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DNA methylation is a major control program that modulates gene expression in a plethora of organisms. Gene silencing through methylation occurs through the activity of DNA methyltransferases, enzymes that transfer a methyl group from S-adenosyl-L-methionine to the carbon 5 position of cytosine. DNA methylation patterns are established by the de novo DNA methyltransferases (DNMTs) DNMT3A and DNMT3B and are subsequently maintained by DNMT1. Aging and age-related diseases include defined changes in 5-methylcytosine content and are generally characterized by genome-wide hypomethylation and promoter-specific hypermethylation. These changes in the epigenetic landscape represent potential disease biomarkers and are thought to contribute to age-related pathologies, such as cancer, osteoarthritis, and neurodegeneration. Some diseases, such as a hereditary form of sensory neuropathy accompanied by dementia, are directly caused by methylomic changes. Epigenetic modifications, however, are reversible and are therefore a prime target for therapeutic intervention. Numerous drugs that specifically target DNMTs are being tested in ongoing clinical trials for a variety of cancers, and data from finished trials demonstrate that some, such as 5-azacytidine, may even be superior to standard care. DNMTs, demethylases, and associated partners are dynamically shaping the methylome and demonstrate great promise with regard to rejuvenation. [ABSTRACT FROM AUTHOR]

OBJECTIVES: The objective of this study was to identify the determinants of late prenatal care (PNC) initiation among minority women in Washington, DC. METHODS: DC-resident, African American women (n = 303) were recruited at 14 PNC facilities, representing the various types of PNC facilities located in DC: 4 hospital-based clinics, 5 community-based clinics, and 5 private practices. The women were interviewed at their first prenatal care visits to determine their perceptions of 63 barriers, motivators and facilitators influencing PNC initiation; substance use; and sociodemographic background. PNC initiation was classified as early (prior to the 20th week of gestation) or late (after the 20th week of gestation). The responses of women who initiated PNC early versus late were compared using bivariate and multivariate statistical procedures. Classification and Regression Trees analysis was used to identify groups at risk of late initiation. RESULTS: Variables contributing to late PNC initiation included maternal age not between 20 and 29 years, unemployment, no history of previous abortions, consideration of abortion, lack of money to pay for PNC, and no motivation to learn how to protect ones health. Three risk groups for late PNC initiation included 1) women consideringabortion and not employed outside their homes; 2) women not considering abortion who had no previous abortion experience; and 3) teenagers not considering abortion and with no previous abortions. CONCLUSIONS: The results of this study indicate that psychosocial barriers are more important than structural barriers. Of the psychosocial barriers, the major determinants of late PNC initiation were consideration of abortion and previous abortion experience. [ABSTRACT FROM AUTHOR]

Abstract Background Altered permeability of the blood–brain barrier (BBB) is a feature of numerous neurological conditions including multiple sclerosis, cerebral malaria, viral hemorrhagic fevers and acute hemorrhagic leukoencephalitis. Our laboratory has developed a murine model of CD8 T cell-initiated central nervous system (CNS) vascular permeability in which vascular endothelial growth factor (VEGF) signaling plays a prominent role in BBB disruption. Findings In this study, we addressed the hypothesis that in vivo blockade of VEGF signal transduction through administration of peptide (ATWLPPR) to inhibit neuropilin-1 (NRP-1) would have a therapeutic effect following induction of CD8 T cell-initiated BBB disruption. We report that inhibition of NRP-1, a co-receptor that enhances VEGFR2 (flk-1) receptor activation, decreases vascular permeability, brain hemorrhage, and mortality in this model of CD8 T cell-initiated BBB disruption. We also examine the expression pattern of VEGFR2 (flk-1) and VEGFR1 (flt-1) mRNA expression during a time course of this condition. We find that viral infection of the brain leads to increased expression of flk-1 mRNA. In addition, flk-1 and flt-1 expression levels decrease in the striatum and hippocampus in later time points following induction of CD8 T cell-mediated BBB disruption. Conclusion This study demonstrates that NRP-1 is a potential therapeutic target in neuro-inflammatory diseases involving BBB disruption and brain hemorrhage. Additionally, the reduction in VEGF receptors subsequent to BBB disruption could be involved in compensatory negative feedback as an attempt to reduce vascular permeability.

Abstract Background Chronic ankle stiffness can develop for numerous reasons after traumatic injury, and may adversely affect patient gait, mobility, and function. Although standard physical therapeutic techniques typically resolve this stiffness, some cases may be recalcitrant to these measures, making it difficult to restore range-of-motion. The purpose of this study was to evaluate a static progressive stretch orthosis for the treatment of chronic ankle stiffness. Methods Twenty-six patients (26 ankles) who had chronic post-traumatic ankle stiffness were studied. The patients began treatment at a mean of 47 weeks (range, 6 to 272 weeks) following their initial injury using a static progressive stretch orthosis. A patient-directed protocol was used for 30 minutes per day, 1 to 3 times per day, until the range-of-motion was considered to have plateaued. Mean treatment time was 10 weeks (range, 3 to 19 weeks). Treatment duration, range-of-motion, and complications with the device were assessed. Results The overall mean improvement in motion (combined dorsiflexion and plantar flexion) was 17 degrees (range, 2 to 44 degrees). There was a mean improvement in dorsiflexion of 9 degrees (range, -2 to 20 degrees), and a mean improvement of 8 degrees of plantar flexion (range, -10 to 35 degrees). There were no reports of numbness or skin problems. Conclusions The outcomes of this study suggest that a patient-directed treatment protocol using a static progressive stretch orthosis was an effective ancillary method for the treatment of chronic post-traumatic ankle stiffness that was refractory to standard physical therapy techniques.

Abstract Background The extent to which susceptibility to brain hemorrhage is derived from blood-derived factors or stromal tissue remains largely unknown. We have developed an inducible model of CD8 T cell-initiated blood-brain barrier (BBB) disruption using a variation of the Theiler's murine encephalomyelitis virus (TMEV) model of multiple sclerosis. This peptide-induced fatal syndrome (PIFS) model results in severe central nervous system (CNS) vascular permeability and death in the C57BL/6 mouse strain, but not in the 129 SvIm mouse strain, despite the two strains' having indistinguishable CD8 T-cell responses. Therefore, we hypothesize that hematopoietic factors contribute to susceptibility to brain hemorrhage, CNS vascular permeability and death following induction of PIFS. Methods PIFS was induced by intravenous injection of VP2121-130 peptide at 7 days post-TMEV infection. We then investigated brain inflammation, astrocyte activation, vascular permeability, functional deficit and microhemorrhage formation using T2*-weighted magnetic resonance imaging (MRI) in C57BL/6 and 129 SvIm mice. To investigate the contribution of hematopoietic cells in this model, hemorrhage-resistant 129 SvIm mice were reconstituted with C57BL/6 or autologous 129 SvIm bone marrow. Gadolinium-enhanced, T1-weighted MRI was used to visualize the extent of CNS vascular permeability after bone marrow transfer. Results C57BL/6 and 129 SvIm mice had similar inflammation in the CNS during acute infection. After administration of VP2121-130 peptide, however, C57BL/6 mice had increased astrocyte activation, CNS vascular permeability, microhemorrhage formation and functional deficits compared to 129 SvIm mice. The 129 SvIm mice reconstituted with C57BL/6 but not autologous bone marrow had increased microhemorrhage formation as measured by T2*-weighted MRI, exhibited a profound increase in CNS vascular permeability as measured by three-dimensional volumetric analysis of gadolinium-enhanced, T1-weighted MRI, and became moribund in this model system. Conclusion C57BL/6 mice are highly susceptible to microhemorrhage formation, severe CNS vascular permeability and morbidity compared to the 129 SvIm mouse. This susceptibility is transferable with the bone marrow compartment, demonstrating that hematopoietic factors are responsible for the onset of brain microhemorrhage and vascular permeability in immune-mediated fatal BBB disruption.

Abstract Background Recent studies suggest that there is a learning curve for metal-on-metal hip resurfacing. The purpose of this study was to assess whether implant positioning changed with surgeon experience and whether positioning and component sizing were associated with implant longevity. Methods We evaluated the first 361 consecutive hip resurfacings performed by a single surgeon, which had a mean follow-up of 59 months (range, 28 to 87 months). Pre and post-operative radiographs were assessed to determine the inclination of the acetabular component, as well as the sagittal and coronal femoral stem-neck angles. Changes in the precision of component placement were determined by assessing changes in the standard deviation of each measurement using variance ratio and linear regression analysis. Additionally, the cup and stem-shaft angles as well as component sizes were compared between the 31 hips that failed over the follow-up period and the surviving components to assess for any differences that might have been associated with an increased risk for failure. Results Surgeon experience was correlated with improved precision of the antero-posterior and lateral positioning of the femoral component. However, femoral and acetabular radiographic implant positioning angles were not different between the surviving hips and failures. The failures had smaller mean femoral component diameters as compared to the non-failure group (44 versus 47 millimeters). Conclusions These results suggest that there may be differences in implant positioning in early versus late learning curve procedures, but that in the absence of recognized risk factors such as intra-operative notching of the femoral neck and cup inclination in excess of 50 degrees, component positioning does not appear to be associated with failure. Nevertheless, surgeons should exercise caution in operating patients with small femoral necks, especially when they are early in the learning curve.

Abstract Acute hemorrhagic leukoencephalomyelitis (AHLE) is a rare neurological condition characterized by the development of acute hemorrhagic demyelination and high mortality. The pathomechanism of AHLE, as well as potential therapeutic approaches, have remained elusive due to the lack of suitable animal models. We report the first murine model of AHLE using a variation of the Theiler's Murine Encephalitis Virus (TMEV) MS model. During acute TMEV infection, C57BL/6 mice do not normally undergo demyelination. However, when 7 day TMEV infected C57BL/6 mice are intravenously administered the immunodominant CD8 T cell peptide, VP2121–130, animals develop characteristics of human AHLE based on pathologic, MRI and clinical features including microhemorrhages, increased blood-brain barrier permeability, and demyelination. The animals also develop severe disability as assessed using the rotarod assay. This study demonstrates the development of hemorrhagic demyelination in TMEV infected C57BL/6 mice within 24 hours of inducing this condition through intravenous administration of CD8 T cell restricted peptide. This study is also the first demonstration of rapid demyelination in a TMEV resistant non-demyelinating strain without transgenic alterations or pharmacologically induced immunosuppression.

Objective: We hypothesized that learning through multiple sensory modalities would improve knowledge recall and recognition in orthopedic surgery residents and medical students., Design: We developed a virtual study assistant, named Socratic Artificial Intelligence Learning (SAIL), based on a custom-built natural language processing algorithm. SAIL draws from practice questions approved by the American Board of Orthopaedic Surgery and quizzes users through a conversational, voice-enabled Web interface. We performed a randomized controlled study using a within-subjects, repeated measures design., Setting: Participants first took a pretest to assess their baseline knowledge. They then underwent 10 days of spaced repetition training with practice questions using 3 modalities: oral response, typed response, and multiple-choice. Recall and recognition of the practiced knowledge were assessed via a post-test administered on the first day, first week, and 2 months after the training period., Participants: Twenty-four volunteers, who were medical students and orthopedic surgery residents at multiple US medical institutions., Results: The oral, typed, and multiple-choice modalities produced similar recall and recognition rates. Although participants preferred using the traditional multiple-choice modality to study for standardized examinations, many were interested in supplementing their study routine with SAIL and believe that SAIL may improve their performance on written and oral examinations., Conclusions: SAIL is not inferior to the multiple-choice modality for learning orthopedic core knowledge. These results indicate that SAIL can be used to supplement traditional study methods. COMPETENCIES: medical knowledge; practice-based learning and improvement., (Copyright © 2024 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Usage of the phrase "biological age" has picked up considerably since the advent of aging clocks and it has become commonplace to describe an aging clock's output as biological age. In contrast to this labeling, biological age is also often depicted as a more abstract concept that helps explain how individuals are aging internally, externally, and functionally. Given that the bulk of molecular aging is tissue-specific and aging itself is a remarkably complex, multifarious process, it is unsurprising that most surveyed scientists agree that aging cannot be quantified via a single metric. We share this sentiment and argue that, just like it would not be reasonable to assume that an individual with an ideal grip strength, VO 2 max, or any other aging biomarker is biologically young, we should be careful not to conflate an aging clock with whole-body biological aging. To address this, we recommend that researchers describe the output of an aging clock based on the type of input data used or the name of the clock itself. Epigenetic aging clocks produce epigenetic age, transcriptomic aging clocks produce transcriptomic age, and so forth. If a clock has a unique name, such as our recently developed epigenetic aging clock CheekAge, the name of the clock can double as the output. As a compromise solution, aging biomarkers can be described as indicators of biological age. We feel that these recommendations will help scientists and the public differentiate between aging biomarkers and the much more elusive concept of biological age., (© 2024 Tally Health. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

While earlier first-generation epigenetic aging clocks were trained to estimate chronological age as accurately as possible, more recent next-generation clocks incorporate DNA methylation information more pertinent to health, lifestyle, and/or outcomes. Recently, we produced a non-invasive next-generation epigenetic clock trained using Infinium MethylationEPIC data from more than 8,000 diverse adult buccal samples. While this clock correlated with various health, lifestyle, and disease factors, we did not assess its ability to capture mortality. To address this gap, we applied CheekAge to the longitudinal Lothian Birth Cohorts of 1921 and 1936. Despite missing nearly half of its CpG inputs, CheekAge was significantly associated with mortality in this longitudinal blood dataset. Specifically, a change in one standard deviation corresponded to a hazard ratio (HR) of 1.21 (FDR q = 1.66e-6). CheekAge performed better than all first-generation clocks tested and displayed a comparable HR to the next-generation, blood-trained DNAm PhenoAge clock (HR = 1.23, q = 2.45e-9). To better understand the relative importance of each CheekAge input in blood, we iteratively removed each clock CpG and re-calculated the overall mortality association. The most significant effect came from omitting the CpG cg14386193, which is annotated to the gene ALPK2 . Excluding this DNA methylation site increased the FDR value by nearly threefold (to 4.92e-06). We additionally performed enrichment analyses of the top annotated CpGs that impact mortality to better understand their associated biology. Taken together, we provide important validation for CheekAge and highlight novel CpGs that underlie a newly identified mortality association., Competing Interests: MS, DK, TC, and AJ are all current or former full-time employees of the company Tally Health. The authors declare that this study received funding from Tally Health, NY, USA. The funder had the following involvement in the study: publication fee. The authors have no other conflicts of interest to declare., (Copyright © 2024 Shokhirev, Kramer, Corley, Cox, Cuellar and Johnson.)

The Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative reassesses using the inhibition of hERG potassium channels by drugs as the major determinant for the potential to cause drug-induced Torsades de Pointes (TdP) cardiac arrhythmias. Here we report our findings on the next phase of CiPA: Determination of hERG inhibitory properties using the standard CiPA-defined data acquisition protocol, here called the standard protocol, at physiological temperature (37 degrees Celsius). To do this, we measured inhibition of hERG1a potassium channels stably expressed in HEK293 cells by the small molecule verapamil, using manual whole-cell patch-clamp electrophysiology recordings with the standard protocol, which is characterized, in part, by a series of 10 s duration voltage steps to 0 mV, ultimately leading to a cumulative recording time of approximately 30 min. Using the standard protocol, we measured an IC 50 for verapamil of 225 nM, a Hill coefficient of 1, and time constant of inhibition at 0 mV of 0.64 s. But, using the standard protocol resulted in a very low (5 %) experimental success rate per cell, which had low practicality for future experiments. To address the 5 % success rate, we generated a revised protocol characterized, in part, by a series of 3 s duration voltage steps to 0 mV, leading to a cumulative recording time of approximately 10 min. Using the revised protocol, we found an IC 50 for verapamil of 252 nM, a Hill coefficient of 0.8, and time constant of inhibition at 0 mV of 0.67 s. The values measured with the revised protocol were similar to those measured using the standard protocol and, furthermore, our success rate using the revised protocol rose to 25 %, an increase of 5-fold over the standard protocol, and more in line with the success rate for biophysical studies. In summary, we captured key pharmacological data for subsequent analysis in CiPA using a revised protocol with an increased success rate and an overall enhanced feasibility and practicality. We propose that the revised protocol may be more pragmatic for generation of some hERG channel drug inhibition data for CiPA and other regulatory sciences., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Objective: We sought to evaluate accurate and reproducible detection of Myxobolus cerebralis (Mc), the causative agent of whirling disease, by using nested polymerase chain reaction (nPCR) and three previously established real-time quantitative PCR (qPCR) assays: K18S (Kelley 18S), C18S (Cavender 18S), and Hsp70 (heat shock protein 70). We used a "fit for purpose" approach combined with intra- and interlaboratory testing to identify a molecular testing method that would be equivalent to the currently accepted nPCR procedure for Mc., Methods: Assay performance was compared using a combination of intra- and interlaboratory testing that used synthetic gBlocks along with naturally and experimentally infected fish tissue. North American isolates representing geographically distinct locations were also tested using all three assays., Result: The K18S and C18S assays exhibited high assay sensitivity, intra- and interlaboratory repeatability of sample replicates, and reproducible identification of all test samples across multiple laboratories. In contrast, the Hsp70 assay failed to detect several positive samples at low DNA concentrations during intra- and interlaboratory testing. The K18S assay was the only procedure that demonstrated perfect detection accuracy when testing geographically distinct Mc isolates. Results demonstrated the K18S assay is robust under variable test conditions, is more accurate than the C18S and Hsp70 assays, and provides detection capabilities equivalent to those of the currently accepted nPCR confirmation assay "gold standard" that is described in the American Fisheries Society-Fish Health Section (AFS-FHS) Blue Book., Conclusion: The "fit for purpose" approach and preliminary completion of the World Organization for Animal Health validation pathway demonstrate that the K18S assay provides an alternate method for Mc testing. This work provides the foundation for acceptance of the K18S assay into the AFS-FHS Blue Book as a standardized test procedure for Mc., (© 2024 American Fisheries Society.)

Friction from knitted clothing can cause discomfort and skin issues, underscoring the importance of tactile comfort for wearers. Seamless knitted garments are assumed to be comfortable to wear, yet there is little understanding of their tactile comfort in comparison to linked seams - the most common form of knitted garment. This novel study examines the influence of a garments knitted structural architecture on clothing comfort and wearability by investigating skin friction and tactile perception across ten body regions in both male and female participants, using two commonly utilised materials and seam designs: cotton and merino wool with plain and linked seams. The impact of seam design and regional factors on skin friction and tactile perception was analysed, revealing varying levels across tested body regions. Removing seams exposed a greater surface area to skin contact, leading to higher perceived friction levels. As such, structural elements in knitted garments enhance wearer comfort.

Background: Advance care planning (ACP) is the process of having conversations with patients to ensure preferences are known and support patient healthcare goals. ACP and the Age-Friendly Health Systems (AFHS) Initiative's, "What Matters," are synergistic approaches to patient-centered conversations. Implementation and measurement of ACP in primary care (PC) are variables in quality and consistency. We examined whether participation in an ACP learning collaborative (LC) would improve knowledge and ability to conduct ACP discussions and increase the frequency of documented ACP in participating practices., Methods: The WWAMI (Washington, Wyoming, Alaska, Montana, and Idaho) region Practice and Research Network (WPRN) and the Northwest Geriatrics Workforce Enhancement Center collaboratively organized a 9-month virtual LC. It consisted of 4 synchronous, 1.5-h sessions, technical support, and a panel of ACP experts. A Wilcoxon rank sum test assessed differences in knowledge from a pre-post survey. Documentation of ACP in the EHR was collected after at least one plan-do-study-act cycle., Results: We enrolled 17 participants from 6 PC practices (3 hospital-affiliated; 3 Federally Qualified Health Centers) from the WPRN. Two practices did not complete all LC activities. There was a trend toward increased ACP knowledge and skills overall especially in having discussions patients and families (pre-mean 2.9 [SD = 0.7]/post-mean 4.0[SD = 1.1], p < 0.05). 4/6 practices observed an increase in EHR documentation post-collaborative (median 16.3%, IQR 1.3%-36.9%)., Conclusions: The LC increased PC providers knowledge and skills of ACP and AFHS's What Matters, reported ACP EHR documentation, and contributed to practice change., (© 2024 The Author(s). Journal of the American Geriatrics Society published by Wiley Periodicals LLC on behalf of The American Geriatrics Society.)

Globally, approximately 400,000 youth are diagnosed with pediatric cancer each year. Treatment-related side effects, psychosocial challenges, and frequent school absences may adversely impact learning and the education experience among these youth. Efforts to enhance interagency collaboration between health care settings and community schools are imperative to facilitate school reintegration. The Standards for the Psychosocial Care of Children with Cancer and Their Families outline specific guidelines related to the continuity of education for students impacted by pediatric cancer. In particular, the Academic Continuity and School Reentry Support and Monitoring and Assessment of Neuropsychological Outcomes standards of care highlighted within this article align with extant programmatic efforts for transitioning hospitalized school-aged children back into community schools. This article aims to describe systematic programmatic efforts within hospital-based psychosocial programs that are consistent with the Standards for the Psychosocial Care of Children with Cancer and Their Families, as well as interagency collaboration with community schools to support student-centered education for youth impacted by pediatric cancer. Resources for school psychologists, teachers, hospital-based programs, and others involved in student-centered education for pediatric cancer patients and survivors are presented. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Epigenetic aging clocks are computational models that predict age using DNA methylation information. Initially, first-generation clocks were developed to make predictions using CpGs that change with age. Over time, next-generation clocks were created using CpGs that relate to both age and health. Since existing next-generation clocks were constructed in blood, we sought to develop a next-generation clock optimized for prediction in cheek swabs, which are non-invasive and easy to collect. To do this, we collected MethylationEPIC data as well as lifestyle and health information from 8045 diverse adults. Using a novel simulated annealing approach that allowed us to incorporate lifestyle and health factors into training as well as a combination of CpG filtering, CpG clustering, and clock ensembling, we constructed CheekAge, an epigenetic aging clock that has a strong correlation with age, displays high test-retest reproducibility across replicates, and significantly associates with a plethora of lifestyle and health factors, such as BMI, smoking status, and alcohol intake. We validated CheekAge in an internal dataset and multiple publicly available datasets, including samples from patients with progeria or meningioma. In addition to exploring the underlying biology of the data and clock, we provide a free online tool that allows users to mine our methylomic data and predict epigenetic age., (© 2024. The Author(s).)

Objectives: A working group conducted a survey on the use of the principle of buffer space (BS), which in case of emergencies, could benefit healthcare settings. The aim of the preliminary investigation is to define new research lines in hospitals' functional design., Background: The global experience of the COVID-19 pandemic highlighted challenges faced by hospitals when responding promptly to emergencies, including spatial reorganization and suspension of ordinary medical activities for ensuring adequate management of the emergency surge of patients., Methods: The group designed questionnaires to be administered to healthcare staff and healthcare designers aimed at understanding varied conceptions and features of BSs. Content across the two surveys overlapped significantly, allowing for direct comparisons of responses, while also including tailored questions in relation to the respective experience and skills of the two groups of respondents., Results: 102 healthcare professionals and 56 designers took part to the survey. Analysis of the responses permitted for initial recommendations regarding BS typology including (a) proximity to the emergency department (ED), intensive care units (ICUs), and inpatient wards (IWs); (b) location within hospitals but separate from other medical areas; (c) need for independent access; (d) organizational and spatial features similar to ED, ICUs, and IWs; (e) existing as a fully flexible operational space; and (f) BS bed capacity to be approximately 12% of ED beds., Conclusions: Although the analysis is related to the Italian context, the expansion of this preliminary research to alternate healthcare facilities and geographic areas is necessary for reaching a wide consensus by different professionals on this field. It serves as a starting point for future investigations regarding the implementation of BS in hospital settings., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

We report genome sequences of six mycobacteriophages. Each virus was isolated from a soil sample and belongs to the siphovirus morphology. Genomes are 41,901-60,613 bp in length, contain between 62 and 103 protein-coding genes, with up to 40% of those genes having a predicted function., Competing Interests: The authors declare no conflict of interest.

Human astrovirus (HAstV) is a nonenveloped RNA virus and has been implicated in acute gastroenteritis among children and elderly. However, there exists a substantial dearth of information on HAstV strains circulating in Nigeria. Viral-like particles were purified from archived 254 stool samples of children with acute flaccid paralysis between January and December 2020 from five states in Nigeria, using the NetoVIR protocol. Extracted viral RNA and DNA were subjected to a reverse transcription step and subsequent random polymerase chain reaction amplification. Library preparation and Illumina sequencing were performed. Using the virome paired-end reads pipeline, raw reads were processed into genomic contigs. Phylogenetic and pairwise identity analysis of the recovered HAstV genomes was performed. Six near-complete genome sequences of HAstV were identified and classified as HAstV4 (n = 1), HAstV5 (n = 1), HAstV8 (n = 1), and MLB-3 (n = 3). The HAstV5 belonged to a yet unclassified sublineage, which we tentatively named HAstV-5d. Phylogenetic analysis of open reading frames 1a, 1b, and 2 suggested recombination events inside the MAstV1 species. Furthermore, phylogenetic analysis implied a geographic linkage between the HAstV5 strain from this study with two strains from Cameroon across all the genomic regions. We report for the first time the circulation of HAstV genotypes 4, 8, and MLB-3 in Nigeria and present data suggestive for the existence of a new sublineage of HAstV5. To further understand the burden, diversity, and evolution of HAstV, increased research interest as well as robust HAstV surveillance in Nigeria is essential., (© 2024 Wiley Periodicals LLC.)

NAD + , a pivotal coenzyme central to metabolism, exhibits a characteristic decline with age. In mice, NAD + levels can be elevated via treatment with apigenin, a natural flavonoid that inhibits the NAD + -consuming glycoprotein CD38. In animal models, apigenin positively impacts both sleep and longevity. For example, apigenin improves learning and memory in older mice, reduces tumor proliferation in a mouse xenograft model of triple-negative breast cancer, and induces sedative effects in mice and rats. Moreover, apigenin elongates survival in fly models of neurodegenerative disease and apigenin glycosides increase lifespan in worms. Apigenin's therapeutic potential is underscored by human clinical studies using chamomile extract, which contains apigenin as an active ingredient. Collectively, chamomile extract has been reported to alleviate anxiety, improve mood, and relieve pain. Furthermore, dietary apigenin intake positively correlates with sleep quality in a large cohort of adults. Apigenin's electron-rich flavonoid structure gives it strong bonding capacity to diverse molecular structures across receptors and enzymes. The effects of apigenin extend beyond CD38 inhibition, encompassing agonistic and antagonistic modulation of various targets, including GABA and inflammatory pathways. Cumulatively, a large body of evidence positions apigenin as a unique molecule capable of influencing both aging and sleep. Further studies are warranted to better understand apigenin's nuanced mechanisms and clinical potential., Competing Interests: DK and AJ are full-time employees of Tally Health (New York, NY, United States). The authors declare that this study received funding from Tally Health, NY, USA. The funder had the following involvement in the study: publication fee. The authors have no other conflicts of interest to declare., (Copyright © 2024 Kramer and Johnson.)

The clothing fabric and skin interact continuously across the many regions of users' bodies during wear, which can lead to both physical skin damage and discomfort. Therefore, this investigation aimed to explore the regional differences in skin friction, tactile perception, and sensitivity in both females and males during the skin-textile interaction. The static and dynamic friction coefficient and textile perception (texture, stickiness, pleasantness, and discomfort) were measured across the 36 selected testing body areas by using a friction measurement device. The results revealed there was a significant difference in skin friction, tactile perceptions, and sensitivity across the various body regions. The anterior neck had the highest skin friction in both females and males, and participants generally rated higher texture perception in their anterior aspects compared to posterior and lateral regions. There was no significant difference in skin friction, tactile perception ratings, and sensitivity between females and males. Practitioner summary: This study sought to examine regional variations in skin friction, tactile perception, and sensitivity during the skin-textile interaction. There was a significant difference in skin friction, tactile perceptions, and sensitivity across the various body regions and no significant sex effect on skin friction, tactile perception ratings, and sensitivity.

Five subcluster C1 mycobacteriophages, Blackbrain, Cactojaque, Kboogie, Trinitium, and YoungMoneyMata, were isolated from soil using the host Mycobacterium smegmatis mc 2 155. The genome sizes range from 154,512 to 156,223 bp. The largest genome encodes 237 predicted proteins, 34 tRNAs, and 1 transfer-messenger RNA (tmRNA)., Competing Interests: The authors declare no conflict of interest.

In this randomized study, use of alcohol-based hand-rub disinfection significantly reduced bacterial bioburden of stethoscopes in routine clinical use. Prior cleaning of stethoscopes on the study day did not affect baseline contamination rates, which suggests that the efficacy of alcohol disinfection is short-lived and may need to be repeated between patients.

The restriction of calories, branched-chain amino acids, and methionine have all been shown to extend lifespan in model organisms. Recently, glycine was found to boost longevity in genetically heterogenous mice. This simple amino acid similarly extends lifespan in rats and improves health in mammalian models of age-related disease. While compelling data indicate that glycine is a pro-longevity molecule, divergent mechanisms may underlie its effects on aging. Glycine is abundant in collagen, a building block for glutathione, a precursor to creatine, and an acceptor for the enzyme glycine N-methyltransferase (GNMT). A review of the literature strongly implicates GNMT, which clears methionine from the body by taking a methyl group from S-adenosyl-L-methionine and methylating glycine to form sarcosine. In flies, Gnmt is required for reduced insulin/insulin-like growth factor 1 signaling and dietary restriction to fully extend lifespan. The geroprotector spermidine requires Gnmt to upregulate autophagy genes and boost longevity. Moreover, the overexpression of Gnmt is sufficient to extend lifespan and reduce methionine levels. Sarcosine, or methylglycine, declines with age in multiple species and is capable of inducing autophagy both in vitro and in vivo. Taken all together, existing evidence suggests that glycine prolongs life by mimicking methionine restriction and activating autophagy., Competing Interests: Declaration of Competing Interest All authors are full-time employees of the biotechnology company Tally Health, Inc. The authors have no other conflicts of interest to declare., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: This study aims to provide metadesign indications for the improvement of healthcare facilities, emphasizing the role of spatial design in the management of epidemic health emergencies., Study Design: A parallel mixed-method study including literature reviews, survey creation, and survey distribution was performed., Methods: Data were collected between August and October 2020 capturing information related to the first wave of the COVID-19 pandemic, utilizing a review of existing literature, a comparison of existing hospital planning guidelines and assessment tools, and distribution of a survey to analyze design changes within selected Italian hospitals., Results: Among the changes identified, the most frequently identified included the conversion of space into intensive care units, space expansion, and the usage of wayfinding strategies for the reduction of cross-contamination risks. There was limited attention given to solutions with a human-centered approach, and those that addressed physical and psychological well-being of all users, including healthcare staff. The solutions were collected and systematized into a list of metadesign guidelines., Conclusions: The resulting indications represent a starting point for developing design solutions to aid healthcare facilities in facing future epidemics.

Bacteriophage genomes represent an enormous level of genetic diversity and provide considerable potential to acquire new insights about viral genome evolution. In this study, the genome sequences of sixteen Bacillus -infecting bacteriophages were explored through comparative genomics approaches to reveal shared and unique characteristics. These bacteriophages are in the Salasmaviridae family with small (18,548-27,206 bp) double-stranded DNA genomes encoding 25-46 predicted open reading frames. We observe extensive nucleotide and amino acid sequence divergence among a set of core-function genes that present clear synteny. We identify two examples of sequence directed recombination within essential genes, as well as explore the expansion of gene content in these genomes through the introduction of novel open reading frames. Together, these findings highlight the complex evolutionary relationships of phage genomes that include old, common origins as well as new components introduced through mosaicism.

Alzheimer's disease (AD) is an incredibly complex and presently incurable age-related brain disorder. To better understand this debilitating disease, we collated and performed a meta-analysis on publicly available RNA-Seq, microarray, proteomics, and microRNA samples derived from AD patients and non-AD controls. 4089 samples originating from brain tissues and blood remained after applying quality filters. Since disease progression in AD correlates with age, we stratified this large dataset into three different age groups: < 75 years, 75-84 years, and ≥ 85 years. The RNA-Seq, microarray, and proteomics datasets were then combined into different integrated datasets. Ensemble machine learning was employed to identify genes and proteins that can accurately classify samples as either AD or control. These predictive inputs were then subjected to network-based enrichment analyses. The ability of genes/proteins associated with different pathways in the Molecular Signatures Database to diagnose AD was also tested. We separately identified microRNAs that can be used to make an AD diagnosis and subjected the predicted gene targets of the most predictive microRNAs to an enrichment analysis. The following key themes emerged from our machine learning and bioinformatics analyses: cell death, cellular senescence, energy metabolism, genomic integrity, glia, immune system, metal ion homeostasis, oxidative stress, proteostasis, and synaptic function. Many of the results demonstrated unique age-specificity. For example, terms highlighting cellular senescence only emerged in the earliest and intermediate age ranges while the majority of results relevant to cell death appeared in the youngest patients. Existing literature corroborates the importance of these hallmarks in AD., Competing Interests: Conflict of Interest Although this work was done independently, the authors would like to share that they are full-time employees of the biotechnology company Tally Health, Inc. (Greenwich, Connecticut, USA)., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Epigenetic aging clocks are computational models that use DNA methylation sites to predict age. Since cheek swabs are non-invasive and painless, collecting DNA from buccal tissue is highly desirable. Here, we review 11 existing clocks that have been applied to buccal tissue. Two of these were exclusively trained on adults and, while moderately accurate, have not been used to capture health-relevant differences in epigenetic age. Using 130 common CpGs utilized by two or more existing buccal clocks, we generate a proof-of-concept predictor in an adult methylomic dataset. In addition to accurately estimating age (r = 0.95 and mean absolute error = 3.88 years), this clock predicted that Down syndrome subjects were significantly older relative to controls. A literature and database review of CpG-associated genes identified numerous genes (e.g., CLOCK , ELOVL2 , and VGF ) and molecules (e.g., alpha-linolenic acid, glycine, and spermidine) reported to influence lifespan and/or age-related disease in model organisms., Competing Interests: All authors are full-time employees of the biotechnology company Tally Health, Inc. The authors have no other conflicts of interest to declare., (© 2022 The Author(s).)

Investment in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing in Africa over the past year has led to a major increase in the number of sequences that have been generated and used to track the pandemic on the continent, a number that now exceeds 100,000 genomes. Our results show an increase in the number of African countries that are able to sequence domestically and highlight that local sequencing enables faster turnaround times and more-regular routine surveillance. Despite limitations of low testing proportions, findings from this genomic surveillance study underscore the heterogeneous nature of the pandemic and illuminate the distinct dispersal dynamics of variants of concern-particularly Alpha, Beta, Delta, and Omicron-on the continent. Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve while the continent faces many emerging and reemerging infectious disease threats. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century.

A major physiological role of hERG1 (human Ether-á-go-go-Related Gene 1) potassium channels is to repolarize cardiac action potentials. Two isoforms, hERG1a and hERG1b, associate to form the potassium current I K r in cardiomyocytes. Inherited mutations in hERG1a or hERG1b cause prolonged cardiac repolarization, long QT syndrome, and sudden death arrhythmia. hERG1a subunits assemble with and enhance the number of hERG1b subunits at the plasma membrane, but the mechanism for the increase in hERG1b by hERG1a is not well understood. Here, we report that the hERG1a N-terminal region expressed in trans with hERG1b markedly increased hERG1b currents and increased biotin-labeled hERG1b protein at the membrane surface. hERG1b channels with a deletion of the N-terminal 1b domain did not have a measurable increase in current or biotinylated protein when coexpressed with hERG1a N-terminal regions, indicating that the 1b domain was required for the increase in hERG1b. Using a biochemical pull-down interaction assay and a FRET hybridization experiment, we detected a direct interaction between the hERG1a N-terminal region and the hERG1b N-terminal region. Using engineered deletions and alanine mutagenesis, we identified a short span of amino acids at positions 216 to 220 within the hERG1a "N-linker" region that were necessary for the upregulation of hERG1b. We propose that direct structural interactions between the hERG1a N-linker region and the hERG1b 1b domain increase hERG1b at the plasma membrane. Mechanisms regulating hERG1a and hERG1b are likely critical for cardiac function, may be disrupted by long QT syndrome mutants, and serve as potential targets for therapeutics., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Competing Interests: None

Although chronological age correlates with various age-related diseases and conditions, it does not adequately reflect an individual's functional capacity, well-being, or mortality risk. In contrast, biological age provides information about overall health and indicates how rapidly or slowly a person is aging. Estimates of biological age are thought to be provided by aging clocks, which are computational models (e.g., elastic net) that use a set of inputs (e.g., DNA methylation sites) to make a prediction. In the past decade, aging clock studies have shown that several age-related diseases, social variables, and mental health conditions associate with an increase in predicted biological age relative to chronological age. This phenomenon of age acceleration is linked to a higher risk of premature mortality. More recent research has demonstrated that predicted biological age is sensitive to specific interventions. Human trials have reported that caloric restriction, a plant-based diet, lifestyle changes involving exercise, a drug regime including metformin, and vitamin D3 supplementation are all capable of slowing down or reversing an aging clock. Non-interventional studies have connected high-quality sleep, physical activity, a healthy diet, and other factors to age deceleration. Specific molecules have been associated with the reduction or reversal of predicted biological age, such as the antihypertensive drug doxazosin or the metabolite alpha-ketoglutarate. Although rigorous clinical trials are needed to validate these initial findings, existing data suggest that aging clocks are malleable in humans. Additional research is warranted to better understand these computational models and the clinical significance of lowering or reversing their outputs., (© 2022 Tally Health. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

Purpose . See-through head-mounted displays (HMDs) can be used to view fluoroscopic imaging during orthopedic surgical procedures. The goals of this study were to determine whether HMDs reduce procedure time, number of fluoroscopic images required, or number of head turns by the surgeon compared with standard monitors. Methods . Sixteen orthopedic surgery residents each performed fluoroscopy-guided drilling of 8 holes for placement of tibial nail distal interlocking screws in an anatomical model, with 4 holes drilled while using HMD and 4 holes drilled while using a standard monitor. Procedure time, number of fluoroscopic images needed, and number of head turns by the resident during the procedure were compared between the 2 modalities. Statistical significance was set at P < .05. Results . Mean (SD) procedure time did not differ significantly between attempts using the standard monitor (55 [37] seconds) vs the HMD (56 [31] seconds) ( P = .73). Neither did mean number of fluoroscopic images differ significantly between attempts using the standard monitor vs the HMD (9 [5] images for each) ( P = .84). Residents turned their heads significantly more times when using the standard monitor (9 [5] times) vs the HMD (1 [2] times) ( P < .001). Conclusions . Head-mounted displays lessened the need for residents to turn their heads away from the surgical field while drilling holes for tibial nail distal interlocking screws in an anatomical model; however, there was no difference in terms of procedure time or number of fluoroscopic images needed using the HMD compared with the standard monitor.

Objectives: This study aims to provide metadesign indications for the improvement of healthcare facilities, emphasizing the role of spatial design in the management of epidemic health emergencies., Study Design: A parallel mixed-method study including literature reviews, survey creation, and survey distribution was performed., Methods: Data were collected between August and October 2020 capturing information related to the first wave of the COVID-19 pandemic, utilizing a review of existing literature, a comparison of existing hospital planning guidelines and assessment tools, and distribution of a survey to analyze design changes within selected Italian hospitals., Results: Among the changes identified, the most frequently identified included the conversion of space into intensive care units, space expansion, and the usage of wayfinding strategies for the reduction of cross-contamination risks. There was limited attention given to solutions with a human-centered approach, and those that addressed physical and psycho-logical well-being of all users, including healthcare staff. The solutions were collected and systematized into a list of metadesign guidelines., Conclusions: The resulting indications represent a starting point for developing design solutions to aid healthcare facilities in facing future epidemics.

Objectives: The present study investigated how development of the /t/-/k/ contrast is affected by the unique perceptual constraints imposed on young children using cochlear implants (CIs). We hypothesized that children with CIs would demonstrate unique patterns of speech acquisition due to device limitations, rather than straightforward delays due to a lack of auditory input in the first year of life before implantation. This study focused on the contrast between /t/ and /k/ because it is acquired early in the sequence of development, requires less advanced motor control than later-acquired place contrasts, is differentiated by spectral cues (which are particularly degraded when processed by CIs), and is not easily differentiated by visual cues alone. Furthermore, perceptual confusability between /t/ and /k/ may be exacerbated in front-vowel contexts, where the spectral energy for /k/ is shifted to higher frequencies, creating more spectral overlap with /t/., Design: Children with CIs (n = 26; ages 31 to 66 mo) who received implants around their first birthdays were matched to peers with normal hearing (NH). Children participated in a picture-prompted auditory word-repetition task that included over 30 tokens of word-initial /t/ and /k/ consonants. Tokens were balanced across front-vowel and back-vowel contexts to assess the effects of coarticulation. Productions were transcribed and coded for accuracy as well as the types of errors produced (manner of articulation, voicing, or place of articulation errors). Centroid frequency was also calculated for /t/ and /k/ tokens that were produced correctly. Mixed-effects models were used to compare accuracy, types of errors, and centroid frequencies across groups, target consonants, and vowel contexts., Results: Children with CIs produced /t/ and /k/ less accurately than their peers in both front- and back-vowel contexts. Children with CIs produced /t/ and /k/ with equal accuracy, and /k/ was produced less accurately in front-vowel contexts than in back-vowel contexts. When they produced errors, children with CIs were more likely to produce manner errors and less likely to produce voicing errors than children with NH. Centroid frequencies for /t/ and /k/ were similar across groups, except for /k/ in front-vowel contexts: children with NH produced /k/ in front-vowel contexts with higher centroid frequency than children with CIs, and they produced /k/ and /t/ with equal centroid frequencies in front-vowel contexts., Conclusions: Children with CIs not only produced /t/ and /k/ less accurately than peers with NH, they also demonstrated idiosyncratic patterns of acquisition, likely resulting from receiving degraded and distorted spectral information critical for differentiating /t/ and /k/. Speech-language pathologists should consider perceptual confusability of consonants (and their allophonic variations) during their assessment and treatment of this unique population of children., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

The course-based research experience (CRE) with its documented educational benefits is increasingly being implemented in science, technology, engineering, and mathematics education. This article reports on a study that was done over a period of 3 years to explicate the instructional processes involved in teaching an undergraduate CRE. One hundred and two instructors from the established and large multi-institutional SEA-PHAGES program were surveyed for their understanding of the aims and practices of CRE teaching. This was followed by large-scale feedback sessions with the cohort of instructors at the annual SEA Faculty Meeting and subsequently with a small focus group of expert CRE instructors. Using a qualitative content analysis approach, the survey data were analyzed for the aims of inquiry instruction and pedagogical practices used to achieve these goals. The results characterize CRE inquiry teaching as involving three instructional models: 1) being a scientist and generating data; 2) teaching procedural knowledge; and 3) fostering project ownership. Each of these models is explicated and visualized in terms of the specific pedagogical practices and their relationships. The models present a complex picture of the ways in which CRE instruction is conducted on a daily basis and can inform instructors and institutions new to CRE teaching.

Background: In the United States, New York State's health care system experienced unprecedented stress as an early epicenter of the coronavirus disease 2019 (COVID-19) pandemic. This study aims to assess the level of hopelessness in New York State physicians working on the frontlines during the first wave of the COVID-19 outbreak., Methods: A confidential online survey sent to New York State health care workers by the state health commissioner's office was used to gather demographic and hopelessness data as captured by a brief Hopelessness Scale. Adjusted linear regression models were used to assess the associations of physician age, sex, and number of triage decisions made, with level of hopelessness., Results: In total, 1330 physicians were included, of whom 684 were male (51.4%). Their average age was 52.4 years (SD=12.7), with the majority of respondents aged 50 years and older (55.2%). Almost half of the physician respondents (46.3%) worked directly with COVID-19 patients, and 163 (12.3%) were involved in COVID-19-related triage decisions. On adjusted analysis, physicians aged 40 to 49 years had significantly higher levels of hopelessness compared with those aged 50 years or more (μ=0.441, SD=0.152, P=0.004). Those involved in 1 to 5 COVID-19-related triage decisions had a significantly lower mean hopelessness score (μ=-0.572, SD=0.208, P=0.006) compared with physicians involved in none of these decisions., Conclusion: Self-reported hopelessness was significantly higher among physicians aged 40 to 49 years and those who had not yet been involved in a life or death triage decision. Further work is needed to identify strategies to support physicians at high risk for adverse mental health outcomes during public health emergencies such as the COVID-19 pandemic., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Fused Filament Fabrication (FFF), a commonly used additive manufacturing technology, is now employed widely in biomedical fields for fabricating geometrically complex biodegradable devices. Structural voids arising from the printing process exist within the objects manufactured by FFF. This paper reveals the underlying mechanism of how the printing parameters and voids affect the degradation behaviours of devices made of biodegradable polyesters. It was found that both voids and internal architecture (layer height, for instance) affect the degradation rate by interacting with the reaction-diffusion process. Large suppression of the degradation rate was found when auto-catalytic hydrolysis and diffusion are significant. Degradation rate reduced in an approximately logarithmic manner as void size increased. The extent this effect depended on the strength of auto-catalytic hydrolysis and diffusion, void size and overall device size. The internal architecture of FFF products (regulated by printing parameters) influences the degradation rate by altering the diffusion speed of acid catalysts (regulated by diffusion path length). Both void size and internal architecture should be considered in fabricating biodegradable devices using FFF. STATEMENT OF SIGNIFICANCE: A geometric model that relates printing parameters with voids of FFF is developed to characterise the structure of FFF components. Such a model, when coupled with a degradation model, offers end-to-end simulation capability (e.g. from printing parameters to degradation rate) for predicting degradation properties. The model is validated against the in vitro degradation data obtained in this study. To our knowledge, the impact of printing parameters and voids on degradation is investigated here for the first time. It is found that both the void size and the internal architecture determined by the printing parameters play an essential role in regulating degradation behaviours., Competing Interests: Declaration of Competing Interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled,“How do the printing parameters of Fused Filament Fabrication and the structural voids influence the degradation of biodegradable devices?”., (Copyright © 2021 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Objectives: Computed tomography (CT) myocardial perfusion imaging (CT-MPI) with hyperemia induced by regadenoson was evaluated for the detection of myocardial ischemia, safety, relative radiation exposure, and patient experience compared with single-photon emission computed tomography (SPECT) imaging., Materials and Methods: Twenty-four patients (66.5 y, 29% male) who had undergone clinically indicated SPECT imaging and provided written informed consent were included in this phase II, IRB-approved, and FDA-approved clinical trial. All patients underwent coronary CT angiography and CT-MPI with hyperemia induced by the intravenous administration of regadenoson (0.4 mg/5 mL). Patient experience and findings on CT-MPI images were compared to SPECT imaging., Results: Patient experience and safety were similar between CT-MPI and SPECT procedures and no serious adverse events due to the administration of regadenoson occurred. SPECT resulted in a higher number of mild adverse events than CT-MPI. Patient radiation exposure was similar during the combined coronary computed tomography angiography and CT-MPI (4.4 [2.7] mSv) and SPECT imaging (5.6 [1.7]  mSv) (P-value 0.401) procedures. Using SPECT as the reference standard, CT-MPI analysis showed a sensitivity of 58.3% (95% confidence interval [CI]: 27.7-84.8), a specificity of 100% (95% CI: 73.5-100), and an accuracy of 79.1% (95% CI: 57.9-92.87). Low apparent sensitivity occurred when the SPECT defects were small and highly suspicious for artifacts., Conclusions: This study demonstrated that CT-MPI is safe, well tolerated, and can be performed with comparable radiation exposure to SPECT. CT-MPI has the benefit of providing both complete anatomic coronary evaluation and assessment of myocardial perfusion., Competing Interests: U.J.S. receives institutional research support from Astellas, Bayer, General Electric, and Siemens Healthineers. U.J.S. has received honoraria for speaking and consulting from Bayer, Elucid, Guerbet, HeartFlow Inc., and Siemens Healthineers. C.N.D.C. is a consultant for/receives institutional research support from Bayer and Siemens. A.V.-S. receives institutional research support from Siemens Healthineers. The remaining authors declare no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

In our recent transcriptomic meta-analysis, we used random forest machine learning to accurately predict age in human blood, bone, brain, heart, and retina tissues given gene inputs. Although each tissue-specific model utilized a unique number of genes for age prediction, we found that the following six genes were prioritized in all five tissues: CHI3L2 , CIDEC , FCGR3A , RPS4Y1 , SLC11A1 , and VTCN1 . Since being selected for age prediction in multiple tissues is unique, we decided to explore these pan-tissue clock genes in greater detail. In the present study, we began by performing over-representation and network topology-based enrichment analyses in the Gene Ontology Biological Process database. These analyses revealed that the immunological terms "response to protozoan," "immune response," and "positive regulation of immune system process" were significantly enriched by these clock inputs. Expression analyses in mouse and human tissues identified that these inputs are frequently upregulated or downregulated with age. A detailed literature search showed that all six genes had noteworthy connections to age-related disease. For example, mice deficient in Cidec are protected against various metabolic defects, while suppressing VTCN1 inhibits age-related cancers in mouse models. Using a large multitissue transcriptomic dataset, we additionally generate a novel, minimalistic aging clock that can predict human age using just these six genes as inputs. Taken all together, these six genes are connected to diverse aspects of aging.

Machine learning models capable of predicting age given a set of inputs are referred to as aging clocks. We recently developed an aging clock that utilizes 491 plasma protein inputs, has an exceptional accuracy, and is capable of measuring biological age. Here, we demonstrate that this clock is extremely predictive (r = 0.95) when used to measure age in a novel plasma proteomic dataset derived from 370 human subjects aged 18-69 years. Over-representation analyses of the proteins that make up this clock in the Gene Ontology and Reactome databases predominantly implicated innate and adaptive immune system processes. Immunological drugs and various age-related diseases were enriched in the DrugBank and GLAD4U databases. By performing an extensive literature review, we find that at least 269 (54.8 %) of these inputs regulate lifespan and/or induce changes relevant to age-related disease when manipulated in an animal model. We also show that, in a large plasma proteomic dataset, the majority (57.2 %) of measurable clock proteins significantly change their expression level with human age. Different subsets of proteins were overlapped with distinct epigenetic, transcriptomic, and proteomic aging clocks. These findings indicate that the inputs of this age predictor likely represent a rich source of anti-aging drug targets., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Problem: Children often experience pain and anxiety during a hospital stay. Effective pain and anxiety management plays a crucial role in healing. However, recent literature has highlighted multiple barriers to managing pain and anxiety in children, such as parent and provider fears of the adverse effects of pain and anxiety medications., Eligibility Criteria: A database search was conducted for articles published between 2009 and 2019 to evaluate the impact of nurse-led, music-based interventions as an adjunct method of pain and anxiety management in hospitalized children. Articles were included if study subjects were ages 0-21 years old, the study used live or recorded music as an intervention, and occurred in an inpatient setting., Sample: A total of seven randomized control trials and one quasi-experimental study were included for analysis., Results: There is consistent and significant evidence that music can reduce anxiety in hospitalized children before and during procedures. Results with respect to pain and vital signs, often viewed as the physiologic analogs to pain, were mixed., Conclusions: Music-based interventions are safe for hospitalized children. Several studies highlighted the importance of patient preference in selecting music for children. A heavy reliance on pre-recorded audio, delivered via headphones illustrates the feasibility and cost-effectiveness of music-based interventions., Implications: Nurse-led, music-based interventions have been shown to be an affordable, safe, effective, and feasible alternative for managing anxiety in hospitalized children. Music should be considered as an adjunct therapy to traditional anxiety treatment. Further research is needed to determine the effects of music on pain., Competing Interests: Declaration of Competing Interest None. This integrative literature review did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. A portion of this content was presented at the Nursing for Children Network Regional Pediatric Nursing Conference held virtually in October 2020., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Here, we report genome sequences of 10 Bacillus cereus group-infecting bacteriophages. Each virus was isolated from an environmental sample, contained a double-stranded DNA genome, and belonged to the Myoviridae family. Nine phages exhibit a conserved genome structure, and one phage appears novel in genome structure, sequence, and protein content.

Purpose: To assess five theoretical foundations underlying thermosensory testing using local thermal stimuli., Methods: Thermal sensation, discomfort and the confidence of thermal sensation scores were measured in 9 female and 8 male volunteers in response to 17 physical contact temperature stimuli, ranging between 18-42 °C. These were applied to their dorsal forearm and lateral torso, across two sessions., Results: Thermal sensation to physical temperature relationships followed a positive linear and sigmoidal fit at both forearm (r 2  = 0.91/r 2  = 0.91, respectively) and lateral torso (r 2  = 0.90/ r 2  = 0.91, respectively). Thermal discomfort to physical temperature relationships followed second and third-order fits at both forearm (r 2  = 0.33/r 2  = 0.34, respectively) and lateral torso (r 2  = 0.38/r 2  = 0.39, respectively) test sites. There were no sex-related or regional site differences in thermal sensation and discomfort across a wide range of physical contact temperatures. The median confidence of an individual's thermal sensation rating was measured at 86%., Conclusion: The relation between thermal sensation and physical contact temperature was well described by both linear and sigmoidal models, i.e., the distance between the thermal sensation anchors is close to equal in terms of physical temperatures changes for the range studied. Participants rated similar thermal discomfort level in both cold and hot thermal stimuli for a given increase or decrease in physical contact temperature or thermal sensation. The confidence of thermal sensation rating did not depend on physical contact temperature.