Novel coronavirus disease (COVID-19) is spreading rapidly and creating a huge economic, social and public health challenge worldwide. Although currently an effective vaccine is ready, its distribution is limited, and hence the only currently available lever to reduce transmission is to identify and isolate individuals who are contagious. Thus, testing for SARS CoV-2 has a paramount importance. However, testing in many African countries including Ethiopia has multidimensional growing challenges. Here, we tried to identify, categorize and summarize the challenges of COVID-19 testing in Africa from Ethiopian experience. Novel coronavirus disease COVID-19) is spreading rapidly and creating a huge economic, social, and public health challenge worldwide [9 is spreOne of the critical challenges we are facing is the inadequate well-trained human capital in terms of sample collection and delivery, testing and test result dispatching: it is well known that quality of sample has a significant impact in the diagnostic accuracy of any diseases . At the Our second challenge is lack of infrastructure: health infrastructure in particular laboratory facilities with trained personnel, is very limited in sub-Saharan African countries . AccordiLack of reference laboratories is also another challenge: the currently available nucleic acid-based tests for SARS CoV-2 can miss 30-40% of those actually infected  because The fifth challenge is cultural values: health seeking behaviour, the concept to disease origin and dynamics in relation to scientific knowledge in African population is low  As a resLast, we also have challenges from the lack of data and weak statistical capacity: the capacity of African countries including Ethiopia in addressing healthcare challenges remains hindered by a lack of data coverage, stemming from weak statistical capacity despite its importance for evidence-based decision-making and policy formulation. Authorities have inadequate access to and use of data and have the problem of using latest statistical methodologies. This represents a significant challenge for the timely production of quality data, which is the most crucial in times of epidemic emergency .In conclusion, the Ethiopian government at various levels is showing high commitment to contain the pandemic before it causes significant damage to the community. The FMOH has prepared national guidelines for disease prevention, patient´s management, and diagnosis to contain the pandemic. Standardized approaches and expanding of laboratory facilities is also ongoing as one of priority areas to speed up testing. However, widespread testing seems impossible for Ethiopia unless all barriers and bottlenecks are critically considered and managed properly.Therefore, we recommend the followings points for health authorities to take immediate actions: 1) They should enhance integrated capacity building both in human capital at various levels of the process and infrastructure development; 2) Technology based data collection system, tracking and communication system needs to be strengthen; 3) They should strengthen emergency use authorization without compromising quality; 4) Expanding testing facilities and encouraging the use of alternative testing methods such as pooling both at direct biological samples and nucleic acid (RNA) shall be started; 5) Establishing reference laboratory which design, implement, and monitor both internal and external quality control tests shall be enhanced; 6) Rapid adoption and validation of point of care tests for diagnosis of COVID-19 in our country shall be encouraged; 7) Integration of SARS-CoV-2 diagnosis with existing platform which are already widely used for TB & HIV testing shall be implemented; 8) Looking for more funds and support from international agencies and donors to support establishment of testing site and maintain testing service without interruption shall be enforced.


Know your enemy (the disease and pathogen) through supporting innovative research. Government and the industry should invest strongly and continuously in research related to African swine fever. Important research areas include African swine fever virus (ASFV) biology, ASFV-host interaction, point-of-contact diagnostics, safe and efficacious vaccines, swine farm biosafety and biosecurity risk management systems, and high containment facilities that are suitable for African swine fever research.Science and technology alone are not enough without purpose and direction. All stakeholders of the swine industry should develop and enact science-based policies on foreign animal disease outbreak emergency management.To eradicate swine fevers, leaders of the swine industry and governments should work together. Governments should ensure their goals and policies are fully supported by swine farm owners, farm employees, pork processing plants, animal health companies, veterinarians, regulatory agencies, social media, and the public.The transboundary nature of emerging and re-emerging high consequence animal infectious disease threats requires global cooperation. This international cooperation should be not only in outbreak management, but also in research for a broader biomedical, social, and ecological understanding of disease systems.John Steinbeck drew the title of his novel “Of Mice and Men” from a line in a Robert Burns poem “To a mouse”: “The best-laid plans of mice and men/Go often awry.” Unlike John Steinbeck who used the title to mirror the characters who were struggling during the Great Depression to the mouse whose nest was accidentally destroyed by the poet , we chosSwine fevers and swine flu are different diseases caused by completely different viruses. However, swine fevers and swine flu are often regarded as the same disease by the public. This is in part due to the 2009 H1N1 influenza pandemic where the human influenza virus contained genetic segments from the swine influenza virus . Swine fVaccines are the most cost-effective tools for animal infectious disease control and prevention in disease-endemic regions. Based on the nature and/or production method of antigens, vaccines can be classified into five different categories: 1) tissue-derived vaccines (inactivated or live) with little or no antigen purification; 2) inactivated vaccines in which pathogens are inactivated by the chemical methods after they are processed from cell culture or fermentation systems; 3) MLV vaccines with naturally or genetically modified attenuated live microbes; 4) subunit vaccines in which the antigens are purified from native pathogen cultures or recombinant expression systems; and 5) nucleotide (DNA and RNA) vaccines in which partial genetic segments from the pathogens are used to directly induce antigen expression in the immunized animal or incorporated into microbial vectors for antigen expression and delivery.The selection of a certain type of vaccine for field use in animal disease control and prevention should be based on its safety and efficacy profile and cost-effective analysis, not how the vaccine is produced. The first three categories  of vaccines have been used in the field since the late 1800s and the last two categories of vaccines (subunit and nucleotide) were developed with new technologies in the last few decades . For manIn addition to vaccines, diagnostics are also essential tools for animal disease control and prevention. For antigen/pathogen detection, antigen capture antibody enzyme-linked immunosorbent assay (ELISA), real-time quantitative polymerase chain reaction (PCR), lateral flow assay (LFA), and a fluorescent antibody test (FAT) are routinely used in a laboratory setting. Various forms  of ELISA have been developed to detect antigen/pathogen-specific antibodies in animals after vaccination or infection. Virus serum neutralization assays (and surrogate assays like hemagglutination inhibition) are still very useful for characterizing antibody responses.Diagnostics that can differentiate infected from vaccinated animals (DIVA) are crucial tools for animal disease control and eradication. DIVA assays are extremely useful for the control of a newly emerging infectious disease or a foreign animal disease as they can enable the “vaccinate-to-live” strategy by which vaccinated animals can be raised and processed for food production and consumption and/or international trade. Genetic DIVA assays are designed to identify the genetic difference between a vaccine antigen and a virulent field pathogen. Serological DIVA assays target the difference in host immune response to the vaccine strain (after vaccination) and virulent field strain (after infection).Pigs with CSF, also known as hog cholera, have clinical signs such as high fever, loss of appetite, lethargy, and high mortality rate. CSF/hog cholera was first reported in the Ohio river valley in the 1830s, and it still causes significant economic losses to the swine industry in Asia and presents a significant agricultural security threat to CSF-free countries such as the United States. CSF is probably one of the earliest swine viral diseases identified by animal disease researchers in the early 20th century. It was the United States Department of Agriculture (USDA) scientists Emil Alexander de Schweinitz and Marion Dorset who first demonstrated in 1903 that the highly contagious hog cholera was caused by a virus (not a bacterium) and hogs that survived from the infection were immune from future infection .Hog cholera/CSF caused devastating losses to American swine producers since the late 1800s. According to USDA’s historical data, “Outbreaks in 1886, 1887, and 1896 each killed more than 13% of the Nation’s hogs; more than 10% died during the 1913 outbreak. The disease was still costing producers $50 million a year in the early 1960’s” . Around Although the eradication of CSF from the United States in 1978 was a great success story, one must remember that many important pieces of research were carried out before the 17-yr effort (1961 to 1978), with the support from the pork industry as well as State and Federal governments. After the initial federal ban (1963) on interstate shipment of virulent CSF virus or of feeder pigs and breeding stock vaccinated with CSF vaccines, use of MLV vaccines and inactivated vaccines continued until banned in 1969 . Most ofActions and governmental regulations associated with CSF control in the United States played an important role in the development of animal health policies in general. Since the discovery that pigs injected with hyperimmune serum could be protected from CSF virus challenge in 1907 , anti-hoGiven the social and economic importance of pork production in the United States at the beginning of the 20th century, perhaps it was not a surprise that one of the earliest anti-hog cholera serum plants in the Kansas City area was created by Mason Peters, a lawyer and former U.S. congressman in Kansas . He saw Furthermore, the Virus-Serum-Toxin Act, which enacted federal regulation of veterinary biologics in 1913, was passed largely because of public concerns over the safety and efficacy of veterinary vaccines from Europe and hog cholera products being produced and marketed across the country . The newThe successful eradication of CSF in the United States was the result of a determined and comprehensive approach including 1) more than 60 yr of scientific research and development on CSF virus and the disease management tools ; 2) science-based regulatory decisions from all levels of government; and 3) the public and private partnership of all stakeholders related to the swine industry. We can summarize the best-laid plan in CSF prevention and control (the U.S. story) as:Know your enemy (the disease and pathogen) through supporting innovative research.Develop and implement science-based governmental policies at both state and federal levels.Ensure the cooperation of all stakeholders of the pork industry including pig producers, animal health companies, veterinarians, and regulatory agencies.It has been clearly demonstrated that CSF can be eradicated with less ideal tools (vaccines and diagnostics) in a country with large and intensive swine production systems. Nevertheless, CSF remains one of the most devastating diseases of swine in many other large pork-producing countries such as China, Vietnam, Thailand, Japan, South Korea, and the Philippines. This phenomenon is intriguing as these countries have produced or have had access to the C-strain CSF vaccines that are affordable, available, safe, and efficacious against all known genotypes of the CSF virus.rns  has been recently generated by our group (rns-specific mAb. This is an example of a positive DIVA marker.The C-strain MLV vaccine is an attenuated live virus and can provide complete protection against wild-type CSFV with the onset of effective immunity just 5 d after vaccination . The onlur group . A cELISWith the help and guidance from the Food and Agriculture Organization (FAO) and the World Animal Health Organization (OIE), many if not all CSF endemic countries in Asia have developed national policies for CSF control and eradication . Thus, iThere is no doubt that CSF outbreaks can be effectively controlled by routine and high coverage vaccination with the C-strain vaccine, but the success of this approach requires government support in providing sufficient and qualified field veterinarians and establishing an effective disease diagnostic and epidemic information network. More importantly, the government at all levels  should provide sufficient technical support and financial compensation to swine producers whose pigs might have to be culled due to localized CSF outbreaks. Furthermore, government, industry associations, and the media can also play an important role in raising public awareness that CSF can and should be eradicated soon. Without an effective eradication plan, CSF will continue to negatively affect general consumers due to pork price increase and overall inflation when pork production is disrupted by disease outbreaks.Thus, the eventual eradication of CSF from CSF endemic countries may depend on whether and when all stakeholders of the pork industry can form a real partnership and work cooperatively for the same goal. To make this partnership effective, pork producers and animal health companies also must equally contribute to control and eradication efforts. These efforts will include strict compliance with government regulations on vaccination and animal movement; eliminate production, marketing, and use of CSF vaccines when a vaccination ban is placed in effect in the final stages of a CSF eradication plan.Although CSF and ASF share similar clinical signs such as high fever, loss of appetite, lethargy, and high mortality rate, these two diseases are caused by two distinct and unrelated viruses. The CSFV is a small (12.3 kb) RNA virus with only four structural proteins, while the ASFV is a large DNA virus (170 to 190 kb genome) with more than 50 structural proteins . Since AThree conditions might explain why ASF research in China was not a priority before 2018: 1) limited preparations for ASF research—there were very limited high containment (biosafety level 3) research facilities in China that were available for animal studies on foreign animal diseases such as ASF; 2) false security—CSF and foot and mouth disease (FMD), two other highly contagious and devastating swine viral diseases are largely controlled in China via mass vaccination; and 3) false optimism—because ASF has been largely eradicated in Europe in the 1990s, it was not hard to imagine that ASF could be controlled quickly by culling pigs infected with ASF virus. Consequently, research on ASF as a foreign animal disease was not carried out as a priority in China to develop the tools essential for the prevention and control of ASF.https://finance.huanqiu.com/article/9CaKrnJY1uN and http://www.cpwnews.com/content-23-9199-1.html), the General Administration of Customs of China (GACC) and the Ministry of Agriculture (MOA) organized several ASF-specific emergency response drills in northern provinces and cities including Inner Mongolia, Hebei, Beijing, and Tianjin in 2016 and 2017. The risk of importing transboundary animal diseases associated with the “One Belt One Road” Initiative (BRI) was highlighted as the rationale behind these exercises.Before the rapid spread of ASF in China that was first reported in August 2018, policymakers in China were aware of the serious threat of ASF and had implemented an ASF-specific national policy—“Technical Specification for Prevention and Treatment of African Swine Fever” in 2015 . Based ohttps://www.sohu.com/a/238415268_267831?_f=index_pagerecom_417). However, what happened next was puzzling: the second ASF case was confirmed 12 d later in Zhengzhou (http://www.xinhuanet.com /fortune/2018-08/16/c_1123281884.htm), which is 1300 km south of Shenyang.Although no direct evidence that ASFVs were introduced to China via commercial activities of the BRI, there are two intriguing relevant observations: 1) the first ASF outbreak was likely started in mid-June  on a swine farm in the outskirts of Shenyang , the proIt is even more troubling and puzzling that tens of millions of pigs were lost due to ASF outbreaks all over China and some of its neighboring countries in less than 1 yr. These losses probably eclipsed the total number of pigs lost on the entire planet to ASF over the previous 90 yr. ASF meetings in China were often packed with hundreds of swine producers with the hope to find a miracle weapon to control or prevent ASF on their farms . WithoutAfter ASF outbreaks started in China, swine producers quickly learned that, unlike CSF or FMD that could be effectively controlled by mass vaccination, there is no commercial ASF vaccine in the world. Without a tool to implement a “vaccinate-to-live” policy, millions of pigs were culled in the early days of ASF outbreaks in China. Although this control measure seems to be in line with OIE and FAO guidelines, the losses and disruption it created soon became unbearable for at least two reasons: 1) the social and economic impact associated with the huge increase of pork price in a few months after the number of pigs available for the market was reduced quickly and dramatically, and 2) the environmental risk associated with disposing of thousands of pigs on farms in a short period of time.Without an available safe and efficacious vaccine, swine producers quickly realized that they have to significantly improve biosafety and biosecurity measures on farms to prevent the introduction of ASFV, and use “targeted culling—pull the bad tooth” to remove ASFV infected pigs from the facility to avoid further disease spreading and to preserve the herd. “Reopening” some of the infected farms for production became possible after carrying out intensive disinfection of the infected facility. In addition, significant changes have to be made in biosafety practices to minimize the risks associated with many factors associated with swine production. These risk factors include culled pigs, lagoons, pigs and feed purchased from outside suppliers, selling pigs to others (trucks and personnel from outside vendors), drinking water, boots and coveralls, insects, rodents and pests on farms, swine semen, and use of veterinary pharmaceuticals and vaccines. Implementing policies to incentivize employees to follow biosafety rules and remodeling the current facility for better biosafety control are also common practices for many swine operations. However, many of these changes are very costly and can only be effectively managed by well-funded large operations. Nevertheless, various “Reopening” or “Re-grow” plans have been developed and tested to raise pigs before a highly efficacious vaccine is available.If a successful plan for ASF prevention and control could be developed, it should resemble the plan that facilitated the U.S. eradication of CSF more than 40 yr ago. Briefly:Know your enemy (the disease and pathogen) through supporting innovative research.Invest strongly and continuously in research related to ASFV, ASFV–host interaction, point-of-contact diagnostics, safe and efficacious vaccines, swine farm biosafety and biosecurity risk management systems, and high containment facilities that are suitable for ASF research.Develop and implement science-based governmental policies at both state and federal levels.Develop and implement science-based animal disease outbreak emergency management policies that will encourage the full participation and support of pork producers and consumers: swine farmers, pork processing plants, and the public. These policies must consider: 1) what will happen if the government does not compensate swine producers for their loss due to ASF outbreaks? 2) how can swine farmers properly cull/dispose of thousands of pigs in a short period of time?, and 3) how do the processing plants/slaughterhouses deal with ASFV positive products?Ensure the cooperation of all stakeholders including pig producers, animal health companies, veterinarians, regulatory agencies, social media, and the public.Because the public is a significant stakeholder of the pork industry, it is not enough to tell the public that ASFV does not infect people. Instead, the swine industry should educate the public that ASF outbreaks affect the livelihood of many parts of the society including swine producers, workers on the farm, grain and feed producers, pork processing plants, grocery stores, truck drivers, animal health companies, restaurants, international and regional pork/grain/feed importers and exporters, and all consumers of pork products. Animal health companies should only manufacture and sell safe and efficacious ASF vaccines, and swine producers should only use authorized ASF vaccines. Veterinarians should employ only field tested, effective immunization, and biocontrol practices. Additionally, ASFV positive products should not be produced, transported, sold, or consumed by anyone. Swine production security is a “weakest-link in the chain” problem. Therefore, the only way to achieve long-lasting security of the system is to improve the strength of the weakest link through full cooperation and regulatory compliance among all stakeholders.CSF and ASF are swine viral diseases with high consequential social and economic impacts in endemic countries. Successful prevention and control of ASF and CSF requires not only safe and efficacious vaccines and fast and accurate diagnostic tools but also science-based government policies that ensure the cooperation of all stakeholders of the swine industry. Science and technology alone are not enough without the effective partnership of the public.Despite recent devastating outbreaks of ASF and CSF in Asia, the countries of North America and Europe demonstrated decades ago that ASF and CSF can be eradicated with proper government policy and adequate scientific and technological tools. The world has indeed changed since then, notably with ever-increasing high-density swine production and globalization, which demands more innovative approaches to solve new problems:What is the best way to cull/dispose of thousands of pigs in a short period of time in a restricted area to take into consideration of animal welfare, economic and environmental impact, and technical feasibility?Because large quantities of various disinfectants are used to inactivate the ASFV on swine farms, the negative impacts of these biosafety measures on environment, food safety, and human health should be carefully investigated.The transboundary nature of emerging and re-emerging high consequence animal infectious disease threats requires global cooperation not only in outbreak management, but also in research for a broader biomedical, social, and ecological understanding of disease systems.


We examine the relationship between social integration and cognitive impairment and dementia among older adults using longitudinal data from Waves 1-8 of the National Health and Aging Trends Study (NHATS). The sample includes 7,492 respondents age 65 and older at baseline. We test multidimensional measures of social integration and cognitive well-being using discrete-time hazard models. The risk of dementia is calculated by a series of performance-based tests. Measures include levels of dementia: no dementia, cognitive impairment not dementia (CIND), and dementia, and three domains of cognition functioning: orientation, executive function, and memory. Social integration is an additive index measured by several questions, including marital status, living arrangement, social network, social contact, and social participation. Our results indicate that people with higher social integration have a lower risk of both cognitive impairment (not dementia) and dementia compared to those with lower social integration. This pattern continued across specific domains of cognitive functioning, including lower risk of orientation impairment, executive function impairment, and memory impairment for those with higher social integration. Tests of both gender and racial interactions did not yield any significant differences. Our findings demonstrate the strong association between social integration and lower risk of dementia among older adults. This study can speak to policy makers as the life expectancy of Americans increases and the aging population grows, highlighting the importance of giving support to older adults who are lack of social connectedness.


Substantiation of abuse, neglect, and exploitation (ANE) data collected during the Identification, Services, and Outcomes (ISO) Matrix pilot included some outlier scores warranting further investigation. To examine outliers and other unexpected findings in greater detail, we completed case reviews and caseworker interviews to explore why outlier cases did not follow the expected patterns of substantiation decisions. Cases were selected on a random basis from those with self-neglect outlier scores. Several factors were found to have contributed to the extreme scores in all three categories of confirmed, inconclusive, and unfounded abuse. In this study, no valid ISO Matrix scores were found that contradicted the substantiation decision. Instead, analysis revealed that most of the errors occurred: 1) in application of the intended procedures showing need for further training, and 2) some needed changes to the procedures of the ISO Matrix based on feedback from caseworkers.


Background: In the United States, hepatocellular carcinoma is the ninth leading cause of cancer mortality. Hepatocellular carcinoma disproportionately affects individuals of African ancestry with the rates being higher amongst individuals of foreign-born African ancestry. This study explored knowledge, attitudes, and behaviors toward viral hepatitis transmission, screening, and vaccination among recent African immigrants in Minnesota and identify ways to improve early detection and screening methods.Methods: A community based participatory research (CBPR) team with minority researchers and community members sought to gain insight on persons of African Ancestry knowledge, attitudes, and behaviors related to viral hepatitis by conducting a qualitative research study. The CBPR team developed a focus group moderator's guide with semi-structured questions related to transmission, screening, and vaccination of viral hepatitis. We conducted seven focus groups using bilingual, bicultural moderators with participants from local Ethiopian, Liberian and Kenyan communities from August 10th, 2014 to October 11th, 2014. Focus groups were audio recorded and transcribed. The CBPR team categorized the data into themes and subthemes with consensus using traditional content analysis.Results: Community partners recruited 63 participants with a majority identifying as male (51%). Participants lacked knowledge of viral hepatitis screening, vaccination, and treatment. Participants were aware of some behaviors that increased risk of acquisition of hepatitis. Participants endorsed a strategy of developing and delivering educational materials for African immigrants. Moreover, access to care and cultural awareness were mentioned as pivotal for prevention and treatment of viral hepatitis.Conclusions: Findings from this pilot study provide insight on areas of research focus. Having a research team consisting of members from the community helped to increase trust and foster an understanding of shared community values. Information from this study provides evidence to support the development culturally appropriate strategies to address disparities in viral hepatitis in these communities. Hepatocellular carcinoma (HCC) is the most common primary cancer of the liver  and has The 2012 Cancer Report by the Minnesota Department of Health reported the incidence and mortality rates due to liver cancer among the Black population were higher than their White counterparts . AfricanThe incidence of HCC in the African continent is increasing due to rising numbers of viral hepatitis infections –17. ThesA recent hospital-based study examined HBV and HCV infection among Somalis seen at Mayo Clinic and compared them to non-Somali Olmsted County residents (90% of whom were White). Among Somalis, the adjusted-frequency of HBsAg positivity (chronic HBV) was 10-fold higher than in non-Somalis, HBcAb positivity (prior HBV exposure) was 5-folder higher than in non-Somalis and anti-HCV positivity (chronic HCV) was 3-fold higher than in non-Somalis . SubsequThe purpose of this study was to identify societal and cultural barriers to the prevention, screening, and treatment of viral hepatitis in African immigrants and refugees in the United States. We conducted a qualitative pilot study to assess the knowledge, attitudes, and behaviors of African immigrants (AI) to provide pilot data for the eventual development a community-engaged intervention to (a) increase awareness and (b) reduce the burden of viral hepatitis and HCC in these communities.A CBPR partnership formed in 2013, called Somali Health Advisory Council (SHAC), between an academic medical center and three AI communities in Minnesota. The research team included members from Mayo Clinic Rochester and AIs from Ethiopia, Liberia, and Kenya. The Mayo Clinic Institutional Review Board approved the study. The team jointly designed the study and selected a qualitative research approach using focus groups to address the specific aims.The SHAC designed the recruitment process with the research team. We used purposive sampling  and planFocus groups allowed for observations of non-verbal behaviors and interactions as well as group dynamics and to elicit shared cultural meanings . The focSeveral study participants had low levels of English proficiency. To ensure participants understood the risks and benefits of our study, the purpose of the study was stated in their native language by an interpreter. Participants provided written informed consent and received a copy of the informed consent form. Participants received a $20 gift certificate and a light meal for their time.Prior to starting the focus group discussions, facilitators (a) introduced themselves, (b) outlined the structure of the focus group, (c) instructed in the importance of confidentiality, and (d) collected selected sociodemographic information through a brief survey.Focus groups facilitated in native language were transcribed verbatim and translated into English by WG and LT. Data were de-identified and unique IDs given to each participant and moderator. Participants were asked general questions pertaining to beliefs of health which progressed to specific questions pertaining to viral hepatitis and liver cancer . The focMembers  from the research team independently conducted initial review and coded transcripts. The research team used a strategic validation process to ensure that inductive thematic saturation was reached. Preliminary thematic groups were generated and were linked to interview texts. Emerging themes were discussed and presented at team meetings. During these meetings, discordant codes were discussed until consensus was reached. Differences between the three community groups and by gender were explored.n = 63) from the three AI communities. Participants self-identified as Ethiopian-Amhara, Ethiopian-Oromo, Liberian, or Kenyan. Males constituted about half [32 (51%)] and the mean age ± SD was 46.6 ± 19.4 years. Eleven percent of participants reported not having medical insurance and the mean ± SD years lived in the US was 12.2 ± 6 years. Approximately a third had completed college and 16% had postgraduate training . In total, seven focus groups were conducted  lack of knowledge of viral hepatitis; (b) cultural and societal barriers associated with viral hepatitis; and (c) need for culturally relevant health education. There were no differences noted between communities or by gender, thus the results are consistent for the three communities.The knowledge of viral hepatitis across indicated limited understanding and awareness of the infection . Most paI don't think any community is fully familiar with knowledge about hepatitis, whether it's A, B, C.” Moreover, several participants did not know the exact location or understand the basic function of the liver and had little understanding of the impact of liver disease on health.When asked, “What is viral hepatitis?” several members mentioned they did not know what viral hepatitis is and needed more information. For instance, one participant mentioned, “there are different types of hepatitis and that it can be transmitted” but “didn't have access to information about the different kinds.” Others mentioned a person might feel fatigued, have an enlarged stomach, and yellow coloration of skin and eyes. However, participants were unaware that most chronic viral hepatitis is asymptomatic and symptoms arise after the liver is compromised for several decades.When asked what cultural practices contribute to liver disease progression, most participants were aware that alcohol consumption led to long-term liver disease and associated complications. There was lack of awareness of secondary and tertiary prevent once a person is diagnosed with hepatitis by some participants. One participant maintained that “through kissing or through handshakes,” while another stated it is “transmitted through coughing” (airborne). Others were convinced the acquisition and transmission viral hepatitis was through “starvation,” likening the round belly of a liver disease patient to a starving child's belly.Participants expressed a wide range of responses and evident confusion regarding modes of viral hepatitis acquisition. Several examples participants mentioned were sexual contact, bodily fluids, and blood transfusions. A participant stated viral hepatitis is contracted “Participants discussed the role of cleanliness in reducing viral hepatitis transmission. Others further suggested changing dietary habits , utilizing clean syringes, reducing smoking habits and exercising regularly. However, some believed minimizing alcohol consumption reduced the risk of developing liver disease and viral hepatitis.birdheellee”; Amharic: “bird's disease”). In the Liberian group, the general term used to describe viral hepatitis was “yellow jaundice.” Most participants believed viral hepatitis was a disease not necessarily infectious; however, a small proportion felt it was infectious.Viral hepatitis is a complex set of infections not quite understood by the three communities. From the focus group discussions, participants lacked awareness of the scientific terms associated with the infection. Across the different communities, descriptive terms for viral hepatitis were related to symptoms of disease . Lastly, several participants felt it is important for individuals to start discussing the infections freely to increase awareness and save lives are saved. More importantly, participants recognized that the need to address traditional medicine and use of herbs to treat hepatitis.To our knowledge, this is the first qualitative research study examining knowledge, attitudes, and behaviors toward viral hepatitis amongst recent AIs in Minnesota. The findings illustrate that general knowledge of viral hepatitis transmission, prevention, and liver disease progression is poor among the three AI Minnesotan communities. The novel findings of this study were: (a) the willingness of participants to learn about these infections, the progression and development of disease, and optimal means of prevention and disease management, and (b) the open and welcoming attitude of the participants toward receiving screening for HBV and HCV in their community settings.Various barriers to accessing care for viral hepatitis and liver disease within AI communities were described. One study assessing barriers to screening and vaccination amongst Korean-Americans identified lack of adequate health insurance, culturally competent providers, and a culturally specific notion of when one needs to access care as contributors to this disparity . This waOverall, knowledge of viral hepatitis in the AI communities studied was quite minimal. Previous studies have shown that immigrant Asian and African communities have low levels of understanding of the causes and risk factors for liver cancer –32. In aOur results indicate that participants had some level of understanding of the various modes of transmission of HBV and HCV. However, further education is needed to reinforce and enhance understanding of the different modes of transmission. This was evident as several participants mention that coughing and kissing were methods of contracting the infections. In addition, the lack of symptoms in the early stages of viral hepatitis appeared to be a barrier to seeking screening, as many participants expressed that people in their communities only seek health care for symptomatic illness. This supports previous research showing that lack of symptoms contributes to and increases the reluctance to seek screening –40.In our study, access to medical care was linked to legal documentation status. According to the African Migration Insider, ~200,000 Kenyan nationals living in the US do not have proper documentation . This waAnother subtheme that emerged as a barrier is language and understanding. This notion is quite consistent with previous research –51. WaysThe limitations of our study are that it is not generalizable to the larger United States AI populations. Recruitment for the focus groups was limited by the sample size, as this was a pilot study with insufficient resources to conduct additional focus group sessions to allow for a more comprehensive comparison between groups . Moreover, the focus group participants were self-selected and may not represent the majority of the population. However, there were specific themes that were repetitive across the different focus group sessions.General knowledge of viral hepatitis transmission, prevention and liver disease progression is not well-understood among the AI communities in Minnesota. Similar studies were conducted in West Africa and Afro-Caribbean/Afro-Latinx populations. To our knowledge this is the first study to assess the perceptions and behaviors of viral hepatitis in an East African population, in particular from Kenya and Ethiopia. Although, Liberians are of West African descent, this study sought to determine the unique cultural and societal barriers to receiving treatment for viral hepatitis infection in this community. Currently, studies conducted in the United States on viral hepatitis infection fail to consider the disease implications for the AI community. A recent study by Ogumwobi et al. found that first generation African immigrants had limited knowledge the acquisition of hepatitis B . Thus, tAll datasets generated for this study are included in the article/All study protocols, involved human participants, were approved by the Mayo Clinic Institutional Review Board and were in accordance with the ethical standards of the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. This article does not contain any studies including animal subjects. All participants provided written informed consent and received a copy of the informed consent form.EM, NG, and HS contributed to study concept and design, acquisition of data, data analysis, interpretation of data, and drafting of the manuscript. LK, HK, WG, LT, AO, HA, IW, LA, AW, HAA, HMA, and SM contributed to study concept and design, acquisition of data, interpretation of data, and critical revision of the manuscript. JY and CP contributed to study concept and design, interpretation of data, and critical revision of the manuscript. LR and JB-B contributed to study concept and design, interpretation of data, critical revision, and final approval of the manuscript. All authors contributed to manuscript revision, read, and approved the submitted version.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.


Social media has substantially changed how people confront health issues. However, a comprehensive understanding of how social media has altered the foci and methods in public health research remains lacking.This study aims to examine research themes, the role of social media, and research methods in social media–based public health research published from 2000 to 2018.A dataset of 3419 valid studies was developed by searching a list of relevant keywords in the Web of Science and PubMed databases. In addition, this study employs an unsupervised text-mining technique and topic modeling to extract research themes of the published studies. Moreover, the role of social media and research methods adopted in those studies were analyzed.This study identifies 25 research themes, covering different diseases, various population groups, physical and mental health, and other significant issues. Social media assumes two major roles in public health research: produce substantial research interest for public health research and furnish a research context for public health research. Social media provides substantial research interest for public health research when used for health intervention, human-computer interaction, as a platform of social influence, and for disease surveillance, risk assessment, or prevention. Social media acts as a research context for public health research when it is mere reference, used as a platform to recruit participants, and as a platform for data collection. While both qualitative and quantitative methods are frequently used in this emerging area, cutting edge computational methods play a marginal role.Social media enables scholars to study new phenomena and propose new research questions in public health research. Meanwhile, the methodological potential of social media in public health research needs to be further explored. Social media has deeply penetrated people’s lives in many aspects. In developing and developed societies, social media has played a significant role in health management and disease control . Social Agencies widely use social media to fulfill different health purposes. For the general public, social media is used to satisfy its orientation for health information, linking with health services and communication with others who share the same health interests . For pubThese studies have demonstrated the increase of scholarly interest in empirical research conducted on social media platforms with public health goals, including the social media–based public health research in this study -21. AlthFurthermore, most prior systematic reviews have adopted a top-down approach and therefore may have narrowed the view by overlooking certain nuances and novelties that have been emerging. This study adopts a bottom-up approach  to underRQ 1: What are the major publication trends of social media–based public health research since 2000?RQ 2: What are the major research themes in social media–based public health research since 2000?RQ 3: What role does social media play in social media–based public health research since 2000?RQ 4: What are the major research methods adopted in social media–based public health research since 2000?To examine how social media has been adopted and integrated into public health research, a list of terms was identified and the Web of Science  and PubMed databases were searched see . Lists oThe lists of disease and social media keywords were combined pairwise and submitted to search titles, abstracts, and keywords of published studies in the databases of the Web of Science and PubMed. The publication period was limited to between 2000 and 2018. The article language was limited to English, and document type was limited to scholarly journal articles. Considering the PubMed database includes numerous medical and clinical studies that are beyond the research scope of this study, the search results were refined by setting the broad subject terms as related categories, such as public health and medical informatics to reduce the noise in the search results. This search strategy led to the identification of 5271 articles in the two databases. Then, another round of data checking to remove unqualified studies such as non–social media–related articles, duplicate records, and clinical studies was implemented. Finally, a dataset of 3419 articles was collected for further analysis. Ultimately, document level information of the 3419 articles from the databases, including authors, article title, journal title, abstract, author keywords, and cited references, was retrieved.An automatic text-mining approach was adopted to extract research themes in the field of social media–based public health research. As the abstracts of published studies conveyed the themes or foci of the articles , the artNumerous LDA topic models were estimated with various numbers of topics. These models were evaluated on the basis of three main criteria: (1) a substantial proportion of articles exists under each topic, (2) themes show independence with one another and the lists of top terms of topics are not highly overlapped or not relevant, (3) models differing in theme number are compared to identify the nuanced differences and determine the best theme extraction by assuring that each term list is coherent. Finally, a topic model with 25 topics, which presented adequate discrimination between topics and convergence within a topic, was selected. The articles were classified into the research theme with which they had the greatest probability scores.To understand how social media has been integrated into public health research with different thematic foci, a manual content analysis was conducted among a randomly selected sample of 500 abstracts (20 from articles in each theme) to understand the role of social media. A coding scheme was developed by two authors of this study. The two authors first separately coded a subsample of 60 randomly selected abstracts to construct the coding scheme. After several rounds of exploration and discussion, they achieved a satisfying intercoder reliability (as measured with a Cohen kappa). The role of social media is categorized into two main types. First, social media provides a substantial research interest for public health research, which includes the use of social media for intervention, as human-computer interaction characteristics, as platforms of social influence, and for risk assessment or disease prevention. Second, social media is employed as a context in public health research with social media as mere reference, as participant recruitment tool, or as data source. Categories and their definitions are further illustrated in the analytical findings section also see .Finally, the research methods adopted by social media–based public health research were identified by searching a list of keywords associated with various research methods among the titles, abstracts, and keywords of the retrieved studies. Publication trends in the field of social media–based public health research in the past two decades were presented in 3 dimensions: growth of overall publications, growth of publications by specific diseases, and growth of journal outlets.Empirical studies in this area were relatively limited in the first decade (2000 to 2010), which demonstrated a minimal increase as shown in Social media has been increasingly incorporated into the studies of certain types of diseases in the past decades. Dramatic increases in research occurred on cancer, HIV, diabetes, obesity, and alcohol use after 2010. Other diseases, such as influenza, hepatitis A, hepatitis B, dengue, Ebola, MERS, asthma, and oral disease, showed a relatively slow growth rate that remained quite stable from 2000 to 2018.For the journal outlets, a total of 799 journals published studies in these areas see . Table 1The 25 extracted research themes were labeled on the basis of the top 15 most frequently used terms associated with each theme and the articles assigned to the theme. The percentages in The 25 research themes were further grouped into 6 research clusters on the basis of similar concerns and associations. The first cluster was on health education, which comprises 4 themes: health education–school and students, health education–family and oral/dental health, mHealth and medical decisions, and pregnancy. Health education aims to prevent diseases through improving people’s knowledge and health efficacy. School and family, as the main scenes for the students to learn health beliefs and behaviors, have been the foci of health education. Sexual health education on condom use and pregnancy have also attracted increasing scholarly attention.The second cluster was on health management with the help of mHealth. The themes mHealth and weight control, mHealth and diabetes management, digital campaigns in targeted populations, social media and alcohol drinking, substance usage and cessation, food and asthma, and vaccination and immunization all fell into this cluster. This indicates the functional attributes of social media to help manage health problems. Social media use is used to intervene in certain unhealthy behaviors and promote healthy behavior adoption.The third cluster, cancer studies, includes women’s cancer, reproductive cancer, cancer survivor, and caregiving on social media. Cancer is one of the world’s largest health problems and a significant cause of death. Thus, continuous attention has been paid to cancer studies.The fourth cluster, infectious diseases, includes HIV as a key topic: mHealth and HIV; men and HIV; and infectious disease, health campaign, and stigma belong to this cluster. In this line of research, social media provides breakthrough channels to reach risky subgroups and focuses more attention on campaigns to reduce the stigma surrounding infectious diseases.The fifth cluster was on mental health issues. This cluster consists of two themes: mental health and substance use and mental health–depression and digital technology. Mental health problems have been prominent in modern society. Digital technology is considered a cause and a solution to mental health issues.The sixth cluster was on extended health research empowered by social media: health and human mobility, health marketing, surveillance and Twitter, and eHealth–miscellaneous. These research areas have flourished due to the availability of geographical information, mass user behavioral data, and extensive online discourse on social media platforms.Social media is integrated into public health research by providing a new research context or producing new substantial interest in public health research.When social media was adopted as a research context, social media was specifically considered as a mere reference, a platform for participant recruitment, and as a data source. When social media was adopted as a mere reference, research mostly used social media as a tool to offer intervention and facilitate the health management of individuals. For the role of a platform for recruitment, research either recruited participants through distributing questionnaires or posting participant recruitment announcements on social media  or employed users of certain social media platforms as the study target group (Grindr for the men who have sex with men group). For the role of data source, social media could contribute to collecting data in text, image, video, and app interface formats and collecting published posts and articles for meta-analysis or scope review.When social media produced substantial interests for public health research, social media was used for intervention; employed to study human-computer interaction characteristics; used as a platform of social influence; and used for disease surveillance, risk assessment, or prevention. Under these 4 broad categories, the role of social media is described as follows:For public health intervention, the 4 subroles of social media in the published studies are as follows: (1) interactive intervention tool targeted at changing personal and environmental risky health factors, (2) intervention information-distributing tool , (3) source for health information seeking, such as YouTube and other platforms, and (4) usability test of social media platforms as intervention instruments.Under this role, social media was used to serve the goal of revealing (1) the public’s attitudes toward technology and social media for health use, (2) characteristics and behaviors of social media users and groups, (3) factors affecting the health behaviors or attitudes of users on social media, and (4) consequences/influences on health behaviors caused by (popular) social media.Social networking and interaction between different individuals and groups on social media could facilitate the change of health behaviors through the following approaches: (1) building online (support) groups for patients, such as cancer patient groups on Facebook, (2) promoting physician-patient communication or information seeker–provider communication, (3) enhancing health-related marketing, such as precision advertising, and (4) changing public health behavior at a macro level. All of these approaches are representations of social influence in online communities.The digital traces of online behaviors and massive online discourse granted opportunities to understand health conditions at a population level. For instance, Google trends and search query records could grant references to predict the possibility of a flu outbreak at an early stage.Among the dimension of social media as research context , “as a mPublic health research with social media data was dominated by traditional quantitative research methods, whereas cutting edge computational methods played a minor role. Among all the articles, 30.6% employed survey method, 24.0% employed experiment design, 22.7% employed qualitative methods , 8.3% included employed digital methods , and 5.6% employed traditional content analysis.With a bottom-up approach, this study provided a panoramic mapping of the landscape of social media–based public health research. By analyzing publication trends, research themes, roles of social media, and research methods adopted in this emerging research area, this study concluded that (1) social media has penetrated almost all the health-related processes and domains since 2010, showing a dramatic increase in the research body; (2) existing social media–based public health research mainly focuses on 25 themes in 6 clusters; (3) social media generally played two roles in public health research: generating substantial research interest and providing a research context/platform; (4) existing social media–based public health research is dominated by traditional research methods while the share of computational method is on the rise. The panoramic mapping can help scholars understand the state of the art in this research area and what is under- or overstudied in this field. This study can enable scholars across various disciplines to understand each other’s needs and contribute jointly to health promotion and disease control. Here, three notable issues that possess theoretical and methodological implications in social media–based public health research are elaborated.Social media has infiltrated almost all health-related processes and domains with the rapid advancement of social and mobile media. This dramatic change has entailed many new phenomena to be explored in public health research. The findings of this study are consistent with previous studies that found that almost one-third of internet studies have focused on eHealth and mHealth since 2009  and a trWhen public health research meets social media, new topics have emerged and attracted the attention of public health scholars : mHealthThis relatively new domain calls for in-depth exploration. New phenomena and new questions raised by social media are of practical and theoretical significance for public health research. Timely responses to those new phenomena via scientific research can promote the advancement of the domain to keep up with technology advances and establish a realistic understanding of what social media can and cannot do in public health. Meanwhile, public health research should delve into scientific research questions behind those new phenomena and address them either by exploiting the existing body of knowledge or exploring new methods and knowledge to extend the domain.When public health research meets social media, the dominant research methods are traditional quantitative methods, despite the growing interest in computational methods among public health scholars. The methodological potentials of social media for public health research can and should be further tapped. Specifically, the potential of social media in participant recruitment and measurement development has direct and salient implications to public health research.Social media substantially facilitates participant recruitment in public health research. Recruiting research participants from specific groups of individuals who have sensitive health issues or are stigmatized in society, such as people living with HIV/AIDS or individuals with mental health issues, remains a significant challenge for public health scholars ,47. GiveSocial media contributes to public health research by providing refreshed measurements of existing concepts or new observations of emerging phenomena. Rich semantic information in digital traces can provide a social telescope  with whiSocial media–based public health research lies in the crossroad between public health studies and social science studies on information and communication technologies (ICTs)  and beneFrom an overview of social media–based public health research, the dominating approach of these published studies considers public health issues as the substantial interests and ultimate outcomes rather than regard social media as an equally important area of concern. Many articles used limited space to describe the use of social media in health promotion campaigns or projects ,65. The Despite the strengths and contributions, this study has certain limitations. First, the study may suffer from the file drawer effect given that only studies indexed in Web of Science and PubMed were included. Empirical studies published in other outlets were not considered here. Future studies are warranted to expand the pools to conference proceedings and articles indexed in other databases. Second, this study used numerous diseases as search terms in the initial search, but the list remains incomplete. Some important diseases, such as mental disorders, were not incorporated. Despite this, the topic modeling captured mental health as a major theme. Further research is suggested to include mental health keywords as search terms. Third, LDA topic modeling is a well-recognized method to identify related themes through document-word matrices. However, the results of the topic modeling were not as neat as expected. No standard and quantitative thresholds exist for researchers to choose the optimal number of topics. Future studies are encouraged to replicate this study and examine the reliability of such themes.This study examined research themes, roles of social media, and research methods in social media–based public health research published from 2000 to 2018. This research identifies 25 research themes covering different diseases, various population groups, physical and mental health topics, and other significant issues. Social media assumes two major roles in public health research: one is to produce substantial research interest for public health research and the other is to furnish a research context for public health research. Social media enables scholars to study new phenomena and propose new research questions in public health research. Meanwhile, the methodological potential of social media in public health research needs further exploration.


Existing health informatics curriculum requirements mostly use a competency-based approach rather than a skill-based one.The main objective of this study was to assess the current skills training requirements in graduate health informatics curricula to evaluate graduate students’ confidence in specific health informatics skills.A quantitative cross-sectional observational study was developed to evaluate published health informatics curriculum requirements and to determine the comprehensive health informatics skill sets required in a research university in New York, United States. In addition, a questionnaire to assess students’ confidence about specific health informatics skills was developed and sent to all enrolled and graduated Master of Science students in a health informatics program.The evaluation was performed in a graduate health informatics program, and analysis of the students’ self-assessments questionnaire showed that 79.4% (81/102) of participants were not confident  about developing an artificial intelligence app, 58.8% (60/102) were not confident about designing and developing databases, and 54.9% (56/102) were not confident about evaluating privacy and security infrastructure. Less than one-third of students  were confident (extremely confident and very confident) that they could evaluate the use of data capture technologies and develop mobile health informatics apps .Health informatics programs should consider specialized tracks that include specific skills to meet the complex health care delivery and market demand, and specific training components should be defined for different specialties. There is a need to determine new competencies and skill sets that promote inductive and deductive reasoning from diverse and various data platforms and to develop a comprehensive curriculum framework for health informatics skills training. The National Center for Education Statistics defines competency as a combination of skills, abilities, and knowledge needed to perform a specific task . The 21sThe first international recommendations to develop health informatics educational activities were published by the International Medical Informatics Association (IMIA) in 2000 . IMIA deWith the adoption of digital technologies around the world, several countries have focused on education initiatives to improve populations’ 21st century digital skills . ProfessAs there are several international and national initiatives to develop health informatics competencies, determining the standard comprehensive health information skill sets has always been a challenging task because of the continually evolving technology. National health informatics organizations and accreditation agencies have been specifying their own standards because of the lack of universal standards. For example, Canada’s Health Informatics Association  developed 51 competencies about information management, information technology, clinical/health services, Canadian Health System, organizational and behavioral management, project management, and analysis and evaluation in 2009 . The AusAnother notable development was the formation of the eHealth Collaboration Workforce Development Workgroup in 2013. A Web-based database about health information technology competencies to identify the gaps between information and communication technology (ICT) competency and knowledge deficiencies was built by the United States and the European Union (EU) . This coThe accreditation process evaluates an academic institution’s effectiveness in achieving its stated mission, and the graduate education programs that participate in the voluntary accreditation process should comply with the regional, national, or independent accrediting agencies’ core curriculum requirements. This is an important process to ensure the accountability of academic training programs and is widely considered as the de facto standard for quality assessment and continuous improvement.In the United States, although the CAHIIM accredits undergraduate and graduate health informatics programs, the American Health Information Management Association (AHIMA) and the Commission on Certification for Health Informatics and Information Management certify individuals. In 2012, CAHIIM published the curriculum requirements for a master’s in health informatics degree and 3 mandatory facets about (1) the design, analysis, implementation, and management of information systems; (2) sociotechnical aspects; human-computer interaction; and structure, function, and transfer of information; and (3) computer networks, security, programming, database, and systems administration were determined . In addiIn 2017, CAHIIM revised the accreditation standards for master’s degree programs in health informatics and published a revised version of core competencies that consists of the following foundational domains: (1) health; (2) information science and technology; (3) social and behavioral science; (4) health information science and technology; (5) human factors and sociotechnical systems; (6) social and behavioral aspects of health; (7) social, behavioral, and information science and technology applied to health; (8) professionalism; (9) interprofessional collaborative practice; and (10) leadership  14,17,1.core informatics competencies in 2001, the AMIA education committee proposed establishing a medical informatics certification program the following year. AMIA’s working groups have been working on the definition and description of clinical informatics subspecialty and determining core competencies for biomedical and health informatics . Fo. Fo13]. Health informatics graduates need hands-on experience with various health informatics tools and apps to develop skills and the ability to apply this practical expertise to unfamiliar situations, serve as subject-matter experts, and lead and manage innovative projects. Regional, national, and international accreditation standards, and in-demand technical skills to use and develop patient-centered health informatics systems could be taken into consideration when determining health informatics curriculum components. It is also essential to capture students’ perspectives before developing skills training components and to develop an up-to-date health informatics skills training framework depending on different medical specialties and health care needs for physicians, nurses, pharmacists, and medical and laboratory technologists. Developing new terminologies that will clearly specify the difference between competency-based and skill-based approaches for each health informatics discipline might be useful. Further studies that evaluate employers’ feedback and students’ perceptions after they get hired are suggested to determine the potential gaps and needs in health informatics skills training.


Arthritis has a high prevalence globally and includes over 100 types, the most common of which are rheumatoid arthritis, osteoarthritis, psoriatic arthritis, and inflammatory arthritis. All types of arthritis share common features of disease, including monocyte infiltration, inflammation, synovial swelling, pannus formation, stiffness in the joints and articular cartilage destruction. The exact etiology of arthritis remains unclear, and no cure exists as of yet. Anti-inflammatory drugs (NSAIDs and corticosteroids) are commonly used in the treatment of arthritis. However, these drugs are associated with significant side effects, such as gastric bleeding and an increased risk for heart attack and other cardiovascular problems. It is therefore crucial that we continue to research the pathogenesis of arthritis and seek to discover novel modes of therapy. This editorial summarizes and discusses the themes of the 27 articles published in our Special Issue “Research of Pathogenesis and Novel Therapeutics in Arthritis 2.0”, a continuation of our 2019 Special Issue “Research of Pathogenesis and Novel Therapeutics in Arthritis”. These Special Issues detail important novel research discoveries that contribute to our current understanding of arthritis. Arthritis has a high prevalence globally and includes over 100 types, the most common of which are rheumatoid arthritis (RA), osteoarthritis (OA), psoriatic arthritis (PsA) and inflammatory arthritis. All types of arthritis share common features of disease, including monocyte infiltration, inflammation, synovial swelling, pannus formation, stiffness in the joints and articular cartilage destruction. The exact etiology of arthritis remains unclear, and no cure exists as of yet. Anti-inflammatory drugs (NSAIDs and corticosteroids) are commonly used in the treatment of arthritis. However, these drugs are associated with significant side effects, such as gastric bleeding and an increased risk for heart attack and other cardiovascular problems. It is therefore crucial that we continue to research the pathogenesis of arthritis and seek to discover novel modes of therapy.Our call for papers for this Special Issue—Research of Pathogenesis and Novel Therapeutics in Arthritis 2.0—Attracted a diverse collection of articles, which were closely examined by a panel of expert reviewers, who selected 27 (18 research papers and 9 reviews) for publication in this Special Issue. The majority of the research papers investigated the pathogenesis of arthritis and new biomarkers; three examined novel strategies in the treatment of arthritis. All of these papers are discussed below.+ modulation in methotrexate responders and nonresponders [+ monocytes enhances osteoclast activation in patients with PsA, report Lin and colleagues [(i) The pathogenesis of arthritis. Research performed by Kmiolek and colleagues offers insights into how the interplay between transcriptional factors and microRNAs (miRNAs) contributes to RA pathogenesis . Sanz ansponders , while Lsponders . The presponders . Upregullleagues , while olleagues . Akagi alleagues . Teixeirlleagues .(ii) New biomarkers. Khanfar and colleagues describe preclinical findings showing that the transcription factor Nkx2-3 appears to regulate the development of autoimmune arthritis, probably via B cell signaling . Li and (iii) Novel strategies in the treatment of arthritis. Chou and colleagues discuss how the inhibition of discoidin domain receptors 1 (Ddr1) reduces chondrocyte apoptosis and promotes chondrocyte autophagy, leading to the attenuation of cartilage degradation, and so may therefore be a potential disease-modifying therapy for preventing OA progression . Mendez Reviews. The nine reviews discuss recent findings on novel pathogenic aspects of inflammatory joint diseases and interesting investigations into treatment aspects of arthritis. Ailioaie and Litscher discuss the benefits of using photobiomodulation in juvenile idiopathic arthritis and adult RA , while KWe hope that this Special Issue will provide new research insights and directions that ultimately inspire new arthritis prevention and treatment strategies.


To assess the importance of ensuring medicine quality in order to achieve universal health coverage (UHC).We developed a systems map connecting medicines quality assurance systems with UHC goals to illustrate the ensuing impact of quality-assured medicines in the implementation of UHC. The association between UHC and medicine quality was further examined in the context of essential medicines in low- and middle-income countries (LMICs) by analyzing data on reported prevalence of substandard and falsified essential medicines and established indicators for UHC. Finally, we examined the health and economic savings of improving antimalarial quality in four countries in sub-Saharan Africa: the Democratic Republic of the Congo (DRC), Nigeria, Uganda, and Zambia.p = 0.05) and with an indicator for government effectiveness (p = 0.04). We estimated that investing in improving the quality of antimalarials by 10% would result in annual savings of $8.3 million in Zambia, $14 million in Uganda, $79 million in two DRC regions, and $598 million in Nigeria, and was more impactful compared to other potential investments we examined. Costs of substandard and falsified antimalarials per malaria case ranged from $7 to $86, while costs per death due to poor-quality antimalarials ranged from $14,000 to $72,000.A systems perspective demonstrates how quality assurance of medicines supports dimensions of UHC. Across 63 LMICs, the reported prevalence of substandard and falsified essential medicines was found to be negatively associated with both an indicator for coverage of essential services (Medicines quality assurance systems play a critical role in reaching UHC goals. By ensuring the quality of essential medicines, they help deliver effective treatments that lead to less illness and result in health care savings that can be reinvested towards UHC. The goal of Universal Health Coverage (UHC) is to ensure that all people obtain the health services they need without suffering financial hardship when paying for them . SustainQuality health services cannot be delivered without quality-assured medicines. Ensuring medicine quality is paramount in providing safe and effective health care and reducing overall health care costs. The World Health Organization (WHO) estimates that, on average, 1 in 10 medical products circulating in low- and middle-income countries (LMICs) is substandard or falsified . WHO defThe pharmaceutical system operates within a complex health system, where pharmaceutical good governance can be viewed as a component of health systems strengthening necessary to support UHC . EnsurinThe Lancet’s Commission on Essential Medicines Policies estimated that between $13 and $25 per capita (US$77.4 to $151.9 billion) is required to finance a basic package of essential medicines in all LMICs [Financing and procurement of medicines play an important role in UHC schemes, where medicine quality needs to be safeguarded . Globallll LMICs –16. UHC This study uses systems mapping to conceptually illustrate the benefits of ensuring medicine quality in UHC. We subsequently examined the association between UHC and medicine quality in the context of essential medicines in LMICs using data on substandard and falsified medicines prevalence and UHC indicators. The study also demonstrates the health and economic costs of poor-quality medicines that could be averted by quality assurance interventions where savings could be reinvested in UHC, using antimalarials as a case study.Systems mapping has been increasingly used in health to help understand indirect effects in complex systems –20. WithThis research mapped the series of stages where quality assurance processes and interventions are necessary to ensure the quality of medicines reaching patients, illustrating the flow of medicines from manufacturing to utilization. We illustrated the linkages between health systems and health insurance processes, and the resulting benefits to patients. The systems map also illustrates the three dimensions of UHC, demonstrating how medicine quality assurance processes and interventions, and the ensuing benefits, relate to the UHC dimensions . FinallyTo relate the conceptual linkage between UHC and medicine quality portrayed through our systems map to real world indicators, we investigated the potential association between UHC and medicine quality indicators utilizing existing data. Two indicators from the WHO were used to determine progress towards UHC: an indicator on essential services coverage; and an indicator on the proportion of the population with large household expenditures on health as a share of total household expenditures . The WHOIn addition, two indicators for government effectiveness and regulatory quality were abstracted from the World Governance Indicators of the World Bank . The govWe examined how these indicators were associated with estimated prevalence of poor-quality medicines for each country, using data on reported prevalence of substandard and falsified essential medicines among 63 LMICs previously gathered from a systematic literature review and meta-analysis . SubstanTo illustrate the potential health and economic impact that can result from ensuring the quality of antimalarials, we analyzed the current landscape of the impact of poor-quality antimalarials in a case study. Four countries were included in our analysis: the Democratic Republic of the Congo (DRC), Nigeria, Uganda, and Zambia –28. MalaEstimates of country-specific impact were obtained from the Substandard and Falsified Antimalarial Research Impact (SAFARI) model, an agent-based model we built that simulates malaria disease progression, care seeking, and outcomes for children under age five –28. The In order to compare the impact of poor-quality antimalarials across countries, we calculated the potential savings in each country if the reported prevalence of substandard and falsified antimalarials were to be reduced by 10%. We estimated this impact by comparing a baseline scenario using the reported prevalence of substandard and falsified antimalarials, to a scenario where 10% more antimalarials were quality-assured. This provided an estimate of the health and economic benefits a health system would experience by investing in quality assurance mechanisms that increased the supply and utilization of quality-assured antimalarials and reduced use of substandard and falsified antimalarials by 10%. The savings are estimated in fewer deaths, fewer hospitalizations, lower costs of care, and productivity gains simulated when poor-quality antimalarials are replaced with quality-assured antimalarials. The economic impact of poor-quality antimalarials was further assessed at an individual level to demonstrate the cost of poor-quality medicines per malaria case, and the cost attributable to substandard and falsified medicines for each additional malaria death, hospitalization, and disability-adjusted life year (DALY). This was calculated by taking the total savings in direct costs and productivity losses averted from reducing the prevalence of substandard and falsified antimalarials by 10% and dividing it by estimated reductions in deaths, hospitalizations, and DALYs.To contextualize the impact of improving medicine quality, we compared a scenario in which no poor-quality antimalarials were present, to other options that governments may consider in reducing malaria burden. We simulated two additional interventions: a scenario in which there were no stockouts of antimalarials, and one in which only Artemisinin-based Combination Therapies (ACTs) were taken as first-line therapy. Moreover, low-quality anti-infectives can induce further costs to health systems and society by contributing to the development of antimicrobial resistance. We simulated the impact of widespread ACT resistance in a hypothetical scenario where the efficacy of ACTs were reduced to efficacy of other malaria treatments, impacting the duration and severity of malarial illness among children.Quality-assured medicines bring further benefits (orange rectangles). Appropriate use of quality-assured medicines contributes to maintaining medicine efficacy by delaying the development of antimicrobial resistance , 30. WheAverting the need for additional health care when beneficiaries are healthier with quality-assured medicines can trigger a number of health system mechanisms (purple rectangles). When beneficiaries require less health care, the health system is less burdened and the quality of health services could improve . HealthiRegulatory oversight and quality assurance mechanisms throughout the supply chain reinforce the system that ensures patients can obtain and use quality-assured medicines. These are the backbone of the key interventions (yellow rectangles) within the system, broken down to be those affecting medicine delivery, administration, or UHC. These interventions include best practices , policies , regulations , and education  –36. WithThe systems map connects the mechanisms to build effective medicines quality assurance systems with the health and economic benefits that quality-assured medicines can bring to UHC, highlighting the need for investments in strengthening these systems to achieve UHC.We sought evidence to further describe the linkages between medicine quality and UHC by examining the association between existing data on the reported prevalence of substandard and falsified medicines  and UHC p value 0.054; Across countries, we found that coverage of essential services by health insurance schemes was found to be negatively associated with reported prevalence of poor-quality medicines  after controlling for GDP per capita. This lack of observable association does not indicate that poor-quality medicines do not result in larger household expenditures. It instead suggests that, given the data available, poor-quality medicines may not be the main driver of enhanced expenditures where other factors are at play. Furthermore, data on catastrophic health spending was not available for all countries, resulting in a lower number of observations for this analysis compared to others (51 compared to 63 countries).No significant association was found between large health expenditures and reported prevalence of substandard and falsified medicines  and 23.8% (Kinshasa) of total savings ($813 thousand to $20 million) across countries. The model results suggest that assuring the quality of antimalarials would result in considerable savings in productivity, largely composed of the potential economic productivity that a child would contribute over a lifetime if death or disability due to poor-quality antimalarials were averted. We estimated that reducing poor-quality antimalarials by 10% would reduce productivity losses annually by $7.5 million in Zambia and $578 million in Nigeria.We estimated that substandard and falsified antimalarials contribute between $7 per malaria case in Zambia, and $86 per malaria case in the Katanga region in DRC. Each additional death due to poor quality antimalarials approximately cost between $14,300 per death in Katanga, and $72,500 per death in Nigeria. Each additional pediatric malaria hospitalization attributable to substandard and falsified medicines cost between $584 per hospitalization in Kinshasa, and $26,800 per hospitalization in Nigeria. The costs at an individual level are heavily influenced by the cost of care, amount of care seeking, number of malaria cases, and the GDP per capita in each country.Despite the many differences between countries, this study consistently observed that substandard and falsified essential medicines were associated with key components of UHC such as coverage of essential medicines, government effectiveness, and regulatory quality. Using systems mapping, we illustrated the conceptual link between UHC and regulatory measures to improve the quality of medicines. With the conceptual mapping as guidance, we demonstrated that a relationship can be observed between medicine quality and UHC indicators within existing data. We then showed the importance to a health system of investing in the quality of medicines, and the potential savings that could be reinvested in UHC dimensions . We show that improving antimalarial quality would not only save millions by improving outcomes—it can also help avert the immense costs associated with potential development of drug resistance . Using hInterventions aimed at ensuring medicine quality, such as good practices in manufacturing and distribution, or establishing an essential medicines list, strengthen institutions necessary for maintaining continued access to quality-assured medicines and quality services –48. UHC Recent literature has drawn attention to potential negative unintended consequences in UHC implementation, where incentives for procuring cheaper medicines to meet increased demand under UHC can lead to arbitrage opportunities and proliferation of suppliers of cheaper, non-quality-assured medicines , 50. TheOur analysis has a number of limitations. Agent-based models provide results that depend on the quality of data inputs. Because data on substandard and falsified medicines, care-seeking, and costs for malaria in LMICs are limited, we performed extensive literature searches and analysis of the most recent quality data for our inputs. Epidemiological data and cost inputs were probabilistically ranged to account for uncertainty in outcomes . In addiDespite these limitations, this study contributes to emerging analyses regarding the role that medicines quality assurance systems play in UHC, and conceptually highlights the importance of ensuring medicine quality in order to achieve UHC goals. Our systems map can be used as a conceptual and advocacy tool to make a case for the importance of investing in medicine quality assurance with UHC among a broad range of stakeholders. The system mapping approach can also be adapted and customized to explore medicine quality assurance and UHC within local specific contexts. Cost-savings implications of ensuring medicine quality and providing UHC can assist policy makers, governments, civil society, and other stakeholders, when prioritizing health interventions and engaging with health insurers and other financing agencies. In addition, this analysis highlights the critical role that Medicines Regulatory Authorities play in UHC through several key functions, such as enforcement of good practices for manufacturing, registration, distribution and storage; establishing pharmacovigilance and medicines quality post-marketing surveillance programs; and enforcing regulatory actions to withdraw poor-quality medicines from circulation. Thus, ensuring the use of quality-assured medicines is critical in UHC and investing in medicine quality assurance systems and interventions is vital for the long-term success of UHC planning in LMICs.S1 Fig(TIF)Click here for additional data file.S1 Table(DOCX)Click here for additional data file.


Thus, this review is written with an objective to provide information on the evolution, background, methodical advances, and potential scope of the field for cardiovascular research and medicine. We begin with a review of literatures on optogenetic proteins related to their origin, structure, types, mechanism of action, methods to improve their performance, and the delivery vehicles and methods to express such proteins on target cells and tissues for cardiovascular research. Next, we reviewed historical and recent literatures to demonstrate the scope of optogenetics for cardiovascular research and regenerative medicine and examined that cardiac optogenetics is vital in mimicking heart diseases, understanding the mechanisms of disease progression and also in introducing novel therapies to treat cardiac abnormalities, such as arrhythmias. We also reviewed optogenetics as promising tools in providing high-throughput data for cardiotoxicity screening in drug development and also in deciphering dynamic roles of signaling moieties in cell signaling. Finally, we put forth considerations on the need of scaling up of the optogenetic system, clinically relevant in vivo and in silico models, light attenuation issues, and concerns over the level, immune reactions, toxicity, and ectopic expression with opsin expression. Detailed investigations on such considerations would accelerate the translation of cardiac optogenetics from present in vitro and in vivo animal studies to clinical therapies.Optogenetics is an elegant approach of precisely controlling and monitoring the biological functions of a cell, group of cells, tissues, or organs with high temporal and spatial resolution by using optical system and genetic engineering technologies. The field evolved with the need to precisely control neurons and decipher neural circuity and has made great accomplishments in neuroscience. It also evolved in cardiovascular research almost a decade ago and has made considerable progress in both  They observed that hippocampal neurons, expressing NpHR, elicited outward currents with fast kinetics (<20 ms) when voltage-clamped and produced rapid membrane hyperpolarization (~100 ms) when current-clamped  is found in halobacteria where it is utilized for light-induced, inward-chloride transport across the outer membrane Lanyi, . Thus, iin vivo and in situ settings, not attainable with conventional optical dyes  and with the first construction and efficient plasma membrane localization of the voltage-sensitive fluorescent probe (VSFP2.1) in mammalian cells by Dimitrov et al. , based on bacterial rhodopsin or voltage sensing domain (VSD) of voltage sensitive proteins, are also gaining greater attention in the field , higher calcium permeability and light sensitivity (CatCh), increased expression and photocurrent (ChR2-XXL), and higher tissue penetrability (ReaChR)  to conjugation with single fluorescent protein (for overcoming the broad spectrum barriers associated with FRET system) and now further to mutations in the fluorescent proteins and linker optimization  and utilize physical cues, such as electric field (electroporation), ultrasound waves (sonoporation), laser pulse (photoporation), hydrodynamic pressure (hydroporation) etc., to enhance gene delivery  and possess ability to replicate independent of the host genome  and Rev recognition element (RRE) required for the export of vector and transfer of un-spliced mRNA from nucleus to cytoplasm , respectively while AAP region encodes protein for virion assembly -mCherry in 100 μl of PBS and injected intravenously (left jugular vein) in anesthetized CD1 wild-type mice  in the dissociated transduced cardiomyocytes. They also reported that ventricular stimulations were evoked on the transduced mice hearts by optical pacing (shown by broad QRS complexes) and the responses were dependent on the illumination parameters, such as light intensity and irradiation area. These results depict the ability of AAV vector in successful transduction of the optogenetic proteins in the intact cardiomyocytes  site for successful gene expression, where (1) promoters provide transcription start site and transcription regulatory sequence to control transgene expression both temporally and spatially, (2) introns play a role in mRNA stabilization and translocation from nucleus to the cytoplasm, (3) protein coding sequence enables ribosome scan and recognize start and stop sites for mRNA, and (4) poly(A) site forms the transcriptional stop signals  which provide selective and higher anion conductance to cause cell inhibition with lower light intensity, when compared to traditional halorhodopsin (NpHR). They found that action potential duration of cultured NRVM was shortened to variable extents by delivering pulsed light (510 nm) at different intervals or of different intensities  during the repolarization phase  light pulses delivered to the atria or ventricles and ventricular extrabeats were induced with prolonged ventricular illumination , terminated electrically induced sustained ventricular tachycardia (success rate ~85%) (2) when the illumination area is reduced (<143 mm2) (in silico work showed that the same approach in the human heart would require light pulses of longer wavelength (669 nm) and higher intensity  . They al143 mm2) . ConcomiSimilarly, Burton et al.  and Croc2) using single light pulses  of 100 ms and 1,000 ms durations ; a detailed schematic and experimental set up of the system is provided in Recently Nyns et al.  also invCardiotoxicity is one of the primary reasons for drug withdrawal. In the United States, it contributes to ~20% of withdrawal at each phase of drug development and post-market surveillance process , cAMP levels were increased for up to 646% of the baseline levels   up-conversion nanoparticles to convert highly tissue penetrable near infrared waves to visible light (Entcheva, in vivo applications (Entcheva, in vitro and in vivo studies have provided proof-of concept for the translational potential of cardiac optogenetics. In addition, emerging scope of optogenetics in modulating the dynamic roles of signaling moieties needed during crucial biological functions, such as cell signaling, differentiation and migration are greatly expanding the dimensions of in vitro and in vivo research. Future investigations on such emerging scopes would greatly enhance the clinical success of the field for cardiovascular regenerative medicine.Another concern with the clinical translation of optogenetics is the limitations on light penetration due to highly dense and light-scattering cardiac tissues, specifically with applications of blue light for the excitation of ChR2 opsins (Entcheva, JJ and WZ wrote the manuscript. MR revised the manuscript.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.


Transforming primary care practice to improve the health of older adults is a major focus of the Geriatric Workforce Enhancement Program (GWEP). Using the 4Ms of an Age-Friendly Health System  as a framework, presenters will describe their GWEP’s ongoing development, training, and evaluation initiatives aimed at increasing providers’ knowledge and practice skills, and improving older adult’s health outcomes. These initiatives are creating increased professional competencies in geriatric care that will: 1) help older adults maximize their health and wellbeing, and 2) better support caregivers and families. In this symposium, presenters from three GWEPs, Pennsylvania State University, Rush University Medical Center, and Saint Louis University will describe AFHS initiatives with rural and urban primary care partner sites. Educational and programmatic initiatives and strategies that map onto the 4Ms that will be discussed including geriatric assessment, dementia-focused interventions, falls prevention, opioid assessment, and caregiver well-being and support. Outcomes in older adult’s health and functional status will be discussed. Presenters will highlight the importance of building AFHS in primary care and strategies to bridge this framework into the community.