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The directional learning path our Indigenous Knowloegde (IK) reveals, is happening and emerging in a way that is based in our lore and systems. What I refer to here in Australia is over 60, 000 years of continuous cultural knowledge connected around 60,000 years’ worth of campfires. The pattern which we gather and sit around these campfires is in circle. And the circle pattern we have gathered around these times creates a distinct flow of energy and knowledge transfer. The distinct pattern of IK transfer at Deakin’s Indigenous Knowledge System Lab (IKSL) now, can be understood in four ways, IK in Production; Transmission; Application and Regeneration. We see emergence through the patterns and stories that are brought through following the whisps of smoke from the fire – the unseen made known through the form of smoke - dgumge. To pay homage to our beginnings in shares and development of knowledge’s we write together as part of the ‘IK pattern’ of yarning (Yunkaporta, 2019), we use in Labs – us/only, us/twos and us/all ways of communicating. This paper is a way for us/two, Dr. Rhonda Coopes – palawa and Dr. John Davis – Cobble Cobble, as fellow countrywomen and men, camped around these IKSL fires, to give some markers, lay some tracks, make sense of the paths we take through the ever-emerging patterns of IKSL yarns, actions, and project activities.

This paper characterizes a pandemic as a kind of contagion, and describes a contagion as a two-level, two-direction, reflexive feedback loop system. In such a system, expert opinions for managing a pandemic can act as self-fulfilling prophecies due to how they influence collective belief formation. However, when multiple experts produce multiple expert opinions that act as self-fulfilling prophecies, this can fragment a society’s response to a pandemic, worsening rather than ameliorating it. This paper models this possible outcome by distinguishing two competing expert opinions, appealing respectively to people in club good and common pool types of employment/health insurance situations, and argues that to combat fragmentation of opinion about how to address a pandemic, public health policy needs to attend to the nature of public reasoning. It argues this entails asking how just and legitimate deliberative institutions can function in an ‘inclusive and noncoercive’ way that allows society to reconcile competing visions regarding how to combat system-wide crises such as pandemics.

Alzheimer's disease (AD) is the most common form of dementia, and risk-influencing genetics implicates microglia and neuroimmunity in the pathogenesis of AD. Induced pluripotent stem cell (iPSC)-derived microglia (iPSC-microglia) are increasingly used as a model of AD, but the relevance of historical immune stimuli to model AD is unclear. We performed a detailed cross-comparison over time on the effects of combinatory stimulation of iPSC-microglia, and in particular their relevance to AD. We used single-cell RNA sequencing to measure the transcriptional response of iPSC-microglia after 24 h and 48 h of stimulation with prostaglandin E2 (PGE2) or lipopolysaccharide (LPS)+interferon gamma (IFN-γ), either alone or in combination with ATPγS. We observed a shared core transcriptional response of iPSC-microglia to ATPγS and to LPS+IFN-γ, suggestive of a convergent mechanism of action. Across all conditions, we observed a significant overlap, although directional inconsistency to genes that change their expression levels in human microglia from AD patients. Using a data-led approach, we identify a common axis of transcriptomic change across AD genetic mouse models of microglia and show that only LPS provokes a transcriptional response along this axis in mouse microglia and LPS+IFN-γ in human iPSC-microglia. This article has an associated First Person interview with the first author of the paper.

Distributed acoustic sensing (DAS) systems are a recent technological development for seismic observations over a broad range of frequencies with a wide variety of applications. Typically, fibre-optic cables are buried underground or cemented into well casings where the cables are well-coupled to the ground. Quick and temporary surface deployment of cables has great potential utility in areas where rapid surveying and minimal disturbance of the subsurface are desired. However, proper mechanical coupling between the fibre and the ground is still a challenge for temporary surface deployments. Here we test four different coupling strategies for a DAS system deployed in a grassy field, including uncoupled, pinned under tension to the ground, weighted down by carpeting, and weighted down by a sandbag. We compare the DAS data to vertical component geophone data and estimated horizontal geophone data to assess the fidelity of DAS ground motion recordings. We find a completely uncoupled fibre is capable of recording seismic energy up to ∼10 m away from the source, while the pinned and weighted fibre record signals over several tens of metres. The DAS recordings compare favourably with the estimated horizontal displacement records from the multi-channel seismic system. There is a good agreement between the phase of the signals acquired by the DAS system with that of the geophones, but there is a mismatch of up to a factor of two in the absolute amplitude at some frequencies. We perform several standard analysis techniques, including refraction and multi-channel analysis of surface waves, on the coupled DAS data. Finally, the instrument response of the coupled DAS data to ground motions is determined using the estimated horizontal component from the multi-channel seismic system. Surface deployments of DAS systems provide a complementary set of observations to standard vertical geophone deployments, for instance, if multi-component geophones are not available. Also, there are some advantages in speed and ease of deployment of DAS in comparison to geophones depending on the coupling strategy used.

(1) Background: High-frequency heart rate variability (HF-HRV) is an essential ultradian rhythm that reflects the activity of the PNS to decelerate the heart. It is unknown how HF-HRV varies across the menstrual cycle (MC), and whether progesterone mediates this potential variation. (2) Methods: We enrolled 33 women in the study to attend eight clinic visits across the MC, during which we measured their resting HF-HRV and collected samples for the analysis of luteinizing hormone (LH) and progesterone. We realigned the study data according to the serum LH surge to the early follicular, mid-follicular, periovulatory, early luteal, mid-luteal and late luteal subphases. (3) Results: Pairwise comparisons between all the subphases showed significant differences between the early follicular and periovulatory subphases (β = 0.9302; p ≤ 0.001) and between the periovulatory and early luteal subphases (β = −0.6955; p ≤ 0.05). Progesterone was positively associated with HF-HRV in the early follicular subphase but not the periovulatory subphase (p ≤ 0.05). (4) Conclusions: The present study shows a significant drop in HF-HRV in the anticipation of ovulation. Further research in this area is critical given the marked cardiovascular disease mortality in women.

Background: Allopregnanolone is one of the most studied neuroactive steroids; yet, despite its relevance to neuropsychiatric research, it is not known how it, as well as its ratio to progesterone, varies across all six subphases of the menstrual cycle. Two enzymes—5α-dihydroprogesterone and 5α-reductase—convert progesterone to allopregnanolone, and, based on immunohistochemical studies in rodents, the activity of 5α-reductase is considered the rate-limiting step in the formation of allopregnanolone. It is not clear, however, whether the same phenomenon is observed across to the menstrual cycle, and, if so, at what point this takes place. Methods: Thirty-seven women completed the study during which they attended eight clinic visits across one menstrual cycle. We analyzed their allopregnanolone and progesterone serum concentrations using ultraperformance liquid chromatography–tandem mass spectrometry, and we implemented a validated method to realign the data from the original eight clinic study visits, following which we imputed the missing data. Hence, we characterized allopregnanolone concentrations, and the ratio of allopregnanolone:progesterone at six menstrual cycle subphases: (1) early follicular, (2) mid-follicular, (3) periovulatory, (4) early luteal, (5) mid-luteal, and (6) late luteal. Results: There were significant differences in allopregnanolone levels between (1) early follicular and early luteal, (2) early follicular and mid-luteal, (3) mid-follicular and mid-luteal, (4) periovulatory and mid-luteal, and (5) mid-luteal and late luteal. We detected a sharp drop in allopregnanolone:progesterone ratio in the early luteal subphase. Within the luteal subphase, the ratio was the lowest in the mid-luteal subphase. Conclusions: Allopregnanolone concentrations are the most distinct, relative to the other subphases, in the mid-luteal subphase. The shape of the allopregnanolone trajectory across the cycle is similar to that of progesterone; however, the proportion of the two neuroactive steroid hormones is drastically different due to enzymatic saturation, which takes place at the start of the early luteal subphase, but continuing through, and peaking, in the mid-luteal subphase. Hence, the estimated activity of 5α-reductase decreases, but does not cease, at any point across the menstrual cycle.

Figure S3. Pathways regulated by ∆Np63-induced and -repressed genes.

Figure S5. TGFβ regulates ΀�Np63 expression via miR-22-3p, miR-30a-5p, miR-203a-3p and miR-222-3p.

This file contains the following: Supplementary Figure 1: Representative H&E staining and immunohistochemistry for keratin 5 of a metastasis in the lung of a tumor-bearing TAp63-/- mouse. Supplementary Figure 2: TAp63-deficient tumors exhibit deregulated mRNA and miRNA expression. Supplementary Figure 3: TAp63-regulated miR-30c-2* and miR-497-5p suppresses cuSCC through induction of cell death and cell cycle arrest. Supplementary Figure 4: Identification of miRNA targets through the use of TMT-LC-MS/MS. Supplementary Figure 5: Inhibition of miR-30c-2-3p and miR-497-5p targets affects cuSCC cell proliferation and survival. Supplementary Figure 6: AURKA is a viable therapeutic target in cuSCC. Supplementary Methods and Materials. Supplementary References.

Figure S6. Correlation between �Np63 and microRNAs expression in cancer cell lines.

Figure S1. �Np63 promotes breast cancer cell growth in vivo

Table S4. PCA scores for each patient in the four COCA molecular subtypes from TCGA.

Table S2. Differential expressed microRNAs in MCF10DCIS cells treated with TGFβ.

Figure S2. �Np63 expression is essential for breast cancer lung colonization.

Table S1. List of pathways enriched in ∆Np63-induced and -repressed gene signatures.

Figure S4. TGFβ inhibits expression of ΀�Np63 via canonical Smad-dependent signaling in breast cancer.

ΔNp63 is a transcription factor of the p53 family and has crucial functions in normal development and disease. The expression pattern of ΔNp63 in human cancer suggests dynamic regulation of this isoform during cancer progression and metastasis. Many primary and metastatic tumors express high levels of ΔNp63, while ΔNp63 loss is crucial for tumor dissemination, indicating an oscillatory expression of ΔNp63 during cancer progression. Here, we use genetically engineered orthotopic mouse models of breast cancer to show that while depletion of ΔNp63 inhibits primary mammary adenocarcinoma development, oscillatory expression of ΔNp63 in established tumors is crucial for metastatic dissemination in breast cancer. A TGFβ-regulated miRNA network acted as upstream regulators of this oscillatory expression of ΔNp63 during cancer progression. This work sheds light on the pleiotropic roles of ΔNp63 in cancer and unveils critical functions of TGFβ in the metastatic process.Significance:This study unveils TGFβ signaling and a network of four miRNAs as upstream regulators of ΔNp63, providing key information for the development of therapeutic strategies to treat cancers that commonly overexpress ΔNp63.

Supplementary information includes Supplementary figure legends, Materials and Methods, and Reference

TAp63 is a p53 family member and potent tumor and metastasis suppressor. Here, we show that TAp63−/− mice exhibit an increased susceptibility to ultraviolet radiation–induced cutaneous squamous cell carcinoma (cuSCC). A human-to-mouse comparison of cuSCC tumors identified miR-30c-2* and miR-497 as underexpressed in TAp63-deficient cuSCC. Reintroduction of these miRNAs significantly inhibited the growth of cuSCC cell lines and tumors. Proteomic profiling of cells expressing either miRNA showed downregulation of cell-cycle progression and mitosis-associated proteins. A mouse to human and cross-platform comparison of RNA-sequencing and proteomics data identified a 7-gene signature, including AURKA, KIF18B, PKMYT1, and ORC1, which were overexpressed in cuSCC. Knockdown of these factors in cuSCC cell lines suppressed tumor cell proliferation and induced apoptosis. In addition, selective inhibition of AURKA suppressed cuSCC cell proliferation, induced apoptosis, and showed antitumor effects in vivo. Finally, treatment with miR-30c-2* or miR-497 miRNA mimics was highly effective in suppressing cuSCC growth in vivo. Our data establish TAp63 as an essential regulator of novel miRNAs that can be therapeutically targeted for potent suppression of cuSCC.Significance:This study provides preclinical evidence for the use of miR-30c-2*/miR-497 delivery and AURKA inhibition in the treatment of cuSCC, which currently has no FDA-approved targeted therapies.See related commentary by Parrales and Iwakuma, p. 2439

Supplementary Table 1: Differentially expressed genes in TAp63-/- cuSCC vs. TAp63-/- skin Supplementary Table 2: Differentially expressed miRNAs in TAp63-/- cuSCC vs. TAp63-/- skin Supplementary Table 3: microRNA-mRNA pair analysis of TAp63-/- cuSCC vs. TAp63-/- skin: Underexpressed miRNAs and overexpressed mRNAs. Supplementary Table 4: microRNA-mRNA pair analysis of TAp63-/- cuSCC vs. TAp63-/- skin: Overexpressed miRNAs and underexpressed mRNAs. Supplementary Table 5: Differentially expressed mRNAs from TAp63-/- cuSCC vs cuSCC and Human cuSCC vs. skin. Supplementary Table 6: Differentially expressed miRNAs from TAp63-/- cuSCC vs cuSCC and Human cuSCC vs. skin. Supplementary Table 7: GSEA of common differentially expressed mRNAs in TAp63-/- cuSCC and human cuSCC. Supplementary Table 8: Differentially expressed proteins in miR-30c-2* mimic transfected COLO16 cells measured by TMT-6-plex LC-MS/MS. Supplementary Table 9: Differentially expressed proteins in miR-497 mimic transfected COLO16 cells measured by TMT-6-plex LC-MS/MS. Supplementary Table 10: miRNA target prediction of corresponding mRNAs for the differentially expressed proteins in the miR-30c-2* transfected COLO16 cells. Supplementary Table 11: miRNA target prediction of corresponding mRNAs for the differentially expressed proteins in the miR-497 transfected COLO16 cells. Supplementary Table 12: Overexpressed mRNAs in both mouse TAp63-/- cuSCC and human cuSCC RNA-Seq signatures

Table S3. List of 64 TGFβ-induced microRNAs that are predicted to have binding sites to 3'UTR of p63 by miRWalk algorithm.

Acute autoimmune hemolytic anemia requires rapid stabilization, typically through the administration of high-dose corticosteroids. However, it is important to consider reactivation of latent infection and how immune suppression can interfere with molecular screening tools. In this case report, we present a patient with Rheumatoid Arthritis/Systemic Lupus Erythematosus experiencing severe autoimmune hemolytic anemia complicated by an unknown latent tuberculosis infection.

High throughput genomic data analysis is becoming an increasingly integral part of biomedical research. The information derived from gene expression analysis helps in diagnosing the treatment modality given to the patient. However, the amount of data is humongous and becomes complex to examine manually. Unsupervised machine learning algorithms perform complex tasks on an unlabelled data by clustering to comprehend the underlying structure and behaviour of the pattern. Clustering microarray data, examines the differential expressed genes found by grouping the genes based on the similarity of the expression values. In this study, we propose to elucidate the best clustering algorithm for gene expression data on various clinical conditions. The proposed study was carried on three gene expression datasets of Severe acute respiratory syndrome, Amyotrophic lateral sclerosis and Parkinson’s disease. Differentially expressed genes were found at three p-values 0.01, 0.05, 0.001 and the most significant number of genes were retrieved at p-value 0.05. We experimented the differential expressed genes on three clustering algorithms, namely Hierarchical clustering, k-means clustering and fuzzy clustering of the three diseases. The performance of the three clustering algorithms was evaluated using the internal validity index, wherein Hierarchical clustering was found to be best for gene expression data.

Youth-focused researchers and practitioners need conceptual models to consider paths for youth citizenship and social justice which are attenuated to the context, social support, visibility, and structure of engagement opportunities. This article will expand upon the initial conceptual model created by Brennan et al. in this special issue by examining how it can be useful for both research and practice. Specifically, this model can help researchers and practitioners to: (1) remain aware of contextual factors affecting youth engagement; (2) understand how different forms of youth engagement fit within the model; and (3) consider strategies and research to encourage more radical forms of youth engagement. The paper will provide support for the conceptual validity of the model by examining theories which align with it and contextual factors to consider during its application. The paper will then apply the model to differentiate between two forms of youth engagement and conclude with a summary of areas for future research and application.

Sensory features (i.e., atypical responses to sensory stimuli) are included in the current diagnostic criteria for autism spectrum disorder. Yet, large population-based studies have not examined these features. This study aimed to determine the prevalence of sensory features among autistic children, and examine associations between sensory features, demographics, and co-occurring problems in other areas. Analysis for this study included a sample comprised of 25,627 four- or eight-year-old autistic children identified through the multistate Autism and Developmental Disabilities Monitoring Network (2006-2014). We calculated the prevalence of sensory features and applied multilevel logistic regression modeling. The majority (74%; 95% confidence interval: 73.5%-74.5%) of the children studied had documented sensory features. In a multivariable model, children who were male and those whose mothers had more years of education had higher odds of documented sensory features. Children from several racial and ethnic minority groups had lower odds of documented sensory features than White, non-Hispanic children. Cognitive problems were not significantly related to sensory features. Problems related to adaptive behavior, emotional states, aggression, attention, fear, motor development, eating, and sleeping were associated with higher odds of having documented sensory features. Results from a large, population-based sample indicate a high prevalence of sensory features in autistic children, as well as relationships between sensory features and co-occurring problems. This study also pointed to potential disparities in the identification of sensory features, which should be examined in future research. Disparities should also be considered clinically to avoid reduced access to supports for sensory features and related functional problems. LAY SUMMARY: In a large, population-based sample of 25,627 autistic children, 74% had documented differences in how they respond to sensation. We also identified significant associations of sensory features with adaptive behavior and problems in other domains. Sensory features were less common among girls, children of color, and children of mothers with fewer years of education, suggesting potential disparities in identification.

It is not clear whether progesterone and estradiol associate with premenstrual food cravings, which significantly contribute to cardiometabolic adverse effects associated with obesity. We sought to investigate this question in the present study based on the prior literature showing a protective effect of progesterone on drug craving and extensive neurobiological overlaps between food and drug cravings. We enrolled 37 non-illicit drug- or medication-using women in the study to provide daily ratings of premenstrual food cravings and other symptoms across two-three menstrual cycles, based on which we classified them as premenstrual dysphoric disorder (PMDD) or control participants. In addition, the participants provided blood samples at eight clinic visits across the menstrual cycle. We aligned their mid-luteal progesterone and estradiol using a validated method which relies upon the peak serum luteinizing hormone and analyzed estradiol and progesterone using ultraperformance liquid chromatography tandem mass spectrometry. Hierarchical modeling, adjusted for BMI, showed a significant inverse effect of progesterone (p = 0.038) but no effect of estradiol on premenstrual food cravings. The association was not unique to PMDD or control participants. Results of research to date in humans and rodents showing that progesterone has dampening effects on the salience of the reinforcer translate to premenstrual food cravings.

Human survival and wellbeing require appropriate responses to stress, including a highly coordinated and efficient nervous system control of the heart rhythm. During stress, a greater disinhibition of the vagal nerve is reflective of poor stress adaptability, which may be relevant in premenstrual dysphoric disorder (PMDD)—a debilitating affective condition thought to be marked by dysregulated stress processing and sensitivity to allopregnanolone. In the present study, women with PMDD (n = 17) and healthy controls (n = 18), who did not take medication, smoke, or consume illicit drugs, and who were free of other psychiatric conditions, participated in the Trier Social Stress Test, during which we measured the high frequency of the heart rate (HF-HRV) and allopregnanolone using ultra-performance liquid chromatography tandem mass spectrometry. Relative to their baseline, women who have PMDD, but not the healthy controls, experienced a reduction in HF-HRV during stress anticipation (p ≤ 0.05) and stress (p ≤ 0.01). Their recovery from stress was significantly delayed (p ≤ 0.05). Absolute peak HF-HRV change from baseline was significantly predicted by baseline allopregnanolone only in the PMDD group (p ≤ 0.01). The present study shows how an interaction between stress and allopregnanolone—which have both been separately implicated in PMDD—underlies PMDD expression.

Primary open-angle glaucoma (POAG) is the most common subtype of glaucoma. We evaluate the cost-effectiveness of polygenic risk score (PRS) profiling as a screening tool for POAG.We used a Markov cohort model to evaluate the cost-effectiveness of implementing PRS screening in the UK and Australia, conducted from the healthcare payer's perspective. We used published data to calculate prevalence, transition probabilities, utility, cost and other parameters in the model. Our main outcome measure was the incremental cost-effectiveness ratio (ICER) and secondary outcomes were years of blindness avoided and a 'Blindness ICER'. We did one-way as well as two-way deterministic and probabilistic sensitivity analyses.The proposed screening programme for POAG in the UK is predicted to result in ICER of £24,783 (95% CI: £13,373-66,960) and would avoid 1 year of blindness at ICER of £10,095 (95% CI: £5513-27,656). In Australia, it is predicted to result in ICER of AU$34,252 (95% CI: AU$21,324-95,497) and would avoid 1 year of blindness at ICER of AU$13,359 (95% CI: AU$8143-37,448). Using the willingness to pay thresholds of $54,808 and £30,000, the proposed screening model is 79.2% likely to be cost-effective in Australia and is 60.2% likely to be cost-effective in the UK, respectively.We describe and model the cost-efficacy of incorporating a polygenic risk score for POAG screening in Australia and the UK for the first time and results indicated this is a promising cost-effectiveness strategy.

The goals of this work are the evaluation of the performances of official methods in the challenging determination of Cr(VI) in Cr(III)-rich particulate matter, and the development of a novel and robust analytical protocol for this issue. A liquid chromatography inductively coupled plasma mass spectrometry apparatus (LC-ICP-MS), together with an isotope-enriched spike addition technique, was used to allow the study of Cr(III)/Cr(VI) interconversions during the extraction step. An original separation strategy based on Cr(OH)3 head-column stacking was developed to tolerate high concentrations of Cr(III) (up to 10 mg/kg, with a Cr(VI) limit of detection of 0.51 µg/kg) without the need of any sample pretreatment. After observing, the official extraction protocols always yield false positive values in the challenging situation of particulate matter of leather industries (where huge amounts of Cr(III) are present), a new extraction strategy was developed. The novel procedure involves a 48-h extraction at room temperature using a pH-8 phosphate buffer, which demonstrated that no Cr(III)/Cr(VI) interconversions occur during this phase. To get rid of any possible interference caused by co-extracted substances, the measurement of the redox potential, together with the addition of a Fe(II)/Fe(III) redox buffer was performed to fix chromium speciation during the overall analytical protocol.

The regulation of DHEA-sulfate by steroid sulfotransferase (SULT) and steryl-sulfatase (STS) enzymes is a vital process for the downstream formation of many steroid hormones. DHEA-sulfate is the most abundant steroid hormone in the human body; thus, DHEA-sulfate and its hydrolyzed form, DHEA, continue to be evaluated in numerous studies, given their importance to human health. Yet, a basic question of relevance to the reproductive-age female population—whether the two steroid hormones vary across the menstrual cycle—has not been addressed. We applied a validated, multi-step protocol, involving realignment and imputation of study data to early follicular, mid-late follicular, periovulatory, and early, mid-, and late luteal subphases of the menstrual cycle, and analyzed DHEA-sulfate and DHEA serum concentrations using ultraperformance liquid chromatography tandem mass spectrometry. DHEA-sulfate levels started to decrease in the early luteal, significantly dropped in the mid-luteal, and returned to basal levels by the late luteal subphase. DHEA, however, did not vary across the menstrual cycle. The present study deep-mapped trajectories of DHEA and DHEA-sulfate across the entire menstrual cycle, demonstrating a significant decrease in DHEA-sulfate in the mid-luteal subphase. These findings are relevant to the active area of research examining associations between DHEA-sulfate levels and various disease states.

The fifth annual summer research summit organized by the Center of Excellence (COE) in Health Equity, Training and Research, Baylor College of Medicine (BCM), was held on May 17, 2022. The theme of this year’s summit was ‘Academic-Community Partnerships: Change Agents for Advancing Health Equity.’ Given the ongoing pandemic, the summit was conducted virtually through digital platforms. This program was intended for both BCM and external audiences interested in advancing health equity, diversity, and inclusion in healthcare among healthcare providers and trainees, biomedical scientists, social workers, nurses, and individuals involved in talent acquisition and development, such as hiring managers (HR professionals), supervisors, college and hospital affiliate leadership and administrators, as well as diversity and inclusion excellence practitioners. We had attendees from all regions of the United States as well as from Saudi Arabia. The content in this Book of Abstracts encapsulates a summary of the research efforts by the BCM COE scholars (which includes post-baccalaureate students, medical students, clinical fellows, and junior faculty from BCM) as well as the external summit participants. The range of topics in this year’s summit was quite diverse, encompassing disparities in relation to maternal and child health (MCH), immigrant health, cancers, vaccination uptakes, and COVID-19 infections. Various solutions were ardently presented to address these disparities, including community engagement and partnerships, improvement in health literacy, and the development of novel technologies and therapeutics. With this summit, BCM continues to build on its long history of educational outreach initiatives to promote diversity in medicine by focusing on programs aimed at increasing the number of diverse and highly qualified medical professionals ready to introduce effective and innovative approaches to reduce or eliminate health disparities. These programs will improve information resources, clinical education, curricula, research, and cultural competence as they relate to minority health issues and social determinants of health. The year’s summit was a great success! Copyright © 2022 Dongarwar et al. Published by Global Health and Education Projects, Inc. This is an open-access article distributed under the terms of the Creative Commons Attribution License CC BY 4.0.

COVID-19 was originated in Wuhan, China, in December 2019 and has been declared a pandemic disease by WHO. The number of infected cases continues unabated and so far, no specific drug approved for targeted therapy. Hence, there is a need for drug discovery from traditional medicine. Tiryaq-e-Wabai is a well-documented formulation in Unani medicine for its wide use as prophylaxis during epidemics of cholera, plague and other earlier epidemic diseases. The objective of the current study is to generate in-silico evidence and evaluate the potency of Tiryaq-e-Wabai against SARS-CoV-2 spike (S) glycoprotein and main protease (3CLpro). The structures of all phytocompounds used in this study were retrieved from PubChem database and some were built using Marvin Sketch. The protein structure of the SARS-CoV-2 S glycoprotein and 3CLpro was retrieved from the PDB ID: 6LZG and 7BQY respectively. AutoDock Vina was used to predict top ranking poses with best scores. The results of the molecular docking showed that phytocompounds of Tiryaq-e-Wabai exhibited good docking power with spike glycoprotein and 3CLpro. Among tested compounds Crocin from Zafran and Aloin A from Sibr showed strong binding to spike glycoprotein and 3CLpro respectively. Molecular dynamics simulation confirmed the stability of the S glycoprotein-Crocin and 3CLpro-Aloin A complexes. The Unani formulation Tiryaq-e-Wabai has great potential to inhibit the SARS-CoV-2, which have to be substantiated with further in-vitro and in-vivo studies. Keywords: In-silico study, SARS-CoV-2, Tiryaq-e-Wabai, Unani formulation, Crocin, Aloin A

As the consequences of climate change become better understood, there is growing agreement among development practitioners and academics on the need for mainstreaming climate adaptation into social protection. This review paper assesses the progress in mainstreaming efforts, revealing that there has been considerable progress made to date. However, a number of critical issues relating to the challenges of such mainstreaming in the context of developing countries and the conceptual framework needed to assess the outcomes of such developmental programmes are yet to be addressed. These issues are examined in this paper.