End-of-Life Care of a Patient With Pontine Stroke and Prolonged Hospitalization: A Case Report.

Stroke is a leading cause of long-term disability in the United States that can lead to loss of function and consciousness. With the abrupt onset of the brain insult, end-of-life care discussions are an important attribute of respecting the patient's best wishes and upholding the ethical principles of autonomy, beneficence, nonmaleficence, fidelity, and justice. Furthermore, the topic of extending life support to individuals with poor prognostic factors of improvement in quality of life and functional recovery has been a continued topic of debate due to a multitude of factors, including the wishes of the patient, familial emotions, cultural beliefs, and religious influences. This case involves a patient who suffered from a left pontine stroke, necessitating multiple end-of-life care conversations. Despite no clinical improvement for several years, the patient required prolonged hospitalization and ongoing ventilator use.

How Far Has Radiofrequency Thermocoagulation Come Along as a Treatment Procedure in Treating Trigeminal Neuralgia Patients?

Trigeminal neuralgia (TN) refers to sudden shooting pain in areas innervated by trigeminal nerves originating from the Gasserian ganglion. Physicians initially manage it by prescribing drugs, such as carbamazepine. Surgical intervention is the next best option if patients do not respond to drug treatments. These procedures include microvascular decompression, rhizotomy, balloon compression, and gamma knife surgery. However, less optimal patient outcomes, recurrences, adverse effects, and high costs have necessitated alternative surgical interventions to treat such patients. Radiofrequency thermocoagulation (RFT) has emerged as a minimally invasive, safer, and effective surgical option in treating TN patients. Despite research showing RFT's safety and effectiveness, neurosurgical healthcare providers do not frequently use it to treat TN patients. Lack of universal standardized protocol, and minimal awareness of its efficacy in specific cohorts, such as geriatric patients, may lead to RFT underutilization. Hence, this review highlights RFT's advancement as a robust alternative to traditional surgical approaches in treating TN patients. In addition, it identifies RFT's areas of improvement and its safety and effectiveness in treating elderly TN patients. We followed the Systematic Reviews and Meta-Analyses guidelines for systematic reviews and conducted a literature search between July 2022 and March 2023. Our findings indicate that RFT has evolved significantly over the last decade and a half as a minimally invasive and effective treatment procedure for TN patients. It is more effective as a combined continuous and pulsed RFT than its other subtypes in treating primary TN patients. Moreover, RFT via a transverse puncture through the supraorbital foramen results in lesser inter- and post-procedural complications. Further, there is a slightly lesser incidence of post-procedural adverse effects and complications with RFT through the foramen rotundum. Besides, RFT, performed at a lower temperature of 65 degrees Celsius and a voltage between 64.51 and 79.29 volts, effectively provides pain relief and long-term patient satisfaction. RFT is safe and effective in patients over 60 with primary TN. Interestingly, it is also safe and effective in treating patients over 70 with poor fitness standards of Class II or higher. Despite these remarkable findings, there is still a substantial gap in the literature, specifically concerning the standardized protocol for temperature, voltage, and puncture methods of RFT. Despite the sufficient evidence of combined continuous and pulsed RFT's superiority in efficacy and safety, most researchers still utilize either pulsed or continuous RFT. Studies vary in not only these aspects but also the patient cohorts. For instance, most researchers focus solely on evaluating RFT's efficacy and safety in patients with primary TN, excluding a critical patient population suffering from secondary TN. Nevertheless, sufficient clinical evidence shows that RFT has come of age in treating primary TN patients. However, more extensive studies with large sample sizes of patients with primary and secondary TN with multiple trigeminal nerve affectation will significantly help standardize RFT protocol and its inclusion in the standard clinical practice in treating TN patients.

Critical land change information enhances the understanding of carbon balance in the United States.

Large-scale terrestrial carbon (C) estimating studies using methods such as atmospheric inversion, biogeochemical modeling, and field inventories have produced different results. The goal of this study was to integrate fine-scale processes including land use and land cover change into a large-scale ecosystem framework. We analyzed the terrestrial C budget of the conterminous United States from 1971 to 2015 at 1-km resolution using an enhanced dynamic global vegetation model and comprehensive land cover change data. Effects of atmospheric CO2 fertilization, nitrogen deposition, climate, wildland fire, harvest, and land use/land cover change (LUCC) were considered. We estimate annual C losses from cropland harvest, forest clearcut and thinning, fire, and LUCC were 436.8, 117.9, 10.5, and 10.4 TgC/year, respectively. C stored in ecosystems increased from 119,494 to 127,157 TgC between 1971 and 2015, indicating a mean annual net C sink of 170.3 TgC/year. Although ecosystem net primary production increased by approximately 12.3 TgC/year, most of it was offset by increased C loss from harvest and natural disturbance and increased ecosystem respiration related to forest aging. As a result, the strength of the overall ecosystem C sink did not increase over time. Our modeled results indicate the conterminous US C sink was about 30% smaller than previous modeling studies, but converged more closely with inventory data.

Ameliorative response to detoxification, psychotherapy, and medical management in patients maintained on opioids for pain.

BACKGROUND AND OBJECTIVES: The prevalence of opioid-induced hyperalgesia (OIH) among patients maintained on opioids for chronic non-malignant pain has not been estimated. As a contribution toward establishing its prevalence, we report a case series of opioid maintained patients whose pain tolerance was measured by the cold pressor test at baseline. METHODS: A case series of 117 patients who had undergone detoxification was reviewed retrospectively. Most patients (n = 108) and selected non-addicted support persons who accompanied them (controls; n = 37) had cold pressor time (CPT) assessments at baseline. Twenty patients had a repeat CPT after 1 month. RESULTS: When 61 patients completed one month abstinent reported pain was improved (51%), unchanged (46%), or worse (3%). Baseline CPT was 48 sec for patients and 102 sec for controls, suggesting that opioid maintained patients were more pain sensitive than opioid naïve controls. CPT increased for 90% of 1-month completers, suggesting improved pain tolerance. Ameliorative response to detoxification, psychotherapy, and medical management, as defined as the absence of worsening pain with removal of opioids, was 97% in this population. CONCLUSION: The difference in CPT between opioid maintained patients and controls, and the response to detoxification, psychotherapy and medical management suggest the possibility that the prevalence of OIH may be high. SCIENTIFIC SIGNIFICANCE: This study adds to the growing evidence that chronic opioid treatment contributes little to the management of chronic pain and in fact appears to frequently make it worse. (Am J Addict 2017;26:738-743).

Polarimeter for the General Fusion SPECTOR machine.

A polarimeter has been designed to measure Faraday rotation and help to understand the profile of its safety factor, q, on the recently built SPECTOR magnetized target fusion machine at General Fusion. The polarimeter uses two counter-rotating, circularly polarized, 118.8 µm beams to probe the plasma. Grad-Shafranov simulations have been used to investigate the effect of measurement error and chord geometry.

Testing the Efficacy of Pharmacological Agents in a Pericardial Target Delivery Model in the Swine.

To date, many pharmacological agents used to treat or prevent arrhythmias in open-heart cases create undesired systemic side effects. For example, antiarrhythmic drugs administered intravenously can produce drops in systemic pressure in the already compromised cardiac patient. While performing open-heart procedures, surgeons will often either create a small port or form a pericardial cradle to create suitable fields for operation. This access yields opportunities for target pharmacological delivery (antiarrhythmic or ischemic preconditioning agents) directly to the myocardial tissue without undesired side effects. We have developed a swine model for testing pharmacological agents for target delivery within the pericardial fluid. While fully anesthetized, each animal was instrumented with a Swan-Ganz catheter as well as left and right ventricle pressure catheters, and pacing leads were placed in the right atrial appendage and the right ventricle. A medial sternotomy was then performed and a pericardial access cradle was created; a plunge pacing lead was placed in the left atrial appendage and a bipolar pacing lead was placed in the left ventricle. Utilizing a programmer and a cardiac mapping system, the refractory period of the atrioventricular node (AVN), atria and ventricles was determined. In addition, atrial fibrillation (AF) induction was produced utilizing a Grass stimulator and time in AF was observed. These measurements were performed prior to treatment, as well as 30 min and 60 min after pericardial treatment. Additional time points were added for selected studies. The heart was then cardiopleged and reanimated in a four chamber working mode. Pressure measurements and function were recorded for 1 hr after reanimation. This treatment strategy model allowed us to observe the effects of pharmacological agents that may decrease the incidence of cardiac arrhythmias and/or ischemic damage, during and after open-heart surgery.

Tissue properties of the fossa ovalis as they relate to transseptal punctures: a translational approach.

OBJECTIVES: This study focused on how catheter size affects transseptal puncture, what transseptal indication means, and whether the swine model is predictive for humans. BACKGROUND: Transseptal puncture is a common procedure that gains access to the left atrium, allowing percutaneous mitral valve repair, left atrial appendage closure, and left-sided ablations. The basic approach has not changed in many years; however, the frequency of transseptal punctures and the size of devices are increasing with emerging treatments. METHODS: A broad range of devices (4 F to 18 F) were advanced through atrial septa of swine hearts; some devices were inserted in both swine and human hearts using 10 F catheters. RESULTS: Greater forces were required to puncture through the septa of human hearts compared to those of swine. Larger catheters used in swine hearts required greater force to advance them through the septa, causing greater dilation of tissue and sometimes tearing the floor of the fossa ovalis; analyses indicated an exponential increase in the size of the iatrogenic atrial septal defect. Specific tissue property testing of the septum primum showed that this tissue sheared at a lower exerted force in a superior to inferior direction. CONCLUSIONS: Results may provide physicians with important knowledge about what to expect when treating a possible iatrogenic atrial septal defect or help them understand the consequences of transseptal punctures. Comparative data between swine and human atrial septal tissue properties provide critical insights between the species and offer clinicians and device designers important information relative to differences in tissue behaviors.

The benefits of the Atlas of Human Cardiac Anatomy website for the design of cardiac devices.

This paper describes how the Atlas of Human Cardiac Anatomy website can be used to improve cardiac device design throughout the process of development. The Atlas is a free-access website featuring novel images of both functional and fixed human cardiac anatomy from over 250 human heart specimens. This website provides numerous educational tutorials on anatomy, physiology and various imaging modalities. For instance, the 'device tutorial' provides examples of devices that were either present at the time of in vitro reanimation or were subsequently delivered, including leads, catheters, valves, annuloplasty rings and stents. Another section of the website displays 3D models of the vasculature, blood volumes and/or tissue volumes reconstructed from computed tomography and magnetic resonance images of various heart specimens. The website shares library images, video clips and computed tomography and MRI DICOM files in honor of the generous gifts received from donors and their families.

High-bandwidth polarimeter for a high density, accelerated spheromak.

A three-beam heterodyne polarimeter has been built to diagnose the PI-1 plasma injector at General Fusion, Inc. The polarimeter measures plasma density and Faraday rotation, which can provide estimates of magnetic field magnitude and direction. Two important calibration steps are required for the polarimeter to produce reasonable Faraday rotation signals. Beam polarization ellipticity must be measured to ensure there is a linear Faraday rotation response. In addition, the two beams travelling through the plasma must be collinear to reduce error due to differences in plasma density. Once calibrated, the Faraday rotation signals are in much better agreement with other diagnostics. For a null signal, the Faraday rotation measurement noise floor is 0.1° at 0.5 MHz bandwidth. Comparing preliminary spheromak Faraday rotation measurements to a model, the maximum error is about 0.3° at 0.5 MHz bandwidth, which is primarily due to electrical noise during the injector's capacitor discharge and limitations of the model. At a bandwidth of 0.5 MHz, the polarimeter has an axial resolution between 6 cm and 30 cm depending on the speed of the spheromak, which varies between 30 km/s and 150 km/s. The spheromak length ranges from 0.75 m to 2 m. Additional polarimeter chords will be added in future upgrades.

Novel imaging of atrial septal defects in isolated human hearts.

Within the adult population living with congenital heart defects, approximately 20 % have an atrial septal defect, which suggests that only 0.4-0.05 % of the entire adult population has an atrial septal defect (ASD). In patients with a left to right atrial shunt, treatments may include closure of the defect with a transcatheter device and/or surgical repair. From the perspective of a physician or engineer, it is vitally important to understand the anatomical nuances of such defects, not only to offer the most optimal treatment for the patient but also to call attention to the potential anatomy of ASDs which may go undetected. To do so, we reanimated two human hearts deemed not viable for transplant from 56-year-old and 68-year-old males. Neither patient history reported any heart conditions that would suggest an atrial defect, yet an ASD was found in each heart. Here, we present sets of images, videos, and 3D reconstructions that provide a clearer view of the anatomy of ASDs in functional human hearts. With an enhanced understanding of 3D functional aspects of ASDs, physicians can make improved decisions regarding treatment options and engineers can optimize device designs.

Class III bilateral posterior crossbite with three horizontally impacted maxillary anterior teeth.

What's in a pretty face? In our world, unfortunately, too much. As orthodontists our goal should be to provide our patients with a stable, functional occlusion. Consider, however, the importance of changing our patients' future by significantly improving their facial esthetics. The combination of a very narrow maxillary arch, three absent upper left incisors, and a protrusive lower jaw provide a platform for dramatic improvement in our patients' facial esthetics.

Assessment of Transport Mechanisms Underlying the Bicoid Morphogen Gradient.

Morphogen gradients dictate the spatial patterning of multicellular organisms and are established via transport mechanisms. One of the best-characterized morphogens, Bicoid, acts as a polarity determinant in the Drosophila embryo through spatial-temporal control of gap gene expression. The prevailing model for establishment of the gradient has been localized anterior translation, subsequent diffusion, and spatially uniform degradation, consistent with the observed exponential anterior-posterior decay. However, a recent direct measurement of the Bicoid diffusion coefficient via fluorescence recovery after photobleaching (FRAP) resulted in a surprisingly low estimate, which challenged the prevailing model and led to more complicated active transport models. Here, we reassessed this conclusion using a detailed computational model of the FRAP experiment and analysis. In our model, we found disagreement between the input diffusion coefficient and the resulting estimated diffusion coefficient, as measured by previous methods. By using the model to reproduce the original data, we estimate that Bicoid's mitotic diffusion coefficient is 3-fold larger than the originally reported value. Thus, the long-standing diffusive transport model still holds.

Cardiac remodeling as a consequence of atrial fibrillation: An anatomical study of perfusion-fixed human heart specimens.

BACKGROUND: Atrial fibrillation (AF) causes a continuum of atrial anatomical remodeling. METHODS: Using a library of perfusion-fixed human hearts, specimens with AF were compared to controls. During this preliminary assessment study, direct measurements were taken of atrial volume, pulmonary vein (PV) circumference, and left atrial (LA) wall thicknesses. RESULTS: Hearts with AF typically had larger atrial volumes, as well as a much larger variation in volume compared to controls (range of 59.6-227.1 mL in AF hearts compared to 65.1-115.9 mL in controls). For all hearts, right PVs were larger than left PVs (mean: 171.4 ± 84.6 mm([2]) for right and 118.2 ± 50.1 mm([2]) for left, P < 0.005). LA wall thicknesses ranged from 0.7 mm to 3.1 mm for both AF and control hearts. CONCLUSIONS: Hearts with AF had a large range of sizes which is consistent with the progression of atrial remodeling during AF. The large range of thicknesses will influence the amount of energy needed to create transmural lesions during ablation procedures.

Regioselective synthesis of folate receptor-targeted agents derived from epothilone analogs and folic acid.

Efficient regioselective syntheses of conjugates of folic acid and cytotoxic agents derived from natural epothilones are described. These folate receptor (FR) targeting compounds are water soluble and incorporate a hydrophilic peptide-based spacer unit and a reducible self-immolative disulfide-based linker system between the FR-targeting ligand and the parent drug.

MRI assessment of pacing induced ventricular dyssynchrony in an isolated human heart.

This study demonstrates the capabilities of MRI in the assessment of cardiac pacing induced ventricular dyssynchrony, and the findings support the need for employing more physiological pacing. A human donor heart deemed non-viable for transplantation, was reanimated using an MR compatible, four-chamber working perfusion system. The heart was imaged using a 1.5T MR scanner while being paced from the right ventricular apex (RVA) via an epicardial placed lead. Four-chamber, short-axis, and tagged short-axis cines were acquired in order to track wall motion and intramyocardial strain during pacing. The results of this study revealed that the activation patterns of the left ventricle (LV) during RVA pacing demonstrated intraventricular dyssynchrony; as the left ventricular mechanical activation proceeded from the septum and anterior wall to the lateral wall, with the posterior wall being activated last. As such, the time difference to peak contraction between the septum and lateral wall was approximately 125 msec. Likewise, interventricular dyssynchrony was demonstrated from the four-chamber cine as the time difference between the peak LV and RV free wall motion was 180 msec. With the ongoing development of MR safe and MR compatible pacing systems, we can expect MRI to be added to the list of imaging modalities used to optimize cardiac resynchronization therapy (CRT) and/or alternate site pacing.

Strategy to prevent drug-related hypersensitivity in folate-targeted hapten immunotherapy of cancer.

Cancer vaccine/immunotherapy rarely involves systemic administration of an immunogenic compound to an actively immunized host. We have developed such a strategy that utilizes folate to deliver antigenic haptens [e.g., fluorescein (FITC) and dinitrophenyl] to folate receptor-positive tumors in a hapten-pre-vaccinated host. Here, we investigated the safety of this novel approach and developed strategies to prevent drug-related hypersensitivity. Using FITC as the model hapten, we identified a potential source of allergic species in folate-FITC preparations by LC-MS/MS. In mice and guinea pigs, we tested the significance of this impurity by passive cutaneous anaphylaxis and active systemic anaphylaxis assays. We studied the effect of immunogen (e.g., KLH-FITC) dose and derived a desensitization regimen that was further evaluated in a murine tumor model. Administration of folate-FITC with low multi-haptenated contaminants (e.g. bis-FITC) resulted in hypersensitivity in underimmunized animals. However, this drug-related hypersensitivity may be independently prevented by (1) increasing the immunogen dose and/or (2) desensitizing animals with folate-FITC during vaccination. In addition, such manipulation in vivo did not appear to negatively alter the effectiveness of immunotherapy. This study provided confidence on the safety of folate-hapten-targeted cancer immunotherapy in an actively immunized host.

An estimate of carbon emissions from 2004 wildfires across Alaskan Yukon River Basin.

BACKGROUND: Wildfires are an increasingly important component of the forces that drive the global carbon (C) cycle and climate change as progressive warming is expected in boreal areas. This study estimated C emissions from the wildfires across the Alaskan Yukon River Basin in 2004. We spatially related the firescars to land cover types and defined the C fractions of aboveground biomass and the ground layer (referring to the top 15 cm organic soil layer only in this paper) consumed in association with land cover types, soil drainage classes, and the C stocks in the ground layer. RESULTS: The fires led to a burned area of 26,500 km2 and resulted in the total C emission of 81.1 +/- 13.6 Tg (Tg, Teragram; 1 Tg = 1012 g) or 3.1 +/- 0.7 kg C m-2 burned. Of the total C emission, about 73% and 27% could be attributed to the consumption of the ground layer and aboveground biomass, respectively. CONCLUSION: The predominant contribution of the ground layer to the total C emission implies the importance of ground fuel management to the control of wildfires and mitigation of C emissions. The magnitude of the total C emission depends on fire extent, while the C loss in kg C m-2 burned is affected strongly by the ground layer and soil drainage condition. The significant reduction in the ground layer by large fires may result in profound impacts on boreal ecosystem services with an increase in feedbacks between wildfires and climate change.