Notes

Pre-clinical development and molecular characterization of an designed sort 1 regulatory T-cell product or service suitable for immunotherapy.
Patients received a median of two red blood cell transfusions within the first 2weeks of diagnosis and a median of one AIHA-directed medication (range one to four), most commonly corticosteroids and rituximab.

AIHA after HSCT is rare but occurs more commonly in patients transplanted for nonmalignant diagnoses. While some pediatric patients who develop AIHA after transplant can be managed on current immunosuppression and supportive care, many require AIHA-directed therapy including second-line medications.
AIHA after HSCT is rare but occurs more commonly in patients transplanted for nonmalignant diagnoses. While some pediatric patients who develop AIHA after transplant can be managed on current immunosuppression and supportive care, many require AIHA-directed therapy including second-line medications.Human is the host of the Epstein-Barr virus (EBV) especially in childhood and adolescence. Most of them are asymptomatic infection and self-limiting. However, for those patients who suffer from immune dysfunction, EBV infection will be life-threatening. Epstein-Barr virus-associated hemophagocytic lymphohistocytosis (EBV-HLH) is one of the severe effects. The diagnosis and differential diagnosis of EBV-HLH and other EBV infectious diseases are mentioned in this paper. The molecular biology mechanism and complications of EBV-HLH are equally briefly presented. It also provides a practical method for the genetic diagnosis of such diseases and the differential diagnosis with other human immunodeficiency diseases for medical scientists in routine clinical practice.
In Australia, people residing remotely typically experience increased travel time to health services, and remote health services often have unfavourable population-to-provider ratios. The state of Victoria was treated as a case study and a spatial analysis investigated the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) point-of-care-test (POCT) site location (Major City, Inner Regional or Outer Regional) on the mean travel time for closest residents and the number of closest residents.

A network analysis established the travel time from every mesh block in Victoria to the closest POCT site. Inferential analyses investigated the impact of POCT site location on travel time and the number of closest residents.

Compared to urban locations, the mean travel time for closest residents to rural POCT sites was significantly higher, while rural POCT sites had significantly fewer residents to service.

Findings confirm Australian health service literature suggesting that rural regions have poorer proximate availability of health services, while also contrasting to literature indicating that Australian rural regions have fewer health services per capita. Implications for public health Localities within outer regional Victoria are candidates for a localised response to reduce unnecessary travel. Employing innovative service models may improve health service access and use and reduce population-to-provider ratios in rural locations.
Findings confirm Australian health service literature suggesting that rural regions have poorer proximate availability of health services, while also contrasting to literature indicating that Australian rural regions have fewer health services per capita. Implications for public health Localities within outer regional Victoria are candidates for a localised response to reduce unnecessary travel. Employing innovative service models may improve health service access and use and reduce population-to-provider ratios in rural locations.
To describe the ophthalmoscopic, in-vivo imaging, fluorescein angiography, and therapeutic photocoagulation outcome in a case of bilateral optic nerve colobomas associated with focal unilateral retinal detachment in a dog.

Pretraining eye examination of a 1.6-year-old female German shepherd service dog showed a focal juxta-papillary bullous retinal separation in the right eye. In vivo imaging and angiography were performed under general anesthesia using optical coherence tomography. Nonoverlapping diode laser burns were applied through an operating microscope adapter to selected areas along the leading margins of the detachment.

The funduscopic examination and in-vivo imaging revealed bilateral optic nerve colobomas associated with a focal bullous detachment in the right eye. Fluorescein angiography showed absence of blood vessel leakage and absence of staining inside of the retinal elevation. Photocoagulation induced immediate changes in retinal layer reflectivity. Three months post-photocoagulation, the retinal detachment had improved and scarring of the burns was visible. One and two years post-procedure, the retinal detachment resolved.

Optical coherence tomography (OCT) imaging provides a detailed analysis of the retinal abnormalities associated with the clinical lesion. Laser retinopexy is a valid therapeutic option to limit the extension of the detachment.
Optical coherence tomography (OCT) imaging provides a detailed analysis of the retinal abnormalities associated with the clinical lesion. Laser retinopexy is a valid therapeutic option to limit the extension of the detachment.Maternal and perinatal death surveillance and response (MPDSR) is a health systems process entailing the continuous cycle of identification, notification, and review of maternal and perinatal deaths (Surveillance), followed by actions to improve service delivery and quality of care and Response. Prior to the COVID-19 pandemic, there were an estimated 4.6 million maternal and newborn deaths and stillbirths each year. During the pandemic, maternal and perinatal health outcomes have worsened, especially in low- and middle-income countries, highlighting the urgent need to galvanize MPDSR to end preventable mortality and strengthen health systems.
The aim of this study was to evaluate the diagnostic accuracy of
-fluorodeoxyglucose-positron emission tomography (
F-FDG PET) and PET/computed tomography (PET/CT) in imaging primary and metastatic lesions in Ewing sarcoma (ES).

PubMed, Cochrane, Scopus, and Web of Science were searched for relevant studies. Data concerning
F-FDG PET/CT diagnostic accuracy were extracted and then analyzed using Open Meta-analyst software. Reported diagnostic accuracy outcomes included sensitivity, specificity, negative likelihood ratio (NLR), positive likelihood ratio (PLR), and diagnostic odds ratio.

Thirty-one studies with a total of 735 patients were included in this meta-analysis. The sensitivity and specificity of
F-FDG PET/CT were 92.6% and 74.1% for total ES lesions, 96.7% and 68.3% for ES primary lesions, 76.1% and 92.4% for lung metastasis, 83.9% and 93.2% for bone metastasis, and 89.9% and 92.6% for ES recurrence, respectively.

F-FDG PET/CT is sensitive and accurate in diagnosing, staging, and detecting the recurrence of ES compared with non-PET imaging. It has high accuracy for diagnosing recurrence of ES in bone metastases; however, CT remains a superior diagnostic method for detecting lung metastasis.
18 F-FDG PET/CT is sensitive and accurate in diagnosing, staging, and detecting the recurrence of ES compared with non-PET imaging. It has high accuracy for diagnosing recurrence of ES in bone metastases; however, CT remains a superior diagnostic method for detecting lung metastasis.We demonstrate a new material by intercalating Mo3S132- into Mg/Al layered double hydroxides (abbr. Mo3S13-LDH), exhibiting excellent capture capability for toxic Hg2+ and noble metal silver (Ag). The as-prepared Mo3S13-LDH displays ultra-high selectivity of Ag+, Hg2+ and Cu2+ in the presence of various competitive ions, with a order of Ag+>Hg2+>Cu2+>Pb2+≥Co2+, Ni2+, Zn2+, Cd2+. For Ag+ and Hg2+, extremely fast adsorption rates (~90% within 10 min, >99% in 1 h) are observed. Much high selectivity is present for Ag+ and Cu2+, especially for trace amounts of Ag+(~1 ppm), achieving a large seperation factor (SFAg/Cu) of ~8000 at the large Cu/Ag ratio of 520. The overwhelming adsorption capacities for Ag+(qmAg=1073 mg/g) and Hg2+(qmHg=594 mg/g) place the Mo3S13-LDH at the top of performing sorbent materials. Most importantly, Mo3S13-LDH captures Ag+ via two paths a) formation of Ag2S due to Ag-S complexation and precipitation, and b) reduction of Ag+ to metallic silver (Ag0). The Mo3S13-LDH is a promising material to extract low-grade silver from copper-rich minerals and trap highly toxic Hg2+ from polluted water.A simple visible light photochemical, nickel-catalyzed synthesis of ketones from carboxylic acid-derived precursors is presented. Hantzsch-ester (HE) functions as a cheap, green and strong photoreductant to facilitate radical generation and also engages in the Ni-catalytic cycle to restore the reactive species. With this dual role, HE allows for the coupling of a large variety of radicals (1°,2°, benzylic, α-oxy & α-amino) with aroyl and alkanoyl moieties, a new feature in reactions of this type. With both precursors deriving from abundant carboxylic acids, this protocol is a welcome addition to the organic chemistry toolbox. The reaction proceeds under mild conditions without the need for toxic metal reagents or bases and shows a wide scope, including pharmaceuticals and complex molecular architectures.In the present study, the participation of protein kinase C (PKC) signaling in prothoracicotropic hormone (PTTH)-stimulated ecdysteroidogenesis in Bombyx prothoracic glands (PGs) is demonstrated and characterized. PTTH stimulated phosphorylation of a 37-kDa protein in Bombyx PGs both in vitro and in vivo, as recognized by a PKC substrate antibody. Treatment with either A23187 or thapsigargin also stimulated this 37 kDa protein phosphorylation. PTTH-stimulated phosphorylation of the 37-kDa protein was markedly attenuated in the absence of Ca2+ . The phospholipase C (PLC) inhibitor, U73122, greatly inhibited PTTH-stimulated phosphorylation of this protein, indicating the involvement of Ca2+ and PLC. A mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) kinase (MEK) inhibitor (U0126), a phosphoinositide 3-kinase (PI3K) inhibitor (LY294002), and a chemical activator of adenosine 5'-monophosphate-activated protein kinase (AMPK) (5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside, AICAR) did not affect PTTH-stimulated phosphorylation of the 37-kDa protein, implying that ERK and PI3K/AMPK are not the upstream signaling pathways for PKC-dependent protein phosphorylation. The mitochondrial oxidative phosphorylation inhibitors (the uncoupler carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP) and diphenylene iodonium (DPI)) inhibited PTTH-stimulated phosphorylation of the 37-kDa protein, indicating its redox regulation. Treatment with PKC inhibitors (either calphostin C, chelerythrine C, or rottlerin) reduced PTTH-stimulated phosphorylation of the 37-kDa protein. PTTH-stimulated ecdysteroidogenesis was also inhibited by treatment with rottlerin, thus further confirming participation of PKC-dependent phosphorylation in PTTH signaling. From these results, we demonstrated that redox-regulated PTTH-stimulated PKC signaling is involved in ecdysteroid secretion in Bombyx PGs. This article is protected by copyright. All rights reserved.In this Perspective article, we describe the visions of the PhotoRedesign consortium funded by the European Research Council of how to enhance photosynthesis. The light reactions of photosynthesis in individual phototrophic species use only a fraction of the solar spectrum, and high light intensities can impair and even damage the process. In consequence, expanding the solar spectrum and enhancing the overall energy capacity of the process, while developing resilience to stresses imposed by high light intensities, could have a strong positive impact on food and energy production. So far, the complexity of the photosynthetic machinery has largely prevented improvements by conventional approaches. Therefore, there is an urgent need to develop concepts to redesign the light-harvesting and photochemical capacity of photosynthesis, as well as to establish new model systems and toolkits for the next generation of photosynthesis researchers. The overall objective of PhotoRedesign is to reconfigure the photosynthetic light reactions so they can harvest and safely convert energy from an expanded solar spectrum. To this end, a variety of synthetic biology approaches, including de novo design, will combine the attributes of photosystems from different photoautotrophic model organisms, namely the purple bacterium Rhodobacter sphaeroides, the cyanobacterium Synechocystis sp. PCC 6803 and the plant Arabidopsis thaliana. In parallel, adaptive laboratory evolution will be applied to improve the capacity of reimagined organisms to cope with enhanced input of solar energy, particularly in high and fluctuating light.Rosmarinic acid (RA), an ester of caffeic acid and 3, 4-dihydroxyphenyllactic acid, has anti-inflammatory and neuroprotective activities. Herein, this study investigated in silico the drug-likeness and the potential molecular targets to RA. Moreover, it tested the antidepressant-like potential of RA in the lipopolysaccharide (LPS)-induced depression model. RA (MW = 360.31 g/mol) meets the criteria of both Lipinski's rule of five and the Ghose filter. It also attends to relevant pharmacokinetic parameters. Target prediction analysis identified RA's potential targets and biological activities, including the peroxisome proliferator-activated receptor (PPAR) and the cannabinoid receptors CB1 and CB2 . In vivo, RA's acute, repetitive, and therapeutic administration showed antidepressant-like effect since it significantly reduced the immobility time in the tail suspension test and increased grooming time in the splash test. Further, the pretreatment with antagonists of CB1 , CB2 , and PPAR-γ receptors significantly blocked the antidepressant-like effect of RA. Altogether, our findings suggest that cannabinoid receptors/PPAR-γ signaling pathways are involved with the antidepressant-like effect of RA. Moreover, this molecule meets important physicochemical and pharmacokinetic parameters that favor its bioavailability. RA constitutes a promising, innovative, and safe molecule for the pharmacotherapy of major depressive disorder.Herpes simplex encephalitis (HSE) is one of the most serious diseases of the nervous system in humans. However, its pathogenesis is still only poorly understood. Although several mouse models of predominantly herpes simplex virus 1 (HSV-1) infections mimic different crucial aspects of HSE, central questions remain unanswered. They comprise the specific temporofrontal tropism, viral spread within the central nervous system (CNS), as well as potential molecular and immunological barriers that drive virus into latency while only rarely resulting in severe HSE. We have recently proposed an alternative mouse model by using a pseudorabies virus (PrV) mutant that more faithfully represents the striking features of human HSE temporofrontal meningoencephalitis with few severely, but generally only moderately to subclinically affected mice as well as characteristic behavioral abnormalities. Here, we characterized this animal model using 6- to 8-week-old female CD-1 mice in more detail. Long-term investigation over 6 months consistently revealed a biphasic course of infection accompanied by recurring clinical signs including behavioral alterations and mainly mild meningoencephalitis restricted to the temporal and frontal lobes. By histopathological and immunological analyses, we followed the kinetics and spatial distribution of inflammatory lesions as well as the underlying cytokine expression in the CNS over 21 days within the acute phase of infection. Affecting the temporal lobes, the inflammatory infiltrate was composed of lymphocytes and macrophages showing a predominantly lymphocytic shift 15 days after infection. A strong increase was observed in cytokines CXCL10, CCL2, CCL5, and CXCL1 recruiting inflammatory cells to the CNS. Unlike the majority of infected mice, strongly affected animals demonstrated extensive temporal lobe edema, which is typically present in severe human HSE cases. In summary, these results support the validity of our animal model for in-depth investigation of HSE pathogenesis.It has been shown that 18β-glycyrrhetinic acid (18β-GA), the main bioactive compound of licorice, can modulate oxidative stress and metabolic processes in liver and skin. Given the critical role of oxidative stress and energy metabolism in exercise-induced fatigue, we hypothesized that 18β-GA could exert an ergogenic action by inhibiting excess reactive oxygen species (ROS) induction and promoting energy production in muscles. Mice were gavage-fed with 18β-GA for four consecutive days. Running ability was assessed based on the exhaustive treadmill test with high- and moderate-intensity. Western blot analysis, enzyme-linked immunosorbent assay, and immunofluorescence staining were used to measure the changes of muscle fatigue-related markers, oxidative stress status, and energy metabolism in response to 18β-GA exposure. Treatment with 18β-GA significantly increased the exhaustive running distance (~37%) in the high-intensity exercise, but not in the moderate-intensity exercise. Mechanistically, reduction of oxidative stress and induction of antioxidants (SOD, CAT, and GSH) by 18β-GA were observed. Moreover, 18β-GA treatment caused an improved preservation of muscle glycogen (12%), which was associated with upregulation of glucose transporter 4 (GLUT4) (91%) and increased insulin level (17%). The findings of the present study clearly suggest that 18β-GA holds excellent potential as a novel bioactive agent against high-intensity exercise-induced fatigue.The use of soluble fusion proteins of pattern recognition receptors (PRRs) used in the detection of exogenous and endogenous ligands has helped resolve the roles of PRRs in the innate immune response to pathogens, how they shape the adaptive immune response and function in maintaining homeostasis. Using the immunoglobulin (Ig) crystallisable fragment (Fc) domain as a fusion partner the PRR fusion proteins are soluble, stable, easily purified, have increased affinity due to the Fc homodimerization properties, and consequently have been used in a wide range of applications such as flow cytometry, screening of protein and glycan arrays and immunofluorescent microscopy. This review will predominantly focus on the recognition of pathogens by the cell membrane expressed glycan binding proteins of the C-type lectin receptor (CLR) subgroup of PRRs. PRRs bind to conserved pathogen associated molecular patterns (PAMPs), such as glycans, usually located within or on the outer surface of the pathogen. Significantly, many glycans structures are identical on both host and pathogen (e.g. the Lewis (Le) X glycan), allowing the use of Fc CLR fusion proteins with known endogenous and/or exogenous ligands as tools to identify pathogen structures able to interact with the immune system. Screens of highly purified pathogen-derived cell wall components have enabled identification of many unique PAMP structures recognised by CLRs. This review highlights studies using Fc CLR fusion proteins, with emphasis on the PAMPs found in fungi, bacteria, viruses, and parasites. The structure and unique features of the different CLR families is presented using examples from a broad range of microbes whenever possible.
Although esophageal dysmotility is common in systemic sclerosis (SSc)/scleroderma, little is known regarding the pathophysiology of motor abnormalities driving reflux severity and dysphagia. This study aimed to assess primary and secondary peristalsis in SSc using a comprehensive esophageal motility assessment applying high-resolution manometry (HRM) and functional luminal imaging probe (FLIP) Panometry.

A total of 32 patients with scleroderma (28 female; ages 38-77; 20limited SSc, 12 diffuse SSc) completed FLIP Panometry and HRM. Secondary peristalsis, i.e., contractile responses (CR), was classified on FLIP Panometry by pattern of contractility as normal (NCR), borderline (BCR), impaired/disordered (IDCR), or absent (ACR). Primary peristalsis on HRM was assessed according to the Chicago classification.

The manometric diagnoses were 56% (n=18) absent contractility, 22% (n=7) ineffective esophageal motility (IEM), and 22% (n=7) normal motility. Secondary peristalsis (CRs) included 38% (n=12) ACR, 38% (ngh future study to examine clinical outcomes remains necessary.The green alga Chlamydomonas reinhardtii is one of the most studied microorganisms in photosynthesis research and for biofuel production. A detailed understanding of the dynamic regulation of its carbon metabolism is therefore crucial for metabolic engineering. Post-translational modifications can act as molecular switches for the control of protein function. Acetylation of the ɛ-amino group of lysine residues is a dynamic modification on proteins across organisms from all kingdoms. Here, we performed a mass spectrometry-based profiling of proteome and lysine acetylome dynamics in Chlamydomonas under varying growth conditions. Chlamydomonas liquid cultures were transferred from mixotrophic (light and acetate as carbon source) to heterotrophic (dark and acetate), or photoautotrophic (light only) growth conditions for 30 h before harvest. In total, 5863 protein groups and 1376 lysine acetylation sites were identified with a FDR less then 1 %. As a major result of this study, our data shows that dynamic changes in abundance of lysine acetylation on various enzymes involved in photosynthesis, fatty acid metabolism, and the glyoxylate cycle are depending on acetate and light. Exemplary determination of acetylation site stoichiometries revealed particularly high occupancy levels on K175 of the large subunit of RuBisCO and K99 and K340 of peroxisomal citrate synthase, respectively, under heterotrophic conditions. The lysine acetylation stoichiometries correlated with increased activities of cellular citrate synthase, and the known inactivation of the Calvin-Benson cycle under heterotrophic conditions. In conclusion, the newly identified dynamic lysine acetylation sites may have a great potential for genetic engineering of metabolic pathways in Chlamydomonas.Herein, apoptotic mechanism of Moracin D was explored in prostate cancer cells in association with peroxisome proliferator-activated receptor gamma (PPAR-γ)-related signaling involved in lipid metabolism. Moracin D augmented cytotoxicity and sub G1 population in PC3 and DU145 prostate cancer cells, while DU145 cells were more susceptible to Moracin D than PC3 cells. Moracin D attenuated the expression of caspase-3, poly (ADP-ribose) polymerase (PARP), B-cell lymphoma 2 (Bcl-2), and B-cell lymphoma-extra-large (Bcl-xL) in DU145 cells. Consistently, Moracin D significantly augmented the number of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells in DU145 cells. Interestingly, Moracin D activated PPAR-γ and phospho-protein kinase C delta (p-PKC-δ) and inhibited phospho-protein kinase C alpha (p-PKC-α) in DU145 cells. Furthermore, STRING bioinformatic analysis reveals that PPAR-γ interacts with nuclear factor-κB (NF-κB) that binds to PKC-α/PKC-δ or protein kinase B (AKT) or extracellular signal-regulated kinase (ERK). Indeed, Moracin D decreased phosphorylation of NF-κB, ERK, and AKT in DU145 cells. Conversely, PPAR-γ inhibitor GW9662 reduced the apoptotic ability of Moracin D to activate caspase 3 and PARP in DU145 cells. Taken together, these findings provide a novel insight that activation of PPAR-γ/p-PKC-δ and inhibition of p-PKC-α are critically involved in Moracin D-induced apoptosis in DU145 prostate cancer cells.Epidermolysis Bullosa is a dermatologic condition characterized by skin fragility and the formation of painful blisters all over the body. The course of this chronic hereditary disorder involves multiple painful procedures for which adequate analgesia is an ongoing challenge. This case report follows a previously-described pediatric patient with the Dowling-Meara variant of Epidermolysis Bullosa who was treated with at-home nitrous oxide for daily procedural analgesia. We report on the long-term effectiveness of this treatment in addition to any side effects encountered as a result of this treatment.MicroRNAs (miRNAs or miRs) serve essential roles in the pathogenic process of spinal cord injury (SCI). The present study investigated the role of miR-378-3p and autophagy-related 12 (ATG12) in SCI. RT-qPCR was used to detect the mRNA expression levels of miR-378-3p and ATG12. Cell viability and membrane integrity were evaluated using CCK-8 and LDH assays. For the analysis of the interaction between miR-378-3p and ATG12, a dual-luciferase reporter assay was conducted. The hindlimb function of rats was detected with the Basso, Beattie and Bresnahan score, and the motor deficit index score was used to evaluate nerve function. Using these approaches, it was identified that miR-378-3p expression was downregulated, while that of ATG12 was upregulated in SCI tissues and in cells exposed to hypoxia. Hypoxia repressed the expression of miR-378-3p via hypoxia-inducible factor 1-α. The overexpression of miR-378-3p exerted anti-apoptotic effects on nerve cells by directly repressing ATG12. The infusion of miR-378-3p improved hindlimb motor function and the neurological functions of rats with contusion SCI, which contributed to amelioration of functional deficits and the relief of contusion SCI. Therefore, it was concluded that upregulated expression of miR-378-3p in PC12 or N2A cells repressed the apoptosis of nerve cells, and the administration of miR-378-3p in model rats with contusion SCI improved neurological and motor functions.
Many people experience psychological trauma during their lifetime, often negatively affecting their mental and physical health. Post-traumatic growth is a positive psychological change that may occur in an individual after having processed and coped with trauma. This journey, however, has not been studied enough.

The purpose of this phenomenological study was to explore people's experience of suffering psychological trauma, the personal effects of the trauma and the transition from trauma to post-traumatic growth.

A purposeful sample of seven women and five men, aged 34-52, were selected whose backgrounds and history of trauma varied, but who had all experienced post-traumatic growth. One to two interviews were conducted with each one, in all 14 interviews.

This study introduces a unique mapping of the challenging journey from trauma to post-traumatic growth through lived experiences of people who have experienced trauma as well as post-traumatic growth. Participants had different trauma experience, bsults suggest that the journey to post-traumatic growth includes a recovery process and certain influencing factors that must be considered. This information has implications for professionals treating and supporting people who have suffered traumas.
Excessive daytime sleepiness (EDS) is a frequent and disabling symptom of Parkinson's disease (PD) without approved treatment. THN102 is a novel combination drug of modafinil and low-dose flecainide.

The aim of this study is to evaluate the safety and efficacy of THN102 in PD patients with EDS.

The method involved a randomized, double-blind, placebo-controlled, crossover trial testing two doses of THN102 (200 mg/d modafinil with 2 mg/d [200/2] or 18 mg/d flecainide [200/18]) versus placebo; 75 patients were exposed to treatment. The primary endpoint was safety. The primary efficacy outcome was the change in Epworth Sleepiness Scale (ESS) score.

Both doses of THN102 were well tolerated. ESS significantly improved with THN102 200/2 (least square means vs. placebo [95% confidence interval, CI] -1.4 [-2.49; -0.31], P=0.012) but did not change significantly with the 200/18 dosage.

THN102 was well tolerated and showed a signal of efficacy at the 200/2 dose, supporting further development for the treatment of EDS in PD. © 2021 International Parkinson and Movement Disorder Society.
THN102 was well tolerated and showed a signal of efficacy at the 200/2 dose, supporting further development for the treatment of EDS in PD. © 2021 International Parkinson and Movement Disorder Society.
The Cockcroft-Gault (CG) creatinine-based equation is still used to estimate glomerular filtration rate (eGFR) for drug dosage adjustment. Incorrect eGFR may lead to hazardous over- or underdosing METHODS In a cross-sectional analysis, CG was validated against measured GFR (mGFR) in 14,804 participants and compared with the Modification-of-Diet-in-Renal-Diseases (MDRD), Chronic-Kidney-Disease-Epidemiology (CKD-EPI), Lund-Malmö-Revised (LMR), and European-Kidney-Function-Consortium (EKFC) equations. Validation focused on bias, imprecision, and accuracy (percentage of estimates within ±30% of mGFR, P30), overall and stratified for mGFR, age, and body mass index at mGFR <60 mL/min, as well as classification in mGFR stages.

The CG equation performed worse than the other equations, overall and in mGFR, age and BMI subgroups in terms of bias (systematic overestimation), imprecision and accuracy except for patients ≥65 years where bias and P30 were similar to MDRD and CKD-EPI, but worse than LMR and EKFC. In subjects with mGFR<60 mL/min and at BMI [18.5-25[kg/m
, all equations performed similarly and for BMI<18.5kg/m
CG and LMR had the best results though all equations had poor P30-accuracy. At BMI≥25kg/m
the bias of the CG increased with increasing BMI (+17.2mL/min at BMI≥40kg/m
). The four more recent equations also classified mGFR stages better than CG.

The CG equation showed poor ability to estimate GFR overall and in analyses stratified for GFR, age, and BMI. CG was inferior to correctly classify the patients in the mGFR staging compared to more recent creatinine-based equations.
The CG equation showed poor ability to estimate GFR overall and in analyses stratified for GFR, age, and BMI. CG was inferior to correctly classify the patients in the mGFR staging compared to more recent creatinine-based equations.Cancer therapy-induced oral mucositis (OM) is one of the most troublesome morbidities after radio-chemotherapy. Age, nutritional status, tumor type, oral hygiene, and treatment method are the determinants for OM incidence. In addition, oxygen-free radicals can act as a trigger for an inflammatory milieu that causes OM. Based on the debilitating nature of OM, finding a safe and inexpensive agent with anti-inflammatory, anti-microbial, and antioxidative properties can be valuable for this situation. Considering the harmful effects of some chemical agents, herbal medicine has been suggested as a potential alternative owing to unique properties such as safety, availability and low cost. Many studies have illustrated several pharmacological properties of herbal medicines in recent years, such as anti-inflammatory, anti-microbial, and antioxidative activities, which are essential factors in the palliation of cancer therapy-induced OM. This review aimed to evaluate herbal medicines' effects on cancer therapy-induced OM. According to this comprehensive review, it is concluded that medicinal plants and phytochemicals can be used as practical agents in the palliation of cancer therapy-induced OM without any serious side effects.Reduced adherence after heart transplantation increases the risk for acute rejection. Therefore, the aim of this study was to evaluate the patient's satisfaction with outpatient care and quality of life (QOL) after pediatric and adult heart transplantation. Observational study after pediatric (n = 22) and adult (n = 65) heart transplantation and the parents of the pediatric patients (n = 22) to evaluate the patients' satisfaction with outpatient care and QOL. Established standardized questionnaires were used for patient satisfaction (ZAP survey) and QOL (SF36); the latter was compared with the cohort of the BGS98 survey (BGS98 cohort). ZAP score excellent results with almost all values >80. QOL pediatric cohort showed significantly higher values in physical functioning (P = 0.041) and role physical (P = 0.003) but significantly lower values in the sub-scale general health (P = 0.02) compared to adult cohort. In comparison with BGS98 cohort, children showed almost similar results, whereas adult cohort showed worse values in physical and emotional functioning, but higher values regarding general health. The QOL of patients after pediatric heart transplantation is comparable to a standardized reference population in Germany, whereas adult patients show reduced physical and emotional functioning, but better values regarding general health. The patients' satisfaction with the outpatient care is very high.
Although it is known that solid organ transplant recipients fare worse after COVID-19 infection, data on the impact of COVID-19 on clinical outcomes and allograft function in lung transplant (LTx) recipients are limited and based mainly on reports with short follow-up.

In this nationwide study, all LTx recipients with COVID-19 diagnosed from February 1st, 2020 to April 30th, 2021, were included. The patients were followed until August 1
2021, or death. We analysed demographics, clinical features, therapeutic management, and outcomes, including lung function.

Forty-seven patients were identified median age was 59 (10-78) years, 53.1% were male, and median follow-up was 194 (23-509) days. COVID-19 was asymptomatic or mild at presentation in 48.9%. Nine patients (19.1%) were vaccinated pre-COVID infection. Two patients (4.3%) died within 28 days of testing positive, and the overall survival rate was 85.1%. The patients with asymptomatic or mild symptoms had a higher median % expected forced expiratory volume during the first second than the patients with worse symptoms (p=0.004).

LTx recipients develop the entire spectrum of COVID-19, and in addition to previously acknowledged risk factors, lower pre-COVID lung function was associated with more severe disease presentation.
LTx recipients develop the entire spectrum of COVID-19, and in addition to previously acknowledged risk factors, lower pre-COVID lung function was associated with more severe disease presentation.Alopecia areata (AA) is a relatively common nonscarring hairloss disease characterized by an autoimmune response to anagen hair follicles (HFs). Accumulated evidence suggests that collapse of the HF immune privilege subsequent to triggering events, represented by viral infection, leads to autoimmune response in which autoreactive cytotoxic CD8+NKG2D+ T cells mainly target exposed HF autoantigens. AA had been recognized as type 1 inflammatory disease, but recent investigations have suggested some roles of type 2- and Th17-associated mediators in AA pathogenesis. The significance of psychological stress in AA pathogenesis is less emphasized nowadays, but psychological comorbidities, such as depression and anxiety, attract greater interest in AA management. In this regard, the disease severity may not solely be evaluated by the extent of hair loss. Use of trichoscopy markedly improved the resolution of the diagnosis and evaluation of the phase of AA, which is indispensable for the optimization of treatment. For is and pathophysiology, and update on therapeutic approaches with future perspectives are summarized for AA, following the current version of the JDA AA management guidelines.The mammalian lactoperoxidase system, consisting of lactoperoxidase and the H2 O2 -producing enzyme duox, is our first line of defence against airborne microbes. This system catalyses the production of hypoiodite and hypoiodous acid in the presence of sufficient iodine. These products are highly efficient at destroying the H1N1 virus and the respiratory syncytial virus (RSV). Japan has not been affected as much as other nations during the COVID-19 pandemic (death rate about 10% of the United States), and we think this is due to a diet high in iodine. With this in mind, we suggest four actions to prevent SARS-CoV-2 infections. First, health professionals should study the preventative effect of increasing iodine in the diets of the aged, institutionalized, diabetics andsmokers. Second, the recommended daily intake (RDI) for iodine should be significantly increased, to at least double, the current RDI. Governments should encourage the use and distribution of cheap iodized salts, kelp and seaweed. Third, more research should be done around the physiology and the protective effects of the lactoperoxidase system. Finally, the degradation products of the SARS-CoV-2 viral particle by hypoiodite and hypoiodous acid should be characterized; portions of the damaged particle are likely to elicit stronger immunity and better vaccines.Invited for the cover of this issue are Oleksandr Grygorenko and co-workers at Enamine Ltd., Institute of Organic Chemistry NAS Ukraine, and Taras Shevchenko National University of Kyiv. The image depicts a musical allegory for chemical synthesis a guitar player in a flask, creating notes that become an orgoboron compound. Read the full text of the article at 10.1002/chem.202102108.Acne and rosacea are common inflammatory skin conditions present in numerous racial and ethnic groups. There are distinct differences in clinical presentation, exacerbating factors, potential triggers and consequences of both conditions in individuals with skin of colour (SOC, Fitzpatrick skin type III-VI). For example, acne can be complicated by the development of post-inflammatory hyperpigmentation and keloids scarring in SOC, this can influence treatment choice. Although rosacea is reported less frequently in skin of colour, this may be due to a delayed diagnosis or late presentation due to the difficulty in discerning the classical feature of erythema in darker skin tones. In such cases, additional clues in the history and examination may assist in making the diagnosis. This review aims to summarise nuances in the both diagnosis and management of two these common skin conditions in patients with skin of colour to support clinicians in providing an individualised treatment approach.Quercetin, widely distributed in fruits and vegetables, is a flavonoid known for its antioxidant, antiviral, antimicrobial, and antiinflammatory properties. Several studies highlight the potential use of quercetin as an antiviral, due to its ability to inhibit the initial stages of virus infection, to be able to interact with proteases important for viral replication, and to reduce inflammation caused by infection. Quercetin could also be useful in combination with other drugs to potentially enhance the effects or synergistically interact with them, in order to reduce their side effects and related toxicity. Since there is no comprehensive compilation about antiviral activities of quercetin and derivates, the aim of this review is providing a summary of their antiviral activities on a set of human viral infections along with mechanisms of action. Thus, the following family of viruses are examined Flaviviridae, Herpesviridae, Orthomyxoviridae, Coronaviridae, Hepadnaviridae, Retroviridae, Picornaviridae, Pneumoviridae, and Filoviridae.
Recent studies have shown low caspofungin concentrations in critically ill patients. In some patients, the therapeutic target, area under the total plasma concentration curve in relation to the minimal inhibition concentration (AUC
/MIC), seems not to be achieved and therapeutic drug monitoring (TDM) has been proposed. Caspofungin is highly protein-bound and the effect of reduced plasma protein levels on pharmacodynamics has not been investigated.

Fungal killing activity of caspofungin in vitro was investigated under varying levels of human plasma protein.

Time-kill studies were performed with clinically relevant caspofungin concentrations of 1-9mg/L on four blood isolates of C.glabrata, three susceptible and one strain with reduced susceptibility, in human plasma and plasma diluted to 50% and 25% using Ringer's acetate.

Enhanced fungal killing of the three susceptible strains was observed in plasma with lower protein content (p<.001). AUC
/MIC required for a 1 log
CFU/ml kill at 24h in 50% ag TDM based on total plasma concentrations.Aesthetic ultrasound is used for fat reduction and to improve skin appearance. In this review, the fundamental mechanisms by which ultrasound can alter tissue are outlined. The technologies that are commercially available or under development are discussed. Finally, recommendations are made for safe and effective use of aesthetic ultrasound.
To explore the diagnostic value of contrast-enhanced ultrasound (CEUS) combined with the Chinese Thyroid Imaging Reporting and Data System (C-TIRADS) for differentiation of benign and malignant thyroid nodules.

A retrospective analysis of the conventional ultrasound and CEUS data of 388 nodules in 355 patients who had undergone thyroid nodule resection was conducted. All nodules had clear pathological results. The CEUS observation indexes included the enhancement degree in the arterial phase (no enhancement, scant punctate-linear enhancement, mild enhancement, moderate enhancement, and high enhancement) and wash-out patterns (rapid wash-out, slow wash-out, and isochronous wash-out). Chi-square test between groups and receiver operating characteristic curves (ROC) were used to determine the malignant (+1 point) and benign (-1 point) observation indexes that were statistically significant for the differentiation between benign and malignant thyroid nodules. The CEUS and C-TIRADS malignant and benign indexes. The C-TIRADS + CEUS score has a higher value for distinguishing benign from malignant thyroid nodules than the C-TIRADS score alone.
The CEUS feature of mild enhancement in the arterial phase and rapid wash-out pattern are suggestive of malignancy and isochronous wash-out pattern is suggestive of benignity. The C-TIRADS + CEUS score has a higher value for distinguishing benign from malignant thyroid nodules than the C-TIRADS score alone.
Serum small dense low-density lipoprotein cholesterol (sdLDL-C) and lipoprotein(a) [Lp(a)] levels are related to coronary disease, but their specific associations with coronary arteriostenosis in Takayasu arteritis (TA) have not been ascertained. This study explored the correlations between serum sdLDL-C and Lp(a) levels and coronary arteriostenosis in TA patients as well as the degree of artery stenosis.

This retrospective study included 190TA patients and 154healthy subjects. TA patients were divided into three categories based on the degree of coronary stenosis Group I, stenosis >50%; Group II, stenosis 1%-50%; and Group III, stenosis 0%. Independent risk factors for coronary arteriostenosis in TA were identified by logistic regression, followed by receiver operating characteristic curve analysis to determine the specificity and sensitivity of risk factors and Youden's Index score calculation to determine the cutoff points.

Takayasu arteritis patients had significantly higher serum levels of sdLDL-C and Lp(a) than healthy controls (p<0.0001). The total cholesterol, triglyceride, LDL-C, sdLDL-C, and Lp(a) levels and the sdLDL-C/LDL-C ratio in Group I were significantly higher than those in Groups II and III (p<0.05). An elevated serum sdLDL-C level elevated the risk of coronary arteriostenosis by 5-fold (cutoff value, 0.605mmol/l). An increased serum Lp(a) level increased the risk of coronary arteriostenosis by 3.9-fold (cutoff value, 0.045g/l). An elevated sdLDL-C/LDL-C ratio increased the risk of coronary arteriostenosis by 2.1-fold (cutoff value, 0.258).

Serum sdLDL-C and Lp(a) levels and sdLDL-C/LDL-C ratio may be used as diagnostic factors for coronary arteriostenosis in TA patients.
Serum sdLDL-C and Lp(a) levels and sdLDL-C/LDL-C ratio may be used as diagnostic factors for coronary arteriostenosis in TA patients.
Atopic eczema (AE), also known as atopic dermatitis, is a chronic inflammatory skin condition that causes significant burden. Phototherapy is sometimes used to treat AE when topical treatments, such as corticosteroids, are insufficient or poorly tolerated.

To assess the effects of phototherapy fortreating AE.

We searched the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, and ClinicalTrials.gov to January 2021.

We included randomised controlled trials in adults or children with any subtype or severity of clinically diagnosed AE. Eligible comparisons were any type of phototherapy versus other forms of phototherapy or any other treatment, including placebo or no treatment.

We used standard Cochrane methodology. For key findings, we used RoB 2.0 to assess bias, and GRADE to assess certainty of the evidence. Primary outcomes were physician-assessed signs and patient-reported symptoms. Secondary outcomes were Investigator Global Assessment (IGA), health-related quality of life (HRQoL), safeence for UVA1 compared to NB-UVB or PUVA, and NB-UVB compared to PUVA was very low certainty. More information is needed on the safety and effectiveness of all aspects of phototherapy for treating AE.
Compared to placebo or no treatment, NB-UVB may improve physician-rated signs, patient-reported symptoms, and IGA after 12 weeks, without a difference in withdrawal due to adverse events. Evidence for UVA1 compared to NB-UVB or PUVA, and NB-UVB compared to PUVA was very low certainty. More information is needed on the safety and effectiveness of all aspects of phototherapy for treating AE.Essential oil products are increasingly used in indoor environments and have been found to negatively contribute to indoor air quality. Moreover, the chemicals and fragrances emitted by those products may affect the central nervous system and cognitive function. This study uses a double-blind between-subject design to investigate the cognitive impact of exposure to the emissions from essential oil used in an ultrasonic diffuser. In a simulated office environment where other environmental parameters were maintained constant, 34 female and 25 male university students were randomly allocated into four essential oil exposure scenarios. The first two scenarios contrast lemon oil to pure deionized water, while the latter two focus on different levels of particulate matter differentiated by HEPA filters with non-scented grapeseed oil as the source. Cognitive function was assessed using a computer-based battery consisting of five objective tests that involve reasoning, response inhabitation, memory, risk-taking, and decision-making. Results show that exposure to essential oil emissions caused shortened reaction time at the cost of significantly worse response inhabitation control and memory sensitivity, indicating potentially more impulsive decision-making. The cognitive responses caused by scented lemon oil and non-scented grapeseed oil were similar, as was the perception of odor pleasantness and intensity.
Measurements comparing relative stopping power (RSP) accuracy of state-of-the-art systems representing single-energy and dual-energy computed tomography (SECT/DECT) with proton CT (pCT) and helium CT (HeCT) in biological tissuesamples.

We used 16 porcine and bovine samples of various tissue types and water, covering an RSP range from 0.90±0.06 to 1.78±0.05. Samples were packed and sealed into 3D-printed cylinders (d = 2cm, h = 5cm) and inserted into an in-house designed cylindrical PMMA phantom (d = 10cm, h = 10cm). We scanned the phantom in a commercial SECT and DECT (120kV; 100kV & 140kV/Sn (tin-filtered)); and acquired pCT and HeCT (E ∼ 200MeV/u, 2
steps, ∼ 6.2 × 10
(p)/∼ 2.3 × 10
(He) particles/projection) with a particle imaging prototype. RSP maps were calculated from SECT/DECT using stoichiometric methods and from pCT/HeCT using the DROP-TVS algorithm. We estimated the average RSP of each tissue per modality in cylindrical volumes of interest and compared it to ground truth RSP taken fromology and a pCT/HeCT prototype, DECT provided the most accurate RSP prediction, closely followed by particle imaging. The novel modalities pCT and HeCT have the potential to further improve on RSP accuracies with work focusing on the origin and correction of ring artefacts. Future work will study accuracy of proton treatment plans using RSP maps from investigated imaging modalities.Oxford Houses (OHs) are a large network of self-run community-based settings for individuals with substance use disorders. This present study explored a model based on conceptualizing recovery home social systems as dynamic multirelational (multiplex) social networks. The model is developed from data obtained from 42 OH recovery homes in three parts of the US, addressing whole networks of friendship, close friendship, and willingness to loan money. Findings indicated that close friend and loan relationships mutually reinforced each other over time as they coevolved. These types of insights can help community psychologists to better understand complex network dynamics in community-based settings.
To investigate associations between alcohol use, psychological treatment attendance, and clinical outcomes.

We analysed electronic health records for N = 7,986 patients accessing psychological treatment for common mental disorders. Data were collected for pre-treatment alcohol use (average units per week) and severity of dependence (SDS), number of therapy contacts attended, pre- and post-treatment anxiety (GAD-7), and depression (PHQ-9) symptom severity. Hierarchical regression was used to examine associations between alcohol use/dependence and post-treatment symptom severity controlling for intake severity and relevant confounders.

After controlling for confounders, alcohol use had significant nonlinear associations with pre-treatment depression severity (R
 = .54, p < .01, cubic trend), and post-treatment anxiety (R
 = .23, p < .01, quadratic trend). Alcohol use was not significantly associated with intake anxiety, post-treatment depression or treatment duration. SDS was not significantly a.
Depression and anxiety problems often co-occur with alcohol use and dependence. Conventional wisdom in the field suggests that heavy alcohol users may not engage well or benefit from psychological therapies for depression and anxiety. We found no empirical support for the above assumptions in a large clinical sample. Alcohol consumption was not significantly associated with treatment attendance or depression treatment outcomes. A nonlinear association between alcohol use and anxiety outcomes suggests that moderate drinkers may have some shared characteristic that favours treatment response.Two messenger RNA (mRNA) vaccines developed by Pfizer-BioNTech and Moderna are being rolled out. Despite the high volume of emerging evidence regarding adverse events (AEs) associated with the COVID-19 mRNA vaccines, previous studies have thus far been largely based on the comparison between vaccinated and unvaccinated control, possibly highlighting the AE risks with COVID-19 mRNA vaccination. Comparing the safety profile of mRNA vaccinated individuals with otherwise vaccinated individuals would enable a more relevant assessment for the safety of mRNA vaccination. We designed a comparative safety study between 18 755 and 27 895 individuals who reported to VigiBase for adverse events following immunization (AEFI) with mRNA COVID-19 and influenza vaccines, respectively, from January 1, 2020, to January 17, 2021. We employed disproportionality analysis to rapidly detect relevant safety signals and compared comparative risks of a diverse span of AEFIs for the vaccines. The safety profile of novel mRNA vaccines was divergent from that of influenza vaccines.
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