Nemabiome metabarcoding shows a high prevalence of Haemonchus contortus and predominance of Camelostrongylus mentulatus in alpaca herds in the northern UK.

Gastrointestinal nematodes (GINs) are a common threat faced by pastoral livestock. Since their major introduction to the UK in the early 1990s, South American camelids have been cograzed with sheep, horses, and other livestock, allowing exposure to a range of GIN species. However, there have been no molecular-based studies to investigate the GIN populations present in these camelids. In the current study, we sampled nine alpaca herds from northern England and southern Scotland and used high-throughput metabarcoded sequencing to describe their GIN species composition. A total of 71 amplicon sequence variants (ASVs) were identified representing eight known GIN species. Haemonchus contortus was the most prevalent species found in almost all herds in significant proportions. The identification of H. contortus in other livestock species is unusual in the northern UK, implying that alpacas may be suitable hosts and potential reservoirs for infection in other hosts. In addition, the camelid-adapted GIN species Camelostrongylus mentulatus was identified predominantly in herds with higher faecal egg counts. These findings highlight the value of applying advanced molecular methods, such as nemabiome metabarcoding to describe the dynamics of gastrointestinal nematode infections in novel situations. The results provide a strong base for further studies involving cograzing animals to confirm the potential role of alpacas in transmitting GIN species between hosts.

Pannexin 1 dysregulation in Duchenne muscular dystrophy and its exacerbation of dystrophic features in mdx mice.

BACKGROUND: Duchenne muscular dystrophy (DMD) is associated with impaired muscle regeneration, progressive muscle weakness, damage, and wasting. While the cause of DMD is an X-linked loss of function mutation in the gene encoding dystrophin, the exact mechanisms that perpetuate the disease progression are unknown. Our laboratory has demonstrated that pannexin 1 (Panx1 in rodents; PANX1 in humans) is critical for the development, strength, and regeneration of male skeletal muscle. In normal skeletal muscle, Panx1 is part of a multiprotein complex with dystrophin. We and others have previously shown that Panx1 levels and channel activity are dysregulated in various mouse models of DMD. METHODS: We utilized myoblast cell lines derived from DMD patients to assess PANX1 expression and function. To investigate how Panx1 dysregulation contributes to DMD, we generated a dystrophic (mdx) mouse model that lacks Panx1 (Panx1-/-/mdx). In depth characterization of this model included histological analysis, as well as locomotor, and physiological tests such as muscle force and grip strength assessments. RESULTS: Here, we demonstrate that PANX1 levels and channel function are reduced in patient-derived DMD myoblast cell lines. Panx1-/-/mdx mice have a significantly reduced lifespan, and decreased body weight due to lean mass loss. Their tibialis anterior were more affected than their soleus muscles and displayed reduced mass, myofiber loss, increased centrally nucleated myofibers, and a lower number of muscle stem cells compared to that of Panx1+/+/mdx mice. These detrimental effects were associated with muscle and locomotor functional impairments. In vitro, PANX1 overexpression in patient-derived DMD myoblasts improved their differentiation and fusion. CONCLUSIONS: Collectively, our findings suggest that PANX1/Panx1 dysregulation in DMD exacerbates several aspects of the disease. Moreover, our results suggest a potential therapeutic benefit to increasing PANX1 levels in dystrophic muscles.

COMPARISON OF SUBCUTANEOUS ALFAXALONE AND SUBCUTANEOUS ALFAXALONE-DEXMEDETOMIDINE FOR SEDATION IN THE HOUSTON TOAD (ANAXYRUS HOUSTONENSIS).

The Houston toad (Anaxyrus houstonensis), a primarily terrestrial amphibian of south-central Texas, has been listed as federally endangered since 1970. Sedation is an important tool for obtaining diagnostics and providing treatment in this species. This prospective, randomized, and blinded study compared the sedative effects of SC alfaxalone (Protocol A) at approximately 12 mg/kg (median [range] = 12.70 [12.09-13.95] mg/kg] to SC alfaxalone-dexmedetomidine (Protocol AD) at approximately 12 mg/kg (median [range] = 12.68 [12.16-13.56] mg/kg) and 0.1 mg/kg (median [range] = 0.1 [0.07-0.13] mg/kg), respectively, in adult Houston toads (n = 26). Toads from Protocol AD received atipamezole SC at approximately 1 mg/kg (median [range] = 0.96 [0.75-1.25] mg/kg) 45 min postinduction, whereas toads from Protocol A received the equivalent volume of SC sterile saline at the same time point. Heart rate, gular rate, and times to first effect, loss of righting reflex, ability to position for radiographs, loss of nociception, return of righting reflex, and full recovery were recorded. A significantly greater number of toads lost righting reflex, positioned for radiographs, and lost nociception with Protocol AD compared with Protocol A. Additionally, time to return of righting reflex and time to full recovery were significantly longer with Protocol AD than with Protocol A. The protocols did not differ significantly in time to first effect, time to radiographic positioning, or time to loss of nociception. Histologic examination of four toads euthanized during the study revealed acute injection site reactions from all administered drugs, including saline. No clinical adverse reactions were observed. This study demonstrates that the combination of SC alfaxalone and dexmedetomidine results in deeper sedation than SC alfaxalone alone, but also correlates with longer recovery times despite antagonist administration.

Association of Traumatic Brain Injury and Glioblastoma Multiforme: A Case Series.

Glioblastoma multiforme (GBM) is an aggressive variant of central nervous system gliomas that carries a dismal prognosis. Although GBM is the most frequently occurring and malignant type of glioma accounting for more than 60% of all brain tumors in adults, its overall incidence is rare, occurring at a rate of 3.21 per 100,000 persons. Little is known about the etiology of GBM, but one proposed theory is that GBM pathogenesis may be linked to a chronic inflammatory course initiated by traumatic injury to the brain. Limited case reports have suggested an association between GBMs and traumatic brain injury (TBI), but larger case-control and epidemiologic studies have been inconclusive. We present three service members (two active duty and one retired) who developed GBM near the original site of prior head trauma. Each service member's military occupation was in the special operations community and shared a common theme of TBI following head trauma/injury. The current research on the association between TBI and GBM is limited and conflicting, predominantly due to the low incidence of the disease in the general population. Evidence has indicated that TBI should be considered a chronic disease with long-term health impacts, including long-term disability, dementia, epilepsy, mental health conditions, and cardiovascular diseases. With the addition of our patients, as well as a recently published study proposing a molecular association between trauma and GBM, further research is needed to better understand the potential relationship.

CT imaging of intrauterine devices (IUD): expected findings, unexpected findings, and complications.

Intrauterine devices (IUDs) are a commonly used form of long-acting reversible contraception, which either contain copper or levonorgestrel to prevent pregnancy. Although symptomatic patients with indwelling IUDs may first undergo ultrasound to assess for device malposition and complications, IUDs are commonly encountered on CT in patients undergoing evaluation for unrelated indications. Frequently, IUD malposition and complications may be asymptomatic or clinically unsuspected. For these reasons, it is important for the radiologist to carefully scrutinize the IUD on any study in which it is encountered. To do so, the radiologist must recognize that normally positioned IUDs are located centrally within the uterine cavity. IUDs are extremely effective in preventing pregnancy, though inadvertent pregnancy risk is higher with malpositioned IUDs. Presence of fibroids or Mullerian abnormalities may preclude proper IUD placement. Radiologists play an important role in identifying complications when they arise and special considerations when planning for an IUD placement. There is a wide range of IUD malposition, affecting IUDs differently depending on the type of IUD and its mechanism of action. IUD malposition is the most common complication, but embedment and/or partial perforation can and can lead to difficulty when removed. Retained IUD fragments can result in continued contraceptive effect. Perforated IUDs do not typically cause intraperitoneal imaging findings.

Comparison of interpersonal quality of contraceptive counseling delivered via telehealth versus in person.

OBJECTIVES: This study aimed to compare the interpersonal quality of contraceptive counseling between telehealth and in-person visits. STUDY DESIGN: Patients at a single Title X-funded clinic selected their preferred counseling modality (in person or telehealth via video or telephone) when scheduling an appointment for contraception. After counseling, we invited patients to complete a survey and recorded their desired contraceptive method. We assessed the quality of counseling using the Interpersonal Quality in Family Planning scale. We reviewed the electronic medical record to identify any subsequent clinician visit. We performed between-group comparisons using Mann-Whitney U, χ2, and Fisher exact tests. RESULTS: From March 2021 to June 2022, 360 patients were eligible to participate, and 296 (82%) completed the survey and were included in the analysis; 150 (51%) completed counseling in person, and 146 (49%) completed counseling via telehealth. In the telehealth group, 102 (70%) chose telephone, and 44 (30%) chose video. Respondent characteristics were similar between groups. The majority of respondents in both groups reported high quality of counseling, defined as a top score on the Interpersonal Quality in Family Planning scale (75.0% telehealth respondents and 80.0% in person, p = 0.30). Compared to respondents completing in-person counseling, telehealth respondents were less likely to have a subsequent clinician visit (89.0% versus 100.0%, p < 0.001). CONCLUSIONS: The majority of respondents reported high-quality contraceptive counseling without significant difference between the modalities. However, respondents choosing telehealth were less likely to have a subsequent clinician visit. Given the higher uptake of telephone compared to video, telehealth via telephone may be more accessible or acceptable to some patients. IMPLICATIONS: Contraceptive counseling via telehealth has similar high interpersonal quality when compared to traditional, in-person visits. However, barriers may exist for patients who choose telehealth contraceptive counseling to access subsequent in-person care. Utilization of telehealth for contraceptive visits may provide opportunities for more equitable health care and to expand contraceptive access.

Inhibition of PANX1 Channels Reduces the Malignant Properties of Human High-Risk Neuroblastoma.

Pannexin 1 (PANX1) is expressed in many tissue types including tissues of neural origin. Neuroblastoma (NB) is a neural crest-derived malignancy mainly occurring in children. The majority of NB patients present with high-risk disease for which current therapies are ineffective. Here, we show that while PANX1 is expressed in NB of all stages, high PANX1 expression in high-risk NB is associated with a reduced survival probability. PANX1 channel inhibition using probenecid (PBN) or carbenoxolone (CBX) reduced the proliferation of our panel of high-risk NB cell lines. We show that expression of the Y10F PANX1 mutant, which cannot be phosphorylated on tyrosine 10 and acts in a dominant-negative manner, curtailed NB cell proliferation. Furthermore, PBN and CBX treatment halted the growth of NB spheroids and in some cases triggered the regression of established NB spheroids. Finally, both drugs reduced the progression of high-risk NB in vivo. Together our data indicate that PANX1 channels regulate human NB malignant properties and that the use of PBN or CBX may provide a new therapeutic approach for high-risk NB.

A Three-Step Method for the Preparation of N-Substituted 3,4-Dihydroisoquinolin-1(2H)-ones and Heteroaryl-Fused 3,4-Dihydropyridin-2(1H)-ones from 2-Bromobenzoate Precursors.

We demonstrate a general method for the preparation of diverse N-substituted 3,4-dihydroisoquinolin-1(2H)-one compounds through an overall three-step cross-coupling/cyclization/N-deprotection/N-alkylation sequence. In the first step, ethyl 2-bromobenzoates and 2-bromo-1-carboxyethyl heterocycles are cross-coupled with commercially available potassium (2-((tert-butoxycarbonyl)amino)ethyl)trifluoroborate to produce (hetero)aryl-substituted 3-[(N-Boc-2-carboxyethyl)phenyl]ethylamines. In a subsequent two-stage process, these (hetero)arylethylamines undergo base-mediated ring closure followed by N-deprotection and N-alkylation to produce N-substituted 3,4-dihydroisoquinolin-1(2H)-ones and heteroaryl-fused N-benzyl 3,4-dihydropyridin-2(1H)-ones. Mechanistic work was performed to elucidate the order of transformations for the latter two-stage process. The method was also extended to the production of N-benzyl isoindolin-1-one and N-benzyl 2,3,4,5-tetrahydro-1H-benzo[c]azepin-1-one.

Heteroatom Manipulation of Zeolite Crystallization: Stabilizing Zn-FAU against Interzeolite Transformation.

The preparation of metastable zeolites is often restricted to a limited range of synthesis conditions, which is exemplified in commercial syntheses lacking organics to stabilize the crystal structure. In the absence of an organic structure-directing agent, interzeolite transformation is a common phenomenon that can lead to undesirable products or impurities. Many studies have investigated the substitution of Si and Al in zeolite frameworks with alternative elements (heteroatoms) as a means of tailoring the properties of zeolites; however, relatively few studies have systematically explored the impact of heteroatoms on interzeolite transformations and their concomitant effects on zeolite crystallization. In this study, we examine methods to prepare isostructures of faujasite (FAU), which is one of the most commercially relevant zeolites and also a thermodynamically metastable structure. A survey of multivalent elements revealed that zinc is capable of stabilizing FAU at high temperatures and inhibiting its frequent transformation to zeolite gismondine (GIS). Using combined experimental and computational studies, we show that zinc alters the chemical nature of growth mixtures by sequestering silicates. Zinc heteroatoms incorporate in the FAU framework with a loading-dependent coordination. Our collective findings provide an improved understanding of driving forces for the FAU-to-GIS interzeolite transformation where we observe that heteroatoms (e.g., zinc) can stabilize zeolite FAU over a broad range of synthesis conditions. Given the growing interest in heteroatom-substituted zeolites, this approach to preparing zinc-containing FAU may prove applicable to a broader range of zeolite structures.

Bovine Tuberculosis Epidemiology in Cameroon, Central Africa, Based on the Interferon-Gamma Assay.

Despite sub-Saharan Africa (SSA) accounting for ~20% of the global cattle population, prevalence estimates and related risk factors of bovine tuberculosis (bTB) are still poorly described. The increased sensitivity of the IFN-γ assay and its practical benefits suggest the test could be useful to investigate bTB epidemiology in SSA. This study used a population-based sample to estimate bTB prevalence, identify risk factors and estimate the effective reproductive rate in Cameroonian cattle populations. A cross-sectional study was conducted in the North West Region (NWR) and the Vina Division (VIN) of Cameroon in 2013. A regional stratified sampling frame of pastoral cattle herds produced a sample of 1,448 cattle from 100 herds. In addition, a smaller cross-sectional study sampled 60 dairy cattle from 46 small-holder co-operative dairy farmers in the NWR. Collected blood samples were stimulated with bovine and avian purified protein derivatives, with extracted plasma screened using the IFN-γ enzyme-linked immunosorbent assay (Prionics Bovigam®). Design-adjusted population prevalences were estimated, and multivariable mixed-effects logistic regression models using Bayesian inference techniques identified the risk factors for IFN-γ positivity. Using the IFN-γ assay, the prevalence of bTB in the dairy cattle was 21.7% (95% CI: 11.2-32.2). The design-adjusted prevalence of bTB in cattle kept by pastoralists was 11.4% (95% CI: 7.6-17.0) in the NWR and 8.0% (95% CI: 4.7-13.0) in the VIN. A within-herd prevalence estimate for pastoralist cattle also supported that the NWR had higher prevalence herds than the VIN. Additionally, the estimates of the effective reproductive rate R t were 1.12 for the NWR and 1.06 for the VIN, suggesting different transmission rates within regional cattle populations in Cameroon. For pastoral cattle, an increased risk of IFN-γ assay positivity was associated with being male (OR = 1.89; 95% CI:1.15-3.09), increasing herd size (OR = 1.02; 95% CI:1.01-1.03), exposure to the bovine leucosis virus (OR = 2.45; 95% CI: 1.19-4.84) and paratuberculosis (OR = 9.01; 95% CI: 4.17-20.08). Decreased odds were associated with contacts at grazing, buffalo (OR = 0.20; 95% CI: 0.03-0.97) and increased contact with other herds [1-5 herds: OR = 0.16 (95% CI: 0.04-0.55); 6+ herds: OR = 0.18 (95% CI: 0.05-0.64)]. Few studies have used the IFN-γ assay to describe bTB epidemiology in SSA. This study highlights the endemic situation of bTB in Cameroon and potential public health risks from dairy herds. Further work is needed to understand the IFN-γ assay performance, particularly in the presence of co-infections, and how this information can be used to develop control strategies in the SSA contexts.

Sex-dependent role of Pannexin 1 in regulating skeletal muscle and satellite cell function.

The development and regeneration of skeletal muscle are mediated by satellite cells (SCs), which ensure the efficient formation of myofibers while repopulating the niche that allows muscle repair following injuries. Pannexin 1 (Panx1) channels are expressed in SCs and their levels increase during differentiation in vitro, as well as during skeletal muscle development and regeneration in vivo. Panx1 has recently been shown to regulate muscle regeneration by promoting bleb-based myoblast migration and fusion. While skeletal muscle is largely influenced in a sex-specific way, the sex-dependent roles of Panx1 in regulating skeletal muscle and SC function remain to be investigated. Here, using global Panx1 knockout (KO) mice, we demonstrate that Panx1 loss reduces muscle fiber size and strength, decreases SC number, and alters early SC differentiation and myoblast fusion in male, but not in female mice. Interestingly, while both male and female Panx1 KO mice display an increase in the number of regenerating fibers following acute injury, the newly formed fibers in male Panx1 KO mice are smaller. Overall, our results demonstrate that Panx1 plays a significant role in regulating muscle development, regeneration, and SC number and function in male mice and reveal distinct sex-dependent functions of Panx1 in skeletal muscle.

The Relationship between Father-Child Rough-and-Tumble Play and Children's Working Memory.

Rough-and-tumble play (RTP) between fathers and children has been linked to many social, emotional, and behavioural child outcomes, such as reduced aggression and increased self-regulation. This study extends our understanding of the importance of RTP to the development of the executive function, working memory. Father-child dyads (N = 30) were asked to play two RTP games that were videorecorded for later observational coding. Fathers were also asked to report the frequency with which they play RTP games with their child. Two measures of working memory were also collected. The working-memory index of the Wechsler Preschool and the Primary Scale of Intelligence-Fourth Edition were used to measure working-memory ability, and the working-memory subscale of the Behaviour Rating Inventory of Executive Function was used as a measure of working-memory problems. RTP frequency was associated with improved working-memory ability and fewer working-memory problems. RTP quality was associated with higher working-memory ability. This study adds to the growing evidence of the importance of father-child RTP for child development.

Bovine Tuberculosis Antemortem Diagnostic Test Agreement and Disagreement in a Naturally Infected African Cattle Population.

The interferon-gamma (IFN-γ) assay and single comparative cervical skin test (SCITT) are used to estimate bovine tuberculosis (bTB) prevalence globally. Prevalence estimates of bTB, caused by Mycobacterium bovis, are poorly quantified in many Sub-Saharan African (SSA) cattle populations. Furthermore, antemortem diagnostic performance can vary at different stages of bTB pathogenesis and in different cattle populations. In this study, we aim to explore the level of agreement and disagreement between the IFN-γ assay and SCITT test, along with the drivers for disagreement, in a naturally infected African cattle population. In, 2013, a pastoral cattle population was sampled using a stratified clustered cross-sectional study in Cameroon. A total of 100 pastoral cattle herds in the North West Region (NWR) and the Vina Division (VIN) were sampled totalling 1,448 cattle. Individual animal data and herd-level data were collected, and animals were screened using both the IFN-γ assay and SCITT. Serological ELISAs were used to detect exposure to immunosuppressing co-infections. Agreement analyses were used to compare the performance between the two bTB diagnostic tests, and multivariable mixed-effects logistic regression models (MLR) were developed to investigate the two forms of IFN-γ assay and SCITT binary disagreement. Best agreement using the Cohen's κ statistic, between the SCITT (>2 mm) and the IFN-γ assay implied a 'fair-moderate' agreement for the NWR [κ = 0.42 (95%CI: 0.31-0.53)] and 'poor-moderate' for the VIN [κ = 0.33 (95% CI: 0.18-0.47)]. The main test disagreement was the animals testing positive on the IFN-γ assay and negative by the SCITT. From MLR modeling, adults (adults OR: 7.57; older adults OR = 7.21), females (OR = 0.50), bovine leucosis (OR = 2.30), and paratuberculosis positivity (OR = 6.54) were associated with IFN-γ-positive/SCITT-negative disagreement. Subsets to investigate diagnostic test disagreement for being SCITT-positive and IFN-γ-negative also identified that adults (adults OR = 15.74; older adults OR = 9.18) were associated with IFN-γ-negative/SCITT-positive disagreement. We demonstrate that individual or combined use of the IFN-γ assay and SCITT can lead to a large variation in bTB prevalence estimates. Considering that animal level factors were associated with disagreement between the IFN-γ assay and SCITT in this study, future work should further investigate their impact on diagnostic test performance to develop the approaches to improve SSA prevalence estimates.

A Cross-Sectional, Population-Based, Seroepidemiological Study of Rift Valley Fever in Cameroonian Cattle Populations.

Rift Valley fever (RVF) is an important emerging zoonoses causing abortion and neonatal deaths in livestock and hemorrhagic fever in humans. It is typically characterized by acute epidemics with abortion storms often preceding human disease and these events have been associated with the El Niño weather cycles. Outside of areas that experience epidemics, little is known about its epidemiology. Here, we present results from a serological study using biobank samples from a study of cattle conducted in 2013 at two sites in Cameroon. A total of 1,458 cattle from 100 herds were bled and sera screened using a commercially available RVF ELISA. The overall design-adjusted animal-level apparent seroprevalence of RVF exposure for the Northwest Region (NWR) of Cameroon was 6.5% (95% CI: 3.9-11.0) and for the Vina Division (VIN) of the Adamawa Region was 8.2% (95% CI: 6.2-11.0). The age-stratified serological results were also used to estimate the force of infection, and the age-independent estimates were 0.029 for the VIN and 0.024 for the NWR. The effective reproductive number was ~1.08. Increasing age and contact with wild antelope species were associated with an increased risk of seropositivity, while high altitudes and contact with buffalo were associated with a reduced risk of seropositivity. The serological patterns are more consistent with an endemical stability rather than the more typical epidemic patterns seen in East Africa. However, there is little surveillance in livestock for abortion storms or in humans with fevers in Cameroon, and it is, therefore, difficult to interpret these observations. There is an urgent need for an integrated One Health approach to understand the levels of human- and livestock-related clinical and asymptomatic disease and whether there is a need to implement interventions such as vaccination.

The Interplay of Environmental Exposures and Mental Health: Setting an Agenda.

BACKGROUND: To date, health-effects research on environmental stressors has rarely focused on behavioral and mental health outcomes. That lack of research is beginning to change. Science and policy experts in the environmental and behavioral health sciences are coming together to explore converging evidence on the relationship-harmful or beneficial-between environmental factors and mental health. OBJECTIVES: To organize evidence and catalyze new findings, the National Academy of Sciences, Engineering, and Medicine (NASEM) hosted a workshop 2-3 February 2021 on the interplay of environmental exposures and mental health outcomes. METHODS: This commentary provides a nonsystematic, expert-guided conceptual review and interdisciplinary perspective on the convergence of environmental and mental health, drawing from hypotheses, findings, and research gaps presented and discussed at the workshop. Featured is an overview of what is known about the intersection of the environment and mental health, focusing on the effects of neurotoxic pollutants, threats related to climate change, and the importance of health promoting environments, such as urban green spaces. DISCUSSION: We describe what can be gained by bridging environmental and psychological research disciplines and present a synthesis of what is needed to advance interdisciplinary investigations. We also consider the implications of the current evidence for a) foundational knowledge of the etiology of mental health and illness, b) toxicant policy and regulation, c) definitions of climate adaptation and community resilience, d) interventions targeting marginalized communities, and e) the future of research training and funding. We include a call to action for environmental and mental health researchers, focusing on the environmental contributions to mental health to unlock primary prevention strategies at the population level and open equitable paths for preventing mental disorders and achieving optimal mental health for all. https://doi.org/10.1289/EHP9889.

Active inclusion of people living with dementia in planning for dementia care and services in low- and middle-income countries.

Involving people living with dementia in service design and planning has become more common in high-income countries. It remains rare in low- and middle-income countries where two-thirds of the world's people with dementia live. In this commentary article, we explore the barriers to inclusion of people living with dementia in planning in low- and middle-income countries and make a case for the inclusion of people living with dementia in care and service planning. We suggest how this can be done at individual, community or national and state level using the following principles: 1) respecting the rights of people living with dementia to self-determination; 2) valuing people living with dementia's unique understanding of dementia; 3) creating a culture of active inclusion which creates a space for people living with dementia to participate and 4) ensuring appropriate accommodations are in place to maximise participation.

Beyond the project: Building a strategic theory of change to address dementia care, treatment and support gaps across seven middle-income countries.

Evidence from middle-income countries indicates high and increasing prevalence of dementia and need for services. However, there has been little investment in care, treatment or support for people living with dementia and their carers. The Strengthening Responses to Dementia in Developing Countries (STRiDE) project aims to build both research capacity and evidence on dementia care and services in Brazil, Indonesia, India, Jamaica, Kenya, Mexico and South Africa. This article presents the Theory of Change (ToC) approach we used to co-design our research project and to develop a strategic direction for dementia care, treatment and support, with stakeholders. ToC makes explicit the process underlying how a programme will achieve its impact. We developed ToCs in each country and across the STRiDE project with researchers, practitioners, people living with dementia, carers and policymakers at different levels of government. This involved (1) an initial ToC workshop with all project partners (43 participants); (2) ToC workshops in each STRiDE country (22-49 participants in each); (3) comparison between country-specific and overall project ToCs; (4) review of ToCs in light of WHO dementia guidelines and action plan and (5) a final review. Our experiences suggest ToC is an effective way to generate a shared vision for dementia care, treatment and support among diverse stakeholders. However, the project contribution should be clearly delineated and use additional strategies to ensure appropriate participation from people living with dementia and their carers in the ToC process.