A multimodal flow reactor for photocatalysis under atmospheric conditions.

Photocatalysis is a promising concept for the direct conversion of solar energy into fuels and chemicals. The design, experimental protocol, and performance of a multimodal and versatile flow reactor for the characterization of powdered and immobilized photocatalysts are herein presented. Ultimately, this instrument enables rigorous evaluation of photocatalysis performance metrics. The apparatus quantifies transient gas-phase reaction products via online real-time gas analyzer mass spectrometry (RTGA-MS). For H2, the most challenging gas, the photocatalytic system's RTGA-MS gas detection sensitivity spans over three orders of magnitude and can detect down to tens of parts per million under atmospheric conditions. Using Pt nanoparticles supported on anatase TiO2 photocatalyst via wet impregnation, the instrument's capability for the characterization of photocatalytic H2 evolution is demonstrated, resulting in an apparent quantum yield (AQY) of 48.1% ± 0.9% at 320 nm, 45.7% ± 0.3% at 340 nm and 31% ± 1% at 360 nm. The photodeposition of Pt on anatase TiO2 was employed to demonstrate the instrument's capability to track the transient behavior of photocatalysts, resulting in an improved 55% ± 2% AQY for H2 evolution at 340 nm from aqueous methanol. This photocatalytic instrument enables systematic study of a wide variety of photocatalytic reactions such as water splitting and CO2 reduction to valuable C2+ fuels and chemicals.

Is there an association between serum soluble interleukin-2 receptor levels and syndrome severity in persistent Complex Regional Pain Syndrome?

OBJECTIVE: A potentially useful biomarker for Complex Regional Pain Syndrome (CRPS) is the serum soluble interleukin-2 receptor (sIL-2R) level, which is a marker for T-cell activation. Elevated serum sIL-2R levels have been described in CRPS patients compared to healthy controls. In T-cell mediated inflammatory diseases such as sarcoidosis and rheumatoid arthritis, the serum sIL-2R levels correlate with disease severity. In this study, we investigate whether an association exists between serum sIL-2R levels in CRPS patients and CRPS severity. METHODS: A cross-sectional cohort study was conducted in a tertiary pain referral center in the Netherlands. Adult CRPS patients diagnosed by the IASP criteria were included between October 2018 until October 2022. The main study parameters were serum sIL-2R levels and the CRPS severity score. RESULTS: Fifty-three CRPS patients were included with a mean syndrome duration of 84 months (Q3 - Q1:180 - 48). The majority had persistent CRPS with a syndrome duration >1 year (n = 52, 98%). The median pain Numerical Rating Score (NRS) was 7 (Q3 - Q1: 8 - 5) and the mean CRPS severity score was 11 (SD ± 2.3). The median serum sIL-2R level was 330 U/mL (Q3 - Q1:451 - 256). No statistically significant correlation was observed between serum sIL-2R levels and the CRPS severity score (rs = 0.15, P = .28). CONCLUSIONS: Our findings suggest that serum sIL-2R levels cannot be used as a biomarker for syndrome severity in persistent CRPS (syndrome duration >1 year). Serial measurements of serum sIL-2R from early CRPS to persistent CRPS are needed to investigate whether serum sIL-2R levels can be used to monitor T-cell mediated inflammatory syndrome activity.

Intermittent versus continuous esketamine infusions for long-term pain modulation in complex regional pain syndrome: protocol of a randomized controlled non-inferiority study (KetCRPS-2).

BACKGROUND: Complex regional pain syndrome (CRPS) is a chronic pain condition of an extremity. While achieving pain relief in CRPS is challenging, esketamine infusions can accomplish pain relief for several weeks post-infusion in a subgroup of CRPS patients. Unfortunately, CRPS esketamine protocols are very heterogeneous in advice on dosage, administration and treatment setting. Currently, no trials are available that study differences between intermittent and continuous esketamine infusions for CRPS. With the current situation of bed shortages, it is difficult to admit patients for several consecutive days for inpatient esketamine treatments. In this study, we investigate whether 6 intermittent outpatient esketamine treatments are not inferior to a continuous 6-day inpatient esketamine treatment in establishing pain relief. In addition, several secondary study parameters will be assessed in order to investigate mechanisms responsible for pain relief by esketamine infusions. Furthermore, the cost-effectiveness will be analyzed. METHODS: In this RCT, the primary objective is to demonstrate that an intermittent esketamine dosing regimen is non-inferior to a continuous esketamine dosing regimen at 3 months follow-up. We will include 60 adult CRPS patients. The inpatient treatment group receives a continuous intravenous esketamine infusion for 6 consecutive days. The outpatient treatment group receives a 6-hour intravenous esketamine infusion every 2 weeks for 3 months. Esketamine dose will be individually tailored and is started at 0.05 mg/kg/h and can be increased to a maximum of 0.2 mg/kg/h. Each patient will be followed for 6 months. The primary study parameter is perceived pain intensity, measured by an 11-point Numerical Rating Scale. Secondary study parameters are conditioned pain modulation, quantitative sensory testing, adverse events, thermography, blood inflammatory parameter, questionnaires about functionality, quality of life and mood and costs per patient. DISCUSSION: If our study reveals non-inferiority between intermittent and continuous esketamine infusions, these findings can be beneficial to increase the availability and flexibility of esketamine infusions through outpatient treatments. Furthermore, the costs of outpatient esketamine infusions could be lower than inpatient esketamine infusions. In addition, secondary parameters may predict response to esketamine treatment. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT05212571 , date of registration 01-28-2022. PROTOCOL VERSION: Version 3, February 2022.

Different Types of Pain in Complex Regional Pain Syndrome Require a Personalized Treatment Strategy.

Complex regional pain syndrome (CRPS) is a debilitating painful state of an extremity that can develop after trauma. CRPS is diagnosed by the new International Association for the Study of Pain (IASP) diagnostic criteria for CRPS. The syndrome is characterized by continuing regional pain with abnormal sensory, motor, sudomotor, vasomotor, edema, and/or trophic signs. The clinical presentation of CRPS can be very heterogeneous because CRPS is a multi-mechanism syndrome. Therefore, mechanism-based subgroups have been suggested to personalize treatment for CRPS. Additionally, the presentation of symptom pain may also be able to identify different subgroups of CRPS. In this review, the types of pain recognized by the IASP-nociceptive, neuropathic, and nociplastic pain-will be discussed as possible subgroups for CRPS. Each pain type should be identified in CRPS patients, with a thorough history taking, physical examination, and diagnostic tests or (novel) biomarkers to optimize treatment effectiveness. Over the course of the syndrome, patients with CRPS probably experience more than one distinct pain type. Therefore, pain specialists should be alert to not only adjust their treatment if underlying pathophysiologic mechanisms tend to change but also to personalize the treatment of the associated type of pain in the CRPS patient.

pH- and Functionalization-Dependent Host-Guest Interactions Between Fluorescein and Various Poly(amidoamine) Dendrimers.

Dendrimers are branched macromolecules that can be functionalized with a large variety of chemical moieties. Dendrimers can therefore be specifically designed to interact with target molecules. Although tailored dendrimers hold promise for targeted drug delivery and wastewater cleanup, these applications require more detailed and systematic studies on how dendrimer-guest interactions depend on environmental conditions. In light of this need, we studied pH-dependent interactions between fluorescein and poly(amidoamine) dendrimers with three different terminal groups. Crucially, both fluorescein and dendrimers have multiple protonation equilibria, which can enable interactions in different pH windows through various possible mechanisms. Such interactions are studied through UV-vis and fluorescence spectroscopies, which reveal a redshift that occurs upon fluorescein-dendrimer binding. The resulting pH-dependent spectra are complex but can be analyzed quantitatively with an open-source mathematical protocol. Consequently, we show that fluorescein binds across four pH units with amine-terminated dendrimers, across two units with hydroxyl-terminated dendrimers and does not interact attractively with carboxyl-terminated dendrimers. These functionalization-dependent host-guest interactions stabilize fluorescein's dianionic form and are predominantly electrostatically driven, with likely auxiliary hydrogen and CH-π bonding. Notably, these auxiliary mechanisms appear too weak to drive dendrimer-fluorescein interactions on their own. Overall, this work yields valuable insights into dendrimer-fluorescein association and provides a readily reproducible framework for studying host-guest interactions.

From a Symptom-Based to a Mechanism-Based Pharmacotherapeutic Treatment in Complex Regional Pain Syndrome.

Complex regional pain syndrome (CRPS) is a debilitating painful condition of a distal extremity that can develop after tissue damage. CRPS is thought to be a multimechanism syndrome and ideally the most prominent mechanism(s) should be targeted by drugs in an individually tailored manner. This review gives an overview of the action and evidence of current and future pharmacotherapeutic options for CRPS. The available options are grouped in four categories by their therapeutic actions on the CRPS mechanisms, i.e. inflammation, central sensitisation, vasomotor disturbances and motor disturbances. More knowledge about the underlying mechanisms of CRPS helps to specifically target important CRPS mechanisms. In the future, objective biomarkers could potentially aid in selecting appropriate mechanism-based drugs in order to increase the effectiveness of CRPS treatment. Using this approach, current and future pharmacotherapeutic options for CRPS should be studied in multicentre trials to prove their efficacy. The ultimate goal is to shift the symptom-based selection of therapy into a mechanism-based selection of therapy in CRPS.

Adaptations of intracellular bacteria to vacuolar or cytosolic niches.

Invasive bacteria colonise their host tissues by establishing niches inside eukaryotic cells, where they grow either in the cytosol or inside a specialised vacuole. These two distinct intracellular lifestyles both present benefits but also impose various constraints on pathogenic microorganisms, in terms of nutrient acquisition, space requirements, exposure to immune responses, and ability to disseminate. Here we review the major characteristics of cytosolic and vacuolar lifestyles and the strategies used by bacteria to overcome challenges specific to each compartment. Recent research providing evidence that these scenarios are not mutually exclusive is presented, with the dual lifestyles of two foodborne pathogens, Listeria monocytogenes and Salmonella Typhimurium, discussed in detail. Finally, we elaborate on the conceptual implications of polyvalence from the perspective of host-pathogen interactions.

Ketamine therapy for chronic pain in The Netherlands: a nationwide survey.

OBJECTIVES: Ketamine is used to treat chronic refractory pain. However, there are no scientific guidelines for ketamine use in the Netherlands. The aim of this survey was to provide an overview of the use of ketamine for chronic pain in the Netherlands. METHODS: All pain clinics in the Netherlands were contacted. A digital survey, available from June 2019 to January 2020, was sent to 68 pain clinics. The survey was completed by one pain physician as a representative of the entire pain department. The survey included questions about ketamine treatment indications, administration, dose, duration, treatment repetition and the inpatient or outpatient setting. RESULTS: The survey was completed by 51 pain clinics (75.0%). Thirty-one clinics used ketamine for chronic pain treatment. The most common indication was Complex Regional Pain Syndrome (83.9%). Pain clinics administered ketamine via intravenous infusions (96.8%), iontophoresis (61.3%), subcutaneous (3.2%) or oral administration (3.2%). Intravenous ketamine treatment was offered in an inpatient setting in 14 pain clinics, in both an inpatient and outpatient setting in 11 pain clinics and in six pain clinics in an outpatient setting. In the outpatient setting, the median starting dose was 5 mg/h (IQR=17.5-5). The median maximum dose was 27.5 mg/h (IQR=100-11.9). The median infusion duration was 6 h (IQR=8-4). In the inpatient setting, the median starting dose was 5 mg/h (IQR=5-1.5) and the median maximum dose was 25 mg/h (IQR=25-14). Patients were admitted to hospital for a median of 4 days (IQR=5-1). CONCLUSIONS: The results of this Dutch nationwide survey study show that there are heterogeneous treatment protocols with different indications, treatment setting and dosing regimen for the treatment of chronic pain with ketamine. This study encourages the formulation of a broader consensus and the development of evidence based guidelines for ketamine treatment.

Habitat patches providing south-north connectivity are under-protected in a fragmented landscape.

As species' ranges shift to track climate change, conservationists increasingly recognize the need to consider connectivity when designating protected areas (PAs). In fragmented landscapes, some habitat patches are more important than others in maintaining connectivity, and methods are needed for their identification. Here, using the Condatis methodology, we model range expansion through an adaptation of circuit theory. Specifically, we map 'flow' through 16 conservation priority habitat networks in England, quantifying how patches contribute to functional South-North connectivity. We also explore how much additional connectivity could be protected via a connectivity-led protection procedure. We find high-flow patches are often left out of existing PAs; across 12 of 16 habitat networks, connectivity protection falls short of area protection by 13.6% on average. We conclude that the legacy of past protection decisions has left habitat-specialist species vulnerable to climate change. This situation may be mirrored in many countries which have similar habitat protection principles. Addressing this requires specific planning tools that can account for the directions species may shift. Our connectivity-led reserve selection procedure efficiently identifies additional PAs that prioritize connectivity, protecting a median of 40.9% more connectivity in these landscapes with just a 10% increase in area.

Effect of intravenous low-dose S-ketamine on pain in patients with Complex Regional Pain Syndrome: A retrospective cohort study.

OBJECTIVE: The objective of this study was to assess the effectiveness of a low-dose intravenous S-ketamine treatment on refractory pain in patients with Complex Regional Pain Syndrome (CRPS). METHODS: In this retrospective study, patients with CRPS who received intravenous S-ketamine from March 2010 to April 2019 were included. According to our inpatient protocol, S-ketamine dose was increased until pain reduction was achieved or side effects were observed. Maximum dose was 14 mg/h and treatment duration was 7 days. Primary outcome parameters were pain scores (Numeric Rating Scale) at baseline (T0), end of infusion (T1), and approximately 4 weeks postinfusion (T2). Patients were categorized as responder/nonresponder at T1 and T2. Patients were considered a responder in case there was pain score reduction of greater than or equal to 2 points or if treatment was reported as successful. RESULTS: Forty-eight patients were included. Mean disease duration was 5 years (interquartile range [IQR] = 6 years). Median pain score significantly decreased from 8 (IQR = 2) at T0 to 6 (IQR = 4) at T1 (p < 0.001). At T1, 62% of the patients were responders. At T2, 48% of the patients remained a responder. A significant proportion of the responders at T1 turned into nonresponders at T2 (p = 0.03). CONCLUSION: In a group of patients with CRPS with refractory pain, low-dose intravenous S-ketamine treatment resulted in effective pain relief during infusion. Although a significant proportion of initial responders became nonresponders at follow-up, half of the patients were still a responder at ~ 4 weeks postinfusion. Further research is needed to investigate mechanisms responsible for pain relief by S-ketamine infusions and to ascertain possible predictors of response to the treatment.

Nanoscale morphological evolution of monocrystalline Pt surfaces during cathodic corrosion.

This paper studies the cathodic corrosion of a spherical single crystal of platinum in an aqueous alkaline electrolyte, to map out the detailed facet dependence of the corrosion structures forming during this still largely unexplored electrochemical phenomenon. We find that anisotropic corrosion of the platinum electrode takes place in different stages. Initially, corrosion etch pits are formed, which reflect the local symmetry of the surface: square pits on (100) facets, triangular pits on (111) facets, and rectangular pits on (110) facets. We hypothesize that these etch pits are formed through a ternary metal hydride corrosion intermediate. In contrast to anodic corrosion, the (111) facet corrodes the fastest, and the (110) facet corrodes the slowest. For cathodic corrosion on the (100) facet and on higher-index surfaces close to the (100) plane, the etch pit destabilizes in a second growth stage, by etching faster in the (111) direction, leading to arms in the etch pit, yielding a concave octagon-shaped pit. In a third growth stage, these arms develop side arms, leading to a structure that strongly resembles a self-similar diffusion-limited growth pattern, with strongly preferred growth directions.

[Hearing and cognition: neurocognitive test batteries in otorhinolaryngology]. / Hören und Kognition: neurokognitive Testbatterien in der HNO-Heilkunde.

BACKGROUND: Hearing and cognition are closely related to each other. Particularly in suboptimal listening situations, cognitive abilities become important to enable speech comprehension. Besides, studies have indicated that hearing impairment is associated with a more rapid mental decline compared to persons with normal hearing. However, hearing loss also has an impact on neurocognitive testing, which is generally based on auditive stimuli. With increasing age, the risk of sensory but also of cognitive impairments increases. So far this comorbidity receives little consideration in otorhinolaryngology. MATERIALS AND METHODS: The paper presents an overview and evaluation of widely used German neurocognitive test batteries for older patients, with regard to the different test modalities and their focus. RESULTS: A multitude of different neurocognitive screening tests and detailed test batteries are available, particularly in the field of dementia. So far, sensory deficits have not been considered in neurocognitive testing, neither concerning application nor interpretation. Normative data adapted to the hearing impaired are still missing. CONCLUSION: With regard to demographic changes and the well-known bias between hearing and cognition, screening of neurocognitive functions should be implemented in basic otorhinolaryngologic diagnostics. More comprehensive test batteries might be useful for research purposes or speech therapy.

Novel protective and risk loci in hip dysplasia in German Shepherds.

Canine hip dysplasia is a common, non-congenital, complex and hereditary disorder. It can inflict severe pain via secondary osteoarthritis and lead to euthanasia. An analogous disorder exists in humans. The genetic background of hip dysplasia in both species has remained ambiguous despite rigorous studies. We aimed to investigate the genetic causes of this disorder in one of the high-risk breeds, the German Shepherd. We performed genetic analyses with carefully phenotyped case-control cohorts comprising 525 German Shepherds. In our genome-wide association studies we identified four suggestive loci on chromosomes 1 and 9. Targeted resequencing of the two loci on chromosome 9 from 24 affected and 24 control German Shepherds revealed deletions of variable sizes in a putative enhancer element of the NOG gene. NOG encodes for noggin, a well-described bone morphogenetic protein inhibitor affecting multiple developmental processes, including joint development. The deletion was associated with the healthy controls and mildly dysplastic dogs suggesting a protective role against canine hip dysplasia. Two enhancer variants displayed a decreased activity in a dual luciferase reporter assay. Our study identifies novel loci and candidate genes for canine hip dysplasia, with potential regulatory variants in the NOG gene. Further research is warranted to elucidate how the identified variants affect the expression of noggin in canine hips, and what the potential effects of the other identified loci are.

Alkali Metal Cation Effects in Structuring Pt, Rh, and Au Surfaces through Cathodic Corrosion.

Cathodic corrosion is an electrochemical etching process that alters metallic surfaces by creating nanoparticles and a variety of etching features. Because these features typically have a preferential orientation, cathodic corrosion can be applied to modify and nanostructure electrode surfaces. However, this application of cathodic corrosion is currently limited by an insufficient chemical understanding of its underlying mechanism. This includes the role of alkali metal cations, which are thought to be crucial in both enabling cathodic corrosion and controlling its final facet preference. This work addresses this knowledge gap by exploring the cathodic corrosion of Pt, Rh, and Au in LiOH, NaOH, and KOH through both experimental and theoretical methods. These methods demonstrate that cations are adsorbed during cathodic corrosion and play a major role in controlling the onset potential and final surface morphology in cathodic corrosion. Interestingly, an equally significant role appears to be played by adsorbed hydrogen, based on calculations using literature density functional theory data. Considering the significance of both hydrogen and electrolyte cations, it is hypothesized that cathodic corrosion might proceed via an intermediate ternary metal hydride. This fundamental insight leads to both metal-specific recommendations and more general guidelines for applying cathodic corrosion to structure metallic surfaces.

Hydrogen adsorption on nano-structured platinum electrodes.

The "hydrogen region" of platinum is a powerful tool to structurally characterize nanostructured platinum electrodes. In recent years, the understanding of this hydrogen region has improved considerably: on Pt(111) sites, there is indeed only hydrogen adsorption, while on step sites, the hydrogen region involves the replacement of adsorbed hydrogen by adsorbed hydroxyl which interacts with co-adsorbed cations. However, the hydrogen region features an enigmatic and less well-understood "third hydrogen peak", which develops on oxidatively roughened platinum electrodes as well as on platinum electrodes with a high (110) step density that have been subjected to a high concentration of hydrogen. In this paper, we present evidence that the peak involves surface-adsorbed hydrogen (instead of subsurface hydrogen) on a locally "reconstructed" (110)-type surface site. This site is unstable when the hydrogen is oxidatively removed. The cation sensitivity of the third hydrogen peak appears different from other step-related peaks, suggesting that the chemistry involved may still be subtly different from the other features in the hydrogen region.

Local structure and composition of PtRh nanoparticles produced through cathodic corrosion.

Alloy nanoparticles fulfill an important role in catalysis. As such, producing them in a simple and clean way is much desired. A promising alloy nanoparticle production method is cathodic corrosion, which generates particles by applying an AC voltage to an alloy electrode. However, this harsh AC potential program might affect the final elemental distribution of the nanoparticles. In this work, we address this issue by characterizing the time that is required to create 1 µmol of Rh, Pt12Rh88, Pt55Rh45 and Pt nanoparticles under various applied potentials. The corrosion time measurements are complemented by structural characterization through transmission electron microscopy, X-ray diffraction and X-ray absorption spectroscopy. The corrosion times indicate that platinum and rhodium corrode at different rates and that the cathodic corrosion rates of the alloys are dominated by platinum. In addition, the structure-sensitive techniques reveal that the elemental distributions of the created alloy nanoparticles indeed exhibit small degrees of elemental segregation. These results indicate that the atomic alloy structure is not always preserved during cathodic corrosion.

Anisotropic etching of rhodium and gold as the onset of nanoparticle formation by cathodic corrosion.

Cathodic corrosion is a phenomenon in which negatively polarized metal electrodes are degraded by cathodic etching and nanoparticle formation. Though these changes are dramatic and sometimes even visible by eye, the exact mechanisms underlying cathodic corrosion are still unclear. This work aims to improve the understanding of cathodic corrosion by studying its onset on rhodium and gold electrodes, which are subjected to various constant cathodic potentials in 10 M NaOH. After this polarization, the electrodes are studied using cyclic voltammetry and scanning electron microscopy, allowing a corrosion onset potential of -1.3 V vs. NHE for rhodium and -1.6 V vs. NHE for gold to be defined. The mildness of the potentials on both metals suggests that cathodic corrosion is less extreme and more ubiquitous than expected. Furthermore, we are able to observe well-defined rectangular etch pits on rhodium. Combined with rhodium cyclic voltammetry, this indicates a strong preference for forming (100) sites during corrosion. In contrast, a (111) preference is indicated on gold by voltammetry and the presence of well-oriented quasi-octahedral nanoparticles. This different etching behavior is suggested to be caused by preferential adsorption of sodium ions to surface defects, as is confirmed by density functional theory calculations.

Anisotropic etching of platinum electrodes at the onset of cathodic corrosion.

Cathodic corrosion is a process that etches metal electrodes under cathodic polarization. This process is presumed to occur through anionic metallic reaction intermediates, but the exact nature of these intermediates and the onset potential of their formation is unknown. Here we determine the onset potential of cathodic corrosion on platinum electrodes. Electrodes are characterized electrochemically before and after cathodic polarization in 10 M sodium hydroxide, revealing that changes in the electrode surface start at an electrode potential of -1.3 V versus the normal hydrogen electrode. The value of this onset potential rules out previous hypotheses regarding the nature of cathodic corrosion. Scanning electron microscopy shows the formation of well-defined etch pits with a specific orientation, which match the voltammetric data and indicate a remarkable anisotropy in the cathodic etching process, favouring the creation of (100) sites. Such anisotropy is hypothesized to be due to surface charge-induced adsorption of electrolyte cations.