Liver failure after treatment with inotuzumab and polychemotherapy including PEG-asparaginase in a patient with relapsed Philadelphia chromosome-negative acute lymphoblastic leukemia.

We present the case of a 58-year-old female patient who presented with an extramedullary B-ALL relapse after prior allogenic HSCT and blinatumomab therapy. The patient died from complications of a drug-induced acute liver failure after a salvage therapy combining inotuzumab ozogamicin (InO)-based induction followed by consolidation with high dose MTX and pegaspargase based on the GMALL protocol for older ALL patients. After a diagnosis of the extramedullary relapse in the form of a retro vesical chloroma, the patient received an individualized multi-agent chemotherapy based on induction chemotherapy for older patients in combination with InO. After four administrations of InO, in combination with vincristine, dexamethasone, cytarabine, and cyclophosphamide, CT-imaging showed a reduction in volume of the chloroma and response to therapy. Consolidation with high-dose methotrexate and pegaspargase was administered. The patient developed toxic liver damage manifested by hyperbilirubinemia and progressive hepatic encephalopathy. The diagnostic criteria for VOD were met, and therapy with defibrotide was initiated. Liver biopsy revealed no histological signs of VOD but instead steatohepatitis indicative of drug-induced toxicity. The patient ultimately died of hemorrhagic shock through postinterventional hemorrhage after liver biopsy. In conclusion, although InO shows promising results in the therapy of r/r ALL with and without additional chemotherapy, the combination with MTX and pegaspargase in an intensively pretreated patient with relapse after HCST may impart an increased risk for liver-related toxicity. Special caution is required when assessing fitness for further liver toxic regimens. A key takeaway is also the reminder that InO can cause liver damage not only in the form of VOD but also through direct hepatocellular toxicity.

Genes and pathways revealed by whole transcriptome analysis of milk derived bovine mammary epithelial cells after Escherichia coli challenge.

Mastitis, inflammation of the mammary gland, is the costliest disease in dairy cattle and a major animal welfare concern. Mastitis is usually caused by bacteria, of which staphylococci, streptococci and Escherichia coli are most frequently isolated from bovine mastitis. Bacteria activate the mammary immune system in variable ways, thereby influencing the severity of the disease. Escherichia coli is a common cause of mastitis in cattle causing both subclinical and clinical mastitis. Understanding of the molecular mechanisms that activate and regulate the host response would be central to effective prevention of mastitis and breeding of cows more resistant to mastitis. We used primary bovine mammary epithelial cell cultures extracted noninvasively from bovine milk samples to monitor the cellular responses to Escherichia coli challenge. Differences in gene expression between control and challenged cells were studied by total RNA-sequencing at two time points post-challenge. In total, 150 and 440 (Padj < 0.05) differentially expressed genes were identified at 3 h and 24 h post-challenge, respectively. The differentially expressed genes were mostly upregulated at 3 h (141/150) and 24 h (424/440) post-challenge. Our results are in line with known effects of E. coli infection, with a strong early inflammatory response mediated by pathogen receptor families. Among the most significantly enriched early KEGG pathways were the TNF signalling pathway, the cytokine-cytokine receptor interaction, and the NF-kappa B signalling pathway. At 24 h post-challenge, most significantly enriched were the Influenza A, the NOD-like receptor signalling, and the IL-17 signaling pathway.

Interface-modulated kinetic differentials in electron and hole transfer rates as a key design principle for redox photocatalysis by Sb2VO5/QD heterostructures.

The efficient conversion of solar energy to chemical energy represents a critical bottleneck to the energy transition. Photocatalytic splitting of water to generate solar fuels is a promising solution. Semiconductor quantum dots (QDs) are prime candidates for light-harvesting components of photocatalytic heterostructures, given their size-dependent photophysical properties and band-edge energies. A promising series of heterostructured photocatalysts interface QDs with transition-metal oxides which embed midgap electronic states derived from the stereochemically active electron lone pairs of p-block cations. Here, we examine the thermodynamic driving forces and dynamics of charge separation in Sb2VO5/CdSe QD heterostructures, wherein a high density of Sb 5s2-derived midgap states are prospective acceptors for photogenerated holes. Hard-x-ray valence band photoemission spectroscopy measurements of Sb2VO5/CdSe QD heterostructures were used to deduce thermodynamic driving forces for charge separation. Interfacial charge transfer dynamics in the heterostructures were examined as a function of the mode of interfacial connectivity, contrasting heterostructures with direct interfaces assembled by successive ion layer adsorption and reaction (SILAR) and interfaces comprising molecular bridges assembled by linker-assisted assembly (LAA). Transient absorption spectroscopy measurements indicate ultrafast (<2 ps) electron and hole transfer in SILAR-derived heterostructures, whereas LAA-derived heterostructures show orders of magnitude differentials in the kinetics of hole (<100 ps) and electron (∼1 ns) transfer. The interface-modulated kinetic differentials in electron and hole transfer rates underpin the more effective charge separation, reduced charge recombination, and greater photocatalytic efficiency observed for the LAA-derived Sb2VO5/CdSe QD heterostructures.

The Effectiveness of Metacognitive Therapy Compared to Behavioral Activation for Severely Depressed Outpatients: A Single-Center Randomized Trial.

INTRODUCTION: Major depressive disorder (MDD) is a highly prevalent and disabling disorder. This study examines two psychotherapy methods for MDD, behavioral activation (BA), and metacognitive therapy (MCT), when applied as outpatient treatments to severely affected patients. METHODS: The study was conducted in a tertiary outpatient treatment center. Patients with a primary diagnosis of MDD (N = 122) were included in the intention-to-treat sample (55.7% female, mean age 41.9 years). Participants received one individual and one group session weekly for 6 months (M). Assessments took place at baseline, pretreatment, mid-treatment (3 M), post-treatment (6 M), and follow-up (12 M). The primary outcome was depressive symptomatology assessed by the Hamilton Rating Scale for Depression at 12 M follow-up. Secondary outcomes included general symptom severity, psychosocial functioning, and quality of life. RESULTS: Linear mixed models indicated a change in depressive symptoms (F(2, 83.495) = 12.253, p < 0.001) but no between-group effect (F(1, 97.352) = 0.183, p = 0.670). Within-group effect sizes were medium for MCT (post-treatment: d = 0.610; follow-up: d = 0.692) and small to medium for BA (post-treatment: d = 0.636, follow-up: d = 0.326). In secondary outcomes, there were improvements (p ≤ 0.040) with medium to large within-group effect sizes (d ≥ 0.501) but no between-group effects (p ≥ 0.304). Response and remission rates did not differ between conditions at follow-up (response MCT: 12.9%, BA: 13.3%, remission MCT: 9.7%, BA: 10.0%). The deterioration rate was lower in MCT than in BA (χ21 = 5.466, p = 0.019, NTT = 7.4). DISCUSSION: Both MCT and BA showed symptom reductions. Remission and response rates were lower than in previous studies, highlighting the need for further improvements in adapting/implementing treatments for severely affected patients with MDD.

Effect of Stereochemically Active Electron Lone Pairs on Magnetic Ordering in Trivanadates.

Stereoactive electron lone pairs derived from filled 5/6s2 states of p-block cations are an intriguing electronic and geometric structure motif that have been exploited for diverse applications such as thermoelectrics, thermochromics, photocatalysis, and nonlinear optics. Layered trivanadates are dynamic intercalation hosts, where the insertion of cations can be used to tune electron correlation, charge localization, and magnetic ordering. However, the interaction of 5/6s2 stereoactive electron lone pairs with layered trivanadates remains unexplored. In this study, we contrast s- and p-block trivanadates and map off-centering in the coordination environment and reduction in symmetry arising from the stereochemical activity of lone pair cations to the emergence of filled antibonding lone-pair 6s2-O 2p hybridized states. The former is studied by high-resolution single-crystal X-ray diffraction studies of TlV3O8 and isostructural RbV3O8 to probe distinct differences in Tl and Rb coordination environments and the resulting modulation of V-V interactions in V3O8 slabs. The latter has been probed by variable-energy hard X-ray photoelectron spectroscopy (HAXPES) measurements, which manifest orbital-specific contributions from bonding and antibonding interactions of stereoactive Tl 6s2 electron lone pairs in TlV3O8. The spectroscopic assignment of valence band states to stereoactive lone pairs is further corroborated by first-principles electronic structure calculations, crystal orbital Hamilton population analyses, and electron localization function maps. The presence of the Tl 6s2 electron lone pair in TlV3O8 brings about the off-centering of Tl+ cations, which leads to anisotropy in Tl-O bonds. The off-centering of Tl ions weakens V-O bonds in one direction, which subsequently strengthens directional V-V coupling. Magnetic measurements reveal ferromagnetic signatures for both RbV3O8 and TlV3O8. However, the differences in V···V interactions significantly affect the energy balance of the superexchange interactions, resulting in an ordering temperature of 140 K for TlV3O8 as compared to 125 K for RbV3O8. The results demonstrate the distinctive effects of stereochemically active lone pairs in modifying electronic structure near the Fermi level and for mediating superexchange interactions.

Entertain Me Well: An Entertaining, Tailorable, Online Platform Delivering CBT for Depression.

Depression prevalence is high, impacting approximately 20% of Americans during their lifetime, and on the rise due to stress and loss associated with the COVID-19 pandemic. Despite the high prevalence of depression, unacceptable treatment access disparities persist. When depression goes untreated, it leads to substantial negative impacts in multiple life domains. Cognitive behavioral therapy (CBT), the gold-standard psychosocial treatment for depression, remains largely unavailable to individuals living with depression, particularly individuals who are members of underrepresented groups in our society. Digital mental health interventions (DMHI) have led to important advances in extending the reach of CBT for depression; however, they are underutilized and treatment engagement remains low. We sought to address some of the current gaps in DMHI by developing an online platform for delivering CBT for depression that is entertaining, simple and straightforward, and tailorable. First, this article introduces our online platform, Entertain Me Well (EMW) and its key innovations, including the use of an engaging, character-driven storyline presented as "episodes" within each session, as well as customizable content that allows for tailoring of text, images, and examples to create content most relevant to the target client population, context, or setting. Next, we describe two EMW depression treatment programs that have been tailored: one for delivery in the rural church setting, called Raising Our Spirits Together, and one tailored for delivery in dialysis centers, called Doing Better on Dialysis. Finally, we discuss future directions for the EMW platform, including the ability to create programs for other common mental health and health conditions, the development of additional character-driven storylines with greater treatment personalization, translation of content in multiple languages, and the use of additional technological innovation, such as artificial intelligence like natural language processing, to enhance platform interactivity.

Non-cell-autonomous OTX2 transcription factor regulates anxiety-related behavior in the mouse.

The OTX2 homeoprotein transcription factor is expressed in the dopaminergic neurons of the ventral tegmental area, which projects to limbic structures controlling complex behaviors. OTX2 is also produced in choroid plexus epithelium, from which it is secreted into cerebrospinal fluid and transferred to limbic structure parvalbumin interneurons. Previously, adult male mice subjected to early-life stress were found susceptible to anxiety-like behaviors, with accompanying OTX2 expression changes in ventral tegmental area or choroid plexus. Here, we investigated the consequences of reduced OTX2 levels in Otx2 heterozygote mice, as well as in Otx2+/AA and scFvOtx2tg/0 mouse models for decreasing OTX2 transfer from choroid plexus to parvalbumin interneurons. Both male and female adult mice show anxiolysis-like phenotypes in all three models. In Otx2 heterozygote mice, we observed no changes in dopaminergic neuron numbers and morphology in ventral tegmental area, nor in their metabolic output and projections to target structures. However, we found reduced expression of parvalbumin in medial prefrontal cortex, which could be rescued in part by adult overexpression of Otx2 specifically in choroid plexus, resulting in increased anxiety-like behavior. Taken together, OTX2 synthesis by the choroid plexus followed by its secretion into the cerebrospinal fluid is an important regulator of anxiety-related phenotypes in the mouse.

Morphogenesis of Liquid Indium Microdroplets on Solid Molybdenum Surfaces during Solidification at Normal Pressure and under Vacuum Conditions.

Electrical and optical applications based on micro- and nanoparticles have specific demands on their interfacial properties. These properties are strongly related to atmospheric conditions to which the particles were exposed during their formation. In this study, metallic In microparticles are synthesized by solidification of In droplets on an amorphous Mo substrate at normal pressure and under vacuum conditions. The influence of ambient pressure on the interface and surface shape is investigated. While solidification at atmospheric pressure leads to collapsed particles with undisturbed contact to the substrate, low pressures result in smooth spherical particles but with cavities inside. Numerical simulations with COMSOL Multiphysics reveal different temperature profiles and heat flux in particles during solidification for both cases. This indicates different starting conditions of the solidification, which leads to the described phenomenon eventually. The investigation of the varying process conditions on the particle shape in combination with the calculated and measured temperature curves over time gives valuable insights into new approaches to synthesize micro- and nanoparticles with defined interfacial properties. Both ambient pressure and cooling rate provide well-controllable and reliable parameters for the realization of different interfacial shapes.

Evidence that gecko setae are coated with an ordered nanometre-thin lipid film.

The fascinating adhesion of gecko to virtually any material has been related to surface interactions of myriads of spatula at the tips of gecko feet. Surprisingly, the molecular details of the surface chemistry of gecko adhesion are still largely unknown. Lipids have been identified within gecko adhesive pads. However, the location of the lipids, the extent to which spatula are coated with lipids, and how the lipids are structured are still open questions. Lipids can modulate adhesion properties and surface hydrophobicity and may play an important role in adhesion. We have therefore studied the molecular structure of lipids at spatula surfaces using near-edge X-ray absorption fine structure imaging. We provide evidence that a nanometre-thin layer of lipids is present at the spatula surfaces of the tokay gecko (Gekko gecko) and that the lipids form ordered, densely packed layers. Such dense, thin lipid layers can effectively protect the spatula proteins from dehydration by forming a barrier against water evaporation. Lipids can also render surfaces hydrophobic and thereby support the gecko adhesive system by enhancement of hydrophobic-hydrophobic interactions with surfaces.

Multimodal electrochemistry coupled microcalorimetric and X-ray probing of the capacity fade mechanisms of Nickel rich NMC - progress and outlook.

Lithium nickel manganese cobalt oxide (NMC) is a commercially successful Li-ion battery cathode due to its high energy density; however, its delivered capacity must be intentionally limited to achieve capacity retention over extended cycling. To design next-generation NMC batteries with longer life and higher capacity the origins of high potential capacity fade must be understood. Operando hard X-ray characterization techniques are critical for this endeavor as they allow the acquisition of information about the evolution of structure, oxidation state, and coordination environment of NMC as the material (de)lithiates in a functional battery. This perspective outlines recent developments in the elucidation of capacity fade mechanisms in NMC through hard X-ray probes, surface sensitive soft X-ray characterization, and isothermal microcalorimetry. A case study on the effect of charging potential on NMC811 over extended cycling is presented to illustrate the benefits of these approaches. The results showed that charging to 4.7 V leads to higher delivered capacity, but much greater fade as compared to charging to 4.3 V. Operando XRD and SEM results indicated that particle fracture from increased structural distortions at >4.3 V was a contributor to capacity fade. Operando hard XAS revealed significant Ni and Co redox during cycling as well as a Jahn-Teller distortion at the discharged state (Ni3+); however, minimal differences were observed between the cells charged to 4.3 and 4.7 V. Additional XAS analyses using soft X-rays revealed significant surface reconstruction after cycling to 4.7 V, revealing another contribution to fade. Operando isothermal microcalorimetry (IMC) indicated that the high voltage charge to 4.7 V resulted in a doubling of the heat dissipation when compared to charging to 4.3 V. A lowered chemical-to-electrical energy conversion efficiency due to thermal energy waste was observed, providing a complementary characterization of electrochemical degradation. The work demonstrates the utility of multi-modal X-ray and microcalorimetric approaches to understand the causes of capacity fade in lithium-ion batteries with Ni-rich NMC.

The Growth of Palliative Practice and End of Life Care in an Academic Teaching Intensive Care Unit.

OBJECTIVE: Dying in the intensive care unit (ICU) has changed over the last twenty years due to increased utilization of palliative care. We sought to examine how palliative medicine (PM) integration into critical care medicine has changed outcomes in end of life including the utilization of do not resuscitate (no cardiopulmonary resuscitation but continue treatment) and comfort care orders (No resuscitation, only comfort medication). Design: Retrospective observational review of critical care patients who died during admission between two decades, 2008 to 09 and 2018 to 19. Setting: Single urban tertiary care academic medical center in Washington, D.C. Patients: Adult patients who were treated in any ICU during the admission which they died. INTERVENTIONS AND MEASUREMENTS: We sought to measure PM involvement across the two decades and its association with end of life care including do not resuscitate (DNR) and comfort care (CC) orders. Main Results: 571 cases were analyzed. Mean age was 65 ± 15, 46% were female. In univariate analysis significantly more patients received PM in 2018 to 19 (40% vs. 27%, p = .002). DNR status increased significantly over time (74% to 84%, p = .002) and was significantly more common in patients who were receiving PM (96% vs. 72%, p < 0.001). CC also increased over time (56% to 70%, p = <0.001), and was more common in PM patients (87% vs. 53%, p < 0.001). Death in the ICU decreased significantly over time (94% to 86%, p = .002) and was significantly lower in PM patients (76% vs. 96%, p < 0.001). The adjusted odds of getting CC for those receiving versus those not receiving PM were 14.51 (5.49-38.36, p < 0.001) in 2008 to 09 versus 3.89 (2.27-6.68, p < 0.001) in 2018 to 19. Conclusion: PM involvement increased significantly across a decade in our ICU and was significantly associated with incidence of DNR and CC orders as well as the decreased incidence of dying in the ICU. The increase in DNR and CC orders independent of PM over the past decade reflect intensivists delivering PM services.

The societal cost of treatment-seeking patients with borderline personality disorder in Germany.

According to previous research, borderline personality disorder (BPD) is associated with high cost-of-illness. However, there is still a shortage of cost-of-illness-studies assessing costs from a broad societal perspective, including direct and indirect costs. Further, there are considerable differences in the results among the existing studies. In the present study, 167 German men and women seeking specialized outpatient treatment for BPD were included. We assessed societal cost-of-illness bottom-up through structured face-to-face interviews and encompassed a wide range of cost components. All costs were calculated for the 2015 price level. Cost-of-illness amounted to € 31,130 per patient and year preceding disorder-specific outpatient treatment. € 17,044 (54.8%) were direct costs that were mostly related to hospital treatment. Indirect costs amounted to € 14,086 (45.2%). Within indirect costs, costs related to work disability were the most crucial cost driver. The present study underlines the tremendous economic burden of BPD. According to the present study, both the direct and indirect costs are of significant importance for the societal costs associated with BPD. Besides the need for more disorder-specific treatment facilities for men and women with BPD, we assume that education and employment are topics that should be specifically targeted and individually supported at an early stage of treatment.Trial Registration: German Clinical Trial Registration, DRKS00011534, Date of Registration: 11/01/2017, retrospectively registered.

Pharmacist involvement with antiepileptic therapy for status epilepticus in the emergency department.

Background Despite there being an estimated 50,000-150,000 emergency department (ED) visits per year related to status epilepticus, there are limited data regarding pharmacist involvement in patient care. The purpose of this study was to evaluate differences in time to antiepileptic drug (AED) administration and appropriate AED use and dose when a pharmacist was present or not. METHODS: Retrospective, single-center, observational study of adult status epilepticus patients presenting to the ED between January 2018 through July 2020. The primary outcome was time to AED administration. Secondary outcomes included occurrence of appropriate AED selection and dose, escalation of care, length of stay (LOS), and 30-day mortality. Wilcoxon rank-sum was used for continuous variables and nominal data was analyzed by Chi-square or Fisher's Exact test, as appropriate. RESULTS: Twenty patients were included; 13 in the pharmacist-present and seven patients in the no-pharmacist-present groups. Median time to first and second AED was 26 min (IQR 17-177) versus 37 min (IQR 21-206), p = 0.58, and 51 min (IQR 30-221) versus 171 min (IQR 99-433), p = 0.07, in the pharmacist-present and no-pharmacist-present groups, respectively. Although there was no difference between groups for appropriate AED selection, those in the pharmacist-present group received a higher median dose of lorazepam equivalents (2.5 mg [IQR 2-4] vs 2 mg [IQR 2-2]; p = 0.04) and were more likely to receive at least 4 mg of lorazepam equivalents (38% vs 0%; p = 0.11). There were no differences in hospital LOS or 30-day mortality. CONCLUSION: Pharmacist presence during status epilepticus patient management was associated with a clinically significant reduction in time to administration of AEDs. Medication doses were more guideline adherent and more patients received a lorazepam dose of at least 4 mg compared to when a pharmacist was not present.

Characterization of nucleic acids from extracellular vesicle-enriched human sweat.

BACKGROUND: The human sweat is a mixture of secretions from three types of glands: eccrine, apocrine, and sebaceous. Eccrine glands open directly on the skin surface and produce high amounts of water-based fluid in response to heat, emotion, and physical activity, whereas the other glands produce oily fluids and waxy sebum. While most body fluids have been shown to contain nucleic acids, both as ribonucleoprotein complexes and associated with extracellular vesicles (EVs), these have not been investigated in sweat. In this study we aimed to explore and characterize the nucleic acids associated with sweat particles. RESULTS: We used next generation sequencing (NGS) to characterize DNA and RNA in pooled and individual samples of EV-enriched sweat collected from volunteers performing rigorous exercise. In all sequenced samples, we identified DNA originating from all human chromosomes, but only the mitochondrial chromosome was highly represented with 100% coverage. Most of the DNA mapped to unannotated regions of the human genome with some regions highly represented in all samples. Approximately 5 % of the reads were found to map to other genomes: including bacteria (83%), archaea (3%), and virus (13%), identified bacteria species were consistent with those commonly colonizing the human upper body and arm skin. Small RNA-seq from EV-enriched pooled sweat RNA resulted in 74% of the trimmed reads mapped to the human genome, with 29% corresponding to unannotated regions. Over 70% of the RNA reads mapping to an annotated region were tRNA, while misc. RNA (18,5%), protein coding RNA (5%) and miRNA (1,85%) were much less represented. RNA-seq from individually processed EV-enriched sweat collection generally resulted in fewer percentage of reads mapping to the human genome (7-45%), with 50-60% of those reads mapping to unannotated region of the genome and 30-55% being tRNAs, and lower percentage of reads being rRNA, LincRNA, misc. RNA, and protein coding RNA. CONCLUSIONS: Our data demonstrates that sweat, as all other body fluids, contains a wealth of nucleic acids, including DNA and RNA of human and microbial origin, opening a possibility to investigate sweat as a source for biomarkers for specific health parameters.

Genotype-Phenotype Relations in Primary Familial Brain Calcification: Systematic MDSGene Review.

This systematic MDSGene review covers individuals with confirmed genetic forms of primary familial brain calcification (PFBC) available in the literature. Data on 516 (47% men) individuals, carrying heterozygous variants in SLC20A2 (solute carrier family 20 member 2, 61%), PDGFB (platelet-derived growth factor subunit B, 12%), XPR1 (xenotropic and polytropic retrovirus receptor, 16%), or PDGFRB (platelet-derived growth factor receptor beta, 5%) or biallelic variants in MYORG (myogenesis-regulating glycosidase, 13%) or JAM2 (junctional adhesion molecule 2, 2%), were extracted from 93 articles. Nearly one-third of the mutation carriers were clinically unaffected. Carriers of PDGFRB variants were more likely to be clinically unaffected (~54%), and the penetrance of SLC20A2 and XPR1 variants (<70%) was lower in comparison to the remaining three genes (>85%). Among the 349 clinically affected patients, 27% showed only motor and 31% only nonmotor symptoms/signs, whereas the remaining 42% had a combination thereof. While parkinsonism and speech disturbance were the most frequently reported motor manifestations, cognitive deficits, headache, and depression were the major nonmotor symptoms/signs. The basal ganglia were always calcified, and the cerebellum, thalamus, and white matter contained calcifications in 58%, 53%, and 43%, respectively, of individuals. In autosomal-dominant PFBC, mutation severity influenced the number of calcified brain areas, which in turn correlated with the clinical status, whereby the risk of developing symptoms/signs more than doubled for each additional region with calcifications. Our systematic analysis provides the most comprehensive insight into genetic, clinical, and neuroimaging features of known PFBC forms, to date. In addition, it puts forth the penetrance estimates and newly discovered genotype-phenotype relations that will improve counseling of individuals with mutations in PFBC genes. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

A Randomized, Double-Blind, Active- and Placebo-Controlled Trial Evaluating a Novel Topical Treatment for Keloid Scars.

Keloid and hypertrophic scars are fibroproliferative disorders resulting from abnormal wound healing in genetically susceptible individuals. Current therapies are often ineffective. Kynurenine shows promise as a topical treatment for keloids and hypertrophic scars. In this study, healthy adult male and female subjects seeking treatment for mature keloid scars were enrolled. Subjects were randomized in double-blind fashion to receive kynurenic acid 0.5% (FS2) cream (Group 1), an active onion extract comparator treatment (Group 2), or the inactive vehicle (Group 3). Each treatment was applied twice-daily. Qualitative assessments were made using the Vancouver Scar Scale (VSS), as well as the Patient and Observer Scar Assessment Scales (POSAS). Among subjects in Group 1, there was a substantial decrease in mean PGSS scores after 30 days of treatment that continued to trend downward, becoming significant versus Group 2 at days 90 and 180 (P<0.05) and versus Group 3 at day 180 (P<0.01). Based on mean VSS scores, subjects in Group 1 achieved beneficial effects that became significant versus Group 2 at day 90 (P<0.01), day 120 (P<0.05), and day 180 (P<0.001) and versus Group 3 at day 180 (P<0.05). There were no significant improvements in Groups 2 or 3. There were no adverse events or local skin reactions. The twice-daily application of FS2 Cream represents a potentially new and effective treatment for mature keloid scars. J Drugs Dermatol. 2021;20(9):964-968. doi:10.36849/JDD.6197.

Practices and Barriers in Sexual History Taking: A Cross-Sectional Study in a Public Adult Primary Care Clinic.

BACKGROUND: Surveys report low frequencies of sexual history (SH) obtained in primary care. Sexually transmitted infections incidence can be reduced with timely screening. It is important to determine whether providers obtain thorough SH and to identify needs for improvement. AIM: To evaluate the frequency and depth of SH taking in primary care. METHODS: In this cross-sectional cohort study, 1,017 primary care visits were reviewed (1,017 adult patients, female 55.26%). 417 patients were seen by male providers and 600 patients were seen by female providers. Multivariate ordered and logit models were deployed. MAIN OUTCOME MEASURES: The primary outcome measures included SH taking rates and completeness based on the 5 P model as described by the Centers for Disease Control and Prevention. RESULTS: All components of SH were explored in 1.08% of visits. Partial SH was obtained in 33.92% of visits. No SH was taken in the majority of visits (65%). SH was more likely to be taken from female patients than from male patients (P < .001), and was less likely to be obtained from older patients as compared to younger individuals (P < .001). There was no significant difference in SH taking between male and female providers (P = .753). The provider title and the level of training were found to be independent predictors of SH taking (P < .001). CLINICAL IMPLICATIONS: The results of this study highlight an unmet need for more comprehensive and consistent SH taking amongst providers, particularly in high-risk settings, so that SH can be used as a valuable tool in preventive care. STRENGTHS & LIMITATIONS: To the best of our knowledge, this is the largest study to date examining SH taking in the primary care setting. Limitations include the retrospective study design, lack of generalizability to other hospitals, and inconsistencies in available data. CONCLUSION: The SH taking rates in primary care clinics are globally low with a variation depending on the provider position or level of training, provider gender, and patient age. Palaiodimos L, Herman HS, Wood E, et al. Practices and Barriers in Sexual History Taking: A Cross-Sectional Study in a Public Adult Primary Care Clinic. J Sex Med 2020;17:1509-1519.

Core level spectroscopies locate hydrogen in the proton transfer pathway - identifying quasi-symmetrical hydrogen bonds in the solid state.

Short, strong hydrogen bonds (SSHBs) have been a source of interest and considerable speculation over recent years, culminating with those where hydrogen resides around the midpoint between the donor and acceptor atoms, leading to quasi-covalent nature. We demonstrate that X-ray photoelectron spectroscopy (XPS) and near-edge X-ray absorption fine structure (NEXAFS) spectroscopy provide deep insight into the electronic structure of the short OHN hydrogen bond of 3,5-pyridinedicarboxylic acid, revealing for the first time distinctive spectroscopic identifiers for these quasi-symmetrical hydrogen bonds. An intermediate nitrogen (core level) chemical shift occurs for the almost centrally located hydrogen compared to protonated (ionic) and non-ionic analogues, and it reveals the absence of two-site disorder. This type of bonding is also evident through broadening of the nitrogen 1s photoemission and 1s → 1π* peaks in XPS and NEXAFS, respectively, arising from the femtosecond lifetimes of hydrogen in the potential wells slightly offset to either side of the centre. The line-shape of the core level excitations are thus related to the population occupancies, reflecting the temperature-dependent shape of the hydrogen potential energy well. Both XPS and NEXAFS provide a distinctive identifier for these quasi-symmetrical hydrogen bonds, paving the way for detailed studies into their prevalence and potentially unique physical and chemical properties.

Randomized, Investigator-Blinded Study to Compare the Efficacy and Tolerance of a 650-microsecond, 1064-nm YAG Laser to a 308-nm Excimer Laser for the Treatment of Mild to Moderate Psoriasis Vulgaris

Background: Phototherapy is a safe and effective modality for the treatment of mild to moderate psoriasis. Objectives: To compare the efficacy and safety of the 650-microsecond, 1064-nm pulsed YAG laser with the excimer laser for the treatment of mild to moderate psoriasis vulgaris of the arms and legs. Methods: Eligible subjects (n=15) aged 54.3 ± 11.7 years enrolled in a randomized, investigator-blinded study. Psoriatic plaques on one side of the body were treated with the 650-microsecond laser and plaques on the other side were treated with the 308-nm excimer laser. Subjects made up to 15 visits, twice weekly, or fewer if full clearance was achieved. Efficacy and tolerance were evaluated by the mPASI scores and local skin reactions, respectively. Results: Both devices showed efficacy in treating psoriatic plaques. Differences between the two devices were not significant for redness, thickness, scaliness, mPASI scores for arms and legs, and overall mPASI scores for the treated psoriatic plaques on each side of the body. The investigator-assessed scores for erosion/ulceration, vesicles, erythema, scaling, edema, and atrophy were low and identical for both sides of the body. Conclusion: The efficacy and tolerance of the 650-microsecond laser is equivalent to that of the excimer laser for the treatment of mild to moderate psoriasis vulgaris of the arms and legs. J Drugs Dermatol. 2020;19(2)176-183. doi:10.36849/JDD.2020.4769

Disruption of Membrane Integrity by the Bacterium-Derived Antifungal Jagaricin.

Jagaricin is a lipopeptide produced by the bacterial mushroom pathogen Janthinobacterium agaricidamnosum, the causative agent of mushroom soft rot disease. Apart from causing lesions in mushrooms, jagaricin is a potent antifungal active against human-pathogenic fungi. We show that jagaricin acts by impairing membrane integrity, resulting in a rapid flux of ions, including Ca2+, into susceptible target cells. Accordingly, the calcineurin pathway is required for jagaricin tolerance in the fungal pathogen Candida albicans Transcriptional profiling of pathogenic yeasts further revealed that jagaricin triggers cell wall strengthening, general shutdown of membrane potential-driven transport, and the upregulation of lipid transporters, linking cell envelope integrity to jagaricin action and resistance. Whereas jagaricin shows hemolytic effects, it exhibited either no or low plant toxicity at concentrations at which the growth of prevalent phytopathogenic fungi is inhibited. Therefore, jagaricin may have potential for agricultural applications. The action of jagaricin as a membrane-disrupting antifungal is promising but would require modifications for use in humans.