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Ocean pollution by plastics is a growing concern for marine wildlife conservation, and seabirds are particularly prone to ingest plastics. We report baseline information on plastic ingestion in 17 procellariiform species along the coast of Brazil and Argentina. Through a collaborative regional effort we found plastic items in 30.2 % of seabird carcasses examined (n = 192), comprised predominantly by mesoplastics (5-25 mm), user plastics, polypropylene, polystyrene and polyethylene. Considering the most representative source-site cohorts, the frequency of occurrence of plastic items varied significantly between sampling site and source of carcasses. Ingestion was highest in petrels and shearwaters. Immature birds ingested the largest number (and total mass) of plastic items followed by chicks and adults. Long-term programs applying standardized sampling protocols are needed to detect spatiotemporal patterns of plastic ingestion across species, and assess the potential effectiveness of remediation actions. Further studies are necessary to assess currently unrecognized health effects of plastic ingestion., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: In the Peruvian Amazon, Plasmodium vivax malaria transmission is maintained due to the high frequency of recurrences. By understanding the recurrence rates of submicroscopic and asymptomatic cases, we can develop informed strategies to prevent transmission more efficiently and disrupt the silent transmission cycle., Methods: A three-year, population-based cohort study was conducted in two sites, Cahuide and Lupuna, within the Loreto region in Peru from 2013 to 2015. The study included 385 individuals and aimed to examine the temporal dynamics of malaria recurrences and their impact on transmission and control., Results: Individuals from Lupuna presented a higher risk of P. vivax infections compared to Cahuide, where most recurrences were asymptomatic and submicroscopic. It is estimated that a great proportion of these recurrences were due to relapses in both communities. The application of molecular diagnostic method proved to be significantly more effective, detecting 2.3 times more episodes during the follow-up (PCR, 1068; microscopy, 467). PCR identified recurrences significantly earlier, at 151 days after an initial infection, compared to microscopy, which detected them on average after 365 days. Community, occupation and previous malaria infections were factors associated with recurrences. Finally, potential infection evolution scenarios were described where one frequent scenario involved the transition from symptomatic to asymptomatic infections with a mean evolution time of 240 days., Conclusions: This study explores the contrast in malaria recurrence risk among individuals from two endemic settings, a consequence of prolonged exposure to the parasite. Through the analysis of the evolution scenarios of P. vivax recurrences, it is possible to have a more complete vision of how the transmission pattern changes over time and is conditioned by different factors., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Garcia Castillo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Aqueous vitrification (glass formation) processes are integral to modern cryopreservation, but experimental methods by which to study them are limited, particularly at the mL volume scales relevant to many biomedical applications. Here, we introduce an inexpensive custom optical platform, the isochoric vitrification cryo-macroscope (or "isovitriscope"), to supplement standard techniques with new qualitative and quantitative data streams. The platform consists of an LED light source, a isochoric (constant-volume) chamber with sapphire optical windows, and a camera, which can operate in two modes. One mode enables sharp visual observation of the glass transition and other low-temperature physical processes, including cracking, annealing, ice and hydrate crystallization, cavity formation, melting, etc. The other mode enables tracking of the optical temperature-evolution of the system via recorded light intensity, which we demonstrate may be used to measure the onset glass transition temperature with accuracy similar to differential scanning calorimetry (DSC), and to identify the temperature coordinates of other phase change events. The isovitriscope thus offers a single device combining the phenomenological insight of conventional visual inspection with the quantitative insight of techniques like calorimetry, at the >1 mL volume scales increasingly relevant to cryopreservation applications. To demonstrate uses of the isochoric optical platform, we herein conduct a series of observational studies examining the rich multi-phase phenomena at play during isochoric vitrification of binary cryoprotectant solutions; the effect of surface wettabilities on crack formation in the glassy state; the analogy between differential calorimetric and optical analysis; and more. In summary, the isochoric vitrification cryo-macroscope, or isovitriscope, adds a valuable new tool for the study of aqueous vitrification processes., Competing Interests: The authors declare no competing interests., (This journal is © The Royal Society of Chemistry.)

Enormous efforts have been made to understand the functions of bioluminescence; however, its relevance in soil ecosystems has barely been investigated. In addition, our understanding of the biological relevance of bioluminescence is hampered by the scarcity of tools to genetically manipulate this trait. Using the symbionts of entomopathogenic nematodes, Photorhabdus bacteria, we show that bioluminescence plays important regulatory roles in multitrophic interactions in the soil. Through genetic modifications and exploiting natural variability, we provide direct evidence for the multifunctional nature of bioluminescence. It regulates abiotic and biotic stress resistance, impacts other trophic levels, including nematodes, insects, and plants, and contributes to symbiosis. Our study contributes to understanding the factors that have driven the evolution and maintenance of this trait in belowground ecosystems., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Microporous glassy polymer membranes suffer from physical aging, which adversely affects their performance in the short time frame. We show that the aging propensity of a model microporous polymer, poly(1-trimethylsilyl-1-propyne) (PTMSP), can be effectively mitigated by blending with as little as 5 wt % porous polymer network (PPN) composed of triptycene and isatin. The aging behavior of these materials was monitored via N 2 pure gas permeability measurements over the course of 3 weeks, showing a 14% decline in PTMSP blended with 5 wt % PPN vs a 41% decline in neat PTMSP. Noteworthy, PPNs are 2 orders of magnitude cheaper than the porous aromatic frameworks previously used to control PTMSP aging. A variety of experimental and computational techniques, such as Positron Annihilation Lifetime Spectroscopy (PALS), free volume measurements, cross-polarization/magic angle spinning (CP/MAS) 13 C NMR, transport measurements and molecular dynamics (MD) simulations were used to uncover the molecular mechanisms leading to enhanced aging resistance. We show that partial PTMSP chain adsorption into the PPN porosity reduces the PTMSP local segmental mobility, leading to improved aging resistance. Permeability coefficients were broken into their elementary sorption and diffusion contributions, to elucidate the mechanism by which the reduced PTMSP local segmental mobility affects selectivity in gas separation applications. Finally, we demonstrate that in these systems, where both chemical and physical interactions take place, transport coefficients must be corrected for thermodynamic nonidealities to avoid erroneous interpretation of the results.

Microquasars are laboratories for the study of jets of relativistic particles produced by accretion onto a spinning black hole. Microquasars are near enough to allow detailed imaging of spatial features across the multiwavelength spectrum. The recent extension measurement of the spatial morphology of a microquasar, SS 433, to TeV gamma rays 1 localizes the acceleration of electrons at shocks in the jet far from the black hole 2 . V4641 Sagittarii (V4641 Sgr) is a similar binary system with a black hole and B-type main-sequence companion star and has an orbit period of 2.8 days (refs.  3,4 ). It stands out for its super-Eddington accretion 5 and for its radio jet, which is one of the fastest superluminal jets in the Milky Way. Previous observations of V4641 Sgr did not report gamma-ray emission 6 . Here we report TeV gamma-ray emission from V4641 Sgr that reveals particle acceleration at similar distances from the black hole as SS 433. Furthermore, the gamma-ray spectrum of V4641 Sgr is among the hardest TeV spectra observed from any known gamma-ray source and is detected above 200 TeV. Gamma rays are produced by particles, either electrons or protons, of higher energies. Because energetic electrons lose energy more quickly the higher their energy, such a spectrum either very strongly constrains the electron-production mechanism or points to the acceleration of high-energy protons. This suggests that large-scale jets from microquasars could be more common than previously expected and that they could be a notable source of galactic cosmic rays 7-9 ., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Recent epidemiological data has shown a sharp increase in stimulant use among older adults, which is notable as older adults may be especially vulnerable to their cardiovascular effects. Results of recent studies have shown an increase in cardiovascular events among older adults using stimulants; however, little data exists comparing cardiovascular safety of these agents head-to-head. Objective: To determine if the incidence of serious cardiovascular events, including myocardial infarction (MI), stroke/transient ischemic attack (TIA), or arrhythmia, are different in patients taking amphetamine/dextroamphetamine compared with patients taking methylphenidate. Methods: Retrospective chart review of veterans 50 years and older at the Veterans Affairs North Texas Health Care System (VANTHCS) who were first prescribed a stimulant between 2015 and 2021. The primary outcome was the difference in composite cardiovascular events between amphetamine/dextroamphetamine and methylphenidate. Secondary outcomes were the composite cardiovascular endpoints compared individually (MI, stroke/TIA, or arrhythmia). Hazard ratios were calculated based off of a time-to-event analysis displayed using a Kaplan-Meier curve for primary and secondary outcomes. Results: 466 veterans were screened for inclusion, 30 were excluded, and 436 were included. There was no difference found in composite cardiovascular events between the 241 veterans in the amphetamine/dextroamphetamine group and the 195 veterans in the methylphenidate group with 12 (5%) vs 8 (4.1%) events respectively ( P = .6635). There was also no difference in time-to-event analysis ( P = .4966). Conclusion: In elderly veterans, there was no difference found in incidence of major cardiovascular events with the use of amphetamine/dextroamphetamine compared with methylphenidate., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: The Abbreviated Injury Scale (AIS) is widely used for body region-specific injury severity. The American Association for the Surgery of Trauma Organ Injury Scale (AAST-OIS) provides organ-specific injury severity but is not included in trauma databases. Previous researchers have used AIS as a surrogate for OIS. This study aims to assess AIS-abdomen concordance with AAST-OIS grade for liver and spleen injuries, hypothesizing concordance in terms of severity (grade of OIS and AIS) and patient outcomes., Study Design: This retrospective study (July 2020 to June 2022) was performed at 3 trauma centers. Adult trauma patients with AAST-OIS grade III to V liver and spleen injury were included. AAST-OIS grade for each organ was compared with AIS-abdomen by evaluating the percentage of AAST-OIS grade correlating with each AIS score as well as rates of operative intervention for these injuries. Analysis was performed with chi-square tests and univariate analysis., Results: Of 472 patients, 274 had liver injuries and 205 had spleen injuries grades III to V. AAST-OIS grade III to V liver injuries had concordances rates of 85.5%, 71%, and 90.9% with corresponding AIS 3 to 5 scores. AAST-OIS grade III to V spleen injuries had concordances rates of 89.7%, 87.8%, and 87.3%, respectively. There was a statistical lack of concordance for both liver and spleen injuries (both p < 0.001). Additionally, there were higher rates of operative intervention for AAST-OIS grade IV and V liver injuries and grade III and V spleen injuries vs corresponding AIS scores (p < 0.05)., Conclusions: AIS should not be used interchangeably with OIS due to lack of concordance. AAST-OIS should be included in trauma databases to facilitate improved organ injury research and quality improvement projects., (Copyright © 2024 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Backgroung: Mild traumatic brain injury (mTBI) encompasses a spectrum of disability including early cognitive impairment (ECI). The Brain Injury Guidelines suggest that patients with mTBI can be safely discharged from the emergency department. Although half of patients with mTBI with intracranial hemorrhage (ICH) have evidence of ECI, it is unclear what percentage of these patients' ECI persists after discharge. We hypothesize a significant proportion of trauma patients with mTBI and ECI at presentation have persistent ECI at 30-day follow-up., Study Design: A single-center prospective cohort study including adult trauma patients with ICH or skull fracture and a Glasgow Coma Scale of 13 to 15 on arrival was performed. Participants were screened for ECI using the Rancho Los Amigos Scale (RLA), and ECI was defined as an RLA less than 8. We compared ECI and non-ECI groups for demographics, injury profile, CT imaging (eg Rotterdam CT score) and outcomes with bivariate analysis. Thirty-day follow-up telephone calls were performed to re-evaluate RLA for persistent ECI and concussion symptoms., Results: From 62 patients with ICH or skull fracture and mTBI, 21 (33.9%) had ECI. Patients with ECI had a higher incidence of subarachnoid hemorrhage (85.7% vs 46.3%, p = 0.003) and higher Rotterdam CT score (p = 0.004) compared with those without ECI. On 30-day follow-up, 6 of 21 (26.6%) patients had persistent ECI. In addition, 7 (33.3%) patients had continued concussion symptoms., Conclusions: More than one-third of mTBI patients with ICH had ECI. At 30-day postdischarge follow-up, more than one-fourth of these patients had persistent ECI and 33% had concussion symptoms. This highlights the importance of identifying ECI before discharge as a significant portion may have ongoing difficulties reintegrating into work and society., (Copyright © 2024 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Pain is a hallmark symptom of knee osteoarthritis (KOA), yet intensity and severity vary widely among individuals. There is a knowledge gap in understanding key characteristics of high-impact chronic pain (HICP) within the context of KOA. Therefore, our first purpose was to examine the prevalence of HICP in a cohort of individuals with radiographic evidence of KOA, and our second purpose was to assess patient-level factors associated with HICP. Data from the Johnston County Health Study were used to compare those with and without HICP. Variables included sociodemographic factors, clinical factors, health care use, and psychosocial distress. HICP status was classified with Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Interference and Physical Function measures. The results indicated that 15.5% (48/310) of participants were classified as having HICP when the PROMIS-Pain Interference cutoff score was used, while 21.2% (66/310) were classified as having HICP with a PROMIS-Physical Function cutoff score. Multivariable analyses indicated that HICP was consistently characterized by increased kinesiophobia and somatization, regardless of PROMIS measure used for HICP status. A secondary insight was that HICP was not consistently characterized by sociodemographic and clinical variables, as these findings were dependent on PROMIS measure used. These findings could be used to develop intervention approaches specific to individuals with KOA and to inform future investigations of sociodemographic and clinical factors associated with HICP. PERSPECTIVE: These findings provide additional information on the characterization of HICP for individuals with KOA. There was consistency in psychosocial factors associated with HICP, while sociodemographic and clinical factors varied based on how HICP status was defined., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: One third of organ donors suffer catastrophic brain injury (CBI). There are no standard guidelines for the management of traumatic CBI prior to brain death, and not all trauma centers have institutional CBI guidelines. In addition, there is high variability in management between institutions with guidelines. Catastrophic brain injury guidelines vary and may include various combinations of hormone therapy, vasopressors, fluid resuscitation, and other practices. We hypothesized that centers with CBI guidelines have higher organ donation rates than those without., Methods: This prospective, observational EAST-sponsored multicenter trial included adult (18+ years old) traumatic-mechanism CBI patients at 33 level I and II trauma centers from January 2022 to May 2023. Catastrophic brain injury was defined as a brain injury causing loss of function above the brain stem and subsequent death. Cluster analysis with linear mixed-effects model including UNOS regions and hospital size by bed count was used to determine whether CBI guidelines are associated with organ donation., Results: A total of 790 CBI patients were included in this analysis. In unadjusted comparison, CBI guideline centers had higher rates of organ donation and use of steroids, whole blood, and hormone therapy. In a linear mixed-effects model, CBI guidelines were not associated with organ donation. Registered organ donor status, steroid hormones, and vasopressin were associated with increased relative risk of donation., Conclusion: There is high variability in management of CBI, even at centers with CBI guidelines in place. While the use of institutional CBI guidelines was not associated with increased organ donation, guidelines in this study were not identical. Hormone replacement with steroids and vasopressin was associated with increased donation. Hormone resuscitation is a common feature of CBI guidelines. Further analysis of individual practices that increase organ donation after CBI may allow for more effective guidelines and an overall increase in donation to decrease the long waiting periods for organ transplant recipients., Level of Evidence: Prognostic; Level III., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Harsh early environmental conditions can exert delayed, long-lasting effects on phenotypes, including reproductive traits such as sexual signals. Indeed, adverse early conditions can accelerate development, increasing oxidative stress that may, in turn, impact adult sexual signals. Among signals, colorations produced by red ketocarotenoids seem to depend on mitochondrial functioning. Hence, they could reveal individual cell respiration efficiency. It has been hypothesized that these traits are unfalsifiable "index" signals of condition due to their deep connection to individual metabolism. Since mitochondrial dysfunction is frequently linked to aging, red ketocarotenoid-based ornaments could also be good signals of a critical fitness component: longevity. We tested this red color per longevity correlation in captive zebra finches. In addition, we experimentally decreased the synthesis of glutathione (a critical intracellular antioxidant) during the first days of the birds' life to resemble harsh early environmental conditions (e.g., undernutrition). Longevity was recorded until the death of the last bird (almost 9 years). Males, but not females, exhibiting a redder bill in early adulthood lived longer than males with paler bills, which agrees with some precedent studies. However, such bill redness-longevity connection was absent among males with inhibited glutathione synthesis. These findings may suggest that environmental factors can alter the reliability of red ketocarotenoid-based sexual signals, making them less unfalsifiable than believed., (© 2024 The Author(s). Journal of Experimental Zoology Part A: Ecological and Integrative Physiology published by Wiley Periodicals LLC.)

Background: A drastic increase in carbapenem resistance among Klebsiella pneumoniae isolates occurred during the period 2019-22. Three epidemiological changes could be evidenced: (i) NDM became the predominant carbapenemase; (ii) NDM-5 replaced NDM-1; and (iii) the emergence of NDM-producing K. pneumoniae ST258 (NDM-KpST258)., Materials and Methods: Carbapenem-resistant K. pneumoniae isolates from patients on the ICU of a university hospital of Buenos Aires were studied during the period 2019-22. Identification was performed by MS and susceptibility by the Phoenix system (broth microdilution for colistin). Carbapenemase production was detected phenotypically. Molecular studies included PCR with specific primers and WGS (in some isolates)., Results: NDM-producing K. pneumoniae was statistically associated with the use of ceftazidime/avibactam between 2019 and April 2021, whereas in the period from May 2021 to December 2022, it seemed to be related to the presence of NDM-5-KpST258. A gradual increase in the number of urease-negative NDM-Kp-ST258 during 2019-22 was observed. The plasmid origin of NDM-5 was supported by its presence on the IncFII incompatibility group plasmid., Conclusions: Our study describes the first outbreak of NDM5-KpST258 at an ICU in Argentina, remarkably associated with considerable changes in the carbapenemase epidemiology. The intrinsic characteristics of ST258 may contribute to increased spread of NDM in hospital settings, resembling KPC-2 dissemination., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

In many vertebrates, dietary yellow carotenoids are enzymatically transformed into 4C-ketocarotenoid pigments, leading to conspicuous red colourations. These colourations may evolve as signals of individual quality under sexual selection. To evolve as signals, they must transmit reliable information benefiting both the receiver and the signaler. Some argue that the reliability of 4C-ketocarotenoid-based colourations is ensured by the tight link between individual quality and mitochondrial metabolism, which is supposedly involved in transforming yellow carotenoids. We studied how a range of carotenoids covary in the feathers and blood plasma of a large number (n > 140) of wild male common crossbills (Loxia curvirostra). Plumage redness was mainly due to 3-hydroxy-echinenone (3HOE). Two other, less abundant, red 4C-ketocarotenoids (astaxanthin and canthaxanthin) could have contributed to feather colour as they are redder pigments. This was demonstrated for astaxanthin but not canthaxanthin, whose feather levels were clearly uncorrelated to colouration. Moreover, moulting crossbills carried more 3HOE and astaxanthin in blood than non-moulting ones, whereas canthaxanthin did not differ. Canthaxanthin and 3HOE can be formed from echinenone, a probable product of dietary β-carotene ketolation. Echinenone could thus be ketolated or hydroxylated to produce canthaxanthin or 3HOE, respectively. In moulting birds, 3HOE blood levels positively correlated to astaxanthin, its product, but negatively to canthaxanthin levels. Redder crossbills also had lower plasma canthaxanthin values. A decrease in hydroxylation relative to ketolation could explain canthaxanthin production. We hypothesize that red colouration could indicate birds' ability to avoid inefficient deviations within the complex enzymatic pathways., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Several medium chain fatty acids and different chemical forms of these acids were evaluated in vitro as treatments of aerobically-exposed corn silage against spoilage and pathogenic microbes and for effects on rumen fermentation. Treatments were control (no additive), myristate (MY), laurate (LA), monolaurin (MLA), methyl ester laurate (MELA), a blend of mono-, di- and triglycerides of laurate (BLA), and monocaprylate (MC). After 24 h of aerobic incubation (37°C), yeast and mold growth were not influenced ( P > 0.05) by treatments, while the net growth of lactic acid bacteria was decreased, albeit slightly, compared to that by untreated controls ( P < 0.01) by all treatments of the air-exposed corn silage. Compared with controls, wild-type enterococci were decreased ( P < 0.01) in MLA, MELA, and BLA. Staphylococcus aureus was reduced ( P < 0.01) with MLA, MELA, BLA, and MC. Total aerobes showed reductions ( P < 0.01) with MLA, BLA, and MC. Listeria monocytogenes numbers were reduced ( P < 0.01) with MELA. Anaerobic incubation (24 h; 39°C) of ruminal fluid (10 mL) with 0.2 g air-exposed and MCFA-treated corn silage revealed higher hydrogen accumulations ( P < 0.01) with MLA and MC over the control treatment. Methane was decreased ( P < 0.01) solely by MLA. There was an increase ( P < 0.01) of acetate with MELA and MC; of propionate with MELA or by BLA; and of butyrate with MLA, MELA, BLA, and MC. Total VFA, hexose fermented, and ammonia were increased ( P < 0.01) with MELA, BLA, and MC. The acetate:propionate ratio was increased ( P < 0.01) with MC. The results showed that treatment of air-exposed corn silage with esterified MCFA had no effect on yeasts and molds but prevented propagation or reduced populations of some unwanted and potentially desirable bacteria. Modest methane reduction was seen during in vitro incubation of rumen fluid suspensions with MLA-treated silage and ammonia accumulations were increased in esterified MCFA-treated silage. Little, if any, other detrimental effects on beneficial ruminal fermentation characteristics were observed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Salinas-Chavira, Arzola-Alvarez, Hume, Fonseca, Ruiz-Barrera, Castillo-Castillo, Ontiveros-Magadan, Jones, Crippen, Poole, Zuñiga-Serrano and Anderson.)

Context: During the COVID-19 pandemic, the United States relied on the public health workforce to control the spread of COVID-19 while continuing to provide foundational public health services. Facing longstanding staffing shortages, state, tribal, local, and territorial (STLT) public health agencies (PHAs) used various strategies and supports to surge the workforce in response to the pandemic., Objectives: The study explored (1) the types of strategies and supports STLT PHAs used to surge the public health workforce during the pandemic, (2) assessments of surge strategies and supports, and (3) approaches to using the range of surge strategies available., Design: We conducted 27 semi-structured interviews in 2023 and performed thematic analysis., Participants: Interviewees included STLT public health officials, leaders of organizations that directly supported the COVID-19 workforce surge, and public health workforce experts indirectly involved in the workforce surge., Results: To surge the workforce, interviewees relied on partnerships, staffing agencies, the National Guard, the Centers for Disease Control and Prevention Foundation's COVID-19 Corps, the Medical Reserve Corps, and other strategies. Interviewees valued strategies that rapidly engaged staff and volunteers at no cost to their PHA and flexible funding from the federal government to support surge efforts but noted shortcomings in the strategies and supports available. Interviewees described using multiple strategies simultaneously but noted challenges in implementing these strategies due to inadequate planning and insufficient staff and resources., Conclusion: The study underscores the need for STLT PHAs to establish mechanisms to surge the workforce as part of ongoing planning for emergency preparedness. Focus areas include building administrative and hiring capacity within STLT PHAs and sustaining partnerships and contractual agreements that helped fill staffing gaps during the pandemic. To support efforts to build workforce capacity to meet future surge management needs, STLT PHAs should consider creative solutions to attract and retain staff, as well as opportunities to engage students in public health work., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Psychosocial evaluation for transplant suitability is required by the Centers for Medicare and Medicaid Services (CMS) as a condition of participation for transplant programs. There are no regulations regarding follow-up reassessment for transplant readiness after waitlisting., Objectives: An evidence-based pilot project was developed and implemented to evaluate the feasibility of psychosocial readiness assessments for waitlisted heart transplantation candidates. The primary aim was to test the feasibility of these assessments in practice from a patient and programmatic perspective., Methods: During a 12-week period, waitlisted outpatients underwent one assessment each. Socioeconomic elements of caregiver support, housing, transportation, and insurance coverage status were assessed by simple using "yes/no" questions. To assess mental health needs, the General Anxiety Disorder-7 questionnaire (GAD-7) and the Patient Health Questionnaire-8 (PHQ-8) tools were utilized. Rescheduled readiness visits and no-show rates were measured. A post-implementation Qualtrics survey was administered to measure team member perceptions of feasibility., Results: A total of 57 patients were assessed during the 12-week period. The primary aim of feasibility was achieved with 93 % of visits performed with freedom from rescheduling or patient no-show to the visit. Additionally, 75 % of team members reported the readiness assessments were feasible to complete in practice., Conclusions: Addressing the non-medical and mental health needs of waitlisted heart transplant patients allows transplant programs to maintain candidates with necessary resources and care. The readiness assessments are feasible in practice and may serve to reduce untoward outcomes in the post-transplant phase by providing targeted care prior to the time of transplant., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Maryjane Farr reports a relationship with TransMedics Inc that includes: consulting or advisory. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

The triggering receptor expressed on myeloid cells-2 (TREM2), a pivotal innate immune receptor, orchestrates functions such as inflammatory responses, phagocytosis, cell survival, and neuroprotection. TREM2 variants R47H and R62H have been associated with Alzheimer's disease, yet the underlying mechanisms remain elusive. Our previous research established that TREM2 binds to heparan sulfate (HS) and variants R47H and R62H exhibit reduced affinity for HS. Building upon this groundwork, our current study delves into the interplay between TREM2 and HS and its impact on microglial function. We confirm TREM2's binding to cell surface HS and demonstrate that TREM2 interacts with HS, forming HS-TREM2 binary complexes on microglia cell surfaces. Employing various biochemical techniques, including surface plasmon resonance, low molecular weight HS microarray screening, and serial HS mutant cell surface binding assays, we demonstrate TREM2's robust affinity for HS, and the effective binding requires a minimum HS size of approximately 10 saccharide units. Notably, TREM2 selectively binds specific HS structures, with 6-O-sulfation and, to a lesser extent, the iduronic acid residue playing crucial roles. N-sulfation and 2-O-sulfation are dispensable for this interaction. Furthermore, we reveal that 6-O-sulfation is essential for HS-TREM2 ternary complex formation on the microglial cell surface, and HS and its 6-O-sulfation are necessary for TREM2-mediated ApoE3 uptake in microglia. By delineating the interaction between HS and TREM2 on the microglial cell surface and demonstrating its role in facilitating TREM2-mediated ApoE uptake by microglia, our findings provide valuable insights that can inform targeted interventions for modulating microglial functions in Alzheimer's disease., Competing Interests: Conflicts of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To examine associations of vibration sensitivity and pressure pain sensitivity with knee osteoarthritis (OA) outcomes across sex and race, which may relate to known sex and race disparities in clinical outcomes., Design: Data were from the 2013-2015 visit of the Johnston County Osteoarthritis Project. Exposures were vibration perception threshold (VPT) measured at the bilateral medial femoral condyle (MFC) and first metatarsophalangeal joint (MTP), and pressure pain threshold (PPT) measured at the bilateral upper trapezius. Outcomes were knee pain severity and presence of knee symptoms, radiographic knee OA, and symptomatic knee OA in each knee. Cross-sectional associations of the exposures with the outcomes were examined using logistic regression models, overall and separately by sex and race., Results: In the VPT and PPT analyses, 851 and 862 participants (mean age 71 years, 68% female, 33% Black, body mass index 31 kg/m 2 ) and 1585 and 1660 knees were included, respectively. Higher VPT (lower vibration sensitivity) at the MFC and first MTP joint was associated with all outcomes. Lower PPT (greater pressure pain sensitivity) was associated with greater knee pain severity. Associations of VPT and PPT with all outcomes were similar among females and males and Black and White individuals., Conclusions: Diminished vibration perception and greater pressure pain sensitivity were cross-sectionally associated with worse knee OA outcomes. Despite differences in VPT and PPT among females and males and Black and White adults, associations with knee OA outcomes did not differ by sex or race, suggesting neurophysiological differences do not relate to established disparities., Competing Interests: Conflict of interest CYL: None; LMT: NIH/NIAMS funding outside this work, Editorial Board Member of Arthritis Care & Research; CA: Editorial Board Member of Arthritis Care & Research; DLG: None; AEN: Associate Editor of Osteoarthritis and Cartilage, Editorial Board Member of Arthritis Care & Research, NIH/NIAMS funding outside this work, honoraria from Nestle Health and MedScape; APG: NIH/NIAMS funding outside this work; KCF: NIH/NIAMS funding outside this work; YMG: Associate Editor of Osteoarthritis and Cartilage, Editorial Board Member of Arthritis Care & Research, NIH/NIAMS funding outside this work., (Copyright © 2024 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

HTLV-1-associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) is a progressive non-remitting and incapacitating disease more frequently seen in women and with a patchy worldwide distribution. HAM/TSP develops in a small percentage of HTLV-1-infected individuals during their lifetime and etiologic factors for disease progression are still unclear. This study aims to describe the first case series of the progression of HAM/TSP in relation to pregnancy. Between January and March of 2012, we reviewed medical charts of women with HAM/TSP currently enrolled in the HTLV-1 cohort at the institute of tropical medicine of Cayetano Heredia University. Inclusion criteria included having a diagnosis of HAM/TSP according to the WHO guidelines and self-reported initial symptoms of HAM/TSP during pregnancy or within six months of delivery. Fifteen women reported having had symptoms compatible with HAM/TSP within four months of delivery. Among them, ten women had no symptoms before pregnancy and reported gait impairment after delivery. Five women with mild gait impairment before pregnancy noticed a worsening of their symptoms after delivery. Symptoms worsened after successive pregnancies. Recent studies have shown that HTLV-1 infection induces a strong T cell-mediated response and that the quality of this response plays a role in HAM/TSP pathogenesis. The relative immunosuppression during pregnancy, including blunting of the T-cell response, might allowed in certain women enhanced replication of HTLV-1 and disease progression in the postpartum. This is the first study looking specifically at HAM/TSP and pregnancy and the number of cases is remarkable. Further prospective studies of HTLV-1-infected women assessing immune markers during pregnancy are warranted. Breastfeeding was the main route of transmission. Strategies to prevent vertical transmission need to be evaluated in HTLV-1 endemic countries of Latin America.

Background: Current guidelines recommend 24-hour telemetry monitoring for isolated sternal fractures (ISFs) with electrocardiogram (ECG) abnormalities or troponin elevation. However, a single-center study suggested ISF patients with minor ECG abnormalities (sinus tachycardia/bradycardia, nonspecific arrhythmia/ST-changes, and bundle branch block) may not require 24-hour telemetry monitoring. This study sought to corroborate this, hypothesizing ISF patients would not develop blunt cardiac injury (BCI)., Materials & Methods: A retrospective study was performed at 8 trauma centers (1/2018-8/2020). Patients with ISF (abbreviated injury scale <2 for the head/neck/face/abdomen/extremities) and minor ECG abnormalities or troponin elevations were included. Patients with multiple rib fractures or hemothorax/pneumothorax were excluded. The primary outcome was an echocardiogram confirmed BCI. The secondary outcome was significant BCI defined as cardiogenic shock, dysrhythmia requiring treatment, post-traumatic cardiac structural defects, unexplained hypotension, or cardiac-related procedures. Descriptive statistics were performed., Results: Of 124 ISF patients with minor ECG abnormalities or troponin elevation, 90% were admitted with a mean stay of 35 hours. Echocardiogram was performed for 31.5% of patients, 10 (25.6%) of which had abnormalities. However, no patient had BCI diagnosed on echocardiography. In total, 2 patients (1.6%) had a significant BCI (atrial fibrillation and supraventricular tachycardia at 10 and 82 hours after injury). No patient died., Conclusions: Following ISF with minor ECG changes or troponin elevation, <2% suffered significant BCI, and none had an echocardiogram diagnosed BCI, despite >30% receiving echocardiogram. These findings challenge the dogma of mandatory observation periods following ISF with associated ECG abnormalities and support the lack of utility for routine echocardiography in these patients., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

DIGEST is a validated, open-source method to grade the severity of pharyngeal dysphagia from the modified barium swallow (MBS) study. Dissemination and implementation of DIGEST is rising, making it critical to understand reliability and facilitators of accurate implementation among users. The aim was to assess reliability of the tool among speech-language pathology (SLP) raters practicing at multiple sites before and after review of a DIGEST training manual and evaluate confidence of DIGEST use pre-and post-training. Thirty-two SLPs from 5 sites participated in a blinded longitudinal DIGEST rating study. Raters were provided a standardized training set of MBS (n = 19). Initial SLP ratings (round 1, R1) were followed by a 2-4 week break before raters rated a re-keyed MBS set (round 2, R2). A minimum 4-8 week wash-out period then preceded self-study of the DIGEST training manual which was followed by a final rating (round 3, R3) and a post-manual survey afterwards. Baseline reliability (R1) of overall DIGEST was on average k = 0.70, reflecting agreement in the substantial range. Seventy-five percent of raters (24/32) demonstrated reliability ≥ 0.61 in the substantial to almost perfect range prior to training. Inter-rater reliability significantly improved from R1 to R3 after review of the DIGEST manual, with the largest change in DIGEST-Efficiency (mean change: DIGEST k = .04, p = .009, DIGEST-Safety k = .07, p = 0.03, and DIGEST-Efficiency k = .14, p = 0.009). Although DIGEST reliability at baseline was adequate in the majority of raters, self-study of the DIGEST training manual significantly improved inter-rater reliability and rater confidence using the DIGEST method, particularly when assigning DIGEST-Efficiency grade. These early data show promise that provider training may be useful to aid in fidelity of DIGEST implementation among SLP clinical users with varying DIGEST experience., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Atrial fibrillation (AF) is common among patients with hypertrophic cardiomyopathy (HCM) with a prevalence greater than 25%. AF in HCM is associated with a high risk of stroke and can be a marker of more advanced cardiomyopathy. Although, it frequently results in cardiac hemodynamic changes which are poorly tolerated, it can be subclinical. Thus, prompt diagnosis and adequate management of AF are essential to minimizing AF-related adverse outcomes in HCM. All HCM patients should be screened for AF regularly, and those with high-risk features should be screened more frequently preferably with extended ambulatory monitoring. Once AF is detected, oral anticoagulation should be initiated. Both general and HCM-specific modifiable risk factors should be addressed and assessment for cardiomyopathy progression should be performed. Although no randomized controlled studies have compared rate versus rhythm control in HCM, early rhythm control could be considered to prevent further LA remodeling., Competing Interests: Dr Weissler-Snir has received speaker fees from Bristol Myer Squibb; and fees for publication steering committee participation for Cytokinetics and research grants from 10.13039/100004374Medtronic. Dr Rader has received consultant and speaker fees from Bristol Myer Squibbs, Medtronic, Recor Medical, and Cytokinetics. Dr Saberi has received consultant/advisor fees from Bristol Myers Squibb; and has received research grants from Bristol Myers Squibb, 10.13039/100014941Cytokinetics, 10.13039/100004336Novartis, and 10.13039/100005646Actelion Pharmaceuticals. Dr Wong is the site principal investigator for clinical trials sponsored by Bristol Myers Squibb, Cytokinetics, and Tenaya Therapeutics; and discloses unpaid advisory board participation for Bristol Myers Squibb and Cytokinetics. Dr Owens has received consulting/research support from 10.13039/100014941Cytokinetics, MyoKardia/Bristol Myers Squibb, Pfizer, Lexicon Pharmaceuticals, Tenaya Therapeutics, Stealth BioTherapeutics, Renovacor, Edgewise Therapeutics, BioMarin Pharmaceuticals, and Lexeo Therapeutics., (© 2024 The Authors.)

Background: This study aimed to examine the effects of a six-week of concurrent training using high-intensity interval plus resistance training on flow-mediated dilation and pulse wave velocity in hypertensive, elevated blood pressure, or normotensive. A secondary goal was to analyze the inter-individual variability., Methods: A randomized controlled clinical trial was executed with 60 adult participants distributed across six groups: three control groups of hypertensive, elevated blood pressure, or normotensive and other three experimental hypertensive, elevated blood pressure, and normotensive groups, each comprising n=10 individuals. Participants underwent a six-week intervention of concurrent exercise using high-intensity interval plus resistance training three-weekly. Flow mediated dilation and pulse wave velocity and secondary vascular assessments were conducted before and after the intervention., Results: The hypertensive exercise group exhibited a significant increase in flow mediated dilation (Δ+7.7%; p=0.003) and a reduction in pulse wave velocity (Δ-1.2ms -1 ; p<0.0001). The normotensive exercise group also showed a significant increase in flow mediated dilation (Δ+8.4%, p=0.002)., Conclusion: The six-week concurrent exercise using high-intensity interval plus resistance training protocol, characterized by its clinical time-efficiency, was effective in improving endothelial function, as demonstrated by increased flow mediated dilation, and in reducing arterial stiffness, indicated by decreased pulse wave velocity., (Copyright © 2024 SEH-LELHA. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: In high-resource settings, the survival of children with immunocompromise (IC) has increased and immunosuppressive therapies are increasingly being used. This study aimed to determine the clinical characteristics, performance of diagnostic tools, and outcome of IC children with tuberculosis (TB) in Europe., Methods: Multicenter, matched case-control study within the Pediatric Tuberculosis Network European Trials Group, capturing TB cases <18 years diagnosed 2000-2020., Results: A total of 417 TB cases were included, comprising 139 children who are IC (human immunodeficiency virus, inborn errors of immunity, drug-induced immunosuppression, and other immunocompromising conditions) and 278 non-IC children as controls. Nonrespiratory TB was more frequent among cases than controls (32.4% vs 21.2%; P = .013). Patients with IC had an increased likelihood of presenting with severe disease (57.6% vs 38.5%; P < .001; odds ratio [95% confidence interval], 2.073 [1.37-3.13]). Children with IC had higher rates of false-negative tuberculin skin test (31.9% vs 6.0%; P < .001) and QuantiFERON-TB Gold assay (30.0% vs 7.3%; P < .001) results at diagnosis. Overall, the microbiological confirmation rate was similar in IC and non-IC cases (58.3% vs 49.3%; P = .083). Although the mortality in children with IC was <1%, the rate of long-term sequelae was significantly higher than in non-IC cases (14.8% vs 6.1%; P = .004)., Conclusions: Children with IC and TB in Europe have increased rates of nonrespiratory TB, severe disease, and long-term sequelae. Immune-based TB tests have poor sensitivity in those children. Future research should focus on developing improved immunological TB tests that perform better in patients with IC, and determining the reasons for the increased risk of long-term sequelae, with the aim to design preventive management strategies., Competing Interests: Potential conflicts of interest . B. S. G. and M. T. have received support from Cepheid for a project on molecular tuberculosis diagnostics unrelated to the study reported here. M. T. has received QuantiFERON-TB assays at reduced pricing or free of charge for tuberculosis diagnostics projects from Cellestis/Qiagen in the past and has received support for conference attendance from Cepheid. The manufacturers had no influence on the study design, data collection, analysis or interpretation, writing of the manuscript, or the decision to submit the data for publication. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

In this research, several analyses were carried out on concentrated fractions of Mexican oregano essential oil ( Poliomintha longiflora Gray) in order to determine its ability to inhibit the growth and the motility of Escherichia coli (swimming), Pseudomonas aeruginosa (swimming), and Proteus vulgaris (swarming); these Gram-negative bacteria associated with urinary tract infections are motile due to the presence of flagella, which is considered an important virulence factor that favors their motility when trying to reach the target organ and cause an infection. Also, the resistance pattern to antibiotics of each strain was determined. The results showed resistance pattern (8 out of 12 antibiotics tested) for P. aureginosa , while E. coli and P. vulgaris were resistant to 4 antibiotics out of the 12 tested. On the other hand, fractionated oregano caused an inhibition of growth and a reduction in motility, varying between fractions and among bacteria. Fraction 4 showed major growth reduction, with MBC values ranging from 0.002 to 23.7 mg/mL. Treatment with fractionated oregano (F1, F2, F3, F4) reduced the motility by 92-81% for P. vulgaris , 90-83% for E. coli , and 100-8.9% for P. aeruginosa . These results demonstrated a higher performance with a lower application dose due to its high content of Carvacrol and Thymol; unlike other concentrated fractions, this synergy of oxygenated monoterpenes may cause greater antimicrobial activity.

Mammalian AIM-2-like receptor (ALR) proteins bind nucleic acids and initiate production of type I interferons or inflammasome assembly, thereby contributing to host innate immunity. In mice, the Alr locus is highly polymorphic at the sequence and copy number level, and we show here that it is one of the most dynamic regions of the genome. One rapidly evolving gene within this region, Ifi207 , was introduced to the Mus genome by gene conversion or an unequal recombination event a few million years ago. Ifi207 has a large, distinctive repeat region that differs in sequence and length among Mus species and even closely related inbred Mus musculus strains. We show that IFI207 controls murine leukemia virus (MLV) infection in vivo and that it plays a role in the STING-mediated response to cGAMP, dsDNA, DMXXA, and MLV. IFI207 binds to STING, and inclusion of its repeat region appears to stabilize STING protein. The Alr locus and Ifi207 provide a clear example of the evolutionary innovation of gene function, possibly as a result of host-pathogen co-evolution.IMPORTANCEThe Red Queen hypothesis predicts that the arms race between pathogens and the host may accelerate evolution of both sides, and therefore causes higher diversity in virulence factors and immune-related proteins, respectively . The Alr gene family in mice has undergone rapid evolution in the last few million years and includes the creation of two novel members, MndaL and Ifi207. Ifi207 , in particular, became highly divergent, with significant genetic changes between highly related inbred mice. IFI207 protein acts in the STING pathway and contributes to anti-retroviral resistance via a novel mechanism. The data show that under the pressure of host-pathogen coevolution in a dynamic locus, gene conversion and recombination between gene family members creates new genes with novel and essential functions that play diverse roles in biological processes., Competing Interests: The authors declare no conflict of interest.

Introduction: The formation of normal bone and bone healing requires the cAMP-responsive element binding protein 3-like-1 (Creb3l1) transmembrane transcription factor, as deletion of the murine CREB3L1 results in osteopenic animals with limited capacity to repair bone after a fracture. Creb3l1 undergoes regulated intramembrane proteolysis (RIP) to release the N-terminal transcription activating (TA) fragment that enters the nucleus and regulates the expression of target genes., Methods: To expand our understanding of Creb3l1's role in skeletal development and skeletal patterning, we aimed to generate animals expressing only the TA fragment of Creb3l1 lacking the transmembrane domain and thereby not regulated through RIP. However, the CRISPR/Cas9-mediated genome editing in zebrafish Danio rerio caused a frameshift mutation that added 56 random amino acids at the C-terminus of the TA fragment (TA+), making it unable to enter the nucleus. Thus, TA+ does not regulate transcription, and the creb3l1TA+/TA+ fish do not mediate creb3l1-dependent transcription., Results: We document that the creb3l1TA+/TA+ fish exhibit defects in the patterning of caudal fin lepidotrichia, with significantly distalized points of proximal bifurcation and decreased secondary bifurcations. Moreover, using the caudal fin amputation model, we show that creb3l1TA+/TA+ fish have decreased regeneration and that their regenerates replicate the distalization and bifurcation defects observed in intact fins of creb3l1TA+/TA+ animals. These defects correlate with altered expression of the shha and ptch2 components of the Sonic Hedgehog signaling pathway in creb3l1TA+/TA+ regenerates., Conclusion: Together, our results uncover a previously unknown intersection between Creb3l1 and the Sonic Hedgehog pathway and document a novel role of Creb3l1 in tissue patterning., (© 2024 S. Karger AG, Basel.)

Background: Disparities in hypertension control are well documented but underaddressed., Methods: RICH LIFE (Reducing Inequities in Care of Hypertension: Lifestyle Improvement for Everyone) was a 2-arm, cluster randomized trial comparing the effect on blood pressure (BP) control (systolic BP ≤140 mm Hg, diastolic BP ≤90 mm Hg), patient activation, and disparities in BP control of 2 multilevel interventions, standard of care plus (SCP) and collaborative care/stepped care (CC/SC). SCP included BP measurement standardization, audit and feedback, and equity-leadership training. CC/SC added roles to address social or medical needs. Primary outcomes were BP control and patient activation at 12 months. Generalized estimating equations and mixed-effects regression models with fixed effects of time, intervention, and their interaction compared change in outcomes at 12 months from baseline., Results: A total of 1820 adults with uncontrolled BP and ≥1 other risk factors enrolled in the study. Their mean age was 60.3 years, and baseline BP was 152.3/85.5 mm Hg; 59.4% were women; 57.4% were Black, 33.2% were White, and 9.4% were Hispanic; 74% had hyperlipidemia; and 45.1% had type 2 diabetes. CC/SC did not improve BP control rates more than SCP. Both groups achieved statistically and clinically significant BP control rates at 12 months (CC/SC: 57.3% [95% CI, 52.7%-62.0%]; SCP: 56.7% [95% CI, 51.9%-61.5%]). Pairwise comparisons between racial and ethnic groups showed overall no significant differences in BP control at 12 months. Patients with coronary heart disease showed greater achievement of BP control in CC/SC than in SCP (64.0% [95% CI, 54.1%-73.9%] versus 50.8% [95% CI, 42.6%-59.0%]; P =0.04), as did patients in rural areas (67.3% [95% CI, 49.8%-84.8%] versus 47.8% [95% CI, 32.4%-63.2%]; P =0.01). Individuals in both arms experienced statistically and clinically significant reductions in mean systolic BP (CC/SC: -13.8 mm Hg [95% CI, -15.2 to -12.5]; SCP: -14.6 mm Hg [95% CI, -15.9 to -13.2]) and diastolic BP (CC/SC: -6.9 mm Hg [95% CI, -7.8 to -6.1]; SCP: -5.5 mm Hg [95% CI, -6.4 to -4.6]) over time. The difference in diastolic BP reduction between CC/SC and SCP over time was statistically significant (-1.4 mm Hg [95% CI, -2.6 to -0.2). Patient activation did not differ between arms. CC/SC showed greater improvements in patient ratings of chronic illness care (Patient Assessment of Chronic Illness Care score) over 12 months (0.12 [95% CI, 0.02-0.22])., Conclusions: Adding a collaborative care team to enhanced standard of care did not improve BP control but did improve patient ratings of chronic illness care., Competing Interests: Dr Boonyasai’s contributions do not necessarily represent the views of the Department of Health and Human Services or the US government. Dr Crews has active research grants from Bayer and Somatus (paid to Johns Hopkins University). The other authors report no conflicts.

Background: The gene cAMP-Responsive Element Binding protein 3-like-1 (CREB3L1) has been implicated in bone development in mice, with CREB3L1 knock-out mice exhibiting fragile bones, and in humans, with CREB3L1 mutations linked to osteogenesis imperfecta. However, the mechanism through which Creb3l1 regulates bone development is not fully understood., Results: To probe the role of Creb3l1 in organismal physiology, we used CRISPR-Cas9 genome editing to generate a Danio rerio (zebrafish) model of Creb3l1 deficiency. In contrast to mammalian phenotypes, the Creb3l1 deficient fish do not display abnormalities in osteogenesis, except for a decrease in the bifurcation pattern of caudal fin. Both, skeletal morphology and overall bone density appear normal in the mutant fish. However, the regeneration of caudal fin postamputation is significantly affected, with decreased overall regenerate and mineralized bone area. Moreover, the mutant fish exhibit a severe patterning defect during regeneration, with a significant decrease in bifurcation complexity of the fin rays and distalization of the bifurcation sites. Analysis of genes implicated in bone development showed aberrant patterning of shha and ptch2 in Creb3l1 deficient fish, linking Creb3l1 with Sonic Hedgehog signaling during fin regeneration., Conclusions: Our results uncover a novel role for Creb3l1 in regulating tissue growth and patterning during regeneration., (© 2024 The Author(s). Developmental Dynamics published by Wiley Periodicals LLC on behalf of American Association for Anatomy.)

Introduction: Extensive research has explored the incorporation of humor in therapy, revealing its potential positive effects on clients' mental well-being and personal growth. However, limited research exists on how coaching could benefit from humor as an intervention and how its utilization impacts the interaction processes and outcomes for both the coachee and coach. Therefore, our research focuses on the use and effects of spontaneous humor within professional dialogues. This paper aims to extract insights from academic literature on humor in adjacent fields and apply these insights to the context of coaching., Methods: This paper offers implications for coaching theory and practice, alongside a proposed research agenda. The initial phase involves analyzing reviews on humor in professional contexts, and coaching. Secondly, following the PRISMA guidelines for review, we identified 13 empirical studies, which address the role of humor in counseling, psychotherapy, and mentoring., Results and Discussion: Our findings suggest that humor serves as a valuable tool for establishing and deepening the working alliance, fostering adaptive coping mechanisms in clients, and enhancing the cognitive and behavioral process. Moreover, humor is shown to be advantageous for professionals in navigating challenging client relationships. These findings hold significance for the realm of coaching practice as well. In light of these insights, we propose the integration of humor use in education toolkits for coaching professionals., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Vendl, Alvarado-Alvarez and Euwema.)

Background: Little is known about the association between active commuting (i.e., walking or cycling to school) with lifestyle parameters and mental health in youths. The objective of the present study was to investigate the association between mental health problems and symptoms of depression, anxiety, and stress with lifestyle (i.e., food habits, screen time, physical activity, and sleep quality), active commuting, and gender., Methods: A total of 511 children and adolescents (boys, n = 249; girls, n = 262) aged 10 to 17 years participated in the study. Lifestyle parameters and mental health were evaluated using the Depression Anxiety and Stress Scale (DASS-21)., Results: Girls reported higher levels of anxiety ( p = 0.001), depression ( p = 0.001), and stress ( p = 0.001). Mental health problems showed a positive association with gender (girls, β = 3.06, p < 0.001) and a negative association with food habits (β = -0.65, p = 0.019). Anxiety was positively associated with gender (β = 7.88, p < 0.001) and negatively associated with food habits (β = -0.23, p = 0.019). Gender (girls) and food habits were also associated with symptoms of depression (β = 2.29, p < 0.001 and β = -0.27, p = 0.005, respectively). Finally, active commuting was inversely associated with stress (β = -1.24, p = 0.008), and stress was positively linked to gender (β = 2.53, p < 0.001)., Conclusions: Active commuting, lifestyle parameters, and gender were associated with mental health in children and adolescents. Moreover, girls reported higher levels of anxiety, symptoms of depression, and stress.

Purpose: To analyze the effects of exergames on rehabilitation outcomes in osteoarthritis (OA) patients., Materials and Methods: A systematic review was reported according to the PRISMA statement. Randomized controlled trials (RCTs) were searched in Pubmed, Scopus, WoS, CINAHL, and PEDro (inception to November 2023). Studies that applied non-immersive exergames and assessed physical, functional, cognitive, pain, and psychosocial outcomes were included. Comparisons were other exercise modalities and non-intervention. Methodological quality was assessed with PEDro scale, and risk of bias (RoB) was assessed with Cochrane RoB-2 tool., Results: Eight studies were included (total of participants = 401). The mean PEDro score was 6.1, and seven studies had high RoB. Seven studies involved knee OA and one cervical OA. The most frequent duration for interventions was four weeks. Exergames were more effective than controls in at least one outcome in all studies. The outcomes for which exergames were most effective were functional disability, postural balance, muscle strength, proprioception, gait, range of motion, pain, quality of life, depression, and kinesiophobia., Conclusion: Non-immersive exergames constitute an effective strategy for optimizing several relevant outcomes in rehabilitation. However, more RCTs with high methodological quality are required to deepen the knowledge about the multidimensional effects of exergames in OA patients.

(1) Background : The growing prevalence of obesity, diabetes, hypertension, and declining physical fitness among children and adolescents due to sedentary lifestyles has increased attention toward preventive intervention to tackle this issue. This study investigated the age-related effects of high-intensity functional training (HIFT), based on bodyweight resistance exercises conducted during physical education lessons, on muscle mass and strength improvement. (2) Methods : Adolescent males (n = 116) were allocated to four HIFT experimental groups (EGs) and four standard physical education program control groups (CGs) according to age (15, 16, 17, and 18 years [y]). The changes in muscle mass (absolute and relative to height [SMI]), hand-grip strength (HGS), sit-ups (SUs), and standing broad jump (SBJ) were analyzed using two-way analysis of variance (ANOVA) with Bonferroni tests. (3) Results : HIFT significantly increased muscle mass and scores in all strength tests ( p < 0.01), while chronological age was significant for HGS ( p < 0.01). Interactions between HIFT and chronological age categories were observed for HGS ( p = 0.01) and SBJ ( p < 0.03). Detailed post hoc tests revealed improvement in muscle mass across all chronological age categories for both approaches ( p < 0.05). The 18y-EG group improved HGS over their control peers ( p < 0.01), the EG groups significantly improved their SU results ( p < 0.01), and SBJ improved in the 15y-EG and 18y-EG groups compared to their control ( p < 0.01). (4) Conclusions : This research highlights the effectiveness of a school-based HIFT program in promoting muscle mass gains and enhancing muscle strength among adolescents. The findings offer valuable insights for implementing bodyweight exercises during physical education classes.

Members of the genus Phytobacter (order Enterobacterales ) are isolated from the natural environment and clinical settings. Identification of Phytobacter strains based on biochemical characteristics is complicated due to taxonomic confusion, and they are often misidentified by automated identification systems in laboratories. In this study we describe the first three clinical cases associated with Phytobacter spp. reported in Argentina. We describe the identification, the molecular analysis using whole genome sequencing and the potential clinical relevance., (© 2024 Published by Elsevier Ltd on behalf of The Healthcare Infection Society.)

Through collaborative efforts, One Health partners have responded to outbreaks of COVID-19 among animals, including those in human care at zoos. Zoos have been faced with numerous challenges, including the susceptibility of many mammalian species, and therefore the need to heighten biosecurity measures rapidly. Robust One Health collaborations already exist in Arizona to address endemic and emerging zoonoses, but these have rarely included zoos. The pandemic shed light on this, and Arizona subsequently expanded its SARS-CoV-2 surveillance efforts to include zoo animals. Testing and epidemiologic support was provided to expedite the detection of and response to zoonotic SARS-CoV-2 infection in zoo animals, as well as to understand possible transmission events. Resulting from this program, SARS-CoV-2 was detected from a rectal swab collected from an 8-yr-old squirrel monkey ( Saimiri sciureus ) from a zoo in Southern Arizona. The animal had rapidly become ill with nonrespiratory symptoms and died in July 2022. Genomic sequencing from the swab revealed mutations consistent with the Omicron (BA.2) lineage. An epidemiologic investigation identified an animal caretaker in close proximity to the affected squirrel monkey who tested positive for COVID-19 the same day the squirrel monkey died. Critical One Health partners provided support to the zoo through engagement of local, state, and federal agencies. Necropsy and pathologic evaluation showed significant necrotizing colitis; the overall clinical and histopathological findings did not implicate SARS-CoV-2 infection alone as a causal or contributing factor in the squirrel monkey's illness and death. This report documents the first identification of SARS-CoV-2 in a squirrel monkey and highlights a successful and timely One Health investigation conducted through multisectoral collaboration.

Background: Leak following surgical repair of traumatic duodenal injuries results in prolonged hospitalization and oftentimes nil per os(NPO) treatment. Parenteral nutrition(PN) has known morbidity; however, duodenal leak(DL) patients often have complex injuries and hospital courses resulting in barriers to enteral nutrition(EN). We hypothesized EN alone would be associated with 1)shorter duration until leak closure and 2)less infectious complications and shorter hospital length of stay(HLOS) compared to PN., Methods: This was a post-hoc analysis of a retrospective, multicenter study from 35 Level-1 trauma centers, including patients >14 years-old who underwent surgery for duodenal injuries(1/2010-12/2020) and endured post-operative DL. The study compared nutrition strategies: EN vs PN vs EN + PN using Chi-Square and Kruskal-Wallis tests; if significance was found pairwise comparison or Dunn's test were performed., Results: There were 113 patients with DL: 43 EN, 22 PN, and 48 EN + PN. Patients were young(median age 28 years-old) males(83.2%) with penetrating injuries(81.4%). There was no difference in injury severity or critical illness among the groups, however there were more pancreatic injuries among PN groups. EN patients had less days NPO compared to both PN groups(12 days[IQR23] vs 40[54] vs 33[32],p = <0.001). Time until leak closure was less in EN patients when comparing the three groups(7 days[IQR14.5] vs 15[20.5] vs 25.5[55.8],p = 0.008). EN patients had less intra-abdominal abscesses, bacteremia, and days with drains than the PN groups(all p < 0.05). HLOS was shorter among EN patients vs both PN groups(27 days[24] vs 44[62] vs 45[31],p = 0.001). When controlling for predictors of leak, regression analysis demonstrated EN was associated with shorter HLOS(β -24.9, 95%CI -39.0 to -10.7,p < 0.001)., Conclusion: EN was associated with a shorter duration until leak closure, less infectious complications, and shorter length of stay. Contrary to some conventional thought, PN was not associated with decreased time until leak closure. We therefore suggest EN should be the preferred choice of nutrition in patients with duodenal leaks whenever feasible., Level of Evidence: IV., Competing Interests: Conflict of Interest: All JTACS disclosure forms have been supplied and are provided as supplemental digital content (http://links.lww.com/TA/D807)., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The brain bidirectionally communicates with the gut to control food intake and energy balance, which becomes dysregulated in obesity. For example, endocannabinoid (eCB) signaling in the small-intestinal (SI) epithelium is upregulated in diet-induced obese (DIO) mice and promotes overeating by a mechanism that includes inhibiting gut-brain satiation signaling. Upstream neural and molecular mechanism(s) involved in overproduction of orexigenic gut eCBs in DIO, however, are unknown. We tested the hypothesis that overactive parasympathetic signaling at the muscarinic acetylcholine receptors (mAChRs) in the SI increases biosynthesis of the eCB, 2-arachidonoyl- sn -glycerol (2-AG), which drives hyperphagia via local CB 1 Rs in DIO. Male mice were maintained on a high-fat/high-sucrose Western-style diet for 60 d, then administered several mAChR antagonists 30 min prior to tissue harvest or a food intake test. Levels of 2-AG and the activity of its metabolic enzymes in the SI were quantitated. DIO mice, when compared to those fed a low-fat/no-sucrose diet, displayed increased expression of cFos protein in the dorsal motor nucleus of the vagus, which suggests an increased activity of efferent cholinergic neurotransmission. These mice exhibited elevated levels of 2-AG biosynthesis in the SI, that was reduced to control levels by mAChR antagonists. Moreover, the peripherally restricted mAChR antagonist, methylhomatropine bromide, and the peripherally restricted CB 1 R antagonist, AM6545, reduced food intake in DIO mice for up to 24 h but had no effect in mice conditionally deficient in SI CB 1 Rs. These results suggest that hyperactivity at mAChRs in the periphery increases formation of 2-AG in the SI and activates local CB 1 Rs, which drives hyperphagia in DIO., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 the authors.)

Background: Shoulder pain is a leading cause of disability. Occupations requiring high upper extremity demands may put workers at greater risk of shoulder injury and resulting pain. We examined associations of occupation with shoulder pain and upper extremity disability in the Johnston County Osteoarthritis Project., Methods: Work industry and occupational tasks for the longest job held were collected from participants. At follow-up ranging from 4-10 years later, participants were asked about shoulder symptoms (pain, aching, or stiffness occurring most days of 1 month in the last year) and given a 9-item, modified Disabilities Arm Shoulder and Hand (DASH) questionnaire to categorize disability from 0-4 (none-worst). Logistic regression and cumulative logit regression models were used to estimate associations with prevalent shoulder symptoms and with worse disability category, respectively. Models were adjusted for cohort, age, sex, race, education and time to follow-up. Sex- and race-stratified associations were evaluated., Results: Among 1560 included participants, mean age was 62 years (standard deviation ± 9 years); 32% were men, and 31% were Black. Compared to the managerial/professional industry, higher odds of both shoulder symptoms and worse upper extremity disability were seen for most industrial groups with physically demanding jobs, particularly the service industry. Work that often or always required lifting/moving > 10 lbs. was associated with higher odds of shoulder symptoms. Work that sometimes or always required heavy work while standing was associated with higher odds of shoulder symptoms, and this association was stronger among men and White workers., Conclusion: Physically demanding occupations were associated with increased occurrence of shoulder pain and disability. Mitigating specific physical work demands may reduce shoulder-related disability., (© 2024. The Author(s).)

This article systematically reviews the advancements in processing litchi peel ( Litchi chinensis ), emphasizing drying, extraction, purification methods, and the potential of bioactive compounds obtained from litchi peel. This work also highlights the impact of various drying techniques on phytochemical profiles, focusing on how methods such as hot air and freeze-drying affect the preservation of bioactive compounds. The study delves into extraction methods, detailing how different solvents and techniques influence the efficiency of extracting bioactive compounds from litchi peel. Furthermore, the purification and characterization of active compounds, showcasing the role of chromatographic techniques in isolating specific bioactive molecules, is discussed. Biological properties and mechanisms of action, such as antioxidant, antihyperglycemic, cardioprotective, hepatoprotective, anti-atherosclerotic, and anticancer activities, are reviewed, providing insight into the potential health benefits of litchi peel compounds. This review highlights the importance of optimizing and selecting accurate drying and extraction methods to maximize the therapeutic effects of litchi peel and its bioactive compounds. This review also reveals the broad pharmacological potential of the isolated compounds, underscoring the need for further research to discover their specific actions and health benefits.

The National Reference Laboratory in Clinical Mycology of Argentina conducted a retrospective review of human coccidioidomycosis cases diagnosed by the National Mycology Laboratory Network of Argentina between 2010 and 2022 to determine the burden of the disease in the country. A total of 100 human coccidioidomycosis cases were documented, with a higher prevalence in male patients (male-to-female ratio of 1.9:1), with a median age of 41 years. Comparing the number of cases between two 10-year periods (2000-2009 and 2010-2019), the increase was 36.51% (from 63 to 86 cases). Among the 100 recorded cases, 79 tested positive using the double immunodiffusion test. Spherules were observed in 19 cases through histopathology or direct microscopic examination and the fungus was isolated in 39 cases. Thirty-six isolates were identified as Coccidioides posadasii through partial sequencing of the Ag2/PRA gene. Catamarca province had the highest number of cases, comprising 64% of the total, with an incidence rate above 1.0-2.5/100,000 inhabitants until 2018. However, there has been a recent downward trend in the region from 2018 to 2022. It is concerning that more than half of diagnosed cases were chronic pulmonary or disseminated forms, indicating a lack of early disease detection. To rectify this issue, it is imperative to conduct targeted training programs for healthcare personnel and enhance public awareness within the endemic area. This will contribute to a better understanding of the true burden of coccidioidomycosis and enable the implementation of appropriate sanitary control measures., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

Academic medicine continues to characterize the experiences of Black and other minoritized faculty in medicine to enhance their careers and promote their advancement. An issue of discussion is tenure and its role in the advancement and retention of this group. Tenure is a sign of national presence, command of an area of study, and can demonstrate support from the institution in terms of permanent employment, eligibility to apply for awards, sit or vote on certain committees or qualify for certain leadership opportunities. Anecdotally there have been reports that tenure is a thing of the past that has lost relevance prompting some to end tenure in their institutions. Reasons for this are complex, however the literature does not include minoritized faculty as a reason for the need to revise or eliminate tenure and tenure earning tracks. The authors discuss 3 reasons why Black and other minoritized faculty should be afforded the opportunity to achieve permanent status in their academic health centers. They include histories of being denied freedom, having information concealed or being giving false information, and being denied permanent academic employment status., Competing Interests: Conflict of interest: None., (© Copyright 2024 by the American Board of Family Medicine.)

Marine litter is a growing environmental problem for which fisheries-sourced waste remains poorly understood. In Peru, there is an ongoing challenge of waste management from the small-scale fisheries fleet given the lack of facilities to receive the variety of debris produced by fishers, which includes hazardous wastes such as batteries. In this study, onboard solid waste production was monitored daily by land-based observers upon landing at the port of Salaverry, Peru, from March to September 2017. The analysed small-scale gillnet and longline fishing fleets produced annually an estimated 11,260 kg of solid waste. Of particular concern is the production of single use plastics (3427 kg) and batteries (861 kg) due to their potential long-lasting impacts on the environment and challenges related to their proper disposal. A management plan for solid waste has been developed for Salaverry; therefore, a subsequent assessment was conducted in 2021-2022 of the behaviours and perceptions of fishers regarding the implementation of this plan. Most fishers (96%) reported disposing of their waste on land, except organic waste which is disposed of at sea. While fishers in Salaverry have become more conscious of the issues surrounding at-sea waste disposal and have an interest in better segregating and managing their waste, there remains a need for improved waste management and recycling protocols and procedures at the port to make this possible., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

Purpose: To explore the genetic background of choroidal and ciliary body melanoma among children and young adults, with special focus on BAP1 germline variants in this age group., Methods: Patients under the age of 25 and with confirmed choroidal or ciliary body melanoma were included in this retrospective, multicenter observational study. Nuclear BAP1 immunopositivity was used to evaluate the presence of functional BAP1 in the tumor. Next-generation sequencing using Ion Torrent platform was used to determine pathogenic variants of BAP1, EIF1AX, SF3B1, GNAQ and GNA11 and chromosome 3 status in the tumor or in DNA extracted from blood or saliva. Survival was analyzed using Kaplan-Meier estimates., Results: The mean age at diagnosis was 17 years (range 5.0-24.8). A germline BAP1 pathogenic variant was identified in an 18-year-old patient, and a somatic variant, based mainly on immunohistochemistry, in 13 (42%) of 31 available specimens. One tumor had a somatic SF3B1 pathogenic variant. Disomy 3 and the absence of a BAP1 pathogenic variant in the tumor predicted the longest metastasis-free survival. Males showed longer metastasis-free survival than females (P = 0.018)., Conclusions: We did not find a stronger-than-average BAP1 germline predisposition for choroidal and ciliary body melanoma among children and young adults compared to adults. Males had a more favorable survival and disomy 3, and the absence of a BAP1 mutation in the tumor tissue predicted the most favorable metastasis-free survival. A BAP1 germline pathogenic variant was identified in one patient (1%), and a somatic variant based mainly on immunohistochemistry in 13 (42%).

The Eastern Tropical and South-Eastern Pacific region is of global biodiversity importance. At COP26, the governments of Costa Rica, Panama, Colombia, and Ecuador committed to the expansion of existing MPAs to create a new Mega MPA, safeguarding the Eastern Tropical Pacific Marine Corridor. It offers a profound step forward in conservation efforts but is not specifically designed to protect against the more diffuse anthropogenic threats, such as plastic pollution. We combine published data with our own unpublished records to assess the abundance and distribution of plastic pollution in the region. Macro- and microplastic concentrations varied markedly and were not significantly different when comparing areas inside and outside existing MPA boundaries. These findings highlight the diffuse and complex nature of plastic pollution and its ubiquitous presence across MPA boundaries. Understanding the sources and drivers of plastic pollution in the region is key to developing effective solutions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: In 2018, the World Health Organization commenced a multi-country validation study of the Cepheid GeneXpert for a range of molecular-based point-of-care (POC) tests in primary care settings. One study arm focused on the evaluation of POC tests for screening 'women at risk' for chlamydia (CT), gonorrhoea (NG) and trichomonas (TV) in four countries - Australia, Guatemala, Morocco and South Africa., Methods: Study participants completed a pre-test questionnaire which included demographics, clinical information and general questions on POC testing (POCT). Two vaginal swab samples (either self-collected or clinician collected) from each patient were tested on the GeneXpert at the POC and at a reference laboratory using quality-assured nucleic acid amplification tests (NAATs)., Results: One thousand three hundred and eighty-three women were enrolled: 58.6% from South Africa, 29.2% from Morocco, 6.2% from Guatemala, and 6.0% from Australia. 1296 samples for CT/NG and 1380 samples for TV were tested by the GeneXpert and the reference NAAT. The rate of unsuccessful tests on the GeneXpert was 1.9% for CT, 1.5% for NG and 0.96% for TV. The prevalence of CT, NG and TV was 31%, 13% and 23%, respectively. 1.5% of samples were positive for all three infections; 7.8% were positive for CT and NG; 2.4% were positive for NG and TV; and 7.3% were positive for CT and TV. Compared to reference NAATs, pooled estimates of sensitivity for the GeneXpert tests were 83.7% (95% confidence intervals 69.2-92.1) for CT, 90.5% (85.1-94.1) for NG and 64.7% (58.1-70.7) for TV (although estimates varied considerably between countries). Estimates for specificity were ≥96% for all three tests both within- and between-countries. Pooled positive and negative likelihood ratios were: 32.7 ([CI] 21.2-50.5) and 0.17 (0.08-0.33) for CT; 95.3 (36.9-245.7) and 0.10 (0.06-0.15) for NG; and 56.5 (31.6-101.1) and 0.35 (0.27-0.47) for TV., Conclusion: This multi-country evaluation is the first of its kind world-wide. Positive likelihood ratios, as well as specificity estimates, indicate the GeneXpert POC test results for CT, NG and TV were clinically acceptable for ruling in the presence of disease. However, negative likelihood ratios and variable sensitivity estimates from this study were poorer than expected for ruling out these infections, particularly for TV., Trial Registration: Ethics approval to conduct the ProSPeRo study was granted by the WHO Ethics Review Committee, as well as local ethics committees from all participating countries., (© 2024. The Author(s).)

Serratia marcescens is a global opportunistic pathogen. In vitro cytotoxicity of this bacterium is mainly related to metalloprotease serralysin (PrtS) activity. Proteolytic capability varies among the different isolates. Here, we characterized protease production and transcriptional regulators at 37°C of two S. marcescens isolates from bronchial expectorations, HU1848 and SmUNAM836. As a reference strain the insect pathogen S. marcescens Db10 was included. Zymography of supernatant cultures revealed a single (SmUNAM836) or double proteolytic zones (HU1848 and Db10). Mass spectrometry confirmed the identity of PrtS and the serralysin-like protease SlpB from supernatant samples. Elevated proteolytic activity and prtS expression were evidenced in the HU1848 strain through azocasein degradation and qRT-PCR, respectively. Evaluation of transcriptional regulators revealed higher eepR expression in HU1848, whereas cpxR and hexS transcriptional levels were similar between studied strains. Higher eepR expression in HU1848 was further confirmed through an in vivo transcriptional assay. Moreover, two putative CpxR binding motifs were identified within the eepR regulatory region. EMSA validated the interaction of CpxR with both motifs. The evaluation of eepR transcription in a cpxR deletion strain indicated that CpxR negatively regulates eepR . Sequence conservation suggests that regulation of eepR by CpxR is common along S. marcescens species. Overall, our data incorporates CpxR to the complex regulatory mechanisms governing eepR expression and associates the increased proteolytic activity of the HU1848 strain with higher eepR transcription. Based on the global impact of EepR in secondary metabolites production, our work contributes to understanding virulence factors variances across S. marcescens isolates., (© 2024 Karla L. De Anda-Mora et al., published by Sciendo.)

RAC1 P29S is the third most prevalent hotspot mutation in sun-exposed melanoma. RAC1 alterations in cancer are correlated with poor prognosis, resistance to standard chemotherapy, and insensitivity to targeted inhibitors. Although RAC1 P29S mutations in melanoma and RAC1 alterations in several other cancers are increasingly evident, the RAC1-driven biological mechanisms contributing to tumorigenesis remain unclear. Lack of rigorous signaling analysis has prevented identification of alternative therapeutic targets for RAC1 P29S -harboring melanomas. To investigate the RAC1 P29S -driven effect on downstream molecular signaling pathways, we generated an inducible RAC1 P29S expression melanocytic cell line and performed RNA-sequencing (RNA-seq) coupled with multiplexed kinase inhibitor beads and mass spectrometry (MIBs/MS) to establish enriched pathways from the genomic to proteomic level. Our proteogenomic analysis identified CDK9 as a potential new and specific target in RAC1 P29S -mutant melanoma cells. In vitro, CDK9 inhibition impeded the proliferation of in RAC1 P29S -mutant melanoma cells and increased surface expression of PD-L1 and MHC Class I proteins. In vivo, combining CDK9 inhibition with anti-PD-1 immune checkpoint blockade significantly inhibited tumor growth only in melanomas that expressed the RAC1 P29S mutation. Collectively, these results establish CDK9 as a novel target in RAC1-driven melanoma that can further sensitize the tumor to anti-PD-1 immunotherapy., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Objectives:  Pharmacogenetics (PGx) is increasingly important in individualizing therapeutic management plans, but is often implemented apart from other types of medication clinical decision support (CDS). The lack of integration of PGx into existing CDS may result in incomplete interaction information, which may pose patient safety concerns. We sought to develop a cloud-based orchestrated medication CDS service that integrates PGx with a broad set of drug screening alerts and evaluate it through a clinician utility study., Methods:  We developed the PillHarmonics service for implementation per the CDS Hooks protocol, algorithmically integrating a wide range of drug interaction knowledge using cloud-based screening services from First Databank (drug-drug/allergy/condition), PharmGKB (drug-gene), and locally curated content (drug-renal/hepatic/race). We performed a user study, presenting 13 clinicians and pharmacists with a prototype of the system's usage in synthetic patient scenarios. We collected feedback via a standard questionnaire and structured interview., Results:  Clinician assessment of PillHarmonics via the Technology Acceptance Model questionnaire shows significant evidence of perceived utility. Thematic analysis of structured interviews revealed that aggregated knowledge, concise actionable summaries, and information accessibility were highly valued, and that clinicians would use the service in their practice., Conclusion:  Medication safety and optimizing efficacy of therapy regimens remain significant issues. A comprehensive medication CDS system that leverages patient clinical and genomic data to perform a wide range of interaction checking and presents a concise and holistic view of medication knowledge back to the clinician is feasible and perceived as highly valuable for more informed decision-making. Such a system can potentially address many of the challenges identified with current medication-related CDS., Competing Interests: PillHarmonics is partially supported by a grant funding (NHGRI 1R43HG011832–01A1). Elimu employees stand to benefit if PillHarmonics becomes a licensable product. No other conflicts of interest reported., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)