Pluripotent stem cells (PSCs) such as embryonic stem cells (ESCs), ESCs derived by somatic cell nuclear transfer (ntESCs), and induced pluripotent stem cells (iPSCs) have unlimited capacity for self-renewal and pluripotency and can give rise to all types of somatic cells. In order to maintain their self-renewal and pluripotency, PSCs need to preserve their telomere length and homeostasis. In recent years, increasing studies have shown that telomere reprogramming is essential for stem cell pluripotency maintenance and its induced pluripotency process. Telomere-associated proteins are not only required for telomere maintenance in both stem cells, their extra-telomeric functions have also been found to be critical as well. Here, we will discuss how telomeres and telomere-associated factors participate and regulate the maintenance of stem cell pluripotency. Telomeres are ends of linear chromosomes that are bound by a host of protein factors and form a complex nucleoprotein structure. In mammalian cells, telomeres are consisted of repetitive [TTAGGG]n sequences and protected by the core six-protein shelterin/telosome complex , including embryonic stem cells (ESCs), nuclear transfer ESCs (ntESCs) and induced pluripotent stem cells (iPSCs), have the potential of unlimited-proliferation and the capacity to differentiate into any cell type. Therefore, PSCs can be used for any cell type replacement and have great value for regenerative medical. Proper regulation of telomere length and telomere-binding proteins is critical for telomere function and genomic stability, both in somatic cells and PSCs. Mouse ESCs and/or iPSCs with short telomeres exhibited unsuccessful teratoma formation and chimera production and failed to produce ES/iPS mice  capable of completely counteracting normal telomere shortening. PSCs can proliferate indefinitely while maintaining pluripotency and avoid telomere attrition and genome instability by elongating and protecting their telomeres. Short telomeres in ESCs lead to reduced pluripotency and unstable differentiation , could activate telomerase genes during reprogramming. For example, OCT3/4 and NANOG could bind to the TERC promoter and activate TERC transcription  and three proteins with no demonstrable DNA-binding activities  , increased TRF1 expression was observed before the onset of telomere elongation  was initially discovered as a protein that could interact with TRF1 (Kim et al., Repressor/activator protein 1 or RAP1 localizes to telomere via its interaction with TRF2 (Li et al., Multiple links have been established between telomere homeostasis and stem cell pluripotency maintenance. Sufficient telomere length is critical for unlimited self-renewal of PSCs. Telomere length and integrity may serve as general signatures to evaluate the quantity of ESCs and iPSCs. Longer telomeres would be advantageous for human ESCs and iPSCs in the application of PSCs in regenerative medicine. However, excessive telomere elongation heightens sensitivity of hESCs to replication stress at overly long telomeres, and causes the formation of C-circles (Rivera et al., Telomere length maintenance in ESCs and iPSCs is regulated by telomere-binding modulators and epigenetic modifications. Additionally, higher level of the shelterin/telosome component TRF1 also correlates with higher pluripotency of stem cells. Numerous studies have elucidated the roles of these telomere-binding proteins in telomere homeostasis. In the future, more focused effort should be made to delineate how stem cell pluripotency is regulated by telomere-binding modulators. Epigenetic changes at telomeres are acquired during reprogramming and ESC differentiation, these epigenetic modifications may provide a more flexible and efficient system to control of telomere length regulation in pluripotent cells. Future studies into how these telomeric chromatin status is regulated and contributes to the telomere homeostasis would provide insights to understand the mechanism of pluripotency maintenance and aging.In vivo studies will be necessary to fully understand the molecular functions of telomere-binding proteins in somatic stem cells and tissue development.Mutations in telomere proteins have been identified in many human diseases including DC. Our previous systematic analysis of human shelterin/telosome knockout cells has revealed functional differences between human and mouse telomeric proteins in telomere length homeostasis and end-protection (Kim et al., The role of telomere binding proteins in the stem cell self-renewal and pluripotency maintenance has been well discussed. However, the functions of these binding proteins in stem cell differentiation are still rarely studied. During the differentiation process, the gradually shorter telomeres may release some of the telomere binding proteins from telomeres or recruit some new factors to telomeres, which may affect the process of differentiation. Future studies should focus on the specific role of these telomere binding modulators in stem cell differentiation. In addition, telomere shortening or uncapping in stem cells leads to cell senescence and aging. However, previous studies usually focus on cellular level, but rarely mention individual level. What are the differences of telomere binding proteins in stem cells between young and elder individuals? How these differences contribute to individual stem cell therapy? Further studies are needed.


Here we present an inexpensive widefield ratiometric fibred OEM system capable of enhancing the contrast between similar spectra of pathologically relevant fluorescent signals without the burden of complex spectral unmixing. As an exemplar, we demonstrate the potential of the platform to detect fluorescently labelled Gram-negative bacteria in the challenging environment of highly autofluorescent lung tissue in whole ex vivo human lungs.Fibre-based optical endomicroscopy (OEM) permits high resolution fluorescence microscopy in endoscopically accessible tissues. Fibred OEM has the potential to visualise pathologies targeted with fluorescent imaging probes and provide an  Future work will include assessing performance in lung tissue with existing infection, in exploiting the capability to unmix multiple targets over multiple wavelengths, and in a label-free imaging regime of lung and other tissues, see appendix, and


Pancreatic ductal adenocarcinoma (PDAC) carries a poor prognosis and is expected to become the second leading cause of cancer mortality in the United States by 2030 . The disPtf1aCreERTM; KrasG12D/+) [in vitro and in vivo, highlighting the significant role of smoking in both tumor formation and progression. In addition to direct effects on PDAC tumor cells, NNK exposure also exerts significant changes in the tumor microenvironment (TME). This includes enhanced infiltration of immunosuppressive cell populations into the TME, including regulatory T-cells (Tregs) and tumor-associated macrophages (TAMs). Additionally, the progression of stromal fibrosis, a major contributor of therapeutic resistance in PDAC, is also heavily influenced by smoking carcinogens, as NNK exposure in vivo results in a marked increase in tumor desmoplasia. Through mechanistic studies, we have demonstrated that the oncogenic effects of NNK exposure are mediated through the activation of CREB through downstream stimulation of the AKT/PI3K pathway. Moreover, inhibition of CREB has shown both direct and indirect influences on PDAC tumor growth, wherein it has directly impeded NNK-induced tumor cell proliferation and indirectly reduced immunosuppressive cell infiltration into TME and stromal fibrosis in PDAC [Cigarette smoking has been extensively described as a major risk factor in the development of numerous solid organ malignancies including pancreatic cancer. Our findings show that exposure to a nicotine-derived nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), significantly accelerates pancreatic precancerous lesion (PanIN) formation in a genetically engineered mouse model of PDAC (sG12D/+) . Further in PDAC .in vivo through activation of the AKT/PI3K pathway [Chronic alcohol consumption is implicated in the pathogenesis of multiple pancreatic disorders through the induction of acinar cell injury. Chronic alcohol exposure prompts a profound inflammatory response through repeated cellular damage in the pancreas, eventually leading to neoplastic transformation and the subsequent development of PDAC. Recent reports have shown that alcohol exerts its pro-tumorigenic effects by initiating a cellular reprogramming event known as acinar-to-ductal metaplasia, eventually advancing to PanIN formation and invasive cancer  pathway . We have pathway . Further pathway . TherefoObesity is another well-established risk factor in PDAC development. Obesity is known to induce a pro-inflammatory state that differentially regulates pro-oncogenic cytokines and growth factors that are key mediators of PDAC progression. We have previously reported that the IL-6/STAT3 pathway is the critical regulator of obesity-induced PDAC growth . There iThe association among multiple modifiable risk factors on the initiation and progression of PDAC is well described; however, our understanding of the diverse cellular mechanisms that are affected by these pathologic states remains unclear. It is apparent that smoking, alcohol exposure, and morbid obesity induce oncogenic effects through direct interaction with PDAC cells, but additionally they seem to exert profound effects on the immune cell population and architecture of the microenvironment that may mediate disease progression and resistance to therapy. Our studies have provided fundamental insights into PDAC carcinogenesis induced by these risk factors and suggest CREB as a key oncogenic driver and therapeutic target in these processes. Further investigations into the central role of CREB in risk factor-associated PDAC are needed to promote our understanding and expand the treatment options available for this deadly malignancy.


Additionally, students whose interviewees experienced intense physical suffering or physical limitations or students who were enrolled in a course with intensive VPD and vaccine curriculum had significantly increased vaccine attitudes. This suggests that introducing students to VPDs can decrease vaccine hesitancy.In 2019, the World Health Organization (WHO) listed vaccine hesitancy in its top ten threats to global health. Vaccine hesitancy is a “delay in acceptance or refusal to vaccinate despite availability of vaccination services”. Urban areas with large amounts of vaccine hesitancy are at risk for the resurgence of vaccine-preventable diseases (VPDs). Many vaccine-hesitant (VH) parents may be unfamiliar with the consequences of VPDs, and thus might be swayed when confronted with the symptoms and dangers of VPDs. As such, we sought to educate college students (future parents) in an urban vaccine-hesitant hotspot by assigning them to interview family or community members who had experienced a VPD. Student vaccine attitudes were assessed by surveys before and after the interviews. Vaccine-hesitant students who conducted a VPD interview but received no additional vaccine educational materials were significantly more likely (interaction term  For months she couldn’t leave the house.” This interview led the student to explain  having students interview individuals who had experienced a VPD or (2) providing intensive vaccine- and VPD-related course material. Combining intervention styles allowed us to assess the strength of each intervention. VPD interviews (intervention group) were most successful at swaying student vaccine attitudes when the coursework did not discuss vaccines or if the interviews had strong themes of physical suffering and limitations. The majority of students in the intervention group who became pro-vaccine and the resulting increase in vaccine attitude scores mirrored those achieved through intensive education (MMBio 261). Thus, encouraging students to conduct VPD interviews may be an easy and effective intervention when the course has little to do with VPDs or lacks vaccine-related content.In courses that do address vaccines, it may be advantageous to first rigorously introduce students to VPD consequences before addressing, lightly, vaccine safety and societal implications. While Bio 100 introduces vaccines through a homework assignment that seeks to correct misconceptions about vaccine safety and societal implications, MMBio 261 begins with rigorous weeks-long sections on immunity and VPDs but only briefly discusses vaccine safety and herd immunity. This may explain why Bio 100 VH students did not have significantly increased post-intervention VASs, only a suggestive upward trend, whereas MMBio 261 VH students had significantly improved post-intervention VASs. The comparison between Bio 100 and MMBio 261 students mirrors earlier research that discussing VPD ramifications has a greater impact on combating vaccine hesitancy than correcting flawed assumptions or asserting an absence of risk about vaccines ,13,14,15This study does have limitations. We did not examine whether an interview-based intervention would be successful in a non-science course. Any biological instruction discussing vaccines might provide some boost to vaccine attitudes. Additionally, for logistical reasons, we did not assess whether the increase in VAS is meaningful by following whether students vaccinate their current and future children. Furthermore, this study focuses on college students and may not be expandable to the general population. Nonetheless, despite these limitations, interview-based interventions and intensive VPD-dependent vaccine education does significantly increase vaccine attitudes, in a population susceptible to anti-vaccine attitudes. Vaccine hesitancy is a complex, situation-dependent problem, and requires unique and tailored interventions. Interview-based interventions are easy to implement and can supplement courses or even community outreach programs seeking to address vaccine hesitancy. Predisposing students to think more favorably about vaccinations by openly discussing the consequences of vaccine-preventable diseases may improve their prospective individual and familial vaccine uptake. Future research should tease apart the contributions of science education and personal familiarity with VPDs towards improving vaccine attitudes in diverse populations.There are two major conclusions of this work. First, an interview-based intervention, where students discuss vaccine-preventable diseases with people who have actually experienced these diseases, can significantly improve attitudes towards vaccination. Second, the subject matter used while teaching about vaccine-preventable diseases matters. In the class with extensive discussion of the diseases themselves, there was a strong increase in vaccine attitudes among vaccine-hesitant students, while this effect was not seen in the class that discussed mostly vaccine safety. Taken together, these findings indicate that increasing familiarity with vaccine-preventable diseases leads to improved attitudes towards vaccination. This should help to create solutions to the worldwide problem of vaccine hesitancy or denial, by indicating aspects of education that are important for affecting those attitudes.


In this study, we examine the association between perceived age discrimination at the workplace and job stress, with depressive symptoms among currently working late-middle-aged adults. In particular, we investigate whether the association between these work-related factors and depression varies by the strength of their social networks. We use data from the Panel on Ageing and Transitions in Health Survey (PATHS) a national study of 1654 Singaporean citizens and permanent residents aged 50 to 59 years, conducted in 2016-2017. We account for age and other sociodemographic characteristics, measures of economic status, occupation, early retirement intentions, personality traits, as well as multiple physical health measures. Our findings indicate that age discrimination at work and job stress are both positively associated with higher depressive symptom scores. The relationship between age discrimination and depressive symptoms however varies by social networks, with age discrimination negatively associated with depressive symptom scores among those with larger friends-based social networks. Our findings indicate that while psychological wellbeing of late middle-aged workers is adversely affected by age discrimination and job stress, these workers benefit from wider and deeper social connections with friends. Our results provide empirical support to previous research that suggests that friends-based social networks yield distinct benefits in terms of subjective well-being and increased self-worth.


Recent technological developments provide individuals with vision impairment the transformative ability to upload pictures they take and promptly receive descriptions from remote workers. This study aimed to: identify challenges for visually impaired individuals to use such technology to obtain health-related information and provide recommendations for crowd-workers and the future development of assistive artificial intelligence (AI) design. In spring and summer of 2019, we analyzed 265 images of medication packages submitted by users of a visual question answering (VQA) application called VizWiz -- a smartphone application that provides near realtime assistance to visually impaired users by employing crowd-workers. We developed a 4-category coding scheme to analyze image quality, with two independent coders achieving excellent intercoder reliability (85%-95%). Of the 265 images, we found less than half were legible (46%), contained clear indicators for information sought (40%), or had minimum background noise (40%); while only a small percentage contained complete information (6%). Through thematic analysis of the data, we also highlight seven challenges with queries submitted by vision impaired users . Based on our findings, we make recommendations for the future design of VQA technologies, such as VizWiz, for visually impaired users. We also suggest that there is both great need and potential for user-centered design research to significantly enhance such assistive technologies. While this study did not focus exclusively on data submitted by aging adults, many VizWiz users are, in fact, aging adults, and such assistive technologies have strong implications for the design of assistive technology for this age group.


This paper explores how perceptions of unfair treatment shape healthcare satisfaction across race/ethnicity. We investigate the overall impact of life course exposure to healthcare discrimination on current healthcare satisfaction across race/ethnicity among a sample of midlife and older Black, Latinx, and White Americans age 50+ in the Health and Retirement Study. We then test whether everyday healthcare discrimination mediates the impact of major medical discrimination on healthcare satisfaction, controlling for sociodemographic factors, mental and physical health characteristics, functional status, life course stress exposure, and lifetime and everyday discrimination in contexts beyond healthcare settings. Black Americans had poorer healthcare satisfaction than White Americans. Everyday discrimination in healthcare settings mediated a modest amount of the relationship between lifetime healthcare discrimination and healthcare satisfaction, and this association varied in strength across White, Black, and Latinx Americans. Results underscore the need for future work identifying and addressing mechanisms shaping healthcare satisfaction.