Which roads lead to access? A global landscape of six COVID-19 vaccine innovation models.

BACKGROUND: Unequal and inequitable access to Covid-19 vaccines in low- and middle-income countries (L&MICs) was a major political, ethical and public health failure in the pandemic. However, vaccine developers' practices were not monolithic, but rather, took diverse approaches to supplying different countries, with important implications for global access. RESULTS: Using data on R&D investments, regulatory approvals, manufacturing and purchase agreements, and vaccine deliveries, we identified six distinct innovation models that apply across the 14 COVID-19 vaccines with more international presence from 2020-2022. "Western Early Arrivers" Pfizer/BioNTech and Moderna supplied the largest volumes quickly and prioritized high-income countries (HICs) from registration to vaccine delivery. "Western Latecomers" Janssen and Novavax supplied intermediate volumes later, also prioritizing HICs but with a greater proportion to L&MICs. "Major Chinese Developers" Sinopharm and Sinovac supplied intermediate volumes early, primarily to middle-income countries (MICs). "Russian Developer" Gamaleya completed development early but ultimately supplied small volumes, primarily to middle-income countries (MICs). "Cosmopolitan Developer" Oxford/AstraZeneca supplied large volumes early to HICs and MICs at the lowest prices. Finally, "Small MIC Developers" CanSino, Bharat Biotech, Medigen, Finlay Institute and the Center for Genetic Engineering and Biotechnology (CGEB), exported relatively small volumes to a few MICs. Low-income countries (LICs) were not targeted by any developer, and received far fewer doses, later, than any other income group. Almost all developers received public funding and other forms of support, but we found little evidence that such support was leveraged to expand global access. CONCLUSIONS: Each of the six innovation models has different implications for which countries get access to which vaccines, how quickly, and at which prices. Each offers different strengths and weaknesses for achieving equitable access. Our findings also suggest that Western firms had the greatest capacity to develop and deliver vaccines quickly during the pandemic, but such capacity is rapidly becoming more globally distributed with MICs playing a significant role, especially in supplying other MICs. Given the critical role of public support in enabling pandemic vaccine development and supply, governments have both the capacity and responsibility to craft international rules that will make responses to future pandemics more equitable and effective.

Metal-free photocatalytic cross-electrophile coupling enables C1 homologation and alkylation of carboxylic acids with aldehydes.

In contemporary drug discovery, enhancing the sp3-hybridized character of molecular structures is paramount, necessitating innovative synthetic methods. Herein, we introduce a deoxygenative cross-electrophile coupling technique that pairs easily accessible carboxylic acid-derived redox-active esters with aldehyde sulfonyl hydrazones, employing Eosin Y as an organophotocatalyst under visible light irradiation. This approach serves as a versatile, metal-free C(sp3)-C(sp3) cross-coupling platform. We demonstrate its synthetic value as a safer, broadly applicable C1 homologation of carboxylic acids, offering an alternative to the traditional Arndt-Eistert reaction. Additionally, our method provides direct access to cyclic and acyclic ß-arylethylamines using diverse aldehyde-derived sulfonyl hydrazones. Notably, the methodology proves to be compatible with the late-stage functionalization of peptides on solid-phase, streamlining the modification of intricate peptides without the need for exhaustive de-novo synthesis.

A Robust Method to Perform In Vitro and In Planta Interbacterial Competition Assays: Killing Plant Pathogens by a Potent Biocontrol Agent.

Interbacterial competition assays have become an essential tool for understanding the interactions between bacteria and their ability to outcompete one another in natural environments. This is especially relevant when studying the type VI secretion system (T6SS), a contact-dependent bacterial weapon that can be used to kill or inhibit the growth of other competing bacteria. Some beneficial environmental microorganisms such as Pseudomonas putida rely on the T6SS as their primary biocontrol mechanism to eliminate resilient plant pathogens. Competition assays are an essential methodology in this field that allows us to understand the efficacy of this bacterial nanoweapon. This chapter outlines the methodology for conducting in vitro and in planta competition assays between P. putida, a well-known biocontrol agent, and phytopathogenic bacterial species of economic and scientific interest.

Visceral fat sympathectomy ameliorates systemic and local stress response related to chronic sleep restriction.

Disturbance of sleep homeostasis encompasses health issues, including metabolic disorders like obesity, diabetes, and augmented stress vulnerability. Sleep and stress interact bidirectionally to influence the central nervous system and metabolism. Murine models demonstrate that decreased sleep time is associated with an increased systemic stress response, characterized by endocrinal imbalance, including the elevated activity of hypothalamic-pituitary-adrenal axis, augmented insulin, and reduced adiponectin, affecting peripheral organs physiology, mainly the white adipose tissue (WAT). Within peripheral organs, a local stress response can also be activated by promoting the formation of corticosterone. This local amplifying glucocorticoid signaling is favored through the activation of the enzyme 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1). In WAT, 11ß-HSD1 activity is upregulated by the sympathetic nervous system, suggesting a link between sleep loss, augmented stress response, and a potential WAT metabolic disturbance. To gain more understanding about this relationship, metabolic and stress responses of WAT-sympathectomized rats were analyzed to identify the contribution of the autonomic nervous system to stress response-related metabolic disorders during chronic sleep restriction. Male Wistar rats under sleep restriction were allowed just 6 h of daily sleep over eight weeks. Results showed that rats under sleep restriction presented higher serum corticosterone, increased adipose tissue 11ß-HSD1 activity, weight loss, decreased visceral fat, augmented adiponectin, lower leptin levels, glucose tolerance impairment, and mildly decreased daily body temperature. In contrast, sympathectomized rats under sleep restriction exhibited decreased stress response (lower serum corticosterone and 11ß-HSD1 activity). In addition, they maintained weight loss, explained by a reduced visceral fat pad, leptin, and adiponectin, improved glucose management, and persisting decline in body temperature. These results suggest autonomic nervous system is partially responsible for the WAT-exacerbated stress response and its metabolic and physiological disturbances.

Te Oranga O Te Roro: kaumatua perspectives on the development of a mobile app for mate wareware (dementia) awareness.

AIM: Mate wareware (dementia) presents a significant social and economic burden for Maori in Aotearoa New Zealand. Previous literature has highlighted the need to improve health literacy for Maori regarding the causes and management of mate wareware, yet there is a lack of Maori-centred educational resources. It was determined that a mobile phone application (app) could meet this need and that early consultation with Maori was required to ensure the digital solution would be culturally safe and relevant. METHOD: This study explored the perspectives of kaumatua (Maori elders) regarding how to cater the mate wareware mobile app to Maori. Through a qualitative approach based on Kaupapa Maori principles, two focus groups were held with 15 kaumatua. Focus group data were thematically analysed. RESULTS: The analysis identified four themes related to the content of the proposed app and its design features. "Information about mate wareware" and "Caregiver support" were prominent themes that kaumatua prioritised for inclusion in the proposed app. To ensure uptake, kaumatua emphasised that the "Access" and "Appeal" of the proposed app should be considered. CONCLUSION: The findings have informed the design of the Mate Wareware app and should be considered when developing other digital health interventions for Maori.

Rising pharmaceutical innovation in the Global South: a landscape study.

BACKGROUND: There is growing interest in pharmaceutical innovation in low- and middle-income countries (LMICs), but information on existing activities, capacities, and outcomes is scarce. We mapped available data at the global level, and studied the national pharmaceutical innovation systems of Bangladesh and Colombia to shed light on pharmaceutical research and development (R&D) in the Global South, including challenges and prospects, to help fill existing knowledge gaps. METHODS: We gathered and analyzed data from three types of sources: literature, semi-structured interviews with key informants, and publicly available data on R&D funding, R&D scientific capacity measured by human resources, and clinical trial activities. RESULTS: Pharmaceutical R&D activities are occurring in many LMICs, but 16 countries have emerged as frontrunners. Investment in R&D in LMICs has increased in the past decade, particularly from middle-income countries (MICs). Capacity is also growing, with an increase in the number of research organizations and the amount of funding available from external sources. The total number of clinical trials and the proportion of trials in LMICs increased markedly, and there is also growing activity in the earlier, more innovative and riskier Phase 1 and 2 trials. Non-commercial entities comprise the majority of clinical trial funders and sponsors in LMICs. Finally, investments have borne fruit, as indicated by a number of innovative medicines developed in LMICs. The Bangladesh and Colombia country studies showed that there is still a need for both targeted R&D policies to strengthen capacities in the pharmaceutical sector, and more government support to overcome the challenges of a lack of funding and coordination among different actors. CONCLUSIONS: By triangulating between the data sources, it was possible to paint a broad picture of who was involved in pharmaceutical R&D in LMICs, in which particular countries, for which diseases, in which R&D phases, and with what results-as well as how these trends have changed over time. Prioritizing pharmaceutical R&D is an important strategy for better meeting health needs. The trendlines are promising, but focused attention is still needed to realize the potential for greater innovation in the Global South.

ß-Turn Induction by a Diastereopure Azepane-Derived Quaternary Amino Acid.

ß-Turns are one of the most common secondary structures found in proteins. In the interest of developing novel ß-turn inducers, a diastereopure azepane-derived quaternary amino acid has been incorporated into a library of simplified tetrapeptide models in order to assess the effect of the azepane position and peptide sequence on the stabilization of ß-turns. The conformational analysis of these peptides by molecular modeling, NMR spectroscopy, and X-ray crystallography showed that this azepane amino acid is an effective ß-turn inducer when incorporated at the i + 1 position. Moreover, the analysis of the supramolecular self-assembly of one of the ß-turn-containing peptide models in the solid state reveals that it forms a supramolecular helical arrangement while maintaining the ß-turn structure. The results here presented provide the basis for the use of this azepane quaternary amino acid as a strong ß-turn inducer in the search for novel peptide-based bioactive molecules, catalysts, and biomaterials.

Living with Dementia in Aotearoa (LiDiA): A Feasibility Study for a Dementia Prevalence Study in Maori and Non-Maori Living in New Zealand.

INTRODUCTION: Recent estimations have projected a threefold increase in dementia prevalence in Aotearoa New Zealand (NZ) by 2050, particularly in Maori and Pacific peoples. However, to date, there are no national data on dementia prevalence, and overseas data are used to estimate the NZ dementia statistics. The aim of this feasibility study was to prepare the groundwork for the first full-scale NZ dementia prevalence study that is representative of Maori, European, Pacific and Asian peoples living in NZ. METHODS: The main feasibility issues were: (i) Sampling to ensure adequate community representation from the included ethnic groups, (ii) Preparing a workforce to conduct the fieldwork and developing quality control, (iii) Raising awareness of the study in the communities (iv) Maximizing recruitment by door-knocking, (v) Retaining those we have recruited to the study and (vi) Acceptability of study recruitment and assessment using adapted versions of the 10/66 dementia protocol in different ethnic groups living in South Auckland. RESULTS: We found that a probability sampling strategy using NZ Census data was reasonably accurate and all ethnic groups were sampled effectively. We demonstrated that we were able to train up a multi-ethnic workforce consisting of lay interviewers who were able to administer the 10/66 dementia protocol in community settings. The response rate (224/297, 75.5%) at the door-knocking stage was good but attrition at subsequent stages was high and only 75/297 (25.2%) received the full interview. CONCLUSIONS: Our study showed that it would be feasible to conduct a population-based dementia prevalence study using the 10/66 dementia protocol in Maori, European and Asian communities living in NZ, utilizing a qualified, skilled research team representative of the families participating in the study. The study has demonstrated that for recruitment and interviewing in Pacific communities a different but culturally appropriate approach is required.

Impacts of the COVID-19 lockdown on self-reported mood and self-rated health of community-dwelling adults with chronic illness.

AIM: To determine whether self-reported mood or self-rated health were affected in community-dwelling adults with chronic illness following COVID-19 lockdown. METHODS: This was a repeated cross-sectional study using secondary data. We included New Zealanders aged 40+ who underwent International Residential Instrument (interRAI) assessments in the year prior to COVID-19 lockdown (25 March 2019-24 March 2020) or in the year following COVID-19 lockdown (25 March 2020-24 March 2021). Pairwise comparisons were made between each pre-lockdown quarter and its respective post-lockdown quarter to account for seasonality patterns. Data from 45,553 (pre-lockdown) and 45,349 (post-lockdown) assessments were analysed. Outcomes (self-reported mood, self-rated health) were stratified by socio-demographic variables. RESULTS: Self-reported mood improved in the first quarter post-lockdown among those aged 80+, as well as among women, people of European ethnicity, those living alone and those living in more deprived areas. Self-rated health improved in these same groups, as well as among those aged 65-79, and among men. No differences in self-reported mood or self-rated health were found in the second, third, or fourth quarters post-lockdown. CONCLUSIONS: Self-reported mood and self-rated health of community-dwelling adults with chronic illness were not negatively affected following COVID-19 lockdown, and temporarily improved among some sub-groups. However, the longer-term impacts of the COVID-19 pandemic need to be closely monitored.

Genomic and epigenomic profile of thyroid cancer.

Thyroid cancer is the most common malignancy of the endocrine system, and its incidence has been steadily increasing. Advances in sequencing have allowed analysis of the entire cancer genome, and has provided new information on the genetic lesions and modifications responsible for the onset, progression, dedifferentiation and metastasis of thyroid carcinomas. Moreover, integrated genomics has advanced our understanding of the development of cancer and its behavior, and has facilitated the identification of new genetic mutations and molecular pathways. The functional analysis of epigenetic modifications, such as DNA methylation, histone acetylation and non-coding RNAs, have contributed to define new regulatory mechanisms that control cell malignancy in thyroid cancer, especially aggressive forms. Here we review the most recent advances in genomics and epigenomics of thyroid cancer, which have resulted in a new classification and interpretation of the initiation and progression of thyroid tumors, providing new tools and opportunities for further investigation and for the clinical development of new treatment strategies.

Current therapies for hypertrophic cardiomyopathy: a systematic review and meta-analysis of the literature.

AIMS: The aim of this study was to synthesize the evidence on the effect of the current therapies over the pathophysiological and clinical characteristics of patients with hypertrophic cardiomyopathy (HCM). METHODS AND RESULTS: A systematic review and meta-analysis of 41 studies identified from 1383 retrieved from PubMed, Web of Science, and Cochrane was conducted. Therapies were grouped in pharmacological, invasive and physical exercise. Pharmacological agents had no effect on functional capacity measured by VO2max (1.11 mL/kg/min; 95% CI: -0.04, 2.25, P < 0.05). Invasive septal reduction therapies increased VO2max (+3.2 mL/kg/min; 95% CI: 1.78, 4.60, P < 0.05). Structured physical exercise programmes did not report contraindications and evidenced the highest increases on functional capacity (VO2max + 4.33 mL/kg/min; 95% CI: 0.20, 8.45, P < 0.05). Patients with left ventricular outflow tract (LVOT) obstruction at rest improved their VO2max to a greater extent compared with those without resting LVOT obstruction (2.82 mL/kg/min; 95% CI: 1.97, 3.67 vs. 1.18; 95% CI: 0.62, 1.74, P < 0.05). Peak LVOT gradient was reduced with the three treatment options with the highest reduction observed for invasive therapies. Left ventricular ejection fraction was reduced in pharmacological and invasive procedures. No effect was observed after physical exercise. Symptomatic status improved with the three options and to a greater extent with invasive procedures. CONCLUSIONS: Invasive septal reduction therapies increase VO2max, improve symptomatic status, and reduce resting and peak LVOT gradient, thus might be considered in obstructive patients. Physical exercise emerges as a coadjuvant therapy, which is safe and associated with benefits on functional capacity. Pharmacological agents improve reported NYHA class, but not functional capacity.

Yap governs a lineage-specific neuregulin1 pathway-driven adaptive resistance to RAF kinase inhibitors.

BACKGROUND: Inactivation of the Hippo pathway promotes Yap nuclear translocation, enabling execution of a transcriptional program that induces tissue growth. Genetic lesions of Hippo intermediates only identify a minority of cancers with illegitimate YAP activation. Yap has been implicated in resistance to targeted therapies, but the mechanisms by which YAP may impact adaptive resistance to MAPK inhibitors are unknown. METHODS: We screened 52 thyroid cancer cell lines for illegitimate nuclear YAP localization by immunofluorescence and fractionation of cell lysates. We engineered a doxycycline (dox)-inducible thyroid-specific mouse model expressing constitutively nuclear YAPS127A, alone or in combination with endogenous expression of either HrasG12V or BrafV600E. We also generated cell lines expressing dox-inducible sh-miR-E-YAP and/or YAPS127A. We used cell viability, invasion assays, immunofluorescence, Western blotting, qRT-PCRs, flow cytometry and cell sorting, high-throughput bulk RNA sequencing and in vivo tumorigenesis to investigate YAP dependency and response of BRAF-mutant cells to vemurafenib. RESULTS: We found that 27/52 thyroid cancer cell lines had constitutively aberrant YAP nuclear localization when cultured at high density (NU-YAP), which rendered them dependent on YAP for viability, invasiveness and sensitivity to the YAP-TEAD complex inhibitor verteporfin, whereas cells with confluency-driven nuclear exclusion of YAP (CYT-YAP) were not. Treatment of BRAF-mutant thyroid cancer cells with RAF kinase inhibitors resulted in YAP nuclear translocation and activation of its transcriptional output. Resistance to vemurafenib in BRAF-mutant thyroid cells was driven by YAP-dependent NRG1, HER2 and HER3 activation across all isogenic human and mouse thyroid cell lines tested, which was abrogated by silencing YAP and relieved by pan-HER kinase inhibitors. YAP activation induced analogous changes in BRAF melanoma, but not colorectal cells. CONCLUSIONS: YAP activation in thyroid cancer generates a dependency on this transcription factor. YAP governs adaptive resistance to RAF kinase inhibitors and induces a gene expression program in BRAFV600E-mutant cells encompassing effectors in the NRG1 signaling pathway, which play a central role in the insensitivity to MAPK inhibitors in a lineage-dependent manner. HIPPO pathway inactivation serves as a lineage-dependent rheostat controlling the magnitude of the adaptive relief of feedback responses to MAPK inhibitors in BRAF-V600E cancers.

Alkyl Radical Generation via C-C Bond Cleavage in 2-Substituted Oxazolidines.

There is an urgent need to develop uncharged radical precursors to be activated under mild photocatalyzed conditions. 2-Substituted-1,3-oxazolidines (E ox < 1.3 V vs SCE, smoothly prepared from the corresponding aldehydes) have been herein employed for the successful release of tertiary, α-oxy, and α-amido radicals under photo-organo redox catalysis. The reaction relies on the unprecedented C-C cleavage occurring from the radical cation of these heterocyclic derivatives. Such a protocol is applied to the visible-light-driven conjugate radical addition onto Michael acceptors and vinyl (hetero)arenes under mild metal-free conditions.

Inhibiting ERK dimerization ameliorates BRAF-driven anaplastic thyroid cancer.

BACKGROUND: RAS-to-ERK signaling is crucial for the onset and progression of advanced thyroid carcinoma, and blocking ERK dimerization provides a therapeutic benefit in several human carcinomas. Here we analyzed the effects of DEL-22379, a relatively specific ERK dimerization inhibitor, on the activation of the RAS-to-ERK signaling cascade and on tumor-related processes in vitro and in vivo. METHODS: We used a panel of four human anaplastic thyroid carcinoma (ATC) cell lines harboring BRAF or RAS mutations to analyze ERK dynamics and tumor-specific characteristics. We also assessed the impact of DEL-22379 on the transcriptional landscape of ATC cell lines using RNA-sequencing and evaluated its therapeutic efficacy in an orthotopic mouse model of ATC. RESULTS: DEL-22379 impaired upstream ERK activation in BRAF- but not RAS-mutant cells. Cell viability and metastasis-related processes were attenuated by DEL-22379 treatment, but mostly in BRAF-mutant cells, whereas in vivo tumor growth and dissemination were strongly reduced for BRAF-mutant cells and mildly reduced for RAS-mutant cells. Transcriptomics analyses indicated that DEL-22379 modulated the transcriptional landscape of BRAF- and RAS-mutant cells in opposite directions. CONCLUSIONS: Our findings establish that BRAF- and RAS-mutant thyroid cells respond differentially to DEL-22379, which cannot be explained by the previously described mechanism of action of the inhibitor. Nonetheless, DEL-22379 demonstrated significant anti-tumor effects against BRAF-mutant cells in vivo with an apparent lack of toxicity, making it an interesting candidate for the development of combinatorial treatments. Our data underscore the differences elicited by the specific driver mutation for thyroid cancer onset and progression, which should be considered for experimental and clinical approaches.

Leptin and adiponectin regulate the activity of nuclei involved in sleep-wake cycle in male rats.

Epidemiological and experimental evidence recognize a relationship between sleep-wake cycles and adiposity levels, but the mechanisms that link both are not entirely understood. Adipose tissue secretes adiponectin and leptin hormones, mainly involved as indicators of adiposity levels and recently associated to sleep. To understand how two of the main adipose tissue hormones could influence sleep-wake regulation, we evaluated in male rats, the effect of direct administration of adiponectin or leptin in the ventrolateral preoptic nuclei (VLPO), a major area for sleep promotion. The presence of adiponectin (AdipoR1 and AdipoR2) and leptin receptors in VLPO were confirmed by immunohistochemistry. Adiponectin administration increased wakefulness during the rest phase, reduced delta power, and activated wake-promoting neurons, such as the locus coeruleus (LC), tuberomammillary nucleus (TMN) and hypocretin/orexin neurons (OX) within the lateral hypothalamus (LH) and perifornical area (PeF). Conversely, leptin promoted REM and NREM sleep, including increase of delta power during NREM sleep, and induced c-Fos expression in VLPO and melanin concentrating hormone expressing neurons (MCH). In addition, a reduction in wake-promoting neurons activity was found in the TMN, lateral hypothalamus (LH) and perifornical area (PeF), including in the OX neurons. Moreover, leptin administration reduced tyrosine hydroxylase (TH) immunoreactivity in the LC. Our data suggest that adiponectin and leptin act as hormonal mediators between the status of body energy and the regulation of the sleep-wake cycle.

Evaluation of the multimorbidity network and its relationship with clinical phenotypes in chronic obstructive pulmonary disease: The GALAXIA study.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a complex and heterogeneous condition, in which taking into consideration clinical phenotypes and multimorbidity is relevant to disease management. Network analysis, a procedure designed to study complex systems, allows to represent connections between the distinct features found in COPD. METHODS: Network analysis was applied to a cohort of patients with COPD in order to explore the degree of connectivity between different diseases, taking into account the presence of two phenotypic traits commonly used to categorize patients in clinical practice: chronic bronchitis (CB+ /CB- ) and the history of previous severe exacerbations (Ex+ /Ex- ). The strength of association between diseases was quantified using the correlation coefficient Phi (ɸ). RESULTS: A total of 1726 patients were included, and 91 possible links between 14 diseases were established. Although the four phenotypically defined groups presented a similar underlying comorbidity pattern, with special relevance for cardiovascular diseases and/or risk factors, classifying patients according to the presence or absence of CB implied differences between groups in network density (mean ɸ: 0.098 in the CB- group and 0.050 in the CB+ group). In contrast, between-group differences in network density were small and of questionable significance when classifying patients according to prior exacerbation history (mean ɸ: 0.082 among Ex- subjects and 0.072 in the Ex+ group). The degree of connectivity of any given disease with the rest of the network also varied depending on the selected phenotypic trait. The classification of patients according to the CB- /CB+ groups revealed significant differences between groups in the degree of conectivity between comorbidities. On the other side, grouping the patients according to the Ex- /Ex+ trait did not disclose differences in connectivity between network nodes (diseases). CONCLUSIONS: The multimorbidity network of a patient with COPD differs according to the underlying clinical characteristics, suggesting that the connections linking comorbidities between them vary for different phenotypes and that the clinical heterogeneity of COPD could influence the expression of latent multimorbidity. Network analysis has the potential to delve into the interactions between COPD clinical traits and comorbidities and is a promising tool to investigate possible specific biological pathways that modulate multimorbidity patterns.

Diagnostic accuracy of 10/66 dementia protocol in Maori kaumatua (elders) living in Aotearoa New Zealand.

AIMS: Dementia is an important health concern for Maori and therefore it is essential to explore the extent and impact of dementia in this community. The 10/66 dementia protocol, a widely used research tool for measuring the prevalence of dementia, was developed to minimise cultural and educational bias in comparisons of dementia prevalence across different countries and/or cultures. The aims of this study are to (i) adapt the 10/66 dementia protocol for use in research within the Maori community and (ii) test the diagnostic accuracy of the adapted (ie, Maori-friendly) 10/66 dementia protocol against the reference standard of a clinical diagnosis of dementia (or no dementia). METHOD: The sample included Maori aged 65 and over who had been assessed at a local memory service. Ten dementia cases and 10 controls were included. The sample was further enriched by the inclusion of 6 controls from a concurrent dementia-prevalence feasibility study in the local community. The Maori-friendly 10/66 dementia protocol was measured against the reference standard. Sensitivity, specificity, positive and negative predictive values and Youden's Index were calculated. RESULTS: The Maori-friendly 10/66 dementia protocol had a sensitivity of 90.0% (95% CI 62.8-99.4), specificity of 93.8% (95% CI 75.3-99.6), positive predictive value of 90.0% (95% CI 62.8-99.4), negative predictive value of 93.8% (95% CI 75.3-99.6) and Youden's Index of 0.83. CONCLUSIONS: Our study results provide preliminary evidence that the Maori-friendly 10/66 dementia protocol has adequate discriminatory abilities for the diagnosis of dementia. Our study also demonstrates that the Maori-friendly 10/66 dementia protocol has the potential to be used in a dementia-population-based study for Maori in Aotearoa New Zealand.