Surveillance To Track Progress Toward Poliomyelitis Eradication - Worldwide, 2021-2022.

Since the Global Polio Eradication Initiative (GPEI) was established in 1988, the number of wild poliovirus (WPV) cases has declined by >99.9%, and WPV serotypes 2 and 3 have been declared eradicated (1). By the end of 2022, WPV type 1 (WPV1) transmission remained endemic only in Afghanistan and Pakistan (2,3). However, during 2021-2022, Malawi and Mozambique reported nine WPV1 cases that were genetically linked to Pakistan (4,5), and circulating vaccine-derived poliovirus (cVDPV) outbreaks were detected in 42 countries (6). cVDPVs are oral poliovirus vaccine-derived viruses that can emerge after prolonged circulation in populations with low immunity allowing reversion to neurovirulence and can cause paralysis. Polioviruses are detected primarily through surveillance for acute flaccid paralysis (AFP), and poliovirus is confirmed through stool specimen testing. Environmental surveillance, the systematic sampling of sewage and testing for the presence of poliovirus, supplements AFP surveillance. Both surveillance systems were affected by the COVID-19 pandemic's effects on public health activities during 2020 (7,8) but improved in 2021 (9). This report updates previous reports (7,9) to describe surveillance performance during 2021-2022 in 34 priority countries.* In 2022, a total of 26 (76.5%) priority countries met the two key AFP surveillance performance indicator targets nationally compared with 24 (70.6%) countries in 2021; however, substantial gaps remain in subnational areas. Environmental surveillance expanded to 725 sites in priority countries, a 31.1% increase from the 553 sites reported in 2021. High-quality surveillance is critical to rapidly detect poliovirus transmission and enable prompt poliovirus outbreak response to stop circulation. Frequent monitoring of surveillance guides improvements to achieve progress toward polio eradication.

Impact of COVID-19 and lockdown on COPD admissions to Christchurch Hospital, New Zealand 2020-2021: a combined quantitative and qualitative study.

BACKGROUND: During the year following New Zealand's first COVID-19 lockdown, a 33% reduction in chronic obstructive pulmonary disease (COPD)-related admissions occurred and persisted beyond this period at Christchurch Hospital. AIM: To identify contributing factors which may have resulted in a persistent decrease in COPD hospitalisation rates at Christchurch Hospital following the 2020 COVID-19 lockdown. METHODS: Using an explanatory sequential mixed-methods research design, we (i) retrospectively analysed hospital admissions and primary healthcare access by people with COPD (n = 1358) in Canterbury before, during and after COVID lockdown (24 March 2019 to 2021) and (ii) undertook individual interviews from a sample of patients (n = 14). RESULTS: Patients who were not re-admitted following the COVID-19 lockdown had fewer general practice encounters, acute primary care access, antibiotic and prednisone prescriptions. Proportionally fewer Maori and more Pacific patients were admitted with COPD following lockdown. Positive contributing factors at a primary care level included improvements in primary care interactions and medication management. At a patient and community level, there were improvements in lifestyle, self-management practices, social support and contact precautions. However, a subgroup of patients described negative effects such as social isolation. CONCLUSION: A combination of patient, primary care and community-level factors led to an overall persistent decrease in COPD admissions following the COVID-19 lockdown. Future targeted and individualised measures focusing on these modifiable factors may decrease future COPD-related hospital admissions. The study design facilitated further explanation about factors that contributed to the persistent decrease in hospital admissions among people living with COPD and has underscored the importance of social support, patient empowerment and reduction in barriers in accessing care in admission reduction.

Surveillance to Track Progress Toward Polio Eradication - Worldwide, 2020-2021.

Since the Global Polio Eradication Initiative (GPEI) was established in 1988, the number of reported poliomyelitis cases worldwide has declined by approximately 99.99%. By the end of 2021, wild poliovirus (WPV) remained endemic in only two countries (Pakistan and Afghanistan). However, a WPV type 1 (WPV1) case with paralysis onset in 2021, was reported by Malawi a year after the World Health Organization (WHO) African Region (AFR) was certified as WPV-free and circulating vaccine-derived poliovirus (cVDPV) cases were reported from 31 countries during 2020-2021 (1,2). cVDPVs are oral poliovirus vaccine-derived viruses that can emerge after prolonged circulation in populations with low immunity and cause paralysis. The primary means of detecting poliovirus transmission is through surveillance for acute flaccid paralysis (AFP) among persons aged <15 years, with confirmation through stool specimen testing by WHO-accredited laboratories, supplemented by systematic sampling of sewage and testing for the presence of poliovirus (environmental surveillance). The COVID-19 pandemic caused disruptions in polio vaccination and surveillance activities across WHO regions in 2020; during January-September 2020, the number of reported cases of AFP declined and the interval between stool collection and receipt by laboratories increased compared with the same period in 2019 (3). This report summarizes surveillance performance indicators for 2020 and 2021 in 43 priority countries* and updates previous reports (4). In 2021, a total of 32 (74%) priority countries† met two key surveillance performance indicator targets nationally, an improvement from 2020 when only 23 (53%) met both targets; however, substantial national and subnational gaps persist. High-performing poliovirus surveillance is critical to tracking poliovirus transmission. Frequent monitoring of surveillance indicators could help identify gaps, guide improvements, and enhance the overall sensitivity and timelines of poliovirus detection to successfully achieve polio eradication.

Progress Toward Polio Eradication - Worldwide, January 2019-June 2021.

In 1988, when the Global Polio Eradication Initiative (GPEI) began, polio paralyzed >350,000 children across 125 countries. Today, only one of three wild poliovirus serotypes, type 1 (WPV1), remains in circulation in only two countries, Afghanistan and Pakistan. This report summarizes progress toward global polio eradication during January 1, 2019-June 30, 2021 and updates previous reports (1,2). In 2020, 140 cases of WPV1 were reported, including 56 in Afghanistan (a 93% increase from 29 cases in 2019) and 84 in Pakistan (a 43% decrease from 147 cases in 2019). As GPEI focuses on the last endemic WPV reservoirs, poliomyelitis outbreaks caused by circulating vaccine-derived poliovirus (cVDPV) have emerged as a result of attenuated oral poliovirus vaccine (OPV) virus regaining neurovirulence after prolonged circulation in underimmunized populations (3). In 2020, 32 countries reported cVDPV outbreaks (four type 1 [cVDPV1], 26 type 2 [cVDPV2] and two with outbreaks of both); 13 of these countries reported new outbreaks. The updated GPEI Polio Eradication Strategy 2022-2026 (4) includes expanded use of the type 2 novel oral poliovirus vaccine (nOPV2) to avoid new emergences of cVDPV2 during outbreak responses (3). The new strategy deploys other tactics, such as increased national accountability, and focused investments for overcoming the remaining barriers to eradication, including program disruptions and setbacks caused by the COVID-19 pandemic.

Surveillance to Track Progress Toward Polio Eradication - Worldwide, 2019-2020.

When the Global Polio Eradication Initiative (GPEI) was established in 1988, an estimated 350,000 poliomyelitis cases were reported worldwide. In 2020, 140 wild poliovirus (WPV) cases were confirmed, representing a 99.99% reduction since 1988. WPV type 1 transmission remains endemic in only two countries (Pakistan and Afghanistan), but outbreaks of circulating vaccine-derived poliovirus (cVDPV) occurred in 33 countries during 2019-2020 (1,2). Poliovirus transmission is detected primarily through syndromic surveillance for acute flaccid paralysis (AFP) among children aged <15 years, with confirmation by laboratory testing of stool specimens. Environmental surveillance supplements AFP surveillance and plays an increasingly important role in detecting poliovirus transmission. Within 2 weeks of COVID-19 being declared a global pandemic (3), GPEI recommended continuing surveillance activities with caution and paused all polio supplementary immunization activities (4). This report summarizes surveillance performance indicators for 2019 and 2020 in 42 priority countries at high risk for poliovirus transmission and updates previous reports (5). In 2020, 48% of priority countries* in the African Region, 90% in the Eastern Mediterranean Region, and 40% in other regions met AFP surveillance performance indicators nationally. The number of priority countries rose from 40 in 2019 to 42 in 2020.† Analysis of 2019-2020 AFP surveillance data from 42 countries at high risk for poliovirus transmission indicates that national and subnational nonpolio AFP rates and stool specimen adequacy declined in many priority countries, particularly in the African Region, suggesting a decline in surveillance sensitivity and quality. The findings in this report can be used to guide improvements to restore a sensitive surveillance system that can track poliovirus transmission and provide evidence of interruption of transmission.

Updated Characterization of Outbreak Response Strategies for 2019-2029: Impacts of Using a Novel Type 2 Oral Poliovirus Vaccine Strain.

Delays in achieving the global eradication of wild poliovirus transmission continue to postpone subsequent cessation of all oral poliovirus vaccine (OPV) use. Countries must stop OPV use to end all cases of poliomyelitis, including vaccine-associated paralytic polio (VAPP) and cases caused by vaccine-derived polioviruses (VDPVs). The Global Polio Eradication Initiative (GPEI) coordinated global cessation of all type 2 OPV (OPV2) use in routine immunization in 2016 but did not successfully end the transmission of type 2 VDPVs (VDPV2s), and consequently continues to use type 2 OPV (OPV2) for outbreak response activities. Using an updated global poliovirus transmission and OPV evolution model, we characterize outbreak response options for 2019-2029 related to responding to VDPV2 outbreaks with a genetically stabilized novel OPV (nOPV2) strain or with the currently licensed monovalent OPV2 (mOPV2). Given uncertainties about the properties of nOPV2, we model different assumptions that appear consistent with the evidence on nOPV2 to date. Using nOPV2 to respond to detected cases may reduce the expected VDPV and VAPP cases and the risk of needing to restart OPV2 use in routine immunization compared to mOPV2 use for outbreak response. The actual properties, availability, and use of nOPV2 will determine its effects on type 2 poliovirus transmission in populations. Even with optimal nOPV2 performance, countries and the GPEI would still likely need to restart OPV2 use in routine immunization in OPV-using countries if operational improvements in outbreak response to stop the transmission of cVDPV2s are not implemented effectively.

AIF promotes a JNK1-mediated cadherin switch independently of respiratory chain stabilization.

Apoptosis-inducing factor (AIF) is a mitochondrial flavoprotein occasionally involved in cell death that primarily regulates mitochondrial energy metabolism under normal cellular conditions. AIF catalyzes the oxidation of NADH in vitro, yet the significance of this redox activity in cells remains unclear. Here, we show that through its enzymatic activity AIF is a critical factor for oxidative stress-induced activation of the mitogen-activated protein kinases JNK1 (c-Jun N-terminal kinase), p38, and ERK (extracellular signal-regulated kinase). AIF-dependent JNK1 signaling culminates in the cadherin switch, and genetic reversal of this switch leads to apoptosis when AIF is suppressed. Notably, this widespread ability of AIF to promote JNK signaling can be uncoupled from its more limited role in respiratory chain stabilization. Thus, AIF is a transmitter of extra-mitochondrial signaling cues with important implications for human development and disease.

Health and Demographic Surveillance Systems Within the Child Health and Mortality Prevention Surveillance Network.

Health and demographic surveillance systems (HDSSs) provide a foundation for characterizing and defining priorities and strategies for improving population health. The Child Health and Mortality Prevention Surveillance (CHAMPS) project aims to inform policy to prevent child deaths through generating causes of death from surveillance data combined with innovative diagnostic and laboratory methods. Six of the 7 sites that constitute the CHAMPS network have active HDSSs: Mozambique, Mali, Ethiopia, Kenya, Bangladesh, and South Africa; the seventh, in Sierra Leone, is in the early planning stages. This article describes the network of CHAMPS HDSSs and their role in the CHAMPS project. To generate actionable health and demographic data to prevent child deaths, the network depends on reliable demographic surveillance, and the HDSSs play this crucial role.

Using intervention mapping to design a self-management programme for older people with chronic conditions.

Self-management programmes provide strategies to optimise health while educating and providing resources for living with enduring illnesses. The current paper describes the development of a community-based programme that combines a transdiagnostic approach to self-management with mindfulness to enhance psychological coping for older people with long-term multimorbidity. The six steps of intervention mapping (IM) were used to develop the programme. From a needs assessment, the objectives of the programme were formulated; the theoretical underpinnings then aligned to the objectives, which informed programme design, decisions on implementation, programme adoption and evaluation steps. Bandura's social cognitive theory informed the methods and practical strategies of delivery. Among the features addressed with participants are transdiagnostic dimensions such as fatigue, pain, breathlessness, sleep disturbances. The programme utilises mindfulness to aid coping and ameliorate the psychological distresses associated with chronicity. Findings from an initial feasibility study and subsequent pilot assisted in conceptualising our programme. In conclusion, applying IM gave the planners confidence the programme is robust and evidence-based with clearly articulated links between the behavioural goals and design elements to obtain the desired outcomes.

Characteristics of and Precipitating Circumstances Surrounding Suicide Among Persons Aged 10-17 Years - Utah, 2011-2015.

In 2015, suicide was the third leading cause of death among persons aged 10-17 years (1), and in Utah, the age-adjusted suicide rate was consistently higher than the national rate during the past decade (2). In January 2017, the Utah Department of Health (UDOH) invited CDC to assist with an epidemiologic investigation of suicides among youths aged 10-17 years during 2011-2015 to identify precipitating factors. CDC analyzed data from the Utah Violent Death Reporting System (UTVDRS), National Vital Statistics System, and additional information collected in the field. During 2011-2015 in Utah, 150 youths died by suicide. Approximately three fourths of decedents were male (77.4%) and aged 15-17 years (75.4%). During this period, the unadjusted suicide rate per 100,000 youths in Utah increased 136.2%, from 4.7 per 100,000 population (2011) to 11.1 (2015), whereas among youths nationwide, the rate increased 23.5%, from 3.4 to 4.1. Among suicide decedents with circumstances data available, more than two thirds (68.3%) had multiple precipitating circumstances, including mental health diagnosis (35.2%), depressed mood (31.0%), recent crisis (55.3%), and history of suicidal ideation or attempt (29.6%). CDC's technical package of policies, programs, and practices to prevent suicide supported by the best available evidence can be used as a suicide prevention resource (3).

Suicidal Ideation and Attempts Among Students in Grades 8, 10, and 12 - Utah, 2015.

Suicidal thoughts and behaviors among youths are important public health concerns in Utah, where the suicide rate among youths consistently exceeds the national rate and has been increasing for nearly a decade (1). In March 2017, CDC was invited to assist the Utah Department of Health (UDOH) with an investigation to characterize the epidemiology of fatal and nonfatal suicidal behaviors and identify risk and protective factors associated with these behaviors, among youths aged 10-17 years. This report presents findings related to nonfatal suicidal behaviors among Utah youths. To examine the prevalence of suicidal ideation and attempts among Utah youths and evaluate risk and protective factors, data from the 2015 Utah Prevention Needs Assessment survey were analyzed. Among 27,329 respondents in grades 8, 10, and 12, 19.6% reported suicidal ideation and 8.2% reported suicide attempts in the preceding 12 months. Significant risk factors for suicidal ideation and attempts included being bullied, illegal substance or tobacco use in the previous month, and psychological distress. A significant protective factor for suicidal ideation and attempts was a supportive family environment. UDOH, local health departments, and other stakeholders are using these findings to develop tailored suicide prevention strategies that address multiple risk and protective factors for suicidal ideation and attempts. Resources such as CDC's Preventing Suicide: A Technical Package of Policy, Programs, and Practices (2) can help states and communities identify strategies and approaches using the best available evidence to prevent suicide, which include tailored strategies for youths.

Reporting Deaths Among Children Aged <5 Years After the Ebola Virus Disease Epidemic - Bombali District, Sierra Leone, 2015-2016.

Mortality surveillance and vital registration are limited in Sierra Leone, a country with one of the highest mortality rates among children aged <5 years worldwide, approximately 120 deaths per 1,000 live births (1,2). To inform efforts to strengthen surveillance, stillbirths and deaths in children aged <5 years from multiple surveillance streams in Bombali Sebora chiefdom were retrospectively reviewed. In total, during January 2015-November 2016, 930 deaths in children aged <5 years were identified, representing 73.3% of the 1,269 deaths that were expected based on modeled estimates. The "117" telephone alert system established during the Ebola virus disease (Ebola) epidemic captured 683 (73.4%) of all reported deaths in children aged <5 years, and was the predominant reporting source for stillbirths (n = 172). In the absence of complete vital events registration, 117 call alerts markedly improved the completeness of reporting of stillbirths and deaths in children aged <5 years.

Apoptosis Inducing Factor Binding Protein PGAM5 Triggers Mitophagic Cell Death That Is Inhibited by the Ubiquitin Ligase Activity of X-Linked Inhibitor of Apoptosis.

Apoptosis inducing factor (AIF) plays a well-defined role in controlling cell death but is also a critical factor for maintaining mitochondrial energy homeostasis; how these dueling activities are balanced has remained largely elusive. To identify new AIF binding partners that may define the continuum of AIF cellular regulation, a biochemical screen was performed that identified the mitochondrial phosphoglycerate mutase 5 (PGAM5) as an AIF associated factor. AIF binds both the short and long isoforms of PGAM5 and can reduce the ability of PGAM5 to control antioxidant responses. Transient overexpression of either PGAM5 isoform triggers caspase activation and cell death, and while AIF could reduce this caspase activation neither AIF expression nor caspase activity is required for PGAM5-mediated death. PGAM5 toxicity morphologically and biochemically resembles mitophagic cell death and is inhibited by the AIF binding protein X-linked inhibitor of apoptosis (XIAP) in a manner that depends on the ubiquitin ligase activity of XIAP. The phosphatase activity of PGAM5 was not required for cell death, and comparison of phosphatase activity between short and long PGAM5 isoforms suggested that only the long isoform is catalytically competent. This property correlated with an increased ability of PGAM5L to form dimers and/or higher order oligomers in intact cells compared to PGAM5S. Overall this study identifies an AIF/PGAM5/XIAP axis that can regulate PGAM5 activities related to the antioxidant response and mitophagy.

Basal metabolic state governs AIF-dependent growth support in pancreatic cancer cells.

BACKGROUND: Apoptosis-inducing factor (AIF), named for its involvement in cell death pathways, is a mitochondrial protein that regulates metabolic homeostasis. In addition to supporting the survival of healthy cells, AIF also plays a contributory role to the development of cancer through its enzymatic activity, and we have previously shown that AIF preferentially supports advanced-stage prostate cancer cells. Here we further evaluated the role of AIF in tumorigenesis by exploring its function in pancreatic cancer, a disease setting that most often presents at an advanced stage by the time of diagnosis. METHODS: A bioinformatics approach was first employed to investigate AIF mRNA transcript levels in pancreatic tumor specimens vs. normal tissues. AIF-deficient pancreatic cancer cell lines were then established via lentiviral infection. Immunoblot analysis was used to determine relative protein quantities within cells. Cell viability was measured by flow cytometry; in vitro and Matrigel™ growth/survival using Coulter™ counting and phase contrast microscopy; and glucose consumption in the absence and presence of Matrigel™ using spectrophotometric methods. RESULTS: Archival gene expression data revealed a modest elevation of AIF transcript levels in subsets of pancreatic tumor specimens, suggesting a possible role in disease progression. AIF expression was then suppressed in a panel of five pancreatic cancer cell lines that display diverse metabolic phenotypes. AIF ablation selectively crippled the growth of cells in vitro in a manner that directly correlated with the loss of mitochondrial respiratory chain subunits and altered glucose metabolism, and these effects were exacerbated in the presence of Matrigel™ substrate. This suggests a critical metabolic role for AIF to pancreatic tumorigenesis, while the spectrum of sensitivities to AIF ablation depends on basal cellular metabolic phenotypes. CONCLUSIONS: Altogether these data indicate that AIF supports the growth and survival of metabolically defined pancreatic cancer cells and that this metabolic function may derive from a novel mechanism so far undocumented in other cancer types.

Clinical effectiveness of transdiagnostic health management interventions for older people with multimorbidity: a quantitative systematic review.

AIM: The aim of this study was to evaluate the clinical effectiveness (improvement in health status and/or functioning and use of health services) of transdiagnostic health management interventions for people aged 65 years and older. BACKGROUND: The care of older people with multimorbidity is of increasing concern for nurses. A transdiagnostic approach to health management interventions (promote self-management or lifestyle) may be apposite for providing older people with the skills to manage symptoms that may or may not be disease-specific. DESIGN: Quantitative systematic review. REVIEW METHODS: Cochrane methods using Cochrane's Effective Practice and Organization of Care Methods (EPOC) for assessing risk of bias and the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) for assessing the weight of evidence. DATA SOURCES: Medline, CINAHL, PubMed and PsycINFO 1999-2014. RESULTS: Twelve studies were included in the review (n = 10,393). All 12 studies provided results for health outcomes (health status and functioning) and six provided results for health outcomes and health service utilization. Ten studies reported statistically significant improvements in health outcomes but of these studies only two were of low risk of bias. Three studies identified some statistically significant reductions in health service utilization. The weight of evidence for the health management interventions included in the review, were low/moderate for improvements in health status and low for improvements in health service utilization. CONCLUSION: While there is some very preliminary evidence suggesting that structured transdiagnostic health management interventions may be clinically effective for older people with multimorbidity the effect sizes are small and the quality of this evidence is generally low.

Associations between gestational anthropometry, maternal HIV, and fetal and early infancy growth in a prospective rural/semi-rural Tanzanian cohort, 2012-13.

BACKGROUND: Healthcare access and resources differ considerably between urban and rural settings making cross-setting generalizations difficult. In resource-restricted rural/semi-rural environments, identification of feasible screening tools is a priority. The objective of this study was to evaluate gestational anthropometry in relation to birth and infant growth in a rural/semi-rural Tanzanian prospective cohort of mothers and their infants. METHODS: Mothers (n = 114: 44 HIV-positive) attending antenatal clinic visits were recruited in their second or third trimester between March and November, 2012, and followed with their infants through 6-months post-partum. Demographic, clinical, and infant feeding data were obtained using questionnaires administered by a Swahili-speaking research nurse on demographic, socioeconomic, clinical, and infant feeding practices. Second or third trimester anthropometry (mid-upper arm circumference [MUAC], triceps skinfold thickness, weight, height), pregnancy outcomes, birth (weight, length, head circumference) and infant anthropometry (weight-for-age z-score [WAZ], length-for-age z-score [LAZ]) were obtained. Linear regression and mixed effect modeling were used to evaluate gestational factors in relation to pregnancy and infant outcomes. RESULTS AND DISCUSSION: Gestational MUAC and maternal HIV status (HIV-positive mothers = 39%) were associated with infant WAZ and LAZ from birth to 6-months in multivariate models, even after adjustment for infant feeding practices. The lowest gestational MUAC tertile was associated with lower WAZ throughout early infancy, as well as lower LAZ at 3 and 6-months. In linear mixed effects models through 6-months, each 1 cm increase in gestational MUAC was associated with a 0.11 increase in both WAZ (P < 0.001) and LAZ (P = 0.001). Infant HIV-exposure was negatively associated with WAZ (ß = -0.65, P < 0.001) and LAZ (ß = -0.49, P < 0.012) from birth to 6-months. CONCLUSIONS: Lower gestational MUAC, evaluated using only a tape measure and minimal training that is feasible in non-urban clinic and community settings, was associated with lower infant anthropometric measurements. In this rural and semi-rural setting, HIV-exposure was associated with poorer anthropometry through 6-months despite maternal antiretroviral access. Routine assessment of MUAC has the potential to identify at-risk women in need of additional health interventions designed to optimize pregnancy outcomes and infant growth. Further research is needed to establish gestational MUAC reference ranges and to define interventions that successfully improve MUAC during pregnancy.

Supported self-management in long-term conditions in an African context.

Self-management is an important strategy to improve quality of life, appropriately manage long-term health conditions, and reduce the economic burden of long-term health conditions. However, equitable healthcare access remains an issue, and the focus on 'self' in self-management is problematic. Our review aims to explore the conceptualisation and evolution of supported self-management in an African context and its relevance to physiotherapy. A state-of-the-art review of the literature was undertaken by the authors. The authors knowledge of the subject area and a database search retrieved recent articles exploring patients' and healthcare providers' understanding of supported self-management in Africa. Relevant articles were read, and data summaries of included studies were extracted and tabulated. Findings were organised deductively. Sixteen studies, 11 primary research, and 5 reviews (2016-2023) undertaken in a variety of sub-Saharan countries with healthcare workers (~n = 177) and people (~n = 16 115) living with a mix of non-communicable and communicable conditions were considered in this state-of-the-art review. Self-management perceptions were drawn from Western authors spanning development research and understanding of the concepts in Western thinking. We conclude that imported concepts, such as supported self-management for long-term conditions, should be considered within local health delivery solutions. These should be embedded in an understanding of traditional African health systems. Clinical implications: There is a need to develop locally derived African solutions. Self-management strategies for long-term health conditions should be developed, considering traditional holistic African health systems.

Patients' perspectives on planned interventions tested in the Otago MASTER feasibility trial: an implementation-based process evaluation study.

BACKGROUND: Patients are key stakeholders of clinical research, and their perspectives are relevant for researchers when planning and conducting clinical trials. Numerous aspects of trial process can influence participants' experiences. Their experiences within a trial can impact retention rates. Poor treatment adherence may bias treatment effect estimates. One way to improve recruitment and adherence is to design trials that are aligned with patients' needs and preferences. This study reports a process evaluation of the Otago MASTER feasibility trial. OBJECTIVES: Our aims were to investigate the patients' perceptions of the trial interventions through individual interviews. METHODS: Twenty-five participants were recruited for the feasibility trial and were allocated to two groups: tailored or standardised exercise. Sixteen participants agreed to take part in individual semi-structured interviews. Interviews were transcribed verbatim, and all interviews were analysed thematically using an iterative approach. RESULTS: Our key findings suggest participants: (1) took part in the study to access healthcare services and contribute to research; (2) valued interventions received; (3) reported certain barriers and facilitators to participate in the trial; and (4) highlighted areas for improvement when designing the full trial. CONCLUSION: Participants volunteered to access healthcare and to contribute to research. Participants valued the personalised care, perceived that their engagement within the trial improved their self-management and self-efficacy behaviour, valued the time spent with clinicians, and the empathetic environment and education received. Facilitators and barriers will require careful consideration in the future as the barriers may impact reliability and validity of future trial results.

The enzymatic activity of apoptosis-inducing factor supports energy metabolism benefiting the growth and invasiveness of advanced prostate cancer cells.

Apoptosis-inducing factor (AIF) promotes cell death yet also controls mitochondrial homeostasis and energy metabolism. It is unclear how these activities are coordinated, and the impact of AIF upon human disease, in particular cancer, is not well documented. In this study we have explored the contribution of AIF to the progression of prostate cancer. Analysis of archival gene expression data demonstrated that AIF transcript levels are elevated in human prostate cancer, and we found that AIF protein is increased in prostate tumors. Suppression of AIF expression in the prostate cancer cell lines LNCaP, DU145, and PC3 demonstrated that AIF does not contribute to cell toxicity via a variety of chemical death triggers, and growth under nutrient-rich conditions is largely unaffected by AIF ablation. However, under growth stress conditions, AIF depletion from DU145 and PC3 cell lines led to significant reductions in cell survival and growth that were not observed in LNCaP cells. Moreover AIF-deficient PC3 cells exhibited substantial reduction of tumorigenic growth in vivo. This reduced survival correlated with decreased expression of mitochondrial complex I protein subunits and concomitant changes in glucose metabolism. Finally, restoration of AIF-deficient PC3 cells with AIF variants demonstrated that the enzymatic activity of AIF is required for aggressive growth. Overall these studies show that AIF is an important factor for advanced prostate cancer cells and that through control of energy metabolism and redox balance, the enzymatic activity of AIF is critical for this support.