N-Si Heterolysis by Chiral (BOX)Cu(OTf)2 Catalysts for the Synthesis of Indole and Carbazole Glycosides.

Chiral Cu(II) bisoxazolines have been shown to catalyze the coupling of acetyl-protected carbohydrates with N-silylated indoles to give the corresponding N-glycosides. Preliminary mechanistic experiments indicated that catalysis occurs through formation of a Cu-indolide complex with concomitant formation of TMS-OTf which together activate the sugar and deliver the indole nucleophile.

Cytomegalovirus infection and cardiovascular outcomes in abdominal organ transplant recipients: A systematic review and meta-analysis.

INTRODUCTION: Despite advancements in Cytomegalovirus (CMV) management, its impact on graft function, mortality, and cardiovascular (CV) health of organ transplant recipients (OTR) remains a significant concern. We investigated the association between CMV infection and CV events (CVE) in organ (other than heart) transplant recipients. METHODS: We conducted a comprehensive literature search in PubMed and EMBASE, including studies that reported on CMV infection or disease and post-transplantation CVE. Studies of heart transplant recipients were excluded. RESULTS: We screened 3875 abstracts and 12 clinical studies were included in the final analysis, mainly in kidney and liver transplant recipients. A significant association was observed between CMV infection and an increased risk of CVE, with a pooled unadjusted hazard ratio (HR) of 1.99 (95% Confidence Intervals [CI] 1.45-2.73) for CMV infection and 1.59 (95% CI 1.21-2.10) for CMV disease. Pooled adjusted HR were 2.17 (95% CI 1.47-3.20) and 1.77 (95% CI 0.83-3.76), respectively. Heterogeneity was low (I2 = 0%) for CMV infection, suggesting consistent association across studies, and moderate-to-high for CMVdisease (I2 = 50% for unadjusted, 53% for adjusted HR). DISCUSSION: We found a significant association between CMV infection and CV risk in abdominal OTR, underscoring the importance of proactive CMV surveillance and early treatment. Future research should aim for more standardized methodologies to fully elucidate the relationship between CMV and CV outcomes, potentially informing novel preventive and therapeutic strategies that could benefit the CV health of OTR.

New Hyperacusis Therapy Combines Psychoeducation, Sound Exposure, and Counseling.

PURPOSE: The aim of this study was to investigate the short- and long-term effects of a new cognitive sound exposure therapy (CSET) in patients with hyperacusis. METHOD: A new therapy was developed to reduce hyperacusis using sound exposure combined with breathing and relaxation strategies from both acceptance and commitment therapy and cognitive behavioral therapy. Patients who were referred to the Speech and Hearing Centers located in Hengelo and Zwolle in the Netherlands and aged ≥ 18 years with hyperacusis as main complaint and no or mild hearing loss were included in this study. Patients were seen for CSET between June 2020 and August 2022. The sessions took place biweekly. Sessions ended when exposure reached a level with a maximum of 70-80 dB SPL. Short-term effects between the start and the end of therapy were based on tolerable level of sound exposure (dB SPL), subjective-level hinderance of hyperacusis, and sensitivity to sound using the Hyperacusis Questionnaire (HQ). The long-term effect was based on HQ 6 months after the end of therapy. Linear mixed-effects and regression models were applied to study outcomes over time. RESULTS: In total, 30 patients, 15 men and 15 women, aged between 24 and 76 years were included in this study. The mean number of sessions during therapy was 6 and ranged between 4 and 8. Results showed an increase of exposure level (mean change was +23.7 dB with an SD of 7.9, p < .001), a decrease in sensitivity to daily sounds (mean [SD] change was -1.6 [2.1], p < .001), and a decrease in HQ (mean [SD] change was -9.8 [4.9], p < .001), between the start and the end of therapy. There was no significant change in HQ after the end of therapy and 6 months later; mean (SD) change was 0.2 (4.3), p = .81. CONCLUSIONS: The evaluation of CSET indicated a decrease in short- and long-term sensitivity to sound in patients with hyperacusis. Additionally, CSET has shown a positive impact, not only for the sounds used in the therapy sessions but also in transferring benefits to everyday sounds. The results of combining psychoeducation, sound exposure, and counseling are promising and warrant further evaluation.

Canadian Cardiovascular Society/Canadian Cardiovascular Critical Care Society/Canadian Association of Interventional Cardiology Clinical Practice Update on Optimal Post Cardiac Arrest and Refractory Cardiac Arrest Patient Care.

Survival to hospital discharge among patients with out-of-hospital cardiac arrest (OHCA) is low and important regional differences in treatment practices and survival have been described. Since the 2017 publication of the Canadian Cardiovascular Society's position statement on OHCA care, multiple randomized controlled trials have helped to better define optimal post cardiac arrest care. This working group provides updated guidance on the timing of cardiac catheterization in patients with ST-elevation and without ST-segment elevation, on a revised temperature control strategy targeting normothermia instead of hypothermia, blood pressure, oxygenation, and ventilation parameters, and on the treatment of rhythmic and periodic electroencephalography patterns in patients with a resuscitated OHCA. In addition, prehospital trials have helped craft new expert opinions on antiarrhythmic strategies (amiodarone or lidocaine) and outline the potential role for double sequential defibrillation in patients with refractory cardiac arrest when equipment and training is available. Finally, we advocate for regionalized OHCA care systems with admissions to a hospital capable of integrating their post OHCA care with comprehensive on-site cardiovascular services and provide guidance on the potential role of extracorporeal cardiopulmonary resuscitation in patients with refractory cardiac arrest. We believe that knowledge translation through national harmonization and adoption of contemporary best practices has the potential to improve survival and functional outcomes in the OHCA population.

Protracted Exposure to a Sub-background Radiation Environment Negatively Impacts the Anhydrobiotic Recovery of Desiccated Yeast Sentinels.

ABSTRACT: Experiments that examine the impacts of subnatural background radiation exposure provide a unique approach to studying the biological effects of low-dose radiation. These experiments often need to be conducted in deep underground laboratories in order to filter surface-level cosmic radiation. This presents some logistical challenges in experimental design and necessitates a model organism with minimal maintenance. As such, desiccated yeast ( Saccharomyces cerevisiae ) is an ideal model system for these investigations. This study aimed to determine the impact of prolonged sub-background radiation exposure in anhydrobiotic (desiccated) yeast at SNOLAB in Sudbury, Ontario, Canada. Two yeast strains were used: a normal wild type and an isogenic recombinational repair-deficient rad51 knockout strain ( rad51 Δ). Desiccated yeast samples were stored in the normal background surface control laboratory (68.0 nGy h -1 ) and in the sub-background environment within SNOLAB (10.1 nGy h -1 ) for up to 48 wk. Post-rehydration survival, growth rate, and metabolic activity were assessed at multiple time points. Survival in the sub-background environment was significantly reduced by a factor of 1.39 and 2.67 in the wild type and rad51 ∆ strains, respectively. Post-rehydration metabolic activity measured via alamarBlue reduction remained unchanged in the wild type strain but was 26% lower in the sub-background rad51 ∆ strain. These results demonstrate that removing natural background radiation negatively impacts the survival and metabolism of desiccated yeast, highlighting the potential importance of natural radiation exposure in maintaining homeostasis of living organisms.

Overview of Bacterial Protein Toxins from Pathogenic Bacteria: Mode of Action and Insights into Evolution.

Bacterial protein toxins are secreted by certain bacteria and are responsible for mild to severe diseases in humans and animals. They are among the most potent molecules known, which are active at very low concentrations. Bacterial protein toxins exhibit a wide diversity based on size, structure, and mode of action. Upon recognition of a cell surface receptor (protein, glycoprotein, and glycolipid), they are active either at the cell surface (signal transduction, membrane damage by pore formation, or hydrolysis of membrane compound(s)) or intracellularly. Various bacterial protein toxins have the ability to enter cells, most often using an endocytosis mechanism, and to deliver the effector domain into the cytosol, where it interacts with an intracellular target(s). According to the nature of the intracellular target(s) and type of modification, various cellular effects are induced (cell death, homeostasis modification, cytoskeleton alteration, blockade of exocytosis, etc.). The various modes of action of bacterial protein toxins are illustrated with representative examples. Insights in toxin evolution are discussed.

Toxins, Pathogenicity, Anti-Toxins, a Bicentennial Contribution.

The bicentenary of Louis Pasteur's birth raises the opportunity to revisit the activity and influence of L [...].

An eight-year follow-up on auditory outcomes after neonatal hearing screening.

OBJECTIVE: The aim of this study is to assess the neonatal click Auditory Brainstem Response (ABR) results in relation to the subsequently determined mean hearing loss (HL) over 1, 2 and 4 kHz, as well as over 2 and 4 kHz. METHODS: Between 2004-2009, follow-up data were collected from Visual Reinforcement Audiometry (VRA) at 1 and 2 years and playaudiometry at 4 and 8 years of newborns who had failed neonatal hearing screening in the well-baby clinics and who had been referred to a single Speech and Hearing center. Hearing Level data were compared with ABR threshold-levels established during the first months of life. The Two One-Sided Tests equivalence procedure for paired means was applied, using a region of similarity equal to 10 dB. RESULTS: Initially, in 135 out of 172 children referred for diagnostic procedures hearing loss was confirmed in the neonatal period. In 106/135 of the HL children the eight-year follow-up was completed. Permanent conductive HL was established in 5/106 cases; the hearing thresholds were predominantly stable over time. Temporary conductive HL was found in 48/106 cases and the loss disappeared by 4 years of age at the latest. Sensorineural hearing loss (SNHL) was found in 53/106 cases, of which 13 were unilateral and 40 bilateral. ABR levels were equivalent (within a 10 dB range) to VRA levels at age 1 and 2 and play audiometry levels at age 4 and 8, both when VRA and play audiometry were averaged over both frequency ranges. CONCLUSION: Long term follow-up data of children with SNHL suggest that the initial click ABR level established in the first months of life, are equivalent to the hearing threshold measured at the age of 1, 2, 4 and 8 years for both mean frequency ranges. Click ABR can reliably be used as starting point for long-term hearing rehabilitation.

Analytical interference of intravascular contrast agents with clinical laboratory tests: a joint guideline by the ESUR Contrast Media Safety Committee and the Preanalytical Phase Working Group of the EFLM Science Committee.

The Contrast Media Safety Committee of the European Society of Urogenital Radiology has, together with the Preanalytical Phase Working Group of the EFLM Science Committee, reviewed the literature and updated its recommendations to increase awareness and provide insight into these interferences.

Bioprospecting the potential of the microbial community associated to Antarctic marine sediments for hydrocarbon bioremediation.

Microorganisms that inhabit the cold Antarctic environment can produce ligninolytic enzymes potentially useful in bioremediation. Our study focused on characterizing Antarctic bacteria and fungi from marine sediment samples of King George and Deception Islands, maritime Antarctica, potentially affected by hydrocarbon influence, able to produce enzymes for use in bioremediation processes in environments impacted with petroleum derivatives. A total of 168 microorganism isolates were obtained: 56 from sediments of King George Island and 112 from Deception Island. Among them, five bacterial isolates were tolerant to cell growth in the presence of diesel oil and gasoline and seven fungal were able to discolor RBBR dye. In addition, 16 isolates (15 bacterial and one fungal) displayed enzymatic emulsifying activities. Two isolates were characterized taxonomically by showing better biotechnological results. Psychrobacter sp. BAD17 and Cladosporium sp. FAR18 showed pyrene tolerance (cell growth of 0.03 g mL-1 and 0.2 g mL-1) and laccase enzymatic activity (0.006 UL-1 and 0.10 UL-1), respectively. Our results indicate that bacteria and fungi living in sediments under potential effect of hydrocarbon pollution may represent a promising alternative to bioremediate cold environments contaminated with polluting compounds derived from petroleum such as polycyclic aromatic hydrocarbons and dyes.

Concentrations, sources and risks of polycyclic aromatic hydrocarbons in sediments from the Parnaiba Delta basin, Northeast Brazil.

The Parnaíba River is the main river in the Parnaíba Delta basin, the largest delta in the Americas. About 18 polycyclic aromatic hydrocarbons (PAHs) were identified and the environmental risk associated with the sediments was evaluated. The study found that PAHs levels ranged from 5.92 to 1521.17 ng g-1, which was classified as low to high pollution, and that there were multiple sources of pollution along the river, with pyrolytic sources predominating, mainly from urban activity such as trucking, although the influence of rural activity cannot be ruled out. PAHs correlated with black carbon and organic matter and showed high correlation with acenaphthylene, phenanthrene, pyrene, benzo(a)anthracene, chrysene, benzo(ghi)perylene, and ∑PAHs. The benzo(a)pyrene levels were classified as a risk to aquatic life because the threshold effect level and the probable effect level were exceeded. In addition, the sediments were classified as slightly contaminated with a benzo(a)pyrene toxicity equivalent value of 108.43 ng g-1. Thus, the priority level PAH exhibited carcinogenic and mutagenic activity that posed a potential risk to human health.

Evaluation of microneedling depth of penetration in management of atrophic acne scars: a split-face comparative study.

BACKGROUND: Microneedling is a technique of repeated puncturing or drilling of the skin to induce repair and collagen induction. There are many reported important factors determining the efficacy of microneedling treatment. The extent of injury needed to produce the desired effect in each condition is one of these important factors. OBJECTIVES: We designed the present split-face comparative study to evaluate the use and effectiveness of two different depths of penetration of Dermapen needles in the management of atrophic postacne scars. PATIENTS AND METHODS: The present study involved 14 subjects with atrophic postacne scars. In each patient, both sides of the face were treated with six sessions of microneedling, using Dermapen at 2-week intervals. A split-face study design was performed. The right (Rt) side of the face was treated with Dermapen using 2.5 mm needle length, while the left (Lt) side was treated using 1.5 mm needle length. RESULTS: There was a significantly better percentage of improvement of acne scars on the Rt side of the face compared to the Lt side (P = 0.02) after six sessions. Both sides of the face showed improvement of collagen bundles and elastic fibers characteristics after six sessions. CONCLUSIONS: The use of 2.5 mm depth proved to be more effective both clinically and histologically in the management of atrophic postacne scars.

Analytical interference of intravascular contrast agents with clinical laboratory tests: a joint guideline by the ESUR Contrast Media Safety Committee and the Preanalytical Phase Working Group of the EFLM Science Committee.

The Contrast Media Safety Committee of the European Society of Urogenital Radiology has, together with the Preanalytical Phase Working Group of the EFLM Science Committee, reviewed the literature and updated its recommendations to increase awareness and provide insight into these interferences. CLINICAL RELEVANCE STATEMENT: Contrast Media may interfere with clinical laboratory tests. Awareness of potential interference may prevent unwanted misdiagnosis. KEY POINTS: • Contrast Media may interfere with clinical laboratory tests; therefore awareness of potential interference may prevent unwanted misdiagnosis. • Clinical Laboratory tests should be performed prior to radiological imaging with contrast media or alternatively, blood or urine collection should be delayed, depending on kidney function.

Stimulus-Induced Relief of Intentionally Incorporated Frustration Drives Refolding of a Water-Soluble Biomimetic Foldamer.

Frustrated, or nonoptimal, interactions have been proposed to be essential to a protein's ability to display responsive behavior such as allostery, conformational signaling, and signal transduction. However, the intentional incorporation of frustrated noncovalent interactions has not been explored as a design element in the field of dynamic foldamers. Here, we report the design, synthesis, characterization, and molecular dynamics simulations of the first dynamic water-soluble foldamer that, in response to a stimulus, exploits relief of frustration in its noncovalent network to structurally rearrange from a pleated to an intercalated columnar structure. Thus, relief of frustration provides the energetic driving force for structural rearrangement. This work represents a previously unexplored design element for the development of stimulus-responsive systems that has potential application to materials chemistry, synthetic biology, and molecular machines.

Association of dyslipidemia with single nucleotide polymorphisms of the cholesteryl ester transfer protein gene and cardiovascular disease risk factors in a highly admixed population.

BACKGROUND AND AIMS: Cardiovascular diseases (CVD) are major causes of mortality worldwide, leading to premature deaths, loss of quality of life, and extensive socioeconomic impacts. Alterations in normal plasma lipid concentrations comprise important risk factors associated with CVD due to mechanisms involved in the pathophysiology of atherosclerosis. Genetic markers such as single nucleotide polymorphisms (SNPs) are known to be associated with lipid metabolism, including variants in the cholesteryl ester transfer protein (CETP) gene. Thus, the study's objective was to assess the relationship among lipid profile, socioeconomic and demographic characteristics, health status, inflammatory biomarkers, and CETP genetic variants in individuals living in a highly admixed population. METHODS: The study comprises an analysis of observational cross-sectional data representative at the population level from a highly admixed population, encompassing 901 individuals from three age groups (adolescents, adults, and older adults). Socioeconomic, demographic, health, and lifestyle characteristics were collected using semi-structured questionnaires. In addition, biochemical markers and lipid profiles were obtained from individuals' blood samples. After DNA extraction, genotyping, and quality control according to Affymetrix's guidelines, information on 15 SNPs in the CETP gene was available for 707 individuals. Lipid profile and CVD risk factors were evaluated by principal component analysis (PCA), and associations between lipid traits and those factors were assessed through multiple linear regression and logistic regression. RESULTS: There were low linear correlations between lipid profile and other individuals' characteristics. Two principal components were responsible for 80.8 % of the total variance, and there were minor differences in lipid profiles among individuals in different age groups. Non-HDL-c, total cholesterol, and LDL-c had the highest loadings in the first PC, and triacylglycerols, VLDL-c and HDL-c were responsible for a major part of the loading in the second PC;, whilst HDL-c and LDL-c/HDL-c ratio were significant in the third PC. In addition, there were minor differences between groups of individuals with or without dyslipidemia regarding inflammatory biomarkers (IL-1ß, IL- 6, IL-10, TNF-α, CRP, and MCP-1). Being overweight, insulin resistance, and lifestyle characteristics (calories from solid fat, added sugar, alcohol and sodium, leisure physical activity, and smoking) were strong predictors of lipid traits, especially HDL-c and dyslipidemia (p < 0.05). The CETP SNPs rs7499892 and rs12691052, rs291044, and rs80180245 were significantly associated with HDL-c (p < 0.05), and their inclusion in the multiple linear regression model increased its accuracy (adjusted R2 rose from 0.12 to 0.18). CONCLUSION: This study identified correlations between lipid traits and other CVD risk factors. In addition, similar lipid and inflammatory profiles across age groups in the population suggested that adolescents might already present a significant risk for developing cardiovascular diseases in the population. The risk can be primarily attributed to decreased HDL-c concentrations, which appear to be influenced by genetic factors, as evidenced by associations between SNPs in the CETP gene and HDL-c concentrations, as well as potential gene-diet interactions. Our findings underscore the significant impact of genetic and lifestyle factors on lipid profile within admixed populations in developing countries.

Expanded molecular detection of MPL codon p.W515 and p.S505N mutations in myeloproliferative neoplasms.

BACKGROUND: Patients negative for the JAK2 p.V617F somatic variant are frequently reflexed to testing for MPL exon 10 variants. Detection of these variants via multiplexed allele-specific PCR followed by fragment analysis has been previously published. The present study builds on this concept by improving the detection of the p.W515A variant, adding a second allele-specific primer to detect the p.W515R variant, and incorporating an improved primer for p.S505N detection. METHODS: The W515 amplification employs 5'-labeled allele-specific forward primers to detect p.W515K, p.W515L, p.W515R, and p.W515A. The p.S505N amplification includes an allele-specific reverse primer with a tail extension. Fragments were subject to capillary electrophoresis on an ABI 3500 Genetic Analyzer and analyzed using GeneMapper 6.0 (Thermo Fisher Scientific). RESULTS: Thirty MPL-negative and 13 MPL-positive samples previously tested by a reference laboratory were tested with the MPL LDT. Results were 100% concordant. The MPL LDT has a limit of detection of at least 5% VAF for the p.W515 variants and 10% VAF for the p.S505N variant. CONCLUSION: Current MPL assays are predominantly focused on p.W515L/K and p.S505N mutations. We have engineered an MPL test for detecting p.W515A/L/K/R and p.S505N variants, thereby increasing the diagnostic yield with little additional expense or technician time.