Leave No Photon Behind: Artificial Intelligence in Multiscale Physics of Photocatalyst and Photoreactor Design.

Although solar fuels photocatalysis offers the promise of converting carbon dioxide directly with sunlight as commercially scalable solutions have remained elusive over the past few decades, despite significant advancements in photocatalysis band-gap engineering and atomic site activity. The primary challenge lies not in the discovery of new catalyst materials, which are abundant, but in overcoming the bottlenecks related to material-photoreactor synergy. These factors include achieving photogeneration and charge-carrier recombination at reactive sites, utilizing high mass transfer efficiency supports, maximizing solar collection, and achieving uniform light distribution within a reactor. Addressing this multi-dimensional problem necessitates harnessing machine learning techniques to analyze real-world data from photoreactors and material properties. In this perspective, the challenges are outlined associated with each bottleneck factor, review relevant data analysis studies, and assess the requirements for developing a comprehensive solution that can unlock the full potential of solar fuels photocatalysis technology. Physics-informed machine learning (or Physics Neural Networks) may be the key to advancing this important area from disparate data towards optimal reactor solutions.

Advancements in the Design and Development of Dry Powder Inhalers and Potential Implications for Generic Development.

Dry powder inhalers (DPIs) are drug-device combination products where the complexity of the formulation, its interaction with the device, and input from users play important roles in the drug delivery. As the landscape of DPI products advances with new powder formulations and novel device designs, understanding how these advancements impact performance can aid in developing generics that are therapeutically equivalent to the reference listed drug (RLD) products. This review details the current understanding of the formulation and device related principles driving DPI performance, past and present research efforts to characterize these performance factors, and the implications that advances in formulation and device design may present for evaluating bioequivalence (BE) for generic development.

Therapeutic Yoga for the Management of Chronic Nonspecific Neck Pain: Current Evidence and Mechanisms.

Chronic nonspecific neck pain (CNNP), which is neck pain in the absence of attributable structural and neurological findings, is often challenging for medical and rehabilitation professionals to treat. Conventional treatments such as medications and physical therapy often fail to provide lasting relief, which leads patients to pursue complementary therapies such as yoga. This review discusses the evidence from nine studies, including four randomized controlled trials, which suggests that a supervised yoga program may decrease pain intensity, disability, and mood symptoms in adults with CNNP. Cervical range of motion and quality of life (both physical and mental) may also improve with yoga intervention, although this is less consistent across studies. Evidence of yoga's superiority to other exercise-based practices such as pilates was conflicting. Adverse effects of yoga, such as exacerbation of neck pain, were relatively uncommon, minor, and often transient. This article also comprehensively reviews the pathophysiology of CNNP, therapeutic mechanisms of yoga, and limitations in the evidence (including risk-of-bias assessment). Future studies should attempt to: (1) compare the effectiveness of different lineages of yoga for individuals with CNNP, (2) determine the optimal length and duration of these yoga interventions, (3) better characterize the physical and psychological mechanisms of yoga, (4) compare yoga to other exercise- and mindfulness-based practices, (5) evaluate the effect of yoga on sleep in the CNNP population, and (6) explore the applicability/efficacy of virtual yoga instruction.

Successful application of spinal cord stimulation in a patient with refractory bilateral meralgia paresthetica.

We present a 38-year-old morbidly obese male who presented with functionally limiting bilateral anterior thigh pain consistent with meralgia paresthetica. His symptoms had been unresponsive to conservative measures which included physical therapy, oral medications and multiple nerve blocks. Patient underwent a trial of spinal cord stimulation (SCS), experiencing 70% of pain relief. He then underwent permanent SCS implant. At subsequent follow-ups 3 and 6 months later, he continued to report 70% improvement of his pain, as well as improved function and quality of life. To our knowledge, this is only the second reported case of successful treatment of meralgia paresthetica with SCS, and the first in a morbidly obese patient.

We report a case of a 38-year-old obese male who presented with meralgia paresthetica, a condition characterized by abnormal sensation and nerve pain to the outer aspect of the thigh, limiting his ability to perform activities of daily living. His pain was unresponsive to multiple treatment options such as physical therapy, oral medications and a series of injections with local anesthetic and corticosteroid medications. We then proceeded with spinal cord stimulation, which consists of implanting a device that provides low levels of electrical current to the spinal cord, in hopes of alleviating his pain. After implantation of the device, at 3- and 6-month follow-ups, he was able to achieve 70% improvement of his pain, with the ability to perform his daily activities. This is the second case reported of the use of spinal cord stimulation for this type of condition.

Cervical spinal cord infarction due to impingement of an anomalous right vertebral artery by thoracic osteophyte.

INTRODUCTION: Spinal cord infarction in a young, otherwise healthy individual is a rare occurrence. The anterior spinal artery and posterior spinal arteries are the primary contributors to the vascular supply of the cervical supply, and these arteries arise as descending branches of the vertebral arteries. Historically, many cases have demonstrated individual variations in the vertebral arteries, such as differences in dominancy, patency, origin, and insertion. The clinical significance of these variations remains poorly understood. CASE PRESENTATION: We present a patient who sustained a spinal cord infarction at C2-C5 resulting in incomplete quadriplegia. The mechanism of injury was unclear, although the patient reported an awkward jumping motion earlier that day that preceded the onset of upper extremity weakness. After resolution of the acute phase, he was diagnosed with "Man-in-the-Barrel" syndrome. Angiographic evaluation revealed an anomalous non-dominant right vertebral artery with several pathological features: origin at the descending aorta, insertion into the right posterior inferior cerebellar artery, and impingement along its course by an anterior thoracic osteophyte. DISCUSSION: The vertebral arteries play an important role in the vascular supply of the cervical spine. While vertebral artery pathology such as dissection or occlusion have been documented in rare cases to result in spinal cord infarction, this case illustrates an example of clinically significant sequelae that can occur in the setting of anomalous vertebral arteries even in the absence of occlusion or dissection. Furthermore, to our knowledge this is the first reported case of a spinal cord infarction resulting from osteophytic vertebral artery impingement.

Iatrogenic Cushing syndrome following lumbar medial branch block in a patient with HIV on ritonavir and darunavir.

We present a case report of a 62-year old female with HIV and chronic facetogenic back pain who underwent bilateral L3-L4 and L4-L5 medial branch nerve blocks using triamcinolone acetonide 80 mg. 2 weeks later she presented to the emergency department with acute anxiety/depression and was discharged with psychiatric follow-up. 2 weeks after this she presented to the outpatient HIV clinic with persistent uncontrolled depression alongside classic cushingoid features (e.g., buffalo hump, moon facies). She was diagnosed with iatrogenic Cushing syndrome caused by a drug-drug interaction between triamcinolone and ritonavir, a protease inhibitor and a CYP3A4 enzyme inhibitor. While the literature describes the interaction of ritonavir with intra-articular/intranasal/epidural triamcinolone, this is the first documented occurrence following a nerve block procedure. Symptoms resolved within 6 months alongside discontinuation of protease inhibitor therapy.

Lay abstract We report a 62-year old woman with history of HIV and depression who developed Cushing syndrome, which is a state of steroid excess in the body, after a nerve block procedure for treatment of back pain. Her first symptoms were worsening anxiety and depression, causing her to go to the emergency department. Unfortunately, the relationship to the steroids was not identified at the time. Later, she developed increased fat deposition in her face and upper neck, which is characteristic of Cushing syndrome. The HIV medications responsible for this adverse event were determined to be ritonavir and darunavir, which are classified as protease inhibitors. Her symptoms improved within 6 months in association with discontinuation of ritonavir and darunavir. This is the first known case of Cushing syndrome following a nerve block procedure for back pain, although previous cases have documented this occurrence following other forms of steroid treatments.

Waveguide photoreactor enhances solar fuels photon utilization towards maximal optoelectronic - photocatalytic synergy.

A conventional light management approach on a photo-catalyst is to concentrate photo-intensity to enhance the catalytic rate. We present a counter-intuitive approach where light intensity is distributed below the electronic photo-saturation limit under the principle of light maximization. By operating below the saturation point of the photo-intensity induced hydroxide growth under reactant gaseous H2+CO2 atmosphere, a coating of defect engineered In2O3-x(OH)y nanorod Reverse Water Gas Shift solar-fuel catalyst on an optical waveguide outperforms a coated plane by a factor of 2.2. Further, light distribution along the length of the waveguide increases optical pathlengths of the weakly absorptive green and yellow wavelengths, which increases CO product rate by a factor of 8.1-8.7 in the visible. Synergistically pairing with thinly doped silicon on the waveguide enhances the CO production rate by 27% over the visible. In addition, the persistent photoconductivity behavior of the In2O3-x(OH)y system enables CO production at a comparable rate for 2 h after turning off photo-illumination, enhancing yield with 44-62% over thermal only yield. The practical utility of persistent photocatalysis was demonstrated through outdoor solar concentrator tests, which after a day-and-night cycle showed CO yield increase of 19% over a day-light only period.

Thalamic Dementia in Acute Inpatient Rehabilitation-Role for Amantadine?

ABSTRACT: Thalamic dementia is an uncommon type of stroke that presents with disorientation, behavioral changes, and impairment of executive functions, with relative preservation of motor functions. It is typically caused by paramedian territory infarctions of the thalamus, most often due to ischemic insult at the tip of the basilar artery. In this report, we present a case of bilateral thalamic infarcts resulting in thalamic dementia with severe behavioral manifestations in a 64-yr-old man with no preexisting neuropsychiatric comorbidities. A trial of amantadine, a dopamine-promoting agent, in the acute rehabilitation unit in an attempt to manage his agitation led to multiple weeks of dramatic behavioral improvement and increased participation in therapies. Dopamine receptors are believed to be present at increased densities in thalamic nuclei with mesolimbic projections, suggesting that they are able to modulate limbic functions such as arousal, emotion, and memory. This case report, aimed both to increase the awareness of this uncommon stroke syndrome and describe the observed effect of amantadine, will ultimately help clinicians properly recognize thalamic dementia, minimize unnecessary investigations, and develop effective neurorehabilitation strategies in these patients.

HIV Neuropathy-Associated Foot Drop, a Presenting Sign of HIV Infection, Resolving After Initiation of Antiretroviral Therapy: A Clinical Vignette.

ABSTRACT: Peripheral neuropathy is one of the most frequent complaints in patients with HIV. Many complex syndromes exist, with the etiology being secondary to the disease process itself, antiretroviral medication, or immune reconstitution. However, isolated mononeuropathy is rare. In this case, we present a previously healthy man who complained of several months of worsening right foot drop that did not improve with physical therapy or lifestyle interventions. He had begun to use an solid ankle-foot orthotic on this right lower limb to minimize tripping and prevent falls. He had no other neuromuscular involvement or constitutional complaints. Nerve conduction study of the right lower limb showed decreased peak amplitude, prolonged distal latency, and decreased conduction velocity of the deep peroneal nerve. Electromyography revealed abnormal insertional activity and absent motor unit action potentials in both the right tibialis anterior and right extensor digitorum brevis muscles. Magnetic resonance imaging of the right lower limb was suggestive of acute/subacute denervation of the right tibialis anterior muscle. An extensive laboratory workup revealed active HIV infection with a significant viral load. Once the diagnosis was made, the patient was started on antiretroviral treatment. Six months later, his foot drop had entirely resolved, in association with significant improvements in viral load and CD4 count. He has since been ambulating without assistive devices and his HIV/AIDS disease process remains well controlled. This clinical vignette is the first, to our knowledge, to illustrate that an acute focal mononeuropathy causing foot drop and gait dysfunction in an otherwise healthy-appearing individual can be a heralding sign of HIV/AIDS. Furthermore, it also suggests that this functional deficit can be reversed with timely initiation of antiretroviral treatment. Early recognition, diagnosis, and treatment in this patient have not only led to an uncomplicated AIDS disease course but also restored his ability to ambulate with complete independence and improved his quality of life.

Renal and perinephric abscesses involving Lactobacillus jensenii and Prevotella bivia in a young woman following ureteral stent procedure.

 is a gram-positive bacillus in the female genital tract believed to be a commensal organism that inhibits the growth of more virulent pathogens. Prevotella bivia is a gram-negative bacillus species also typically commensal in the female genital tract. Lactobacillus as the primary causative agent in perinephric abscesses and bacteremia has been documented, albeit very uncommon and opportunistic. Prevotella bivia is not classically associated with perinephric abscesses but has been implicated in rare cases of pelvic inflammatory disease and tubo-ovarian abscesses. In this report, we present a 26-year-old immunocompetent woman with a recent history of nephrolithiasis treated with lithotripsy, ureteral stent placement and removal, and antibiotics who was admitted for fever and severe right flank pain. Imaging showed a right-sided renal and perinephric abscesses colonized by Lactobacillus jensenii and Prevotella bivia. Blood cultures were also positive for Lactobacillus species. Per literature review, intravenous ceftriaxone and metronidazole were administered with successful resolution of abscesses and negative repeat blood cultures. To our knowledge, this is the first case of simultaneous renal system abscesses caused by Lactobacillus and Prevotella species. Nephrolithiasis and prior antibiotics likely contributed to the opportunistic pathogenesis in this otherwise immunocompetent patient.

Shining light on CO2: from materials discovery to photocatalyst, photoreactor and process engineering.

Heterogeneous catalysis, a process in which the reaction of gaseous or liquid chemical reagents is facilitated at the surface of a solid material, is responsible for the majority of industrial-scale chemical and fuel production reactions. The energy required to drive these reactions has historically been derived from the combustion of non-renewable fossil fuels and carries an unavoidably large carbon footprint. More recently, the development of environmentally responsible and sustainable chemical industries is increasingly motivated by greenhouse gas-induced climate change, thus creating demand for eco-friendly heterogeneous catalytic processes. This includes innovative approaches enabled by renewable forms of energy, such as the electrification of chemical and petrochemical processes, utilization of CO2 as a feedstock and the incorporation of light into catalytic reactions. Herein we review the conversion of solar energy to chemical energy using CO2, and describe how the photophysical and photochemical properties of nanostructured metal oxide photocatalysts have been engineered to efficiently incorporate light into heterogeneous gas-solid CO2 hydrogenation reactions. Realizing high photonic and energy efficiencies in these systems has demanded innovation in not only photocatalyst engineering, but also photoreactor and process engineering. Rather than exclusively providing an in-depth discussion of the chemistry and science within each individual study, this Tutorial Review highlights the multidisciplinary character of photocatalysis studies by covering the four essential components of a typical research work in this field (materials engineering, theoretical modelling, reactor engineering and process development) via case studies of the archetypal indium oxide catalyst materials. Through advances in these four components, progress has been made towards the ultimate goal of industrializing the production of CO2-derived chemicals and fuels.

Hybrid Photo- and Thermal Catalyst System for Continuous CO2 Reduction.

Heterogeneous thermal catalytic processes are vital for industrial production of fuels, fertilizers, and other chemicals necessary for sustaining human life. However, these processes are highly energy-intensive, requiring a vast consumption of fossil fuels. An emerging class of heterogeneous catalysts that are thermally driven but also exhibit a photochemically enhanced rate can potentially reduce process energy intensity by partially substituting conventional heat (where fossil fuels are needed) with solar energy. Such catalyst systems have yet to be practically utilized. Here, we demonstrate a compact electrically heated photo- and thermal annular reactor module to reduce CO2 to CO, via the reverse water gas shift reaction. A first-principles-based design approach was taken in developing a SiO2 on an Al photo- and thermal catalyst system for the model photo- and thermal indium oxide hydroxide (In2O3-x(OH)y) catalysts. A 5-fold light enhancement in the CO production rate and over 70 h of stable CO production were achieved. This represents the highest light enhancement effect reported for this model photocatalyst to date. The reactor presented herein allows continuous operation and a significant reduction of 31% in heater power consumption when provided with an additional 2 suns of irradiation, demonstrating the strong photo- and thermal-harvesting performances of the catalyst system developed in this work.

Osmotic Gradients in Epithelial Acini Increase Mechanical Tension across E-cadherin, Drive Morphogenesis, and Maintain Homeostasis.

Epithelial cells spontaneously form acini (also known as cysts or spheroids) with a single, fluid-filled central lumen when grown in 3D matrices. The size of the lumen is dependent on apical secretion of chloride ions, most notably by the CFTR channel, which has been suggested to establish pressure in the lumen due to water influx. To study the cellular biomechanics of acini morphogenesis and homeostasis, we used MDCK-2 cells. Using FRET-force biosensors for E-cadherin, we observed significant increases in the average tension per molecule for each protein in mature 3D acini as compared to 2D monolayers. Increases in CFTR activity resulted in increased E-cadherin forces, indicating that ionic gradients affect cellular tension. Direct measurements of pressure revealed that mature acini experience significant internal hydrostatic pressure (37 ± 10.9 Pa). Changes in CFTR activity resulted in pressure and/or volume changes, both of which affect E-cadherin tension. Increases in CFTR chloride secretion also induced YAP signaling and cellular proliferation. In order to recapitulate disruption of acinar homeostasis, we induced epithelial-to-mesenchymal transition (EMT). During the initial stages of EMT, there was a gradual decrease in E-cadherin force and lumen pressure that correlated with lumen infilling. Strikingly, increasing CFTR activity was sufficient to block EMT. Our results show that ion secretion is an important regulator of morphogenesis and homeostasis in epithelial acini. Furthermore, this work demonstrates that, for closed 3D cellular systems, ion gradients can generate osmotic pressure or volume changes, both of which result in increased cellular tension.

Towards Solar Methanol: Past, Present, and Future.

This work aims to provide an overview of producing value-added products affordably and sustainably from greenhouse gases (GHGs). Methanol (MeOH) is one such product, and is one of the most widely used chemicals, employed as a feedstock for ≈30% of industrial chemicals. The starting materials are analogous to those feeding natural processes: water, CO2, and light. Innovative technologies from this effort have global significance, as they allow GHG recycling, while providing society with a renewable carbon feedstock. Light, in the form of solar energy, assists the production process in some capacity. Various solar strategies of continually increasing technology readiness levels are compared to the commercial MeOH process, which uses a syngas feed derived from natural gas. These strategies include several key technologies, including solar-thermochemical, photochemical, and photovoltaic-electrochemical. Other solar-assisted technologies that are not yet commercial-ready are also discussed. The commercial-ready technologies are compared using a technoeconomic analysis, and the scalability of solar reactors is also discussed in the context of light-incorporating catalyst architectures and designs. Finally, how MeOH compares against other prospective products is briefly discussed, as well as the viability of the most promising solar MeOH strategy in an international context.

Spatial Proliferation of Epithelial Cells Is Regulated by E-Cadherin Force.

Cell proliferation and contact inhibition play a major role in maintaining epithelial cell homeostasis. Prior experiments have shown that externally applied forces, such as stretch, result in increased proliferation in an E-cadherin force-dependent manner. In this study, the spatial regulation of cell proliferation in large epithelial colonies was examined. Surprisingly, cells at the center of the colony still had increased proliferation as compared to cells in confluent monolayers. E-cadherin forces were found to be elevated for both cells at the edge and center of these larger colonies when compared to confluent monolayers. To determine if high levels of E-cadherin force were necessary to induce proliferation at the center of the colony, a lower-force mutant of E-cadherin was developed. Cells with lower E-cadherin force had significantly reduced proliferation for cells at the center of the colony but minimal differences for cells at the edges of the colony. Similarly, increasing substrate stiffness was found to increase E-cadherin force and increase the proliferation rate across the colony. Taken together, these results show that forces through cell-cell junctions regulate proliferation across large groups of epithelial cells. In addition, an important finding of this study is that junction forces are dynamic and modulate cellular function even in the absence of externally applied loads.

The Desmosomal Cadherin Desmoglein-2 Experiences Mechanical Tension as Demonstrated by a FRET-Based Tension Biosensor Expressed in Living Cells.

Cell-cell junctions are critical structures in a number of tissues for mechanically coupling cells together, cell-to-cell signaling, and establishing a barrier. In many tissues, desmosomes are an important component of cell-cell junctions. Loss or impairment of desmosomes presents with clinical phenotypes in the heart and skin as cardiac arrhythmias and skin blistering, respectively. Because heart and skin are tissues that are subject to large mechanical stresses, we hypothesized that desmosomes, similar to adherens junctions, would also experience significant tensile loading. To directly measure mechanical forces across desmosomes, we developed and validated a desmoglein-2 (DSG-2) force sensor, using the existing TSmod Förster resonance energy transfer (FRET) force biosensor. When expressed in human cardiomyocytes, the force sensor reported high tensile loading of DSG-2 during contraction. Additionally, when expressed in Madin-Darby canine kidney (MDCK) epithelial or epidermal (A431) monolayers, the sensor also reported tensile loading. Finally, we observed higher DSG-2 forces in 3D MDCK acini when compared to 2D monolayers. Taken together, our results show that desmosomes experience low levels of mechanical tension in resting cells, with significantly higher forces during active loading.

Decompression for botulinum toxin-exacerbated cervical myeloradiculopathy in the setting of congenital stenosis and Arnold-Chiari I malformation.

INTRODUCTION: We present a case describing the management of a woman with severe, functionally limiting cervical myeloradiculopathy in the setting of congenital cervical canal stenosis and Arnold-Chiari I malformation. CASE PRESENTATION: The subject is a 57-year-old woman with prior anterior cervical discectomy and fusion who presented with left-sided neck pain associated with radiculopathy, migraine, gait incoordination, and cervical dystonia. Cervical stenosis and Chiari malformation were confirmed using MRI. Conservative management with botulinum toxin, oral muscle relaxants, and cervical brace led to gradual exacerbation of symptoms. Due to failure of conservative management, surgical decompression with C3-C6 posterior laminoplasty was performed, resulting in complete resolution of all symptoms and markedly improved quality of life. DISCUSSION: This case reports a severe and nonspecific presentation of cervical myeloradiculopathy. Surgery for cervical myeloradiculopathy is controversial, and conservative therapy is initially preferred. However, in this case, conservative treatments likely led to paraspinal weakness, cervical hypermobility, and biomechanical instability, resulting in exacerbation of symptoms. Stretch/shear forces have been postulated to accelerate cervical myelopathy, and excessive cervical instability and range of motion are significant predictors of deterioration. In this case, surgical decompression with posterior cervical laminoplasty after 1 year of conservative management yielded significant pain relief and functional restoration, indicating the utility of this procedure even in the presence of Arnold-Chiari I malformation. This case illustrates that decompression can be effective for refractory cervical myeloradiculopathy associated with Chiari malformation, congenital stenosis, and prior anterior instrumentation, and highlights the potential risks of prolonged conservative management.

Lymph node biophysical remodeling is associated with melanoma lymphatic drainage.

Tissue remodeling is a characteristic of many solid tumor malignancies including melanoma. By virtue of tumor lymphatic transport, remodeling pathways active within the local tumor microenvironment have the potential to be operational within lymph nodes (LNs) draining the tumor interstitium. Here, we show that lymphatic drainage from murine B16 melanomas in syngeneic, immune-competent C57Bl/6 mice is associated with LN enlargement as well as nonuniform increases in bulk tissue elasticity and viscoelasticity, as measured by the response of whole LNs to compression. These remodeling responses, which quickly manifest in tumor-draining lymph nodes (TDLNs) after tumor inoculation and before apparent metastasis, were accompanied by changes in matrix composition, including up to 3-fold increases in the abundance of soluble collagen and hyaluronic acid. Intranodal pressures were also significantly increased in TDLNs (+1 cmH2O) relative to both non-tumor-draining LNs (-1 cmH2O) and LNs from naive animals (-1 to 2 cmH2O). These data suggest that the reorganization of matrix structure, composition, and fluid microenvironment within LNs associated with tumor lymphatic drainage parallels remodeling seen in primary malignancies and has the potential to regulate the adhesion, proliferation, and signaling function of LN-resident cells involved in directing melanoma disease progression.