Privilege Status Research Articles

Molecular heterogeneity of quiescent melanocyte stem cells revealed by single-cell RNA-sequencing.

Melanocyte stem cells (McSCs) of the hair follicle are a rare cell population within the skin and are notably underrepresented in whole-skin, single-cell RNA sequencing (scRNA-seq) datasets. Using a cell enrichment strategy to isolate KIT+/CD45- cells from the telogen skin of adult female C57BL/6J mice, we evaluated the transcriptional landscape of quiescent McSCs (qMcSCs) at high resolution. Through this evaluation, we confirmed existing molecular signatures for qMcCS subpopulations (e.g., Kit+, Cd34+/-, Plp1+, Cd274+/-, Thy1+, Cdh3+/-) and identified novel qMcSC subpopulations, including two that differentially regulate their immune privilege status. Within qMcSC subpopulations, we also predicted melanocyte differentiation potential, neural crest potential, and quiescence depth. Taken together, the results demonstrate that the qMcSC population is heterogeneous and future studies focused on investigating changes in qMcSCs should consider changes in subpopulation composition.

Dandruff lesional scalp skin exhibits epidermal T cell infiltration and a weakened hair follicle immune privilege.

Dandruff is characterised by the presence of perivascular leukocytes and mild inflammation; however, the immune microenvironment of dandruff-affected scalp skin and the potential changes to the hair follicle's (HF) physiological immune privilege (HF IP) remain unknown. Here, we characterised the HF immune microenvironment and immune privilege status in dandruff-affected scalp skin. We assessed relevant key parameters in healthy versus dandruff-affected human scalp biopsies using quantitative immunohistomorphometry, laser capture microdissection, and RNA sequencing. The number of epidermal CD4+ and CD8+ T cells was increased in lesional dandruff scalp skin, while the number of MHC class II+/CD1a+ Langerhans cells was decreased in the infundibulum. The number of intrafollicular and perifollicular CD4+ T cells and CD8+ T cells, perifollicular CD68+ macrophages, and tryptase+ mast cells remained unchanged. Interestingly, MHC class Ia and ß2-microglobulin protein expression were significantly increased specifically in the suprabulbar outer root sheath (ORS) compartment of dandruff-associated HFs. RNAseq analysis of laser capture micro-dissected suprabulbar ORS compartment revealed antigen presentation pathway as the top regulated canonical pathway, along with the upregulation of HF-IP genes such as HLA-C, HLA-DP, and TAP1, which are normally down-regulated in healthy HFs. Intrafollicular protein expression of known HF IP guardians (CD200 and α-MSH) and 'danger signals' (MICA and CXCL10) remained unaltered at the IP sites of dandruff lesional HFs compared to non-lesional and healthy HFs. Instead, the expression of macrophage migration inhibiting factor (MIF), another HF IP guardian, was reduced. Together, this work shows that dandruff is associated with epidermal T-cell infiltration and a weakened HF IP in the suprabulbar ORS of HFs in dandruff lesional scalp.

The crosstalk between PTEN-induced kinase 1-mediated mitophagy and the inflammasome in the pathogenesis of alopecia areata.

Alopecia areata (AA) is a T-cell-mediated autoimmune disease that causes chronic, relapsing hair loss; however, its precise pathogenesis remains to be elucidated. Recent studies have provided compelling evidence of crosstalk between inflammasomes and mitophagy-a process that contributes to the removal of damaged mitochondria. Our previous studies showed that the NLR family pyrin domain containing 3 (NLRP3) inflammasome is important for eliciting and progressing inflammation in AA. In this study, we detected mitochondrial DNA damage in AA-affected scalp tissues and IFNγ and poly(I:C) treated outer root sheath (ORS) cells. In addition, IFNγ and poly(I:C) treatment increased mitochondrial reactive oxygen species (ROS) levels in ORS cells. Moreover, we showed that mitophagy induction alleviates IFNγ and poly(I:C)-induced NLRP3 inflammasome activation in ORS cells. Lastly, PTEN-induced kinase 1 (PINK1) knockdown increased NLRP3 inflammasome activation, indicating that PINK1-mediated mitophagy plays a critical role in NLRP3 inflammasome activation in ORS cells. This study supports previous studies showing that oxidative stress disrupts immune privilege status and promotes autoimmunity in AA. The results emphasize the significance of crosstalk between mitophagy and inflammasomes in the pathogenesis of AA. Finally, mitophagy factors regulating mitochondrial dysfunction and inhibiting inflammasome activation could be novel therapeutic targets for AA.

Impact of an Urban Project ECHO: Safety-Net Clinician Self-Efficacy Across Conditions

To mitigate the lack of specialty healthcare, Project ECHO (Extension for Community Health Outcomes) trains community-based primary care clinicians to better prevent the progression of, manage, and treat common health conditions. ECHO-Chicago launched in 2010 as the first urban-centered ECHO program, focusing on safety-net clinicians, and has trained over 5,175 community clinicians across 34 topic areas. This paper examines self-efficacy among ECHO-Chicago participants across 11 clinical series, including a novel use of qualitative themes from self-efficacy questions. Five years of baseline and postseries survey data were collected from 2014 to 2019, resulting in 951 participants. Paired t-tests assessed change from baseline survey to postsurvey, and Cohen's d determined effect size. Change was assessed by individual series, adult or pediatric focus, participants' prescription privilege status, and across series by qualitative question theme. Metrics included total change, any improvement, a 10% target, and a clinical competency threshold. Analysis occurred from July 2020 to January 2022. All clinical series achieved statistically significant improvement in self-efficacy, and most had a large effect size. A total of 80% had any improvement, 65% met the 10% target of 0.7 points, and 52% met the competency threshold of 5.0 in the postsurvey. Prescribers had a significantly greater increase in their self-efficacy scores than nonprescribers. With a comparison across series, each theme achieved statistical significance, with most reaching large effect sizes. ECHO-Chicago successfully increased participants' self-efficacy. This inquiry adds an urban focus, years of data, multiple series, and a novel qualitative theme component to enable comparisons across rather than solely within the ECHO series.

584 Dandruff is associated with perturbations of hair follicle immune privilege, and the infundibular and epidermal immune microenvironment

Dandruff is a common scalp condition. The immune-microenvironment of dandruff scalp skin remains poorly characterised and the hair follicle’s physiological immune privilege (HF IP) status in dandruff is completely unknown. We hypothesised that the latter might be important in the context of dandruff-associated inflammation as the HF IP status is expected to impact on overall scalp skin immunophysiology. We analysed the expression of HF IP biomarkers (CD200, MHC class I, β2M, MHC class II) and HF IP guardians (α-MSH and MIF), and quantified intra- and perifollicular immune cells (CD4, CD8 and CD68) in healthy versus dandruff scalp (non-lesional and lesional) biopsies by quantitative immunohistomorphometry(n= 5-8).

Ocular Gene Therapy: A Literature Review with Special Focus on Immune and Inflammatory Responses.

Gene therapy has emerged as a research topic of choice in recent years. The eye in particular is one of few organs of the body for which gene therapy has received Food and Drug Administration approval, and it remains a field of great interest for gene therapy development. However, its associated immune and inflammatory reactions may render the treatment ineffective or harmful, which are of particular concern for the eyes due to their susceptibility to inflammation. The severity of immune and inflammatory reactions depends on the choice of vector and its route of administration. Furthermore, most preclinical and clinical studies have shown that the dose of vectors is correlated with the degree of humoral response and ocular inflammation. The route of administration directly impacts the degree of immune and inflammatory reaction. Subretinal delivery produces a weaker humoral response than the intravitreal route. However, some studies have demonstrated that the subretinal delivery induces a stronger inflammatory reaction. On the other hand, several instances of vision loss due to severe late onset intraocular inflammation were reported in a clinical trial involving intravitreal delivery of viral vectors. When compared with the intravitreal route, suprachoroidal gene delivery has been shown to produce weaker humoral response. However, unlike the subretinal space, the suprachoroidal space is not known to have immune privilege status. Inflammatory reactions following ocular gene therapy are typically mild and most clinical and preclinical studies have shown that they can be controlled with topical, local or systemic steroids. However, severe inflammatory responses may occur and require aggressive management to avoid permanent vision loss. Further investigations are required to elucidate and expand our knowledge of inflammatory reactions, and their optimal management, following ocular gene therapy.

Leadership for equality in education: 50 years marching forward or marching on the spot?

This article examines how Educational Management, Administration and Leadership has embodied the values, concepts and practice of the field of educational leadership over 50 years and so played a part in challenging or sustaining inequality in education. The article explores selected key concepts, equal opportunities, diversity, and social justice, the disciplinary base and prevalent research methods underpinning work on inequality, the geographic location and characteristics of relevant published authors and the two areas which attract most attention, gender and ethnicity/race. All areas embody both a push for change and structural inhibitors that limit its extent. Omissions, silences and displacements are also examined, questioning why, for example, a focus on masculinity, white privilege, learner voice and lower status sectors of education hardly surfaces in half a century. The article concludes that despite the positive achievements of the journal in forwarding equality, there is an equality double bind whereby, like a Trojan virus, parameters limiting change are embedded in the very work that seeks to promote it. A number of positive suggestions for changes in the journal and field are made to encourage researchers and practitioners to detect and resist previous strategies of evasion and limitation.

Implications of RNA Viruses in the Male Reproductive Tract: An Outlook on SARS-CoV-2.

Emerging viral infections continuously pose a threat to human wellbeing. Several RNA viruses have managed to establish access to the male reproductive tract and persist in human semen. The sexual transmission of the virus is of critical public concern. The epidemiological inferences are essential to understand its complexity, particularly the probability of viral transmission from asymptomatic patients or those in the incubation period or from the patient who was previously infected and now fully recovered. From the clinical perspective, negative impacts in the male reproductive tract associated with RNA virus infection have been described, including orchitis, epididymitis, impaired spermatogenesis, and a decrease in sperm quality, which can affect male fertility at different time intervals. The disruption of anatomical barriers due to inflammatory responses might enable the viral invasion into the testis, and the immune privilege status of testes might facilitate a sustained persistence of the virus in the semen. In this review, the current knowledge about other RNA viruses that affect male reproductive health provides the framework to discuss the impact of the SARS-CoV-2 pandemic. The molecular mechanisms, sexual transmission, and viral impacts for mumps, HIV, Zika, and Ebola viruses are explored. We discuss the currently available information on the impact of SARS-CoV-2 and its sequelae in the male reproductive tract, particularly regarding presence in semen, its impact on sexual organs, and sperm quality. To date, no sexual transmission of SARS-CoV-2 has been reported, whereas the identification of viral particles in semen remains conflicting. In the purview of the earlier conducted analyses, it is essential to investigate further the long-term health impacts of SARS-CoV-2 on the male reproductive tract.

Immunoregulation in the testis and its implication in fertility and infections

The testis is designated as one of the immune previleged sites in the body and harbours a unique immunoregulatory environment, which is important for preventing an immune response against sperm antigens which otherwise are recognized as “foreign” by the immune system. The blood-testis barrier along with the unique immune cells repertoire and various immunoregulatory & immunosuppressive factors secreted by the Leydig cells, Sertoli cells and peritubular cells act in concert to maintain the tolerogenic environment in the testis. Abberations in immunotolerant mechanisms in the testis can lead to generation of anti-sperm antibodies that have an association with male infertility. It can also lead to inflammatory conditions of the male reproductive tract manifested as epididymitis and orchitis, generally due to bacterial or viral infections. In addition, non-infectious epididymitis and orchitis, having autoimmune origin have also been reported in males. While the immune privilege status of human testis protects the germ cells from an immune attack, it can also make the testis a succeptible reservoir for viruses such as human immunodeficiency virus-1, Zika virus and severe acute respiratory syndrome coronavirus-2, all of which have adverse consequences on male reproduction.

String of Relationship in the Sky of Multiculturalism: A Reading of Khaled Hosseini’s The Kite Runner

This paper proposes how the relationship that exists between different characters in his novels is experimented in diverse conditions and the characters are tested and tried to discover their unique paths of assimilation with their loved ones to the completion of their circle. Despite the spatial differences, each character is connected with a string of bond which portrays the ‘similarity’ of difference, yet humanity in need of understanding. The physical space and emotional space of Baba’s beautiful house in the Wazir Akbar Khan district is contrasted with the shack of Hassan and Ali breaks the dichotomy of contentment and dissatisfaction. Simultaneously with the diversity of multiculturalism it creates fantasies of escape from ideological and cultural divisions altogether. Interconnected relationship and affections blur the ethnic, social, geographical and economic variances in individual.The characters all experience a personal journey for love in their own way through their words and actions. The genetic ties to the geographies of privilege, ethnic difference and social status often challenged through the personal affinity. Troubled relationship like Baba and Amir, or an enigmatic friendship like Amir and Hassan or passive bond like Ali and Hassan or even a romantic relationship like Amir and Soraya are circulating the web of ontology. Relationship, assimilation and struggle of people cross path with desperate societies resulting a relief from haunting memories. The longing for love and to be loved draw the characters to find the web of their completeness and ultimately that give them the strength to fight back with their vulnerabilities , surpass their limitations, and eventually to purify their guilt through overwhelming acts of self-sacrifice.

A folliculocentric perspective of dandruff pathogenesis: Could a troublesome condition be caused by changes to a natural secretory mechanism?

Dandruff is a common scalp condition, which frequently causes psychological distress in those affected. Dandruff is considered to be caused by an interplay of several factors. However, the pathogenesis of dandruff remains under-investigated, especially with respect to the contribution of the hair follicle. As the hair follicle exhibits unique immune-modulatory properties, including the creation of an immunoinhibitory, immune-privileged milieu, we propose a novel hypothesis taking into account the role of the hair follicle. We hypothesize that the changes and imbalance of yeast and bacterial species, along with increasing proinflammatory sebum by-products, leads to the activation of immune response and inflammation. Hair follicle keratinocytes may then detect these changes in scalp microbiota resulting in the recruitment of leukocytes to the inflammation site. These changes in the scalp skin immune-microenvironment may impact hair follicle immune privilege status, which opens new avenues into exploring the role of the hair follicle in dandruff pathogenesis. Also see the video abstract here: https://youtu.be/mEZEznCYtNs.

Terrified by Technology: How Systemic Bias Distorts U.S. Legal and Regulatory Responses to Emerging Technology

Americans are becoming increasingly aware of the systemic biases we possess and how those biases preclude us from collectively living out the true meaning of our national creed. But to fully understand systemic bias we must acknowledge that it is pervasive and extends beyond the contexts of race, privilege, and economic status. Understanding all forms of systemic bias helps us to better understand ourselves and our shortcomings. At first glance, a human bias against emerging technology caused by systemic risk misperception might seem uninteresting or unimportant. But this Article demonstrates how the presence of systemic bias anywhere, even in an area as unexpected as technology regulation, creates inefficiencies and inequalities that exact heavy costs in the form of human lives, standards of living, and lost economic opportunities. The decision to regulate or implement an emerging technology, like any other complex decision, naturally involves some form of cost-benefit or risk-reward analysis. However, in the context of emerging technology, that analysis is biased by systemic risk misperception. Immutable characteristics existing in emerging technology combine with interrelated characteristics in human decisionmakers and regulators to inflate perceptions of risks and depress perceptions of benefits. This artificial shifting of cost-benefit curves results in suboptimal legislative and regulatory responses to emerging technology, and ultimately, in the loss of American lives.

Students’ Learning Styles in Relation to Service Physical Education Performance

This study aimed to determine the students’ learning styles, whether visual, auditory, or kinesthetic learning style, in relation to their Service Physical Education performance in terms of written and practical exam results. The moderating variables of age, gender, academic status, religion, and course were also considered. This was conducted among Service P.E. students of the Mindanao State University, Marawi City, officially enrolled during the 2nd semester, A.Y. 2015 – 2016. This descriptive-correlation study was conducted among 925 respondents (227 male and 588 female respondents). The VARK Learning Styles Questionnaire developed by Victoria Chislett was used to assess their learning styles. The Service P.E. performance was taken from their partial written and practical exams. The majority of the respondents were15-18 years old; most of the respondents were female; most of the respondents were Tuition Privilege status; most of the respondents were Islam believers while others were non-Muslim, and almost all of the respondents were Bachelor of Science (BS) degree pursuers. In terms of learning styles, it was found out that most of the respondents were visual learners. With regard to the Service P.E. performance, most of the respondents received grades of 1.0-1.25 or excellent in their written exams while most of them were rated 1.50-1.75 or very good in their practical exams. The relationship between the variables found out that there were no significant relationships between the moderating variables of age, religion, and course with their respective p-values of 0.272, 0.188, and 0.355 to the independent variable of learning styles. However, there were significant relationships between the moderating variables of gender, academic status and the independent variable of learning styles. Furthermore, age (p = 0.184), academic status (p = 0.385), religion (p = 0.784), and course (p = 0.869) were not significantly related to written exam performance while gender was significantly related to written exam performance. Practical exam performance showed no relationship with the different moderating variables. For the relationship between learning styles and Service P.E. performance, it was revealed that learning styles had a significant relationship between written exam performance, while no relationship existed between learning styles and practical exam performance. Good performance in the written exams matters most in how the students prepare for it. On the other hand, ability, preparation, and constant correct practice will matter the most in preparation for practical exams. Thus, it is recommended that Physical Education administrators formulate plans to further improve the competencies of Physical Education teachers, especially in identifying the different learning styles of their respective students, to provide appropriate teaching approaches that facilitate effective learning experiences among their students. Physical Education teachers should provide enough time for skills practice so that most of their students will have greater chances of obtaining higher ratings in their practical exams. A similar study should be conducted in the future using other variables or using an equal number of respondents in gender and religion.

Economic geography, to what ends? From privilege to progressive performances of expertise

Recent Exchanges have focused on economic geography’s purported ‘decline’ and its patriarchal and generational privilege, asking ‘who speaks’ for the subdiscipline. This Exchanges piece asks another kind of existential question: what ends does economic geography serve? And how is economic geographical expertise marshalled and performed towards such ends – especially beyond the British context, where much of the debate has focused? Drawing briefly upon collaborative research experiences in Sydney, Australia, I offer thoughts on progressive contributions arising from grounded empirical research within cities subject to profound transformation from speculative real estate, and hypercharged by global finance. Amid unsolicited plans for massive rezoning of industrial spaces and accompanying displacement of manufacturing, repair and cultural industries, credible economic geographical data assisted activists and sympathetic local decisionmakers by bringing to light the significance of existing spaces of work (especially in industrially zoned land) subject to rezoning plans. Contestation over massive real estate proposals continues in Sydney, but empirical research targeted at public debate has nevertheless already shifted the narrative. While academic privilege and expert status warrants intra-disciplinary critique, what also matters is whether, how and where economic geographers deploy expertise productively towards progressive ends. Hence, critically engaged economic geography flourishes in different forms beyond the discipline's imagined ‘core’ places, even via quite ‘dry’ empirical studies that on the surface do not declare radical intents. Economic geographers are key intermediaries circulating knowledges, active agents in making concrete manifestations of the economy known. And that is a crucial point of intervention.

Enhanced Expression of FGF Signaling in Primary Central Nervous System Lymphoma

Introduction:Primary central nervous system lymphoma (PCNSL) is a rare intracranial lymphoma that accounts for less than 1% of all non-Hodgkins lymphomas and 3% of all brain tumors. Histopathologically, approximately 90% of PCNSL cases are categorized as a diffuse large B-Cell lymphoma (DLBCL). DLBCL malignancies are subdivided by Cell of Origin (COO), with the vast majority of PCNSL categorized as non-germinal center B cell (non-GCB) by immunohistochemistry. Gene expression profiling (GEP), however, has shown that immunohistochemically defined non-GCB resolves into two distinct subtypes, namely activated B-cell (ABC) and unclassified (UNC) subtypes. Using the Lymph2Cx molecular COO subtyping assay, we have found that 91% of PCNSL are ABC (unpublished data). Unlike systemic-DLBCL, PCNSL is largely confined to and rarely metastasizes outside of the immune privileged central nervous system. Despite this, PCNSL is one of the most aggressive forms of DLBCL. Given the immune privileged milieu in which PCNSL arises, we hypothesized that this milieu elicits a transcriptional profile that contributes to the enhanced aggressive nature of PCNSL compared to systemic-DLBCL. To investigate this hypothesis, this study assessed the gene expression differences between ABC-PCNSL and ABC-systemic-DLBCL, in order to identify novel players in the pathogenesis of ABC-PCNSL.Methods:A total of 35 HIV negative samples, with proven ABC-subtype COO as per the GEP Lymph2Cx assay, were employed; including 10 ABC systemic-DLBCL and 25 primary ABC PCNSL cases with no concurrent or prior history of systemic DLBCL. Samples were reviewed by a hematopathologist to confirm diagnoses and determine tumor content. Samples with <60% tumor content were macro-dissected before nucleic acid extraction, which was performed using the Qiagen AllPrep DNA/RNA FFPE Kit. Extracted DNA and RNA were quantified using the Qubit HS-kit and NanoDrop respectively. Digital gene expression technology was used to perform the PanCancer Pathways panel (NanoString, Seattle, WA). Differential gene expression analysis was performed using the NanoString specific statistical method NanoStringDiff. Identified gene sets were analyzed using the online Gene Set Enrichment Analysis (GSEA) Molecular Signatures Database (MSigDB).Results:Of the 739 cancer related genes targeted by the PanCancer panel, 256 were found to be significantly differentially expressed in the ABC-PCNSL cohort compared to the ABC-DLBCL cohort (p<0.05). Fifty six genes were upregulated and 200 were downregulated. With a 4.9 fold change, the most significantly overexpressed gene was FGF1 (p=4.7E-11). FGF1 encodes a primary ligand for the fibroblast growth factor receptors (FGFR) -1, -2, -3 and -4; of which, FGFR2 (p=1.0E-7) and FGFR3 (p=0.003) were also significantly overexpressed. Moreover, MSigDB identified the FGF signaling pathway as enriched in the upregulated gene set (5 genes, p=7.4E-9, FDR=6.6E-7). FGFRs are a family of receptors that activate known mitogenic signaling pathways including MAPK signaling, which MSigDB identified as the most enriched pathway in the upregulated gene set (14 genes, p=1.65E-19, FDR=2.2E-16). MSigDB analysis of the 200 down regulated genes revealed that 5 of the top 20 enriched signaling pathways were immune related and included Signaling by interleukins (26 genes, p=2.9E-38, FDR=3.2E-36), Immune cytokine signaling (31 genes, p=1.1 E-34, FDR=1.1E-32), chemokine signaling (28 genes, p=1.5E-34, FDR=1.4E-32), T-cell receptor signaling (24 genes, p=2.4E-34, FDR=1.9E-32) and Toll-like receptor signaling (23 genes, p=4.1E-33, FDR=3.0E-31).Conclusions:We show, for the first time, that ABC-PCNSL and ABC-systemic-DLBCL possess significantly different transcriptional profiles despite identical, molecularly determined, COO status. A principle difference between these DLBCL malignancies is their anatomical location related immune privilege status which is reflected as reduced immune related signaling in the CNS-DLBCL cohort and may have important mitogenic signaling implications. Indeed, the results suggest that the enhanced aggressive nature of PCNSL compared to systemic-DLBCL is mediated, at least in part, by enhanced FGF signaling; a pathway with known roles in cell survival and proliferation. DisclosuresRimsza:NanoString: Other: Inventor on the patent for the Lymph2Cx assay.

Tolerance Induction in Relation to the Eye.

Inflammatory intraocular eye diseases, grouped under the term uveitis are blinding conditions, believed to be mediated by pathogenic autoimmune processes that overcome the protective mechanisms of the immune privilege status of the eye. An animal model for these diseases, named experimental autoimmune uveitis (EAU), is induced by initiation of immunity against ocular-specific antigens, or it develops spontaneously in mice with T-cells that transgenically express TCR specific to the target eye antigen(s). T-Cells specific to ocular antigens are generated in the thymus and their majority are eliminated by exposure to their target antigen expressed in this organ. T-cells that escape this negative selection acquire pathogenicity by their activation with the target antigen. In spontaneous EAU, the microbiota play crucial roles in the acquisition of pathogenicity by providing both antigenic stimulation, by molecules that mimic the target ocular antigen, and an additional stimulation that allows invasion of tissues that harbor the target antigen. The pathogenic process is physiologically inhibited by the peripheral tolerance, composed of antigen-specific T-regulatory (Treg) lymphocytes. Deleting the Tregs enhances the ocular inflammation, whereas adoptively transferring them suppresses the pathogenic response. Potential usage of Treg cells for suppression of autoimmune diseases in humans is under intensive investigation.

Immune cells and vasa vasorum in the tunica media of atherosclerotic coronary arteries.

In coronary artery disease (CAD), the disruption of the tunica media immune privilege manifests as increased leukocyte infiltration and the formation of vasa vasorum. We aimed to characterize the immune privilege status of the tunica media in human coronary arteries (CAs) with atherosclerotic plaques, by comparing the abundance and composition of immune-cell infiltrates within the individual arterial-wall layers, and by evaluating vasa vasorum neovascularization of the tunica media. The tissue samples were obtained from 36 symptomatic patients with diffuse CAD (aged 60-72 years) who underwent coronary endarterectomy. T and B cells, macrophages and endothelial cells in the CAs were detected by immunohistochemistry. Morphological analysis of CAs showed significant atherosclerotic changes in all specimens. In the media, we observed damage and loss of smooth muscle cells, destruction of the extracellular matrix architecture, and fibrosis. There were 43.3% of immune cells in the intima, 50% in the adventitia, and 6.7% in the media. In the media, 51.1% of the immune cells were T cells (p ˂ 0.001 compared to B cells and macrophages; ANOVA, Scheffe post hoc analysis), 23.5% were B cells, and 25.4% were macrophages. The number of vasa vasorum in the media was 1 in 38.9% of CAs, 2-3 in 36.1%, and ≥4 in 25% of CAs. Our results indicate that, in atherosclerotic CAs, the immune privilege of the media is disrupted by the infiltration of T and B cells, macrophages, and the presence of vasa vasorum.

Penatalaksanaan Alopecia Areata (Treatment of Allopecia Areata)

Background: Alopecia Areata (AA) is a disease characterized by loss of hair from the scalp of a sudden. The main principle of treatment of AA that inhibit or alter the immunological response by modulating the inflammatory process that occurs around hair follicles. There are several options in the treatment of AA Purpose: provide insight into a variety of existing AA management. Review: AA is a form of autoimmune disease mediated by T lymphocytes that attack hair follicles and hair loss is characterized by chronic and recurrent. Based on the latest research results, the onset and severity of AA are determined by the interaction between genetic factors and environmental factors of the originator. Currently the hypothesis of AA focuses on the collapse of immune privilege status of a hair follicle and presentation of self-antigens that cause active lymphocytes. Several factors such as genetics, autoantigen, immune cell activity, and stress factors played a role in the pathogenesis of AA. The basic principle of treatment of AA, can be divided into two, namely Immunosuppressant and immunomodulatory will manipulate the inflammatory process intrakutan. Conclusion: Several therapeutic options in the AA include the injection of corticosteroids, minoxidil, immunotherapies, photochemotherapy, calcineurin inhibitors, metrotrexate, sulfasalazzine, azatioprine, laser therapy, PRP therapy, and therapy with stem cells Key word: allopecia areata, treatment

Therapist and Coloniser

This article discusses issues in treating the historical trauma of Māori, the colonised peoples of Aotearoa New Zealand. The advent of Māori psychotherapy has enabled valuable insight into the needs of such clients, but, even as it helps define a space of safety and nurture for Māori, questions arise about how non-Māori practitioners might treat Māori clients from outside this largely intra-cultural process. The article focuses on the response from New Zealand Pākehā (that is, New Zealanders of European descent), due to the fact that they are in the most primary bicultural relationship with Māori, in which an inherent white privilege and coloniser status complicates the relational process. Finally, the article discusses the difficulties Pākehā experience in bridging intercultural divides around cultural competency, power structures, and the importance of cultural self-awareness, which may also have a wider multicultural relevance to other tauiwi (non-Maori) practitioners.&#x0D; Whakarāpopotonga&#x0D; He matapakinga kaupapa whakatika i te hītori whetuki o te Māori, te tangata pēhitia o Aotearoa. Nō te tīmatanga ake o te whakaora hinengaro Māori te whakamanahanga o ngā mātauranga mārihi ki ngā hiahia ō aua kiritaki, engari, ahakoa e āwhinahia ana te tautuhi ātea haumanu, poipoi mō te Māori, ka ara tonu ake te pātai mō te momo whakaora kiritaki Māori ā ngā kaiwhakaora o iwi kē i waho ake i tēnei hātepe ahurei-takitahi. Ka arotika atu tēnei tuhinga ki te urupare mai ā ngā Pākehā, nā te mea ko rātau te kākano rua mātāmua ki te Māori, e puta ake nei te momo hao ā-mā me te tūranga kaipēhitanga hai whakauaua i te hātepe whakawhanaunga. Hai whakamutunga, ka matapakihia te uauatanga o te wheako Pākehā ki te whakawhiti tautuhi ahurei whakapā ki te toa ahurei, te mana whakatakotoranga, me te tokānuku o te tuakiri ahurei, ā, tērā pea he pānga whānui ake anō ki ngā kaimahi (iwi kē) kākano maha.

Personalised genome editing - The future for corneal dystrophies.

The potential of personalised genome editing reaching the clinic has come to light due to advancements in the field of gene editing, namely the development of CRISPR/Cas9. The different mechanisms of repair used to resolve the double strand breaks (DSBs) mediated by Cas9 allow targeting of a wide range of disease causing mutations. Collectively, the corneal dystrophies offer an ideal platform for personalised genome editing; the majority of corneal dystrophies are monogenic, highly penetrant diseases with a known pattern of inheritance. This genetic background coupled with the accessibility, ease of visualisation and immune privilege status of the cornea make a gene editing strategy for the treatment of corneal dystrophies an attractive option. Off-target cleavage is a major concern for the therapeutic use of CRISPR/Cas9, thus current efforts in the gene editing field are focused on improving the genome-wide specificity of Cas9 to minimise the risk of off-target events. In addition, the delivery of CRISPR/Cas9 to different tissues is a key focus; various viral and non-viral platforms are being explored to develop a vehicle that is highly efficient, specific and non-toxic. The rapid pace and enthusiasm with which CRISPR/Cas9 has taken over biomedical research has ensured the personalised medicine revolution has been realised. CRISPR/Cas9 has recently been utilised in the first wave of clinical trials, and the potential for a genome editing therapy to treat corneal dystrophies looks promising. This review will discuss the current status of therapeutic gene editing in relation to the corneal dystrophies.