Comparison of Patient-Reported Outcomes after Local Flap Coverage versus Amputation for Complex Lower Extremity Trauma.

 There is a paucity of patient-reported outcomes (PROs) data in lower extremity salvage. Limb salvage can often be achieved with the use of local muscle flaps or fasciocutaneous flaps. The purpose of this study was to compare PROs of patients who underwent lower extremity salvage using local fasciocutaneous flaps or muscle flaps to lower extremity amputation.

Alzheimer's disease-associated genotypes differentially influence chronic evoked seizure outcomes and antiseizure medicine activity in aged mice.

Introduction: Alzheimer's disease (AD) patients are at greater risk of focal seizures than similarly aged adults; these seizures, left untreated, may worsen functional decline. Older people with epilepsy generally respond well to antiseizure medications (ASMs). However, whether specific ASMs can differentially control seizures in AD is unknown.

Diet composition and sterilization modifies intestinal microbiome diversity and burden of Theiler's virus infection-induced acute seizures.

Objective: Brain infection with Theiler's murine encephalomyelitis virus (TMEV) in C57BL/6J mice can induce acquired epileptogenesis. Diet alters acute seizure incidence in TMEV-infected mice; yet it is unclear whether intestinal dysbiosis may also impact acute or chronic behavioral comorbidities. This study thus assessed the impact of diet formulation and sterilization on acute seizure presentation, gut microbiome composition, and epilepsy-related chronic behavioral comorbidities.

Chronic evoked seizures in young pre-symptomatic APP/PS1 mice induce serotonin changes and accelerate onset of Alzheimer's disease-related neuropathology.

Objective: Hyperexcitability is intimately linked to Alzheimer's disease (AD) pathology, but the precise timing and contributions of neuronal hyperexcitability to disease progression is unclear. Seizure induction in rodent AD models can uncover new therapeutic targets. Further, investigator-evoked seizures can directly establish how hyperexcitability and AD-associated risk factors influence neuropathological hallmarks and disease course at presymptomatic stages.

Chronic evoked seizures in young pre-symptomatic APP/PS1 mice induce serotonin changes and accelerate onset on Alzheimer's disease-related neurpathology.

Objective: People with early-onset Alzheimer's disease (AD) are at elevated seizure risk. Further, chronic seizures in pre-symptomatic stages may disrupt serotonin pathway-related protein expression, precipitating the onset of AD-related pathology and burden of neuropsychiatric comorbidities.

Methods: 2-3-month-old APP/PS1, PSEN2-N141I, and transgenic control mice were sham or corneal kindled for 2 weeks to model chronic seizures.

Chronic seizures induce sex-specific cognitive deficits with loss of presenilin 2 function.

Patients with early-onset Alzheimer's disease (EOAD) are at elevated risk for seizures, including patients with presenilin 2 (PSEN2) variants. Like people with epilepsy, uncontrolled seizures may worsen cognitive function in AD. While the relationship between seizures and amyloid beta accumulation has been more thoroughly investigated, the role of other drivers of seizure susceptibility in EOAD remain relatively understudied.

Can Old Animals Reveal New Targets? The Aging and Degenerating Brain as a New Precision Medicine Opportunity for Epilepsy.

Older people represent the fastest growing group with epilepsy diagnosis. For example, cerebrovascular disease may underlie roughly 30-50% of epilepsy in older adults and seizures are also an underrecognized comorbidity of Alzheimer's disease (AD). As a result, up to 10% of nursing home residents may take antiseizure medicines (ASMs).

Continuous seizure emergency evoked in mice with pharmacological, electrographic, and pathological features distinct from status epilepticus.

Objectives: Benzodiazepines are the standard of care for the management of sustained seizure emergencies, including status epilepticus (SE) and seizure clusters. Seizure clusters are a variably defined seizure emergency wherein a patient has multiple seizures above a baseline rate, with intervening periods of recovery, distinguishing clusters from SE. Although these seizure emergencies are phenotypically distinct, the precise pathophysiological and mechanistic differences between SE and seizure clusters are understudied.

Development of an antiepileptogenesis drug screening platform: Effects of everolimus and phenobarbital.

Objective: The kainic acid (KA)-induced status epilepticus (SE) model in rats is a well-defined model of epileptogenesis. This model closely recapitulates many of the clinical and pathological characteristics of human temporal lobe epilepsy (TLE) that arise following SE or another neurological insult. Spontaneous recurrent seizures (SRS) in TLE can present after a latent period following a neurological insult (traumatic brain injury, SE event, viral infection, etc.

Diurnal burden of spontaneous seizures in early epileptogenesis in the post-kainic acid rat model of epilepsy.

Patients with epilepsy can experience diurnal seizure patterns. However, few studies in rodent models of temporal lobe epilepsy (TLE) routinely quantify the diurnal pattern of spontaneous recurrent seizures (SRS), and those that have conducted such assessments used small groups. This study thus aimed to define whether there was a diurnal pattern of SRS in the early phases of epileptogenesis in a large cohort (n = 40) of post-kainic acid (KA)-induced status epilepticus (SE) male Sprague Dawley rats.

Alzheimer's Disease and Epilepsy: A Perspective on the Opportunities for Overlapping Therapeutic Innovation.

Early-onset Alzheimer's disease (AD) is associated with variants in amyloid precursor protein (APP) and presenilin (PSEN) 1 and 2. It is increasingly recognized that patients with AD experience undiagnosed focal seizures. These AD patients with reported seizures may have worsened disease trajectory.

Antiseizure drug efficacy and tolerability in established and novel drug discovery seizure models in outbred vs inbred mice.

Objective: Initial identification of new investigational drugs for the treatment of epilepsy is commonly conducted in well-established mouse acute and chronic seizure models: for example, maximal electroshock (MES), 6 Hz, and corneal kindling. Comparison of the median effective dose (ED50) of approved antiseizure drugs (ASDs) vs investigational agents in these models provides evidence of their potential for clinical efficacy. Inbred and outbred mouse strains exhibit differential seizure susceptibility.

Loss of presenilin 2 age-dependently alters susceptibility to acute seizures and kindling acquisition.

Patients with Alzheimer's disease (AD) experience seizures at higher rates than the general population of that age, suggesting an underexplored role of hyperexcitability in AD. Genetic variants in presenilin (PSEN) 1 and 2 genes lead to autosomal dominant early-onset AD (ADAD); patients with PSEN gene variants also report seizures. Pharmacological control of seizures in AD may be disease-modifying.

Repeated Intraperitoneal Administration of Low-Concentration Methylcellulose Leads to Systemic Histologic Lesions Without Loss of Preclinical Phenotype.

Methylcellulose (MC; 0.5% concentration) is commonly used when evaluating investigational agents for efficacy in preclinical models of disease. When administered by the oral (PO) route, MC is considered a Food and Drug Administration "generally recognized as safe" compound.

Lamotrigine-resistant corneal-kindled mice: A model of pharmacoresistant partial epilepsy for moderate-throughput drug discovery.

Objective: Despite numerous treatments for epilepsy, over 30% of patients remain resistant to available antiseizure drugs (ASDs). Thus, there is a strong need for more effective ASDs for these individuals. Early ASD discovery has historically relied on acute in vivo seizure models (maximal electroshock, subcutaneous pentylenetetrazol, 6 Hz), which lack the pathophysiology that defines chronic epilepsy.

Complex modeling: a strategy and software program for combining multiple information sources to solve ill posed structure and nanostructure inverse problems.

A strategy is described for regularizing ill posed structure and nanostructure scattering inverse problems (i.e. structure solution) from complex material structures.

Corrugation in exfoliated graphene: an electron microscopy and diffraction study.

Low-energy electron microscopy and microprobe diffraction are used to image and characterize corrugation in SiO(2)-supported and suspended exfoliated graphene at nanometer length scales. Diffraction line-shape analysis reveals quantitative differences in surface roughness on length scales below 20 nm which depend on film thickness and interaction with the substrate. Corrugation decreases with increasing film thickness, reflecting the increased stiffness of multilayer films.

Surgical wound bed preparation of chronic and acute wounds.

Our aging population has presented us with many new challenges. One such challenge is the need to manage an increase in wound-related problems effectively and efficiently. Over time, two parallel, yet divergent, management systems have developed.

The incidence of late cephalohematoma following craniofacial surgery.

Background: Cranial vault remodeling procedures are carried out for both syndromic and nonsyndromic craniosynostosis as well as to correct some acquired deformities of the cranial vault. These procedures improve not only cosmesis but also neurological symptoms. The purpose of this study was to determine the incidence of "late" cephalohematoma, an underreported complication following these complex procedures.

Comparison of wound irrigation and tangential hydrodissection in bacterial clearance of contaminated wounds: results of a randomized, controlled clinical study.

Thorough irrigation of contaminated or infected traumatic and open surgical wounds is considered standard practice. High-power pulse lavage is frequently used to facilitate the removal of surface contaminants and bacteria but studies to compare the results of various irrigation techniques are limited. The purpose of this randomized, controlled clinical study was to compare the ability of a high-pressure parallel waterjet (pressure range 5,025 to 7,360 psi) to pulse lavage (pressure 40 psi) in reducing wound bacterial counts.

Solutions to challenging digital replantations.

Replantation of amputated digits remains one of the most challenging areas in plastic and reconstructive surgery. Complicated cases of digital amputation, such as fingertip amputations, multidigital amputations, and so forth, pose an even greater challenge, requiring extraordinary solutions for successful replantation. The authors present their experience with complicated digital replantations at the University of Medicine and Dentistry of New Jersey-New Jersey Medical School.

Immediate reconstruction of oncologic hemipelvectomy defects.

Background: Soft tissue and bony tumors of the pelvis are rare, but when they occur, treatment presents both an oncologic surgical and a reconstructive challenge. After reconstruction, soft tissue defects can be large and there is usually exposed bone and/or joint. A retroperitoneal abdominal wall defect may also be present.

Stem cells and distraction osteogenesis: endothelial progenitor cells home to the ischemic generate in activation and consolidation.

Background: Ischemia is a limiting factor during distraction osteogenesis. The authors sought to determine the extent of ischemia in the distraction zone and whether endothelial progenitor cells home to the distraction zone and participate in local vasculogenesis.

Methods: Laser Doppler imaging was used to assess the extent of blood flow in the distraction zone in gradually distracted, immediately distracted, and osteotomized rat mandibles during activation and consolidation.

Infection with nontuberculous mycobacterium after injection of adulterated silicone fluid.

A 57-year-old woman presented with a predominantly right-sided cellulitic area of her buttock after receiving multiple bilateral silicone injections in the buttocks. The workup revealed subcutaneous infection with rapidly growing mycobacteria. Surgical management and etiologic factors are discussed, and a review of the literature is presented.