Hydrogels for Local and Sustained Delivery of Bacteriophages to Treat Multidrug-Resistant Wound Infections.

Bacteriophages (phages), viruses that specifically target and kill bacteria, represent a promising strategy to combat multidrug-resistant (MDR) pathogens such as Pseudomonas aeruginosa ( Pa ). However, delivering sufficient concentrations of active phages directly to the infection site remains challenging, with current methods having variable success. Here we present "HydroPhage", an innovative hydrogel system for the sustained release of high-titer phages to effectively treat infections caused by MDR pathogens. Our injectable hydrogels, featuring dual-crosslinking of hyaluronic acid and PEG-based hydrogels through static covalent thioether bonds and dynamic covalent hemithioacetal crosslinks (DCC), encapsulate phages at concentration up to 10 11 PFU/mL, and achieves controlled release of 10 9 PFU daily over a week, surpassing levels of current clinical dosages, with more than 60% total phage recovery. In a preclinical mouse model of extended wound infection, compared to intravenous treatment, we demonstrate enhanced bacterial clearance by localized, high-dose, and repeated phage dosing despite the emergence of bacterial resistance to phages. This work advances the development of clinically practical wound dressings tailored for resistant infections.

Cellular senescence is a double-edged sword in regulating aged immune responses to influenza.

Clearance of senescent cells has demonstrated therapeutic potential in the context of chronic age-related diseases. Little is known, however, how clearing senescent cells affects the ability to respond to an acute infection and form quality immunological memory. We aimed to probe the effects of clearing senescent cells in aged mice on the immune response to influenza (flu) infection. We utilized a p16 trimodality reporter mouse model (p16-3MR) to allow for identification and selective clearance of p16-expressing cells upon administration of ganciclovir (GCV). While p16-expressing cells may exacerbate dysfunctional responses to a primary infection, our data suggest they may play a role in fostering memory cell generation. We demonstrate that although clearance of p16-expressing cells enhanced viral clearance, this also severely limited antibody production in the lungs of flu-infected aged mice. 30 days later, there were fewer flu-specific CD8 memory T cells and lower levels of flu-specific antibodies in the lungs of GCV-treated mice. Furthermore, GCV-treated mice were unable to mount an optimal memory response and demonstrated increased viral load following heterosubtypic challenge. These results suggest that targeting senescent cells may potentiate primary responses while limiting the ability to form durable and protective immune memory with age.

Early Impairment of Cerebral Bioenergetics After Cardiopulmonary Bypass in Neonatal Swine.

Objectives: We previously demonstrated cerebral mitochondrial dysfunction in neonatal swine immediately following a period of full-flow cardiopulmonary bypass (CPB). The extent to which this dysfunction persists in the postoperative period and its correlation with other markers of cerebral bioenergetic failure and injury is unknown. We utilized a neonatal swine model to investigate the early evolution of mitochondrial function and cerebral bioenergetic failure after CPB. Methods: Twenty piglets (mean weight 4.4 ± 0.5 kg) underwent 3 h of CPB at 34 °C via cervical cannulation and were followed for 8, 12, 18, or 24 h (n = 5 per group). Markers of brain tissue damage (glycerol) and bioenergetic dysfunction (lactate to pyruvate ratio) were continuously measured in cerebral microdialysate samples. Control animals (n = 3, mean weight 4.1 ± 1.2 kg) did not undergo cannulation or CPB. Brain tissue was extracted immediately after euthanasia to obtain ex-vivo cortical mitochondrial respiration and frequency of cortical microglial nodules (indicative of cerebral microinfarctions) via neuropathology. Results: Both the lactate to pyruvate ratio (P < .0001) and glycerol levels (P = .01) increased in cerebral microdialysate within 8 h after CPB. At 24 h post-CPB, cortical mitochondrial respiration was significantly decreased compared with controls (P = .046). The presence of microglial nodules increased throughout the study period (24 h) (P = .01, R2 = 0.9). Conclusion: CPB results in impaired cerebral bioenergetics that persist for at least 24 h. During this period of bioenergetic impairment, there may be increased susceptibility to secondary injury related to alterations in metabolic delivery or demand, such as hypoglycemia, seizures, and decreased cerebral blood flow.

Controlling crystal cleavage in focused ion beam shaped specimens for surface spectroscopy.

Our understanding of quantum materials is commonly based on precise determinations of their electronic spectrum by spectroscopic means, most notably angle-resolved photoemission spectroscopy (ARPES) and scanning tunneling microscopy. Both require atomically clean and flat crystal surfaces, which are traditionally prepared by in situ mechanical cleaving in ultrahigh vacuum chambers. We present a new approach that addresses three main issues of the current state-of-the-art methods: (1) Cleaving is a highly stochastic and, thus, inefficient process; (2) fracture processes are governed by the bonds in a bulk crystal, and many materials and surfaces simply do not cleave; and (3) the location of the cleave is random, preventing data collection at specified regions of interest. Our new workflow is based on focused ion beam machining of micro-strain lenses, in which shape (rather than crystalline) anisotropy dictates the plane of cleavage, which can be placed at a specific target layer. As proof-of-principle, we show ARPES results from micro-cleaves of Sr2RuO4 along the ac plane and from two surface orientations of SrTiO3, a notoriously difficult to cleave cubic perovskite.

Validation of the Sexual Discounting Task for Use in Adolescents.

The Sexual Discounting Task (SDT) was developed to evaluate the effects of delay on decision making as it relates to sexual risk-taking behaviors. Though previously validated with other populations, including urban emerging adults, the current study sought to validate the SDT with adolescents. A sample of adolescents (N = 155; 61% female) between ages 14 and 21 (Mage = 19.5 years) was recruited to complete the SDT (involving choices between immediate unprotected sex and delayed sex with a condom with hypothetical sexual partners) and the Delay Discounting Task (a delay discounting task for money outcomes). Additionally, they completed several self-report measures assessing demographics, sexual behavior, and sexual history. If the condom was readily available, respondents were more likely to use a condom for partners who were judged "most likely to have an STI" and for those that participants were "least likely to have sex with." Moreover, when a condom was not immediately available, greater self-reported sexual risk-taking was related to greater sexual discounting (i.e., greater effects of delay on decreasing condom use). Furthermore, sexual discounting was greater among partners deemed more desirable and those judged "least likely to have an STI." Differences in sexual discounting were significant after controlling for immediately available condom use. Findings from the current study suggest that the SDT is clinically meaningful for adolescents and is sensitive to factors that influence real-world decisions to use condoms. Future treatment and prevention should consider delay discounting as an important variable affecting sexual risk behavior.

Identification of Idiopathic Pulmonary Fibrosis and Prediction of Disease Severity via Machine Learning Analysis of Comprehensive Metabolic Panel and Complete Blood Count Data.

BACKGROUND: Diagnosis of idiopathic pulmonary fibrosis (IPF) typically relies on high-resolution computed tomography imaging (HRCT) or histopathology, while monitoring disease severity is done via frequent pulmonary function testing (PFT). More reliable and convenient methods of diagnosing fibrotic interstitial lung disease (ILD) type and monitoring severity would allow for early identification and enhance current therapeutic interventions. This study tested the hypothesis that a machine learning (ML) ensemble analysis of comprehensive metabolic panel (CMP) and complete blood count (CBC) data can accurately distinguish IPF from connective tissue disease ILD (CTD-ILD) and predict disease severity as seen with PFT. METHODS: Outpatient data with diagnosis of IPF or CTD-ILD (n = 103 visits by 53 patients) were analyzed via ML methodology to evaluate (1) IPF vs CTD-ILD diagnosis; (2) %predicted Diffusing Capacity of Lung for Carbon Monoxide (DLCO) moderate or mild vs severe; (3) %predicted Forced Vital Capacity (FVC) moderate or mild vs severe; and (4) %predicted FVC mild vs moderate or severe. RESULTS: ML methodology identified IPF from CTD-ILD with AUCTEST = 0.893, while PFT was classified as DLCO moderate or mild vs severe with AUCTEST = 0.749, FVC moderate or mild vs severe with AUCTEST = 0.741, and FVC mild vs moderate or severe with AUCTEST = 0.739. Key features included albumin, alanine transaminase, %lymphocytes, hemoglobin, %eosinophils, white blood cell count, %monocytes, and %neutrophils. CONCLUSION: Analysis of CMP and CBC data via proposed ML methodology offers the potential to distinguish IPF from CTD-ILD and predict severity on associated PFT with accuracy that meets or exceeds current clinical practice.

Mechanical Analysis of a Novel 3D-printed External Fixator Design Versus Industry-standard External Fixators.

INTRODUCTION: External fixation is a critical component of orthopaedic fracture management and is used for various conditions, including trauma and pediatric orthopaedics. However, the availability and high cost of external fixation devices are a concern, especially in rural and developing countries. 3D printing technology has shown promise in reducing manufacturing costs and improving accessibility to external fixation devices. The purpose of this study was to evaluate the mechanical properties of a fully 3D-printed desktop external fixation device and compare the results with the mechanical properties of commonly used, clinically available external fixators. METHODS: A fully 3D printable external fixator was designed and printed in polylactic acid at two infill densities, 20% and 100%. The mechanical properties of the 3D-printed external fixators and several commercially available fixators were tested according to applicable sections of the American Society for Testing and Materials F1541 standard protocol in axial, medial-lateral, and anterior-posterior orientations. The primary outcomes measured included failure load, safe load, rigidity, and yield load. The mean differences between experimental and control groups were calculated using one-way analysis of variance and Tukey tests. RESULTS: The 20% infill 3D-printed construct showed poor performance compared with commercially available external fixators in all testing conditions and across most variables. The 100% infill 3D-printed construct was comparable with or superior to all commercially available devices in most testing conditions. The cost for printing a single 3D-printed 100% infill external fixator was $14.49 (United States Dollar). DISCUSSION: This study demonstrates that a low-cost desktop 3D printer can create an entirely 3D-printed external fixator that resists clinically relevant forces similar to medical-grade industry-standard external fixators. Therefore, there is potential for customizable and low-cost external fixators to be manufactured with desktop 3D printing for use in remote areas and other resource-constrained environments for fracture care.

Regulatory T cells use heparanase to access IL-2 bound to extracellular matrix in inflamed tissue.

Although FOXP3+ regulatory T cells (Treg) depend on IL-2 produced by other cells for their survival and function, the levels of IL-2 in inflamed tissue are low, making it unclear how Treg access this critical resource. Here, we show that Treg use heparanase (HPSE) to access IL-2 sequestered by heparan sulfate (HS) within the extracellular matrix (ECM) of inflamed central nervous system tissue. HPSE expression distinguishes human and murine Treg from conventional T cells and is regulated by the availability of IL-2. HPSE-/- Treg have impaired stability and function in vivo, including in the experimental autoimmune encephalomyelitis (EAE) mouse model of multiple sclerosis. Conversely, endowing monoclonal antibody-directed chimeric antigen receptor (mAbCAR) Treg with HPSE enhances their ability to access HS-sequestered IL-2 and their ability to suppress neuroinflammation in vivo. Together, these data identify a role for HPSE and the ECM in immune tolerance, providing new avenues for improving Treg-based therapy of autoimmunity.

H2O/HF Scavenging Mechanism in Cellulose-Based Separators for Lithium-Ion Batteries with Enhanced Cycle Life.

Lithium-ion batteries (LIBs) are increasingly being integrated into the transportation industry due to their high energy density, durability, and low cost. With the growing demand for transportation and other emerging applications, there is a concurrent rise in concern over LIB material sourcing and recycling. This urges the development of LIBs with extended cycle lifespans. One mechanism of capacity fading in LIBs is the dissolution of transition metals into the electrolyte after the cathode is etched with hydrofluoric acid (HF). HF is readily generated by the hydrolysis of the LIB electrolyte salt, lithium hexafluorophosphate (LiPF6), which makes minimizing moisture in the electrolyte a priority in manufacturing. In this study, a nonwoven, cellulose-based separator (CBS) is introduced as an alternative separator for battery technologies to scavenge residual water and HF from the electrolyte. The CBS is shown to be capable of scavenging varying amounts of water from the electrolyte based on different drying processes of the CBS, and a mechanism for this water scavenging is identified based on the materials present in the CBS. In addition, the chemical and electrochemical performance of the CBS in real battery conditions is investigated. Results suggest an effective H2O/HF scavenging capability in the CBS that allows LIB coin cells to have over 17% higher capacity retention than those with conventional separators. Furthermore, studies of the industrially manufactured, commercially relevant cylindrical and pouch cells show remarkable 761 and 103% improvements in the 60% capacity lifetime, respectively. The environmental friendliness, low cost, and easy application empowered by the cycle life improvements shown in this work make this nonwoven CBS a promising candidate for improving industry-level LIB performance.

Anti-tumor effect of pH-sensitive drug-loaded nanoparticles optimized via an integrated computational/experimental approach.

The acidic pH of tumor tissue has been used to trigger drug release from nanoparticles. However, dynamic interactions between tumor pH and vascularity present challenges to optimize therapy to particular microenvironment conditions. Despite recent development of pH-sensitive nanomaterials that can accurately quantify drug release from nanoparticles, tailoring release to maximize tumor response remains elusive. This study hypothesizes that a computational modeling-based platform that simulates the heterogeneously vascularized tumor microenvironment can enable evaluation of the complex intra-tumoral dynamics involving nanoparticle transport and pH-dependent drug release, and predict optimal nanoparticle parameters to maximize the response. To this end, SPNCD nanoparticles comprising superparamagnetic cores of iron oxide (Fe3O4) and a poly(lactide-co-glycolide acid) shell loaded with doxorubicin (DOX) were fabricated. Drug release was measured in vitro as a function of pH. A 2D model of vascularized tumor growth was calibrated to experimental data and used to evaluate SPNCD effect as a function of drug release rate and tissue vascular heterogeneity. Simulations show that pH-dependent drug release from SPNCD delays tumor regrowth more than DOX alone across all levels of vascular heterogeneity, and that SPNCD significantly inhibit tumor radius over time compared to systemic DOX. The minimum tumor radius forecast by the model was comparable to previous in vivo SPNCD inhibition data. Sensitivity analyses of the SPNCD pH-dependent drug release rate indicate that slower rates are more inhibitory than faster rates. We conclude that an integrated computational and experimental approach enables tailoring drug release by pH-responsive nanomaterials to maximize the tumor response.

Disease diagnosis and severity classification in pulmonary fibrosis using carbonyl volatile organic compounds in exhaled breath.

BACKGROUND: Pathophysiological conditions underlying pulmonary fibrosis remain poorly understood. Exhaled breath volatile organic compounds (VOCs) have shown promise for lung disease diagnosis and classification. In particular, carbonyls are a byproduct of oxidative stress, associated with fibrosis in the lungs. To explore the potential of exhaled carbonyl VOCs to reflect underlying pathophysiological conditions in pulmonary fibrosis, this proof-of-concept study tested the hypothesis that volatile and low abundance carbonyl compounds could be linked to diagnosis and associated disease severity. METHODS: Exhaled breath samples were collected from outpatients with a diagnosis of Idiopathic Pulmonary Fibrosis (IPF) or Connective Tissue related Interstitial Lung Disease (CTD-ILD) with stable lung function for 3 months before enrollment, as measured by pulmonary function testing (PFT) DLCO (%), FVC (%) and FEV1 (%). A novel microreactor was used to capture carbonyl compounds in the breath as direct output products. A machine learning workflow was implemented with the captured carbonyl compounds as input features for classification of diagnosis and disease severity based on PFT (DLCO and FVC normal/mild vs. moderate/severe; FEV1 normal/mild/moderate vs. moderately severe/severe). RESULTS: The proposed approach classified diagnosis with AUROC=0.877 ± 0.047 in the validation subsets. The AUROC was 0.820 ± 0.064, 0.898 ± 0.040, and 0.873 ± 0.051 for disease severity based on DLCO, FEV1, and FVC measurements, respectively. Eleven key carbonyl VOCs were identified with the potential to differentiate diagnosis and to classify severity. CONCLUSIONS: Exhaled breath carbonyl compounds can be linked to pulmonary function and fibrotic ILD diagnosis, moving towards improved pathophysiological understanding of pulmonary fibrosis.

A clinical marker-based modeling framework to preoperatively predict lymph node and vascular space involvement in endometrial cancer patients.

INTRODUCTION: Endometrial cancer (EC) has high mortality at advanced stages. Poor prognostic factors include grade 3 tumors, deep myometrial invasion, lymph node metastasis (LNM), and lymphovascular space invasion (LVSI). Preoperative knowledge of patients at higher risk of lymph node involvement, when such involvement is not suspected, would benefit surgery planning and patient prognosis. This study implements an ensemble machine learning approach that evaluates Cancer Antigen 125 (CA125) along with histologic type, preoperative grade, and age to predict LVSI, LNM and stage in EC patients. METHODS: A retrospective chart review spanning January 2000 to January 2015 at a regional hospital was performed. Women 18 years or older with a diagnosis of EC and preoperative or within one-week CA125 measurement were included (n = 842). An ensemble machine learning approach was implemented based on a stacked generalization technique to evaluate CA125 in combination with histologic type, preoperative grade, and age as predictors, and LVSI, LNM and disease stage as outcomes. RESULTS: The ensemble approach predicted LNM and LVSI in EC patients with AUROCTEST of 0.857 and 0.750, respectively, and predicted disease stage with AUROCTEST of 0.665. The approach achieved AUROCTEST for LVSI and LNM of 0.750 and 0.643 for grade 1 patients, and of 0.689 and 0.952 for grade 2 patients, respectively. CONCLUSION: An ensemble machine learning approach offers the potential to preoperatively predict LVSI, LNM and stage in EC patients with adequate accuracy based on CA125, histologic type, preoperative grade, and age.

Do pediatric oral suspension acetaminophen and ibuprofen product labeling and online resources facilitate intended use?

Background: Caregivers often have difficulty administering pediatric medications which frequently results in increased dosing error risk. Objective: We examined health literacy characteristics of pediatric over-the-counter (OTC) oral suspension acetaminophen and ibuprofen instructional materials and dosing instruments. Methods: We conducted a descriptive analysis of dosing instructions, measuring syringe characteristics, and internet-based resources among a sample of OTC pediatric oral suspension acetaminophen and ibuprofen products (n = 14). Results: All products included Drug Facts Panels, employed consistent abbreviation use, and stated measuring dosage with syringe provided. However, oral syringe dosing increment markings did not match box or bottle dosing charts. Most products had supplemental English-language internet-based content resources available. Conclusions: While OTC pediatric oral suspension acetaminophen and ibuprofen products labeling included key drug fact elements, there were inconsistencies between medication dosing chart labeling guidelines and oral syringe dosing increments/markings. It is vital that oral dosing syringes are clearly marked to match product dosing chart labeling s as a means of potentially reducing caregiver dosing errors.

Fate of Quasiparticles at High Temperature in the Correlated Metal Sr_{2}RuO_{4}.

We study the temperature evolution of quasiparticles in the correlated metal Sr_{2}RuO_{4}. Our angle resolved photoemission data show that quasiparticles persist up to temperatures above 200 K, far beyond the Fermi liquid regime. Extracting the quasiparticle self-energy, we demonstrate that the quasiparticle residue Z increases with increasing temperature. Quasiparticles eventually disappear on approaching the bad metal state of Sr_{2}RuO_{4} not by losing weight but via excessive broadening from super-Planckian scattering. We further show that the Fermi surface of Sr_{2}RuO_{4}-defined as the loci where the spectral function peaks-deflates with increasing temperature. These findings are in semiquantitative agreement with dynamical mean field theory calculations.

Application timing and duration of LED and HPS supplements differentially influence yield, nutrient bioaccumulation, and light use efficiency of greenhouse basil across seasons.

Three primary factors that impact plant growth and development are light quantity, quality, and duration. Commercial growers can manipulate these parameters using light-emitting diodes (LEDs) to optimize biomass yield and plant quality. There is significant potential to synergize supplemental lighting (SL) parameters with seasonal variation of ambient sunlight to optimize crop light use efficiency (LUE), which could increase biomass while reducing SL electricity costs. To determine the best lighting characteristics and durations for different crops, particularly for enhancing the yield and nutritional quality of high-value specialty crops produced in greenhouses during the winter, a thorough efficacy comparison of progressive incremental daily light integrals (DLIs) using LED and high-pressure sodium (HPS) sources is required. The purpose of this study was to compare the effects of differential application timing and DLIs of supplemental blue (B)/red (R) narrowband wavelengths from LED lighting systems and HPS lamps on greenhouse hydroponic basil (Ocimum basilicum var. 'Genovese') production. We assessed edible biomass, nutrient bioaccumulation, and LUE. Nine light treatments included: one non-supplemented natural light (NL) control, two end-of-day (EOD) HPS treatments applied for 6 h and 12 h, five EOD 20B/80R LED treatments applied for 3 h, 6 h, 9 h, 12 h, 18 h, and one continuous LED treatment (24 h). Each SL treatment provided 100 µmol·m-2·s-1. The DLI of the NL control averaged 9.9 mol·m-2·d-1 during the growth period (ranging from 4 to 20 mol·m-2·d-1). SL treatments and growing seasons significantly impacted biomass and nutrient bioaccumulation; some SL treatments had lower yields than the non-supplemented NL control. January growing season produced the lowest fresh mass (FM) and dry mass (DM) values compared to November, which had the highest. Mineral analyses revealed that both growing seasons and lighting types impacted macro and micronutrient accumulation. Additionally, the efficiency of each treatment in converting electrical energy into biomass varied greatly. EOD supplements using LED and HPS lighting systems both have merits for efficiently optimizing yield and nutrient accumulation in basil; however, biomass and nutrient tissue concentrations highly depend on seasonal variation in ambient sunlight in conjunction with a supplement's spectral quality, DLI, and application schedule.

The development and acceptability of an educational and training intervention for recruiters to neonatal trials: the TRAIN project.

BACKGROUND: Suboptimal or slow recruitment affects 30-50% of trials. Education and training of trial recruiters has been identified as one strategy for potentially boosting recruitment to randomised controlled trials (hereafter referred to as trials). The Training tRial recruiters, An educational INtervention (TRAIN) project was established to develop and assess the acceptability of an education and training intervention for recruiters to neonatal trials. In this paper, we report the development and acceptability of TRAIN. METHODS: TRAIN involved three sequential phases, with each phase contributing information to the subsequent phase(s). These phases were 1) evidence synthesis (systematic review of the effectiveness of training interventions and a content analysis of the format, content, and delivery of identified interventions), 2) intervention development using a Partnership (co-design/co-creation) approach, and 3) intervention acceptability assessments with recruiters to neonatal trials. RESULTS: TRAIN, accompanied by a comprehensive intervention manual, has been designed for online or in-person delivery. TRAIN can be offered to recruiters before trial recruitment begins or as refresher sessions during a trial. The intervention consists of five core learning outcomes which are addressed across three core training units. These units are the trial protocol (Unit 1, 50 min, trial-specific), understanding randomisation (Unit 2, 5 min, trial-generic) and approaching and engaging with parents (Unit 3, 70 min, trial-generic). Eleven recruiters to neonatal trials registered to attend the acceptability assessment training workshops, although only four took part. All four positively valued the training Units and resources for increasing recruiter preparedness, knowledge, and confidence. More flexibility in how the training is facilitated, however, was noted (e.g., training divided across two workshops of shorter duration). Units 2 and 3 were considered beneficial to incorporate into Good Clinical Practice Training or as part of induction training for new staff joining neonatal units. CONCLUSION: TRAIN offers a comprehensive co-produced training and education intervention for recruiters to neonatal trials. TRAIN was deemed acceptable, with minor modification, to neonatal trial recruiters. The small number of recruiters taking part in the acceptability assessment is a limitation. Scale-up of TRAIN with formal piloting and testing for effectiveness in a large cluster randomised trial is required.

Oncoplastic Breast Reduction: A Systematic Review of Postoperative Complications.

Background: Breast-conserving therapy with oncoplastic reduction is a useful strategy for partial mastectomy defect reconstruction. The most recently published systematic review of oncoplastic breast reduction outcomes from 2015 showed wound dehiscence in 4.3%, hematoma in 0.9%, infection in 2.8%, and nipple necrosis in 0.9% of patients. We performed a systematic review of oncoplastic breast reduction literature, comparing outcomes and complication rates reported over the past 8 years. Methods: Studies describing the use of oncoplastic breast reduction and discussion of postoperative complications were included. The primary outcome assessed was the postoperative complication rate; secondary outcomes analyzed were rates of margin expansion, completion mastectomy, and delays in adjuvant therapy due to complications. Results: Nine articles met inclusion criteria, resulting in 1715 oncoplastic breast reduction patients. The mean rate of hematoma was 3%, nipple necrosis was 2%, dehiscence was 4%, infection was 3%, and seroma was 2%. The need for re-excision of margins occurred in 8% of patients, and completion mastectomy in 2%. Finally, delay in adjuvant treatment due to a postoperative complication occurred in 4% of patients. Conclusions: Oncoplastic breast reduction is an excellent option for many patients undergoing breast-conserving therapy; however, postoperative complications can delay adjuvant radiation therapy. Results of this systematic literature review over the past 8 years showed a slight increase in complication rate compared to the most recent systematic review from 2015. With increased popularity and surgeon familiarity, oncoplastic breast reduction remains a viable option for reconstruction of partial mastectomy defects despite a slight increase in complication rate.

Clinical Practice Update: Achilles Tendon Rupture.

Achilles tendon rupture is a common injury. It most often occurs in middle aged men who participate in recreational sports. The injury classically presents with a loud popping noise and immediate pain and weakness of the lower extremity during actions such as jumping or running. The diagnosis is made clinically, but an MRI is often obtained for confirmation of rupture and to aid in surgical planning. Treatment is either operative, with open or minimally invasive approaches, or non-operative, with functional bracing or plaster casting. Surgical treatment was preferred for much of the 20th century, but non-operative treatment has gained significant favor in the past 15 years as new evidence has demonstrated similar long-term outcomes to surgery. Neither treatment option is currently considered superior to the other in all cases. Surgery is associated with a risk for surgical complications and is, therefore, often a poor option for the elderly and those with significant comorbidities. Non-operative management is associated with an increased risk for re-injury which is often undesirable for young and highly active patients. Ultimately, the goals and priorities of each individual patient should guide the decision of which treatment option to pursue.

Senolytic treatment with dasatinib and quercetin does not improve overall influenza responses in aged mice.

Age is the greatest risk factor for adverse outcomes following influenza (flu) infection. The increased burden of senescent cells with age has been identified as a root cause in many diseases of aging and targeting these cells with drugs termed senolytics has shown promise in alleviating many age-related declines across organ systems. However, there is little known whether targeting these cells will improve age-related deficits in the immune system. Here, we utilized a well characterized senolytic treatment with a combination of dasatinib and quercetin (D + Q) to clear aged (18-20 months) mice of senescent cells prior to a flu infection. We comprehensively profiled immune responses during the primary infection as well as development of immune memory and protection following pathogen reencounter. Senolytic treatment did not improve any aspects of the immune response that were assayed for including: weight loss, viral load, CD8 T-cell infiltration, antibody production, memory T cell development, or recall ability. These results indicate that D + Q may not be an appropriate senolytic to improve aged immune responses to flu infection.

A Template for Translational Bioinformatics: Facilitating Multimodal Data Analyses in Preclinical Models of Neurological Injury.

Background: Pediatric neurological injury and disease is a critical public health issue due to increasing rates of survival from primary injuries (e.g., cardiac arrest, traumatic brain injury) and a lack of monitoring technologies and therapeutics for the treatment of secondary neurological injury. Translational, preclinical research facilitates the development of solutions to address this growing issue but is hindered by a lack of available data frameworks and standards for the management, processing, and analysis of multimodal data sets. Methods: Here, we present a generalizable data framework that was implemented for large animal research at the Children's Hospital of Philadelphia to address this technological gap. The presented framework culminates in an interactive dashboard for exploratory analysis and filtered data set download. Results: Compared with existing clinical and preclinical data management solutions, the presented framework accommodates heterogeneous data types (single measure, repeated measures, time series, and imaging), integrates data sets across various experimental models, and facilitates dynamic visualization of integrated data sets. We present a use case of this framework for predictive model development for intra-arrest prediction of cardiopulmonary resuscitation outcome. Conclusions: The described preclinical data framework may serve as a template to aid in data management efforts in other translational research labs that generate heterogeneous data sets and require a dynamic platform that can easily evolve alongside their research.