A bacterial protease depletes c-MYC and increases survival in mouse models of bladder and colon cancer.

Is the oncogene MYC upregulated or hyperactive? In the majority of human cancers, finding agents that target c-MYC has proved difficult. Here we report specific bacterial effector molecules that inhibit cellular MYC (c-MYC) in human cells. We show that uropathogenic Escherichia coli (UPEC) degrade the c-MYC protein and attenuate MYC expression in both human cells and animal tissues.

A pain science education and walking program to increase physical activity in people with symptomatic knee osteoarthritis: a feasibility study.

Introduction: Nine of 10 people with knee osteoarthritis are inactive. Unhelpful pain beliefs may negatively influence physical activity levels. Targeting these unhelpful pain beliefs, through contemporary pain science education (PSE), may provide benefit.

Antihistamine safety in older adult dermatologic patients.

Twenty percent of Americans will be older than 65 years by 2030, and without a dedicated geriatrics curriculum in many residency trainings programs, dermatologists may be less familiar with age-associated adverse effects of common dermatologic medications. Herein, we provide a practical guide and clinical safety pearls for the use of antihistamines in older adults. This Review aims to address the risks of antihistamines, anticholinergic burden and polypharmacy, pertinent preexisting medical conditions, and safe alternatives for aging adult patients.

Experiences of pregnant mothers using a social media based antenatal support service during the COVID-19 lockdown in the UK: findings from a user survey.

Objectives: The COVID-19 pandemic has seen unprecedented restrictions on face-to-face healthcare encounters. This has led to an increase in the use of online healthcare resources by service users. Pregnant women have always been a group particularly motivated to seek out information online.

Lateral segmental mandibulectomy reconstruction with bridging reconstruction plate and anterolateral thigh free flap: a case series of 30 consecutive patients.

Lateral posterior segmental mandibular defects present a reconstructive challenge and an osseous flap would be the gold standard to reconstruct such a defect. However, combining a mandibular reconstruction plate (MRP) with a soft-tissue free flap (to restore mucosal integrity and provide durable coverage of the plate itself) offers an alternative option for posterior segmental mandibular defects in patients who are not suitable for osseous reconstruction, or do not choose it. We retrospectively reviewed 30 consecutive patients (19 male and 11 female) who underwent reconstruction of a segmental mandibulectomy defect using a bridging MRP and anterolateral thigh (ALT) free flap.

Associations of diabetes self-management characteristics, HbA1c, and psychosocial outcomes with depressive symptoms in a contemporary sample of adolescents with type 1 diabetes.

Aims: We sought to examine the associations between diabetes self-management, HbA1c, and psychosocial outcomes with the frequency of depressive symptoms.

Methods: We surveyed 301 teens (50% male, 22% non-white), mean age of 15.0±1.

Performance Evaluation of Porous Graphene as Filter Media for the Removal of Pharmaceutical/Emerging Contaminants from Water and Wastewater.

Graphene and its counterparts have been widely used for the removal of contaminants from (waste)water but with limited success for the removal of pharmaceutical contaminants. Driven by this need, this study reports, for the first time, the removal of pharmaceuticals from real contaminated water samples using porous graphene (PG) as a filter-based column. This work systematically evaluates the performance of PG as a filter medium for the removal of widely consumed pharmaceutical/emerging contaminants (ECs) such as atenolol, carbamazepine, ciprofloxacin, diclofenac, gemfibrozil and ibuprofen.

Opioid Treatment for Neonatal Opioid Withdrawal Syndrome: Current Challenges and Future Approaches.

Chronic intrauterine exposure to psychoactive drugs often results in neonatal opioid withdrawal syndrome (NOWS). When nonpharmacologic measures are insufficient in controlling NOWS, morphine, methadone, and buprenorphine are first-line medications commonly used to treat infants with NOWS because of in utero exposure to opioids. Research suggests that buprenorphine may be the leading drug therapy used to treat NOWS when compared with morphine and methadone.

Cell-free DNA (cfDNA) and Exosome Profiling from a Year-Long Human Spaceflight Reveals Circulating Biomarkers.

Liquid biopsies based on cell-free DNA (cfDNA) or exosomes provide a noninvasive approach to monitor human health and disease but have not been utilized for astronauts. Here, we profile cfDNA characteristics, including fragment size, cellular deconvolution, and nucleosome positioning, in an astronaut during a year-long mission on the International Space Station, compared to his identical twin on Earth and healthy donors. We observed a significant increase in the proportion of cell-free mitochondrial DNA (cf-mtDNA) inflight, and analysis of post-flight exosomes in plasma revealed a 30-fold increase in circulating exosomes and patient-specific protein cargo (including brain-derived peptides) after the year-long mission.

Discordant neutralizing antibody and T cell responses in asymptomatic and mild SARS-CoV-2 infection.

Understanding the nature of immunity following mild/asymptomatic infection with SARS-CoV-2 is crucial to controlling the pandemic. We analyzed T cell and neutralizing antibody responses in 136 healthcare workers (HCW) 16-18 weeks after United Kingdom lockdown, 76 of whom had mild/asymptomatic SARS-CoV-2 infection captured by serial sampling. Neutralizing antibodies (nAb) were present in 89% of previously infected HCW.

Post-acute COVID-19 associated with evidence of bystander T-cell activation and a recurring antibiotic-resistant bacterial pneumonia.

Here, we describe the case of a COVID-19 patient who developed recurring ventilator-associated pneumonia caused by that acquired increasing levels of antimicrobial resistance (AMR) in response to treatment. Metagenomic analysis revealed the AMR genotype, while immunological analysis revealed massive and escalating levels of T-cell activation. These were both SARS-CoV-2 and specific, and bystander activated, which may have contributed to this patient's persistent symptoms and radiological changes.

Optimizing aminoglycoside selection for KPC-producing Klebsiella pneumoniae with the aminoglycoside-modifying enzyme (AME) gene aac(6')-Ib.

Objectives: KPC-producing Klebsiella pneumoniae (KPC-Kp) isolates commonly co-harbour the aminoglycoside-modifying enzyme (AME) gene aac(6')-Ib, which encodes an AME that can confer resistance to some of the commercially available aminoglycosides. We sought to determine the influence of AAC(6')-Ib in KPC-Kp on the pharmacodynamic activity of aminoglycosides.

Methods: Six KPC-Kp clinical isolates, three with and three without aac(6')-Ib, were analysed.

Active bacterial modification of the host environment through RNA polymerase II inhibition.

Unlike pathogens, which attack the host, commensal bacteria create a state of friendly coexistence. Here, we identified a mechanism of bacterial adaptation to the host niche, where they reside. Asymptomatic carrier strains were shown to inhibit RNA polymerase II (Pol II) in host cells by targeting Ser2 phosphorylation, a step required for productive mRNA elongation.

Transcriptional response modules characterize IL-1β and IL-6 activity in COVID-19.

Dysregulated IL-1β and IL-6 responses have been implicated in the pathogenesis of severe Coronavirus Disease 2019 (COVID-19). Innovative approaches for evaluating the biological activity of these cytokines are urgently needed to complement clinical trials of therapeutic targeting of IL-1β and IL-6 in COVID-19. We show that the expression of IL-1β or IL-6 inducible transcriptional signatures (modules) reflects the bioactivity of these cytokines in immunopathology modelled by juvenile idiopathic arthritis (JIA) and rheumatoid arthritis.

Transcriptional response modules characterise IL-1β and IL-6 activity in COVID-19.

Dysregulated IL-1β and IL-6 responses have been implicated in the pathogenesis of severe Coronavirus Disease 2019 (COVID-19). Innovative approaches for evaluating the biological activity of these cytokines are urgently needed to complement clinical trials of therapeutic targeting of IL-1β and IL-6 in COVID-19. We show that the expression of IL-1β or IL-6 inducible transcriptional signatures (modules) reflects the bioactivity of these cytokines in immunopathology modelled by juvenile idiopathic arthritis (JIA) and rheumatoid arthritis.

Innovative features and functionalities of an artificial pancreas system: What do youth and parents want?

Aims: Participant-driven solutions may help youth and families better engage and maintain use of diabetes technologies. We explored innovative features and functionalities of an ideal artificial pancreas (AP) system suggested by youth with type 1 diabetes and parents.

Methods: Semi-structured interviews were conducted with 39 youth, ages 10-25 years, and 44 parents.

Anaerobic Soil Disinfestation Efficacy Against Is Affected by Soil Temperature, Amendment Type, Rate, and C:N Ratio.

A meta-analysis of anaerobic soil disinfestation (ASD) efficacy against and f. sp. was conducted emphasizing effects of environment and organic amendment characteristics and pot and field studies conducted on ASD amendment C:N ratio and soil temperature effects on f.

Temporal Telomere and DNA Damage Responses in the Space Radiation Environment.

Telomeres, repetitive terminal features of chromosomes essential for maintaining genome integrity, shorten with cell division, lifestyle factors and stresses, and environmental exposures, and so they provide a robust biomarker of health, aging, and age-related diseases. We assessed telomere length dynamics (changes over time) in three unrelated astronauts before, during, and after 1-year or 6-month missions aboard the International Space Station (ISS). Similar to our results for National Aeronautics and Space Administration's (NASA's) One-Year Mission twin astronaut (Garrett-Bakelman et al.

Circulating miRNA Spaceflight Signature Reveals Targets for Countermeasure Development.

We have identified and validated a spaceflight-associated microRNA (miRNA) signature that is shared by rodents and humans in response to simulated, short-duration and long-duration spaceflight. Previous studies have identified miRNAs that regulate rodent responses to spaceflight in low-Earth orbit, and we have confirmed the expression of these proposed spaceflight-associated miRNAs in rodents reacting to simulated spaceflight conditions. Moreover, astronaut samples from the NASA Twins Study confirmed these expression signatures in miRNA sequencing, single-cell RNA sequencing (scRNA-seq), and single-cell assay for transposase accessible chromatin (scATAC-seq) data.

Multi-omic, Single-Cell, and Biochemical Profiles of Astronauts Guide Pharmacological Strategies for Returning to Gravity.

The National Aeronautics and Space Administration (NASA) Twins Study created an integrative molecular profile of an astronaut during NASA's first 1-year mission on the International Space Station (ISS) and included comparisons to an identical Earth-bound twin. The unique biochemical profiles observed when landing on Earth after such a long mission (e.g.

Telomere Length Dynamics and DNA Damage Responses Associated with Long-Duration Spaceflight.

Telomere length dynamics and DNA damage responses were assessed before, during, and after one-year or shorter duration missions aboard the International Space Station (ISS) in a comparatively large cohort of astronauts (n = 11). Although generally healthy individuals, astronauts tended to have significantly shorter telomeres and lower telomerase activity than age- and sex-matched ground controls before and after spaceflight. Although telomeres were longer during spaceflight irrespective of mission duration, telomere length shortened rapidly upon return to Earth, and overall astronauts had shorter telomeres after spaceflight than they did before; inter-individual differences were identified.

Clonal Hematopoiesis Before, During, and After Human Spaceflight.

Clonal hematopoiesis (CH) occurs when blood cells harboring an advantageous mutation propagate faster than others. These mutations confer a risk for hematological cancers and cardiovascular disease. Here, we analyze CH in blood samples from a pair of twin astronauts over 4 years in bulk and fractionated cell populations using a targeted CH panel, linked-read whole-genome sequencing, and deep RNA sequencing.