University herbaria are uniquely important.

University herbaria play critical roles in biodiversity research and training and provide interdisciplinary academic environments that foster innovative uses of natural history collections. Universities have a responsibility to steward these important collections in perpetuity, in alignment with their academic missions and for the good of science and society.

Circadian-Dependent Intermittent Fasting Influences Ischemic Tolerance and Dendritic Spine Remodeling.

BACKGROUND: Preconditioning by intermittent fasting is linked to improved cognition and motor function, and enhanced recovery after stroke. Although the duration of fasting was shown to elicit different levels of neuroprotection after ischemic stroke, the impact of time of fasting with respect to the circadian cycles remains unexplored. METHODS: Cohorts of mice were subjected to a daily 16-hour fast, either during the dark phase (active-phase intermittent fasting) or the light phase (inactive-phase intermittent fasting) or were fed ad libitum. Following a 6-week dietary regimen, mice were subjected to transient focal cerebral ischemia and underwent behavioral functional assessment. Brain samples were collected for RNA sequencing and histopathologic analyses. RESULTS: Active-phase intermittent fasting cohort exhibited better poststroke motor and cognitive recovery as well as reduced infarction, in contrast to inactive-phase intermittent fasting cohort, when compared with ad libitum cohort. In addition, protection of dendritic spine density/morphology and increased expression of postsynaptic density protein-95 were observed in the active-phase intermittent fasting. CONCLUSIONS: These findings indicate that the time of daily fasting is an important factor in inducing ischemic tolerance by intermittent fasting.

Care First-Fund Later (CareFFuL): an end-of-life home care quality improvement project.

Previous work found referrals for end-of-life care are made late in the dying process and assessment processes for care funding, through continuing healthcare fast-track funding often inhibit people being able to die at home. The average time to discharge was 6.3 days and 29% died in hospital, as median survival was only 15 days.We aimed to support discharge to home within 1 day by December 2023 for patients, wishing to die at home, referred to the end-of-life discharge team in a medium-sized district general hospital in Southwest England.In phase 1, we identified 13 people on a patient-by-patient basis, learning from obstacles. Barriers identified included sourcing of equipment, communication between teams and clunky paperwork. Median time to discharge was 2 days (range within 24 hours to 8 days) with 2/13 (15.4%) dying prior to discharge. In phase 2, we extended the pilot, and 104 patients were identified; 94 people were discharged to home, with a median of wait of 1 day (range 0-7) to discharge, and 10 (9.6%) died prior to discharge (median 1 day; range 0-4). Median survival from discharge for the 94 who achieved their wishes to go home to die was 9 days (range 1-205 days). Only 26/94 (27.7%) people survived more than 30 days.Rapid decision-making and structures to support home-based end-of-life care can support more people to die in their preferred place of care, by using a community-based rapid response team instead of, or in parallel with continuing healthcare fast-track funding referral applications. Current pathways and funding models are not fit for purpose in an urgent care scenario when we have only one chance to get it right.

Antigenic Characterization of Circulating and Emerging SARS-CoV-2 Variants in the U.S. throughout the Delta to Omicron Waves.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved into numerous lineages with unique spike mutations and caused multiple epidemics domestically and globally. Although COVID-19 vaccines are available, new variants with the capacity for immune evasion continue to emerge. To understand and characterize the evolution of circulating SARS-CoV-2 variants in the U.S., the Centers for Disease Control and Prevention (CDC) initiated the National SARS-CoV-2 Strain Surveillance (NS3) program and has received thousands of SARS-CoV-2 clinical specimens from across the nation as part of a genotype to phenotype characterization process. Focus reduction neutralization with various antisera was used to antigenically characterize 143 SARS-CoV-2 Delta, Mu and Omicron subvariants from selected clinical specimens received between May 2021 and February 2023, representing a total of 59 unique spike protein sequences. BA.4/5 subvariants BU.1, BQ.1.1, CR.1.1, CQ.2 and BA.4/5 + D420N + K444T; BA.2.75 subvariants BM.4.1.1, BA.2.75.2, CV.1; and recombinant Omicron variants XBF, XBB.1, XBB.1.5 showed the greatest escape from neutralizing antibodies when analyzed against post third-dose original monovalent vaccinee sera. Post fourth-dose bivalent vaccinee sera provided better protection against those subvariants, but substantial reductions in neutralization titers were still observed, especially among BA.4/5 subvariants with both an N-terminal domain (NTD) deletion and receptor binding domain (RBD) substitutions K444M + N460K and recombinant Omicron variants. This analysis demonstrated a framework for long-term systematic genotype to antigenic characterization of circulating and emerging SARS-CoV-2 variants in the U.S., which is critical to assessing their potential impact on the effectiveness of current vaccines and antigen recommendations for future updates.

Pleistocene glaciation advances the cryptic speciation of Stellera chamaejasme L. in a major biodiversity hotspot.

The mountains of Southwest China comprise a significant large mountain range and biodiversity hotspot imperiled by global climate change. The high species diversity in this mountain system has long been attributed to a complex set of factors, and recent large-scale macroevolutionary investigations have placed a broad timeline on plant diversification that stretches from 10 million years ago (Mya) to the present. Despite our increasing understanding of the temporal mode of speciation, finer-scale population-level investigations are lacking to better refine these temporal trends and illuminate the abiotic and biotic influences of cryptic speciation. This is largely due to the dearth of organismal sampling among closely related species and populations, spanning the incredible size and topological heterogeneity of this region. Our study dives into these evolutionary dynamics of speciation using genomic and eco-morphological data of Stellera chamaejasme L. We identified four previously unrecognized cryptic species having indistinct morphological traits and large metapopulation of evolving lineages, suggesting a more recent diversification (~2.67-0.90 Mya), largely influenced by Pleistocene glaciation and biotic factors. These factors likely influenced allopatric speciation and advocated cyclical warming-cooling episodes along elevational gradients during the Pleistocene. The study refines the evolutionary timeline to be much younger than previously implicated and raises the concern that projected future warming may influence the alpine species diversity, necessitating increased conservation efforts.

An antioxidant and anti-ER stress combination therapy elevates phosphorylation of α-Syn at serine 129 and alleviates post-TBI PD-like pathology in a sex-specific manner in mice.

Clinical studies have shown that traumatic brain injury (TBI) increases the onset of Parkinson's disease (PD) in later life by >50%. Oxidative stress, endoplasmic reticulum (ER) stress, and inflammation are the major drivers of both TBI and PD pathologies. We presently evaluated if curtailing oxidative stress and ER stress concomitantly using a combination of apocynin and tert-butylhydroquinone and salubrinal during the acute stage after TBI in mice reduces the severity of late-onset PD-like pathology. The effect of multiple low doses of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on post-TBI neurodegeneration was also evaluated. The combo therapy elevated the level of phosphorylation at serine 129 (pS129) of α-Syn in the pericontusional cortex of male mice at 72 h post-TBI. Motor and cognitive deficits induced by TBI lasted at least 3 months and the combo therapy curtailed these deficits in both sexes. At 3 months post-TBI, male mice given combo therapy exhibited significantly lesser α-Syn aggregates in the SN and higher TH+ cells in the SNpc, compared to vehicle control. However, the aggregate number was not significantly different between groups of female mice. Moreover, TBI-induced loss of TH+ cells was negligible in female mice irrespective of treatment. The MPTP treatment aggravated PD-like pathology in male mice but had a negligible effect on the loss of TH+ cells in female mice. Thus, the present study indicates that mitigation of TBI-induced oxidative stress and ER stress at the acute stage could potentially reduce the risk of post-TBI PD-like pathology at least in male mice, plausibly by elevating pS129-α-Syn level.

Improving Students Access to Primary Health Care Through School-Based Health Centers.

BACKGROUND: More than 20 million children in the United States lack access to primary health care. PRACTICE LEARNING: Research shows that students with regular access to physical and mental health services have fewer absences, are more social, less likely to participate in risky behaviors, have improved focus and higher test scores. IMPLICATION FOR SCHOOL HEALTH POLICY, PRACTICE, AND EQUITY: School-based health centers (SBHCs) can be an important, valuable and viable health care delivery option to meet the full-range of primary health care needs of students where they spend the majority of their wake hours, ie, in school. Children in rural and other underserved communities, as well as those underinsured, non-insured, economically challenged, underserved, and the most vulnerable among us are especially at risk. CONCLUSIONS: This paper discusses the history, value, and importance of SBHCs from myriad perspectives, including physical and emotional wellbeing, academic and social success, and the promotion of a positive transition to adulthood. In addition, the authors' experiences that resulted in building the first SBHC in the Mid-Hudson Valley Region of New York State are shared. These experiences form the foundation for creating an important roadmap for individuals and school leaders that are interested in bringing a SBHC to their school and district.

Discovery of TNG908: A Selective, Brain Penetrant, MTA-Cooperative PRMT5 Inhibitor That Is Synthetically Lethal with MTAP-Deleted Cancers.

It has been shown that PRMT5 inhibition by small molecules can selectively kill cancer cells with homozygous deletion of the MTAP gene if the inhibitors can leverage the consequence of MTAP deletion, namely, accumulation of the MTAP substrate MTA. Herein, we describe the discovery of TNG908, a potent inhibitor that binds the PRMT5·MTA complex, leading to 15-fold-selective killing of MTAP-deleted (MTAP-null) cells compared to MTAPintact (MTAP WT) cells. TNG908 shows selective antitumor activity when dosed orally in mouse xenograft models, and its physicochemical properties are amenable for crossing the blood-brain barrier (BBB), supporting clinical study for the treatment of both CNS and non-CNS tumors with MTAP loss.

A new nuclear phylogeny of the tea family (Theaceae) unravels rapid radiations in genus Camellia.

Molecular analyses of rapidly radiating groups often reveal incongruence between gene trees. This mainly results from incomplete lineage sorting, introgression, and gene tree estimation error, which complicate the estimation of phylogenetic relationships. In this study, we reconstruct the phylogeny of Theaceae using 348 nuclear loci from 68 individuals and two outgroup taxa. Sequence data were obtained by target enrichment using the recently released Angiosperm 353 universal probe set applied to herbarium specimens. The robustness of the topologies to variation in data quality was established under a range of different filtering schemes, using both coalescent and concatenation approaches. Our results confirmed most of the previously hypothesized relationships among tribes and genera, while clarifying additional interspecific relationships within the rapidly radiating genus Camellia. We recovered a remarkably high degree of gene tree heterogeneity indicative of rapid radiation in the group and observed cytonuclear conflicts, especially within Camellia. This was especially pronounced around short branches, which we primarily associate with gene tree estimation error. Our analysis also indicates that incomplete lineage sorting (ILS) contributed to gene-tree conflicts and accounted for approximately 14 % of the explained variation, whereas inferred introgression levels were low. Our study advances the understanding of the evolution of this important plant family and provides guidance on the application of target capture methods and the evaluation of key processes that influence phylogenetic discordances.

Key to the North American tribes and genera of herb, rose, bramble, and inquiline gall wasps (Hymenoptera, Cynipoidea, Cynipidaesensu lato).

Robust keys exist for the family-level groups of Cynipoidea. However, for most regions of the world, keys to genera are not available. To address this gap as it applies to North America, a fully illustrated key is provided to facilitate identification of the tribes and genera of rose gall, herb gall, and inquiline gall wasps known from the region. For each taxon covered, a preliminary diagnosis and an updated overview of taxonomy, biology, distribution, and natural history are provided.

Collections are truly priceless.

Last month, Duke University in North Carolina announced that it was shuttering its herbarium. The collection consists of nearly 1 million specimens representing the most comprehensive and historic set of plants from the southeastern United States. It also includes extensive holdings from other regions of the world, especially Mexico, Central America, and the West Indies. Duke plans to disperse these samples to other institutions for use or storage over the next 2 to 3 years, but this decision reflects a lack of awareness by academia that such collections are being leveraged as never before. With modern technologies spanning multiple fields of study, the holdings in herbaria and other natural history collections are not only facilitating a deeper and broader understanding of the past and present world but are also providing tools to meet both known and unforeseen challenges facing humanity. Science and society can hardly risk the loss of such an important resource.

Incorporating plant phenological responses into species distribution models reduces estimates of future species loss and turnover.

Anthropogenetic climate change has caused range shifts among many species. Species distribution models (SDMs) are used to predict how species ranges may change in the future. However, most SDMs rarely consider how climate-sensitive traits, such as phenology, which affect individuals' demography and fitness, may influence species' ranges. Using > 120 000 herbarium specimens representing 360 plant species distributed across the eastern United States, we developed a novel 'phenology-informed' SDM that integrates phenological responses to changing climates. We compared the ranges of each species forecast by the phenology-informed SDM with those from conventional SDMs. We further validated the modeling approach using hindcasting. When examining the range changes of all species, our phenology-informed SDMs forecast less species loss and turnover under climate change than conventional SDMs. These results suggest that dynamic phenological responses of species may help them adjust their ecological niches and persist in their habitats as the climate changes. Plant phenology can modulate species' responses to climate change, mitigating its negative effects on species persistence. Further application of our framework will contribute to a generalized understanding of how traits affect species distributions along environmental gradients and facilitate the use of trait-based SDMs across spatial and taxonomic scales.

Safety and effectiveness of diazepam nasal spray in male and female patients: Post hoc analysis of data from a phase 3 safety study.

Sex differences in drug pharmacokinetics include variations in the expression of the cytochrome P450 enzymes, which are involved in the metabolism of benzodiazepines. It is unclear whether sex influences outcomes associated with intranasally administered drugs. A post hoc analysis of sex differences was conducted to evaluate the effectiveness and safety of diazepam nasal spray, which included examining changes in the number of days between seizure clusters over time (SEIzure interVAL [SEIVAL]). Diazepam nasal spray is approved for acute treatment of seizure clusters in patients with epilepsy aged ≥6 years. Data from a phase 3 safety study were used to determine the proportion of second doses used within 24 h (ie, a proxy for effectiveness) and SEIVAL. Adverse events were recorded. Of 163 treated patients, 89 were female, and 74 were male. Approximately 16% of both sexes self-administered the study drug. A slightly higher proportion of seizure clusters was treated with a second dose in female (14.7%) than male (9.4%) patients. SEIVAL increased significantly and substantially over a year for all patients. The safety profile was generally similar between the sexes. These results suggest that potential sex differences in benzodiazepine pharmacokinetics do not meaningfully influence outcomes associated with diazepam nasal spray. PLAIN LANGUAGE SUMMARY: Some drugs may have differences in absorption and metabolism between genders that could translate into differences in safety and effectiveness. This safety study looked at diazepam nasal spray for treating seizure clusters in patients at least 6 years old. It found that safety was about the same for females and males. For both groups, most clusters stopped after only 1 dose of the drug, and the time between treated clusters got longer over a year.

Medicinal plants meet modern biodiversity science.

Plants have been an essential source of human medicine for millennia. In this review, we argue that a holistic, interdisciplinary approach to the study of medicinal plants that combines methods and insights from three key disciplines - evolutionary ecology, molecular biology/biochemistry, and ethnopharmacology - is poised to facilitate new breakthroughs in science, including pharmacological discoveries and rapid advancements in human health and well-being. Such interdisciplinary research leverages data and methods spanning space, time, and species associated with medicinal plant species evolution, ecology, genomics, and metabolomic trait diversity, all of which build heavily on traditional Indigenous knowledge. Such an interdisciplinary approach contrasts sharply with most well-funded and successful medicinal plant research during the last half-century, which, despite notable advancements, has greatly oversimplified the dynamic relationships between plants and humans, kept hidden the larger human narratives about these relationships, and overlooked potentially important research and discoveries into life-saving medicines. We suggest that medicinal plants and people should be viewed as partners whose relationship involves a complicated and poorly explored set of (socio-)ecological interactions including not only domestication but also commensalisms and mutualisms. In short, medicinal plant species are not just chemical factories for extraction and exploitation. Rather, they may be symbiotic partners that have shaped modern societies, improved human health, and extended human lifespans.

Non-pharmacological interventions for traumatic brain injury.

Heterogeneity and variability of symptoms due to the type, site, age, sex, and severity of injury make each case of traumatic brain injury (TBI) unique. Considering this, a universal treatment strategy may not be fruitful in managing outcomes after TBI. Most of the pharmacological therapies for TBI aim at modifying a particular pathway or molecular process in the sequelae of secondary injury rather than a holistic approach. On the other hand, non-pharmacological interventions such as hypothermia, hyperbaric oxygen, preconditioning with dietary adaptations, exercise, environmental enrichment, deep brain stimulation, decompressive craniectomy, probiotic use, gene therapy, music therapy, and stem cell therapy can promote healing by modulating multiple neuroprotective mechanisms. In this review, we discussed the major non-pharmacological interventions that are being tested in animal models of TBI as well as in clinical trials. We evaluated the functional outcomes of various interventions with an emphasis on the links between molecular mechanisms and outcomes after TBI.

Mandatory fortification of rice in the public distribution system in India: An ethics perspective.

In response to the continuing high prevalence of anaemia recorded in the National Family Health Survey-5, the Indian government launched a policy for mandatory iron fortification of the rice provided through public nutrition programmes in India. This was done even though a rigorous evidence analysis had already concluded that rice fortification was not effective in preventing anaemia or iron deficiency at the population level. Fortification also poses a potential risk of iron toxicity over time, but there is no stated time period for the policy's implementation. The risk is particularly high in segments of the population who already have a high habitual iron intake, and who could be exposed to simultaneous fortification in different staples and food commodities along with the ongoing weekly Iron and Folic Acid tablets supplementation programme. Finally, this fortification policy also requires significant additional funding and resources to implement. It is crucial to examine such mandatory health actions, and to weigh the benefits and risks of harm, using the principles of public health ethics.

Reducing the Likelihood of Opioid Overdose Fatalities on College and University Campuses: An Action Plan and Model.

For more than two decades there has been a continuous rise in opioid overdose related deaths. The majority of the deaths include the age range when, traditionally, individuals are likely to attend college or university. As a result, Vassar College has taken the important initiative and created and implemented a new opioid overdose intervention strategy and action plan called AED+. AED+ expands on the Model of Greater Awareness, Training and Increased Availability of and Accessibility to Life Saving Intervention Devices; a model that was created based on AED devices improving outcomes of out-of-hospital cardiac arrest emergencies. Similar to AED's improving out-of-hospital cardiac arrest outcomes, the + component of the AED+ initiative increases awareness and provides basic, targeted education about naloxone and its use. Furthermore, the education includes information about naloxone's greater availability and its more immediate access across the campus by students, staff, faculty, administrators, and visitors in the event of a suspected opioid overdose. Starting in May 2023, members of the school's Health Service and senior administrative leaders identified it necessary to be proactive and not reactive to managing an opioid overdose in the campus community. Although Vassar College has not recently experienced an opioid overdose, it is confidently projected that these targeted actions will proactively and positively reduce the likelihood of opioid-related fatalities on campus. Furthermore, it is the purpose of this article to share the AED+ model so other colleges and universities can modify it to best fit their unique setting in order to improve opioid overdose outcomes.

Plasticity and not adaptation is the primary source of temperature-mediated variation in flowering phenology in North America.

Phenology varies widely over space and time because of its sensitivity to climate. However, whether phenological variation is primarily generated by rapid organismal responses (plasticity) or local adaptation remains unresolved. Here we used 1,038,027 herbarium specimens representing 1,605 species from the continental United States to measure flowering-time sensitivity to temperature over time (Stime) and space (Sspace). By comparing these estimates, we inferred how adaptation and plasticity historically influenced phenology along temperature gradients and how their contributions vary among species with different phenology and native climates and among ecoregions differing in species composition. Parameters Sspace and Stime were positively correlated (r = 0.87), of similar magnitude and more frequently consistent with plasticity than adaptation. Apparent plasticity and adaptation generated earlier flowering in spring, limited responsiveness in late summer and delayed flowering in autumn in response to temperature increases. Nonetheless, ecoregions differed in the relative contributions of adaptation and plasticity, from consistently greater importance of plasticity (for example, southeastern United States plains) to their nearly equal importance throughout the season (for example, Western Sierra Madre Piedmont). Our results support the hypothesis that plasticity is the primary driver of flowering-time variation along temperature gradients, with local adaptation having a widespread but comparatively limited role.

Analyses of patients who self-administered diazepam nasal spray for acute treatment of seizure clusters.

For acute treatment of seizure clusters in patients with epilepsy, intranasal administration of acute seizure therapies has been shown to provide accessibility and ease of use to care partners as well as the potential for self-administration by patients. Diazepam nasal spray (Valtoco®) was approved by the US Food and Drug Administration for acute treatment of intermittent, stereotypic episodes of frequent seizure activity (ie, seizure clusters, acute repetitive seizures) in patients with epilepsy aged ≥6 years. Self-administration consistent with the prescribing information is feasible and was reported by a subgroup of patients (n = 27 of 163) in a long-term phase 3 safety study. Data regarding self-administration among these patients with seizure clusters are examined here to explore the safety profiles and measures of effectiveness, as well as the quality of life of those who self-treated. In addition, this focused look at patients who self-administered diazepam nasal spray may offer some insights into the characteristics of patients who may be appropriate for self-administration.

Action Plan and Model to Reduce Potential Opioid Overdose Deaths on K-12 Campuses.

School communities are not immune to the alarming increase in opioid-related deaths occurring in the United States during the past decade. The purpose of this article is to share how a middle school in New York State, beginning in the late fall of 2022, successfully implemented a program to reduce the likelihood of opioid overdose deaths in their building through expansion of the accessibility of and education and training in use of naloxone, an opioid antagonist. The program is applicable for all K-12 campuses and follows the Model of Greater Awareness, Improved Training, and Increased Availability of and Accessibility to Intervention Devices, based on the steps successfully used for out-of-hospital cardiac arrest emergencies. Because opioid addiction does not discriminate, it is confidently projected that these targeted actions will proactively and positively reduce the likelihood of opioid overdose deaths in our school setting, including for students, faculty, staff, administrators, and visitors, when and should they occur.