Search

Emily Ames, Maggie Sanders,* Marley Jacobs,* Thomas A Vida Department of Medical Education, Kirk Kerkorian School of Medicine at UNLV, Las Vegas, NV, USA*These authors contributed equally to this workCorrespondence: Thomas A Vida, Department of Medical Education, Kirk Kerkorian School of Medicine at UNLV, 625 Shadow Ln, Las Vegas, NV, 89106, USA, Email thomas.vida@unlv.eduAbstract: Inflammatory skin diseases impose a significant burden on patients and healthcare systems worldwide. Among these, hidradenitis suppurativa (HS) is particularly notable for its chronic and recurrent nature. Recurrent nodules, abscesses, and scarring in apocrine gland-rich areas characterize the disease, including the groin, axillae, and perianal regions. Despite its considerable physical and psychological impact, the precise mechanisms driving HS remain elusive. Recent advancements in understanding the inflammatory processes involved in HS have highlighted the TNF-alpha, IL-1β, and IL-17/IL-23 pathways, which play crucial roles in initiating and perpetuating the disease. Moreover, specific microRNAs (miRNAs), such as miR-24-1-5p, miR146a-5p, mirR-26a-5p, miR-206, miR-338-3p, and miR-338-5p, are involved in these inflammatory processes. Dysregulation of these miRNAs contributes to aberrant cytokine expression and persistent inflammation, foreseeably exacerbating HS disease progression. This narrative review hypothesizes that miRNA dysregulation triggers aberrant expression in specific inflammatory pathways, contributing to HS’s clinical manifestations and progression. We explore the implicated miRNAs’ potential as biomarkers for earlier disease detection and as novel therapeutic targets. Identifying miRNA dysregulation offers new opportunities for earlier and more accurate diagnosis, potentially allowing clinicians to intervene before severe disease manifestations occur. Furthermore, therapeutic strategies to modulate miRNA expression could target the inflammatory pathways driving HS, leading to more personalized and effective treatments. This review also discusses future research directions to enhance the clinical management of HS. A better understanding of miRNA involvement in HS offers new avenues for research and management, ultimately improving patient outcomes and quality of life.Keywords: chronic inflammation, sebaceous glands, inflammatory pathways, immunosuppressant drugs, miRNA dysregulation

Objective: Exposure to 60% high fat diet (HFD) leads to a robust consummatory preference over well-balanced chow standard diet (SD) when mice are presented with a choice. This passive HFD-induced SD devaluation following HFD challenge and withdrawal is highlighted by the significant reduction in SD food intake even in states of caloric deprivation. The elements of HFD that lead to this SD depreciation remains unclear. Possibly important factors include the amount and type of fat contained in a diet as well as past eating experiences dependent on sensory properties including taste and post ingestive feedback. We aimed to explore the role of these components to HFD-induced SD devaluation. Methods: Wildtype mice were longitudinally presented discrete HFDs in conjunction with SD and feeding and metabolic parameters were analyzed. A separate cohort of animals were assessed for acute HFD preference in 3 conditions: 1) ad libitum fed (sated), 2) overnight fasted (physiologically hungry), and 3) ad libitum fed (artificially hungry), elicited through chemogenetic Agouti-related peptide (AgRP) neuron activation. Population dynamics of AgRP neurons were recorded to distinct inaccessible and accessible diets both before and after consummatory experience. Transient receptor potential channel type M5 (TRPM5) knockout mice were used to investigate the role of fat taste perception and preference to HFD-induced SD devaluation. The clinically approved lipase inhibitor orlistat was used to test the contribution of fat absorption to HFD-induced SD devaluation. Results: HFD-induced SD devaluation is dependent on fat content, composition, and preference. This effect scaled both in strength and latency with higher percentages of animal fat. 60% HFD was preferred and almost exclusively consumed in preference to other diets across hours and days, but this was not as evident upon initial introduction over seconds and minutes, suggesting ingestive experience is critical. Optical fiber photometry recordings of AgRP activity supported this notion as neuronal suppression by the different diets was contingent on prior intake. While taste transduced via TRPM5 influenced HFD-evoked weight gain, it failed to impact either HFD preference or HFD-induced SD devaluation. Perturbation of post ingestive feedback through orlistat-mediated diminishment of fat absorption prevented HFD-evoked weight gain and abolished HFD-induced SD devaluation. Conclusions: Post ingestive feedback via fat digestion is vital for expression of HFD-induced SD devaluation.

IntroductionOur study set out to identify the benefits for veterinary workers of structured daily well-being practices on compassion satisfaction, burnout, and secondary traumatic stress. Suggested origins of high rates of psychological stress and burnout are significant occupational concerns for veterinary workers. Many professional helpers experience an extreme state of tension and preoccupation from exposure to the suffering of those being helped. Veterinary workers are further impacted by negative associations and moral distress experienced due to limitations in the provision of quality medical care for veterinary patients. These negative experiences exist despite veterinary professionals’ work being worthwhile and highly valued.MethodsA randomized controlled study was performed over 6 months. Volunteer participants were members of a team of veterinary workers at a 24-h emergency and specialty hospital. Study participants were asked to incorporate daily well-being practice(s) into existing routines whereas control participants were not. Measures of well-being and the negative impacts of serving as veterinary helpers were assessed by having participants complete the Professional Quality of Life (ProQOL) self-assessment at baseline and at 1, 3 and 6 months. Composite scores for compassion satisfaction, burnout and secondary traumatic stress were calculated.ResultsBaseline ProQOL scores were similar between study participants and controls. Baseline compassion satisfaction (CS), burnout scores (BS), and secondary traumatic stress (STS) scores for those instituting well-being practices were 37.6 (+/− 3.6), 26 (+/− 5.3), and 26.6 (+/− 5.2). Study participants had higher compassion satisfaction scores at 6 months with mean CS scores (n = 15) of 40.1 (+/− 6.8) and adjusted scores that were on average 3.0 (95% CI 0–6.1) higher than the control group (p = 0.048). Significant differences in BS or STS scores were not seen.DiscussionImprovements were seen in CS but not BO/STS for those caregivers who implemented well-being practices into their daily routines. Factors that likely contributed to successful implementation of well-being practices include educational resources, supportive leadership, accessibility, and consistent acknowledgement and positive rewards. Proposed supportive elements and resources for maintenance of well-being practices within a team of veterinary workers include provision of a psychologically safe community and team support (including formal or informal “buddy systems”).

The vulnerability of research participants is a critical topic for the 2024 revision of the Declaration of Helsinki, with the proposal to include “social value. ” However, this proposal has been withdrawn and the relationship between the two concepts has not been clarified. This paper attempts to clarify: (1) the recent reform for the ethical inclusion of vulnerable study participants to promote diversity; (2) the social value, prerequisite for everyone, especially for those who are vulnerable and the most in need; (3) the requirements for promoting the inclusion of vulnerable participants, in particular the review of the norms for placebo-controlled trials and post-trial access; (4) finally, the direction of research ethics reform to achieve social value and equitable global health.

Abstract Attaining high crop yields and increasing carbon storage in agricultural soils, while avoiding negative environmental impacts on water quality, soil erosion, and biodiversity, requires accurate and precise management of crop inputs and management practices. The long-term analysis of spatial and temporal patterns of crop yields provides insights on how yields vary in a field, with parts of field constantly producing either high yields or low yields and other parts that fluctuate from one year to the next. The concept of yield stability has shown to be informative on how plants translate the effects of environmental conditions (e.g., soil, climate, topography) across the field and over the years in the final yield, and as a valuable layer in developing prescription maps of variable fertilizer rate inputs. Using known relationships between soil health and crop yields, we hypothesize that areas with measured constantly low yield will return low carbon to the soil affecting its heath. On this premises, yield stability zones (YSZ) provide an effective and practical integrative measure of the small-scale variability of soil health on a field relative basis. We tested this hypothesis by measuring various metrics of soil health from commercial farmers’ fields in the north central Midwest of the USA in samples replicated across YSZ, using a soil test suite commonly used by producers and stakeholders active in agricultural carbon credits markets. We found that the use of YSZ allowed us to successfully partition field-relative soil organic carbon (SOC) and soil health metrics into statistically distinct regions. Low and stable (LS) yield zones were statistically lower in normalized SOC when compared to high and stable (HS) and unstable (US) yield zones. The drivers of the yield differences within a field are a series of factors ranging from climate, topography and soil. LS zones occur in areas of compacted soil layers or shallow soils (edge of the field) on steeper slopes. The US zones occurring with high water flow accumulation, were more dependent on topography and rainfall. The differences in the components of the overall soil health score (SHS) between these YSZ increased with sample depth suggesting a deeper topsoil in the US and HS zones, driven by the accumulation of water, nutrients, and carbon downslope. Comparison of the field management provided initial evidence that zero tillage reduces the magnitude of the variance in SOC and soil health metrics between the YSZ.

Abstract Agricultural soils can act as a sink for large quantities of soil organic carbon (SOC) but can also be sources of carbon to the atmosphere. The international standard for assessing SOC stock and measuring stock change stipulates fixed depth sampling to at least 30 cm. The tendency of bulk density (BD) to decrease with decreasing disturbance and increasing SOC concentration and the assumption of constant SOC and BD within this depth profile promotes error in the estimates of SOC stock. A hypothetical but realistic change in BD from 1.5 to 1.1 g cm−3 from successive fixed depth sampling to 30 cm underestimates SOC stock change by 17%. Significant effort has been made to evaluate and reduce this fixed depth error by using the equivalent soil mass (ESM) approach, but with limited adoption. We evaluate the error in SOC stock assessment and change generated from fixed depth measurements over time relative to the ESM approach and propose a correction that can be readily adopted under current sampling and analytical methods. Our approach provides a more accurate estimate of SOC stock accumulation or loss that will help incentivize management practice changes that reduce the environmental impacts of agriculture and further legitimize the accounting practices used by the emerging carbon market and organizations that have pledged to reduce their supply chain greenhouse gas (GHG) footprints.

University degrees are usually delivered in defined sessions--by term, semester, or in week-based blocks--whereby students are required to complete their studies by the due date. Term or session-based schedules that require students to complete the study within set timeframes are, however, potentially restrictive. Temporal challenges associated with work and life can impede progress and add to the specific problem of student attrition in online learning. As universities seek to deliver innovative options for their students, increased attention is being paid to alternate models of delivery. This paper reports on the development of a hyperflexible online Master of Business Administration (MBA) course by a regional university in Australia, which has grown to more than 1,000 students since its launch in 2017. Delivered entirely online, the degree was specifically designed to address an inequity; MBA programs are traditionally expensive, and in Australia, the requirement for students to travel to attend residential schools and examinations adds significant cost to already expensive tuition fees. This paper analyzed enrollment data, course analytics over a two-year period, and student surveys conducted at the end of the second year of delivery (n = 98) to evaluate the development and implementation of the course as a hyperflexible course whereby students have almost complete control over their study at the postgraduate tertiary level. Results highlight the potential for the model to enable student success through flexibility.

Background: Adolescents are a unique population with significant unmet health needs. They are often excluded from research that may benefit them as they are perceived as vulnerable and needing protection from research participation. For Research Ethics Committees, conflicting positions in statutes, regulations and ethical guidelines about who provides informed consent for adolescent involvement in health research can be a significant barrier to approving adolescent research. For researchers, the requirement for parental/guardian proxy consent or prolonged approval processes may potentially result in the exclusion of those adolescents most vulnerable and at risk, particularly if issues such as gender-based violence, gender identity, sexuality and sexual practices are in question. Objectives: To describe the challenges to adolescent research and suggest strategies to address these. Method: We consider the legal and ethical framework in South Africa regarding the consenting age for adolescents in research, outline the challenges and, using examples of best practices, suggest strategies to address the current conundrum. Results: We suggest three principles to guide Research Ethics Committees on their approach to reviewing health research involving adolescents. Strategies to develop ethically acceptable approaches to adolescent research and consent processes are described, which include community involvement. We elaborate on examples of nuanced approaches to adolescent research. Conclusion: The inclusion of adolescents in research is critical in informing appropriate and effective health services for this vulnerable population, whilst providing an opportunity to link them into care and services where relevant.

Abstract Background The National Health Insurance (NHI) is a proposed health policy in South Africa that aims to change the structure of the current health system. Public involvement in policy making is important and it is a constitutional requirement in the legislation development process in South Africa. Patients are key stakeholders and should be engaged in NHI policy process. Before patients can be engaged, they need to be provided with sufficient information about the NHI. Therefore, the aim of this exploratory study was to examine the levels of patient awareness of the NHI, which is a requisite for meaningful engagement. Methods This was a cross sectional study of 244 patients from the follow-up clinics at the Department of Internal Medicine, Charlotte Maxeke Johannesburg Academic Hospital in the Gauteng Province, South Africa. The patients were interviewed using a structured interview process and a questionnaire. Descriptive statistics and logistic regression analyses were conducted. Results The majority (79.51%) of the participants were not aware of the proposed National Health Insurance (NHI) in South Africa even though the NHI policy process commenced in 2011. Of the participants who were aware of the NHI, 86% responded that they had not been provided with an opportunity to be involved in the policy making process of the NHI. The odds of awareness were higher for male (OR: 2.08, 95% CI: 1.11–3.9, p value: 0.02) than female participants; White (OR: 2.36, 95% CI: 1.06–5.26, p value: 0.04) and Indian (OR: 2.76, 95% CI: 0.10–7.60, p value: 0.05) participants when compared to Black participants; and retired (OR: 3.13, 95% CI: 1.35–7.25, p value: 0.008) than unemployed participants. Conclusion The levels of awareness of the NHI were low among the participants from Department of Internal Medicine, CMJAH. Without the awareness and information about the NHI, patients are not equipped to be involved in the NHI policy process in a meaningful way. Public patients are the intended beneficiaries of universal health coverage, therefore they should be prioritized in the NHI community engagement process to ensure that the NHI is community and patient centred.

T-cell-dependent bispecific antibodies (TDBs) are promising cancer immunotherapies that recruit patients’ T cells to kill cancer cells. There are many TDBs in clinical trials, demonstrating their widely recognized therapeutic potential. However, their complex, multi-step mechanism of action (MoA), which includes bispecific antigen binding, T-cell activation, and target-cell killing, presents unique challenges for biological characterization and potency assay selection. Here, we describe the development of a single reporter-gene potency assay for a TDB (TDB1) that is MoA reflective and sensitive to binding of both antigens. Our reporter-gene assay measures T-cell activation using Jurkat cells engineered to express luciferase under the control of an NFkB response element. The potencies of select samples were measured both by this assay and by a flow-cytometry-based cell-killing assay using human lymphocytes as effector cells. Correlating the two sets of potency results clearly establishes our reporter-gene assay as MoA reflective. Furthermore, correlating potencies for the same panel of samples against binding data measured by binding assays for each individual arm demonstrates that the reporter-gene potency assay reflects dual-antigen binding and can detect changes in affinity for either arm. This work demonstrates that one reporter-gene assay can be used to measure the potency of TDB1 while capturing key aspects of its MoA, thus serving as a useful case study of selection and justification of reporter-gene potency assays for TDBs. Furthermore, our strategy of correlating reporter-gene potency, target-cell killing, and antigen binding for each individual arm serves as a useful example of a thorough, holistic approach to biological characterization for TDBs that can be applied to other bispecific molecules.

BackgroundCardiac rehabilitation (CR) is clinically proven to reduce morbidity and mortality; however, many eligible patients do not enroll in treatment. Furthermore, many enrolled patients do not complete their full course of treatment. This is greatly influenced by socioeconomic factors but is also because of patients’ lack of understanding of the importance of their care and a lack of motivation to maintain attendance. ObjectiveThis study aims to explore the potential benefits of virtual reality (VR) walking trails within CR treatment, specifically with regard to patient knowledge retention, satisfaction with treatment, and the overall attendance of treatment sessions. MethodsNew CR patients were enrolled and randomized on a rolling basis to either the control group or intervention group. Intervention patients completed their time on the treadmill with VR walking trails, which included audio-recorded education, whereas control patients completed the standard of care therapy. Both groups were assisted by nursing staff for all treatment sessions. Primary outcomes were determined by assessing 6-minute walk test improvement. In addition, secondary outcomes of patients’ cardiac knowledge and satisfaction were assessed via a computer-based questionnaire; patient adherence to the recommended number of sessions was also monitored. Cardiac knowledge assessment included a prerehabilitation education quiz, and the same quiz was repeated at patients’ final visit and again at the 2-month follow-up. The satisfaction questionnaire was completed at the final visit. ResultsBetween January 2018 and May 2019, 72 patients were enrolled—41 in the intervention group and 31 in the control group. On the basis of the results of the prerehabilitation and postrehabilitation 6-minute walk test, no significant differences were observed between the intervention and control groups (P=.64). No statistical differences were observed between groups in terms of education (P=.86) or satisfaction (P=.32) at any time point. The control group had statistically more favorable rates of attendance, as determined by the risk group comparison (P=.02) and the comparison of the rates for completing the minimum number of sessions (P=.046), but no correlation was observed between the study group and reasons for ending treatment. ConclusionsAlthough no improvements were seen in the VR intervention group over the control group, it is worth noting that limitations in the study design may have influenced these outcomes, not the medium itself. Furthermore, the qualitative information suggests that patients may have indeed enjoyed their experience with VR, even though quantitative satisfaction data did not capture this. Further considerations for how and when VR should be applied to CR are suggested in this paper. Trial RegistrationClinicalTrials.gov NCT03945201; https://clinicaltrials.gov/ct2/show/NCT03945201