dwarfism can represent good study systems to test the roles of life-history traits in population demography by comparing genetic structure between related but phenotypically divergent ecotypes.MethodsIn this study, we examined an ecotypic taxon pair of the world’s smallest goldenrod (stem height 2.6 cm) in alpine habitats and its closely related lowland taxon (30–40 cm) found on Yakushima Island, Japan. Genetic variation in chloroplast DNA sequences, nuclear microsatellites and genome-wide single-nucleotide polymorphisms were used to investigate 197 samples from 16 populations, to infer the population genetic demography and compare local genetic structure of the ecotypes.Key ResultsWe found a pronounced level of genetic differentiation among alpine dwarf populations, which were much less geographically isolated than their lowland counterparts. In particular, several neighbouring dwarf populations (located ~500 m apart) harboured completely different sets of chloroplast haplotypes and nuclear genetic clusters. Demographic modelling revealed that the dwarf populations have not exchanged genes at significant levels after population divergence.ConclusionsThese lines of evidence suggest that substantial effects of genetic drift have operated on these dwarf populations. The low-growing stature and reduced fecundity (only 3.1 heads per plant) of the dwarf plants may have reduced gene flow and rare long-distance seed dispersal among habitat patches, although the effects of life-history traits require further evaluation using ecological approaches.

Recent studies revealed that green spaces in urban areas are critical for conservation of native biodiversity and that assessment of the present flora of green spaces in urban areas is critical for protection of the native biodiversity. The Komaba Campus of the University of Tokyo embraces a relevant green area, located in a highly urbanised area in Tokyo Metropolis (35.66 N 139.68 E, Japan). The total area of this Campus is 25.4 ha, from which, 4.5 ha are covered by vegetation. Although intense urbanisation can be observed around the Campus, new insect species had been reported for the Campus area, suggesting that the biodiversity on the Campus still demands some attention. Differently from fauna surveys, no flora survey has been done for more than 30 years on the Campus. In this study, we have extensively surveyed the plants diversity on the Komaba Campus of the University of Tokyo, aiming for an update of the plants list on this green urban area in Tokyo. The survey covered all herbaceous and arboreous plants growing wild on the Campus. Garden plants were excluded in this survey because these plants were supposed to be cultivated. The final dataset contained, in total, 324 taxa, from which 234 were herbaceous plants and 90 were arboreous plants. The top three taxa are as follows: Poaceae (38 taxa), Asteraceae (34 taxa) and Rosaceae (14 taxa), respectively. This is the first update to the Flora of the Komaba Campus of the University of Tokyo in 30 years and represent an important contribution to conservation of native species in the Tokyo metropolis.

Background & Aims In 2016, the World Health Assembly passed a resolution to eliminate viral hepatitis as a public health threat by 2030. We aimed to examine the status of the global viral hepatitis response. Methods In 2017, the World Health Organization (WHO) asked the Ministries of Health in all 194 Member States to complete a Country Profile on Viral Hepatitis policy uptake indicators, covering national plans/funding, engagement of civil society, testing guidance, access to treatment, and strategic information. Results Of 194 Member States, 135 (70%) responded, accounting for 87% of the global population infected with hepatitis B virus (HBV) and/or C virus (HCV). Of those responding, 84 (62%) had developed a national plan, of which, 49 (58%) had dedicated funding, and 62 (46%) had engaged with civil society; those engaged with civil society were more likely to have a funded plan than others (52% vs. 23%, p = 0.001). Guidance on testing pregnant women (for HBV) and people who inject drugs (for HCV) was available in 70% and 46% of Member States, respectively; 59% and 38% of Member States reported universal access to optimal therapies for HBV and HCV, respectively. Conclusions Most people living with hepatitis B and C reside in a country with a national hepatitis strategy. Governments who engaged with civil society were more advanced in their response. Member States need to finance these national strategies and ensure that those affected have access to hepatitis services as part of efforts to achieve universal health coverage. Lay summary The World Health Organization’s goal to eliminate viral hepatitis as a public health threat by 2030 requires global action. Our results indicate that progress is being made by countries to scale-up national planning efforts; however, our results also highlight important gaps in current policies., Graphical abstract Unlabelled Image, Highlights • Countries are making progress across all WHO regions in responding to viral hepatitis • Governments engaged with Civil Society are more advanced in their national planning efforts • Financing remains an issue with a minority of countries with a national plan having some dedicated funding • Stronger surveillance and monitoring systems are needed to direct hepatitis elimination plans

Hepatitis B vaccine (HepB), which has been available since 1982, provides lifelong protection against hepatitis B virus (HBV) infection and the associated 20%-30% increased lifetime risk for developing cirrhosis or hepatocellular carcinoma among >95% of vaccine recipients (1). Before HepB introduction into national childhood immunization schedules, the estimated hepatitis B surface antigen (HBsAg) prevalence in the World Health Organization (WHO) Western Pacific Region (WPR)* was >8% in 1990 (2). In 2005, the WPR was the first WHO region to establish a hepatitis B control goal, with an initial target of reducing HBsAg prevalence to

Summary Background In 2016, the UN General Assembly set a global target of 3 million oral pre-exposure prophylaxis (PrEP) users by 2020. With this target at an end, we aimed to assess global trends in the adoption of WHO PrEP recommendations into national guidelines and numbers of PrEP users, defined as people who received oral PrEP at least once in a given year, and to estimate future trajectories of PrEP use. Methods In this global summary and forecasting study, data on adoption of WHO PrEP recommendations and numbers of PrEP users were obtained through the Global AIDS Monitoring system and WHO regional offices. Trends in these indicators for 2016–19 by region and for 2019 by country were described, including by gender and priority populations where data were available. PrEP user numbers were forecasted until 2023 by selecting countries with at least 3 years of PrEP user data as example countries in each region to represent possible future PrEP user trajectories. PrEP user growth rates observed in example countries were applied to countries in corresponding regions under different scenarios, including a COVID-19 disruption scenario with static global PrEP use in 2020. Findings By the end of 2019, 120 (67%) of 180 countries with data had adopted the WHO PrEP recommendations into national guidelines (23 in 2019 and 30 in 2018). In 2019, there were about 626 000 PrEP users across 77 countries, including 260 000 (41·6%) in the region of the Americas and 213 000 (34·0%) in the African region; this is a 69% increase from about 370 000 PrEP users across 66 countries in 2018. Without COVID-19 disruptions, 0·9–1·1 million global PrEP users were projected by the end of 2020 and 2·4–5·3 million are projected by the end of 2023. If COVID-19 disruptions resulted in no PrEP user growth in 2020, the projected number of PrEP users in 2023 is 2·1–3·0 million. Interpretation Widespread adoption of WHO PrEP recommendations coincided with a global increase in PrEP use. Although the 2020 global PrEP target will be missed, strong future growth in PrEP use is possible. New PrEP products could expand the PrEP user base, and, with greater expansion of oral PrEP, further adoption of WHO PrEP recommendations, and simplified delivery, PrEP could contribute to ending AIDS by 2030. Funding Unitaid, Bill & Melinda Gates Foundation, and WHO.

Background: With the 2020 global target of three million oral pre-exposure prophylaxis (PrEP) users set during the UN General Assembly in 2016 at an end, we assessed global trends in the adoption of World Health Organization (WHO) PrEP recommendations into national guidelines and numbers of PrEP users, and estimated future trajectories of PrEP users. Methods: Data obtained through the Global AIDS Monitoring (GAM) and WHO regional offices was collated to report numbers of PrEP users and WHO PrEP recommendations adoption by country for 2016-2019. To forecast PrEP user numbers until 2023, model countries were selected in each region. PrEP use growth rates observed in these model countries were applied to countries in corresponding regions under different scenarios, including a COVID-19 disruption scenario with static global PrEP use in 2020. Findings: In 2019, there were 630,000 PrEP users across 76 countries (41% in Americas and 36% in African region), a 70% increase from 2018. 121 countries had adopted the WHO PrEP recommendations in national guidelines: 33 countries in 2018 and 23 in 2019. Without COVID-19 disruptions, 1·0-1·1 million global PrEP users by the end of 2020 and 2·4-5·2 million by 2023 were projected. If COVID-19 disruptions result in no PrEP user growth in 2020, there would be 0·7-1·6 million fewer PrEP users in 2023 (vs. no disruptions). Interpretation: Widespread adoption of WHO PrEP recommendations coincided with a global increase in PrEP use. While the 2020 global PrEP target will be missed, we estimated future growth in PrEP use. In many countries, PrEP user numbers are small relative to new HIV infections and PrEP recommendations are not implemented at scale. New PrEP products could expand the PrEP user base and, with greater oral PrEP use through simplified delivery, PrEP could significantly contribute to ending AIDS by 2030. Funding Statement: We thank Unitaid for providing the funding necessary to this work. Declaration of Interests: The authors declare no conflict of interests.

Objectives: To estimate prevalence levels of and time trends for active syphilis, gonorrhoea and chlamydia in women aged 15–49 years in four countries in the Pacific (Fiji, the Federated States of Micronesia [FSM], Papua New Guinea [PNG] and Samoa) to inform surveillance and control strategies for sexually transmitted infections (STIs). Methods: The Spectrum-STI model was fitted to data from prevalence surveys and screenings of adult female populations collected during 1995−2017 and adjusted for diagnostic test performance and to account for undersampled high-risk populations. For chlamydia and gonorrhoea, data were further adjusted for age and differences between urban and rural areas. Results: Prevalence levels were estimated as a percentage (95% confidence interval). In 2017, active syphilis prevalence was estimated in Fiji at 3.89% (2.82 to 5.06), in FSM at 1.48% (0.93 to 2.16), in PNG at 3.91% (1.67 to 7.24) and in Samoa at 0.16% (0.07 to 0.37). For gonorrhoea, the prevalence in Fiji was 1.63% (0.50 to 3.87); in FSM it was 1.59% (0.49 to 3.58); in PNG it was 11.0% (7.25 to 16.1); and in Samoa it was 1.61% (1.17 to 2.19). The prevalence of chlamydia in Fiji was 24.1% (16.5 to 32.7); in FSM it was 23.9% (18.5 to 30.6); in PNG it was 14.8% (7.39 to 24.7); and in Samoa it was 30.6% (26.8 to 35.0). For each specific disease within each country, the 95% confidence intervals overlapped for 2000 and 2017, although in PNG the 2017 estimates for all three STIs were below the 2000 estimates. These patterns were robust in the sen sitivity analyses. Discussion: This study demonstrated a persistently high prevalence of three major bacterial STIs across four countries in WHO’s Western Pacific Region during nearly two decades. Further strengthening of strategies to control and prevent STIs is warranted.

We conducted a nationwide retrospective study in Japan to evaluate the effectiveness of oral amoxicillin or ampicillin as alternatives to injectable benzathine penicillin G for treating pregnant women with syphilis and preventing congenital syphilis (CS). We investigated 80 pregnant women with active syphilis treated with amoxicillin or ampicillin during 2010–2018. Overall, 21% (15/71) had pregnancies resulting in CS cases, and 3.8% (3/80) changed therapies because of side effects. Among 26 patients with early syphilis, no CS cases occurred, but among 45 with late syphilis, 15 (33%) CS cases occurred. Among 57 patients who started treatment >60 days before delivery, 8 (14%) had CS pregnancy outcomes. We found oral amoxicillin potentially ineffective for preventing CS cases among pregnant women with late syphilis but potentially effective in those with early syphilis. Prospective studies are needed to definitively evaluate the efficacy of amoxicillin for the treatment of pregnant women with syphilis to prevent CS.

Selenium, one of the essential trace minerals, is present in vivo in form of selenoproteins. Iodothyronine deiodinase, a selenoprotein, is involved in the activation and inactivation of thyroid hormone. Therefore, patients with selenium deficiency may present changes in thyroid hormone levels due to inhibition of T4 to T3 conversion; however, this assumption is still under debate. In the present study, we retrospectively investigated the thyroid function in 22 patients with selenium deficiency. Thyroid stimulating hormone (TSH) and free T4 (FT4) levels were increased in 3 (14%) and 5 (23%) patients, respectively, and free T3 (FT3) levels were decreased in 6 (27%) patients. The FT4/FT3 ratio was significantly higher in patients with selenium deficiency than that in the control group. There appeared to be a positive correlation between the decreased rate of selenium levels and FT4/FT3 ratio, thereby indicating that patients with severe selenium deficiency also exhibited abnormal thyroid hormone levels. Furthermore, when selenium was supplemented in seven patients with abnormal thyroid hormone levels, the TSH, FT4, and FT4/FT3 ratio were significantly decreased and FT3 levels were increased. Collectively, patients with selenium deficiency could present the characteristics of not only low FT3 but also high FT4 and FT4/FT3 ratio.

We developed 10 novel simple sequence repeat markers from expressed sequence tags for the honey locust seed beetle, Megabruchidius dorsalis Fahraeus 1839 (Coleoptera: Bruchidae, using de novo transcriptome analysis based on next-generation sequencing. In a M. dorsalis Harataima (Kanagawa-pref.) population, the number of alleles per locus ranged from 2 to 6, with an average of 4.0. Observed and expected heterozygosities ranged from 0.13 to 0.72 and 0.17 to 0.72, respectively. We initially developed 11 novel markers, but one was eliminated because it showed significant linkage disequilibrium with another locus after Bonferroni correction. To check the applicability of the remaining 10 markers, we used them to analyze two additional geographic populations (Yashima, Akita-pref., and Kameoka, Kyoto-pref.). Mean numbers of alleles per locus in the Yashima and Kameoka populations were 2.6 and 2.9, respectively, with corresponding mean observed heterozygosities of 0.36 and 0.52. These results based on the two additional populations confirm that our developed markers worked efficiently. The simple sequence repeat markers developed from expressed sequence tags in the present study should, therefore, be useful for explicating the population genetic structure of M. dorsalis and for future paternal analyses.

The often patchy distribution of serpentine geology can lead to abrupt changes in soil and microclimates. Thus, serpentine areas provide an ideal natural setting to understand how divergent selection drives the process of local adaptation in edaphically specialized plants. When the serpentine ecotype is surrounded by a related nonserpentine ecotype, a balance of natural selection and potential gene flow should maintain the different ecotypes over very short distances. We aimed to reveal the mechanisms allowing soil ecotypes of a goldenrod species to co‐occur sympatrically in Japan. We performed field surveys to characterize microenvironments and flowering phenology of each ecotype, common garden and reciprocal transplant experiments and artificial crossing, and population genetic analysis to investigate the levels of genetic differentiation between ecotypes. Growth chamber experiments show that serpentine plants showed lower specific leaf area (SLA) and greater resource allocation to their root systems than did their nonserpentine counterparts, a potential adaptation to drier and less fertile soil condition in serpentine habitats. Reciprocal transplant studies demonstrated a clear pattern of local adaptation in the plant growth rate. Importantly, serpentine populations completed flowering by midsummer versus late summer in nonserpentine plants. This pattern is consistent with the hypothesis that early flowering ensures reproductive success, before the microclimatic conditions becomes severe in open habitats. Although prezygotic isolation was a strong barrier to gene flow, genetic differentiation was very low, indicating a recent origin for the serpentine ecotypes and/or gene flow at low frequencies. Synthesis. The findings indicate that the early flowering times of serpentine ecotypes, which would have been selected for by microclimates in serpentine areas, can play roles in local adaptation, but also population isolation via a by‐product of diverged reproductive timings. This study contributes to general understanding of the initial stages of plant ecological speciation under potential gene flow in very small geographic scales.

Physical and psychosocial changes during adolescence could influence the psychological well-being and adherence to antiretroviral therapy (ART) of adolescents living with HIV. However, few studies have assessed these two important issues in Zambia. This study aimed at addressing this gap by examining adolescents' depressive symptoms and ART adherence. This was a mixed-methods study conducted from April to July 2014. We recruited 200 adolescents, ages 15 to 19, who were already aware of their HIV status. We measured depressive symptoms using the short form of the Center for Epidemiologic Studies Depression Scale, and self-reported three-day adherence to ART. We performed logistic regression analysis to identify factors associated with depressive symptoms and non-adherence to ART. For qualitative data, we examined challenges over ART adherence using thematic analysis. Out of 190 adolescents, 25.3% showed high scores of depressive symptoms. Factors associated with depressive symptoms were unsatisfactory relationships with family (Adjusted Odds Ratio [AOR] 3.01; 95% Confidence Interval [CI] 1.20-7.56); unsatisfactory relationships with health workers (AOR 2.68; 95% CI 1.04-6.93); and experience of stigma (AOR 2.99; 95% CI 1.07-8.41). Of all participants, 94.2% were taking ART, but 28.3% were non-adherent. Factors associated with non-adherence to ART were loss of a mother (AOR 3.00; 95% CI 1.05-8.58) and lack of basic knowledge about HIV (AOR 3.25; 95% CI 1.43-7.40). Qualitative data identified the following challenges to ART adherence: management of medication, physical reactions to medicine, and psychosocial distress. The evidence suggests that depressive symptoms and non-adherence to ART were priority issues in late adolescence in Zambia. Health workers should be aware of these issues, and the care and treatment services should be tailored to respond to age-specific needs.

Introduction: Mongolia's health ministry prioritizes control of Sexually Transmitted Infections, including syphilis screening and treatment in antenatal care (ANC). Methods: Adult syphilis prevalence trends were fitted using the Spectrum-STI estimation tool, using data from ANC surveys and routine screening over 1997–2016. Estimates were combined with programmatic data to estimate numbers of treated and untreated pregnant women with syphilis and associated incidence congenital syphilis (CS) and CS-attributable adverse birth outcomes (ABO), which we compared with CS case reports. Results: Syphilis prevalence in pregnant women was estimated at 1.7% in 2000 and 3.0% in 2016. We estimated 652 CS cases, of which 410 ABO, in 2016. Far larger, annually increasing numbers of CS cases and ABO were estimated to have been prevented: 1654 cases, of which 789 ABO in 2016 − thanks to increasing coverages of ANC (99% in 2016), ANC-based screening (97% in 2016) and treatment of women diagnosed (81% in 2016). The 42 CS cases reported nationally over 2016 (liveborn infants only) represented 27% of liveborn infants with clinical CS, but only 7% of estimated CS cases among women found syphilis-infected in ANC, and 6% of all estimated CS cases including those born to women with undiagnosed syphilis. Discussion/Conclusion: Mongolia's ANC-based syphilis screening program is reducing CS, but maternal prevalence remains high. To eliminate CS (target

BACKGROUND AND AIMS: The processes and mechanisms underlying lineage diversification are major topics in evolutionary biology. Eurasian goldenrod species of the Solidago virgaurea complex show remarkable morphological and ecological diversity in the Japanese Archipelago, with ecotypic taxa well adapted to specific environments (climate, edaphic conditions and disturbance regimes). The species complex is a suitable model to investigate the evolutionary processes of actively speciating plant groups, due to its ability to evolve in relation to environmental adaptation and its historical population dynamics. METHODS: Two chloroplast markers, 18 nuclear microsatellite markers and ddRAD-sequencing were used to infer population genetic demography of S. virgaurea complex with its related species/genera. KEY RESULTS: Our analysis showed that populations in Japan form an evolutionary unit, which was genetically diverged from adjacent continental populations. The phylogenetic structure within the archipelago strongly corresponds to the geography, but interestingly there is no concordance between genetic structure and ecotypic boundaries; neighbouring populations of distinct ecotypes share a genetic background. CONCLUSIONS: We propose that the traits specific to the ecotypic entities are maintained by natural selection or are very recently generated and have little effect on the genomes, making genome-wide genetic markers unsuitable for detecting ecotypic differentiation. Furthermore, some sporadically distributed taxa (found as rheophytes and alpine plants) were repeatedly generated from a more widespread taxon in geographically distant areas by means of selection. Overall, this study showed that the goldenrod complex has a high ability to evolve, enabling rapid ecological diversification over a recent timeframe.

Every year, an estimated 180 000 babies in the Western Pacific Region are infected by hepatitis B, 13 000 by syphilis and 1400 by HIV through mother-to-child transmission. (1) These infections can be largely prevented by antenatal screening, treatment and timely vaccination for newborns. Despite challenges in controlling each disease, major achievements have been made. National immunization programmes have reduced the regional hepatitis B prevalence from over 8% in 1990 to 0.93% among children born in 2012. In addition, HIV testing and treatment have helped keep the regional prevalence of HIV infections at 0.1%. In contrast, the number of maternal syphilis cases is still high in the Western Pacific Region, with an estimated 45 million cases in 2012. Elimination of mother-to-child transmission of these infections cannot be achieved through vertically applied programming and require using and augmenting to the shared Maternal, Newborn and Child Health platform to coordinate, integrate and enable cost efficiencies for these elimination efforts. The Regional Framework for Triple Elimination of Mother-to-Child Transmission of HIV, Hepatitis B and Syphilis in Asia and the Pacific 2018-2030 offers such a coordinated approach towards achieving the triple elimination of mother-to-child transmission of HIV, hepatitis B and syphilis and provides guidance for decision-makers, managers and health professionals working in programmes addressing maternal, newborn and child health, HIV, hepatitis, sexually transmitted infections and immunization.

Premise of the study The aboveground part of one-leaf plants (Gesneriaceae) consists of a unique shoot-like unit called a phyllomorph, which is composed of a growing lamina and one petiolode (a stem- and petiole-like organ). The phyllomorph has three meristems: a basal meristem (BM; involved in lamina growth), a petiolode meristem (PM; required for midrib and petiolode growth), and a groove meristem (GM; contributes to inflorescence and new phyllomorph development). Although the GM has a tunica-corpus structure like a conventional shoot apical meristem (SAM), the vegetative GM of a one-leaf plant does not form any organ primordia and has been considered a defective or suppressed SAM. In this study, we evaluated the nature of the three meristems to reconsider their roles in phyllomorph development in the one-leaf species Monophyllaea glabra. Methods Mitotic activities of meristem cells were monitored by incorporation of a thymidine analog (EdU) into DNA. Orthologs of SHOOTMERISTEMLESS (STM) and PHANTASTICA, ROUGH SHEATH2, ASYMMETRIC LEAVES1 (PHAN/RS2/AS1) were isolated from M. glabra, and their expression patterns were investigated by quantitative reverse transcription polymerase chain reaction in combination with a laser microdissection technique. Key results Mitotic activities were detected in all three phyllomorph meristems. Strong expression of the STM and PHAN/RS2/AS1 orthologs was detected in the vegetative GM and BM, respectively. Conclusions The vegetative GM is an active meristem that expresses the STM ortholog. We postulate that the GM is required for growth of a phyllomorph by providing undifferentiated cells and/or growth regulators to the BM and/or PM.

Background The Regional Framework for Triple Elimination of Mother-to-Child Transmission (EMTCT) of HIV, Hepatitis B (HBV) and Syphilis in Asia and the Pacific 2018-30 was endorsed by the Regional Committee of WHO Western Pacific in October 2017, proposing an integrated and coordinated approach to achieve elimination in an efficient, coordinated and sustainable manner. This study aims to assess the population impacts and cost-effectiveness of this integrated approach in the Cambodian context. Methods Based on existing frameworks for the EMTCT for each individual infection, an integrated framework that combines infection prevention procedures with routine antenatal care was constructed. Using decision tree analyses, population impacts, cost-effectiveness and the potential reduction in required resources of the integrated approach as a result of resource pooling and improvements in service coverage and coordination, were evaluated. The tool was assessed using simulated epidemiological data from Cambodia. Results The current prevention programme for 370,000 Cambodian pregnant women was estimated at USD$2.3 ($2.0–$2.5) million per year, including the duration of pregnancy and up to 18 months after delivery. A model estimate of current MTCT rates in Cambodia was 6.6% (6.2–7.1%) for HIV, 14.1% (13.1–15.2%) for HBV and 9.4% (9.0–9.8%) for syphilis. Integrating HIV and syphilis prevention into the existing antenatal care framework will reduce the total time required to provide this integrated care by 19% for health care workers and by 32% for pregnant women, resulting in a net saving of $380,000 per year for the EMTCT programme. This integrated approach reduces HIV and HBV MTCT to 6.1% (5.7–6.5%) and 13.0% (12.1–14.0%), respectively, and substantially reduces syphilis MCTC to 4.6% (4.3–5.0%). Further introduction of either antiviral treatment for pregnant women with high viral load of HBV, or hepatitis B immunoglobulin (HBIG) to exposed newborns, will increase the total cost of EMTCT to $4.4 ($3.6–$5.2) million and $3.3 ($2.7–$4.0) million per year, respectively, but substantially reduce HBV MTCT to 3.5% (3.2–3.8%) and 5.0% (4.6–5.5%), respectively. Combining both antiviral and HBIG treatments will further reduce HBV MTCT to 3.4% (3.1–3.7%) at an increased total cost of EMTCT of $4.5 ($3.7–$5.4) million per year. All these HBV intervention scenarios are highly cost–effective ($64–$114 per disability-adjusted life years averted) when the life benefits of these prevention measures are considered. Conclusions The integrated approach, using antenatal, perinatal and postnatal care as a platform in Cambodia for triple EMTCT of HIV, HBV and syphilis, is highly cost-effective and efficient.

The dinuclear palladium(I) complexes [L(Ar2 HGe)Pd(μ-GeAr2 )2 Pd(GeHAr2 )L] (Ar=Ph, p-Tol; L=PMe3 , tBuNC) contain terminal germyl and bridging germylene ligands with the experimentally observed Ge⋅⋅⋅Ge bond lengths of 2.8263(4) Å (L=PMe3 ) and 2.928(1) Å (L=tBuNC), which are close to the longest Ge-Ge bond reported to date [2.714(1) Å]. Significant Ge⋅⋅⋅Ge interactions between the germylene and germyl ligands (PMe3 complexestBuNC complexes) are supported by DFT calculations, Wiberg bond indices (WBI), and natural bond orbital (NBO) analyses. Exchanging tBuNC for PMe3 ligands increases the Ge⋅⋅⋅Ge interaction, and simultaneously activates two Pd-Ge bonds. Adding the chelating diphosphine 1,2-bis(diethylphosphino)ethane (depe) to the PMe3 complexes results in the intramolecular coupling of germyl and germylene ligands followed by extrusion of a digermane.

Melanie Taylor and colleagues discuss progress towards eliminating vertical transmission of HIV and syphilis.

Summary Early stages of ecological speciation can create populations with an ecology and reproduction timing distinct from those of related populations. Landscape genetic models incorporating environmental heterogeneity and population-specific reproductive traits enable the processes of population genetic differentiation to be inferred. We investigated genome-wide genetic variation in ecotypic populations of Solidago virgaurea sensu lato, a herbaceous plant inhabiting a wide range of habitats (woodlands, serpentine barrens and alpine grasslands) and displaying remarkable variation in flowering time. Simultaneous evaluation of environmental factors revealed an overwhelming effect of soil type differences on neutral genetic differentiation, compared with elevational differences. This result probably reflects the abrupt environmental changes generated by geological boundaries, whereas mountain slopes exhibit clinal changes, facilitating gene exchange between neighbouring populations. Temporal isolation was positively associated with genetic differentiation, with some early-flowering serpentine populations having allele frequencies distinct from adjacent nonserpentine populations. Overall, this study highlights the importance of ecological processes and of evolution of flowering time to promote genetic differentiation of S. virgaurea populations in a complex landscape.

Aim Postnatal depression has demonstrated long-term consequences on child cognitive and emotional development; however, the link between maternal and child pathology has not been clearly identified. We conducted a prospective study using self-rating questionnaires to clarify the association between bonding disorder and maternal mood during pregnancy and after childbirth. Methods A total of 389 women participated in this study and completed questionnaires. Participants were asked to complete the Edinburgh Postnatal Depression Scale (EPDS) and the Mother-to-Infant Bonding Scale four times during pregnancy and the postpartum period. Results We found statistically significant weak to moderate correlations (r = 0.14–0.39) between the EPDS and Mother-to-Infant Bonding Scale scores at each testing period. Women who experienced low mood tended to have stronger bonding disorder. Furthermore, the effectiveness of attachment between the mother and child was closely related to the mood of the mother as measured by the EPDS. Conclusion We observed different patterns of bonding and maternal mood. Distinct subtypes regarding maternal mood and formation of mother-to-infant attachment suggests that analysis of bonding disorder should be performed considering the course of maternal depressive symptoms.

(R,R)-Ac6c4BD homopeptides form helical structures with slight control of the helical screw sense to the right-handed form. The chiral acetal moieties in (R,R)-Ac6c4BD are changeable in the peptide state.

During leaf development, a decrease in cell number often triggers an increase in cell size. This phenomenon, called compensation, suggests that some system coordinates cell proliferation and cell expansion, but how this is mediated at the molecular level is still unclear. The fugu2 mutants in Arabidopsis (Arabidopsis thaliana) exhibit typical compensation phenotypes. Here, we report that the FUGU2 gene encodes FASCIATA1 (FAS1), the p150 subunit of Chromatin Assembly Factor1. To uncover how the fas1 mutation induces compensation, we performed microarray analyses and found that many genes involved in the DNA damage response are up-regulated in fas1. Our genetic analysis further showed that activation of the DNA damage response and the accompanying decrease of cell number in fas1 depend on ATAXIA TELANGIECTASIA MUTATED (ATM) but not on ATM AND RAD3 RELATED. Kinematic analysis suggested that the delay in the cell cycle leads to a decrease in cell number in fas1 and that loss of ATM partially restores this phenotype. Consistently, both cell size phenotypes and high ploidy phenotypes of fas1 are also suppressed by atm, supporting that the ATM-dependent DNA damage response leads to these phenotypes. Altogether, these data suggest that the ATM-dependent DNA damage response acts as an upstream trigger in fas1 to delay the cell cycle and promote entry into the endocycle, resulting in compensated cell expansion.