Conectar
by Siobhán O’Connor, Sandra M. Malone, Joseph Firnhaber, Sinéad O’Keeffe, John McNamara, Anna Donnla O’Hagan
While mental health literacy is an important component to successful help-seeking, rural populations often face gaps in both knowledge and service provision. Informed by the Theory of Planned Behaviour and Self-Efficacy Theory, we designed the ‘Skills for Resilience’ as a brief, once-off, community-based educational intervention to increase Irish farmers’ mental health literacy and help-seeking intentions. We adopted a quasi-experimental between (group: intervention and control) and within-group design (time: baseline [T1], immediately post-intervention [T2], and ≥ 1 month post-intervention [T3]). A total of 72 participants (intervention n = 37; control n = 35) were recruited from knowledge-sharing discussion groups. Although recruitment was also open to women, all discussion groups consisted of men. A trained facilitator delivered a discussion lasting between 30 and 90 minutes. Five intervention participants also participated in a qualitative interview after T3. Our results identified intervention participants’ mental health literacy increased significantly at T2 and T3 compared to T1, but did not increase between T2 and T3. Mental health literacy was also significantly greater in the intervention group compared to the control group at T2 and T3. Help-seeking intentions and self-efficacy in seeking mental healthcare also increased significantly at T2 compared to T1, but did not increase between T1 and T3 or T2 and T3. There were no significant changes in outcome measures for the control group at any time point. Through reflexive thematic analysis we identified that the intervention also addressed stigma against mental health (Theme 1) and provided important resources for participants and their community’s present and future coping (Theme 2). At T3, 100% of participants enjoyed the discussion and would recommend the intervention to other farmers. This intervention provides a successful example of integrating the Theory of Planned Behaviour and Self-Efficacy Theory to improve mental health literacy in farmers using a brief, educational intervention.by Claudia Castro, Jacquelyn Badillo, Melissa Tumen-Velasquez, Adam M. Guss, Thomas S. Collins, Frank Harmon, Devin Coleman-Derr
Recent wildfires near vineyards in the Pacific United States have caused devastating financial losses due to smoke taint in wine. When wine grapes (Vitis vinifera) are exposed to wildfire smoke, their berries absorb volatile phenols derived from the lignin of burning plant material. Volatile phenols are released during the winemaking process giving the finished wine an unpleasant, smokey, and ashy taste known as smoke taint. Bacteria are capable of undergoing a wide variety of metabolic processes and therefore present great potential for bioremediation applications in many industries. In this study, we identify two strains of the same species that colonize the grape phyllosphere and are able to degrade guaiacol, a main volatile phenol responsible for smoke taint in wine. We identify the suite of genes that enable guaiacol degradation in Gordonia alkanivorans via RNAseq of cells growing on guaiacol as a sole carbon source. Additionally, we knockout guaA, a cytochrome P450 gene involved in the conversion of guaiacol to catechol; ΔguaA cells cannot catabolize guaiacol in vitro, providing evidence that GuaA is necessary for this process. Furthermore, we analyze the microbiome of berries and leaves exposed to smoke in the vineyard to investigate the impact of smoke on the grape microbial community. We found smoke has a significant but small effect on the microbial community, leading to an enrichment of several genera belonging to the Bacilli class. Collectively, this research shows that studying microbes and their enzymes has the potential to identify novel tools for alleviating smoke taint.by Adedapo Olufemi Bashorun, Larry Kotei, Abdoulie F. Jallow, Ousubie Jawla, Emmanuel U. Richard-Ugwuadu, Muhammed Jagana, Lamin Bah, Amadou Tijan Bah, Karamo Conteh, Mamadou S.K. Jallow, Mehrab Karim, Bai Lamin Dondeh, Anne Segonds-Pichon, Gary M. Clifford, Iacopo Baussano, Bruno Pichon, David Jeffries, Ed Clarke
Human papillomavirus (HPV) infection is a primary cause of preventable deaths from cervical cancer, a condition of profound inequality with approximately 90% of deaths occurring in low- and middle-income countries, particularly in sub-Saharan Africa. In May 2018, the WHO Director-General declared a Joint Global Commitment to Cervical Cancer Elimination, highlighting the critical role of HPV vaccines in achieving this goal. However, there is a lack of systemically collected data on HPV prevalence in The Gambia, and impact data from high-income countries may not be reliably extrapolated to West African settings due to geographical variation in HPV types and distinct behavioural, biological, and sociodemographic exposures. The Gambia introduced a two-dose HPV vaccination schedule in 2019, but coverage has been very low, interrupted mainly by the COVID-19 pandemic. This presents a key opportunity to generate vital baseline data on HPV prevalence in the population before potential scale-up of vaccination efforts. The PHASE survey, a multi-stage cluster survey, aims to establish the baseline, population prevalence estimates of high-risk and low-risk, vaccine-type and non-vaccine-type HPV infection in 15- to 49-year-old females in The Gambia by measuring urinary HPV-DNA. The survey will also quantify the effects of various exposures on HPV prevalence, including sexual behaviour, the presence of other sexually-transmitted infections (STIs) - Neisseria gonorrhoea (NG), Chlamydia trachomatis (CT), Trichomonas vaginalis (TV), Mycoplasma genitalium (MG), syphilis, as well as blood borne viruses, human immunodeficiency virus (HIV), hepatitis B and hepatitis C; obstetric history, socio-demographic characteristics, and cervical cancer screening and/or treatment. Additionally, the study will provide important antimicrobial resistance (AMR) data for NG and MG in sub-Saharan Africa, a region poorly represented in global surveillance programs. This data is needed to guide regional treatment guidelines and advocate for new solutions, including gonococcal vaccines. The AMR data are expected to immediately influence recommendations regarding the appropriate choice of antibiotics for syndromic STI management in West Africa and hence to address an important driver of AMR in the sub-region. Leveraging on the Medical Research Council Unit The Gambia funded Health Demographic Surveillance system (HDSS) as its sampling frame, the survey will utilize validated diagnostic assays and culturally sensitive data collection methods, to ensure both scientific rigor and local relevance. Tools such as Audio Computer-Assisted Self-Interviewing (ACASI) technology, developed in consultation with local community advisory boards, are included to reduce social desirability bias in reporting sexual behaviour. This approach aims to maximize both the reliability and cultural appropriateness of the findings. This study directly addresses the critical need for baseline epidemiological data on HPV in a West African setting to accelerate vaccine impact and drive new interventions towards cervical cancer elimination. By understanding other factors that influence HPV (like other STIs, sexual behaviour, etc.), the study aims to ensure that, when the vaccine’s impact is measured later, changes in other confounding factors that may impact on HPV prevalence can be accounted for. The study will also establish the population prevalence of the measured STIs and their relationship to common symptoms and other adverse health outcomes related to STIs.by Michael Seid, David Bridgeland, Christine L. Schuler, David M. Hartley
Improving the healthcare system is a persistent and pressing challenge. Collaborative Learning Health Systems, or Learning Health Networks (LHNs), are a novel, replicable organizational form in healthcare delivery that show substantial promise for improving health outcomes. To realize that promise requires a scientific understanding that can serve LHNs’ improvement and scaling. We translated social and organizational theories of collaboration to a computational (agent-based) model to develop a computer simulation of an LHN and demonstrate the potential of this new tool for advancing the science of LHNs. Model sensitivity analysis showed a small number of parameters with outsized effect on outcomes. Contour plots of these influential parameters allow exploration of alternative strategies for maximizing model outcomes of interest. A simulated trial of two common health system interventions – pre-visit planning and use of a registry – suggested that the efficacy of these could depend on LHN current state. By translating heuristic theories of LHNs to a specifiable, reproducible, and explicit model, this research advances the scientific study of LHNs using tools available from complex systems science.by Cheyenne R. Wagi, Renee McDowell, Anyssa Wright, Kathleen L. Egan, Christina S. Meade, April M. Young, Madison N. Enderle, Angela T. Estadt, Kathryn E. Lancaster
BackgroundHepatitis C virus (HCV) and injection drug use among young women are dramatically rising in the rural United States. From 2004 to 2017, heroin use among non-pregnant women increased 22.4% biennially, mirroring increases in HCV cases, especially among younger populations. Young women who inject drugs (YWID, ages 18–35) face elevated HCV risk due to biological, behavioral, and socio-cultural factors. Barriers to HCV testing and treatment services further delay diagnoses, fuel transmission, and limit access to harm reduction services. This study applies the Theoretical Domains Framework (TDF) to identify factors influencing HCV testing and treatment among YWID in rural Appalachia Ohio.
MethodsWe conducted in-depth interviews with YWID (n = 30) in 2023 to understand their HCV testing and treatment experiences in rural Appalachia Ohio. Interviews were transcribed, inductively coded, and analyzed using grounded theory. Identified themes were mapped onto the TDF domains.
ResultsKey TDF domains influencing HCV care included knowledge, beliefs about consequences, and intentions. While YWID knew where to get tested, they expressed uncertainty about treatment value and access while actively using drugs. Social influences, stigma, and mistreatment by healthcare providers created barriers to treatment. Environmental context and resources, such as transportation, also influenced access to care.
ConclusionsYWID in rural Appalachia face barriers to HCV care, such as gaps in knowledge about HCV treatment, which is compounded by gendered stigma, and logistical challenges. Rapidly changing treatment restrictions led to misinformation about treatment access. These gaps highlight the need for interventions specifically designed to address YWID lived experiences.
by Charlotte J. Whiffin, Kathleen Joy O. Khu, Brandon G. Smith, Isla Kuhn, Santhani M. Selveindran, Laura Hobbs, Samin Davoody, Yusuf Docrat, Orla Mantle, Upamanyu Nath, Lara Onbaşı, Stasa Tumpa, Ignatius N. Esene, Harry Mee, Fergus Gracey, Shobhana Nagraj, Tom Bashford, Angelos G. Kolias, Peter J. Hutchinson
Following calls for more qualitative research in neurosurgery, this scoping review aimed to describe the range and reach of qualitative studies relevant to the field of neurosurgery and the patients and families affected by neurosurgical conditions. A systematic search was conducted in September 2024 across six databases: Medline via Ebsco; Embase via OVID; PsycINFO via Ebsco; Scopus; Web of Science Core Collection; and Global Health via Ebsco. Eligibility criteria were based on Population, Concept, and Context. The search identified 18,809 hits for screening with 812 included in the final analysis. Seven themes were identified from a content analysis of study aims: 1 Perspectives of living with a neurosurgical condition; 2 Family perspectives; 3 Perceptions of neurosurgery; 4 Perceptions of general healthcare care; 5 Decision making; 6 Advancing neurosurgery; and, 7 Understanding neurosurgical conditions. Traumatology was identified as the most researched sub-specialty (43.2%) yet few studies were led explicitly by a neurosurgeon (1.6%) or those with a neurosurgical affiliation (10.5%). Lead authors were predominantly from high income countries (93.7%), as were most multi-author teams (86.6%). There was a trend towards increasing publication over time; however, only 8.4% of papers were published in neurosurgical specific journals. The data set had an average Field Weighted Citation Impact of 0.96 and Field Weighted Views Impact of 1.11, 18.9% were cited in policy documents in 15 countries. This scoping review provides a comprehensive picture of the current qualitative research base in neurosurgery and suggests ways to improve the conduct and reporting of such studies in the future. Addressing these challenges is crucial if qualitative research is to advance the neurosurgical evidence base in a rigorous way.by Alessandro Roman, Charlotte Linthout, Ben Raymond, Constantianus J. M. Koenraadt
Various vector control strategies are in place to reduce the spread of arthropod-borne viruses. Some of these, such as application of insecticides, are encountering operational challenges and a reduced overall effectiveness due to evolution of resistance. Alternative approaches for mosquito population control, such as the sterile insect technique, depend on efficient mass-rearing of healthy mosquitoes prior to mass-release in the field. Therefore, improving efficiency and quality of mass-rearing techniques is crucial to obtain fit mosquitoes. Previous studies have shown that Acetic Acid Bacteria of the genus Asaia can have a mutualistic effect on larval development in different mosquito species and can thus contribute to improved rearing output. However, whether improved performance in the larval stages may have knock-on effects in the adult stage, for example by increasing their capability to transmit arbovirus, remains unclear. Such effects may jeopardize future control efforts. We tested the effects of two Asaia species, Asaia krungthepensis and Asaia bogorensis, on development time and adult size under two rearing conditions: individual rearing and group rearing of Culex pipiens larvae. Besides investigating development and size, we also investigated whether Asaia spp. exposure during the larval stage can influence the vector competence of Culex pipiens pipiens for West Nile virus (WNV). Our work shows the potential of improving mass-rearing efficiency by employing Asaia krungthepensis as a mutualist for Culex pipiens pipiens. Importantly, this study reveals no significant increase in dissemination and transmission rate of WNV by Culex pipiens pipiens when inoculated with Asaia spp., although an increase in viral titer in the legs and the saliva was observed when the mosquitoes were inoculated with the two Asaia species. Interestingly, we confirmed that Asaia spp. bacteria did not establish as a permanent member of the microbiota of Culex pipiens pipiens. As Asaia spp. did not establish in adult mosquitoes, the observed change in WNV titers can be a result of indirect interactions of Asaia with the native Culex pipiens pipiens microbiome. Our results stress the importance of carefully evaluating host-symbiont interactions to avoid the potential of releasing mosquitoes with enhanced vector competence.by Kayab Khandakar, Jabin Tasnin Upoma, Taib Hasan, A. H. M. Iftekharul Ferdous, Diponkar Kundu, Md. Omar Faruk, Md. Feroz Ali, Md. Shahorin Islam Shaun
Excessive hormone release, the possibility of sleep disturbances, and a brief and quick improvement in the functioning of many organs, the physiological system, the nerves, etc. are all consequences of the abuse of incentive medications. Illegal narcotics have terrible long-term impacts on human health, including the possibility of death, in addition to their immediate effects. These consequences highlight the need for more obviousness and accuracy in the detection of illicit drugs, as well as for their detection to be done gently, effectively, and consistently. This work introduces an illicit drug sensor based on PCF, with an eye toward these as the primary targets. Three illegal drugs – ketamine, amphetamine, and cocaine – have been simulated for the sensor. Two types of circular air holes in cladding of varying sizes have been developed for a single core PCF. The cladding has three-layer chain and wind turbine-shaped air holes, and a circular air hole in the core region that will be used to field test drug samples, all included to achieve low confinement losses and high sensitivity. A maximum Relative Sensitivity (RS) of 99.92%, 99.12% and 98.83% at ketamine, amphetamine, and cocaine respectively is revealed by the recently established PCF analysis, which was presented out right away. Furthermore, we looked at the Confinement Loss (CL) associated with these illicit drugs, which was around 1.275 × 10−7 dB/m, 2.653 × 10−9 dB/m, and 4.106 × 10−10 dB/m, besides Effective Material Loss (EML) of 0.0042 cm-1, 0.0044 cm-1 and 0.0045 cm-1. Refractive index changes in PCF are usually the cause of action for PCF-based biosensors. These modifications have an impact on how light travels within the fiber. Drug molecules interact with light as a result of changes in the optical properties of the core that occur during light propagation through it.by Rebecca Lane, Filipa Alves-Costa, Rachael Gribble, Anna Taylor, Louise M. Howard, Nicola T. Fear, Deirdre MacManus
Research suggests that the prevalence of Intimate Partner Violence and Abuse (IPVA) use (i.e., perpetration) and experience (i.e., victimisation) is higher among military compared to civilian populations and that military-related factors, such as deployment and deployment-related trauma, are associated with IPVA. However, the mechanisms underlying the associations between military factors and IPVA use and experience are not well understood. This study explores narratives of how military personnel perceive military life to influence IPVA within relationships. Semi-structured interviews were conducted with 40 UK military serving and ex-serving personnel (29 male, 11 female) and analysed using Framework analysis. Three superordinate themes were derived describing how elements of military life were perceived by personnel and veterans to impact on relationships and contribute to IPVA: Demands of military work; Military cultural spill-over; and Deployment-related difficulties with psychosocial functioning and mental health. The findings highlight risky periods for relationship conflict and IPVA, especially during reintegrations following deployments, but also show the impact of other military factors which provide significant context for IPVA. Our findings emphasise how difficulties with psychosocial functioning and communication, as well as deployment-related traumas and reintegration challenges, can influence relationships and IPVA behaviours among military personnel and veterans. Such experiences are aggravated or perpetuated by occupational demands, military socialization or institutionalisation, and the hypermasculine military environment. Targeted interventions to improve emotion regulation, conflict resolution and mentalizing skills may be especially useful for minimising harm resulting from relationship conflict and preventing IPVA.by Weam Mohamed Meargni Ahmed, Malaz M. Abdalmotalib, Mohamed H. Elbadawi, Galia Tajelsir Fadulelmula Mohammed, Waad Mohamed Ibrahim Mohamed, Fatima Salih Babiker Mohammed, Hajar Saad Salih, Hiba Omer Yousif Mohamed
BackgroundArtificial intelligence (AI) is revolutionizing education globally, yet its adoption in medical education remains inadequately understood. ChatGPT, a generative AI tool, offers promising yet doubtful potential for enhancing academic and clinical training.
MethodsThis study employed an analytical cross-sectional design, involving 1,443 Sudanese medical students who participated through an online, structured questionnaire. The questionnaire was designed to assess ChatGPT awareness, usage, and associated factors. Statistical analysis was performed using SPSS software to identify key determinants influencing ChatGPT awareness and usage among the participants.
ObjectiveThis study investigates the levels of awareness, attitude, and usage of ChatGPT among Sudanese medical students, identifying key socio-demographic, economic, and institutional factors influencing its adoption.
ResultsAmong the participants, 65.8% were aware of ChatGPT, yet only 41.9% reported using it. Gender differences were statistically significant, with males demonstrating higher usage rates (p 300,000 SDGs) showed significantly greater usage (p Conclusions
The findings underscore the urgent need for targeted interventions, including curriculum reform to integrate AI literacy, enhanced digital infrastructure, and gender-equity initiatives. Addressing these systemic gaps will scale up AI adoption in medical education. This study provides actionable insights for educators and policymakers, emphasizing the urgency of bridging socio-economic and institutional inequities to foster equitable access to AI tools in medical training.
by Laurie M. Heller, Urszula Oszczapinska, Jessica M. Smith, Megan M. Julien
We conducted nine experiments to determine why a sound’s pleasantness can be altered by movies, abstract paintings, and words. In Expt. 1, unpleasant sounds, such as the sound of a person sniffing, were paired either with their original video track or with video tracks depicting neutral events that could plausibly have produced the sound, such as pulling tissues out of a tissue box. While the unpleasant sounds were mildly unpleasant to an unscreened population, these sounds were expected to be more unpleasant for people who have misophonia, a condition in which certain everyday sounds are unbearable. Consistent with past literature, neutral video tracks increased the sounds’ pleasantness for the non-misophonic and misophonic populations, by 0.98 and 1.59 points, respectively (on an 11-point scale). Movies rated as having better audio-visual matches produced greater changes in pleasantness, consistent with the hypothesis that source reassignment caused the changes. Expt. 2 found a consistent result when the video tracks were replaced with written event descriptions, although the effect size was reduced. Expt. 3 inverted Expt. 1 and found that unpleasant video tracks decreased the pleasantness of neutral sounds by 2.12 points, but better-matching movies did not produce greater changes in pleasantness. In Expts. 4–6, we sought an alternative to the source reassignment explanation by obtaining ratings of audio-visual synchrony, cross-modal agreement in symbolism, source plausibility, and sound identifiability. No complete explanation was found for the effect of unpleasant videos. Furthermore, pleasant abstract paintings increased the pleasantness of unpleasant sounds by 0.37 points, correlating with cross-modal agreement but not with audio-visual match. Taken together, different types and patterns of match ratings can help discern the causal mechanisms by which visual stimuli affect sound pleasantness (e.g., source reassignment, cross-modal agreement).by Eugénie M. Kamabu, Justin L. Paluku, William P. Howlett, Abid M. Sadiq, Eliada B. Nziku, Doreen T. Eliah, Ibrahim Ali Ibrahim Muhina, Fuad H. Said, Tumaini E. Mirai, Elifuraha W. Mkwizu, Furaha S. Lyamuya, Elichilia R. Shao, Kajiru G. Kilonzo, Venance P. Maro, Sarah J. Urasa, Nyasatu G. Chamba
BackgroundAmong acute stroke patients (ASPs), diabetes mellitus (DM) is associated with a higher risk of death, functional dependency, and recurrence. This study aimed to determine the impact of DM on the 30-day mortality among admitted ASPs in northern Tanzania.
Materials and methodsThis was a hospital-based prospective cohort study performed among ASPs with and without DM who were admitted to Kilimanjaro Christian Medical Centre from November 2022 to May2023. ASPs were followed for 30 days after the onset of an acute stroke to identify the primary outcome, which was all-cause mortality. Descriptive statistics, logistic regression, and survival analysis were conducted,
ResultsOut of 213 ASP, 82 (38.5%) had DM. The overall crude mortality rate was 46.9%. ASPs with DM had a higher mortality rate of 53.7% compared with those without DM (42.7%). A higher proportion of acute stroke patients with DM (84.1%) had a poor outcome (mRS 3-6) (p = 0.038). DM was statistically non-significant for 30-day mortality (aHR 1.56; 95% CI: 0.73–3.32; p = 0.252). However, fever (p = 0.005), severe admission Glasgow coma scale (p = 0.005), severe stroke (p = 0.008), elevated serum creatinine (p = 0.008), and an abnormal respiratory pattern (p = 0.042), were predictors of 30-day mortality,
ConclusionThis study demonstrated a high mortality in ASPs. Although DM did not have a significant impact on 30-day mortality, other factors, such as altered mental state, stroke severity, fever, elevated creatinine, and abnormal respiration, need to be accounted for that may have a significant impact on the mortality in ASPs. These findings highlight the significant burden of DM in stroke patients and underscore the importance of early diagnosis and treatment of ASPs, in the hopes of improving clinical practice and guidelines and reducing morbidity and mortality in Tanzania.
by Rhonda M. Merwin, Patrick J. Smith, J.A. Riley, Jordan Infield, Christine O’Connell, Dorothy Mayo, Ashley A. Moskovich, Lauren Hill, Hilary Winthrop, Amy Bush, Ernaya Johnson, Francesca Scheiber, Anthony D. Sung
Introduction: Allogeneic hematopoietic stem cell transplant (HCT) has the potential to cure patients with hematologic malignancies, but treatment-related morbidity and mortality is high. Transplant outcomes are optimized by patients maintaining physical activity. The aim of the current study was to examine whether a brief Acceptance and Commitment Therapy (ACT) intervention is acceptable to HCT patients and caregivers and helps patients engage in healthy behavior despite physical and emotional discomfort. Methods: Patients ≥ 18 years of age who were undergoing allogenic HCT for any cancer or non-cancer illness and their caregivers were invited to complete six ACT sessions between transplant day − 30 and day + 90. Multiple small cohorts of n = 3 dyads were enrolled, and the protocol content was iterated after each cohort to reflect the experiences and breadth of concerns of individuals undergoing HCT. Acceptability was indexed by session completion rates and acceptability surveys. Pre-post 6-minute walk distance was collected as an index of physical function as part of standard care. Results: Sixteen HCT dyads enrolled in the study; 12 continued to treatment. Most participants completed all assigned sessions. Participants perceived ACT to be helpful and 70% (5 of 7) of the patients with pre-post 6-minute walk test data showed improvement. Conclusion: ACT is an acceptable and potentially useful intervention for individuals undergoing HCT. Additional controlled studies are warranted.by Ian C. Lock, Nathan H. Leisenring, Warren Floyd, Eric S. Xu, Lixia Luo, Yan Ma, Erin C. Mansell, Diana M. Cardona, Chang-Lung Lee, David G. Kirsch
BackgroundThe tumor suppressor p53 (Trp53), also known as p53, is the most commonly mutated gene in cancer. Canonical p53 DNA damage response pathways are well characterized and classically thought to underlie the tumor suppressive effect of p53. Challenging this dogma, mouse models have revealed that p53-driven apoptosis and cell cycle arrest are dispensable for tumor suppression. Here, we investigated the inverse context of a p53 mutation predicted to drive the expression of canonical targets but is detected in human cancer.
MethodsWe established a novel mouse model with a single base pair mutation (GAG>GAT, p53E221D) in the DNA-Binding domain that has wild-type function in screening assays, but is paradoxically found in human cancer in Li-Fraumeni syndrome. Using mouse p53E221D and the analogous human p53E224D mutants, we evaluated expression, transcriptional activation, and tumor suppression in vitro and in vivo.
ResultsExpression of human p53E224D from cDNA translated to a fully functional p53 protein. However, p53E221D/E221D RNA transcribed from the endogenous locus is mis-spliced resulting in nonsense-mediated decay. Moreover, fibroblasts derived from p53E221D/E221D mice do not express a detectable protein product. Mice homozygous for p53E221D exhibited increased tumor penetrance and decreased life expectancy compared to p53WT/WT animals.
ConclusionsMouse p53E221D and human p53E224D mutations lead to splice variation and a biologically relevant p53 loss of function in vitro and in vivo.
by Laura S. Mkumba, Fortunata Nasuwa, Blandina T. Mmbaga, Aisa M. Shayo, Coleen K. Cunningham, Karen E. O’Donnell, Dorothy E. Dow
Youth living with HIV (YLWH) face psychosocial challenges and HIV-related stigma, which impact adherence to antiretroviral therapy (ART). This study was designed to understand better the change in mental health symptoms and experiences with stigma among YLWH in Tanzania who completed the original pilot Sauti ya Vijana (SYV), a mental health and life skills group intervention. YLWH who completed SYV and demonstrated a change of ≥2 points in either direction on their Patient Health Questionnaire PHQ-9 (depression screener) from baseline to 18 months were purposively sampled. HIV Stigma was measured using 10-questions from the Berger HIV Stigma Scale, and findings ranged from 4–16 for internal stigma and 6–24 for external stigma. In-depth interviews (IDI) were conducted in Kiswahili and included topics such as history of mental health challenges, perceptions of stigma, and experiences with the SYV intervention. Interviews were transcribed, translated to English, and analyzed for emergent themes. Ten youth, 18–25 years of age, were interviewed; 70% were male. Mean (SD) PHQ-9 scores were 7.3 (SD = 3.5) at baseline and 5.6 (SD = 5.0) at 18 months. All participants reported experiencing intermittent episodes of mental health challenges due to difficult interpersonal relationships and fear of stigma. Youth relied on peer support and skills from the SYV intervention to cope with mental health challenges and stigma. Participants reported fear of being stigmatized by others, which led to behaviors such as skipping medication or avoiding situations for worry about unintentional disclosure. All participants endorsed experiencing external stigma on the HIV stigma scale; however, only 3 of 10 participants reported experiencing enacted stigma when directly asked to describe an experience during in-depth interviews. Participants described how SYV helped them have “more confidence”, accept themselves, and incorporate positive coping skills such as relaxation (deep breathing) when they felt stressed. The findings suggest SYV helped YLWH accept themselves, develop positive coping methods, and identify and form peer social support; but stigma remains common. Descriptions of stigma were not recognized as such; experiences of enacted stigma were acknowledged by some participants. More research is needed to understand and measure mental distress and wellness as well as stigma in this population so that interventions may more accurately detect change in key outcomes.by Féline E. V. Scheijmans, Roosmarijn van der Wal, Margot L. Zomers, Johannes J. M. van Delden, W. Ludo van der Pol, Ghislaine J. M. W. van Thiel
ObjectivesSolidarity-based healthcare systems are being challenged by the incremental costs of new and expensive medicines for cancer and rare diseases. To regulate reimbursement of such drugs, the Dutch government introduced a policy instrument known as the Coverage Lock (CL) in 2015. Little is known about the public opinion regarding such policy instruments and their consequences, i.e., reimbursement of some, but not all, expensive medicines. We aimed to identify the preferences of Dutch citizens regarding the reimbursement of expensive medicines, and to investigate the views of the public on the use of the CL as a healthcare policy instrument and their input for improvement.
MethodsWeb-based survey of a representative sample of 1999 Dutch citizens aged 18 years and older (panel of research company Kantar Public). Potential respondents were approached via e-mail. Several policy measures, real-life cases and statements related to the CL were presented in the survey to respondents. Their responses were analysed by tabulating descriptive statistics (proportions and percentages).
Results1179 individuals (response rate 59%) filled in the questionnaire. Although a majority considered the CL policy unjustified, they preferred it to the alternative policy measures that were presented. In four real-life case descriptions of patients in need of expensive medicines, respondents most often indicated effectiveness, lack of availability of alternative treatment and improved quality of life due to treatment as reasons for a positive reimbursement decision. An unfavourable cost-benefit ratio was their main reason to be against reimbursement. Some argued that withholding reimbursement was a way of informing manufacturers that extremely high prices are unacceptable.
ConclusionThere is public support for patients in need of expensive medicine. Many respondents supported the CL as a reimbursement policy. However, there is a wish to optimize the interpretation of the assessment criteria and the weight these are attributed in decision making about reimbursement of expensive innovative medicine for patients.
by Mahmoud A. A. Ibrahim, Doaa G. M. Mahmoud, Alaa H. M. Abdelrahman, Khlood A. A. Abdeljawaad, Gamal A. H. Mekhemer, Tamer Shoeib, Mohamed A. El-Tayeb, Peter A. Sidhom, Paul W. Paré, Mohamed-Elamir F. Hegazy
Mycobacterium tuberculosis is a lethal human pathogen, with the key flavoenzyme for catalyzing bacterial cell-wall biosynthesis, decaprenylphosphoryl-D-ribose oxidase (DprE1), considered an Achilles heal for tuberculosis (TB) progression. Inhibition of DprE1 blocks cell wall biosynthesis and is a highly promising antitubercular target. Macozinone (PBTZ169, a benzothiazinone (BTZ) derivative) is an irreversible DprE1 inhibitor that has attracted considerable attention because it exhibits an additive activity when combined with other anti-TB drugs. Herein, 754 BTZ analogs were assembled in a virtual library and evaluated against the DprE1 target using a covalent docking approach. After validation of the employed covalent docking approach, BTZ analogs were screened. Analogs with a docking score less than –9.0 kcal/mol were advanced for molecular dynamics (MD) simulations, followed by binding energy evaluations utilizing the MM-GBSA approach. Three BTZ analogs–namely, PubChem-155-924-621, PubChem-127-032-794, and PubChem-155-923-972– exhibited higher binding affinities against DprE1 compared to PBTZ169 with ΔGbinding values of –77.2, –74.3, and –65.4 kcal/mol, versus –49.8 kcal/mol, respectively. Structural and energetical analyses were performed for the identified analogs against DprE1 throughout the 100 ns MD simulations, and the results demonstrated the great stability of the identified BTZ analogs. Physicochemical and ADMET characteristics indicated the oral bioavailability of the identified BTZ analogs. The obtained in-silico results provide promising anti-TB inhibitors that are worth being subjected to in-vitro and in-vivo investigations.by Lilah M. Besser, Sarah N. Forrester, Milla Arabadjian, Michael P. Bancks, Margaret Culkin, Kathleen M. Hayden, Elaine T. Le, Isabelle Pierre-Louis, Jana A. Hirsch
BackgroundResearchers have increasingly recognized the importance of structural and social determinants of health (SSDOH) as key drivers of a multitude of diseases and health outcomes. The Multi-Ethnic Study of Atherosclerosis (MESA) is an ongoing, longitudinal cohort study of subclinical cardiovascular disease (CVD) that has followed geographically and racially/ethnically diverse participants starting in 2000. Since its inception, MESA has incorporated numerous SSDOH assessments and instruments to study in relation to CVD and aging outcomes. In this paper, we describe the SSDOH data available in MESA, systematically review published papers using MESA that were focused on SSDOH and provide a roadmap for future SSDOH-related studies.
Methods and findingsThe study team reviewed all published papers using MESA data (n = 2,125) through January 23, 2023. Two individuals systematically reviewed titles, abstracts, and full text to determine the final number of papers (n = 431) that focused on at least one SSDOH variable as an exposure, outcome, or stratifying/effect modifier variable of main interest (discrepancies resolved by a third individual). Fifty-seven percent of the papers focused on racialized/ethnic groups or other macrosocial/structural factors (e.g., segregation), 16% focused on individual-level inequalities (e.g. income), 14% focused on the built environment (e.g., walking destinations), 10% focused on social context (e.g., neighborhood socioeconomic status), 34% focused on stressors (e.g., discrimination, air pollution), and 4% focused on social support/integration (e.g., social participation). Forty-seven (11%) of the papers combined MESA with other cohorts for cross-cohort comparisons and replication/validation (e.g., validating algorithms).
ConclusionsOverall, MESA has made significant contributions to the field and the published literature, with 20% of its published papers focused on SSDOH. Future SSDOH studies using MESA would benefit by using recently added instruments/data (e.g., early life educational quality), linking SSDOH to biomarkers to determine underlying causal mechanisms linking SSDOH to CVD and aging outcomes, and by focusing on intersectionality, understudied SSDOH (i.e., social support, social context), and understudied outcomes in relation to SSDOH (i.e., sleep, respiratory health, cognition/dementia).
by Geertje van Wijk, Lisa van Antwerpen, Femke A. Hoefnagels, Sjef J. J. M. Staps, Marieke C. E. Battjes-Fries
ObjectiveAn increasing number of children in the Netherlands is overweight or obese, which is largely attributable to an unhealthy lifestyle and unhealthy living environment. Nutrition education and greening the schoolyard, for example with a vegetable garden, have independently been studied and are shown to be effective in teaching children a healthy lifestyle and providing a healthy living environment. However, the feasibility of combining nutrition education and greening the schoolyard has not been studied yet. Therefore, this study aimed to provide insight into primary schools’ vision on making this combination, and the feasibility of doing so.
MethodsIn this study a qualitative research design was used. The theoretical frameworks of Proctor et al. and Sekhon et al. were used to develop the interview guide. Twelve semi-structured interviews were conducted with members of school teams and school directors. The interviews were transcribed verbatim and analyzed using the thematical analysis of Braun and Clarke.
ResultsAccording to the interviewees, three facets are essential to make the combination of greening schoolyards and nutrition education feasible and successful. Firstly, the interviewees mentioned that the school team and school directors of schools must be able to see the connection between greening the schoolyard and nutrition education. Additionally, support is needed among the parents, school team, pupils and local community. Finally, the interviewees stated that schools must be able to integrate greening the schoolyard and nutrition education into their existing curriculum.
ConclusionsThe results of this study showed that combining greening schoolyards and nutrition education in primary schools is feasible and successful when vision, support and integration are present. Future research should investigate the vision of the local community and parents on making the combination, and the effects of the combination on pupils and their environment.
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