Unleashing the potential of vanillic acid: A new twist on nature's recipe to fight inflammation and circumvent azole-resistant fungal infections.

Vanillic acid (VA) - a naturally occurring phenolic compound in plants - is not only used as a flavoring agent but also a prominent metabolite post tea consumption. VA and its associated compounds are believed to play a significant role in preventing diseases, underscoring the need for a systematic investigation. Herein, we report a 4-step synthesis employing the classical organic reactions, such as Willamson's alkylation, Fischer-Spier reaction, and Steglich esterification, complemented with a protection-deprotection strategy to prepare 46 VA derivatives across the five series (1a-1i, 2a-2i, 3, 3a-3i, 4a-4i, 5a-5i) in high yields. The synthesized compounds were investigated for their antifungal, anti-inflammatory, and toxic effects. Notably, compound 1a demonstrated remarkable ROS inhibition with an IC50 value of 5.1 ± 0.7 µg/mL, which is more than twice as effective as the standard ibuprofen drug. A subset of the synthesized derivatives (2b, 2c, 2e, 3b-3d, 4a-4c, 5a, and 5e) manifested their antifungal effect against drug-resistant Candida strains. Compound 5g, in particular, revealed synergism with the established antifungal drugs amphotericin B (AMB) and fluconazole (FLZ), doubling FLZ's potency against azole resistant Candida albican ATCC 36082. Furthermore, 5g improved the potency of these antifungals against FLZ-sensitive strains, including C. glabrata ATCC 2001 and C. parapsilosis ATCC 22019, as well as various multidrug-resistant (MDR) Candida strains, namely C. albicans ATCC 14053, C. albicans CL1, and C. krusei SH2L OM341600. Additionally, pharmacodynamics of compound 5g was examined using time-kill assay, and a benign safety profile was observed with no hemolytic activity in whole blood, and no cytotoxicity towards the normal BJ human cell line. The synergistic potential of 5g was further investigated through both experimental methods and docking simulations.These findings highlight the therapeutic potential of VA derivatives, particularly in addressing inflammation and circumventing FLZ resistance in Candida albicans.

Cross-subunit catalysis and a new phenomenon of recessive resurrection in Escherichia coli RNase E.

RNase E is a 472-kDa homo-tetrameric essential endoribonuclease involved in RNA processing and turnover in Escherichia coli. In its N-terminal half (NTH) is the catalytic active site, as also a substrate 5'-sensor pocket that renders enzyme activity maximal on 5'-monophosphorylated RNAs. The protein's non-catalytic C-terminal half (CTH) harbours RNA-binding motifs and serves as scaffold for a multiprotein degradosome complex, but is dispensable for viability. Here, we provide evidence that a full-length hetero-tetramer, composed of a mixture of wild-type and (recessive lethal) active-site mutant subunits, exhibits identical activity in vivo as the wild-type homo-tetramer itself ('recessive resurrection'). When all of the cognate polypeptides lacked the CTH, the active-site mutant subunits were dominant negative. A pair of C-terminally truncated polypeptides, which were individually inactive because of additional mutations in their active site and 5'-sensor pocket respectively, exhibited catalytic function in combination, both in vivo and in vitro (i.e. intragenic or allelic complementation). Our results indicate that adjacent subunits within an oligomer are separately responsible for 5'-sensing and cleavage, and that RNA binding facilitates oligomerization. We propose also that the CTH mediates a rate-determining initial step for enzyme function, which is likely the binding and channelling of substrate for NTH's endonucleolytic action.

Phytochemical Characterizations of Maranthes polyandra (Benth.) Prance.

Two new ursane-type triterpenoids, named Polyanside A (1) and B (2), along with eleven known compounds (3-13), were isolated and elucidated from Maranthes polyandra (Benth.) Prance. The structures of these compounds were elucidated based on chemical evidence and multiple spectroscopic data. Isolated compounds were evaluated for anti-cancer, anti-inflammatory activities, and cytotoxicity on a normal human cell line (BJ). None of them showed activity and cytotoxicity. The hexane fraction was analyzed by GC-MS, resulting in the identification of forty-one compounds. This is the first comprehensive study on the phytochemistry of M. polyandra.

Promoting Interdisciplinary, Participatory Approaches to Address Childhood Asthma Disparities in an Urban Black Community.

Black children are twice as likely as non-Hispanic white children to have asthma due to an interplay of socioeconomic, historical, and industrial factors. The underlying socio-economic and structural inequities result in poor adherence to recommended asthma management treatments. National guidelines suggest asthma action plans (AAPs) as a tool for patient self-management, yet they remain underutilized. Boot Camp Translation (BCT), rooted in community-based participatory research, provides a method for engaging communities to improve health literacy. This article describes the successful use of BCT to develop a culturally relevant AAP promotion campaign in West Louisville, a predominantly Black community that experiences social and health disparities.

State-led opioid overdose prevention efforts: Challenges, solutions and lessons learned from the CDC Prevention for States Program (PfS).

Background: The Centers for Disease Control and Prevention's Prevention for States (PfS) program funded 29 state health departments to prevent opioid overdose by implementing evidence-based prevention strategies. The objectives of this analysis were to describe the scope of activities implemented across the four PfS strategies and identify implementation challenges. Methods: PfS recipients submitted annual progress reports (APRs) to state support staff at CDC from 2015 to 2017. APR data were used to calculate the number of required and optional activities implemented under each PfS strategy. APR data were qualitatively analyzed using a systematic content analysis approach to identify key implementation challenges. Results: From 2015 to 2017, PfS recipients implemented 177 activities across four strategies from 2015 to 2017. Cross-cutting implementation challenges were (1) multi-sector collaboration, (2) lack of knowledge and misperceptions about opioid used disorder (OUD) among some partners and local communities and; (3) management and access to opioid data among PfS recipients. Conclusions: PfS recipients implemented an array of prevention interventions to address the opioid overdose crisis and encountered several cross-cutting implementation challenges. Challenges and state driven solutions over the course of implementing PfS led to several lessons learned and actions that CDC enacted to continue to support and expand overdose prevention.

Emotion regulation, optimism and quality of life among Gastric Ulcer Patients.

OBJECTIVE: The study was aimed to investigate the association among emotion regulation, optimism and quality of life among gastric ulcer patients. METHODS: The Cross-sectional study was conducted in public sector hospitals of Lahore, during January-June 2017. Sample of study was comprised of 100 patients diagnosed with gastric ulcer, aged 25-55 years, selected through non-probability purposive sampling technique. Demographic information sheet, Emotion Regulation Scale by John, Gross 2003, Life Orientation Test-Revised by Sheer, Carver 2002, Quality of Life Enjoyment and Satisfaction Questionnaire by Endicott 1993 were used for data collection. SPSS 21 version was used for data analysis. RESULTS: Out of total 100 participants 41 (41%) were men and 59 (59%) were women, with mean age of (M= 44.89, SD= 7.99). There was significant positive correlation among emotion regulation, optimism and quality of life (p<0.01). Optimism and emotion regulation were observed as significant predictors of quality of life (p<0.01). Significant gender differences were found in emotion regulation (p< 0.01), optimism (p< 0.01) and quality of life (p<0.01), with men scoring higher as compared to women. One way ANOVA showed significant differences between emotion regulation, optimism and quality of life among different age groups of gastric ulcer patients (p< 0.01). CONCLUSION: Quality of life of gastric ulcer patients can be greatly improved by effectively using emotion regulation strategies and optimistic approach.

Delay or Avoidance of Medical Care Because of COVID-19-Related Concerns - United States, June 2020.

Temporary disruptions in routine and nonemergency medical care access and delivery have been observed during periods of considerable community transmission of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19) (1). However, medical care delay or avoidance might increase morbidity and mortality risk associated with treatable and preventable health conditions and might contribute to reported excess deaths directly or indirectly related to COVID-19 (2). To assess delay or avoidance of urgent or emergency and routine medical care because of concerns about COVID-19, a web-based survey was administered by Qualtrics, LLC, during June 24-30, 2020, to a nationwide representative sample of U.S. adults aged ≥18 years. Overall, an estimated 40.9% of U.S. adults have avoided medical care during the pandemic because of concerns about COVID-19, including 12.0% who avoided urgent or emergency care and 31.5% who avoided routine care. The estimated prevalence of urgent or emergency care avoidance was significantly higher among the following groups: unpaid caregivers for adults* versus noncaregivers (adjusted prevalence ratio [aPR] = 2.9); persons with two or more selected underlying medical conditions† versus those without those conditions (aPR = 1.9); persons with health insurance versus those without health insurance (aPR = 1.8); non-Hispanic Black (Black) adults (aPR = 1.6) and Hispanic or Latino (Hispanic) adults (aPR = 1.5) versus non-Hispanic White (White) adults; young adults aged 18-24 years versus adults aged 25-44 years (aPR = 1.5); and persons with disabilities§ versus those without disabilities (aPR = 1.3). Given this widespread reporting of medical care avoidance because of COVID-19 concerns, especially among persons at increased risk for severe COVID-19, urgent efforts are warranted to ensure delivery of services that, if deferred, could result in patient harm. Even during the COVID-19 pandemic, persons experiencing a medical emergency should seek and be provided care without delay (3).

Salivary Alpha-Amylase as a Biomarker of Stress in Behavioral Medicine.

In recent years, research in behavioral medicine has become increasingly focused on understanding how chronic and acute exposure to stress impacts health outcomes. During stress, the body's physiological stress systems are activated. These systems closely interact with the immune system and are, thus, importantly implicated in the onset and maintenance of disease states. While much of the research in behavioral medicine that has investigated the effects of stress on disease has focused on the role of the hypothalamic-pituitary-adrenal axis and its downstream biomarker, cortisol, it is evident that the autonomic nervous system (ANS) also plays a crucial role in both the biological stress process and the manifestation and maintenance of stress-related symptoms. In recent years salivary alpha-amylase (sAA) has emerged as a valid and reliable marker of ANS activity in stress research and is therefore an important biomarker to consider in behavioral medicine. In this commentary, we will highlight research relevant for behavioral medicine that has utilized sAA measurements, both basally, and in response to stress, to examine ANS function in clinical populations. We will additionally summarize findings from studies that have examined the effects of various targeted interventions on changes in sAA levels. Through this, our aim is to present evidence that sAA can serve as a feasible biomarker of ANS (dys)function in health and disease. To this end, we will also highlight important methodological considerations for readers to keep in mind when including sAA assessments in their own studies. The overarching goal of this brief commentary is to highlight how a multidimensional approach toward physiological stress measurement can allow researchers to develop a better understanding of physical health and disease states.

MicroRNAs as biomarkers for human glioblastoma: progress and potential.

Glioblastoma multiforme (GBM) is the most common malignant glioma. Despite innovative research efforts in tumor therapy, the outcome for most diagnosed patients remains poor; therefore, early diagnosis of GBM is the most effective method for achieving better patient outcomes. In recent years, combined research efforts including cellular, molecular, genetic, and bioinformatics methods have been used to investigate GBM, and the results show that variations in miRNA expression occur in GBM tissues and biological fluids. Some highly stable miRNAs circulate in the blood and cerebrospinal fluid (CSF) of both healthy individuals and diagnosed patients, thus raising the possibility that miRNAs may serve as novel diagnostic markers. In addition, increased understanding of the miRNA and mRNA interactions involved in GBM progression may lead to discovering predictive biomarkers, some of which are clinically relevant for targeted therapy and predicting prognosis. However, as this field is relatively new, some studies have yielded conflicting results. To progress in the field, different advanced techniques must be combined, including bioinformatics methods and molecular and cellular techniques. In addition, we must overcome the various challenges in non-invasive GBM biomarker detection. Here, we discuss the progress and potential of miRNAs as biomarkers for GBM and related signaling pathways. Studying the clinical relevance and applicability of these biomarkers may alter GBM patient diagnosis and treatment.

Addressing Health Insurance Literacy Gaps in an Urban African American Population: A Qualitative Study.

Health insurance and health systems literacy needs are evolving with changes to the U.S. healthcare system. Following the implementation of the Affordable Care Act, many residents in West Louisville, Kentucky, a predominantly African American community, gained health insurance coverage for the first time. A qualitative study was conducted to assess residents' health insurance and health systems needs and to identify ways of assisting residents with navigating the healthcare system and utilizing their health insurance coverage. Twelve focus groups were conducted with a total of eighty-seven residents. Round one explored participants' experiences with health insurance, and round two examined their health information delivery preferences. An inductive thematic analysis was performed. Participants revealed the complexity of the health insurance system, many citing difficulty understanding health insurance concepts and finding suitable healthcare providers. High costs, mistrust in the healthcare system, and perceived public-private disparities were barriers to effective health insurance utilization. Health insurance materials in their current form have limited value in translating health insurance and health systems information to the West Louisville population. Alternative forms of information delivery, such as locally accessible and culturally competent community health workers may be better received and more successfully utilized by the community.

Executive function and mothering: challenges faced by teenage mothers.

Previous research has established that in comparison to adult mothers teen mothers respond less sensitively to their infants. In adults, components of executive functions relate directly to maternal sensitivity. Since teenagers are known to have a less developed prefrontal cortex and greater difficulties in parenting, this study sought to determine whether the association between executive processes and mothering exists among teenagers. Two groups of mothers, teens (n = 30) and adults (n = 27), who were approximately 4-6 months postpartum, completed tasks assessing spatial working memory and attentional set shifting (cognitive flexibility) using the Cambridge Neuropsychological Test Automated Battery. Mothers were videotaped interacting with their infants and were later coded for various maternal behaviors. As predicted, teenagers performed more poorly than adults on tasks of cognitive flexibility and were less sensitive in their infant interactions. Among both groups there was a negative association between executive function and mothering; however, depending on the age of the mother different executive function tasks were relevant.

Update on the Basic Understanding of Fusarium graminearum Virulence Factors in Common Wheat Research.

Wheat is one of the most important food crops, both in China and worldwide. Wheat production is facing extreme stresses posed by different diseases, including Fusarium head blight (FHB), which has recently become an increasingly serious concerns. FHB is one of the most significant and destructive diseases affecting wheat crops all over the world. Recent advancements in genomic tools provide a new avenue for the study of virulence factors in relation to the host plants. The current review focuses on recent progress in the study of different strains of Fusarium infection. The presence of genome-wide repeat-induced point (RIP) mutations causes genomic mutations, eventually leading to host plant susceptibility against Fusarium invasion. Furthermore, effector proteins disrupt the host plant resistance mechanism. In this study, we proposed systematic modification of the host genome using modern biological tools to facilitate plant resistance against foreign invasion. We also suggested a number of scientific strategies, such as gene cloning, developing more powerful functional markers, and using haplotype marker-assisted selection, to further improve FHB resistance and associated breeding methods.

A Cross-sectional Survey-based Study of Knowledge, Attitude, and Practice Towards Uses of Cosmetics and Cosmetovigilance in India.

Background: In India, the cosmetics industry has expanded significantly because of changing lifestyles and increased awareness. In terms of earning the most money from the personal care and cosmetics industry in 2021, India is ranked fourth globally. Many cosmetics sold in India include ingredients that cannot be used on humans. Objective: To assess knowledge, attitudes, and practice toward the uses of cosmetics and cosmetovigilance in India. Methods: A cross-sectional study was conducted, from April to May 2022, among the general population living in the Delhi NCR region, India. Study questionnaires (printed and survey link) were distributed in public as well as at workplaces for the survey. Results: Around 268 (54.78%) females and 223 (45.21%) males participated in the survey. Amongst the total respondents - 407 (83%) agreed that they are using cosmetic products on a daily basis, females 229 (85.44%), being the majority users compared to males 178 (80%), with a significant P value = 0.011. Most of the people reported side effects of shampoos - 7.13% (hair fall, hair thinning, dryness of the scalp, itching), followed by allergic reactions to moisturizers - 5.70%. Conclusion: Because of the right safety and effectiveness mentorship of cosmetics, regulatory agencies and stakeholders should adopt this broadly. Cosmetovigilance needs to be put into practice.

The potential of epiphytic hydrocarbon-utilizing bacteria on legume leaves for attenuation of atmospheric hydrocarbon pollutants.

The leaves of two legumes, peas and beans, harbored on their surfaces up to 9×107 cells g⁻¹ of oil-utilizing bacteria. Less numbers, up to 5×105 cells g⁻¹ inhabited leaves of two nonlegume crops, namely tomato and sunflower. Older leaves accommodated more of such bacteria than younger ones. Plants raised in oily environments were colonized by much more oil-utilizing bacteria than those raised in pristine (oil-free) environments. Similar numbers were counted on the same media in which nitrogen salt was deleted, indicating that most phyllospheric bacteria were probably diazotrophic. Most dominant were Microbacterium spp. followed by Rhodococcus spp., Citrobacter freundii, in addition to several other minor species. The pure bacterial isolates could utilize leaf tissue hydrocarbons, and consume considerable proportions of crude oil, phenanthrene (an aromatic hydrocarbon) and n-octadecane (an alkane) in batch cultures. Bacterial consortia on fresh (but not on previously autoclaved) leaves of peas and beans could also consume substantial proportions of the surrounding volatile oil hydrocarbons in closed microcosms. It was concluded that phytoremediation through phyllosphere technology could be useful in remediating atmospheric hydrocarbon pollutants.

Hair cortisol levels in women with medically unexplained symptoms.

Stress has been demonstrated to be involved in the development of medically unexplained symptoms. A key underlying mechanism could be lower levels of cortisol, which can contribute to symptoms such as fatigue or pain. However, the literature is highly equivocal, which may be due to methodological limitations inherent in short-term cortisol assessment. The aim of this case-control study was to investigate, for the first time, whether individuals with different forms of medically unexplained symptoms show altered hair cortisol concentrations, a long-term marker of hypothalamic-pituitary-adrenal functioning. Two groups of women with medically unexplained symptoms were recruited. The first had a functional somatic syndrome, characterised by specific medically unexplained symptoms (i.e., chronic fatigue syndrome, fibromyalgia, or irritable bowel syndrome, n = 33). The second had somatic symptom disorder, characterised by excessive thoughts, feelings, and behaviours devoted to various medically unexplained symptoms (n = 23). These groups were contrasted with healthy controls (n = 30), and women with depression (n = 27). Cortisol representing the previous three months was extracted from hair. Chronic stress and childhood trauma were assessed (retrospectively). Women with somatic symptom disorder had lower hair cortisol than healthy controls and women with functional somatic syndromes. No differences in hair cortisol were found between healthy controls, functional somatic syndromes, and depression. Neither childhood trauma nor chronic stress was correlated with hair cortisol. Provided that our findings are replicated, they may suggest that hypocortisolism is found in a specific subgroup of individuals with medically unexplained symptoms, and potentially in those characterised by excessive thoughts, feelings, and behaviours about symptoms.

Health Insurance Literacy Perceptions and the Needs of a Working-Class Community.

BACKGROUND: Despite increases in the number of insured Americans, consumers continue to face barriers in accessing care. Low levels of health insurance literacy (HIL) are associated with suboptimal use of health insurance coverage. There remains a need to further contextualize the relationship between HIL and access to care, especially among insured working-class people. Objective This study was conducted to understand the pathways through which HIL affects health care decision-making and access to care in an urban working-class population. METHODS: Using a qualitative descriptive approach, we conducted five focus groups with 45 adult residents of South Louisville, Kentucky. The questions explored participants' experiences of insurance enrollment, use, and health care system navigation, as well as their perceptions and needs regarding accessing health insurance information. Using inductive thematic analysis, transcripts were open coded independently by team members, a focused coding framework was agreed upon, and emergent themes were identified through constant comparison techniques. KEY RESULTS: Most participants placed high value on their insurance, considering it the most important benefit employers offer. Despite having adequate HIL, most participants expressed frustration with the amount of time and effort they spent to determine the best insurance plan, obtain covered health services, and settle claims, often with ineffective results. Despite having insurance, cost considerations influenced many participants' decisions to accept certain tests or treatments, in some cases resulting in delayed or foregone care. CONCLUSIONS: The findings of this qualitative study indicate that obtaining health care is strongly influenced both by the individual context of HIL knowledge, experience, and life circumstances, and by the structural context of the complex, bureaucratic, and costly health care system. Interventions to improve HIL should include practical examples and real-life scenarios, because HIL gained from experiential narratives was the most useful in navigating the health care system.[HLRP: Health Literacy Research and Practice. 2022;6(2):e61-e69.] Plain Language Summary: By conducting focus groups with a working-class population, this study contextualizes the pathways through which HIL affects consumers' health care decision-making and access to care. Findings demonstrate that obtaining health care is strongly influenced both by the individual context of HIL knowledge, experience, and life circumstances, and by the structural context of the complex, bureaucratic, and costly health care system.

Does childhood trauma impact daily psychobiological stress in somatic symptom disorder? An ambulatory assessment study.

Objectives: Somatic symptom disorder is characterized by excessive thoughts, feelings, and behaviors dedicated to bodily symptoms, which are often medically unexplained. Although 13% of the population are affected by this disorder, its aetiopathogenesis is not fully understood. Research in medically unexplained conditions (e.g., fibromyalgia) points to increased psychosocial stress and alterations in stress-responsive bodily systems as a potential contributing factor. This pattern has often been hypothesized to originate from early life stress, such as childhood trauma. The aim of this study was to examine, for the first time, whether individuals with somatic symptom disorder exhibit elevated levels of self-reported daily stress and alterations in the autonomic nervous system and hypothalamic-pituitary-adrenal axis, both in comparison to healthy controls and individuals with depressive disorders, and whether reports of childhood trauma influence these alterations. Methods: A total of N = 78 individuals were recruited into this study. Of these, n = 27 had a somatic symptom disorder, n = 23 were healthy controls, and n = 28 had a depressive disorder. All individuals underwent a 14-day measurement period at home, with five assessments of self-reported stress, salivary alpha-amylase, and cortisol per day. Childhood trauma was assessed by the Childhood Trauma Questionnaire. Results: Individuals with somatic symptom disorder exhibited higher daily stress levels (p = 0.063) as well as a less pronounced alpha-amylase awakening response (p = 0.050), compared to healthy controls (statistical trends). Moreover, they were characterized by significantly attenuated diurnal cortisol concentrations (p < 0.001). A nearly identical pattern was observed in individuals with depression. In individuals with somatic symptom disorder and depressive disorders, childhood trauma was, by trend, associated with a more pronounced alpha-amylase awakening response (b = -0.27, p = 0.077). Conclusions: This study provides preliminary evidence for elevated daily stress and blunted sympathetic and hypothalamic-pituitary-adrenal axis activity in individuals with somatic symptom disorder and depressive disorders. Further studies will help to uncover the conditions under which these dysregulations develop into medically unexplained vs. depressive symptoms.

A Thematic Analysis of Overdose Prevention and Response Efforts in States Experiencing Declines in Rates of Opioid-Involved Overdose Deaths.

OBJECTIVE: To address the opioid overdose epidemic, it is important to understand the broad scope of efforts under way in states, particularly states in which the rate of opioid-involved overdose deaths is declining. The primary objective of this study was to examine core elements of overdose prevention activities in 4 states with a high rate of opioid-involved overdose deaths that experienced a decrease in opioid-involved overdose deaths from 2016 to 2017. METHODS: We identified 5 states experiencing decreases in age-adjusted mortality rates for opioid-involved overdoses from 2016 to 2017 and examined their overdose prevention programs via program narratives developed with collaborators from each state's overdose prevention program. These program narratives used 10 predetermined categories to organize activities: legislative policies; strategic planning; data access, capacity, and dissemination; capacity building; public-facing resources (eg, web-based dashboards); training resources; enhancements and improvements to prescription drug monitoring programs; linkage to care; treatment; and community-focused initiatives. Using qualitative thematic analysis techniques, core elements and context-specific activities emerged. RESULTS: In the predetermined categories of programmatic activities, we identified the following core elements of overdose prevention and response: comprehensive state policies; strategic planning; local engagement; data access, capacity, and dissemination; training of professional audiences (eg, prescribers); treatment infrastructure; and harm reduction. CONCLUSIONS: The identification of core elements and context-specific activities underscores the importance of implementation and adaptation of evidence-based prevention strategies, interdisciplinary partnerships, and collaborations to address opioid overdose. Further evaluation of these state programs and other overdose prevention efforts in states where mortality rates for opioid-involved overdoses declined should focus on impact, optimal timing, and combinations of program activities during the life span of an overdose prevention program.

In silico evaluation of molecular virus-virus interactions taking place between Cotton leaf curl Kokhran virus- Burewala strain and Tomato leaf curl New Delhi virus.

BACKGROUND: Cotton leaf curl disease (CLCuD) is a disease of cotton caused by begomoviruses, leading to a drastic loss in the annual yield of the crop. Pakistan has suffered two epidemics of this disease leading to the loss of billions in annual exports. The speculation that a third epidemic of CLCuD may result as consequence of the frequent occurrence of Tomato leaf curl New Delhi virus (ToLCNDV) and Cotton leaf curl Kokhran Virus-Burewala Strain (CLCuKoV-Bu) in CLCuD infected samples, demand that the interactions taking between the two viruses be properly evaluated. This study is designed to assess virus-virus interactions at the molecular level and determine the type of co-infection taking place. METHODS: Based on the amino acid sequences of the gene products of both CLCuKoV-Bu and ToLCNDV, protein structures were generated using different software, i.e., MODELLER, I-TASSER, QUARKS, LOMETS and RAPTORX. A consensus model for each protein was selected after model quality assessment using ERRAT, QMEANDisCo, PROCHECK Z-Score and Ramachandran plot analysis. The active and passive residues in the protein structures were identified using the CPORT server. Protein-Protein Docking was done using the HADDOCK webserver, and 169 Protein-Protein Interaction (PPIs) were performed between the proteins of the two viruses. The docked complexes were submitted to the PRODIGY server to identify the interacting residues between the complexes. The strongest interactions were determined based on the HADDOCK Score, Desolvation energy, Van der Waals Energy, Restraint Violation Energy, Electrostatic Energy, Buried Surface Area and Restraint Violation Energy, Binding Affinity and Dissociation constant (Kd). A total of 50 ns Molecular Dynamic simulations were performed on complexes that exhibited the strongest affinity in order to validate the stability of the complexes, and to remove any steric hindrances that may exist within the structures. RESULTS: Our results indicate significant interactions taking place between the proteins of the two viruses. Out of all the interactions, the strongest were observed between the Replication Initiation protein (Rep) of CLCuKoV-Bu with the Movement protein (MP), Nuclear Shuttle Protein (NSP) of ToLCNDV (DNA-B), while the weakest were seen between the Replication Enhancer protein (REn) of CLCuKoV-Bu with the REn protein of ToLCNDV. The residues identified to be taking a part in interaction belonged to domains having a pivotal role in the viral life cycle and pathogenicity. It maybe deduced that the two viruses exhibit antagonistic behavior towards each other, and the type of infection may be categorised as a type of Super Infection Exclusion (SIE) or homologous interference. However, further experimentation, in the form of transient expression analysis, is needed to confirm the nature of these interactions and increase our understanding of the direct interactions taking place between two viruses.

Enhancing the design and utilization of asthma action plans through community-based participatory research in an urban African American community.

BACKGROUND: Across the U.S., large inequities in asthma prevalence and outcomes persist, disproportionately affecting low-income, minoritized children. West Louisville is particularly impacted by these inequities due to a complex interplay of socioeconomic, historical, and industrial processes. Additionally, low health literacy and mistrust in healthcare exacerbate poor asthma self-management. OBJECTIVE: To engage community members and health professionals to address childhood asthma management in a marginalized community experiencing significant health inequities. PATIENT INVOLVEMENT: Although prior asthma knowledge was not required, the majority of our community advisory council (CAC) members either had asthma or cared for children/grandchildren with asthma. Through facilitated decision-making using the Boot Camp Translation approach, the CAC chose to focus on improving asthma self-management in their community through enhancing the design and utilization of asthma action plans (AAPs). METHODS: Upon adding inhaler images to a user-friendly AAP, the CAC developed and implemented a provider incentive program and a health communication campaign to promote the Tool's utilization. Evaluation of the intervention consisted of a short questionnaire measuring relevant patient demographics and campaign knowledge, and phone interviews with providers to gather feedback on the incentive and Tool design. RESULTS: Over the short two-month intervention, a total of 8 practices with 28 providers used 153 Tools to provide asthma self-management counseling. The majority of providers preferred the enhanced Tool to other AAPs they had used. Inhaler images facilitating improved communication regarding asthma medications. DISCUSSION: Using a participatory approach, a community preferred intervention targeting barriers to effective asthma control increased provider utilization and community awareness of AAPs and bridged a communication gap between patients and providers. PRACTICAL VALUE: Leveraging community members' (including patients/caregivers) and health professionals' expertise led to the development of an enhanced patient-education tool and an effective provider incentive program with the potential to improve childhood asthma management in marginalized populations.