Liver Steatosis is Prevalent in Lean People With HIV and Associated With Exposure to Antiretroviral Treatment-A Cross-sectional Study.

Background: Steatotic liver disease is suggested to have a higher prevalence and severity in people with HIV (PHIV), including in those with a normal body mass index (BMI). In this study, we used data from the 2000HIV cohort to (1) assess the prevalence of liver steatosis and fibrosis in lean versus overweight/obese PHIV and (2) assess associations in these subgroups between steatosis and fibrosis with traditional risk factors and HIV-specific characteristics. Methods: The 2000HIV study cohort comprises 1895 virally suppressed PHIV that were included between 2019 and 2021 in 4 HIV treatment centers in the Netherlands. The majority (58.5%) underwent vibration-controlled transient elastography for the assessment of liver steatosis and fibrosis. The prevalence of steatosis (controlled attenuation parameter ≥263 dB/m) and fibrosis (liver stiffness measurement ≥7.0 kPa) was estimated. Multiple factors including HIV characteristics and antiretroviral drugs were tested in a logistic regression model for association with steatosis and fibrosis. Analyses were performed separately for lean (Asian descent: BMI < 23 kg/m2, other descent: BMI < 25 kg/m2) and overweight/obese (other BMI) participants. Results: Of 1050 PHIV including 505 lean and 545 overweight/obese PHIV, liver steatosis was observed in 37.7% of the overall study population, 19.7% of lean, and 54% of overweight/obese PHIV, whereas fibrosis was observed in 9.0% of the overall study population, 5.9% of lean, and 12.0% of overweight/obese PHIV.All associations with fibrosis and most associations with steatosis concerned metabolic factors such as type 2 diabetes mellitus (overall population: adjusted odds ratio [aOR] for steatosis: 2.3 [1.21-4.4], P = .011; aOR for fibrosis: 3.7 [1.82-7.53], P < .001). Furthermore, in lean PLHIV, liver steatosis was associated with CD4 and CD8 counts at enrollment, dual therapy, and history of treatment with raltegravir (aOR: 3.6 [1.53-8.47], P = .003), stavudine (aOR: 3.73 [1.69-8.2], P = .001), and indinavir (aOR: 3.86 [1.59-9.37], P = .003). These associations were not observed in overweight/obese PHIV. Conclusions: Liver steatosis was highly prevalent, affecting approximately one-fifth of lean PHIV and half of overweight/obese PHIV. Fibrosis was observed in a minority. Both steatosis and fibrosis were associated with traditional metabolic risk factors. In addition, (prior) exposure to specific antiretroviral drugs was associated liver steatosis in lean, but not in overweight/obese PHIV. Implementing increased screening protocols could enhance the identification of steatotic liver disease in lean PHIV.

Why dental schools should engage with dental support organizations.

It is incumbent on dental educators to prepare students for careers in various practice settings and modalities. As the dental practice market continues to evolve away from a predominantly solo private practice model, schools are tasked with training future providers to deliver quality care to diverse patient populations in diverse settings. While no single health delivery model will solve access to care, exposing dental students to various practice environments prepares them to better understand and navigate nontraditional postgraduate practice opportunities. The University of California, Los Angeles (UCLA) School of Dentistry established a community-based clinical education (CBCE) program that has grown to include dental support organizations. By partnering with a more diverse portfolio of practice types, including large corporate entities, the UCLA CBCE program has strengthened its financial accountability while also delivering on the goal of enhancing dental education and improving access to care for vulnerable populations.

HIV immunological non-responders are characterized by extensive immunosenescence and impaired lymphocyte cytokine production capacity.

Introduction: Immunological non-responders (INR) are people living with HIV (PLHIV) who fail to fully restore CD4+ T-cell counts despite complete viral suppression with antiretroviral therapy (ART). INR are at higher risk for non-HIV related morbidity and mortality. Previous research suggest persistent qualitative defects. Methods: The 2000HIV study (clinical trials NTC03994835) enrolled 1895 PLHIV, divided in a discovery and validation cohort. PLHIV with CD4 T-cell count <350 cells/mm3 after ≥2 years of suppressive ART were defined as INR and were compared to immunological responders (IR) with CD4 T-cell count >500 cells/mm3. Logistic and rank based regression were used to analyze clinical data, extensive innate and adaptive immunophenotyping, and ex vivo monocyte and lymphocyte cytokine production after stimulation with various stimuli. Results: The discovery cohort consisted of 62 INR and 1224 IR, the validation cohort of 26 INR and 243 IR. INR were older, had more advanced HIV disease before starting ART and had more frequently a history of non-AIDS related malignancy. INR had lower absolute CD4+ T-cell numbers in all subsets. Activated (HLA-DR+, CD38+) and exhausted (PD1+) subpopulations were proportionally increased in CD4 T-cells. Monocyte and granulocyte immunophenotypes were comparable. INR lymphocytes produced less IL-22, IFN-γ, IL-10 and IL-17 to stimuli. In contrast, monocyte cytokine production did not differ. The proportions of CD4+CD38+HLA-DR+ and CD4+PD1+ subpopulations showed an inversed correlation to lymphocyte cytokine production. Conclusions: INR compared to IR have hyperactivated and exhausted CD4+ T-cells in combination with lymphocyte functional impairment, while innate immune responses were comparable. Our data provide a rationale to consider the use of anti-PD1 therapy in INR.

Cardiometabolic Differences in People Living with HIV Receiving Integrase Strand Transfer Inhibitors Compared to Non-nucleoside Reverse Transcriptase Inhibitors: Implications for Current ART Strategies.

In people living with HIV (PLHIV), integrase strand transfer inhibitors (INSTIs) are part of the first-line combination antiretroviral therapy (cART), while non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens are alternatives. Distinct cART regimens may variably influence the risk for non-AIDS comorbidities. We aimed to compare the metabolome and lipidome of INSTI and NNRTI-based regimens. The 2000HIV study includes asymptomatic PLHIV (n = 1646) on long-term cART, separated into a discovery cohort with 730 INSTI and 617 NNRTI users, and a validation cohort encompassing 209 INSTI and 90 NNRTI users. Baseline plasma samples from INSTI and NNRTI users were compared using mass spectrometry-based untargeted metabolomic (n = 500) analysis. Perturbed metabolic pathways were identified using MetaboAnalyst software. Subsequently, nuclear magnetic resonance spectroscopy was used for targeted lipoprotein and lipid (n = 141) analysis. Metabolome homogeneity was observed between the different types of INSTI and NNRTI. In contrast, higher and lower levels of 59 and 45 metabolites, respectively, were found in the INSTI group compared to NNRTI users, of which 77.9% (81/104) had consistent directionality in the validation cohort. Annotated metabolites belonged mainly to 'lipid and lipid-like molecules', 'organic acids and derivatives' and 'organoheterocyclic compounds'. In pathway analysis, perturbed 'vitamin B1 (thiamin) metabolism', 'de novo fatty acid biosynthesis', 'bile acid biosynthesis' and 'pentose phosphate pathway' were detected, among others. Lipoprotein and lipid levels in NNRTIs were heterogeneous and could not be compared as a group. INSTIs compared to individual NNRTI types showed that HDL cholesterol was lower in INSTIs compared to nevirapine but higher in INSTIs compared to doravirine. In addition, LDL size was lower in INSTIs and nevirapine compared to doravirine. NNRTIs show more heterogeneous cardiometabolic effects than INSTIs, which hampers the comparison between these two classes of drugs. Targeted lipoproteomic and lipid NMR spectroscopy showed that INSTI use was associated with a more unfavorable lipid profile compared to nevirapine, which was shifted to a more favorable profile for INSTI when substituting nevirapine for doravirine, with evidently higher fold changes. The cardiovascular disease risk profile seems more favorable in INSTIs compared to NNRTIs in untargeted metabolomic analysis using mass-spectrometry.

Traditional Cardiovascular Risk Factors Are Stronger Related to Carotid Intima-Media Thickness Than to Presence of Carotid Plaques in People Living With HIV.

Background Cardiovascular disease is a major cause of morbidity and mortality in people living with HIV, who are at higher risk than the general population. We assessed, in a large cohort of people living with HIV, which cardiovascular, HIV-specific, and lipoproteomic markers were associated with carotid intima-media thickness (cIMT) and carotid plaque presence. We also studied guideline adherence on lipid-lowering medication in individuals with high and very high risk for cardiovascular disease. Methods and Results In 1814 individuals with a median (interquartile range) age of 53 (44-60) years, we found a carotid plaque in 909 (50.1%) and a median (interquartile range) intima-media thickness of 0.66 (0.57-0.76) mm. Ultrasonography was used for the assessment of cIMT and plaque presence. Univariable and multivariable regression models were used for associations with cIMT and presence of plaques. Age, Black race, body mass index, type 2 diabetes, and smoking (pack years) were all positively associated with higher cIMT. Levels of high-density lipoprotein cholesterol, specifically medium and large high-density lipoprotein subclasses, were negatively associated with higher cIMT. Only age and prior myocardial infarction were positively related to the presence of a carotid plaque. Lipid-lowering treatment was prescribed in one-third of people living with HIV, who are at high and very high risk for cardiovascular disease. Conclusions Traditional cardiovascular risk factors were significantly associated with higher cIMT but not with carotid plaques, except for age. HIV-specific factors were not associated with both ultrasound measurements. Future studies are needed to elucidate which factors contribute to plaque formation. Improvement of guideline adherence on prescription of lipid-lowering treatment in high- and very high-risk patients for cardiovascular disease is recommended. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03994835.

Role of Fe/Co Ratio in Dual Phase Ce0.8Gd0.2O2-δ-Fe3-xCoxO4 Composites for Oxygen Separation.

Dual-phase membranes are increasingly attracting attention as a solution for developing stable oxygen permeation membranes. Ce0.8Gd0.2O2-δ-Fe3-xCoxO4 (CGO-F(3-x)CxO) composites are one group of promising candidates. This study aims to understand the effect of the Fe/Co-ratio, i.e., x = 0, 1, 2, and 3 in Fe3-xCoxO4, on microstructure evolution and performance of the composite. The samples were prepared using the solid-state reactive sintering method (SSRS) to induce phase interactions, which determines the final composite microstructure. The Fe/Co ratio in the spinel structure was found to be a crucial factor in determining phase evolution, microstructure, and permeation of the material. Microstructure analysis showed that all iron-free composites had a dual-phase structure after sintering. In contrast, iron-containing composites formed additional phases with a spinel or garnet structure which likely contributed to electronic conductivity. The presence of both cations resulted in better performance than that of pure iron or cobalt oxides. This demonstrated that both types of cations were necessary to form a composite structure, which then allowed sufficient percolation of robust electronic and ionic conducting pathways. The maximum oxygen flux is jO2 = 0.16 and 0.11 mL/cm2·s at 1000 °C and 850 °C, respectively, of the 85CGO-FC2O composite, which is comparable oxygen permeation flux reported previously.

Direct Visualization of Distorted Twin Boundaries in Ce-Doped GdFeO3.

Utilizing advanced transmission electron microscopy (TEM), the structure at the (110)-type twin boundary (TB) of Ce-doped GdFeO3 (C-GFO) has been investigated with picometer precision. Such a TB is promising to generate local ferroelectricity within a paraelectric system, while precise knowledge about its structure is still largely missing. In this work, a direct measurement of the cation off-centering with respect to the neighboring oxygen is enabled by integrated differential phase contrast (iDPC) imaging, and up to 30 pm Gd off-centering is highly localized at the TB. Further electron energy loss spectroscopy (EELS) analysis demonstrates a slight accumulation of oxygen vacancies at the TB, a self-balanced behavior of Ce at the Gd sites, and a mixed occupation of Fe2+ and Fe3+ at the Fe sites. Our results provide an informative picture with atomic details at the TB of C-GFO, which is indispensable to further push the potential of grain boundary engineering.

A new approach to drug intravenous compatibility research: the case of obstetric parenteral drugs.

OBJECTIVES: The product information and literature does not provide confirmation of compatibility for co-administration of all commonly used drug pairs in obstetrics. However, there is a need for co-administration of these drugs over one lumen for this group of patients. Therefore, this study focuses on Y-site compatibility. Since different conditions between clinical and laboratory settings can lead to discrepancies in results, a novel approach for drug intravenous compatibility testing was designed to reflect clinical conditions. The aim was to study the compatibility of nine commonly used drug pairs in obstetrics and to evaluate the clinical value of the designed method. METHODS: The clinical situation was reflected by using different temperature ranges (20°C and 37°C), actual Y-site flow ratios, clinically relevant drug pairs and an observation time of 120 min. The clinically relevant drugs pairs include atosiban, nicardipine, amoxicillin/clavulanic acid, oxytocin, remifentanil, labetalol and magnesium sulpfate. Drug pairs were visually assessed according to the European Pharmacopoeia (Ph. Eur.) and pH was measured. When incompatibility of a drug pair seemed likely based on literature review or observed abnormalities during visual assessment, subvisual analysis was performed using a particle counter. Y-site compatibility applied for drug pairs when no visual changes occurred or when no additional particles were formed during the observation time. RESULTS: Eight of the nine combinations showed no visual changes or noticeable changes in pH during the observation time. The amoxicillin/clavulanic-acid-oxytocin combination showed a colour change at 37°C at the actual Y-site flow ratio. However, subvisual particle counting showed no formation of additional particles. CONCLUSIONS: Y-site compatibility was established for all tested drug pairs. The new clinical approach for analysing Y-site compatibility provides a high certainty of outcomes for clinical practice. In this way, clinical complications and use of several additional intravenous catheters can be avoided.

Non-AIDS Events in Individuals With Spontaneous Control of HIV-1: A Systematic Review.

BACKGROUND: Despite antiretroviral therapy (ART), people living with HIV (PLHIV) are at increased risk for non-AIDS-defining events (nADEs), including cardiovascular events, non-AIDS malignances, hepatic disease, and bacterial pneumonia. SETTING: This systematic review seeks to answer the question: are PLHIV who spontaneously control HIV-1 subject to an increased risk of various nADEs relative to noncontrolling PLHIV on ART and people without HIV? METHODS: Databases were searched on June 9, 2021 with a search syntax focused on the elements "HIV," "spontaneous control," and "clinical outcomes": Embase.com (includes Embase and Medline), Medline Ovid (includes PubMed), Cochrane library, Web of Science, and Google Scholar. Included were studies reporting non-AIDS events in spontaneous controllers. Excluded were case reports, conference papers, editorials, and reviews. RESULTS: Of 1134 identified records, 34 were assessed for full-text and 12 studies were included in the qualitative synthesis: 5 cohorts, 2 cross-sectional prevalence studies, 4 cross-sectional imaging studies, and one case series. Four of 5 cohort studies showed that spontaneous controllers have a similar risk to develop nADEs compared with PLHIV on suppressive ART, specifically cardiovascular events, non-AIDS malignancies, hepatic disease, and bacterial pneumonia. Cross-sectional imaging studies showed a higher presence of subclinical cardiovascular disease in spontaneous controllers, than in people without HIV. CONCLUSION: Individuals with spontaneous control of HIV-1 do not seem to be at a greater risk to develop different nADEs compared with PLHIV on suppressive ART. More data are needed, because the present conclusions are based on a limited number of studies that show large heterogeneity among them.

Medial Proximal Tibia Physeal Overuse Injury of an Athlete.

Overuse injuries are well described for both upper and lower extremities among skeletally immature athletes. To our knowledge, there is no description in the literature of an overuse injury affecting the medial tibial physis that is different from the typical Osgood-Schlatter disease or tibial tubercle apophysitis. In this article we present a 13-year-old athlete with medial proximal tibial widening or epiphysiolysis from overuse playing soccer. We need to be aware that with increased early sports specialization we may see injuries we have not seen before. [Orthopedics. 2022;46(6):e345-e347.].

Immediate impact of bringing a school to the community with a new community-based clinical education program.

OBJECTIVES: To examine the implementation of a community-based clinical education (CBCE) program at the University of California, Los Angeles School of Dentistry (SOD) and the preliminary outcomes on dental students and affiliated clinics. METHODS: A retrospective review was carried out of SOD CBCE program implementation and program data between March 2018 and June 2019 related to patient encounters, pre- and post-rotation student self-assessments, student exit surveys and surveys administered to faculty within affiliate clinics. RESULTS: In five academic quarters, 133 students delivered care for 7556 patients and completed 12,467 procedures in underserved communities. Students reported increased confidence across 14 areas of self-assessment. The percentage of students reporting future plans of working in public health clinics upon graduation increased from 6% to 19%. Affiliate clinic faculty indicated increased care delivery for underserved patients, appointment availability, and job satisfaction. CONCLUSIONS: The newly implemented UCLA SOD CBCE program preliminarily yielded immediate positive outcomes for SOD students and affiliate community clinics.

Rationale and process for N95 respirator sanitation and reuse in the coronavirus disease 2019 (COVID-19) pandemic.

OBJECTIVE: The novel severe acute respiratory coronavirus virus 2 (SARS-CoV-2) was first reported in Wuhan, China, in December 2019 and is notable for being highly contagious and potentially lethal; and SARS-CoV-2 is mainly spread by droplet transmission. The US healthcare system's response to the COVID-19 pandemic has been challenged by a shortage of personal protective equipment (PPE), especially N95 respirators. Restricted use, reuse, and sanitation of PPE have been widely adopted to provide protection for frontline healthcare workers caring for often critically ill and highly contagious patients. Here, we describe our validated process for N95 respirator sanitation. DESIGN: Process development, validation, and implementation. SETTING: Level 1, urban, academic, medical center. METHODS: A multidisciplinary team developed a novel evidence-based process for N95 respirator reprocessing and sanitation using ultraviolet (UV) light. Dose measurement, structural integrity, moisture content, particle filtration, fit testing, and environmental testing were performed for both quality control and validation of the process. RESULTS: The process achieved UV light dosing for sanitation while maintaining the functional and structural integrity of the N95 respirators, with a daily potential throughput capacity of ∼12,000 masks. This process has supported our health system to provide respiratory PPE to all frontline team members. CONCLUSIONS: This novel method of N95 respirator sanitation can safely enable reuse of the N95 respirators essential for healthcare workers caring for patients with COVID-19. Our high-throughput process can extend local supplies of this critical PPE until the national supply is replenished.

The 2000HIV study: Design, multi-omics methods and participant characteristics.

Background: Even during long-term combination antiretroviral therapy (cART), people living with HIV (PLHIV) have a dysregulated immune system, characterized by persistent immune activation, accelerated immune ageing and increased risk of non-AIDS comorbidities. A multi-omics approach is applied to a large cohort of PLHIV to understand pathways underlying these dysregulations in order to identify new biomarkers and novel genetically validated therapeutic drugs targets. Methods: The 2000HIV study is a prospective longitudinal cohort study of PLHIV on cART. In addition, untreated HIV spontaneous controllers were recruited. In-depth multi-omics characterization will be performed, including genomics, epigenomics, transcriptomics, proteomics, metabolomics and metagenomics, functional immunological assays and extensive immunophenotyping. Furthermore, the latent viral reservoir will be assessed through cell associated HIV-1 RNA and DNA, and full-length individual proviral sequencing on a subset. Clinical measurements include an ECG, carotid intima-media thickness and plaque measurement, hepatic steatosis and fibrosis measurement as well as psychological symptoms and recreational drug questionnaires. Additionally, considering the developing pandemic, COVID-19 history and vaccination was recorded. Participants return for a two-year follow-up visit. The 2000HIV study consists of a discovery and validation cohort collected at separate sites to immediately validate any finding in an independent cohort. Results: Overall, 1895 PLHIV from four sites were included for analysis, 1559 in the discovery and 336 in the validation cohort. The study population was representative of a Western European HIV population, including 288 (15.2%) cis-women, 463 (24.4%) non-whites, and 1360 (71.8%) MSM (Men who have Sex with Men). Extreme phenotypes included 114 spontaneous controllers, 81 rapid progressors and 162 immunological non-responders. According to the Framingham score 321 (16.9%) had a cardiovascular risk of >20% in the next 10 years. COVID-19 infection was documented in 234 (12.3%) participants and 474 (25.0%) individuals had received a COVID-19 vaccine. Conclusion: The 2000HIV study established a cohort of 1895 PLHIV that employs multi-omics to discover new biological pathways and biomarkers to unravel non-AIDS comorbidities, extreme phenotypes and the latent viral reservoir that impact the health of PLHIV. The ultimate goal is to contribute to a more personalized approach to the best standard of care and a potential cure for PLHIV.

Unravelling the crystal structure of Nd5.8WO12-δ and Nd5.7W0.75Mo0.25O12-δ mixed ionic electronic conductors.

Mixed ionic electronic conducting ceramics Nd6-y WO12-δ (δ is the oxygen deficiency) provide excellent stability in harsh environments containing strongly reactive gases such as CO2, CO, H2, H2O or H2S. Due to this chemical stability, they are promising and cost-efficient candidate materials for gas separation, catalytic membrane reactors and protonic ceramic fuel cell technologies. As in La6-y WO12-δ, the ionic/electronic transport mechanism in Nd6-y WO12-δ is expected to be largely controlled by the crystal structure, the conclusive determination of which is still lacking. This work presents a crystallographic study of Nd5.8WO12-δ and molybdenum-substituted Nd5.7W0.75Mo0.25O12-δ prepared by the citrate complexation route. High-resolution synchrotron and neutron powder diffraction data were used in combined Rietveld refinements to unravel the crystal structure of Nd5.8WO12-δ and Nd5.7W0.75Mo0.25O12-δ. Both investigated samples crystallize in a defect fluorite crystal structure with space group Fm 3 m and doubled unit-cell parameter due to cation ordering. Mo replaces W at both Wyckoff sites 4a and 48h and is evenly distributed, in contrast with La6-y WO12-δ. X-ray absorption spectroscopy as a function of partial pressure pO2 in the near-edge regions excludes oxidation state changes of Nd (Nd3+) and W (W6+) in reducing conditions: the enhanced hydrogen permeation, i.e. ambipolar conduction, observed in Mo-substituted Nd6-y WO12-δ is therefore explained by the higher Mo reducibility and the creation of additional - disordered - oxygen vacancies.

Processing Ceramic Proton Conductor Membranes for Use in Steam Electrolysis.

Steam electrolysis constitutes a prospective technology for industrial-scale hydrogen production. The use of ceramic proton-conducting electrolytes is a beneficial option for lowering the operating temperature. However, a significant challenge with this type of electrolyte has been upscaling robust planar type devices. The fabrication of such multi-layered devices, usually via a tape casting process, requires careful control of individual layers' shrinkages to prevent warping and cracks during sintering. The present work highlights the successful processing of 50 × 50 mm2 planar electrode-supported barium cerium yttrium zirconate BaZr0.44Ce0.36Y0.2O2.9 (BZCY(54)8/92) half cells via a sequential tape casting approach. The sintering parameters of the half-cells were analyzed and adjusted to obtain defect-free half-cells with diminished warping. Suitably dense and gas-tight electrolyte layers are obtained after co-sintering at 1350 °C for 5 h. We then assembled an electrolysis cell using Ba0.5La0.5CoO3-δ as the steam electrode, screen printed on the electrolyte layer, and fired at 800 °C. A typical Ba0.5La0.5CoO3-δ|BaZr0.44Ce0.36Y0.2O3-δ(15 µm)|NiO-SrZr0.5Ce0.4Y0.1O3-δ cell at 600 °C with 80% steam in the anode compartment reached reproducible terminal voltages of 1.4 V @ 500 mA·cm-2, achieving ~84% Faradaic efficiency. Besides electrochemical characterization, the morphology and microstructure of the layered half-cells were analyzed by a combination of high-angle annular dark-field scanning transmission electron microscopy (HAADF-STEM) and energy-dispersive X-ray spectroscopy. Our results also provide a feasible approach for realizing the low-cost fabrication of large-sized protonic ceramic conducting electrolysis cells (PCECs).

A quantitative analysis of two-fold electrical conductivity relaxation behaviour in mixed proton-oxide-ion-electron conductors upon hydration.

Electrical conductivity relaxation experiments on oxides with three mobile charge carriers, H+, O2- and e-, yield in (de-)hydration experiments kinetic parameters (diffusion coefficients and surface reaction constants). In addition, three amplitude factors are obtained, but they have not been given further consideration because quantitative expressions for their forms are lacking. In this study, the forms of the amplitude factors are derived for a diffusion-limited and a surface-reaction-limited case and a mixed case. In order to demonstrate the benefits of the approach, the electrical conductivity relaxation behaviour of lanthanum tungstate (La5.4WO11.1, LaWO54) was investigated experimentally over the temperature range 923 ≤T/K ≤ 1223. A switch from two-fold non-monotonic relaxation behaviour at high temperatures to two-fold monotonic behaviour at low temperatures upon hydration was observed. The switch in sign of the fast kinetics' amplitude factor can be assigned to the electrochemical mobility of protons surpassing the electron-hole mobility with decreasing temperature.

Direction observation of the grain boundary segregation in molybdenum substituted lanthanum tungstate membranes.

Molybdenum substituted lanthanum tungstate membranes (LWO-Mo) offer a good alternative for the separation of hydrogen from gas mixtures. During several essential steps of the membrane processing, an intensive employment of ZrO2 milling balls is usually inevitable. However, how these milling balls affect the final LWO-Mo membranes, is still largely unknown. Employing comprehensive transmission electron microscopy (TEM) techniques, the residual Zr was found to segregate to the grain boundaries (GBs) of the LWO-Mo, either as thin layers or as individual nanograins. At atomic scale, structural and chemical analyses on these GB features were carried out quantitatively. The segregated Zr took more than half of the W sites of the LWO-Mo, resulting in a strained LWO structure and locally concentrated oxygen vacancies. To minimize any Zr contamination, either a competent alternative for ZrO2 or a careful introduction of certain secondary phases (SPs) was proposed. Our results unravel the processing-induced GB behaviors in LWO-Mo, which pave the way towards further optimized processing for various types of functional membranes.

Patient Selection in Surgical Centers of Expertise in the Treatment of Patients with Moderate to Severe Male Urinary Stress Incontinence.

OBJECTIVE: To analyze decision-making in patients with male urinary incontinence (SUI) in centers of expertise. The artificial urinary sphincter (AUS) remains the gold standard for male patients with moderate to severe SUI but adjustable male slings are a minimally invasive treatment option with good results, hence without a high level of evidence regarding the optimal patient selection. MATERIALS AND METHODS: In total, 220 patients (88 AUS; 132 adjustable slings) were investigated from the DOMINO database that underwent surgery between 2010 and 2012 in 5 urological departments that offer adjustable sling systems as well as AUS systems for patients with moderate to severe urinary incontinence. For statistical analysis, the Mann-Whitney U test was used to identify differences between both groups. RESULTS: Patients selected for an adjustable male sling were less likely to have a neurological disease (5.3 vs. 9.1%; p = 0.030), a prior urethral stricture (22.7 vs. 50.0%; p = 0.001), a prior incontinence surgery (24.4 vs. 45.5%; p = 0.01), or a prior radiation therapy (26.5 vs. 40.1%; p = 0.001). The severity of preoperative incontinence was higher in patients selected for an AUS with a mean pad usage per day of 7.60 versus 5.80 (p < 0.001). Mean postoperative pad usage and patients' subjective perception were comparable in both groups. CONCLUSION: In centers offering both options, the decision-making is mainly based upon presence of radiation therapy and previous failed incontinence surgery. Despite the more complex patient cohort selected for an AUS implantation with a possible impact on the postoperative outcome, the functional results seem to be comparable indicating a proper preoperative patient assessment and selection in this cohort.

Structure-Based Design and Preclinical Characterization of Selective and Orally Bioavailable Factor XIa Inhibitors: Demonstrating the Power of an Integrated S1 Protease Family Approach.

The serine protease factor XI (FXI) is a prominent drug target as it holds promise to deliver efficacious anticoagulation without an enhanced risk of major bleeds. Several efforts have been described targeting the active form of the enzyme, FXIa. Herein, we disclose our efforts to identify potent, selective, and orally bioavailable inhibitors of FXIa. Compound 1, identified from a diverse library of internal serine protease inhibitors, was originally designed as a complement factor D inhibitor and exhibited submicromolar FXIa activity and an encouraging absorption, distribution, metabolism, and excretion (ADME) profile while being devoid of a peptidomimetic architecture. Optimization of interactions in the S1, S1ß, and S1' pockets of FXIa through a combination of structure-based drug design and traditional medicinal chemistry led to the discovery of compound 23 with subnanomolar potency on FXIa, enhanced selectivity over other coagulation proteases, and a preclinical pharmacokinetics (PK) profile consistent with bid dosing in patients.

Utilization of an Orthopedic Hood as Personal Protective Equipment for Intubation of Coronavirus Patients: a Brief Technical Report.

BACKGROUND: The novel coronavirus disease (COVID-19) has afflicted millions of people worldwide since its first case was reported in December 2019. Personal protective equipment (PPE) has been tailored accordingly, but as of April 2020, close to 10 000 health care workers in the United States have contracted COVID-19 despite wearing recommended PPE. As such, standard guidelines for PPE may be inadequate for the health care worker performing high-risk aerosolizing procedures such as endotracheal intubation. In this brief technical report, we describe the integration of an orthopedic hood cover as an item for full barrier protection against COVID-19 transmission. TECHNICAL DESCRIPTION: The Coronavirus Airway Task Force at Virginia Commonwealth University Medical Center approved this initiative and went live with the full barrier suit during the last week of March 2020. The PPE described in this report includes a Stryker T4 Hood, normally used in conjunction with the Stryker Steri-Shield T4 Helmet. Instead of the helmet, the hood is secured to the head via a baseball cap and binder clip. This head covering apparatus is to be used as an accessory to other PPE items that include an N95 mask, waterproof gown, and disposable gloves. The motor ventilation system is not used in order to prevent airborne viral entry into the hood. DISCUSSION: An advantage of the full barrier suit is an additional layer of droplet protection during intubation. The most notable disadvantage is the absence of a ventilation system within the hood covering. CONCLUSION: Modification of existing PPE may provide protection for health care workers during high-risk aerosolizing procedures such as endotracheal intubation. Although the integration of this medical equipment meets the immediate needs of an escalating crisis, further innovation is on the horizon. More research is needed to confirm the safety of modified PPE.