Localized Plasmonic Heating for Single-Molecule DNA Rupture Measurements in Optical Tweezers.

To date, studies on the thermodynamic and kinetic processes that underlie biological function and nanomachine actuation in biological- and biology-inspired molecular constructs have primarily focused on photothermal heating of ensemble systems, highlighting the need for probes that are localized within the molecular construct and capable of resolving single-molecule response. Here we present an experimental demonstration of wavelength-selective, localized heating at the single-molecule level using the surface plasmon resonance of a 15 nm gold nanoparticle (AuNP). Our approach is compatible with force-spectroscopy measurements and can be applied to studies of the single-molecule thermodynamic properties of DNA origami nanomachines as well as biomolecular complexes. We further demonstrate wavelength selectivity and establish the temperature dependence of the reaction coordinate for base-pair disruption in the shear-rupture geometry, demonstrating the utility and flexibility of this approach for both fundamental studies of local (nanometer-scale) temperature gradients and rapid and multiplexed nanomachine actuation.

Structural interactions in polymer-stabilized magnetic nanocomposites.

Superparamagnetic iron oxide nanoparticles (SPIONs) have attracted significant attention because of their nanoscale magnetic properties. SPION aggregates may afford emergent properties, resulting from dipole-dipole interactions between neighbors. Such aggregates can display internal order, with high packing fractions (>20%), and can be stabilized with block co-polymers (BCPs), permitting design of tunable composites for potential nanomedicine, data storage, and electronic sensing applications. Despite the routine use of magnetic fields for aggregate actuation, the impact of those fields on polymer structure, SPION ordering, and magnetic properties is not fully understood. Here, we report that external magnetic fields can induce ordering in SPION aggregates that affect their structure, inter-SPION distance, magnetic properties, and composite Tg. SPION aggregates were synthesized in the presence or absence of magnetic fields or exposed to magnetic fields post-synthesis. They were characterized using transmission electron microscopy (TEM), small angle X-ray scattering (SAXS), superconducting quantum interference device (SQUID) analysis, and differential scanning calorimetry (DSC). SPION aggregate properties depended on the timing of field application. Magnetic field application during synthesis encouraged preservation of SPION chain aggregates stabilized by polymer coatings even after removal of the field, whereas post synthesis application triggered subtle internal reordering, as indicated by increased blocking temperature (TB), that was not observed via SAXS or TEM. These results suggest that magnetic fields are a simple, yet powerful tool to tailor the structure, ordering, and magnetic properties of polymer-stabilized SPION nanocomposites.

Limb Salvage Using Microsurgical Free Tissue Transfer in Severe Frostbite.

PURPOSE: Frostbite is often managed conservatively; however, in severe cases, microsurgical free tissue transfer is required for soft tissue coverage and limb salvage. Given its rarity, the techniques and outcomes of these cases are not well described. The purpose of this report is to present the largest case series, to date, of frostbite injuries requiring microsurgical reconstruction for limb salvage. METHODS: A single-center retrospective review was conducted of all patients who underwent free tissue transfer by a single surgeon from 2008 to 2022. Patients of all ages were included if they suffered a frostbite injury requiring free tissue transfer. Demographics, operative details, and surgical outcomes were recorded. RESULTS: Eight patients with frostbite injuries were included in the report. Patients had frostbite injuries either to the lower extremities (n = 4) or to both upper and lower extremities (n = 4). Sixteen free flaps were done in total including four paired chimeric and eight single free flaps. Flap recipient sites included knees (n = 5), foot/ankle (n = 3), dorsal hands (n = 2), and thumbs (n = 2). All 16 flaps survived. Five patients had complications: four with major complications requiring operative management and two with minor complications requiring conservative management. Mean follow-up time was 505.7 days (range 115-1564). All lower extremity reconstructions were able to weight-bear at an average of 125.2 days post-injury (range 87-164). CONCLUSIONS: This case series demonstrates that free tissue transfer is a robust option for soft tissue coverage and functional limb salvage in patients with severe frostbite injuries to both upper and lower extremities.

Rethinking Oncologic Facial Nerve Reconstruction in the Acute Phase Through Classification of the Level of Injury.

Early facial nerve reconstruction should be offered in every patient with oncological resections of the facial nerve due to the debilitating functional and psychosocial consequences of facial nerve palsy. Oncologic pathology or oncologic resection accounts for the second most common cause of facial nerve palsy. In the case of these acute injuries, selecting an adequate method for reconstruction to optimize functional and psychosocial well-being is paramount. Authors advocate consideration of the level of injury as a framework for approaching the viable options of reconstruction systematically. Authors breakdown oncologic injuries to the facial nerve in three levels in relation to their nerve reconstruction methods and strategies: Level I (intracranial to intratemporal), Level II (intratemporal to extratemporal and intraparotid), and Level III (extratemporal and extraparotid). Clinical features, common clinical scenarios, donor nerves available, recipient nerve, and reconstruction priorities will be present at each level. Additionally, examples of clinical cases will be shared to illustrate the utility of framing acute facial nerve injuries within injury levels. Selecting donor nerves is critical in successful facial nerve reconstruction in oncological patients. Usually, a combination of facial and nonfacial donor nerves (hybrid) is necessary to achieve maximal reinnervation of the mimetic muscles. Our proposed classification of three levels of facial nerve injuries provides a selection guide, which prioritizes methods for function nerve reconstruction in relation of the injury level in oncologic patients while prioritizing functional outcomes.

Systemic thrombolytic and ultrasound-assisted catheter-directed thrombolysis for treatment of acute pulmonary embolism: a 7-year, multicenter experience.

Treatment of acute pulmonary embolism (PE) varies based upon risk stratification and ranges from outpatient oral anticoagulation to emergency surgical embolectomy. Patients with high-risk PE can be considered for systemic thrombolytic (ST) based upon guideline recommendations, but intermediate-risk PE does not currently have strong evidence to guide primary reperfusion strategies via thrombolytic administration. Ultrasound-assisted catheter-directed thrombolysis (USAT) is an alternative reperfusion option to ST but is not currently recommended as first line in any key guidelines due to limited available evidence. This retrospective, multicenter, observational study compares 210 patients treated with USAT (n = 105) or ST (n = 105) for acute high- or intermediate-risk PE in three hospitals. Baseline characteristics were significant in that severity of illness was higher in those that received ST, which limited comparisons of outcomes. The primary outcome of major bleeding in patients receiving USAT was 15.2% and 22.9% in those that received ST. Efficacy of reperfusion strategy was observed to be 86.7% of patients in USAT group and 65.7% in ST group. Reperfusion strategies had no difference in in-hospital death, intensive care length of stay, or hospital length of stay. Predefined subgroup analysis found that high-risk PE had higher mortality (14.7%) than intermediate-risk PE (0%) regardless of reperfusion strategy. Upon multivariate analysis, high-risk PE was the only independent risk factor for major bleeding while USAT therapy and intermediate-risk PE were independent predictors of efficacy. Due to the difference in baseline severity of illness, direct comparisons in primary outcomes to each group was not performed. We have described real world usage of both USAT and ST and which patients were likely to receive each therapy at these institutions.

Malignant Peripheral Nerve Sheath Tumors of the Brachial Plexus: A Single-Center Experience on Diagnosis, Management, and Outcomes.

INTRODUCTION: The incidence of malignant peripheral nerve sheath tumors (MPNSTs) is 0.001%. Commonly, MPNST arise in neurofibromatosis; however, they can occur sporadically, de novo or from a preexisting neurofibroma. Malignant peripheral nerve sheath tumors are aggressive tumors with high rates of local recurrence and metastasis. The prognosis is poor with 5-year survival rates of 15% to 50%. Unfortunately, given the rarity of these tumors, it is not clear how to best manage these patients. The purposes of this study were (1) to discuss our experience with MPNST and particularly our difficulties with diagnosis and management, and (2) to review the literature. MATERIALS AND METHODS: We report on all tumors of the brachial plexus excised between 2013 and 2019. We report 3 cases of MPNST, their treatment, and their outcomes. RESULTS: Thirteen patients underwent surgical excision of an intrinsic brachial plexus mass. Three of these patients (2 male, 1 female; average age, 36 years) were diagnosed with an MPNST. Two patients with an MPNST had neurofibromatosis type 1. All patients with an MPNST had a tumor >8 cm, motor and sensory deficits, and pain. All 3 patients with MPNST underwent a magnetic resonance imaging (MRI) before diagnosis. The average time from initial symptom onset to MRI was 12.3 months. Only 1 of the MRIs suggested a malignant tumor, with no MRI identifying an MPNST. One patient underwent an excisional biopsy, and 2 had incisional biopsies. Because of the lack of diagnosis preoperatively, all patients had positive margins given the limited extent of surgery. Returning for excision in an attempt to achieve negative margins in a large oncologically contaminated field was not possible because defining the boundaries of the initial surgical field was unachievable; therefore, the initial surgery was their definitive surgical management. All patients were referred to oncology and received radiation therapy. CONCLUSIONS: Malignant peripheral nerve sheath tumors must be suspected in enlarging masses (>5 cm) with the constellation of pain, motor, and sensory deficits. Computed tomography- or ultrasound-guided core needle biopsy under brachial plexus block or sedation is required for definitive diagnosis to allow for a comprehensive approach to the patient's tumor with a higher likelihood of disease-free survival.

Surgical Treatment of Parsonage Turner Syndrome With Primary Nerve Transfers: A Case Series and Cadaver Dissection.

ABSTRACT: Parsonage Turner syndrome (PTS) is the development of severe, spontaneous pain with subsequent nerve palsy. Unfortunately, many patients never achieve full functional recovery, and many have chronic pain. The use of nerve transfers in PTS has not been reported in the literature. We present 4 cases of PTS treated surgically with primary nerve transfer and neurolysis of the affected nerve following the absence of clinical and electrodiagnostic recovery at 5 months from onset. In addition, we present a cadaver dissection demonstrating an interfascicular dissection of the anterior interosseous nerve (AIN) into its components to enable a fascicular transfer in partial AIN neuropathy. Two patients with complete axillary neuropathy underwent a neurorrhaphy between the nerve branch to the lateral head of the triceps and the anterior/middle deltoid nerve branch of the axillary nerve. Two patients with partial AIN neuropathy involving the FDP to the index finger (FDP2) underwent a neurorrhaphy between an extensor carpi radialis brevis nerve branch and the FDP2 nerve branch. All patients had neurolysis of the affected nerves. All subjects recovered at least M4 motor strength. The cadaver dissection demonstrates 3 separate nerve fascicles of the AIN into FPL, FDP2, and pronator quadratus that can be individually selected for reinnervation with a fascicular nerve transfer. Functional recovery for patients with PTS with neurolysis alone is variable. Surgical treatment with neurolysis and a nerve transfer to improve functional recovery when no recovery is seen by 5 months is an option.

The Addition of a Nerve Transfer to the Treatment of Peroneal Neuropathy Secondary to Intraneural Ganglion: Case Series.

ABSTRACT: Peroneal intraneural ganglia are rare, and their management is controversial. Presently, the accepted treatment of intraneural ganglia is decompression and ligation of the articular nerve branch. Although this treatment prevents recurrence of the ganglia, the resultant motor deficit of foot drop in the case of intraneural peroneal ganglia is unsatisfying. Foot drop is classically treated with splinting or tendon transfers to the foot. We have recently published a case report of a peroneal intraneural ganglion treated by transferring a motor nerve branch of flexor hallucis longus into a nerve branch of tibialis anterior muscle in addition to articular nerve branch ligation and decompression of the intraneural ganglion to restore the patient's ability to dorsiflex. We have since performed this procedure on 4 additional patients with appropriate follow-up. Depending on the initial onset of foot drop and time to surgery, nerve transfer from flexor hallucis longus to anterior tibialis nerve branch may be considered as an adjunct to decompression and articular nerve branch ligation for the treatment of symptomatic peroneal intraneural ganglion.

Comparison of Ceftriaxone and Antipseudomonal ß-Lactam Antibiotics Utilized for Potential AmpC ß-Lactamase-Producing Organisms.

Background: Induction of antibiotic resistance is associated with increased morbidity and mortality in AmpC ß-lactamase producing Enterobacteriaceae. The use of ceftriaxone is controversial for treatment of these organisms due to concerns for inducible resistance. This study was designed to compare treatment failure rates between ceftriaxone and antipseudomonal ß-lactam antibiotics when used as definitive therapy for organisms most commonly associated with chromosomal AmpC ß-lactamase production. Methods: A retrospective, single-center cohort study was performed enrolling patients hospitalized with monomicrobial Enterobacter, Citrobacter, or Serratia spp. infections. The primary objective compared proportion of treatment failure between groups. All patients received either ceftriaxone or an antipseudomonal ß-lactam alone within 24 hours of culture finalization, and with a duration of at least 72 hours for definitive treatment. Treatment failure was defined as either clinical failure (abnormal white blood cell count or temperature on day 7 or 14 post-antibiotics) or microbiologic failure (regrowth of the same organism at same site within 14 or 21 days). Results: Of 192 total patients, treatment failure was observed in 24/71 patients (34%) receiving ceftriaxone and in 42/121 patients (35%) receiving antipseudomonal ß-lactam (P = .98). No difference was observed between clinical or microbiologic failure rates between groups. The ceftriaxone group had significantly more patients undergoing treatment for urinary tract infections (51% vs 17%, P < .001), but treatment failure rates remained similar between groups when comparing infections of all other sources. Conclusion: Ceftriaxone has comparable treatment failure rates to antipseudomonal ß-lactams for susceptible Enterobacteriaceae infections and may be considered as a therapeutic option. Further, prospective research is needed to validate optimal dosing and application in all sites of infection.

Self-Assembly and sedimentation of 5 nm SPIONs using horizontal, high magnetic fields and gradients.

Superparamagnetic iron oxide nanoparticles (SPIONs) are employed in multiple applications, especially within medical and chemical engineering fields. However, their magnetic separation is very challenging as the magnetophoretic motion is hindered by thermal energy and viscous drag. Recent studies have addressed the recovery of SPIONs by a combination of cooperative magnetophoresis and sedimentation. Nevertheless, the effect of horizontal, high fields and gradients on the vertical sedimentation of SPIONs has not been described. In this work, we report, for the first time, the magnetically facilitated sedimentation of 5 nm particles by applying fields and gradients perpendicular to gravity. The magnetic field was generated by quadrupole magnetic sorters and the process was measured with time by tracking the concentration along the length of a channel contacting the 5 nm SPIONs within the quadrupole field. Our experimental data suggest that aggregates of 60-90 particles are formed in the system; thus, particle agglomeration by dipole-dipole interactions was promoted, and these clusters settled down as a result of gravitational forces. Multiple variables and parameters were evaluated, including the initial SPION concentration, the temperature, the magnetic field and gradient and operation time. It was found that the process was improved by decreasing the initial concentration and the temperature, but the magnitude of the magnetic field and gradient did not significantly affect the sedimentation. Finally, the separation process was rapid, with the systems reaching the equilibrium in approximately 20 minutes, which is a significant advantage in comparison to other systems that require longer times and larger particle sizes.