Development of a brief bedside tool to screen women sexual assault survivors for risk of persistent posttraumatic stress six months after sexual assault.

This study aims to develop and validate a brief bedside tool to screen women survivors presenting for emergency care following sexual assault for risk of persistent elevated posttraumatic stress symptoms (PTSS) six months after assault. Participants were 547 cisgender women sexual assault survivors who presented to one of 13 sexual assault nurse examiner (SANE) programs for medical care within 72 h of a sexual assault and completed surveys one week and six months after the assault. Data on 222 potential predictors from the SANE visit and the week one survey spanning seven broadly-defined risk factor domains were candidates for inclusion in the screening tool. Elevated PTSS six months after assault were defined as PCL-5 > 38. LASSO logistic regression was applied to 20 randomly selected bootstrapped samples to evaluate variable importance. Logistic regression models comprised of the top 10, 20, and 30 candidate predictors were tested in 10 cross-validation samples drawn from 80% of the sample. The resulting instrument was validated in the remaining 20% of the sample. AUC of the finalized eight-item prediction tool was 0.77 and the Brier Score was 0.19. A raw score of 41 on the screener corresponds to a 70% risk of elevated PTSS at 6 months. Similar performance was observed for elevated PTSS at one year. This brief, eight-item risk stratification tool consists of easy-to-collect information and, if validated, may be useful for clinical trial enrichment and/or patient screening.

Relationship between addictions and obesity, physical activity and vascular aging in young adults (EVA-Adic study): a research protocol of a cross-sectional study.

Background: Behavioral and substance addictions are prevalent health problems that, alongside obesity, are linked to reduced physical activity and increased sedentary time. Similarly, arterial stiffness and vascular aging are processes that begin gradually at an early age and are closely associated with morbidity and mortality from cardiovascular diseases. The main objective of this study is to analyze how addictions are related to obesity and body fat distribution, physical activity, sedentary time, arterial stiffness and vascular aging, as well as sleep quality, cognitive function and gender differences in young adults aged between 18 and 34 years. Methods: This cross-sectional descriptive observational study will analyze data from 500 subjects (250 men and 250 women) aged 18-34 without cardiovascular disease, selected by simple random sampling with replacement from the urban population of the city center of Salamanca (34,044 people aged 18-34, with 18,450 women and 15,594 men). Behavioral and substance addictions, as well as sleep quality and cognitive impairment will be assessed using questionnaires. The Pittisburg Sleep Quality Index (PSQI) will be used to measure sleep quality and the Ford questionnaire will be used to measure insomnia in response to stress. For obesity, weight, height, waist and hip circumference, body composition will be measured with the Inbody 230® impedance meter. For physical activity and sedentary time, we will use the Actigraph® accelerometer alongside the international physical activity questionnaire (IPAQ) and the Marshall questionnaire. The Sphygmocor System® will be used for pulse wave analysis and carotid-femoral pulse wave velocity (cfPWV), while the Vasera VS-2000® will measure cardio ankle vascular index (CAVI) and brachial-ankle pulse wave velocity (baPWV). Vascular aging will be calculated with the 10th and 90th percentiles of cfPWV or baPWV. Demographic, analytical variables will be collected, as will data to assess vascular, cardiac, renal, and brain injury. Discussion: Addictions are on the rise in today's society, affecting the mental health and well-being of those who suffer from them, generating important social problems such as job loss, family dysfunction, debt and social isolation. Together with obesity, they are prevalent health problems in young adults and are associated with lower physical activity and higher sedentary time. Meanwhile, arterial stiffness and vascular aging are processes that begin gradually at an early age and determine morbidity and mortality caused by cardiovascular diseases. The results of this project will allow us to understand the situation regarding behavioral and substance addictions in young adults. Better understanding of these addictions will in turn facilitate the development of more effective prevention strategies and intervention programs, which can then reduce the negative impact at both the individual and societal levels. Clinical trial registration: [ClinicalTrials.gov], identifier [NCT05819840].

MYC targeting by OMO-103 in solid tumors: a phase 1 trial.

Among the 'most wanted' targets in cancer therapy is the oncogene MYC, which coordinates key transcriptional programs in tumor development and maintenance. It has, however, long been considered undruggable. OMO-103 is a MYC inhibitor consisting of a 91-amino acid miniprotein. Here we present results from a phase 1 study of OMO-103 in advanced solid tumors, established to examine safety and tolerability as primary outcomes and pharmacokinetics, recommended phase 2 dose and preliminary signs of activity as secondary ones. A classical 3 + 3 design was used for dose escalation of weekly intravenous, single-agent OMO-103 administration in 21-day cycles, encompassing six dose levels (DLs). A total of 22 patients were enrolled, with treatment maintained until disease progression. The most common adverse events were grade 1 infusion-related reactions, occurring in ten patients. One dose-limiting toxicity occurred at DL5. Pharmacokinetics showed nonlinearity, with tissue saturation signs at DL5 and a terminal half-life in serum of 40 h. Of the 19 patients evaluable for response, 12 reached the predefined 9-week time point for assessment of drug antitumor activity, eight of those showing stable disease by computed tomography. One patient defined as stable disease by response evaluation criteria in solid tumors showed a 49% reduction in total tumor volume at best response. Transcriptomic analysis supported target engagement in tumor biopsies. In addition, we identified soluble factors that are potential pharmacodynamic and predictive response markers. Based on all these data, the recommended phase 2 dose was determined as DL5 (6.48 mg kg-1).ClinicalTrials.gov identifier: NCT04808362 .

Rethinking the clinical research protocol: Lessons learned from the COVID-19 pandemic and recommendations for reducing noncompliance.

BACKGROUND/AIMS: Since the onset of the coronavirus disease 2019 (COVID-19) pandemic, 103.4 million cases and 1.1 million deaths have occurred nationally as of November 2023. Despite the benefit of mitigating measures, the pandemic's effect on participant safety is rarely documented. METHODS: This study assessed noncompliance occurring from July 2019 to August 2021 that were stratified by the date of noncompliance (before or after restrictions). Events were described by size, site, noncompliance type, primary category, subcategory, and cause. In addition, noncompliance associated with COVID-19 was analyzed to determine characteristics. RESULTS: In total, 323 noncompliance events occurred across 21,146 participants at risk in 35 protocols. The overall rate of noncompliance increased from 0.008 events per participant to 0.022 events per participant after the COVID-19 restrictions (p < 0.001). For onsite protocols, the median within protocol change in rates was 0.001 (interquartile range = 0.141) after the onset of COVID-19 restrictions (p = 0.54). For large-sized protocols (n ≥ 100), the median within protocol change in rates was also 0.001 (interquartile range = 0.017) after COVID-19 restrictions (p = 0.15). For events related to COVID-19 restrictions, 160/162 (99%) were minor deviations, 161/162 (99%) were procedural noncompliance, and 124/162 (77%) were an incomplete study visit. CONCLUSION: These noncompliance events have implications for clinical trial methodology because nonadherence to trial design can lead to participant safety concerns and loss of trial data validity. Protocols should be written to better facilitate the capture of all safety and efficacy data. This recommendation should be considered when changes occur to the protocol environment that are outside of the study team's control.

What do emergency department pharmacist practitioners know and understand about patient safeguarding? A qualitative study.

BACKGROUND: Pharmacists with additional clinical skills now work in UK emergency departments. Known as Emergency Department Pharmacist Practitioners, the role was developed in response to a shortage of physicians and nurses. They carry out activities typical of traditional hospital pharmacists, but also novel 'practitioner' activities such as examining patients, and acting as designated care provider. The role includes a responsibility to safeguard patients from harm. Professional competence, i.e. to safeguard patients, is underpinned by knowledge of the subject, but also knowledge application. AIM: To investigate what Emergency Department Pharmacist Practitioners know and understand about safeguarding vulnerable children and adults. METHOD: Thirteen Emergency Department Pharmacist Practitioners were interviewed to explore their knowledge and understanding of safeguarding. Interview questions were developed from review of relevant literature, as were vignettes with variables identified and altered to produce different scenarios. Template analysis was used to code data to a priori themes for each of the stages of the initial safeguarding process, and new themes that emerged throughout the process. RESULTS: Six themes were identified in addition to the four a priori themes. Overall, participants frequently described how safeguarding concerns are both recognised and responded to, but seemed more comfortable when responding to medicines related concerns. Factors thought to influence the safeguarding process included: resources and setting; and education, training and experiential learning; and culture. CONCLUSION: While Emergency Department Pharmacist Practitioners interviewed were aware of the safeguarding process, there were some misconceptions as to the roles of different healthcare workers in this process.

Intimate Partner Violence and Immigration in the United States: A Systematic Review.

This systematic review sought to describe the prevalence of intimate partner violence (IPV) victimization among immigrants in the United States (U.S.) and the prevalence of IPV perpetration among immigrants in the U.S. PsycInfo, PubMed, Global Health and Scopus databases were searched for peer-reviewed literature that quantitatively examined IPV in relation to immigration. Twenty-four articles were included in the final review. Past-year IPV victimization rates among immigrants ranged from 3.8% to 46.9% and lifetime IPV victimization rates ranged from 13.9% to 93%; past-year IPV perpetration rates ranged from 3.0% to 24.8% and the one lifetime IPV perpetration rate was 12.8%. Estimates varied widely by country of origin, type of violence measured, and measure used to quantify IPV. Reliance on small convenience samples is problematic when trying to determine the true prevalence of IPV among immigrants. Epidemiological research is needed to improve the accuracy and representativeness of findings.

Anthraquinone-Modified Silica Nanoparticles as Heterogeneous Photocatalyst for the Oxidative Hydroxylation of Arylboronic Acids.

In this work, the synthesis and characterization of a heterogeneous photocatalyst based on spherical silica nanoparticles superficially modified with anthraquinone 2-carboxylic acid (AQ-COOH) are presented. The nanomaterial was characterized by TEM, SEM, FT-IR, diffuse reflectance, fluorescence, NMR, DLS, XRD and XPS. These analyses confirm the covalent linking of AQ-COOH with the NH2 functionality in the nanomaterial and, more importantly, the photocatalyst retains its photophysical properties once bound. The heterogeneous photocatalyst was successfully employed in the aerobic hydroxylation of arylboronic acids to phenols under sustainable reaction conditions. Phenols were obtained in high yields (up to 100 %) with low catalyst loading (3.5 mol %), reaching TOF values of 3.7 h-1 . Using 2-propanol as solvent at room temperature, the visible light photocatalysis produced H2 O2 as a key intermediate to promote the aerobic hydroxylation of arylboronic acids. The heterogeneous photocatalyst was reused at least 5 times, without modification of the nanomaterial structure and morphology. This simple heterogeneous system showed great catalytic activity under sustainable reaction conditions.

Affordable housing through the Low-Income Housing Tax Credit program and opioid overdose emergency department visits.

INTRODUCTION: The United States continues to experience an opioid overdose crisis. As a key social determinant of health, housing insecurity may contribute to initiation of substance use and can threaten outcomes for those with substance use disorders by increasing stress, risky substance use, discontinuity of treatment, and return to use, all of which may increase the risk of overdose. The Low-Income Housing Tax Credit (LIHTC) program supports access to rental housing for low-income populations. By facilitating access to affordable housing, this program may improve housing security, thereby reducing overdose risk. METHODS: We used data from LIHTC Property Data and the State Emergency Department Database (SEDD) to identify the number of LIHTC units available and opioid overdoses discharged from the emergency department (ED) in 13 states between 2005 and 2014. RESULTS: Between 2005 and 2014, mean opioid overdose ED visits were higher in states with fewer LIHTC units (<28 LIHTC units per 100,000 population) at 26.5 per 100,000 population as compared to states with higher LIHTC units (≥28 LIHTC units per 100,000 population) at 21.1 per 100,000. We find that greater availability of LIHTC units was associated with decreased rates of opioid overdose ED visits (RR 0.94; CI 0.90, 1.00). CONCLUSIONS: Given the importance of housing as a key social determinant of health, the provision of affordable housing may mitigate substance misuse and prevent nonfatal opioid overdose.

Perinatal Homicide in the United States: A Systematic Literature Review.

This review focused on literature from the United States evaluating homicide during the perinatal period. It was completed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Seventeen studies met the criteria for inclusion, including: describing prevalence and risk factors related to homicide deaths of pregnant or postpartum birthing individuals; being conducted in the United States; and being published in English 2007 or later. This review found that homicide is an important contributor to maternal mortality and is a leading cause of death during pregnancy and the postpartum period, especially if an individual is Black and under the age of 30. Future efforts must be made to standardize data collection efforts and resolve nuanced terminology that results in interpretation challenges. The United States should examine maternal deaths through the entirety of the perinatal period and fully invest in violence prevention efforts.

Commentary: On measurement error, PSA doubling time, and prostate cancer.

Exposure measurement error is a pervasive problem for epidemiology research projects designed to provide valid and precise statistical evidence supporting postulated exposure-disease relationships of interest. The purpose of this commentary is to highlight an important real-life example of this exposure measurement error problem and to provide a simple and useful diagnostic tool for physicians and their patients that corrects for the exposure measurement error. More specifically, prostate-specific antigen doubling time (PSADT) is a widely used measure for guiding future treatment options for patients with biochemically recurrent prostate cancer. Numerous papers have been published claiming that a low calculated PSADT value (denoted PSADT^) is predictive of metastasis and premature death from prostate cancer. Unfortunately, none of these papers have adjusted for the measurement error in PSADT^, an estimator that is typically computed using the popular Memorial Sloan Kettering website very often visited by both physicians and their patients. For this website, the estimator PSADT^ of the true (but unknown) PSADT for a patient (denoted PSADT∗) is computed as the natural log of 2 (i.e., 0.6931) divided by the estimated slope of the straight-line regression of the natural log of PSA (in ng/mL) on time. We utilize PSADT^ to derive an expression for the probability that the unknown PSADT∗ for a patient is below a specified value C (>0) of concern to both the physician and the patient. This probability is easy to interpret and takes into account the fact that PSADT^ is a statistical estimator with variability. This variability introduces measurement error, namely, the difference between a computed value PSADT^ and the true, but unknown, value PSADT∗. We have developed an Excel calculator that, once the [time, ln(PSA)] values are entered, outputs both the value of PSADT^ and the desired probability. In addition, we discuss problematic statistical issues attendant with PSADT∗ estimation typically based on at most three or four PSA values. We strongly recommend the use of this probability when physicians are discussing PSADT^ values and associated treatment options with their patients. And, we stress that future epidemiology research projects involving PSA doubling time should take into account the measurement error problem highlighted in this Commentary.

Fibrous Dysplasia of the Clivus: Case Report and Literature Review.

Fibrous dysplasia is a benign, developmental bone disorder that causes fibrous replacement of normal skeletal tissue. This may lead to weakness, distortion, and tissue expansion. Fibrous dysplasia can occur anywhere in the body, including the craniofacial area. The clivus is a central skull bone formed by the bases of the sphenoid and occiput, respectively. The clivus is a rare, usually unrecognized, and seldom reported location for the development of fibrous dysplasia. Although fibrous dysplasia of the clivus (FDC) is usually discovered by incidental findings, it can sometimes present with clinical symptoms. In this case, we discuss a 30-year-old male who presents to the emergency room with headaches, altered mental status, and a prior presentation of location-related symptomatic epilepsy. Magnetic resonance imaging depicted a mass in the clivus, low in signal on T1 and mildly hypointense on T2 imaging. Follow-up computed tomography (CT) imaging, as recommended, revealed the classic presentation of FDC. In this paper, we discuss the significance of this condition and the importance of thorough investigation to rule out differential diagnoses that may present with similar acute symptoms as this patient.

TMS over the pre-SMA enhances semantic cognition via remote network effects on task-based activity and connectivity.

BACKGROUND: The continuous decline of executive abilities with age is mirrored by increased neural activity of domain-general networks during task processing. So far, it remains unclear how much domain-general networks contribute to domain-specific processes such as language when cognitive demands increase. The current neuroimaging study explored the potential of intermittent theta-burst stimulation (iTBS) over a domain-general hub to enhance executive and semantic processing in healthy middle-aged to older adults. METHODS: We implemented a cross-over within-subject study design with three task-based neuroimaging sessions per participant. Using an individualized stimulation approach, each participant received once effective and once sham iTBS over the pre-supplementary motor area (pre-SMA), a region of domain-general control. Subsequently, task-specific stimulation effects were assessed in functional MRI using a semantic and a non-verbal executive task with varying cognitive demand. RESULTS: Effective stimulation increased activity only during semantic processing in visual and dorsal attention networks. Further, iTBS induced increased seed-based connectivity in task-specific networks for semantic and executive conditions with high cognitive load but overall reduced whole-brain coupling between domain-general networks. Notably, stimulation-induced changes in activity and connectivity related differently to behavior: While stronger activity of the parietal dorsal attention network was linked to poorer semantic performance, its enhanced coupling with the pre-SMA was associated with more efficient semantic processing. CONCLUSIONS: iTBS modulates networks in a task-dependent manner and generates effects at regions remote to the stimulation site. These neural changes are linked to more efficient semantic processing, which underlines the general potential of network stimulation approaches in cognitive aging.

Implementation of the national antimicrobial stewardship competencies for UK undergraduate healthcare professional education within undergraduate pharmacy programmes: a survey of UK schools of pharmacy.

Background: Pharmacists play a key role in antimicrobial stewardship (AMS). Consensus-based national AMS competencies for undergraduate healthcare professionals in the UK reflect the increasing emphasis on competency-based healthcare professional education. However, the extent to which these are included within undergraduate pharmacy education programmes in the UK is unknown. Objectives: To explore which of the AMS competencies are delivered, including when and at which level, within UK undergraduate MPharm programmes. Methods: A cross-sectional online questionnaire captured the level of study of the MPharm programme in which each competency was taught, the method of delivery and assessment of AMS education, and examples of student feedback. Results: Ten institutions completed the survey (33% response rate). No institution reported covering all 54 AMS competencies and 5 of these were taught at half or fewer of the institutions. Key gaps were identified around taking samples, communication, outpatient parenteral antimicrobial therapy and surgical prophylaxis. The minimum time dedicated to AMS teaching differed between institutions (range 9-119 h), teaching was generally through didactic methods, and assessment was generally through knowledge recall and objective structured clinical examinations. Feedback from students suggests they find AMS and antimicrobial resistance (AMR) to be complex yet important topics. Conclusions: UK schools of pharmacy should utilize the competency framework to identify gaps in their AMS, AMR and infection teaching. To prepare newly qualified pharmacists to be effective at delivering AMS and prescribing antimicrobials, schools of pharmacy should utilize more simulated environments and clinical placements for education and assessment of AMS.

Targeting MYC-driven lymphoma: lessons learned and future directions.

MYC plays a central role in tumorigenesis by orchestrating cell proliferation, growth and survival, among other transformation mechanisms. In particular, MYC has often been associated with lymphomagenesis. In fact, MYC overexpressing lymphomas such as high-grade B-cell lymphoma (HGBL) and double expressor diffuse large B-cell lymphomas (DLBCL), are considered addicted to MYC. In such a context, MYC targeting therapies are of special interest, as MYC withdrawal is expected to result in tumor regression. However, whether high MYC levels are always predictive of increased sensitivity to these approaches is not clear yet. Even though no MYC inhibitor has received regulatory approval to date, substantial efforts have been made to investigate avenues to render MYC a druggable target. Here, we summarize the different classes of molecules currently under development, which mostly target MYC indirectly in aggressive B-cell lymphomas, paying special attention to subtypes with MYC/BCL2 or BCL6 translocations or overexpression.

Researcher-Practitioner Partnerships to Implement and Evaluate Sexual and Relationship Violence Prevention Programs for Boys and Men.

Although male-focused sexual and relationship violence (SRV) prevention programs are widely promulgated, limited guidance concerning how programs should be implemented for rigorous evaluation exists. To help develop evidence for such guidance, this paper reports on 20 interviews with leaders at youth-serving community-based organizations (CBOs) and educational institutions, which are sites for male-focused SRV prevention programs. This study examined: (1) how programs can be designed to engage male participants; and (2) how youth-serving CBOs and educational institutions can partner with researchers for evaluations. Findings underscore the importance of attending to the unique needs of program participants, their parents/guardians, and host organizations.

Reducing MYC's transcriptional footprint unveils a good prognostic gene signature in melanoma.

MYC's key role in oncogenesis and tumor progression has long been established for most human cancers. In melanoma, its deregulated activity by amplification of 8q24 chromosome or by upstream signaling coming from activating mutations in the RAS/RAF/MAPK pathway-the most predominantly mutated pathway in this disease-turns MYC into not only a driver but also a facilitator of melanoma progression, with documented effects leading to an aggressive clinical course and resistance to targeted therapy. Here, by making use of Omomyc, the most characterized MYC inhibitor to date that has just successfully completed a phase I clinical trial, we show for the first time that MYC inhibition in melanoma induces remarkable transcriptional modulation, resulting in severely compromised tumor growth and a clear abrogation of metastatic capacity independently of the driver mutation. By reducing MYC's transcriptional footprint in melanoma, Omomyc elicits gene expression profiles remarkably similar to those of patients with good prognosis, underlining the therapeutic potential that such an approach could eventually have in the clinic in this dismal disease.

Antibiotic discovery against Piscirickettsia salmonis using a combined in silico and in vitro approach.

Piscirickettsia salmonis is one of the main pathogens causing considerable economic losses in salmonid farming. The DNA gyrase of several pathogenic bacteria has been the target of choice for antibiotic design and discovery for years, due to its key function during DNA replication. In this study, we carried out a combined in silico and in vitro approach to antibiotic discovery targeting the GyrA subunit of Piscirickettsia salmonis. The in silico results of this work showed that flumequine (-6.6 kcal/mol), finafloxacin (-7.2 kcal/mol), rosoxacin (-6.6 kcal/mol), elvitegravir (-6.4 kcal/mol), sarafloxacin (-8.3 kcal/mol), orbifloxacin (-7.9 kcal/mol), and sparfloxacin (-7.2 kcal/mol) are docked with good affinities in the DNA binding domain of the Piscirickettsia salmonis GyrA subunit. In the in vitro inhibition assay, it was observed that most of these molecules inhibit the growth of Piscirickettsia salmonis, except for elvitegravir. We believe that this methodology could help to significantly reduce the time and cost of antibiotic discovery trials to combat Piscirickettsia salmonis within the salmonid farming industry.

Unconventional and conventional Pickering emulsions: Perspectives and challenges in skin applications.

Pickering emulsions are free from molecular and classical surfactants and are stabilized by solid particles, creating long-term stability against emulsion coalescence. Additionally, these emulsions are both environmentally and skin-friendly, creating new and unexplored sensorial perceptions. Although the literature mostly describes conventional emulsions (oil-in-water), there are unconventional emulsions (multiple, oil-in-oil and water-in-water) with excellent prospects and challenges in skin application as oil-free systems, permeation enhancers and topical drug delivery agents, with various possibilities in pharmaceutical and cosmetic products. However, up to now, these conventional and unconventional Pickering emulsions are not yet available as commercial products. This review brings to the discussion some important aspects such as the use of phases, particles, rheological and sensorial perception, as well as current trends in the development of these emulsions.

Pharmacokinetic Analysis of Omomyc Shows Lasting Structural Integrity and Long Terminal Half-Life in Tumor Tissue.

MYC is an oncoprotein causally involved in the majority of human cancers and a most wanted target for cancer treatment. Omomyc is the best-characterized MYC dominant negative to date. In the last years, it has been developed into a therapeutic miniprotein for solid tumor treatment and recently reached clinical stage. However, since the in vivo stability of therapeutic proteins, especially within the tumor vicinity, can be affected by proteolytic degradation, the perception of Omomyc as a valid therapeutic agent has been often questioned. In this study, we used a mass spectrometry approach to evaluate the stability of Omomyc in tumor biopsies from murine xenografts following its intravenous administration. Our data strongly support that the integrity of the functional domains of Omomyc (DNA binding and dimerization region) remains preserved in the tumor tissue for at least 72 hours following administration and that the protein shows superior pharmacokinetics in the tumor compartment compared with blood serum.

Adrenal gene expression dynamics support hibernation in 13-lined ground squirrels.

Hibernation is a natural model of extreme physiology in a mammal. Throughout winter, small hibernators repeatedly undergo rapid, dramatic swings in body temperature, perfusion, and oxygen delivery. To gain insight into the molecular mechanisms that support homeostasis despite the numerous challenges posed by this dynamic physiology, we collected 13-lined ground squirrel adrenal glands from at least five individuals representing six key timepoints across the year using body temperature telemetry. Differentially expressed genes were identified using RNA-seq, revealing both strong seasonal and torpor-arousal cycle effects on gene expression. Two novel findings emerge from this study. First, transcripts encoding multiple genes involved in steroidogenesis decreased seasonally. Taken together with morphometric analyses, the data are consistent with preservation of mineralocorticoids but suppression of glucocorticoid and androgen output throughout winter hibernation. Second, a temporally orchestrated, serial gene expression program unfolds across the brief arousal periods. This program initiates during early rewarming with the transient activation of a set of immediate early response (IER) genes, comprised of both transcription factors and the RNA degradation proteins that assure their rapid turnover. This pulse in turn activates a cellular stress response program to restore proteostasis comprised of protein turnover, synthesis, and folding machinery. These and other data support a general model for gene expression across the torpor-arousal cycle that is facilitated in synchrony with whole body temperature shifts; induction of the immediate early response upon rewarming activates a proteostasis program followed by a restored tissue-specific gene expression profile enabling renewal, repair, and survival of the torpid state.NEW & NOTEWORTHY This pioneer study of adrenal gland gene expression dynamics in hibernating ground squirrels leverages the power of RNA-seq on multiple precisely timed samples to demonstrate: 1) steroidogenesis is seasonally reorganized to preserve aldosterone at the expense of glucocorticoids and androgens throughout winter hibernation; 2) a serial gene expression program unfolds during each short arousal whereby immediate early response genes induce the gene expression machinery that restores proteostasis and the cell-specific expression profile before torpor reentry.