Impact of mHealth interventions on maternal, newborn, and child health from conception to 24 months postpartum in low- and middle-income countries: a systematic review.

BACKGROUND: Mobile health (mHealth) technologies have been harnessed in low- and middle-income countries (LMICs) to address the intricate challenges confronting maternal, newborn, and child health (MNCH). This review aspires to scrutinize the effectiveness of mHealth interventions on MNCH outcomes during the pivotal first 1000 days of life, encompassing the period from conception through pregnancy, childbirth, and post-delivery, up to the age of 2 years. METHODS: A comprehensive search was systematically conducted in May 2022 across databases, including PubMed, Cochrane Library, Embase, Cumulative Index to Nursing & Allied Health (CINAHL), Web of Science, Scopus, PsycINFO, and Trip Pro, to unearth peer-reviewed articles published between 2000 and 2022. The inclusion criteria consisted of (i) mHealth interventions directed at MNCH; (ii) study designs, including randomized controlled trials (RCTs), RCT variations, quasi-experimental designs, controlled before-and-after studies, or interrupted time series studies); (iii) reports of outcomes pertinent to the first 1000 days concept; and (iv) inclusion of participants from LMICs. Each study was screened for quality in alignment with the Cochrane Handbook for Systematic Reviews of Interventions and the Joanne Briggs Institute Critical Appraisal tools. The included articles were then analyzed and categorized into 12 mHealth functions and outcome domain categories (antenatal, delivery, and postnatal care), followed by forest plot comparisons of effect measures. RESULTS: From the initial pool of 7119 articles, we included 131 in this review, comprising 56 RCTs, 38 cluster-RCTs, and 37 quasi-experimental studies. Notably, 62% of these articles exhibited a moderate or high risk of bias. Promisingly, mHealth strategies, such as dispatching text message reminders to women and equipping healthcare providers with digital planning and scheduling tools, exhibited the capacity to augment antenatal clinic attendance and enhance the punctuality of child immunization. However, findings regarding facility-based delivery, child immunization attendance, and infant feeding practices were inconclusive. CONCLUSIONS: This review suggests that mHealth interventions can improve antenatal care attendance and child immunization timeliness in LMICs. However, their impact on facility-based delivery and infant feeding practices varies. Nevertheless, the potential of mHealth to enhance MNCH services in resource-limited settings is promising. More context-specific implementation studies with rigorous evaluations are essential.

Heart failure promotes multimorbidity through innate immune memory.

Patients with heart failure (HF) often experience repeated acute decompensation and develop comorbidities such as chronic kidney disease and frailty syndrome. Although this suggests pathological interaction among comorbidities, the mechanisms linking them are poorly understood. Here, we identified alterations in hematopoietic stem cells (HSCs) as a critical driver of recurrent HF and associated comorbidities. Bone marrow transplantation from HF-experienced mice resulted in spontaneous cardiac dysfunction and fibrosis in recipient mice, as well as increased vulnerability to kidney and skeletal muscle insults. HF enhanced the capacity of HSCs to generate proinflammatory macrophages. In HF mice, global chromatin accessibility analysis and single-cell RNA-seq showed that transforming growth factor-ß (TGF-ß) signaling was suppressed in HSCs, which corresponded with repressed sympathetic nervous activity in bone marrow. Transplantation of bone marrow from mice in which TGF-ß signaling was inhibited similarly exacerbated cardiac dysfunction. Collectively, these results suggest that cardiac stress modulates the epigenome of HSCs, which in turn alters their capacity to generate cardiac macrophage subpopulations. This change in HSCs may be a common driver of repeated HF events and comorbidity by serving as a key carrier of "stress memory."

i-MoMCARE: Innovative Mobile Technology for Maternal and Child Health Care in Cambodia-study protocol of a cluster randomized controlled trial.

BACKGROUND: The Government of Cambodia established the village health support groups (VHSGs) in 2003 to facilitate primary healthcare activities, including maternal and child health (MCH) services. However, VHSGs face several challenges that hinder them from performing optimally, including a lack of regular structured training and remuneration and limited and inconsistent support and supervision from the health centers (HCs). This implementation research aims to develop, implement, and evaluate a digital health intervention to improve the performance of VHSGs through better support and supervision and increase the MCH service coverage in rural Cambodia. METHODS: i-MoMCARE, a two-arm cluster randomized controlled trial, will be conducted between 2022 and 2025. Five operational districts (ODs) have been randomized to an intervention arm and the other five ODs to the control arm. The intervention will last for 24 months. Around 200 VHSGs in the intervention arm will be equipped with a mobile application as a job aid and 20 HC staff with a web interface to improve support and supervision of VHSGs. The potential beneficiaries will include pregnant women, mothers, and children under 2 years old. We will measure the outcomes at baseline and endline. The primary outcomes will consist of a composite MCH index constructed from maternal and newborn care indicators, child immunization, and treatment of under-two children. Secondary outcomes will include coverage of selected MCH services. We will conduct the intention-to-treat and per-protocol analyses. We will conduct qualitative interviews with selected beneficiaries and stakeholders to evaluate the intervention's acceptability, feasibility, and scalability. We will also conduct a cost-effective analysis using decision-analytic modeling incorporating a societal perspective that explores different time horizons, intervention effects, and when scaled up to the national level. DISCUSSION: i-MoMCARE is expected to increase MCH service access and coverage in rural Cambodia. It will contribute to advancing digital health use in primary healthcare interventions, which remains in its infancy in the country. Furthermore, the study findings will be a valuable addition to a growing body of literature on the effectiveness and feasibility of mobile health to improve coverage of MCH services in rural low- and middle-income country settings. TRIAL REGISTRATION: ClinicalTrial.gov NCT05639595. Registered on 06 December 2022.

Bioarchaeological study of ancient Teotihuacans based on complete mitochondrial genome sequences and diet isotopes.

BACKGROUND: The Teotihuacan civilisation was the largest one in ancient Mesoamerica. The Teotihuacan city was born in the north-eastern Basin of Mexico around the second century BC, reached its peak in the fourth century AD, and had cultural influence throughout Mesoamerica. At its peak, the size of the city reached more than 20 km2, and the total population is estimated to have increased from 100,000 to 200,000. However, knowledge of the genetic background of the Teotihuacan people is still limited. AIM: We aimed to determine the mitogenome sequences of the Teotihuacan human remains and compare the ancient and present Mesoamericans. In addition, we aimed to identify the food habits of ancient Teotihuacans. SUBJECTS AND METHODS: We determined the mitogenome sequences of human remains dated to 250-636 cal AD using target enrichment-coupled next generation sequencing. We also performed stable isotope analysis. RESULTS: We successfully obtained nearly full-length sequences newly unearthed from a civilian dwelling in the Teotihuacan site. Teotihuacan mitochondrial DNA was classified into the haplogroups in present and ancient Mesoamericans. In addition, Teotihuacan individuals had a diet dependent on C4 plants such as maize. CONCLUSION: Genetic diversity varied among the Teotihuacans.

Developing an infection prevention and control intervention to reduce hospital-acquired infections in Cambodia and Lao People's Democratic Republic: the HAI-PC study protocol.

Background: Hospital-acquired infections (HAIs) are significant public health issues, especially in low-and middle-income countries (LMICs). Hand hygiene and low-level disinfection of equipment practices among healthcare workers are some of the essential measures to reduce HAIs. Various infection prevention and control (IPC) interventions to reduce HAI incidence have been developed. However, effective interventions have not been well developed in the LMICs context. Therefore, this protocol aims to develop, pilot, and assess the feasibility and acceptability of an IPC intervention in Cambodia and the Lao People's Democratic Republic. Methods: This study will consist of four phases guided by the Medical Research Council (MRC) Framework. Three hospitals will be purposely selected - each from the district, provincial, and national levels - in each country. The gap analysis will be conducted in Phase 1 to explore IPC practices among healthcare workers at each hospital through desk reviews, direct observation of hand hygiene and low-level disinfection of equipment practices, in-depth interviews with healthcare workers, and key informant interviews with stakeholders. In Phase 2, an IPC intervention will be developed based on the results of Phase 1 and interventions selected from a systematic literature review of IPC interventions in LMICs. In Phase 3, the developed intervention will be piloted in the hospitals chosen in Phase 1. In Phase 4, the feasibility and acceptability of the developed intervention will be assessed among healthcare workers and representatives at the selected hospitals. National consultative workshops in both countries will be conducted to validate the developed intervention with the national technical working groups. Discussion: The MRC Framework will be employed to develop and evaluate an intervention to reduce HAIs in two LMICs. This theoretical framework will be used to explore the factors influencing hand hygiene compliance among healthcare workers. The gap analysis results will allow us to develop a comprehensive IPC intervention to reduce HAI incidence in Cambodia and Lao People's Democratic Republic. Findings from this protocol will feed into promising IPC interventions to reduce HAI incidence in other resource-limited settings. Clinical trial registration: ClinicalTrial.Gov, identifier NCT05547373.

Effects of COVID-19 on sexual and reproductive health services access in the Asia-Pacific region: a qualitative study of expert and policymaker perspectives.

The COVID-19 pandemic has strained health systems globally, with governments imposing strict distancing and movement restrictions. Little is known about the effects of the COVID-19 pandemic on sexual and reproductive health (SRH). This study examined perceived effects of COVID-19 on SRH service provision and use in the Asia-Pacific region. We conducted a qualitative study using semi-structured interviews with 28 purposively sampled SRH experts in 12 Asia-Pacific countries (e.g. United Nations, international and national non-governmental organisations, ministries of health, academia) between November 2020 and January 2021. We analysed data using the six-stage thematic analysis approach proposed by Braun and Clarke (2019). Interviewees reported that COVID-19 mitigation measures, such as transport restrictions and those that decreased the availability of personal protective equipment (PPE), reduced SRH service provision and use in most countries. SRH needs related to service barriers and gender-based violence increased. Systemic challenges included fragmented COVID-19 response plans and insufficient communication and collaboration, particularly between public and private sectors. SRH service-delivery challenges included COVID-19 response prioritisation, e.g. SRH staff task-shifting to COVID-19 screening and contact tracing, and lack of necessary supplies and equipment. Innovative SRH delivery responses included door-to-door antenatal care and family planning provision in the Philippines, online platforms for SRH education and outreach in Viet Nam, and increasing SRH service engagement through social media in Myanmar and Indonesia. To ensure continuation of SRH services during health emergencies, governments should earmark human and financial resources and prioritise frontline health-worker safety; work with communities and the private sector; and develop effective risk communications.

Diversity in matrilineages among the Jomon individuals of Japan.

BACKGROUND: The Jomon period of Japan is characterised by a unique combination of sedentary and hunting/gathering lifestyles, spanning for more than 10,000 years from the final Pleistocene to the Holocene. The transition from the preceding Palaeolithic period to the Jomon period is known to have begun with the appearance of pottery usage. However, knowledge of the genetic background of the Jomon people is still limited. AIM: We aimed to determine the population-scale complete mitogenome sequences of the Initial Jomon human remains and compare the occurrence of mitochondrial haplogroups in the Jomon period from temporal and regional perspectives. SUBJECTS AND METHODS: For human remains dated to 8200-8600 cal BP, we determined their complete mitogenome sequences using target enrichment-coupled next-generation sequencing. RESULTS: We successfully obtained the complete mitogenome sequences with high depth of coverage and high concordance on consensus sequences. These sequences differed by more than three bases each, except for two individuals having completely identical sequences. Co-existence of individuals with haplogroups N9b and M7a was first observed at the same archaeological site from the Initial Jomon period. CONCLUSION: The genetic diversity within the population was not found to be low even in the Initial Jomon period.

What are the determinants of antiretroviral therapy adherence among stable people living with HIV? A cross-sectional study in Cambodia.

BACKGROUND: Understanding context-specific determinants of antiretroviral therapy (ART) adherence is crucial for developing tailored interventions for improving health outcomes and achieving the UNAIDS' third 95% target. This cross-sectional study explores factors associated with ART adherence among stable people living with HIV on ART in Cambodia. METHODS: We used baseline survey data from a quasi-experimental study conducted in 2021. The participants were recruited from 20 ART clinics in nine provinces for face-to-face interviews. A structured questionnaire collected information on sociodemographic characteristics, ART adherence, perceived ART self-efficacy, mental health, quality of life, stigma, and discrimination. We conducted bivariate and multiple logistic regression analyses to identify factors associated with ART adherence. RESULTS: Out of the 4101 participants, 86.5% reported adhering to ART in the past two months. The adjusted odds of ART adherence were significantly higher among participants in older age groups than those aged 15-29, participants with elevated cholesterol than those without it, participants who exhibited strong self-efficacy in health responsibility to maintain life than those with poor self-efficacy in health responsibility, participants who scored < 3 on the stigma and discrimination scale than those who scored ≥ 3, participants who scored ≥ 42 on the mental component of the quality-of-life scale than those who scored < 42. The adjusted odds of ART adherence were significantly lower in participants who earned > 301 USD per month than those who earned ≤ 100 USD per month. CONCLUSION: The ART adherence rate among stable people living with HIV in this study was comparable to that of the general people living with HIV in Cambodia. The results suggest the need for innovative interventions to further reduce stigma and discrimination and strategies to improve the self-efficacy and mental health of people living with HIV to improve ART adherence.

Health system evaluation in conflict-affected countries: a scoping review of approaches and methods.

INTRODUCTION: Strengthening health systems in conflict-affected settings has become increasingly professionalised. However, evaluation remains challenging and often insufficiently documented in the literature. Many, particularly small-scale health system evaluations, are conducted by government bodies or non-governmental organisations (NGO) with limited capacity to publish their experiences. It is essential to identify the existing literature and main findings as a baseline for future efforts to evaluate the capacity and resilience of conflict-affected health systems. We thus aimed to synthesise the scope of methodological approaches and methods used in the peer-reviewed literature on health system evaluation in conflict-affected settings. METHODS: We conducted a scoping review using Arksey and O'Malley's method and synthesised findings using the WHO health system 'building blocks' framework. RESULTS: We included 58 eligible sources of 2,355 screened, which included examination of health systems or components in 26 conflict-affected countries, primarily South Sudan and Afghanistan (7 sources each), Democratic Republic of the Congo (6), and Palestine (5). Most sources (86%) were led by foreign academic institutes and international donors and focused on health services delivery (78%), with qualitative designs predominating (53%). Theoretical or conceptual grounding was extremely limited and study designs were not generally complex, as many sources (43%) were NGO project evaluations for international donors and relied on simple and lower-cost methods. Sources were also limited in terms of geography (e.g., limited coverage of the Americas region), by component (e.g., preferences for specific components such as service delivery), gendered (e.g., limited participation of women), and colonised (e.g., limited authorship and research leadership from affected countries). CONCLUSION: The evaluation literature in conflict-affected settings remains limited in scope and content, favouring simplified study designs and methods, and including those components and projects implemented or funded internationally. Many identified challenges and limitations (e.g., limited innovation/contextualisation, poor engagement with local actors, gender and language biases) could be mitigated with more rigorous and systematic evaluation approaches.

Sexual and reproductive health services access and provision in Cambodia during the COVID-19 pandemic: a mixed-method study of urban-rural differences.

BACKGROUND: The COVID-19 pandemic pushed governments worldwide to implement unprecedented mitigation measures, including safe-distancing, lockdowns, disruption of non-essential services, border closures and travel restrictions, with both potential to affect rural and urban service-users differently and unintended consequences including reductions in sexual and reproductive health (SRH) services. We aimed to explore rural-urban differences in progress and challenges in SRH services provision in Cambodia, particularly during initial months of the COVID-19 pandemic. METHODS: We used a mixed-methods study design, including a household survey of 423 adolescents and women aged 18-49 and semi-structured interviews with 21 healthcare providers. We analysed survey data using multivariable logistic regression to identify associations between rural-urban setting and contraceptive perceptions or access. We analysed interview data thematically. RESULTS: Rural-urban residence was significantly associated with reported perceptions about and access to contraceptives. Rural participants had higher odds of stating it was possible to change contraceptive methods early in the COVID-19 pandemic, compared with urban participants. Qualitative data showed that although SRH services continued, health-workers faced differential challenges in rural and urban areas, e.g. service-users not attending due to job losses in urban areas and not complying with safe-distancing and mask-wearing requests in rural areas. CONCLUSIONS: COVID-19 and inadequate mitigation responses differentially affected rural and urban SRH service providers and service-users, exacerbating existing socioeconomic stressors while adding new fears of infection, transport constraints, and reduced livelihoods. Added financial support could help mitigate challenges in both rural and urban areas.

Community engagement in health systems interventions and research in conflict-affected countries: a scoping review of approaches.

BACKGROUND: Healthcare research, planning, and delivery with minimal community engagement can result in financial wastage, failure to meet objectives, and frustration in the communities that programmes are designed to help. Engaging communities - individual service-users and user groups - in the planning, delivery, and assessment of healthcare initiatives from inception promotes transparency, accountability, and 'ownership'. Health systems affected by conflict must try to ensure that interventions engage communities and do not exacerbate existing problems. Engaging communities in interventions and research on conflict-affected health systems is essential to begin addressing effects on service delivery and access. OBJECTIVE: This review aimed to identify and interrogate the literature on community engagement in health system interventions and research in conflict-affected settings. METHODS: We conducted a scoping review using Arksey & O'Malley's framework, synthesising the data descriptively. RESULTS: We included 19 of 2,355 potential sources identified. Each discussed at least one aspect of community engagement, predominantly participatory methods, in 12 conflict-affected countries. Major lessons included the importance of engaging community and religious leaders, as well as people of lower socioeconomic status, in both designing and delivering culturally acceptable healthcare; mobilising community members and involving them in programme delivery to increase acceptability; mediating between governments, armed groups and other organisations to increase the ability of healthcare providers to remain in post; giving community members spaces for feedback on healthcare provision, to provide communities with evidence that programmes and initiatives are working. CONCLUSION: Community engagement in identifying and setting priorities, decision-making, implementing, and evaluating potential solutions helps people share their views and encourages a sense of ownership and increases the likely success of healthcare interventions. However, engaging communities can be particularly difficult in conflict-affected settings, where priorities may not be easy to identify, and many other factors, such as safety, power relations, and entrenched inequalities, must be considered.

Gender-Based Violence in the Asia-Pacific Region during COVID-19: A Hidden Pandemic behind Closed Doors.

Since the early stages of the COVID-19 pandemic, there have been reports of increased violence against women globally. We aimed to explore factors associated with reported increases in gender-based violence (GBV) during the pandemic in the Asia-Pacific region. We conducted 47 semi-structured interviews with experts working in sexual and reproductive health in 12 countries in the region. We analysed data thematically, using the socio-ecological framework of violence. Risks associated with increased GBV included economic strain, alcohol use and school closures, together with reduced access to health and social services. We highlight the need to address heightened risk factors, the importance of proactively identifying instances of GBV and protecting women and girls through establishing open and innovative communication channels, along with addressing underlying issues of gender inequality and social norms. Violence is exacerbated during public health crises, such as the COVID-19 pandemic. Identifying and supporting women at risk, as well as preventing domestic violence during lockdowns and movement restrictions is an emerging challenge. Our findings can help inform the adoption of improved surveillance and research, as well as innovative interventions to prevent violence and detect and protect victims.

Operationalising Regional Cooperation for Infectious Disease Control: A Scoping Review of Regional Disease Control Bodies and Networks.

BACKGROUND: The rapid spread of the coronavirus disease 2019 (COVID-19) pandemic demonstrates the value of regional cooperation in infectious disease prevention and control. We explored the literature on regional infectious disease control bodies, to identify lessons, barriers and enablers to inform operationalisation of a regional infectious disease control body or network in southeast Asia. METHODS: We conducted a scoping review to examine existing literature on regional infectious disease control bodies and networks, and to identify lessons that can be learned that will be useful for operationalisation of a regional infectious disease control body such as the Association of Southeast Asian Nations (ASEAN) Center for Public Health Emergency and Emerging Diseases. RESULTS: Of the 57 articles included, 53 (93%) were in English, with two (3%) in Spanish and one (2%) each in Dutch and French. Most were commentaries or review articles describing programme initiatives. Sixteen (28%) publications focused on organisations in the Asian continent, with 14 (25%) focused on Africa, and 14 (25%) primarily focused on the European region. Key lessons focused on organisational factors, diagnosis and detection, human resources, communication, accreditation, funding, and sustainability. Enablers and constraints were consistent across regions/ organisations. A clear understanding of the regional context, budgets, cultural or language issues, staffing capacity and governmental priorities, is pivotal. An initial workshop inclusive of the various bodies involved in the design, implementation, monitoring or evaluation of programmes is essential. Clear governance structure, with individual responsibilities clear from the beginning, will reduce friction. Secure, long-term funding is also a key aspect of the success of any programme. CONCLUSION: Operationalisation of regional infectious disease bodies and networks is complicated, but with extensive groundwork, and focus on organisational factors, diagnosis and detection, human resources, communication, accreditation, funding, and sustainability, it is achievable. Ways to promote success are to include as many stakeholders as possible from the beginning, to ensure that context-specific factors are considered, and to encourage employees through capacity building and mentoring, to ensure they feel valued and reduce staff turnover.

Oral Antibiotic Transition in Patients with Bacteremia with a Urinary Source Due to Extended-Spectrum ß-Lactamase-Producing Escherichia coli.

Transitioning from intravenous to oral antibiotic therapy for Escherichia coli bacteremia could reduce the length of hospital stay and drug costs without compromising efficacy. Despite the expansion of extended-spectrum ß-lactamase (ESBL)-producing E. coli, limited data are available regarding the effectiveness of switching to oral antibiotic therapy in patients with bacteremia caused by this organism. To compare clinical outcomes between oral transition therapy and intravenous therapy in patients with bacteremia due to ESBL-producing E. coli with a urinary source, we conducted a retrospective cohort study at 3 Japanese hospitals. The effects were estimated by Cox hazard analysis using propensity scores. Among 996 patients with bacteremia due to E. coli, 73 were included in the study. In the adjusted analysis weighted by propensity scores including 26 patients in the oral switch group and 47 in the intravenous group, oral transition did not increase the risk of treatment failure within 60 days (adjusted hazard ratio 0.86, 95% confidence interval 0.18-4.10), whereas the length of hospital stay was shorter in the oral switch group than in the intravenous group (median, 12 days vs. 19 days, P = 0.04). Intravenous-to-oral transition may be an effective treatment option that shortens the hospital stay.

Molecular Epidemiology of Enterobacter cloacae Complex Isolates with Reduced Carbapenem Susceptibility Recovered by Blood Culture.

The Enterobacter cloacae complex (ECC) is one of the most common causes of bacteremia and leads to poor clinical outcomes. The aim of this study was to clarify the antimicrobial susceptibility profiles and genetic backgrounds of non-carbapenemase-producing reduced-carbapenem-susceptible (RCS) ECC blood isolates in Japan using agar dilution antimicrobial susceptibility testing, whole-genome sequencing, and quantitative polymerase chain reaction for ampC, ompC, and ompF transcripts. Forty-two ECC blood isolates were categorized into RCS and carbapenem-susceptible groups based on the minimum inhibitory concentration of imipenem. The RCS ECC blood isolates belonged to distinct species and sequence types and produced varying class C ß-lactamases. The E. roggenkampii, E. asburiae, and E. bugandensis isolates belonged only to the RCS group. Some E. hormaechei ssp. steigerwaltii isolates from the RCS group exhibited AmpC overexpression caused by amino acid substitutions in AmpD and AmpR along with ompF downregulation. These findings suggest that non-carbapenemase-producing RCS ECC blood isolates are genetically diverse.

'Science is only half of it': Expert perspectives on operationalising infectious disease control cooperation in the ASEAN region.

Governmental awareness of the potential spread of infectious disease, exemplified by the current Covid-19 pandemic, ideally results in collective action, as countries coordinate a response that benefits all, contributing expertise, resources, knowledge and experience to achieve a common public good. However, operationalising regional cooperation is difficult, with barriers including lack of political will, regional heterogeneity, and existing geopolitical issues. We interviewed 23 people with regional expertise focusing on Asia, Africa, the Americas and Europe. All interviewees held senior positions in regional bodies or networks or had significant experience working with them. Operationalisation of a regional infectious disease body is complex but areas interviewees highlighted-organisational factors (e.g. integration and harmonisation; cross-border issues; funding, financing and sustainability; capacity-building; data sharing); governance and diplomacy (e.g. building collaborations and partnerships; communication; role of communities; diplomacy; leadership; ownership; sovereignty; political commitment); and stakeholders and multilateral agreements-will help promote successful operationalisation. The international infectious disease community has learned valuable lessons from the Covid-19 pandemic, not least the necessity of pooling human, financial and technological resources, constructing positive working relationships with neighbours, and sharing data. Without this kind of regional cooperation, infectious diseases will continue to threaten our future, and the next pandemic may have even more far-reaching effects.

Population dynamics in the Japanese Archipelago since the Pleistocene revealed by the complete mitochondrial genome sequences.

The Japanese Archipelago is widely covered with acidic soil made of volcanic ash, an environment which is detrimental to the preservation of ancient biomolecules. More than 10,000 Palaeolithic and Neolithic sites have been discovered nationwide, but few skeletal remains exist and preservation of DNA is poor. Despite these challenging circumstances, we succeeded in obtaining a complete mitogenome (mitochondrial genome) sequence from Palaeolithic human remains. We also obtained those of Neolithic (the hunting-gathering Jomon and the farming Yayoi cultures) remains, and over 2,000 present-day Japanese. The Palaeolithic mitogenome sequence was not found to be a direct ancestor of any of Jomon, Yayoi, and present-day Japanese people. However, it was an ancestral type of haplogroup M, a basal group of the haplogroup M. Therefore, our results indicate continuity in the maternal gene pool from the Palaeolithic to present-day Japanese. We also found that a vast increase of population size happened and has continued since the Yayoi period, characterized with paddy rice farming. It means that the cultural transition, i.e. rice agriculture, had significant impact on the demographic history of Japanese population.

A biomolecular anthropological investigation of William Adams, the first SAMURAI from England.

William Adams (Miura Anjin) was an English navigator who sailed with a Dutch trading fleet to the far East and landed in Japan in 1600. He became a vassal under the Shogun, Tokugawa Ieyasu, was bestowed with a title, lands and swords, and became the first SAMURAI from England. "Miura" comes from the name of the territory given to him and "Anjin" means "pilot". He lived out the rest of his life in Japan and died in Hirado, Nagasaki Prefecture, in 1620, where he was reportedly laid to rest. Shortly after his death, graveyards designated for foreigners were destroyed during a period of Christian repression, but Miura Anjin's bones were supposedly taken, protected, and reburied. Archaeological investigations in 1931 uncovered human skeletal remains and it was proposed that they were those of Miura Anjin. However, this could not be confirmed from the evidence at the time and the remains were reburied. In 2017, excavations found skeletal remains matching the description of those reinterred in 1931. We analyzed these remains from various aspects, including genetic background, dietary habits, and burial style, utilizing modern scientific techniques to investigate whether they do indeed belong to the first English SAMURAI.

Dissemination of IncF group F1:A2:B20 plasmid-harbouring multidrug-resistant Escherichia coli ST131 before the acquisition of blaCTX-M in Japan.

OBJECTIVES: The Escherichia coli O25-ST131 clone is responsible for global dissemination of the blaCTX-M gene. However, the prevalence of this clone in the digestive tract, devoid of antimicrobial selection, and its molecular epidemiology remain unclear. In this study, we examined the origin of blaCTX-M-positive E. coli O25-ST131 and its distribution. METHODS: We separately sequenced the chromosomal and plasmid genomes of 50 E. coli O25 isolates obtained from faecal samples of patients with diarrhoea in Japan. RESULTS: Although 36 (72%) of 50 E. coli O25 isolates were ST131, only 6 harboured blaCTX-M. According to the fimH and ybbW sequences and fluoroquinolone susceptibility, H30R1 isolates were dominant (27/36; 75%) and possessed IncFII-FIA-FIB with FAB formula subtype F1:A2:B20 plasmids at a high frequency (24/27; 89%). The F1:A2:B20 plasmids possessed more resistance genes such as blaTEM-1, aminoglycoside resistance genes and trimethoprim/sulfamethoxazole resistance genes compared with non-F1:A2:B20 plasmids. In contrast, only one blaCTX-M-14 gene was located on the F1:A2:B20 plasmids, whereas the other three were located on IncFII (F4:A-:B-) (n = 1) and IncZ (n = 2) plasmids. Two H30Rx-ST131 isolates harboured blaCTX-M-15: one was on the chromosome and the other on the IncFIA-R plasmid. The stability and conjugation ability of the F1:A2:B20 plasmids were compared with those of non-F1:A2:B20 plasmids, which revealed higher stability but lower conjugative ability. CONCLUSIONS: These results suggest that E. coli H30R1-ST131 is a multidrug-resistant clone containing several resistance genes in the F1:A2:B20 plasmid, which were widely distributed before the acquisition of blaCTX-M.

A study of 8,300-year-old Jomon human remains in Japan using complete mitogenome sequences obtained by next-generation sequencing.

Ancient human remains have been assigned to their mitochondrial DNA (mtDNA) haplogroups. To obtain efficiently deep and reliable nucleotide sequences of ancient DNA of interest, we achieved target enrichment followed by next-generation sequencing (NGS). Complete mitochondrial genome (mitogenome) sequences were obtained for three human remains from the Iyai rock-shelter site of the Initial Jomon Period in Japan. All the Jomon mitogenomes belong to haplogroup N9b, but no sequences among them were identical. High genetic diversity was clarified even among the Jomon human remains belonging to haplogroup N9b, which has been described as a haplogroup representing the Jomon people.