Long-term Musculoskeletal Consequences of Chemotherapy in Pediatric Mice.

Thanks to recent progress in cancer research, most children treated for cancer survive into adulthood. Nevertheless, the long-term consequences of anticancer agents are understudied, especially in the pediatric population. We and others have shown that routinely administered chemotherapeutics drive musculoskeletal alterations, which contribute to increased treatment-related toxicity and long-term morbidity. Yet, the nature and scope of these enduring musculoskeletal defects following anticancer treatments and whether they can potentially impact growth and quality of life in young individuals remain to be elucidated. Here, we aimed at investigating the persistent musculoskeletal consequences of chemotherapy in young (pediatric) mice. Four-week-old male mice were administered a combination of 5-FU, leucovorin, irinotecan (a.k.a., Folfiri) or the vehicle for up to 5 wk. At time of sacrifice, skeletal muscle, bones, and other tissues were collected, processed, and stored for further analyses. In another set of experiments, chemotherapy-treated mice were monitored for up to 4 wk after cessation of treatment. Overall, the growth rate was significantly slower in the chemotherapy-treated animals, resulting in diminished lean and fat mass, as well as significantly smaller skeletal muscles. Interestingly, 4 wk after cessation of the treatment, the animals exposed to chemotherapy showed persistent musculoskeletal defects, including muscle innervation deficits and abnormal mitochondrial homeostasis. Altogether, our data support that anticancer treatments may lead to long-lasting musculoskeletal complications in actively growing pediatric mice and support the need for further studies to determine the mechanisms responsible for these complications, so that new therapies to prevent or diminish chemotherapy-related toxicities can be identified.

Teams in Transition: Increasing Role of Advanced Practice Providers in Antimicrobial Use and Infectious Diseases Consultation.

Background: Advanced practice providers (APPs) have taken on increasing responsibilities as primary team members in acute care hospitals, but the impact of this practice shift on antimicrobial prescribing and infectious diseases (ID) consultation requests is unknown. Here we describe longitudinal trends in antimicrobial days of therapy (DOT) and ID consultation by attributed provider type in 3 hospitals. Methods: We performed a retrospective time series analysis of antimicrobial use and ID consultation from July 2015 to June 2022 at a major university hospital and 2 community hospitals. We evaluated antimicrobial DOT and ID consultation over time and assessed attribution to 3 groups of providers: attending physicians, trainees, and APPs. We used multinomial logistic regression to measure changes in percentage of DOT and ID consultation across the clinician groups over time using physicians as the referent. Results: Baseline distribution of antimicrobial DOT and ID consultation varied by practice setting, but all subgroups showed increases in the proportion attributable to APPs. Large increases were seen in the rate of ID consultation, increasing by >30% during the study period. At our university hospital, by study end >40% of new ID consults and restricted antimicrobial days were attributed to APPs. Conclusions: Hospitals had differing baseline patterns of DOT attributed to provider groups, but all experienced increases in DOT attributed to APPs. Similar increases were seen in changes to ID consultation. APPs have increasing involvement in antimicrobial use decisions in the inpatient setting and should be engaged in future antimicrobial stewardship initiatives.

"I know now that it's something that you can do something about": Deductive thematic analysis of experiences at an arts-based dementia risk reduction exhibit.

Dementia is one of the leading global health crises. Despite the devastating impacts of the illness, general population knowledge pertaining to risk reduction is still limited. Previous research on the impact of dementia risk reduction campaigns has largely focused on awareness rather than behaviour change. Our research introduced an arts-based exhibit to address dementia modifiability, aiming to enhance effectiveness by providing an immersive experience for altering adults' perceptions of risk reduction and lifestyle behaviours. Interviews were conducted with adults (n = 38 [13 male, 25 female]) who attended an interactive dementia awareness and risk reduction exhibit. Data was analysed using deductive thematic analysis within the Health Belief Model framework to determine key mechanisms of behaviour change. Four key themes encompassing exhibit significance and factors underlying behaviour change were identified. Participants recounted positive experiences, particularly being engaged by the artistic aspects of the exhibit, and recorded heightened engagement in behaviours supporting dementia risk reduction post-exhibit. Areas for improvement included the need for a take-home summary and variation in formats. Participants described prior encounters with dementia and their age as factors which influenced their engagement with dementia risk reduction behaviour, with younger participants reporting lesser engagement with risk reduction information. Our research found that arts-based educational initiatives have the potential to advance public understanding and promote behavioural changes for dementia risk reduction. Our study recommends enhancing the impact of future interventions by employing innovative formats and tailoring them to varied audiences, with a specific emphasis on engaging younger individuals.

Pioneering Patient-Specific Approaches for Precision Surgery Using Imaging and Virtual Reality.

Endovascular treatment of complex vascular anomalies shifts the risk of open surgical procedures to the benefit of minimally invasive endovascular procedural solutions. Complex open surgical procedures used to be the only option for the treatment of a myriad of conditions like pulmonary and aortic valve replacement as well as cerebral aneurysm repair. However, due to advancements in catheter-delivered devices and operator expertise, these procedures (along with many others) can now be performed through minimally invasive procedures delivered through a central or peripheral vein or artery. The decision to shift from an open procedure to an endovascular approach is based on multi-modal imaging, often including 3D Digital Imaging and Communications in Medicine (DICOM) imaging datasets. Utilizing these 3D images, our lab generates 3D models of the pathologic anatomy, thereby allowing the pre-procedural analysis necessary to pre-plan critical components of the catheterization lab procedure, namely, C-arm positioning, 3D measurement, and idealized road-map generation. This article describes how to take segmented 3D models of patient-specific pathology and predict generalized C-arm positions, how to measure critical two-dimensional (2D) measurements of 3D structures relevant to the 2D fluoroscopy projections, and how to generate 2D fluoroscopy roadmap analogs that can assist in proper C-arm positioning during catheterization lab procedures.

Utility of Methicillin-Resistant Staphylococcus aureus Nasal PCR Testing in Pediatric Patients With Suspected Respiratory Infections.

Observational studies in adults suggest nasal methicillin-resistant Staphylococcus aureus (MRSA) swabs have a high negative predictive value (NPV) for ruling out MRSA pneumonia, however, pediatric data are limited. This retrospective study of 505 pediatric patients found a 99.8% NPV among children with suspected respiratory infections.

Experimentally manipulated anger activates implicit cognitions about social hierarchy.

A correlational pilot study (N = 143) and an integrative data analysis of two experiments (total N = 377) provide evidence linking anger to the psychology of social hierarchy. The experiments demonstrate that the experience of anger increases the psychological accessibility of implicit cognitions related to social hierarchy: compared to participants in a control condition, participants in an anger-priming condition completed word stems with significantly more hierarchy-related words. We found little support for sex differences in the effect of anger on implicit hierarchy-related cognition; effects were equivalent across male and female participants. Findings fit with functionalist evolutionary views of anger suggesting that anger may motivate the use of dominance to strive for high social rank in group hierarchies. Implications for downstream behaviour, including aggression and negotiation, are discussed.

A Baker's Dozen of Top Antimicrobial Stewardship Intervention Publications in 2022.

Keeping abreast of the antimicrobial stewardship-related articles published each year is challenging. The Southeastern Research Group Endeavor identified antimicrobial stewardship-related, peer-reviewed literature that detailed an actionable intervention during 2022. The top 13 publications were selected using a modified Delphi technique. These manuscripts were reviewed to highlight actionable interventions used by antimicrobial stewardship programs to capture potentially effective strategies for local implementation.

Fndc5 is translated from an upstream ATG start codon and cleaved to produce irisin myokine precursor protein in humans and mice.

Witmer et al. provide genomic and molecular evidence to demonstrate that Fndc5 (irisin myokine precursor protein) is translated in humans from an overlooked upstream ATG codon.

High fat intake sustains sorbitol intolerance after antibiotic-mediated Clostridia depletion from the gut microbiota.

Carbohydrate intolerance, commonly linked to the consumption of lactose, fructose, or sorbitol, affects up to 30% of the population in high-income countries. Although sorbitol intolerance is attributed to malabsorption, the underlying mechanism remains unresolved. Here, we show that a history of antibiotic exposure combined with high fat intake triggered long-lasting sorbitol intolerance in mice by reducing Clostridia abundance, which impaired microbial sorbitol catabolism. The restoration of sorbitol catabolism by inoculation with probiotic Escherichia coli protected mice against sorbitol intolerance but did not restore Clostridia abundance. Inoculation with the butyrate producer Anaerostipes caccae restored a normal Clostridia abundance, which protected mice against sorbitol-induced diarrhea even when the probiotic was cleared. Butyrate restored Clostridia abundance by stimulating epithelial peroxisome proliferator-activated receptor-gamma (PPAR-γ) signaling to restore epithelial hypoxia in the colon. Collectively, these mechanistic insights identify microbial sorbitol catabolism as a potential target for approaches for the diagnosis, treatment, and prevention of sorbitol intolerance.

Colloidal Nanoparticles of High Entropy Materials: Capabilities, Challenges, and Opportunities in Synthesis and Characterization.

Materials referred to as "high entropy" contain a large number of elements randomly distributed on the lattice sites of a crystalline solid, such that a high configurational entropy is presumed to contribute significantly to their formation and stability. High temperatures are typically required to achieve entropy stabilization, which can make it challenging to synthesize colloidal nanoparticles of high entropy materials. Nonetheless, strategies are emerging for the synthesis of colloidal high entropy nanoparticles, which are of interest for their synergistic properties and unique catalytic functions that arise from the large number of constituent elements and their interactions. In this Perspective, we highlight the classes of materials that have been made as colloidal high entropy nanoparticles as well as insights into the synthetic methods and the pathways by which they form. We then discuss the concept of "high entropy" within the context of colloidal materials synthesized at much lower temperatures than are typically required for entropy to drive their formation. Next, we identify and address challenges and opportunities in the field of high entropy nanoparticle synthesis. We emphasize aspects of materials characterization that are especially important to consider for nanoparticles of high entropy materials, including powder X-ray diffraction and elemental mapping with scanning transmission electron microscopy, which are among the most commonly used techniques in laboratory settings. Finally, we share perspectives on emerging opportunities and future directions involving colloidal nanoparticles of high entropy materials, with an emphasis on synthesis, characterization, and fundamental knowledge that is needed for anticipated advances in key application areas.

Outcomes Following Fully Threaded Intramedullary Nailing of Metacarpal Fractures.

Purpose: Intramedullary screw fixation has emerged as a popular approach for the treatment of displaced metacarpal fractures. The purpose of this study was to investigate the functional and radiographic outcomes of a newly designed, headless noncompressive fully threaded intramedullary nail (TIMN) for the treatment of metacarpal fractures. Methods: A retrospective chart review was performed on patients who were treated with the INnate TIMN (ExsoMed) at a single academic institution with a minimum of 1-year follow-up. Patient-reported functional outcomes included Quick Disabilities for the Arm, Shoulder, and Hand (QuickDASH) questionnaires, return to work and physical activity time, and overall satisfaction. Radiographs were retrospectively reviewed to determine radiographic union, change in angulation, and metacarpal shortening. Results: A total of 49 patients (58 fractures) with a mean age of 36 years (range: 17-75 years) were included. The mean follow-up time was 2.7 years (range: 1.4-4.3 years). Overall, the mean patient satisfaction rating was 4.9 of 5 (range: 3-5). The mean return to work time was 7.2 weeks (range: 0.14-28 weeks), and the mean return to sport or activity was 8.3 weeks (range: 1-28 weeks). Average QuickDASH scores across all patients were 4 (range: 0-56.9). The median radiographic healing time was 6.1 weeks (range: 4.7-15.4 weeks). Mean postoperative shortening in the fifth metacarpal fracture was 3 mm (range: -4.2 to 8 mm) at the initial postoperative visit and 3.6 mm (range: -3.3 to 7.9 mm) at the final radiographic follow-up. Subgroup analysis showed that postoperative shortening was similar, regardless of the fracture pattern. The following four complications were reported: one case of persistent pain and stiffness, one case of carpal tunnel syndrome, one nonunion, and one fractured intramedullary nail. Conclusions: Our findings suggest that the TIMN allows for a reliable return to work and physical activity, high patient satisfaction, low complication rate, and minimal shortening at the final radiographic follow-up. Type of study/level of evidence: Therapeutic IV.

Stochastic model of vesicular stomatitis virus replication reveals mutational effects on virion production.

We present the first complete stochastic model of vesicular stomatitis virus (VSV) intracellular replication. Previous models developed to capture VSV's intracellular replication have either been ODE-based or have not represented the complete replicative cycle, limiting our ability to understand the impact of the stochastic nature of early cellular infections on virion production between cells and how these dynamics change in response to mutations. Our model accurately predicts changes in mean virion production in gene-shuffled VSV variants and can capture the distribution of the number of viruses produced. This model has allowed us to enhance our understanding of intercellular variability in virion production, which appears to be influenced by the duration of the early phase of infection, and variation between variants, arising from balancing the time the genome spends in the active state, the speed of incorporating new genomes into virions, and the production of viral components. Being a stochastic model, we can also assess other effects of mutations beyond just the mean number of virions produced, including the probability of aborted infections and the standard deviation of the number of virions produced. Our model provides a biologically interpretable framework for studying the stochastic nature of VSV replication, shedding light on the mechanisms underlying variation in virion production. In the future, this model could enable the design of more complex viral phenotypes when attenuating VSV, moving beyond solely considering the mean number of virions produced.

Epidemiology and treatment of invasive Bartonella spp. infections in the United States.

OBJECTIVES: Bartonella spp., renowned for cat-scratch disease, has limited reports of dissemination. Tissue and blood cultures have limitations in detecting this fastidious pathogen. Molecular testing (polymerase chain reaction, PCR) and cell-free DNA have provided an avenue for diagnoses. This retrospective observational multicenter study describes the incidence of disseminated Bartonella spp. and treatment-related outcomes. METHODS: Inclusion criteria were diagnosis of bartonellosis via diagnosis code, serology testing of blood, polymerase chain reaction (PCR) of blood, 16/18S tests of blood or tissue, cultures of blood or tissue, or cell-free DNA of blood or tissue from January 1, 2014, through September 1, 2021. Exclusions were patients who did not receive treatment, insufficient data on treatment course, absence of dissemination, or retinitis as dissemination. RESULTS: Patients were primarily male (n = 25, 61.0%), white (n = 28, 68.3%), with mean age of 50 years (SD 14.4), and mean Charlson comorbidity index of 3.5 (SD 2.1). Diagnosis was primarily by serology (n = 34, 82.9%), with Bartonella henselae (n = 40, 97.6%) as the causative pathogen. Treatment was principally doxycycline with rifampin (n = 17, 41.5%). Treatment failure occurred in 16 (39.0%) patients, due to escalation of therapy during treatment (n = 5, 31.3%) or discontinuation of therapy due to an adverse event or tolerability (n = 5, 31.3%). CONCLUSIONS: In conclusion, this is the largest United States-based cohort of disseminated Bartonella spp. infections to date with a reported 39% treatment failure. This adds to literature supporting obtaining multiple diagnostic tests when Bartonella is suspected and describes treatment options.

Does choice of anesthesia during stage 1 sacral neuromodulation testing influence outcomes?

INTRODUCTION: Staged sacral neuromodulation (SNM) testing has been shown to have a high rate of progression to permanent implantation for the management of voiding dysfunction. Stage 1 lead placement (SNM-I) can be performed under monitored anesthesia care (MAC) or general anesthesia (GA). MAC allows for interpretation of sensory and motor responses to optimize lead placement while GA only permits for motor assessment. However, patient discomfort and movement can make lead placement challenging during MAC. Herein we evaluate whether the anesthesia type impacts the progression rate to permanent implantation (SNM-II). MATERIALS AND METHODS: A retrospective chart review was performed for patients who underwent SNM-I in the operating room for wet overactive bladder between 2005 and 2023. Patients were divided into two groups based on the type of anesthesia used, MAC or GA. Clinical variables and progression to SNM-II were compared between cohorts. Progression to SNM-II was based on ≥50% symptomatic improvement during a 1-2 week trial period following SNM-I. RESULTS: Of 121 patients included in the study, 95 (79%) underwent MAC and 26 (21%) GA for SNM-I. No difference in the progression rate to SNM-II was noted between groups (MAC, 68/95 patients, 72%; GA, 19/26, 73%; p = 0.39). We also found no difference when comparing the GA group to the 26 most recent MAC patients (MAC, 20/26 patients, 77%; GA, 19/26, 73%; p = 0.48). CONCLUSION: Types of anesthesia for SNM-I did not affect rate of progression to SNM-II. The result lends support to the reliance on motor responses alone for lead placement during SNM-I.

Successful Treatment of Recalcitrant Mpox Lesions With Intralesional Cidofovir in a Patient With HIV/AIDS.

This case report describes a man in his 50s with HIV/AIDS who presented with widely scattered recalcitrant mpox lesions.

Ten simple rules for managing laboratory information.

Information is the cornerstone of research, from experimental (meta)data and computational processes to complex inventories of reagents and equipment. These 10 simple rules discuss best practices for leveraging laboratory information management systems to transform this large information load into useful scientific findings.

Resilience of Patients Undergoing Knee and Shoulder Arthroscopy Procedures.

INTRODUCTION: Resilience is a person's capacity to overcome adversity. The purpose was to determine what patient factors correlate with resilience using the Brief Resilience Score. We hypothesize that characteristics of female sex, younger age, Workers' Compensation status, and preoperative opioid use are predictors of a lower preoperative resilience score and that patients with positive psychosocial factors would have higher resilience scores. METHODS: Eight hundred nine patients undergoing knee or shoulder arthroscopy were preoperatively categorized into low, normal, and high-resilience groups. Preoperative patient-reported outcome measures (PROMs) and demographics were assessed. Statistical analyses evaluated differences in demographics and PROMs between resilience groups. RESULTS: Analysis disclosed notable differences between low, normal, and high-resilience groups regarding demographics and PROMs. High resilience was seen in older patients, male patients, and patients with positive psychosocial factors. Low resilience scores were discovered in Workers' Compensation patients and those with a history of preoperative opioid use. No difference in resilience scores was observed between smokers and nonsmokers. DISCUSSION: Preoperative resilience score is associated with age, sex, preoperative opioid use, Workers' Compensation status, and smoking status of patients undergoing knee or shoulder arthroscopy.

The nitro to amine reduction: from millions of tons to single molecule studies.

Palladium nanostructures are interesting heterogeneous catalysts because of their high catalytic activity in a vast range of highly relevant reactions such as cross couplings, dehalogenations, and nitro-to-amine reductions. In the latter case, the catalyst Pd@GW (palladium on glass wool) shows exceptional performance and durability in reducing nitrobenzene to aniline under ambient conditions in aqueous solutions. To enhance our understanding, we use a combination of optical and electron microscopy, in-flow single molecule fluorescence, and bench chemistry combined with a fluorogenic system to develop an intimate understanding of Pd@GW in nitro-to-amine reductions. We fully characterize our catalyst in situ using advanced microscopy techniques, providing deep insights into its catalytic performance. We also explore Pd cluster migration on the surface of the support under flow conditions, providing insights into the mechanism of catalysis. We show that even under flow, Pd migration from anchoring sites seems to be minimal over 4 h, with the catalyst stability assisted by APTES anchoring.