Through its Global Action Plan for Influenza Vaccines (GAP), the World Health Organization (WHO) in collaboration with the United States Department of Health and Human Services has produced a checklist to support policy-makers and influenza vaccine manufacturers in identifying key technological, political, financial, and logistical issues affecting the sustainability of influenza vaccine production. This checklist highlights actions in five key areas that are beneficial for establishing successful local vaccine manufacturing. These five areas comprise: (1) the policy environment and health-care systems; (2) surveillance systems and influenza evidence; (3) product development and manufacturing; (4) product approval and regulation; and (5) communication to support influenza vaccination. Incorporating the checklist into national vaccine production programmes has identified the policy gaps and next steps for countries involved in GAP’s Technology Transfer Initiative. Lessons learnt from country experiences provide context and insight that complement the checklist’s goal of simplifying the complexities of influenza prevention, preparedness, and vaccine manufacturing. Its aim is to increase equitable access to pandemic vaccines while contributing to international pandemic preparedness efforts. WHO directly supports 14 developing countries to establish or expand influenza vaccine manufacturing. This support is provided as part of a larger WHO mandate born within the Global Strategy and Plan of Action on Public Health, Innovation and Intellectual Property (GSPA-PHI) Within GAP’s objectives, there is a focus on increasing seasonal influenza vaccination coverage to stimulate global pandemic vaccine production capacity and to strengthen national regulatory competencies. However, the multi-sectorial nature of influenza vaccine manufacturing requires policy-makers and manufacturers to address a mix of technological, political, financial, and logistical issues that collectively affect sustainable production in developing countries •better pandemic preparedness through development of local sources of vaccines;•a more reliable supply of medical products, reducing the likelihood of distribution disruptions;•more efficient supply chains in rural and poor areas and thus improved distribution times;•potential cost savings as locally produced medical products, assuming the production scale is sufficiently large, are less expensive;•higher quality products, better suited to local culture and conditions;•stimulation of local innovation capacity and the development of human capital;•development of export capacity for products, improving the national balance of payments; and•increased employment generation and spill-over effects into other sectors of the economy.GAP objectives also favour sustainable local vaccine production. Local vaccine production offers the following benefits As shown in Local vaccine production and improved access to medical products can be stimulated by coordinated industrial, technology and health policies. Prioritization of local production can galvanize action targeting immediate barriers, such as lack of research and development capacities, resources, and expertise, which will result in broader impacts to the health, science, technology and industry fields. Governments are encouraged to examine these potential investments in light of the broader impact to other fields and as an opportunity to foster and drive industry and innovation locally. The return on investment must be substantial and sustainable for manufacturers to partner.Sustainability also requires a coherent policy environment, reliable government procurement, product quality assurance, and market certainty. In addition to achieving public health objectives, there are strong economic and political drivers to establish and enhance national capacity to manufacture medical technologies.2Over the last 10 years, through the implementation of GAP, WHO has distilled expertise and experiences into a checklist designed to support policy-makers and manufacturers in developing countries who are seeking to improve influenza vaccine sustainability. This checklist addresses the following areas: (1) the policy environment and health-care systems; (2) surveillance systems and influenza evidence; (3) product development and manufacturing; (4) product approval and regulation; and (5) communication to support influenza vaccination.The checklist identifies, for each of the five specified areas, conditions that could increase the likelihood of sustainable local production and the use of influenza vaccines. These conditions are outlined below see also .2.1National stakeholders develop policies to achieve their health objectives, based on recommendations developed by experts, such as Strategic Advisory Group expert (SAGE) on immunization, GAVI alliance, WHO, etc. International recommendations should be adapted to local specificities, while maintaining the global and inclusive approach to combat seasonal and pandemic influenza. Local vaccine production and improved access to medical products can be stimulated by coordinated industrial, technology and health policies.2.1.1•Strong political will and buy-in are critical when establishing influenza as a national and/or regional priority. Establishing strong political will at leadership levels often results in increased resources, high-level public political commitment, cooperation to establish new policies or change existing ones, and enablement to navigate complex regulatory environments•The use of international, regional, and national influenza recommendations to inform local policy development.•Coherence among relevant national health policies and programmes ensures synergies between new and existing programmes.•An established seasonal influenza vaccination programme can mitigate the effects of pandemic influenza events leading to stronger national security preparedness.•A seasonal vaccination programme that leverages existing health system infrastructure and human resources to expand capacities in the routine health-care system.•Inclusion of seasonal influenza vaccination in health insurance schemes or direct provision by the public health sector Six key interconnected desirable components of health system policies are listed below and represented visually in 2.1.2•Interministerial coordination and strategic vision for industrial, health and economic development policies; this is crucial given the multi-sectorial space in which influenza vaccine manufacturing takes place.•Policies that supports the development of good manufacturing practices. The policy environment should encourage scientific and academic institutions to conduct laboratory research as well as stimulate upstream and downstream research on biologicals and biomanufacturing.•Relevant national and regional procurement and distribution policies to promote in-country production and sourcing of materials, in accordance with international agreements with third parties.•Governments and manufacturers’ full awareness of the consequences that multilateral and bilateral trade agreements have on the economic and public health situation of the country with respect to commercialisation, such as the impact of removal of trade barriers for national manufacturers. The development of a skilled local workforce, through governmental incentives and education policies to prevent brain-drain, and partnerships between manufacturers and academia.In addition to health-focused policies, governments interested in developing local sustainable vaccine production are advised to coordinate relevant industrial, procurement, trade, and workforce policies. 2.2•A surveillance system that utilises all available resources, such as sentinel sites, population-based studies, insurance data, hospital and out-patient clinic, and regional data, to ensure regular burden of disease data collection.•Clear definition of which data should be collected and which information systems should be used to accurately and appropriately analyse data that streamlines timely reporting to regional and international databases and dissemination of results.•Investment in local burden of disease and cost-effectiveness studies to build evidence for influenza vaccination policies. If possible, consider probe•Incorporation of morbidity and mortality data from neighbouring areas and various available proxies to understand the impact of seasonal influenza on the country population.•Evidence generated by the data analysis should be framed by larger economic and geopolitical considerations for decision-makers, particularly in the context of global health security and pandemic preparedness.Within any health system, the surveillance system has a critical role in providing relevant, accurate, and timely information for decision- and policy-making. 2.3•A solid business plan that considers the production environment and the marketplace where the product will be sold and used, the production costs and price of the product , the initial investment, and the time to market and regulatory pathway for the product.•Reliable and stable supplies of utilities , with a focus on developing mechanisms that encourage self-sufficiency.•Secure supply chain for all components, taking into account their costs, their foreseeable substitution, and their maintenance.•Identification of available market niches to overcome constraints due to price of the product or size of the market.•Strategies to mitigate business risks by considering seasonality, possible underutilisation of human resources and infrastructure, and additional products manufactured in the facility.•Government and industry policies and programmes to bolster skilled workforce capacity and retention. Strong links and continuous dialogue with academic institutions support the availability of skills necessary to perform every step of the production process and ensure high managerial competencies.•Realistic business and marketing strategies to identify return on investment, based on the potential size of the national, regional, and international markets.•Full adherence to good manufacturing practice (GMP) and quality control procedures to guarantee a smoother production process and quality of the final product, thereby reducing the risk of costs linked to substandard quality steps or by-products.•Strategically plan and design clinical trials and identify relevant partners for clinical trial administration. The product’s reference market is established by focusing on the target populations and reviewing the safety and effectiveness of the product. This also helps to create competitive advantages with the other manufacturers.•Active engagement in advocacy associations and networks that sustain influenza vaccine manufacturing helps to raise awareness of issues faced by manufacturers in developing countries.•Building in flexibility into various parts of the production process, including the sourcing of materials, increases pandemic preparedness. Also, the chosen technologies affect pandemic response time and the ramp-up capacity.Countries implementing policies to initiate local influenza vaccine production must consider the pipeline and manufacturing process. In this respect, the following would be considered advantageous:2.4•The national regulatory authority (NRA) should be able to assess, license, control quality, and conduct surveillance of biological medical products. For countries producing vaccines, the NRA should be able to exercise the six recommended control functions•If the previous condition is met, the national manufacturer can aspire to meet WHO’s recommendation for United Nations prequalification of its product for better viability in local and international markets.•With the emerging global market and the increasing number of novel products, the volume of biological medicinal products crossing national borders continues to rise. Participation in regional harmonisation efforts and integration of regulatory approvals plays a key role in facilitating the accuracy of regulatory work and international capacity building efforts.In terms of creating an enabling regulatory environment for local influenza vaccine production the following considerations merit attention:2.5•A communication policy, plan, and strategy to support the development and implementation of influenza vaccination policies.•Communication research, monitoring, and evaluation of objectives and agreed public health goals.•Partnerships, stakeholders, and public engagement to implement the strategic objectives.•Communication capacity building and training for all actors and stakeholders involved in influenza programmes.•Knowledge translation and information communication technologies (ICTs) that support efficiency and effectiveness of the system and align them with the needs of 21st century information society.An effective national communication system comprises:3Over the last 4 years, WHO has conducted a series of assessments in developing countriesThe first notable lesson is the need for strong political support and government investment to develop a local product. After the 2009 influenza A (H1N1) pandemic, countries realised that they were ill-prepared and that national systems were too weak to protect their population. State involvement and support can take several forms: the development and updating of a pandemic influenza preparedness plan, financial commitment, and long-term supply agreements with manufacturers.A second lesson learnt from countries’ experiences relates to access to health care. Studies show that a high rate of vaccination occurs when there is public or third-party reimbursement of vaccination, through government run health-care centres or insurance schemes The existence of a strong NRA, operating in accordance with international and WHO standards, offers a strong support to the manufacturer during the product development and testing process. This regulatory presence also helps build confidence among the population that the vaccine is safe, effective, and of high quality. The NRA provides further assurance that the product will reach the population under reliable supply conditions, and the product will be monitored for safety throughout its lifespan.Countries and manufacturers receiving technology for influenza vaccine production require skills and staff that are trained appropriately. From the manufacturers’ side, workers need to be trained to use the technology, and in parallel, awareness should be raised among regulators, administrative staff, surveillance system staff, and health-care workers to ensure that once the product is available, it is correctly administered. To this end, major investments in communication and training, especially of health-care workers, are paramount to ensure high levels of vaccination among at-risk populations Despite ample evidence of the disease burden imposed by influenza WHO and countries developing influenza vaccine manufacturing and production capacity that have incorporated the checklist’s recommended targets have reported considerable successes. The use of the checklist has increased interagency communication and strategic planning that benefit both the short- and long-term viability of the influenza vaccine production.4The use of the checklist has proven useful in the identification of policy gaps and opportunities for better coherence of policies, as a tool for policy-makers and manufacturers to address the complexities of influenza prevention and preparedness and vaccine manufacturing. WHO country assessment reports include a compendium of policy options to strengthen sustainability of local production and use of influenza vaccines. These reports will be developed as a reference for countries willing to invest in influenza preparedness through local production, and will be adapted to the local context. By incorporating this checklist into a national vaccine production programmes, countries can cultivate comprehensive platforms for broader pandemic preparedness.


A substantial increase in the number of mumps outbreaks and outbreak-associated cases has occurred in the United States since late 2015 . To assist state and local health departments in responding to mumps outbreaks, CDC issued guidance on use of a third dose of MMR vaccine in the 2012 https://www.cdc.gov/vaccines/acip/recs/grade/about-grade.html). Methods and GRADE tables for the evidence for third dose of mumps virus–containing vaccine can be found at https://www.cdc.gov/vaccines/acip/recs/grade/mumps.html.During March–October 2017, the ACIP Mumps Work Group held biweekly conference calls to review and discuss relevant scientific evidence. Topics addressed included the epidemiology of mumps in the United States since introduction of a routine second dose of MMR vaccine; effectiveness, duration of protection, immunogenicity, and risk factors for 2-dose vaccine failure; and effectiveness, immunogenicity, and safety of a third dose of MMR vaccine. Also assessed were stakeholders’ values attributed to the perceived benefits and harms of a third dose of MMR vaccine, acceptability, and implementation considerations regarding use of a third dose of MMR vaccine. Where scientific data were lacking, the summary of evidence incorporated the opinions of the Mumps Work Group member experts. Quality of evidence related to the benefits and harms of a third dose of mumps virus–containing vaccine was evaluated using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework  during mumps outbreaks was presented, and after a period for public comment, was approved unanimously by the voting ACIP members.Public Health Burden of Mumps. Parotitis occurs in >85% of mumps cases; however, severe manifestations with complications such as orchitis (12%–66%), aseptic meningitis (0.2%–10%), or encephalitis (0.02%–0.3%) were recognized during the prevaccine era   1 month after vaccination; however, antibody titers declined to near baseline by 1 year after vaccination  using passive and active surveillance for adverse events  , thereby limiting reliability of the results, the values regarding the benefits and harms of using a third dose to prevent mumps from the perspective of these stakeholders was based on expert opinion. Experts concluded that students and parents place high value on preventing mumps and its complications as well as preventing the harms associated with loss of productivity that can occur with mumps disease. Experts also concluded students and parents do not have concerns about safety of a third dose of MMR vaccine.The survey of colleges and universities was distributed through the American College Health Association. Among 980 member university student health service administrators, 251 (26%) responded, representing colleges and universities from 47 states  state and territorial health departments and 23 (28%) city or large urban health departments. Among the 61 (75%) responding health departments, 46 (75%) reported having one or more mumps outbreaks in their jurisdiction since January 1, 2016 .Mumps outbreaks have occurred primarily in populations in institutional settings with close contact or in close-knit communities. The current routine recommendation for 2 doses of MMR vaccine appears to be sufficient for mumps control in the general population, but insufficient for preventing mumps outbreaks in prolonged, close-contact settings, even where coverage with 2 doses of MMR vaccine is high. Waning of vaccine-induced immunity with time after receipt of the second vaccine dose in high intensity exposure settings typical of outbreaks contributes to this higher risk for mumps disease in these settings. Protection against severe disease, however, is maintained. Considering the evidence regarding the public health burden of disease and the known risk factors, persons who are at increased risk for acquiring mumps because of an outbreak were identified as a public health priority for receiving a third dose of mumps virus–containing vaccine.A third dose of MMR vaccine has at least a short-term benefit for persons in outbreak settings. No serious adverse events were reported, and rates of nonserious adverse events were low. Because mumps is prevented in persons who receive a third dose, complications will also be prevented. Together, the benefit of added protection through administration of a third dose of MMR vaccine outweighs the low risk for vaccine-associated adverse events. Universities and health departments value the prevention of mumps disease and mumps complications and recognize that there is a potential loss of productivity because of mumps disease. A third dose of MMR vaccine was considered acceptable to students, parents, universities/schools, and health departments. Regarding implementation, an ACIP recommendation would allow health departments to make more rapid decisions regarding use of a third dose of MMR vaccine and increase access to vaccine for persons identified by public health authorities as being at increased risk for mumps because of an outbreak. MMRV vaccine, which is the other vaccine licensed in the United States for the prevention of mumps . In addition, CDC will continue to collect data to assess the impact of receipt of a third dose of mumps virus–containing vaccine on mumps outbreaks.Contraindications and precautions for administration of a third dose of a mumps virus–containing vaccine are the same as those for routine use of the vaccine (1 or 2 doses) (


The effect of employment insecurity on employee health is an important public health issue due to the recent effects of neoliberalism and the global financial crisis (2007–2008) on labor markets. This study aims to evaluate the differences in cardiovascular health status and the use of preventive screening services between standard and nonstandard workers.Waged employees  between the ages of 20 and 64 were grouped into standard  and nonstandard  employees. Data from the Fourth Korea National Health and Nutrition Examination Survey, 2007–2009, a nationwide representative survey, were examined, including cardiovascular health risk behaviors , measured morbidities , and the use of screening services for hypertension and diabetes mellitus.Female nonstandard employees tended to have higher blood pressure than did female standard employees . However, nonstandard employees (both men and women) were less likely to use preventive screening services for hypertension  and diabetes .Nonstandard work is associated with the underuse of screening services and poorer cardiovascular health in a specific population. Policies to reduce employment insecurity and encourage nonstandard employees to receive health screening services should be prioritized. Following the 1997 financial crisis in Asia, significant changes have occurred in employment patterns as a result of neoliberalism and the increased demand for labor market flexibility. Beyond the dichotomous concepts of employment status  . A decadIt has been shown that employment and working conditions affect health status, with nonstandard employees experiencing more adverse effects on their physical and mental health compared to standard employees . EuropeaAlthough South Korea experienced an unprecedented increase in nonstandard work following the 1997–98 financial crisis combined with a poorly equipped social safety net , we were unable to find any systemic studies that examined the differences in individual health behaviors and outcomes between standard and nonstandard workers , 20. TheWe used the Fourth Korean National Health and Nutrition Examination Survey (KNHANES IV), which was conducted by the Korean Ministry of Health and Welfare, for data collection. KNHANES IV used a stratified, multistage sampling design of 24,871 individuals in households across 600 national districts; sampling units were based on geographical area, gender, and age using household registries. The survey is composed of four parts: the Health Interview Survey; the Health Promotion Knowledge, Attitude, and Practice (HP-KAP) Survey; the Nutrition Survey; and the Health Examination Survey. The Health Interview Survey, Health Behavior Survey, and Nutrition Survey are self-administered questionnaires. The Health Examination Survey, consisting of measured variables such as blood pressure (BP), blood glucose level and body mass index (BMI), was conducted by trained nurses. As the survey data analyzed are publicly available, this study was waived by the Institutional Review Board of Seoul National University Hospital.We performed cross-sectional analyses of data from 5,338 individuals who completed the Health Interview Survey, HP-KAP, and Health Examination Survey. The inclusion criteria included individuals who were: (i) aged from 20 to 64, (ii) economically active in the Korean labor market, and (iii) waged employees.We defined full-time, permanent employees as standard employees, and part-time, temporary, and daily employees as nonstandard employees –22. "FulSociodemographic characteristics included age, occupational class, monthly household income, educational level, and marital status. Occupational class was classified as either “manual” or “non-manual” work based on the Korean Standard Classification of Occupations . HousehoThe outcome measures used in this study included health risk behaviors, measured cardiovascular health status, and the use of preventive screening services. All data were obtained by self-administered questionnaires from KNHANES IV, with the exception of the measured variables. Tobacco consumption was classified into two groups: i) current smoker and those who have a lifetime consumption of over 100 cigarettes and ii) ex-smoker who did not fulfill the first criterion or never smoker . The sur2 or higher was regarded as obese.Hypertension was defined as systolic blood pressure (SBP) ≥140 mmHg, diastolic blood pressure(DBP) ≥ 90 mmHg, or taking medication for hypertension, which is in accordance with the Seventh Report of the Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure . All of Participants were asked to answer several questions about the last regular check-up of blood pressure and serum glucose level; these questions were based on the recommended screening intervals from established guidelines on health screening services. The suggested screening intervals were two years  and threAll statistical analyses in this study were performed with the STATA 12.0 software . We calculated the proportions of health outcomes and reported descriptive statistics for each response by gender and employment status. We used multivariate logistic regression adjusted for age, household income, education level, and region. We accounted for survey weights by calculating the adjusted odds ratios (aORs) and 95% confidential intervals (CIs).Both male and female nonstandard employees were less likely to receive preventive screening services for hypertension and diabetes compared to standard employees. Furthermore, we found that female nonstandard employees tended to have higher blood pressure than did female standard employees.Job security only represents part of the psychosocial work environment. Therefore, factors such as occupational categories, increased workload and decreased job control  could partly mediate the effect of job insecurity on cardiovascular health status –31. AlthThe prevention of cardiovascular disease is dependent on the successful control of risk factors, such as high blood pressure, serum glucose levels, and serum cholesterol levels . Since eOur study has several limitations. First, due to the fact that our design is cross-sectional, the direction of causation could not be clearly shown. For example, the “healthy worker effect” operates so that individuals with health problems are more likely to be selected into nonstandard jobs, and thus there is the possibility of reverse causation –38. SecoDespite the aforementioned limitations, our representative national data allowed us to estimate job-security-related disparities in preventive screening services between standard vs. nonstandard employees. More effort is needed to enable nonstandard employees to access and receive regular health screening services based on the social insurance system. To reduce the disparities between standard and nonstandard employees, further attention and effective collaboration involving policymakers, health plan administrators, third-party payers, and health care providers are needed.


Antibody drug conjugate (ADC) consists of a potent cytotoxic agent payload, linked covalently to side chains of particular amino acid residues of a monoclonal antibody (mAb). Most of the cytotoxic agent including the major payload precursors used in ADC are derived from microbial sources . However, it is almost impossible to get antigen targets that are only expressed in tumors cells. Similarly, there are rare chances for complete localization of ADC to lysozyme following internalization, so rational optimizations of ADCs are required. Chapter 3 provides an overview on special consideration during development and characterization of ADC in terms of their quality, safety, purity, and stability. Chapter 4 focuses on linker and conjugation technologies that allow the ADC to retain better pharmacokinetic (PK) properties. Linkers are either non-cleavable  or cleavable (that release the putative drug upon cleavage inside the cellular environment). Alteration of linking chemistry by engineering THIOMABs, and site-specific coupling has been routinely utilized for improvising the PK profile of ADCs. Chapter 5 contains information on strategies and considerations for maintaining the physical and chemical stability of ADC during manufacture. The chapter also includes specific consideration during formulation and logistical considerations for maintaining consistent quality. Chapter 6 presents the specific quality control (QC) assays for characterization of ADC before the initiation of non-clinical and clinical studies. These QC assays are cell-based cytotoxicity assays, immunogenicity assays etc., that need to be completely validated prior to commercialization. Chapter 7 explains the occupational hazard associated with components of ADC. The general guidance for material handling, information on specific facility requirements and engineering control, and personal protective measures for safe manufacturing process are also explained in details.in vitro cellular assays, or in vivo tumor xenograft mouse models are used. Chapter 10 explains the basic considerations for optimizing PK properties of ADCs using bioanalytical tools, in vitro assays, in vivo studies, and mathematical models. Chapter 11 provides the information about regulations for designing, formulating, evaluating and marketing of ADCs, particularly focusing on criteria for approval from Food and Drug Administration (FDA).The development of ADCs is fundamentally reliant on proper characterization and optimization of ADC before clinical use. Part 3 focuses on non-clinical aspects of designing and developments of ADC. Chapter 8 present bioanalytical strategies enabling successful ADC translation from initial designing. The bioanalysis of different components of ADC assists on assessment of integrity, bio-distribution, and PK properties, which correlates to efficacy and safety on patients. As explained in Chapter 9, in order to understand the factors modulating the efficiency of ADC, varieties of experimental models such as: viz antibody (high specificity to target antigen), payload (inhibition of tumor proliferation), and linkers (stability for delivery and efficiency for release) are explained. Chapter 14 presents information about clinical aspects of trastuzumab emtansine , an ADC for the treatment of HER2-positive metastatic breast cancer. Similarly, Chapter 15 presents the clinical aspects of brentuximab vedotin (BV), an ADC with efficacy in CD30-positive malignancies.Part 4 deals with the clinical aspects of ADC and their development as precise therapeutics. Considerations for evaluation of ADCs from phase I and beyond; and list of ADCs that has been already approved for clinical use or in phase trials are provided in Chapter 12. Chapter 13 presents the specific consideration while designing and developing the components of such ADC. The assessment techniques for validating specific requirements for each component of ADC Part 5 provides insight on future perspectives in ADC development by overcoming the present shortcomings. The efficiencies of ADCs are compromised by poor intake, rapid clearance and non-specific action on normal cells. Chapter 17 proposes that the labeled antibodies can be utilized for assessing the specificity, distribution, and dosage effect of particular antibody at specific tumor location. Chapter 18 illustrates the newer opportunities provided by additional cytotoxic drug classes with novel cellular targets, development in linker repertoire and antibody engineering. These advances in bioengineering, linker chemistry and potent cytotoxic payload have made ADC technology a powerful tool for targeted cancer therapy (Sau et al., All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Due to its incomparable advantages, the application of transcriptome sequencing in the study of traditional Chinese medicine attracts more and more attention of researchers, which greatly promote the development of traditional Chinese medicine. In this paper, the applications of transcriptome sequencing in traditional Chinese medicine were summarized by reviewing recent related papers. As an important part of human brilliant culture, Chinese medicine has made an important contribution to the survival and reproduction of mankind. In the modern disease prevention and health care model, the traditional Chinese medicine has great superiority for a thousand years of accumulation of precipitation. In recent years, the transcriptome studies developed rapidly. In animal studies, there are a lot of reports on the discovery of key genes, SNP, gene splicing, and complex disease research , 2. The The transcriptome sequencing technology has experienced three generations change. At present, the second-generation sequencing technology still dominates; the third-generation sequencing technology shows a strong momentum of development. The characteristics comparison of three-generation sequencing technology is shown in Due to lack of genomic data, gene sequence information, and genetic background, the medical plants need a large amount of genetic information in order to analyze the gene function in the whole level. At present, the whole genome sequencing of most medicinal plants cannot be detected, so it is a quick way to compare the gene sequences, discover new genes, and identify the expressed genes by constructing the genomic library (cDNA) or the transcription database. Salvia miltiorrhiza [Panax ginseng C. A. Mey.) transcriptome  obtained 178,145 unique genes where 105,522 genes were discovered for the first time, and 65.6% of the newly independent genes were found in the stems, leaves, and flowers library [Astragalus membranaceus (Fisch.) Bunge) transcriptome  was successfully annotated with 9,732 Unigenes after de novo sequencing, and 2,877 of them were classified into 45 metabolic pathways by KEGG [Large scale transcriptome studies have been carried out both in China and abroad on the medicinal plants such as American ginseng , 10, 11,iorrhiza . Wildungiorrhiza . Ginseng by KEGG .Up to March 2017, more than 50 species of traditional Chinese herbal medicine have been sequenced. Especially since 2014, the transcriptome study of traditional Chinese medicine developed rapidly. We have carried on the statistics to the common traditional Chinese medicine; specific sequence statistics are shown in Secondary metabolites are usually effective constituents or regulatory substances in Chinese medicine. The secondary metabolites include glycosides, alkaloids, saponins, flavonoids, steroids, organic acids, and many key enzymes in metabolic process. The mechanism of “multicomponent and multitarget” has made the secondary metabolites and its regulation mechanism become one of the important contents in the modern Chinese medicine research. Secondary, not only do metabolites play an important role in plants adapting to the special ecological environment and resistance to biotic or abiotic stresses , but many secondary metabolites with special biological activity are important active components of medicinal plants. The description of transcriptome can provide new information about biology and biochemistry, which can be used to find synthesis genes and its expression pattern of secondary metabolites and finally to determine its biosynthetic pathway. Because most of transcriptome studies in medicinal plants focus on the biosynthesis of active compounds and the research about this part is so much, this part is summarized as chemical composition. Lepidium seed is commonly used in traditional Chinese medicine where a variety of medicinal components have been extracted, but the synthesis genetic basis of these substances is still not clear. Lepidium seed transcriptome sequencing found 534 genes involved in the synthesis and metabolism of secondary metabolites. The genes in the biosynthetic pathway of mustard glycosides, flavonoids, and glycosides compounds were, respectively, 4, 19, and 69 Unigenes and 92 Unigenes in the phenylalanine metabolic pathway [Carthamus tinctorius L.) and showed that the genes related to the pathway were conserved [Study on flavonoids related genes and enzymes: pathway . Huang eonserved . Wang etonserved . Dendrobium officinale L. is an important traditional herb with high commercial value and excellent medicinal effect in China. Li et al. (2017) analyzed the genes involved in dendrobine biosynthesis in Dendrobium nobile Lindl., and they found 30 Unigenes encoding proteins were possibly related to the biosynthesis of dendrobine sesquiterpene backbone; MF23 might stimulate dendrobine biosynthesis by regulating the expressions of genes involved in the mevalonate (MVA) pathway and postmodification enzymes might play a major role in dendrobine biosynthesis [ Dendrobium officinale, which got Unigenes related to the enzymes involved in fructose and mannose metabolism and Unigenes associated with putative upstream elements of the alkaloid biosynthetic pathway [ Dendrobium transcription sequencing data found that 25 enzyme genes were involved in alkaloid synthesis [Study on alkaloids related genes and enzymes:ynthesis . Shen eti et al. 17 analyzynthesis . Platycodon grandiflorus are widely used as a crude drug. The active components include a variety of triterpenoid saponins. Tamura et al. (2017) varied cytochrome P450 monooxygenases (P450s) function in triterpenoid saponin biosynthesis of Platycodon grandiflorus by the analysis of three different tissues  using RNA sequencing (RNA-Seq) technology [ Swertia mussotii and screened 39 candidate transcripts involved in secoiridoid biosynthesis [ Picrorhiza kurroa is completely unknown until Vashisht et al. (2016) investigated complete spectrum of different transcription factors and discerned their association with picrosides biosynthesis [ Camptotheca acuminata transcriptome acquired 20 genes involved in the synthesis of camptothecin skeleton, including 13 new genes [Study on terpenes and glycosides related genes and enzymes: the roots ofchnology . Ma et aynthesis . Transcrynthesis . Wu et aynthesis . Wu et aynthesis . In addiew genes . D. Tanguticum, found 22 predicted biosynthetic genes related to RA and two of these genes were identified as candidates by evaluating the correlation coefficient between the RA contents and the expression of the predicted biosynthetic genes in the six organs [ Ganoderma triterpenoids is regulated by 11 upstream pathway key enzymes and 214 candidate cytochrome oxidase genes of downstream biosynthetic pathway [ Lonicera japonica is one of the most important medicinal plants. Chlorogenic acid, luteolin, other flavonoids, and secoiridoids are the most important effective ingredients. Rai et al. (2016) studied the potential candidate genes involved in chlorogenic acid, luteolosides, and secoiridoid biosynthesis pathways of nine tissues of Lonicera japonica and the results showed that different tissues of L. japonica are enriched with sets of Unigenes associated with specific pharmaceutically important metabolic pathways and possess unique medicinal properties [ Pinellia ternata had been studied and identified by de novo sequencing and transcriptome analysis [Study on organic acids related genes and enzymes: Li et al. (2017) by analyzing 18 libraries from six organs, namely, roots, stems, leaves, sepals, flowers, and seeds ofx organs . Li et ax organs . Honeysu pathway . Loniceroperties . Also, tanalysis . Ephedra przewalskii Stapf and found that a total of 16,748 coding genes were involved in 125 metabolic process during seed germination, where metabolic pathways (metabolic pathways) were involved in 3,768 genes, accounting for 22.5% of all encoding genes; then the biosynthesis of the secondary metabolites was involved in 1,888 encoding genes, accounting for 11.27% of all encoding genes; the plant hormone signal transduction accounted for 4.54% (761 encoding genes) [ Andrographis paniculata as a large Chinese herbal medicine, there exist some limitations or barriers for crossability within AP accessions, and the problem is solved by using a combination of crossbreeding and genomic data method [ Loranthus seeds and studied the genes regulations of Loranthus seeds in response to water loss, which make a new understanding of drought tolerance and germination of seeds [Over a long period time, the cultivation of Chinese medicinal herbs is still along the traditional extensive management mode with low planting management: the seeds and seedlings are reproduction or retention by farmers themselves, so the phenomenon of gene isolation, degeneration, and poor disease resistance is very serious; due to the long time extensive planting, the phenomenon is more serious especially in some local varieties; these problems are often covered in the appearance that “Chinese medicinal herbs are difficult to grow” and not recognized. Therefore, using the modern transcriptional technology to study the metabolism pathway and regulation mechanism in the stage of seed germination is helpful for genetic breeding and making the key influencing factors clear in breeding traditional Chinese medicine. Ephedra as one traditional Chinese herbal medicine has a history of more than four thousand years. However, the problems of low germination rate, long breeding period, and low seedling survival rate always existed. Deng et al. (2015) studied the seed transcriptome ofa method . Wei et of seeds . The datIn a large number of Chinese herbal medicines, different parts of the same plant can be classified as different Chinese herbal medicines or pieces, and their pharmacological effects are different. The basis of different parts with different efficacy should be caused by difference chemical composition. And the essence is the difference of gene regulatory network of plant metabolism. Therefore, it is of great significance to research the transcriptome and to reveal the different pharmacological mechanisms for the modernization of traditional Chinese medicine. Lotus plumule and lotus leaf are from the same plant, but the efficacies are significantly different. Lotus plumule is cold in property and can soothe nerves and clear away heart fire; lotus leaf is flat in property and can clear away summer-heat and eliminate dampness. Pharmacological aspects also showed that the lotus plumule can be anticardiac arrhythmia, and lotus leaf has obvious pharmacological activities in weight loss and blood fat. Shan studied the basic reason of different pharmacological effects between lotus plumule and lotus leaf. The study found that the different effects were caused by differences in the chemical composition. The bisbenzylisoquinoline and aporphine alkaloids were the major differences in the composition of the two parts. The different expression pattern of NnCYP80A and NnCYP80 in lotus was suggested to be an important factor that leads to the differentiation of components and finally affected the efficacy . This stSyndrome differentiation and treatment as the main method of clinical diagnosis and treatment of traditional Chinese medicine is the essence of traditional Chinese medicine. Because determining the TCM symptoms often lacks an objective standard in a deep level, it is difficult to achieve the objective quantitatively in real sense. Both traditional Chinese medicine and the transcription group focus on integrity, so the introduction of transcriptional group is conducive to the comprehensive treatment of TCM diagnosis and treatment. The transcriptome of kidney deficiency syndrome based on the 3 kinds of diseases  was analyzed, it was found that there were 332 different expressed genes, and the common signaling pathways associated with kidney yang deficiency syndrome were 37 . CompariIn TCM syndrome differentiation and treatment system, syndrome differentiation is very important, but to understand Chinese patent medicine mechanism of action is more important. Huang et al. by gene chip combined with RT-PCR method discovered that Jinlong capsule plays anti-brain-tumor effect maybe through upregulating VNN1 . In the  Lonicera Japonica transcriptome combined with GC-MS and HPLC technology established the relationship between gene expression amount and the content of active substances [The transcriptome research combined with biochemical experimental data can clarify the mechanism of the active components and better explain the profound connotation of the theory of traditional Chinese medicine from the level of gene expression. For example, American ginseng transcriptome studies combined with experiment induced by methyl jasmonate and real-time PCR experiment identified 5 candidate genes involved in the synthesis of ginsenoside . The stubstances . Graham bstances .The transcription group can provide the information of gene expression regulation system (noncoding RNA), all functional protein sequence, and protein interaction . The est Artemisia scoparia in March, wormwood in April, cut as firewood in May”; namely, in the 3rd lunar month, the capillary wormwood herb has excellent efficacy, with the effect of clearing heat and removing dampness, benefiting gallbladder jaundice, and being diuretic and detoxifying; in April, capillary wormwood herb lost medicinal value and slowly grew into the white Artemisia; this is the best time to eat; and in May, the medicinal and edible values have been lost, only “cut as firewood.” Transcriptome sequencing is an immediate expression of plants, so it has a strict requirement for sampling time.Although the research of Chinese medicine transcription has made great progress, at the same time, we should also be aware of some problems. First, the action mechanism of traditional Chinese medicine is multicomponents and multitargets; the pharmacological interaction cross constitutes a complex pharmacology network. Therefore, only studying some chemical composition or certain types of ingredients to elucidate the pharmacology of traditional Chinese medicine is still one-sided. Second, there are many secondary metabolites in traditional Chinese medicine, and the genome is relatively large, which leads to the lack of genome sequencing or complete genome data and brings some difficulties for the data splicing and annotation. Third, the harvest of Chinese traditional medicine pays attention to the right place and right time and one false step in time will make a great difference in efficacy, such as capillary wormwood herb in traditional Chinese medicine, as the saying goes “HerbaThe concept of “omics” in the transcriptome is consistent with the idea of “whole” in Chinese medicine. Along with the continuous progress of sequencing technology, new technology and new method of proteomics, metabolomics, and network pharmacology, the modernization of traditional Chinese medicine will be developed rapidly.


Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in adults over 50 years old. Genetic, epidemiological, and molecular studies are beginning to unravel the intricate mechanisms underlying this complex disease, which implicate the lipid-cholesterol pathway in the pathophysiology of disease development and progression. Many of the genetic and environmental risk factors associated with AMD are also associated with other complex degenerative diseases of advanced age, including cardiovascular disease (CVD). In this review, we present epidemiological findings associating AMD with a variety of lipid pathway genes, cardiovascular phenotypes, and relevant environmental exposures. Despite a number of studies showing significant associations between AMD and these lipid/cardiovascular factors, results have been mixed and as such the relationships among these factors and AMD remain controversial. It is imperative that researchers not only tease out the various contributions of such factors to AMD development but also the connections between AMD and CVD to develop optimal precision medical care for aging adults. Age-related macular degeneration (AMD) is a progressive blinding disease with no cure at present. In its most advanced stages, it deprives an individual of his or her ability to perform basic activities such as reading, recognizing faces, and driving. Approximately 11 million individuals are affected with AMD in the United States (U.S.) alone, with a global prevalence of 170 million. AMD is thereby the leading cause of visual disability in the industrialized world and the third leading cause globally . Aging iAMD is a neurodegenerative disease that preferentially affects the macular  region of the retina, although the reason for this is not clearly understood. The disease is categorized into early, intermediate, or advanced stages based on the severity of symptoms, including the number and size of drusen accompanied by hyper- or hypopigmentary changes and the presence or absence of choroidal neovascularization. The yellowish lipid-rich, protein-containing drusen deposits accumulate between the retinal pigment epithelium (RPE) and Bruch’s membrane and are symptomatic of early disease. Drusen are considered the “hallmark” of AMD. The term “dry AMD” refers broadly to early or intermediate stages as well as a late stage referred to as geographic atrophy (GA). The advanced GA stage involves the loss of RPE and choroid in at least the macular region of the retina, which leads to a gradual loss of photoreceptors and central vision –8. The tPrecise diagnosis and staging requires an ophthalmic exam that includes fundus imaging of the retina for visualization of symptoms such as drusen deposits, pigmentary changes in the RPE, RPE and neural retinal degeneration and loss, and/or exudative changes in the retina Fig.  8, 11–1–111–13. Most current therapies are directed toward the more advanced neovascular (“wet”) stage of AMD, target established abnormal blood vessel growth through antibody-based inhibition of vascular endothelial growth factor A (VEGFA), and demonstrate a range of efficacy. For a small subset of patients, these therapies result in stable to improved visual acuity without the need for ongoing treatment , 18. HowThe development of new therapeutics, both for wet and dry forms of the disease, has received much attention, with the goal that they may ultimately improve outcomes and reduce the burden of treatment on affected individuals  , 21. TheUnderstanding the relationships among diseases that may share overlapping pathophysiology and/or are co-morbid pathologies with AMD could help to uncover disease etiology in AMD. More importantly, because multiple co-morbidities are common among the aging population, understanding any commonalities in disease pathology among these various conditions will also improve the co-management of co-occurring conditions, such as AMD co-occurring with cardiovascular disease (CVD), allowing for synchronous preventative and/or therapeutic approaches.AMD is a complex disease with many genetic and environmental factors, as well as interactions among these many factors, which influence susceptibility to risk –39. SomeHow these genetic and environmental factors influence the development and progression of disease remains largely unknown. One model for the development of advanced neovascular AMD suggests that the accumulation of drusen disrupts the connection between the RPE and the choroidal blood supply, thereby inducing hypoxia. The hypoxia in turn induces the expression of VEGFA and other pro-angiogenic factors to promote the formation of new vessels . This moDrusen are the hallmark lesions of AMD. The size and number of drusen deposits are generally indicative of disease severity and risk for progression to advanced disease , 54. StuApproximately 20 years ago, Dr. Friedman proposed the “hemodynamic model” of AMD after observing similarities between drusen and atherosclerotic plaques, which he updated over the following decade –60. In tGelfand and Ambati recently published a “revised hemodynamic theory of age-related macular degeneration”, adding to this vascular model . They prAdditionally, a growing appreciation for the involvement of chronic inflammation, endothelial dysfunction, and oxidative stress in both AMD and atherosclerosis has shifted the emphasis of these diseases away from being considered simply lipid-deposition diseases . Tan et The prevalence of AMD varies greatly by ethnicity with non-Hispanic White Europeans having the greatest disease burden. In this review, we refer to race and ethnicities as given by the authors of the original studies. We make no attempt to standardize the designations as each study has its own method for classifying participants.A recent study by Wong et al. calculated pooled prevalence of ethnically diverse population-based studies of AMD (age range of 45–85 years) and confirmed that prevalence was greatest among those individuals of European descent at 12.3–30% with increasing age . RegardlATP-binding cassette transporter A-1 (ABCA1), ABCA7, apolipoprotein C2 (APOC2), APOC4, and phospholipid transfer protein (PLTP); the complement pathway VTN gene; and the angiogenesis-associated matrix metalloproteinase-9 (MMP9) gene. MMP9 was shown specifically to be associated with the neovascular subtype and is the first gene to associate with a single AMD subtype. A number of other lipid associated pathway genes were previously shown by GWAS to associate with AMD, including genes encoding apolipoprotein E (APOE), cholesteryl ester transfer protein (CETP), and hepatic triglyceride lipase (LIPC)  have not to date been associated with CVD [Given the complex and heterogeneous nature of both cardiovascular conditions and AMD, it would stand to reason that not all contributions to disease would be common to both conditions. For example, some genes associated with AMD [e.g., with CVD , 201. Hoand risk factor phenotypes into account simultaneously when examining disease outcome.Clarifying the molecular, physiological, and pathological roles in AMD development and progression of each of the factors presented herein is necessary for a complete understanding of this blinding disease. Insights into the underlying molecular influences, including epigenetic influences (such as DNA methylation or histone modifications), on disease progression will also contribute to the development of improved therapeutic interventions. Not only do clinicians and scientists need to understand the various contributions of each factor, but understanding the interactions among risk/protective factors will also be essential to developing precision medicine in the clinical environment. A 2011 paper by Feehan et al.  divided The epidemiological data presented herein must be validated clinically with randomized, double blind, prospective, interventional, controlled trials and biologically with molecular, cellular, and physiological studies in the laboratory to understand the complex pathophysiology and molecular mechanisms underlying the disease process. Such studies are critical for taking current understanding beyond observing disease associations to determining cause and effect relationships underlying disease, which will allow for targeted therapeutic intervention accordingly. Such interventions are crucial for improving the quality of life for millions of patients worldwide.


A paucity of corroborative psychological and psychiatric evidence may be inhibiting detection of drug intoxication suicides in the United States. We evaluated the relative importance of suicide notes and psychiatric history in the classification of suicide by drug intoxication versus firearm (gunshot wound) plus hanging/suffocation—the other two major, but overtly violent methods.This observational multilevel , multivariable study employed a generalized linear mixed model (GLMM) to analyze pooled suicides and undetermined intent deaths, as possible suicides, among the population aged 15 years and older in the 17 states participating in the National Violent Death Reporting System throughout 2011–2013. The outcome measure was relative odds of suicide versus undetermined classification, adjusted for demographics, precipitating circumstances, and investigation characteristics.A suicide note, prior suicide attempt, or affective disorder was documented in less than one-third of suicides and one-quarter of undetermined deaths. The prevalence gaps were larger among drug intoxication cases than gunshot/hanging cases. The latter were more likely than intoxication cases to be classified as suicide versus undetermined manner of death , as were cases documenting a suicide note , prior suicide attempt , or depression , or bipolar disorder . Stratification by mechanism/cause intensified the association between a note and suicide classification for intoxication cases . Prior suicide attempt  and depression  were associated with suicide classification in intoxication but not gunshot/hanging cases.Without psychological/psychiatric evidence contributing to manner of death classification, suicide by drug intoxication in the US is likely profoundly under-reported. Findings harbor adverse implications for surveillance, etiologic understanding, and prevention of suicides and drug deaths. Following a 19% decline between 1986 and the turn of the century, the United States (US) suicide rate rose from 10.40 per 100,000 population in 2000 to 13.75 in 2015—a 32% increase .Suicide is a highly stigmatized and perpetually undercounted phenomenon in the US . FirearmA meta-analysis of 27 psychological autopsy studies  and a syIn this multilevel , multivariable study of the association between psychological/psychiatric documentation and suicide versus undetermined manner of death classification, based on microdata from the US National Violent Death Reporting System (NVDRS), we first calculated the prevalence of a documented affective disorder, suicide note, and past suicide attempt among suicide and undetermined cases. We then evaluated associations between these variables and suicide versus undetermined classification, and whether emergent associations were more paramount among drug intoxication cases than gunshot and hanging/suffocation cases. Our incorporation of undetermined deaths, as well as registered suicides, not only provided a window on the nature of suicide misclassification within the undetermined manner of death category , but witThe principal data source for this study was the Restricted Access Database in the NVDRS, a state, territory, and incident-based surveillance system that employs public health informatics for making data linkages to produce detailed, individual-level information about suicide and other violent deaths . AdminisManner of death (suicide versus undetermined) was the outcome variable. Individual-level predictors were overtness of selected injury mechanisms/causes (gunshot and hanging/ suffocation versus drug intoxication); suicide note (yes versus no or unknown); prior suicide attempt (yes versus no or unknown); and primary mental diagnosis (depression or bipolar disorder versus none or unknown). Other individual-level covariates were autopsy status; current mental health treatment; crisis in past two weeks; number of intimate partner or legal or job or financial or school problems; blood alcohol concentration (grams per deciliter); number of other specified drug positives; physical health problem; age; sex; race/ethnicity; marital status; and education.Linked to the microdata, there were two county-level medicolegal covariates: selection mode (elected or appointed) of the chief medical examiner or coroner and accreditation status/type of medicolegal death investigation system . The data source for selection mode was a CDC website , and thoPursuant to profiling suicides and undetermined cases, we used a generalized linear mixed model (GLMM) to test the respective hypotheses that: among the pooled cases, the designation of a “suicide” manner of death would be more likely when (1) the injury mechanism/cause was gunshot or hanging/suffocation (as more overtly violent methods of suicide), versus drug intoxication; and there was documentation of (2) a suicide note, (3) a prior suicide attempt, or (4) a primary diagnosis of depression or bipolar disorder. Then we tested our final hypothesis that any observed associations, pertaining to hypotheses 2 through 4, were stronger among drug intoxication than gunshot/hanging cases. GLMM is a two-level model, which was logistic at the individual level and linear at the county level. We included a state-level random effect to incorporate the data structure of counties nested in a state and individuals nested in a county. The statistical software was SAS for Windows, version 9.4 .There were 36,190 suicides and 4,391 undetermined deaths in the 17 NVDRS states between 2011 and 2013 . Thirty-The multilevel, multivariable analysis showed that gunshot/hanging deaths were 41 times more likely than drug intoxication deaths to be classified by medical examiners and coroners as suicides —affirminFocus on a comparison of drug intoxication and gunshot/hanging suicides revealed marked differentials in their respective prevalences of a documented suicide note, prior suicide attempt, and a primary diagnosis of depression and bipolar disorder . PrevaleEven the enriched microdata from the NVDRS showed less than one-third of suicide cases included a record of a comorbid affective disorder, prior suicide attempt, or authenticated suicide note, whether written, typed, digital or audio. Signaling complications for suicide accounting and prevention, our multilevel, multivariable analysis leads us to infer that full and accurate accounting of suicide by opioid and other drug intoxication in the US is far more dependent upon corroborative psychological and psychiatric evidence than is that of suicide by the other two major but overtly violent methods, firearm and hanging/suffocation. We hypothesize that absence of such evidence increases the likelihood that drug intoxication suicides are misclassified in the accident manner of death category, as well as in undetermined. Against the background of highly stressed emergency healthcare ,8 and meDuring the late 1980s, CDC convened an expert multidisciplinary panel to develop operational criteria for suicide determination . This paHeterogeneity of forensic investigation systems, within and across states, may impede accurate classification of suicide and other manners of death in the US ,49. WithIn 2015, CDC hosted an expert meeting to commence addressing the inherent challenges fatal opioid and other drug intoxication cases pose for medical examiner and coroners in accurately assigning suicide and other manners of death . Our resThe first multilevel investigation of the association between psychological/psychiatric documentation and suicide manner of death classification in the US, and in the world to the best of our knowledge, this study was able to factor in heterogeneity across precipitating circumstances of death, medicolegal death investigation systems and practices, and demographics. Only the microdata from the NVDRS Restricted Access Database were appropriate for evaluating our research questions. Essential for valid geographic, sociodemographic, and temporal accounting and comparisons, the NVDRS emphasizes uniform protocols for defining manner of death and achieving consistent data collection, entry, review, and coding practices . HoweverNVDRS data do not include staffing and budgetary information on medicolegal offices, and data collection is not yet uniform and standardized for mental health, substance use, and other circumstances of death. Toxicology is nearly complete in drug and other poisoning cases, but fiscal constraints and associated data deficits make coverage problematic for surveillance and research in non-poisoning cases . The “yeWithout psychological/psychiatric evidence contributing to manner of death classification, suicide by drug intoxication in the US is likely profoundly under-reported. Findings harbor adverse implications for surveillance, etiologic understanding, and prevention of suicides and drug deaths.


During its October 2013 meeting, the Advisory Committee on Immunization Practices (ACIP) recommended use of a third meningococcal conjugate vaccine, MenACWY-CRM , as an additional option for vaccinating infants aged 2 through 23 months at increased risk for meningococcal disease. MenACWY-CRM is the first quadrivalent meningococcal conjugate vaccine licensed for use in children aged 2 through 8 months. MenACWY-D  is recommended for use in children aged 9 through 23 months who are at increased risk for meningococcal disease  (2). ThiRecommendations for routine use of vaccines in children, adolescents and adults are developed by the Advisory Committee on Immunization Practices (ACIP). ACIP is chartered as a federal advisory committee to provide expert external advice and guidance to the Director of the Centers for Disease Control and Prevention (CDC) on use of vaccines and related agents for the control of vaccine-preventable diseases in the civilian population of the United States. Recommendations for routine use of vaccines in children and adolescents are harmonized to the greatest extent possible with recommendations made by the American Academy of Pediatrics (AAP), the American Academy of Family Physicians (AAFP), and the American College of Obstetrics and Gynecology (ACOG). Recommendations for routine use of vaccines in adults are harmonized with recommendations of AAFP, ACOG, and the American College of Physicians (ACP). ACIP recommendations adopted by the CDC Director become agency guidelines on the date published in the Morbidity and Mortality Weekly Report (MMWR)http://www.cdc.gov/vaccines/acip.. Additional information regarding ACIP is available at In monthly teleconferences, the ACIP Meningococcal Vaccines Work Group reviewed safety and immunogenicity data from five phase 3 clinical trials of MenACWY-CRM use in infants aged 2 through 23 months –8. Data Neisseria meningitidis serogroups A, C, W, and Y are conjugated to the diphtheria toxin mutant CRM197 ; hepatitis B virus vaccine; measles, mumps, and rubella vaccine; and measles, mumps, rubella, and varicella vaccine were not affected by MenACWY-CRM administration ,those with functional or anatomic asplenia (including sickle cell disease),healthy infants in communities with a meningococcal disease outbreak for which vaccination is recommended, andthose traveling to or residing in areas where meningococcal disease is hyperendemic or epidemic.Routine vaccination against meningococcal disease is not recommended for children aged 2 months through 10 years.MenACWY-CRM may be used for protection against serogroups A, C, W, and Y in infants aged 2 through 23 months who are recommended for meningococcal vaccination because of an increased risk for meningococcal disease . InfantsBecause of differences in serogroup composition and licensure indication, the same vaccine product should be used for all doses in infants at increased risk for meningococcal disease. However, if the product used for prior doses is unknown or unavailable, the vaccination series can be completed with any age- and formulation-appropriate meningococcal vaccine. Although no data are available on interchangeability of meningococcal vaccines in infants, limited data from a postlicensure study in adolescents suggests safety and immunogenicity of MenACWY-CRM are not adversely affected by prior immunization with MenACWY-D .In previous recommendations, children with functional or anatomic asplenia (including sickle cell disease) were recommended to receive 13-valent pneumococcal conjugate vaccine (PCV13) according to the normal schedule but to delay MenACWY-D vaccination until age 2 years because of immune interference .For children at prolonged increased risk for meningococcal disease, ACIP recommends booster doses of conjugate meningococcal vaccine after completion of the primary series. As stated previously , if the


The impacts of optimal infant feeding practices on diarrhoea have been documented in some developing countries, but not in countries with high diarrhoea mortality as reported by the World Health Organisation/United Nations Children’s Fund. We aimed to investigate the association between infant feeding practices and diarrhoea in sub-Saharan African countries with high diarrhoea mortality.The study used the most recent Demographic and Health Survey datasets collected in nine sub-Saharan African countries with high diarrhoea mortality, namely: Burkina Faso ; Demographic Republic of Congo ; Ethiopia ; Kenya ; Mali ; Niger ; Nigeria ; Tanzania ; and Uganda . Multilevel logistic regression models that adjusted for cluster and sampling weights were used to investigate the association between infant feeding practices and diarrhoea in these nine African countries.Diarrhoea prevalence was lower among children whose mothers practiced early initiation of breastfeeding, exclusive and predominant breastfeeding. Early initiation of breastfeeding and exclusive breastfeeding were significantly associated with lower risk of diarrhoea : 0.77–0.85, P<0.001 and OR = 0.50; 95%CI: 0.43–0.57, respectively). In contrast, introduction of complementary foods  and continued breastfeeding at one year  were significantly associated with a higher risk of diarrhoea.Early initiation of breastfeeding and exclusive breastfeeding are protective of diarrhoea in sub-Saharan African countries with high diarrhoea mortality. To reduce diarrhoea mortality and also achieve the health-related sustainable development goals in sub-Saharan African, an integrated, multi-agency strategic partnership within each country is needed to improve optimal infant feeding practices. In the past three decades, the world has made significant improvements in child survival; however, these gains have been disproportionate between and within countries . DespiteIn recent years, an increasing number of studies have reported on the benefits of the breast milk and optimal breastfeeding practices for the mother-infant pair –9. TheseGlobally, various attempts have been made to improve IYCF practices, including the International Code of Marketing of Breast milk Substitutes–The Code, the baby friendly hospital initiative–BFHI, and the Global Strategy for Infant and Young Child Feeding. Sub-Saharan Africa has one of the highest prevalence of breastfeeding at one year worldwide; however, only 37% of infants aged less than six months are exclusively breastfed . Lower pTo date, no studies have investigated the association between these infant feeding practices  and diarrhoea in sub-Saharan Africa countries with high diarrhoea mortality using country-level data. It is important to focus on high diarrhoea mortality countries as these are the population with the one of the largest disease burden in the region, and where interventions would have maximum impacts. Thus, this study aimed to investigate the association between infant feeding practices and diarrhoea in sub-Saharan African countries, with high diarrhoea mortality. Evidence based on local data is important to provide timely, culturally-appropriate and context-specific information to advocate for targeted interventions to improve optimal infant feeding practices , 32.In many sub-Saharan African countries, government expenditure as source  remains low,  despite The most recent Demographic and Health Survey (DHS) data for Burkina Faso ; Demographic Republic of Congo ; Ethiopia ; Kenya ; Mali ; Niger ; Nigeria ; Tanzania ; and Uganda  were used for this analysis. These countries were selected based on a previous study and a report by the World Health Organisation/United Nations Children Fund which indicated that diarrhoea mortality was highest among these countries in the sub-Saharan African region .Diarrhoea was the main outcome in this study, and was defined as the passage of three or more loose or liquid stool per day. Information on childhood diarrhoea was also obtained from mothers, whether each child under-5 years of age in the household had experienced diarrhoea symptoms in the 2 weeks prior to the interview. Additionally, this study restricted analyses to the youngest living child aged less than 24 months, living with respondent (woman aged 15–49 years), and measurement of diarrhoea was based on the child age group for each IYCF practices consistent with a previously published study .The exposure variables were the infants and young feeding indicators , assessed based on the World Health Organisation (WHO) definitions for assessing IYCF practices.  For thisEarly initiation of breastfeeding: The proportion of children 0–23 months of age who were put to the breast within one hour of birth.Exclusive breastfeeding: The proportion of infants 0–5 months of age who received breast milk as the only source of nourishment, but allowed oral rehydration solution, drops, or syrups of vitamins and medicines.Predominant breastfeeding: The proportion of infants 0–5 months of age who received breast milk as the main source of nourishment, but allows water, water-based drinks, fruit juice, oral rehydration solution, drops, or syrups of vitamins and medicines.Continued breastfeeding at one year: The proportion of children 12–15 months of age who were fed breast milk.Bottle feeding: The proportion of infants 0–23 months of age who received any liquid (including breast milk) or semi-solid food from a bottle with nipple/teat.Introduction of solid, semi-solid and soft foods: The proportion of infants 6–8 months of age who received solid, semi-solid or soft foods.A number of potential confounding factors  were considered in the analyses based on previously published studies , 32. Soca priori effect measure modifiers to assess if the association between IYCF indicators and diarrhoea differ by levels of sanitation type and drinking water source. In the DHS, the source of water and type of sanitation for each household were obtained by asking respondents about the ‘main source of drinking water’ and the ‘type of toilet facility’ that were used by household members. The source of drinking water and type of toilet were categorised as ‘improved’ or ‘unimproved’ in this study based on the taxonomy of the World Health Organisation and United Nation Children’s Fund Joint Monitoring Programme (JMP) for Water and Sanitation [The analyses also included a measure of sanitation (type of toilet) and source of drinking water as nitation . ‘ImprovInitial analyses involved a series of frequency tabulations to describe frequencies (and corresponding percentages) for each of the confounding factors  considered in the study. For the pooled analyses, the selected DHS data were combined, and a single model was used to estimate prevalence and standard errors  of infant feeding indicators associated with diarrhoea using the “svy” command to adjust for sampling weights and the cluster sampling employed in the DHS.Multilevel logistic regression models that adjusted for socio-economic, health service, individual and household factors as common causes (confounders) were used to assess the association between infant feeding practices  and diarrhoea in the selected sub-Saharan African countries using “xlogit” command to estimate the relative risks. The modifying effect of the type of sanitation and drinking water sources on the association between infants feeding indicators and diarrhoea was also examined to determine the interaction between the type of toilet use and drinking water sources, and a given infant feeding indicator based on previous reports , 32. TheThe DHS project obtained the required ethical approvals from the relevant research ethics committee in each country before the surveys were conducted. The ethical institutions included: Burkina Faso ; Demographic Republic of Congo (Ethics Committee of the Demographic Republic of Congo Ministry of Planning); Ethiopia ; Kenya ; Mali ; Niger ; Nigeria ; Tanzania ; and Uganda . Participants were informed of the rationale for the surveys, confidentiality of their responses, and that respondents did not need to answer the questions if they do not feel comfortable doing so. Written informed consents were obtained from participants before being allowed in the surveys; and data used in this study were anonymous and are available to apply for online. Measure DHS/ ICF International approved the usage of the data for this study.From the analyses, children aged 0–23 months whose mothers engaged in early initiation of breastfeeding and exclusive breastfeeding practices had a lower prevalence of diarrhoea compared to children whose mothers did not engage in early initiation of breastfeeding and exclusive breastfeeding practices, respectively . A similIn the current study, infants who received breast milk within the first hour of birth were significantly less likely to experience diarrhoea in the selected sub-Saharan African countries compared to those who did not receive breast milk within one of life . SimilarThe analyses testing the modifying effect of sanitation (type of toilet) on the association between infant feeding practices and diarrhoea found that the impact (in terms of effect sizes) of early initiation of breastfeeding and exclusive breastfeeding on diarrhoea prevention were stronger in infants whose households had improved sanitation . The anaThis study found that diarrhoea prevalence was lower among children whose mothers practiced early initiation of breastfeeding, exclusive and predominant breastfeeding. Infants who were introduced to solid, semi-solid and soft foods and those who continued breastfeeding at one year had a higher prevalence of diarrhoea compared to their counterparts. Early initiation of breastfeeding and exclusive breastfeeding were protective against diarrhoea in the selected sub-Saharan African countries, while introduction solid, semi-solid and soft foods and continued breastfeeding were risk factors for diarrhoea. In households with improved sanitary conditions, the protective effect of early initiation of breastfeeding and exclusive breastfeeding against diarrhoea were stronger.Across various levels of development worldwide, the issue of diarrhoea is most common in the poor and less developed countries, indicating that the problem of diarrhoea is a function of many factors. These factors include: socio-economic status, culture, level of health services or capacity of the primary health care , a lack The mechanisms of optimal infant feeding practices in reducing diarrhoea are well-documented , 13, 16.Despite international commitments  to improve infant feeding practices ; improveExisting evidence-based initiatives and policy responses have proven effective in improving infant feeding practices in many developing contexts , 58. FacThe study found no association between predominant breastfeeding and diarrhoea in the pooled analysis, but the association varied in each country studied. Previous studies have revealed that predominant breastfeeding  was protective against diarrhoea, and was associated with higher intelligence , educatiThe introduction of solid, semi-solid and soft foods (complementary foods) to infants around the age of six months is recommended because breast milk alone is no longer sufficient to meet the nutritional requirements of the infant; and continued breastfeeding until the child is two years and beyond. Our analysis showed that introduction of complementary foods and continued breastfeeding at one year were associated with higher likelihood of the child experiencing diarrhoea, consistent with previous studies , 32. EviPotential limitations of the study should be considered when interpreting the findings. We used self-reported outcome measures, a source of measurement bias. The analyses were based on cross-sectional data, which could make the establishment of a causal relationship between the exposures (infant feeding outcomes) and diarrhoea challenging. Seasonal variations has been reported to influence the incidence of diarrhoea in sub-Saharan Africa , and mayThe study has a number of strengths. The analyses were based on in-country nationally representative samples to ensure adequate generalisability of the study findings, and selection bias is unlikely to influence the observed results given the high response rates (96–99%). The data employed were collected using consistent standardised questionnaires, which provide an important source of information on infant feeding practices and diarrhoea in Africa.  This stuThis study showed that early initiation of breastfeeding and exclusive breastfeeding were protective against diarrhoea, while introduction of solid, semi-solid and soft foods and continued breastfeeding at one year were risk factors for diarrhoea in sub-Saharan African countries with high diarrhoea mortality. There is need for an integrated, multi-agency strategic partnership at all levels within each country to ensure improvement in optimal infant feeding practices, with resultant impact on diarrhoea-related morbidity and mortality as well as achievement of the SDGs.S1 Files(DOCX)Click here for additional data file.


Robotic technology has been used in cardiovascular medicine for over a decade, and over that period its use has been expanded to interventional cardiology and percutaneous coronary and peripheral vascular interventions. The safety and feasibility of robotically assisted interventions has been demonstrated in multiple studies ranging from simple to complex coronary lesions, and in the treatment of iliofemoral and infrapopliteal disease. These studies have shown a reduction in operator exposure to harmful ionizing radiation, and the use of robotics has the intuitive benefit of alleviating the occupational hazard of operator orthopedic injuries. In addition to the interventional operator benefits, robotically assisted intervention has the potential to also be beneficial for patients by allowing more accurate lesion length measurement, stent placement, and patient radiation exposure; however, more investigation is required to elucidate these benefits fully. Robotic technology has been used in medicine for several decades, primarily in the fields of surgery9Despite significant advances in pharmacotherapy and interventional device technology, the performance of percutaneous coronary and peripheral vascular interventional procedures has remained relatively unchanged over the past four decades. As a result, significant occupational hazards exist for interventional operators, who are exposed to the risk of both orthopedic and radiation-related complications. The emergence of robotic technology within the field of interventional cardiology provides cardiologists with a novel, safe, and effective tool to provide remote care for patients while reducing the risk of long-term operator harm. Currently, it is approved by the United States Food and Drug Administration (FDA) for both coronary and peripheral vascular interventions.A significant driving force behind the emergence of robotics in interventional cardiology is the growing evidence highlighting occupational hazards associated with the field.Even more concerning are the long-term consequences of chronic exposure to ionizing radiation. These complications include increased risk of cataract development22In addition to the occupational hazard reduction for the operator, using the robotic platform, operators can make precise lesion length measurements, allowing for the selection of appropriate-length stents.24The clinical efficacy of the prototype robotic PCI system was first reported in 2006 by Beyar et al. with clinical and technical success rates of 100% and 93%, respectively.de novo coronary stenosis of at least 50%,27After the first-in-human feasibility study using robotic PCI,P=1.0) was observed in both the robotic and manually treated patients (P=0.005). Further analysis revealed that the increase in procedure time was only observed in relatively simpler lesions while no difference in procedure time existed as the treated lesion complexity increased . Since then several reports have demonstrated the feasibility of robotic PCI for complex procedures including multi-lesion coronary artery disease, allograft vasculopathy, vein graft PCI, unprotected left main PCI, and ST elevation myocardial infarction (STEMI).patients . No diffncreased . An analThus far, the available clinical data for robotic PCI are based on the CorPath 200 platform, which is set up with the robotic arm and operator cockpit being in the same room as the patient. However, a new emerging concept in the field of robotic PCI is remote robotic interventions or “telestenting” where the interventional cardiologist can perform the procedure using a remotely placed operator cockpit in a room removed from the catheterization suite. The feasibility of “telestenting” was recently reported by Madder et al., in a single-center prospective observational study, enrolling 20 patients with obstructive coronary disease.Although the feasibility of robotic peripheral vascular intervention (PVI) was previously reported with the Hansen Magellan robotic system ,We performed the RAPID  trial,Infrapopliteal lesions account for a significant number of PAD treated percutaneously.While robotic PCI continues to show great promise, a number of limitations and hurdles remain. Although the currently available evidence demonstrates the safety and feasibility of robotic PCI for both simple and complex lesions, its utility in certain complex lesions/scenarios—including STEMI, bifurcation disease requiring advanced stenting techniques, severely calcified lesions requiring atherectomy, and chronic total occlusions—remains unclear. Although small series and case reports have shown encouraging results,Finally, the current CorPath 200 system has only been validated with a 0.014-inch guide wire and rapid exchange balloon and stent systems. Further improvements in the robotic platform and system including compatibility with 0.018 and 0.035-inch guide wires, over-the-wire balloon catheters, drug-coated balloons, intravascular imaging catheters, and atherectomy devices will broaden its application. The development of active guide catheter control in the CorPath GRX system has been an eagerly awaited step and should further enhance the use of this technology for the management of patients with complex coronary disease.in vitro model of the aorta, aortic arch, and stenotic valve with a TAVR simulation program have reported improved ability to navigate through the aorta with significant reduction in equipment contact with the aortic wall which could have an impact on embolic cerebrovascular events during the delivery of large equipment and sheaths.Another exciting development in the field of robotics and interventional cardiology is the potential use of this technology in structural heart disease, specifically transcatheter aortic valve replacement (TAVR) procedures. Early studies using a silicone The development and refinement of robotic systems represents the dawn of a new era in the field of interventional cardiology. In the vast majority of patients treated in clinical practice, robotically assisted PCI is safe and results in clinical outcomes comparable to those using a manual approach. The feasibility of robotic PVI has also been demonstrated. Hence, robotic technology offers a potential solution to the occupational hazards facing interventional physicians by limiting radiation exposure and reducing orthopedic strain. In the future, robotics has the potential to expand the availability of PCI to remote areas with telestenting and to address structural heart disease interventions.


In 2010 and supported by the World Health Organization (WHO), the Pan American Health Organization (PAHO) Member States approved the Strategy and Plan of Action for the Elimination of Mother-to-Child Transmission of HIV and Congenital Syphilis with the goal of reducing the incidence of congenital syphilis to ≤0.5 cases per 1000 live births by 2015.Congenital syphilis is a preventable disease, and there must be zero tolerance for its occurrence as even one case represents a failure of the public health system. Health care professionals know what must be done to prevent congenital syphilis and its complications which include stillbirth, prematurity, nonimmune hydrops fetalis, and neonatal mortality.It is clear that pregnant women must have access to early prenatal care and be screened serologically for syphilis at the first prenatal visit and, in high risk areas, again at 28-32 weeks’ gestation and delivery.,In addition to identification of infected pregnant women, timely treatment is mandatory for prevention of congenital syphilis.Penicillin G is the only known effective antimicrobial agent for preventing vertical transmission of syphilis and treating fetal infection.Treponema pallidum in clinical specimens, thus necessitating reliance on laboratory tests that detect maternal nontreponemal and treponemal IgG antibodies transferred transplacentally to the fetus. Nonetheless, the use of IgM immunoblotting, PCR assays, and rabbit infectivity testing  in research laboratories has allowed evidence-based rationale for the management of infants born to mothers with reactive serologic tests for syphilis.-Unfortunately, the diagnosis of congenital syphilis remains problematic due to the inability to detect or culture Neonates with proven or highly probably syphilis, that is, those who have an abnormal physical examination, serum quantitative nontreponemal serologic titer that is fourfold or higher than the mother's titer, or positive darkfield microscopy or PCR of lesions or body fluids/tissues/placenta,in utero infection, almost none will have central nervous system invasion by T. pallidum if their complete evaluation  is normal.The well-appearing infant with a normal physical examination and born to a mother with untreated or inadequately treated (<4 weeks before delivery or any nonpenicillin G regimen) syphilis remains a diagnostic conundrum. However, while as many as 20% of these infants have a positive IgM immunoblot indicative of As syphilis can be a co-factor for HIV infection, all women and their sexual partner(s) who have syphilis should be tested for HIV infection. Infants born to mothers coinfected with syphilis and HIV do not require different evaluation, therapy or follow-up.All infants with reactive nontreponemal tests should receive careful follow-up examinations and serologic testing  every 2-3 months until the test becomes nonreactive. A reactive serum treponemal test beyond 18 months of age when maternal antibodies have disappeared confirms a diagnosis of congenital syphilis, although as many as 20% of infected infants may serorevert completely to nonreactive syphilis serologic tests.,Recently, a penicillin shortage in Brazil and other parts of the world has posed a serious health threat to fetuses and infants of mothers with syphilis. If preparations of penicillin are unavailable, a 10 day course of ceftriaxone can be considered with careful clinical and serologic follow-up, including repeat CSF evaluation.The lack of timely identification and appropriate treatment of infected infants can have profound consequences in later life. Manifestations of late congenital syphilis involve the central nervous system, bones and joints, teeth, eyes, and skin and include Hutchinson's triad , named after Sir Jonathan Hutchinson (1828-1913) from England.Research and humanitarian efforts must continue to control, treat, and eventually eliminate congenital syphilis globally. The public health impact of syphilis in pregnancy and infancy remains substantial, and only through optimal prenatal healthcare services will elimination of maternal-to-child transmission of syphilis become a reality in the Americas.