Perceptions of social media harms and potential management strategies: vaping case study.

BACKGROUND: The social media landscape is now ubiquitous in people's everyday lives. It is a space where culture, politics, economics and sociological and public health discourses occur. There is mounting evidence that e-cigarette products are being promoted and advertised on social media, a media platform particularly popular with young people. Our research aimed to understand industry professionals' perceptions of social media harms and potential management strategies using vaping as a case study. METHODS: A critical realist perspective guided reflexive thematic analysis of the qualitative in depth, semi structured interviews. Data collection occurred in January and February 2023 with 13 participants working in the areas of public health, digital media, law, governance, tobacco control and advocacy. RESULTS: Two superordinate themes emerged from the data: (1) Fathoming a complex system (social media) that contained the subordinate themes of Traversing Boundaries (crossing borders, crossing sectors) and Ungovernable (global and local landscapes, vested interests, self-regulation and opacity). (2) Addressing complexity (social media)- that contained the subordinate themes of Strengthening Institutions (global to local, policy and legislation, individuals and organisations); Defanging Industry (responsibility and transparency, moderation and algorithms, complaints); and Engaging Citizens (raising awareness, framing messaging). CONCLUSIONS: There was consensus among participants that e-cigarette related social media content can be harmful and government action is urgently needed. There was an identified need for the development of government led national-level regulatory frameworks, with government led appropriate legislation; identification of an organisation or organisations with suitable levels of regulatory power and resources to monitor, enforce and penalise noncompliant social media companies; accompanied by increased community awareness raising of harmful social media content and improved digital literacy.

Not so smart? "Smart" drugs increase the level but decrease the quality of cognitive effort.

The efficacy of pharmaceutical cognitive enhancers in everyday complex tasks remains to be established. Using the knapsack optimization problem as a stylized representation of difficulty in tasks encountered in daily life, we discover that methylphenidate, dextroamphetamine, and modafinil cause knapsack value attained in the task to diminish significantly compared to placebo, even if the chance of finding the optimal solution (~50%) is not reduced significantly. Effort (decision time and number of steps taken to find a solution) increases significantly, but productivity (quality of effort) decreases significantly. At the same time, productivity differences across participants decrease, even reverse, to the extent that above-average performers end up below average and vice versa. The latter can be attributed to increased randomness of solution strategies. Our findings suggest that "smart drugs" increase motivation, but a reduction in quality of effort, crucial to solve complex problems, annuls this effect.

Male sex hormones, aging, and inflammation.

Adequate levels of androgens (eugonadism), and specifically testosterone, are vital compounds for male quality of life, longevity, and positive health outcomes. Testosterone exerts its effects by binding to the androgen receptor, which is expressed in numerous tissues throughout the body. Significant research has been conducted on the impact of this steroid hormone on skeletal, muscle and adipose tissues and on the cardiovascular, immune, and nervous systems. Testosterone levels have also been studied in relation to the impact of diseases, aging, nutrition and the environment on its circulating levels. Conversely, the impact of testosterone on health has also been evaluated with respect to its cardiac and vascular protective effects, body composition, autoimmunity and all-cause mortality. The male aging process results in decreasing testosterone levels over time. The exact mechanisms and impact of these changes in testosterone levels with age on health- and life-span are still not completely clear. Further research is needed to determine the optimal testosterone and androgen levels to protect from chronic age-related conditions such as frailty and osteoporosis.

Virtual Vanderbilt Summer Science Academy highlighted the opportunity to impact early STEMM students career knowledge through narrative.

Due to COVID-19 precautions, the Vanderbilt University summer biomedical undergraduate research program, the Vanderbilt Summer Science Academy (VSSA), rapidly transitioned from offering an in-person training program to a virtual seminar format. Our program typically supports undergraduate development through research and/or clinical experience, meeting with individuals pursuing postgraduate training, and providing career development advice. Evidence supports the idea that summer programs transform undergraduates by clarifying their interest in research and encouraging those who haven't previously considered graduate studies. We were interested in exploring whether a virtual, synchronous program would increase participants' scientific identity and clarify postgraduate career planning. Rather than create a virtual research exposure, our 5-week "Virtual VSSA" program aimed to simulate the casual connections that would naturally be made with post-undergraduate trainees during a traditional summer program. In seminars, presenters discussed 1) their academic journey, explaining their motivations, goals, and reasons for pursuing a career in science as well as 2) a professional story that illustrated their training. Seminars included Vanderbilt University and Medical School faculty, M.D., MD/Ph.D., as well as Ph.D. students from diverse scientific and personal backgrounds. In addition, weekly informational sessions provided an overview of the nature of each degree program along with admissions advice. Through pre-and post-program surveys, we found that students who registered for this experience already strongly identified with the STEMM community (Science, Technology, Engineering, Mathematics, and Medicine). However, participation in the Virtual VSSA increased their sense of belonging. We also uncovered a gap in participants' understanding of postgraduate pathways prior to participation and found that our program significantly increased their self-reported understanding of postgraduate programs. It also increased their understanding of why someone would pursue a Ph.D. or Ph.D./MD versus M.D. These changes did not uniformly impact participants' planned career paths. Overall, by providing personal, tangible stories of M.D., MD/Ph.D., and Ph.D. training, the Virtual VSSA program offered seminars that positively impacted students' sense of belonging with and connection to the STEMM disciplines.

Supporting Health Equity Through Data-Driven Decision-Making: A Local Health Department Response to COVID-19.

COVID-19 highlights preexisting inequities that affect health outcomes and access to care for Black and Brown Americans. The Marion County Public Health Department in Indiana sought to address inequities in COVID-19 testing by using surveillance data to place community testing sites in areas with the highest incidence of disease. Testing site demographic data indicated that targeted testing reached populations with the highest disease burden, suggesting that local health departments can effectively use surveillance data as a tool to address inequities. (Am J Public Health. 2021;111(S3):S197-S200. https://doi.org/10.2105/AJPH.2021.306421).

Drivers and implications of distance decay differ for ectomycorrhizal and foliar endophytic fungi across an anciently fragmented landscape.

Fungal communities associated with plants often decrease in similarity as the distance between sampling sites increases (i.e., they demonstrate distance decay). In the southwestern USA, forests occur in highlands separated from one another by warmer, drier biomes with plant and fungal communities that differ from those at higher elevations. These disjunct forests are broadly similar in climate to one another, offering an opportunity to examine drivers of distance decay in plant-associated fungi across multiple ecologically similar yet geographically disparate landscapes. We examined ectomycorrhizal and foliar endophytic fungi associated with a dominant forest tree (Pinus ponderosa) in forests across ca. 550 km of geographic distance from northwestern to southeastern Arizona (USA). Both guilds of fungi showed distance decay, but drivers differed for each: ectomycorrhizal fungi are constrained primarily by dispersal limitation, whereas foliar endophytes are constrained by specific environmental conditions. Most ectomycorrhizal fungi were found in only a single forested area, as were many endophytic fungi. Such regional-scale perspectives are needed for baseline estimates of fungal diversity associated with forest trees at a landscape scale, with attention to the sensitivity of different guilds of fungal symbionts to decreasing areas of suitable habitat, increasing disturbance, and related impacts of climate change.

Remote monitoring of implantable defibrillators is associated with fewer inappropriate shocks and reduced time to medical assessment in a remote and rural area.

BACKGROUND: Implantable cardioverter defibrillators (ICDs) and cardiac resynchronisation therapy with defibrillators (CRT-D) reduce mortality in certain cardiac patient populations. However, inappropriate shocks pose a problem, having both adverse physical and psychological effects on the patient. The advances in device technology now allow remote monitoring (RM) of devices to replace clinic follow up appointments. This allows real time data to be analysed and actioned and this may improve patient care. AIM: To determine if RM in patients with an ICD is associated with fewer inappropriate shocks and reduced time to medical assessment. METHODS: This was a single centre, retrospective observational study, involving 156 patients implanted with an ICD or CRT-D, followed up for 2 years post implant. Both appropriate and inappropriate shocks were recorded along with cause for inappropriate shocks and time to medical assessment. RESULTS: RM was associated with fewer inappropriate shocks (13.6% clinic vs 3.9% RM; P = 0.030) and a reduced time to medical assessment (15.1 ± 6.8 vs 1.0 ± 0.0 d; P < 0.001). CONCLUSION: RM in patients with an ICD is associated with improved patient outcomes.

Insulin/IGF Signaling and Vitellogenin Provisioning Mediate Intergenerational Adaptation to Nutrient Stress.

The roundworm C. elegans reversibly arrests larval development during starvation [1], but extended early-life starvation reduces reproductive success [2, 3]. Maternal dietary restriction (DR) buffers progeny from starvation as young larvae, preserving reproductive success [4]. However, the developmental basis of reduced fertility following early-life starvation is unknown, and it is unclear how maternal diet modifies developmental physiology in progeny. We show here that extended starvation in first-stage (L1) larvae followed by unrestricted feeding results in a variety of developmental abnormalities in the reproductive system, including proliferative germ-cell tumors and uterine masses that express neuronal and epidermal cell fate markers. We found that maternal DR and reduced maternal insulin/insulin-like growth factor (IGF) signaling (IIS) increase oocyte provisioning of vitellogenin lipoprotein, reducing penetrance of starvation-induced abnormalities in progeny, including tumors. Furthermore, we show that maternal DR and reduced maternal IIS reduce IIS in progeny. daf-16/FoxO and skn-1/Nrf, transcriptional effectors of IIS, are required in progeny for maternal DR and increased vitellogenin provisioning to suppress starvation-induced abnormalities. daf-16/FoxO activity in somatic tissues is sufficient to suppress starvation-induced abnormalities, suggesting cell-nonautonomous regulation of reproductive system development. This work reveals that early-life starvation compromises reproductive development and that vitellogenin-mediated intergenerational insulin/IGF-to-insulin/IGF signaling mediates adaptation to nutrient availability.

A novel proof of concept for capturing the diversity of endophytic fungi preserved in herbarium specimens.

Herbarium specimens represent important records of morphological and genetic diversity of plants that inform questions relevant to global change, including species distributions, phenology and functional traits. It is increasingly appreciated that plant microbiomes can influence these aspects of plant biology, but little is known regarding the historic distribution of microbes associated with plants collected in the pre-molecular age. If microbiomes can be observed reliably in herbarium specimens, researchers will gain a new lens with which to examine microbial ecology, evolution, species interactions. Here, we describe a method for accessing historical plant microbiomes from preserved herbarium specimens, providing a proof of concept using two plant taxa from the imperiled boreal biome (Andromeda polifolia and Ledum palustre subsp. groenlandicum, Ericaceae). We focus on fungal endophytes, which occur within symptomless plant tissues such as leaves. Through a three-part approach (i.e. culturing, cloning and next-generation amplicon sequencing via the Illumina MiSeq platform, with extensive controls), we examined endophyte communities in dried, pressed leaves that had been processed as regular herbarium specimens and stored at room temperature in a herbarium for four years. We retrieved only one endophyte in culture, but cloning and especially the MiSeq analysis revealed a rich community of foliar endophytes. The phylogenetic distribution and diversity of endophyte assemblages, especially among the Ascomycota, resemble endophyte communities from fresh plants collected in the boreal biome. We could distinguish communities of endophytes in each plant species and differentiate likely endophytes from fungi that could be surface contaminants. Taxa found by cloning were observed in the larger MiSeq dataset, but species richness was greater when subsets of the same tissues were evaluated with the MiSeq approach. Our findings provide a proof of concept for capturing endophyte DNA from herbarium specimens, supporting the importance of herbarium records as roadmaps for understanding the dynamics of plant-associated microbial biodiversity in the Anthropocene.This article is part of the theme issue 'Biological collections for understanding biodiversity in the Anthropocene'.

Using collections data to infer biogeographic, environmental, and host structure in communities of endophytic fungi.

Biodiversity collections contain a wealth of information encapsulated both in specimens and in their metadata, providing the foundation for diverse studies in fields such as ecology. Yet biodiversity repositories can present a challenge for ecological inferences because collections rarely are structured with ecological questions in mind: collections may be opportunistic in space or time, may focus on particular taxonomic groups, may reflect different collection strategies in different places or times, or may not be exhaustive in terms of retaining every specimen or having similar metadata for each record. In addition to its primary holdings, the Robert L. Gilbertson Mycological Herbarium at the University of Arizona holds a collection of living specimens of fungi isolated from the interior of healthy plants and lichens (i.e., endophytic and endolichenic fungi). Over the past decade, more than 7000 isolates from the southwestern United States were accessioned, including strains from diverse hosts in more than 50 localities across the biotically rich state of Arizona. This collection is distinctive in that metadata and barcode sequences are available for each specimen, many localities have been sampled with consistent methods, and all isolates obtained in surveys have been retained. Here, we use this herbarium collection to examine endophyte community structure in an ecological and evolutionary context. We then artificially restructure the collection to resemble collections more typical of biodiversity repositories, providing a case study for ecological insights that can be gleaned from collections that were not structured explicitly to address ecological questions. Overall, our analyses highlight the relevance of biogeography, climate, hosts, and geographic separation in endophyte community composition. This study showcases the importance of extensive metadata in collections and highlights the utility of biodiversity collections that can yield emergent insights from many surveys to answer ecological questions in mycology, ultimately providing information for understanding and conserving fungal biodiversity.

Distributions of ectomycorrhizal and foliar endophytic fungal communities associated with Pinus ponderosa along a spatially constrained elevation gradient.

PREMISE OF THE STUDY: Understanding distributions of plant-symbiotic fungi is important for projecting responses to environmental change. Many coniferous trees host ectomycorrhizal fungi (EM) in association with roots and foliar endophytic fungi (FE) in leaves. We examined how EM and FE associated with Pinus ponderosa each vary in abundance, diversity, and community structure over a spatially constrained elevation gradient that traverses four plant communities, 4°C in mean annual temperature, and 15 cm in mean annual precipitation. METHODS: We sampled 63 individuals of Pinus ponderosa in 10 sites along a 635 m elevation gradient that encompassed a geographic distance of 9.8 km. We used standard methods to characterize each fungal group (amplified and sequenced EM from root tips; isolated and sequenced FE from leaves). KEY RESULTS: Abundance and diversity of EM were similar across sites, but community composition and distributions of the most common EM differed with elevation (i.e., with climate, soil chemistry, and plant communities). Abundance and composition of FE did not differ with elevation, but diversity peaked in mid-to-high elevations. CONCLUSIONS: Our results suggest relatively tight linkages between EM and climate, soil chemistry, and plant communities. That FE appear less linked with these factors may speak to limitations of a culture-based approach, but more likely reflects the small spatial scale encompassed by our study. Future work should consider comparable methods for characterizing these functional groups, and additional transects to understand relationships of EM and FE to environmental factors that are likely to shift as a function of climate change.

Preconception Care for the Patient and Family.

Preconception counseling is essential for women of childbearing age and family members who have decided to conceive because the level of well health of the mother and unborn child are affected by decisions and actions of the mother before and during pregnancy. Proactively planning pregnancy includes scheduling a preconception counseling consultation with a provider. Understanding physical, psychological, and emotional needs promotes healthy pregnancy outcomes for mother and baby. This article offers a reflective and holistic perspective of how health care providers frame, prioritize, and engage with the patient and family during the preconception consultation.

Longitudinal Changes in White Matter Fractional Anisotropy in Adult-Onset Niemann-Pick Disease Type C Patients Treated with Miglustat.

Niemann-Pick disease type C (NPC) is a rare neurometabolic disorder resulting in impaired intracellular lipid trafficking. The only disease-modifying treatment currently available is miglustat, an iminosugar that inhibits the accumulation of lipid metabolites in neurons and other cells. This longitudinal diffusion tensor imaging (DTI) study examined how the rate of white matter change differed between treated and non-treated adult-onset NPC patient groups. Nine adult-onset NPC patients (seven undergoing treatment with miglustat, two not treated) underwent DTI neuroimaging. Rates of change in white matter structure as indexed by Tract-Based Spatial Statistics (TBSS) of fractional anisotropy were compared between treated and untreated patients. Treated patients were found to have a significantly slower rate of white matter change in the corticospinal tracts, the thalamic radiation and the inferior longitudinal fasciculus. This is further evidence that miglustat treatment may have a protective effect on white matter structure in the adult-onset form of the disease.

The Rhodococcus equi virulence protein VapA disrupts endolysosome function and stimulates lysosome biogenesis.

Rhodococcus equi (R. equi) is an important pulmonary pathogen in foals that often leads to the death of the horse. The bacterium harbors a virulence plasmid that encodes numerous virulence-associated proteins (Vaps) including VapA that is essential for intracellular survival inside macrophages. However, little is known about the precise function of VapA. Here, we demonstrate that VapA causes perturbation to late endocytic organelles with swollen endolysosome organelles having reduced Cathepsin B activity and an accumulation of LBPA, LC3 and Rab7. The data are indicative of a loss of endolysosomal function, which leads cells to upregulate lysosome biogenesis to compensate for the loss of functional endolysosomes. Although there is a high degree of homology of the core region of VapA to other Vap proteins, only the highly conserved core region of VapA, and not VapD of VapG, gives the observed effects on endolysosomes. This is the first demonstration of how VapA works and implies that VapA aids R. equi survival by reducing the impact of lysosomes on phagocytosed bacteria.

Reproduction regulates Drosophila nutrient intake through independent effects of egg production and sex peptide: Implications for aging.

BACKGROUND: The ratio of protein to carbohydrate (P:C) consumed influences reproduction and lifespan, outcomes that are often maximized by different P:C intake. OBJECTIVE: Determine if reproduction in female Drosophila drives elevated P:C intake. Distinguish whether such a preference is driven by egg production or from male-derived sex peptides in seminal fluid. METHODS: Intake of protein and carbohydrate was measured in a diet-choice assay. Macronutrient intake was calculated for mated and unmated fertile females, mated and unmated sterile females, and both types of female when mated to wildtype males and to males lacking sex peptide. RESULTS: Mated females have high P:C intake relative to unmated females and mated, sterile females. Fertile females mated to wildtype males and to males lacking sex peptide have high P:C intake, but sterile females have similar, low P:C intake when unmated and when mated to males lacking sex peptide. CONCLUSIONS: The metabolic demands of egg production and sex peptides are individually sufficient to drive elevated P:C intake in adult female Drosophila. Reproductive state can thus modulate how animals consume macronutrients, which in turn can impact their health and aging.

Longitudinal assessment of reflexive and volitional saccades in Niemann-Pick Type C disease during treatment with miglustat.

BACKGROUND: Niemann-Pick Type C disease (NPC), is an autosomal recessive neurovisceral disorder of lipid metabolism. One characteristic feature of NPC is a vertical supranuclear gaze palsy particularly affecting saccades. However, horizontal saccades are also impaired and as a consequence a parameter related to horizontal peak saccadic velocity was used as an outcome measure in the clinical trial of miglustat, the first drug approved in several jurisdictions for the treatment of NPC. As NPC-related neuropathology is widespread in the brain we examined a wider range of horizontal saccade parameters and to determine whether these showed treatment-related improvement and, if so, if this was maintained over time. METHODS: Nine adult NPC patients participated in the study; 8 were treated with miglustat for periods between 33 and 61 months. Data were available for 2 patients before their treatment commenced and 1 patient was untreated. Tasks included reflexive saccades, antisaccades and self-paced saccades, with eye movements recorded by an infrared reflectance eye tracker. Parameters analysed were reflexive saccade gain and latency, asymptotic peak saccadic velocity, HSEM-α (the slope of the peak duration-amplitude regression line), antisaccade error percentage, self-paced saccade count and time between refixations on the self-paced task. Data were analysed by plotting the change from baseline as a proportion of the baseline value at each test time and, where multiple data values were available at each session, by linear mixed effects (LME) analysis. RESULTS: Examination of change plots suggested some modest sustained improvement in gain, no consistent changes in asymptotic peak velocity or HSEM-α, deterioration in the already poor antisaccade error rate and sustained improvement in self-paced saccade rate. LME analysis showed statistically significant improvement in gain and the interval between self-paced saccades, with differences over time between treated and untreated patients. CONCLUSIONS: Both qualitative examination of change scores and statistical evaluation with LME analysis support the idea that some saccadic parameters are robust indicators of efficacy, and that the variability observed across measures may indicate locally different effects of neurodegeneration and of drug actions.

Promoting preconception health in primary care.

Recommendations that all women of reproductive age have preconception care integrated into their primary care visits have been made since 1990. By looking at every premenopausal woman as a potential mother and advising her accordingly, primary care PAs can help women improve both their health and pregnancy outcomes.

Longitudinal changes in cerebellar and subcortical volumes in adult-onset Niemann-Pick disease type C patients treated with miglustat.

Niemann-Pick disease type C (NPC) is a rare neurovisceral disorder resulting in impaired intracellular lipid trafficking. The only disease-modifying treatment available to date is miglustat, an iminosugar inhibiting the accumulation of lipid by-products in neurons. This study explored how changes in cerebellar grey and white matter volumes, and in subcortical volumes, related to patient treatment status and disability and ataxia ratings. Nine adult-onset NPC patients and 17 matched controls underwent T1-weighted MRI. One patient was not receiving miglustat, and pre-treatment data were available for a further patient. Semi-automated cerebellar and subcortical segmentation was undertaken, and the rates of change in putamen, hippocampal, thalamic and caudal volumes, and grey and white matter cerebellar volumes, were compared to rates of change in Iturriaga disability score, Brief Ataxia Rating Scale (BARS), and horizontal saccadic gain. Untreated NPC patients appeared to lose cerebellar grey and white matter, bilateral thalamic volume, and right caudate volume faster than treated patients. Cerebellar grey matter volume loss and volume loss in the left thalamus were significantly correlated with Iturriaga disability scale changes. Change in both cerebellar grey and white matter was correlated with decrease in horizontal saccadic gain, but not with change in BARS. This is the first study to examine longitudinal treatment effects of miglustat on cerebellar and subcortical volumes in patients with adult-onset NPC, and is evidence that miglustat may have a protective effect on cerebellar and subcortical structure and function.

RNA polymerase II transcription elongation and Pol II CTD Ser2 phosphorylation: A tail of two kinases.

The transition between initiation and productive elongation during RNA Polymerase II (Pol II) transcription is a well-appreciated point of regulation across many eukaryotes. Elongating Pol II is modified by phosphorylation of serine 2 (Ser2) on its carboxy terminal domain (CTD) by two kinases, Bur1/Ctk1 in yeast and Cdk9/Cdk12 in metazoans. Here, we discuss the roles and regulation of these kinases and their relationship to Pol II elongation control, and focus on recent data from work in C. elegans that point out gaps in our current understand of transcription elongation.

Phosphorylation of RNA polymerase II is independent of P-TEFb in the C. elegans germline.

RNA polymerase II (Pol II) elongation in metazoans is thought to require phosphorylation of serine 2 (Ser2-P) of the Pol II C-terminal domain (CTD) by the P-TEFb complex, CDK-9/cyclin T. Another Ser2 kinase complex, CDK-12/cyclin K, which requires upstream CDK-9 activity has been identified in Drosophila and human cells. We show that regulation of Ser2-P in C. elegans soma is similar to other metazoan systems, but Ser2-P in the germline is independent of CDK-9, and largely requires only CDK-12. The observed differences are not due to differential tissue expression as both kinases and their cyclin partners are ubiquitously expressed. Surprisingly, loss of CDK-9 from germ cells has little effect on Ser2-P, yet CDK-9 is essential for germline development. By contrast, loss of CDK-12 and Ser2-P specifically from germ cells has little impact on germline development or function, although significant loss of co-transcriptional H3K36 trimethylation is observed. These results show a reduced requirement for Pol II Ser2-P in germline development and suggest that generating Ser2-P is not the essential role of CDK-9 in these cells. Transcriptional elongation in the C. elegans germline thus appears to be uniquely regulated, which may be a novel facet of germline identity.