New Innovation: Custom Titanium Zygomaticomaxillary Complex (ZMC) Plate for Facial Reconstruction.

Zygomaticomaxillary complex (ZMC) fractures typically result from traumatic injuries, such as motor vehicle-related incidents, assaults, falls, and sports-related injuries. These fractures characteristically occur along suture lines where the zygomatic bone borders the frontal bone, maxilla, temporal bone, and sphenoid bone, resulting in a "tetrapod" fracture pattern that can be surgically fixated utilizing one, two, and three-point plate and screw fixation. However, fractures with complete loss of bone stock are less common, and standardized methods of fixation are not suitable for such complex fractures. Here, we present an interesting case of implantation of a custom-made alloplastic implant in a patient with complex ZMC fractures with loss of bone stock. A 52-year-old male sustained a traumatic gunshot wound to the face, resulting in significant destruction of bones involving the left orbital floor, left lateral orbital wall, and left zygomatic arch. Routine plating was not feasible, so a custom spanning plating system by DePuy Synthes (Synthes USA Products, LLC, West Chester, PA) was designed using the patient's CT scans. The patient recovered well with no complications. This case illustrates the successful application of patient-specific custom plates for complex ZMC fractures when standard plating methods are not suitable.

Spectral analysis and kinetic modeling of radioluminescence in air and nitrogen.

In this article we present a quantitative analysis of the second positive system of molecular nitrogen and the first negative system of the molecular nitrogen cation excited in the presence of ionizing radiation. Optical emission spectra of atmospheric air and nitrogen surrounding 210Po sources were measured from 250 to 400 nm. Multi-Boltzmann and non-Boltzmann vibrational distribution spectral models were used to determine the vibrational temperature and vibrational distribution function of the emitting N2(C3Πu) and N2+(B2Σ+u) states. A zero-dimensional kinetic model, based on the electron energy distribution function (EEDF) and steady-state excitation and de-excitation of N2(X1Σ+g), N2+(B2Σ+u), N2+(X2Σ+g), N4+, O2+, and N2(C3Πu, v), was developed for the prediction of the relative spectral intensity of both the N2+(B2Σ+u → X2Σ+g) emission band and the vibrational bands of N2(C3Πu → B3Πg) for comparison with the experimental data.

High throughput screening aids clinical decision-making in refractory acute myeloid leukaemia.

BACKGROUND: Despite advances in therapeutics for adverse-risk acute myeloid leukaemia (AML), overall survival remains poor, especially in refractory disease. Comprehensive tumour profiling and pre-clinical drug testing can identify effective personalised therapies. CASE: We describe a case of ETV6-MECOM fusion-positive refractory AML, where molecular analysis and in vitro high throughput drug screening identified a tolerable, novel targeted therapy and provided rationale for avoiding what could have been a toxic treatment regimen. Ruxolitinib combined with hydroxyurea led to disease control and enhanced quality-of-life in a patient unsuitable for intensified chemotherapy or allogeneic stem cell transplantation. CONCLUSION: This case report demonstrates the feasibility and role of combination pre-clinical high throughput screening to aid decision making in high-risk leukaemia. It also demonstrates the role a JAK1/2 inhibitor can have in the palliative setting in select patients with AML.

Persistent long-term opioid use after trauma: Incidence and risk factors.

BACKGROUND: The opioid epidemic in the United States continues to lead to a substantial number of preventable deaths and disability. The development of opioid dependence has been strongly linked to previous opioid exposure. Trauma patients are at particular risk since opioids are frequently required to control pain after injury. The purpose to this study was to examine the prevalence of opioid use before and after injury and to identify risk factors for persistent long-term opioid use after trauma. METHODS: Records for all patients admitted to a Level 1 trauma center over a 1-year period were analyzed. Demographics, injury characteristics, and hospital course were recorded. A multistate Prescription Drug Monitoring Program database was queried to obtain records of all controlled substances prescribed from 6 months before the date of injury to 12 months after hospital discharge. Patients still receiving narcotics at 1 year were defined as persistent long-term users and were compared against those who were not. RESULTS: A total of 2,992 patients were analyzed. Of all patients, 20.4% had filled a narcotic prescription within the 6 months before injury, 53.5% received opioids at hospital discharge, and 12.5% had persistent long-term use after trauma with the majority demonstrating preinjury use. Univariate risk factors for long-term use included female sex, longer length of stay, higher Injury Severity Score, anxiety, depression, orthopedic surgeries, spine injuries, multiple surgical locations, discharge to acute inpatient rehab, and preinjury opioid use. On multivariate analysis, the only significant predictors of persistent long-term prescription opioid use were preinjury use and a much smaller effect associated with use at discharge. CONCLUSION: During a sustained opioid epidemic, concerns and caution are warranted in the use of prescription narcotics for trauma patients. However, persistent long-term opioid use among opioid-naive patients is rare and difficult to predict after trauma. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level III.

Sternectomy Reconstruction Using a Customized Three-Dimensional-Printed Polyetheretherketone Implant.

Complex sternal and chest wall reconstruction can be a challenging clinical situation, with the main objectives being restoration of chest wall rigidity, protection of intrathoracic organs, preservation of respiratory function, and reduction of pain and clicking. The treatment of choice is varied, with several different materials available to aid in adequate reconstruction. We present the case of a 60-year-old male with a post-sternectomy defect and debilitating symptoms who underwent reconstruction with a customized, three-dimensional (3D)-printed polyetheretherketone (PEEK) implant and pectoralis muscle flaps. There were no complications in the perioperative period, and the patient reported significant improvement in pain and subjective improvement in chest stability and respiration. The use of PEEK as a reconstructive material for cardiothoracic defects is a viable and safe method that has several important benefits over other utilized materials in the literature. The early success of this case in relieving patient symptoms opens the door for further exploration of PEEK as an alternative for cardiothoracic reconstruction.

Cholinergic Reinforcement Signaling Is Impaired by Amyloidosis Prior to Its Synaptic Loss.

Alzheimer's disease (AD) is associated with amyloidosis and dysfunction of the cholinergic system, which is crucial for learning and memory. However, the nature of acetylcholine signaling within regions of cholinergic-dependent plasticity and how it changes with experience is poorly understood, much less the impact of amyloidosis on this signaling. Therefore, we optically measure the release profile of acetylcholine to unexpected, predicted, and predictive events in visual cortex (VC)-a site of known cholinergic-dependent plasticity-in a preclinical mouse model of AD that develops amyloidosis. We find that acetylcholine exhibits reinforcement signaling qualities, reporting behaviorally relevant outcomes and displaying release profiles to predictive and predicted events that change as a consequence of experience. We identify three stages of amyloidosis occurring before the degeneration of cholinergic synapses within VC and observe that cholinergic responses in amyloid-bearing mice become impaired over these stages, diverging progressively from age- and sex-matched littermate controls. In particular, amyloidosis degrades the signaling of unexpected rewards and punishments, and attenuates the experience-dependent (1) increase of cholinergic responses to outcome predictive visual cues, and (2) decrease of cholinergic responses to predicted outcomes. Hyperactive spontaneous acetylcholine release occurring transiently at the onset of impaired cholinergic signaling is also observed, further implicating disrupted cholinergic activity as an early functional biomarker in AD. Our findings suggest that acetylcholine acts as a reinforcement signal that is impaired by amyloidosis before pathologic degeneration of the cholinergic system, providing a deeper understanding of the effects of amyloidosis on acetylcholine signaling and informing future interventions for AD.SIGNIFICANCE STATEMENT The cholinergic system is especially vulnerable to the neurotoxic effects of amyloidosis, a hallmark of Alzheimer's disease (AD). Though amyloid-induced cholinergic synaptic loss is thought in part to account for learning and memory impairments in AD, little is known regarding how amyloid impacts signaling of the cholinergic system before its anatomic degeneration. Optical measurement of acetylcholine (ACh) release in a mouse model of AD that develops amyloidosis reveals that ACh signals reinforcement and outcome prediction that is disrupted by amyloidosis before cholinergic degeneration. These observations have important scientific and clinical implications: they implicate ACh signaling as an early functional biomarker, provide a deeper understanding of the action of acetylcholine, and inform on when and how intervention may best ameliorate cognitive decline in AD.

A Novel Brain PET Radiotracer for Imaging Alpha Synuclein Fibrils in Multiple System Atrophy.

Abnormal α-synuclein (α-syn) aggregation characterizes α-synucleinopathies, including Parkinson's disease (PD) and multiple system atrophy (MSA). However, no suitable positron emission tomography (PET) radiotracer for imaging α-syn in PD and MSA exists currently. Our structure-activity relationship studies identified 4-methoxy-N-(4-(3-(pyridin-2-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl)phenyl)benzamide (4i) as a PET radiotracer candidate for imaging α-syn. In vitro assays revealed high binding of 4i to recombinant α-syn fibrils (inhibition constant (Ki) = 6.1 nM) and low affinity for amyloid beta (Aß) fibrils in Alzheimer's disease (AD) homogenates. However, [3H]4i also exhibited high specific binding to AD, progressive supranuclear palsy, and corticobasal degeneration tissues as well as PD and MSA tissues, suggesting notable affinity to tau. Nevertheless, the specific binding to pathologic α-syn aggregates in MSA post-mortem brain tissues was significantly higher than in PD tissues. This finding demonstrated the potential use of [11C]4i as a PET tracer for imaging α-syn in MSA patients. Nonhuman primate PET studies confirmed good brain uptake and rapid washout for [11C]4i.

Surgical Marking Pen Contamination: Writing a Postoperative Infection Into Your Preoperative Plan.

Introduction Preoperative marking is an essential safety practice to prevent "never" events, including wrong site surgery. Moreover, the Joint Commission regulations of the Universal Protocol require that patients be marked to indicate the operative site. Marking typically occurs with a pen or marker, which may be disposable or reusable. Previous studies have demonstrated that methicillin-resistant Staphylococcus aureus (MRSA) can survive in the dark, moist, capped environment of the marking pen and thus could plausibly be a nidus for transmission from patient to patient. The Joint Commission has established no increased risk of postoperative infection with these markings. With this study, we aimed to determine the colonization of surgical marking pens in the plastic surgery population. Methods Two marking pens from five different attending plastic surgeons at a single institution were cultured in standard fashion for aerobic and anaerobic growth. All pens were used repeatedly in office settings for performing patient markings. Those same ten marking pens were then used to mark incision sites on mock patients. Standard povidone-iodine prepping was then performed in a paint-only fashion over the skin markings, and cultures were again taken. A control group consisted of cultures from five sterile pens from the operating room. Each sterile pen was opened, uncapped, and then swabbed. All twenty-five cultures were analyzed in the hospital laboratory in a blinded fashion. Results The five control pens revealed no bacterial growth. Of the 10 direct pen cultures, two samples grew coagulase-negative staphylococci and one culture contained Pseudomonas aeruginosa. The 10-patient marked and prepped specimens showed eight negative cultures and two with coagulase-negative staphylococci. Although Pseudomonas was detected on standard pen culture, no pseudomonal growth was present in any of the samples after patient marking and prepping with povidone-iodine. Conclusions Our findings reaffirm that marking pens may be vehicles for bacterial transmission and expand upon previous studies by describing the presence of bacterial colonization on marking pens even after surgical site preparation with povidone-iodine.

Effects of preexposure to a subthreshold dose of helium particles on the changes in performance produced by exposure to helium particles.

On exploratory class missions, such as a mission to Mars, astronauts will be exposed to doses of particles of high energy and charge and protons up to 30 - 40 cGy. These exposures will most likely occur at random intervals across the estimated 3-yr duration of the mission. As such, the possibility of an interaction between particles must be taken into account: a prior subthreshold exposure to one particle may prevent or minimize the effect of a subsequent exposure (adaptation), or there may be an additive effect such that the prior exposure may sensitize the individual to a subsequent exposure of the same or different radiations. Two identical replications were run in which rats were exposed to a below threshold dose of 4He particles and 2, 24 or 72 h later given either a second below threshold or an above threshold dose of 4He particles and tested for performance on an operant task. The results indicate that preexposure to a subthreshold dose of 4He particles can either sensitize or attenuate the effects of the subsequent dose, depending upon the interval between exposures and the doses. These results suggest that exposure to multiple doses of heavy particles may have implications for astronaut health on exploratory class missions.

Identification of a Putative α-synuclein Radioligand Using an in silico Similarity Search.

PURPOSE: Previous studies from our lab utilized an ultra-high throughput screening method to identify compound 1 as a small molecule that binds to alpha-synuclein (α-synuclein) fibrils. The goal of the current study was to conduct a similarity search of 1 to identify structural analogs having improved in vitro binding properties for this target that could be labeled with radionuclides for both in vitro and in vivo studies for measuring α-synuclein aggregates. METHODS: Using 1 as a lead compound in a similarity search, isoxazole derivative 15 was identified to bind to α-synuclein fibrils with high affinity in competition binding assays. A photocrosslinkable version was used to confirm binding site preference. Derivative 21, the iodo-analog of 15, was synthesized, and subsequently radiolabeled isotopologs [125I]21 and [11C]21 were successfully synthesized for use in in vitro and in vivo studies, respectively. [125I]21 was used in radioligand binding studies in post-mortem Parkinson's disease (PD) and Alzheimer's disease (AD) brain homogenates. In vivo imaging of an α-synuclein mouse model and non-human primates was performed with [11C]21. RESULTS: In silico molecular docking and molecular dynamic simulation studies for a panel of compounds identified through a similarity search, were shown to correlate with Ki values obtained from in vitro binding studies. Improved affinity of isoxazole derivative 15 for α-synuclein binding site 9 was indicated by photocrosslinking studies with CLX10. Design and successful (radio)synthesis of iodo-analog 21 of isoxazole derivative 15 enabled further in vitro and in vivo evaluation. Kd values obtained in vitro with [125I]21 for α-synuclein and Aß42 fibrils were 0.48 ± 0.08 nM and 2.47 ± 1.30 nM, respectively. [125I]21 showed higher binding in human postmortem PD brain tissue compared with AD tissue, and low binding in control brain tissue. Lastly, in vivo preclinical PET imaging showed elevated retention of [11C]21 in PFF-injected mouse brain. However, in PBS-injected control mouse brain, slow washout of the tracer indicates high non-specific binding. [11C]21 showed high initial brain uptake in a healthy non-human primate, followed by fast washout that may be caused by rapid metabolic rate (21% intact [11C]21 in blood at 5 min p.i.). CONCLUSION: Through a relatively simple ligand-based similarity search, we identified a new radioligand that binds with high affinity (<10 nM) to α-synuclein fibrils and PD tissue. Although the radioligand has suboptimal selectivity for α-synuclein towards Aß and high non-specific binding, we show here that a simple in silico approach is a promising strategy to identify novel ligands for target proteins in the CNS with the potential to be radiolabeled for PET neuroimaging studies.

FRETing about the details: Case studies in the use of a genetically encoded fluorescent amino acid for distance-dependent energy transfer.

Förster resonance energy transfer (FRET) is a valuable method for monitoring protein conformation and biomolecular interactions. Intrinsically fluorescent amino acids that can be genetically encoded, such as acridonylalanine (Acd), are particularly useful for FRET studies. However, quantitative interpretation of FRET data to derive distance information requires careful use of controls and consideration of photophysical effects. Here we present two case studies illustrating how Acd can be used in FRET experiments to study small molecule induced conformational changes and multicomponent biomolecular complexes.

Simulations and measurements of bilamellar streak tubes.

Particle-in-cell simulations of a picosecond-resolution bilamellar streak tube are described, and the results are compared to measurements of key specifications. A novel laser diode setup with a small focal spot has been used to investigate the sensitive width of the photocathode, a previously unpublished parameter. Simulations have shown that the tubes, while performing at high spatiotemporal resolution, have electron efficiencies of just 1.6% due to the action of the temporal focusing electrode, contributing to an effective dynamic range of around 10. The virtual photocathode created by this electrode was predicted to be 144 µm, in excellent agreement with the measured width of 136 µm. A simple method to improve the tube's dynamic range by narrowing the slit width is investigated and shown to have a modest simulated improvement.

Everyday Functioning and Entorhinal and Inferior Temporal Tau Burden in Cognitively Normal Older Adults.

BACKGROUND: Performance of cognitively complex "instrumental activities of daily living" (IADL) has previously been related to amyloid deposition in preclinical Alzheimer's disease. OBJECTIVES: We aimed to investigate the relationship between IADL performance and cerebral tau accumulation in cognitively normal older adults. DESIGN: Cross-sectional. SETTING: Data was collected in the Anti-Amyloid Treatment in Asymptomatic Alzheimer's (A4) and Longitudinal Evaluation of Amyloid Risk and Neurodegeneration (LEARN) studies. PARTICIPANTS: Participants (n = 447, age 71.9±4.9 years, 57.5% female) who underwent tau positron emission tomography were selected from the A4 and LEARN studies. MEASUREMENTS: IADL performance was measured using the self- and study partner-reported versions of the Alzheimer's Disease Cooperative Study Activities of Daily Living - Prevention Instrument (ADCS ADL-PI). We also investigated discordance between participants and their study partners. Cross-sectional associations between entorhinal and inferior temporal tau (independent variables) and ADCS ADL-PI total scores, item-level scores and discordance (dependent variables) were investigated in linear and logistic regressions. Analyses were adjusted for age, sex and education and a tau by amyloid interaction was also included. RESULTS: Participants and their study partners reported high levels of IADL performance. Entorhinal and inferior temporal tau were related to study partner but not to self-reported total ADCS ADL-PI scores. The association was not retained after adjustment for global cerebral amyloid burden. At the item level, greater entorhinal tau was associated with study partner-reported difficulties remembering important dates (odds ratio (OR) = 1.24, 95% confidence interval (95%CI) = [1.06, 1.45], p = 0.008) and difficulties remembering the details of TV programs and movies (OR = 1.32, 95%CI = [1.08, 1.61], p = 0.007). Greater inferior temporal tau was associated with self-reported difficulties managing to find personal belongings (OR = 1.23, 95%CI = [1.04, 1.46], p = 0.018) and study partner-reported difficulties remembering the details of TV programs and movies (OR = 1.39, 95%CI = [1.11, 1.75], p = 0.005). Discordance between participant and study partner-report was more likely with greater entorhinal (OR = 1.18, 95%CI = [1.05, 1.33], p = 0.005) and inferior temporal tau burden (OR = 1.29, 95%CI = [1.10, 1.51], p = 0.002). DISCUSSION: We found a cross-sectional relationship between study partner-reported everyday functioning and tau in cognitively normal older adults. Participants were more likely to self-report difficulties differently from their study partners when tau burden was higher. This may hint at an altered early-disease awareness of functional changes and underscores the importance of self-report of IADL functioning in addition to collateral report by a study partner.

Harnessing the intrinsic photochemistry of isoxazoles for the development of chemoproteomic crosslinking methods.

The intrinsic photochemistry of the isoxazole, a common heterocycle in medicinal chemistry, can be applied to offer an alternative to existing strategies using more perturbing, extrinsic photo-crosslinkers. The utility of isoxazole photo-crosslinking is demonstrated in a wide range of biologically relevant experiments, including common proteomics workflows.

Subjective Cognitive Decline in a Registry Sample: Relation to Psychiatric History, Loneliness, and Personality.

BACKGROUND: With the increasing focus on prevention of Alzheimer's disease, there is need for characterization of preclinical populations. Local participant registries offer an opportunity to facilitate research engagement via remote data collection, inform recruitment, and characterize preclinical samples, including individuals with subjective cognitive decline. OBJECTIVES: We sought to characterize subjective cognitive decline in a registry sample, as related to psychiatric history and related variables, including personality and loneliness, quality of life, and factors related to dementia risk (e.g., family history of dementia). DESIGN, SETTING, PARTICIPANTS: Participants were 366 individuals (mean age=67.2 (range 50-88), 65% female, 94% white, 97% non-Hispanic or Latino, 82% with at least a bachelor's degree) with no reported history of mild cognitive impairment or dementia. All participants had expressed interest in research, primarily via community outreach events and prior research involvement. Data was collected via electronic surveys, distributed using REDCap. Electronic questionnaires included questions on demographic variables, subjective cognitive decline, quality of life, loneliness, and personality. RESULTS: There was a high prevalence of risk factors for dementia in the registry sample (68% with family history of dementia, 31% with subjective cognitive decline). Subjective cognitive decline was more common in women and associated with history of depression, but not with family history of dementia. Subjective cognitive decline was also associated with lower conscientiousness and lower emotional stability, as well as higher loneliness and lower quality of life. Among participants who endorsed a psychiatric history, most reported onset more than 10 years prior, rather than within the last 10 years. CONCLUSIONS: Subjective cognitive decline in a registry sample may be more strongly associated with longstanding psychiatric and personality variables, rather than family history of dementia, adding to the literature on characterization of subjective cognitive decline across different settings. These findings highlight the acceptability of remote data collection and the potential of registries to inform recruitment by characterizing registrants, which may help to stratify dementia risk and match participants to eligible trials.

A Severe Case of Siliconoma-induced Hypercalcemia due to Illicit Gluteal Silicone Injections.

Siliconoma-induced hypercalcemia is a rare complication of siliconoma, occurring secondary to a foreign body granulomatous process induced by the introduction of silicone into soft tissue. This is a case report of a woman presenting with sequelae of illicit silicone injections performed in an unknown woman's basement in Florida 20 years before presentation. A 39-year-old woman presented with a 2-month history of 20-pound weight loss, malaise, and intractable vomiting with a remote history of unregulated cosmetic injections to the bilateral gluteal and thigh regions. Her laboratory studies were consistent with severe hypercalcemia secondary to a foreign body granulomatous process. Initially, she was medically managed, with mild improvements in her symptomatic hypercalcemia and later underwent palliative debridement with siliconoma removal. Postoperatively, her course was complicated by delayed wound healing and graft failure, but the surgical defect was later closed successfully with split-thickness skin grafting after months of wound care. Although the procedure was not intended to treat her hypercalcemia, there were significant improvements in serum and ionized calcium in the months following her procedure. Severe hypercalcemia in the context of previous unregulated cosmetic injections or possible silicone implant rupture should prompt consideration of siliconoma-induced hypercalcemia as the underlying etiology. In addition to the established utility of IV fluids, bisphosphonates, and glucocorticoids, there may also be a role for surgical intervention in the management of this unique patient population's hypercalcemia.

Alpha-synuclein from patient Lewy bodies exhibits distinct pathological activity that can be propagated in vitro.

Lewy bodies (LBs) are complex, intracellular inclusions that are common pathological features of many neurodegenerative diseases. They consist largely of aggregated forms of the protein alpha-Synuclein (α-Syn), which misfolds to give rise to beta-sheet rich amyloid fibrils. The aggregation of monomers into fibrils occurs readily in vitro and pre-formed fibrils (PFFs) generated from recombinant α-Syn monomers are the basis of many models of LB diseases. These α-Syn PFFs recapitulate many pathological phenotypes in both cultured cells and animal models including the formation of α-Syn rich, insoluble aggregates, neuron loss, and motor deficits. However, it is not clear how closely α-Syn PFFs recapitulate the biological behavior of LB aggregates isolated directly from patients. Direct interrogation of the cellular response to LB-derived α-Syn has thus far been limited. Here we demonstrate that α-Syn aggregates derived from LB disease patients induce pathology characterized by a prevalence of large somatic inclusions that is distinct from the primarily neuritic pathology induced by α-Syn PFFs in our cultured neuron model. Moreover, these LB-derived aggregates can be amplified in vitro using recombinant α-Syn to generate aggregates that maintain the unique, somatic pathological phenotype of the original material. Amplified LB aggregates also showed greater uptake in cultured neurons and greater pathological burden and more rapid pathological spread in injected mouse brains, compared to α-Syn PFFs. Our work indicates that LB-derived α-Syn from diseased brains represents a distinct conformation species with unique biological activities that has not been previously observed in fully recombinant α-Syn aggregates and demonstrate a new strategy for improving upon α-Syn PFF models of synucleinopathies using amplified LBs.

Non-surgical Management of Complex Refractory Pyoderma Gangrenosum With Negative Pressure Wound Therapy With Instillation.

Pyoderma gangrenosum (PG) is a rare skin disorder primarily treated with immunosuppression medication. We report a case of a large, chronic PG wound treated with adjunct negative pressure wound therapy with instillation and dwell time (NPWTi-d) using nonadherent dressing (Mepitel) and reticular open-cell foam with through holes (ROCF-CC) with positive outcomes. The patient was a 62-year-old female with rheumatoid arthritis, Hashimoto's thyroiditis, lymphedema, and morbid obesity who presented with a 19.5 cm x 13.2 cm x 2.1 cm wound of three years duration on the right posterolateral lower extremity that successfully responded to a multimodality approach of immunosuppression and wound vac therapy. We conclude in our case that NPWTi-d with Mepitel and ROCF-CC enhanced the wound healing process, and we discuss NPWTi-d's potential role and benefit as an adjunctive therapy option for chronic and poorly controlled PG on patients taking concurrent immunosuppression.

Item-Level Investigation of Participant and Study Partner Report on the Cognitive Function Index from the A4 Study Screening Data.

BACKGROUND: Greater subjective cognitive changes on the Cognitive Function Index (CFI) was previously found to be associated with elevated amyloid (Aß) status in participants screening for the A4 Study, reported by study partners and the participants themselves. While the total score on the CFI related to amyloid for both sources respectively, potential differences in the specific types of cognitive changes reported by either participants or their study partners was not investigated. OBJECTIVES: To determine the specific types of subjective cognitive changes endorsed by participants and their study partners that are associated with amyloid status in individuals screening for an AD prevention trial. DESIGN, SETTING, PARTICIPANTS: Four thousand four hundred and eighty-six cognitively unimpaired (CDR=0; MMSE 25-30) participants (ages 65-85) screening for the A4 Study completed florbetapir (Aß) Positron Emission Tomography (PET) imaging. Participants were classified as elevated amyloid (Aß+; n=1323) or non-elevated amyloid (Aß-; n=3163). MEASUREMENTS: Prior to amyloid PET imaging, subjective report of changes in cognitive functioning were measured using the CFI (15 item questionnaire; Yes/Maybe/No response options) and administered separately to both participants and their study partners (i.e., a family member or friend in regular contact with the participant). The impact of demographic factors on CFI report was investigated. For each item of the CFI, the relationship between Aß and CFI response was investigated using an ordinal mixed effects model for participant and study partner report. RESULTS: Independent of Aß status, participants were more likely to report 'Yes' or 'Maybe' compared to the study partners for nearly all CFI items. Older age (r= 0.06, p<0.001) and lower education (r=-0.08, p<0.001) of the participant were associated with higher CFI. Highest coincident odds ratios related to Aß+ for both respondents included items assessing whether 'a substantial decline in memory' had occurred in the last year (ORsp= 1.35 [95% CI 1.11, 1.63]; ORp= 1.55 [95% CI 1.34, 1.79]) and whether the participant had 'seen a doctor about memory' (ORsp= 1.56 [95% CI 1.25, 1.95]; ORp =1.71 [95% CI 1.37, 2.12]). For two items, associations were significant for only study partner report; whether the participant 'Repeats questions' (ORsp = 1.30 [95% CI 1.07, 1.57]) and has 'trouble following the news' (ORsp= 1.46[95% CI 1.12, 1.91]). One question was significant only for participant report; 'trouble driving' (ORp= 1.25 [95% CI 1.04, 1.49]). CONCLUSIONS: Elevated Aß is associated with greater reporting of subjective cognitive changes as measured by the CFI in this cognitively unimpaired population. While participants were more likely than study partners to endorse change on most CFI items, unique CFI items were associated with elevated Aß for participants and their study partners, supporting the value of both sources of information in clinical trials.

Desymmetrization of Diols by Phosphorylation with a Titanium-BINOLate Catalyst.

The desymmetrization of ten prochiral diols by phosphoryl transfer with a titanium-BINOLate complex is discussed. The phosphorylation of nine 1,3-propane diols is achieved in yields of 50-98%. Enantiomeric ratios as high as 92:8 are achieved with diols containing a quaternary C-2 center incorporating a protected amine. The chiral ligand, base, solvent, and stoichiometry are evaluated along with a nonlinear effect study to support an active catalyst species that is oligomeric in chiral ligand. The use of pyrophosphates as the phosphorylating agent in the desymmetrization facilitates a user-friendly method for enantioselective phosphorylation with desirable protecting groups (benzyl, o-nitrobenzyl) on the phosphate product.