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Introduction: Disturbances in body image can have an impact on sexual health and are prevalent in women of reproductive age. Although body image is important, the definition of this concept is inconsistent across the disciplines of nursing, medicine, and psychology. Use of a consistent definition in clinical practice and research could lead to a more comprehensive understanding of disturbances in body image, thereby advancing research-based knowledge and clinical practice. The purpose of this concept development was to advance the concept of body image as it relates to sexual health among women of reproductive age from the perspectives of 3 disciplines with a strong focus on body image: nursing, medicine, and psychology., Methods: Strategies for concept development as described by Rodgers provided the basis for this work. The process includes a search, review, and synthesis of the literature surrounding the concept of interest., Results: Seventy-one articles, mostly qualitative and quantitative descriptive, were included and used to develop the concept. Body image related to sexual health in women of reproductive age is a multifaceted concept that is composed of an emotional and behavioral response to one's perceived appearance, sexuality, and degree of femininity. An individual's body image is influenced by sociocultural identities, race, ethnicity, and health status. It has both physical and psychological impact on health outcomes., Discussion: This interprofessional and comprehensive definition of body image should enhance understanding, assessment, and management of body image disturbances, thus bridging disciplines and enhancing interprofessional research and practice., (© 2021 by the American College of Nurse-Midwives.)

Extremely thermophilic bacteria from the genus Caldicellulosiruptor can degrade polysaccharide components of plant cell walls and subsequently utilize the constituting mono- and oligosaccharides. Through metabolic engineering, ethanol and other industrially important end products can be produced. Previous experimental studies identified a variety of carbohydrate-active enzymes in model species Caldicellulosiruptor saccharolyticus and Caldicellulosiruptor bescii, while prior transcriptomic experiments identified their putative carbohydrate uptake transporters. We investigated the mechanisms of transcriptional regulation of carbohydrate utilization genes using a comparative genomics approach applied to 14 Caldicellulosiruptor species. The reconstruction of carbohydrate utilization regulatory network includes the predicted binding sites for 34 mostly local regulators and point to the regulatory mechanisms controlling expression of genes involved in degradation of plant biomass. The Rex and CggR regulons control the central glycolytic and primary redox reactions. The identified transcription factor binding sites and regulons were validated with transcriptomic and transcription start site experimental data for C. bescii grown on cellulose, cellobiose, glucose, xylan, and xylose. The XylR and XynR regulons control xylan-induced transcriptional response of genes involved in degradation of xylan and xylose utilization. The reconstructed regulons informed the carbohydrate utilization reconstruction analysis and improved functional annotations of 51 transporters and 11 catabolic enzymes. Using gene deletion, we confirmed that the shared ATPase component MsmK is essential for growth on oligo- and polysaccharides but not for the utilization of monosaccharides. By elucidating the carbohydrate utilization framework in C. bescii , strategies for metabolic engineering can be pursued to optimize yields of bio-based fuels and chemicals from lignocellulose. IMPORTANCE To develop functional metabolic engineering platforms for nonmodel microorganisms, a comprehensive understanding of the physiological and metabolic characteristics is critical. Caldicellulosiruptor bescii and other species in this genus have untapped potential for conversion of unpretreated plant biomass into industrial fuels and chemicals. The highly interactive and complex machinery used by C. bescii to acquire and process complex carbohydrates contained in lignocellulose was elucidated here to complement related efforts to develop a metabolic engineering platform with this bacterium. Guided by the findings here, a clearer picture of how C. bescii natively drives carbohydrate utilization is provided and strategies to engineer this bacterium for optimal conversion of lignocellulose to commercial products emerge.

Immune modulation is considered a hallmark of cancer initiation and progression. The recent development of immunotherapies has ushered in a new era of cancer treatment. These therapeutics have led to revolutionary breakthroughs; however, the efficacy of immunotherapy has been modest and is often restricted to a subset of patients. Hence, identification of which cancer patients will benefit from immunotherapy is essential. Multiplex immunofluorescence (mIF) microscopy allows for the assessment and visualization of the tumor immune microenvironment (TIME). The data output following image and machine learning analyses for cell segmenting and phenotyping consists of the following information for each tumor sample: the number of positive cells for each marker and phenotype(s) of interest, number of total cells, percent of positive cells for each marker, and spatial locations for all measured cells. There are many challenges in the analysis of mIF data, including many tissue samples with zero positive cells or "zero-inflated" data, repeated measurements from multiple TMA cores or tissue slides per subject, and spatial analyses to determine the level of clustering and co-localization between the cell types in the TIME. In this review paper, we will discuss the challenges in the statistical analysis of mIF data and opportunities for further research.

The Cox proportional hazard model is one of the most widely used methods in modeling time-to-event data in the health sciences. Due to the simplicity of the Cox partial likelihood function, many machine learning algorithms use it for survival data. However, due to the nature of censored data, the optimization problem becomes intractable when more complicated regularization is employed, which is necessary when dealing with high dimensional omic data. In this paper, we show that a convex conjugate function of the Cox loss function based on Fenchel duality exists, and provide an alternative framework to optimization based on the primal form. Furthermore, the dual form suggests an efficient algorithm for solving the kernel learning problem with censored survival outcomes. We illustrate performance and properties of the derived duality form of Cox partial likelihood loss in multiple kernel learning problems with simulated and the Skin Cutaneous Melanoma TCGA datasets., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Introduction The purpose of this study was to identify themes and concepts derived from responses of physical therapy clinical leaders related to implementing a prevention-focused, home-based older-adult program known as HOP-UP-PT (Home-Based Older Person Upstreaming Prevention Physical Therapy) into their clinical operations. Methods Following Institutional Review Board approval, a retrospective qualitative analysis of transcribed interviews obtained by six undergraduate students participating in the Oakland University Ideas to Business Program (I2B) was conducted. Students interviewed nine local physical therapy clinical managers throughout Michigan using 12 questions developed by content experts. Questions aimed to ascertain the perceived opportunities and barriers to implementing HOP-UP-PT into each respondent's practice setting, clinic demographics, and suggested price point of a prevention-focused continuing education. Interview data was analyzed using the constant comparative method to identify themes and concepts. Results Sixty-seven percent of respondents (n=6) reported practicing in an outpatient setting; 56% of respondents (n=5) indicated 50% or more of their clients were 65 years and older; and 67% of respondents (n=6) suggested a price point of $200-$500 for an eight-hour HOP-UP-PT training course. Three concepts (community involvement and partnership, administrative barriers to an innovative delivery model, and foundational physical therapy [PT] skills utilized in a novel approach) and eight themes (community altruism, referral source expansion, integrated community relationships, current payment methodology challenges, favorability of clinic setting and type, minimal additional training required, willingness to pay for certification training, and prevention-focused or upstream mindset) were identified. Conclusion Physical therapy clinical managers identified a willingness to expand current rehabilitation models and incorporate prevention-focused care delivery into the existing care delivery approach. However, barriers and opportunities must be addressed in advance of a program roll-out to achieve optimal outcomes and cost savings within the healthcare system., Competing Interests: Christopher M. Wilson and Sara K. Arena are co-principals of HOP-UP-PT, LLC. A conflict of interest plan has been approved and is monitored by Oakland University., (Copyright © 2021, Naccarato et al.)

Lung cancer is the second most common cancer and the leading cause of death in both men and women in the world. Lung cancer is heterogeneous in nature and diagnosis is often at an advanced stage as it develops silently in the lung and is frequently associated with high mortality rates. Despite the advances made in understanding the biology of lung cancer, progress in early diagnosis, cancer therapy modalities and considering the mechanisms of drug resistance, the prognosis and outcome still remains low for many patients. Nanotechnology is one of the fastest growing areas of research that can solve many biological problems such as cancer. A growing number of therapies based on using nanoparticles (NPs) have successfully entered the clinic to treat pain, cancer, and infectious diseases. Recent progress in nanotechnology has been encouraging and directed to developing novel nanoparticles that can be one step ahead of the cancer reducing the possibility of multi-drug resistance. Nanomedicine using NPs is continuingly impacting cancer diagnosis and treatment. Chemotherapy is often associated with limited targeting to the tumor, side effects and low solubility that leads to insufficient drug reaching the tumor. Overcoming these drawbacks of chemotherapy by equipping NPs with theranostic capability which is leading to the development of novel strategies. This review provides a synopsis of current progress in theranostic applications for lung cancer diagnosis and therapy using NPs including liposome, polymeric NPs, quantum dots, gold NPs, dendrimers, carbon nanotubes and magnetic NPs., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Cell type classification is an important problem in cancer research, especially with the advent of single cell technologies. Correctly identifying cells within the tumor microenvironment can provide oncologists with a snapshot of how a patient's immune system reacts to the tumor. Wide and deep learning (WDL) is an approach to construct a cell-classification prediction model that can learn patterns within high-dimensional data (deep) and ensure that biologically relevant features (wide) remain in the final model. In this paper, we demonstrate that regularization can prevent overfitting and adding a wide component to a neural network can result in a model with better predictive performance. In particular, we observed that a combination of dropout and ℓ 2 regularization can lead to a validation loss function that does not depend on the number of training iterations and does not experience a significant decrease in prediction accuracy compared to models with ℓ 1 , dropout, or no regularization. Additionally, we show WDL can have superior classification accuracy when the training and testing of a model are completed data on that arise from the same cancer type but different platforms. More specifically, WDL compared to traditional deep learning models can substantially increase the overall cell type prediction accuracy (36.5 to 86.9%) and T cell subtypes (CD4: 2.4 to 59.1%, and CD8: 19.5 to 96.1%) when the models were trained using melanoma data obtained from the 10X platform and tested on basal cell carcinoma data obtained using SMART-seq. WDL obtains higher accuracy when compared to state-of-the-art cell classification algorithms CHETAH (70.36%) and SingleR (70.59%)., Competing Interests: 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., (© 2021 The Authors.)

Lung cancer is a leading cause of cancer deaths worldwide. The management of lung cancer treatment is often ineffective as a result of the development of drug resistance, reactions to treatment, drug-drug interactions or non-specific targeting of the anticancer drugs. Natural compounds show promise and potential activity in lung cancer with very few side effects. While, the combinatorial action of an anti-cancer drug with a natural compound provides synergistic action which helps boost the overall therapeutic action against cancer cells. In cancer, there is a dysregulation of apoptosis which facilitates the cancer cell to survive, resulting in progression of cancer. Many cancer drugs cause mutations of genes that regulate cancer and should kill the cancer cell but lead to chemoresistance. There are many natural compounds that could specifically target different cell signalling pathways associated with cancer progression to provide a cytotoxic effect in the target cell. The importance of these compounds is emerging in many therapies developed with dual action often including a natural compound. In this review, we present a selection of these natural compounds and how they target lung cancer cells with a focus on the cell signalling pathways. Further work is required to delineate the potential action of natural compounds in the treatment against cancer., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Chronic pain often predicts the onset of psychological distress. Symptoms including anxiety and depression after pain chronification reportedly are caused by brain remodeling/recruitment of the limbic and reward/aversion circuitries. Pain is the primary precipitating factor that has caused opioid overprescribing and continued overuse of opioids leading to the current opioid epidemic. Yet experimental pain therapies often fail in clinical trials. Better understanding of underlying pathologies contributing to pain chronification is needed to address these chronic pain related issues. In the present study, a chronic neuropathic pain model persisting 10 weeks was studied. The model develops both anxiety- and pain-related behavioral measures to mimic clinical pain. The manganese-enhanced magnetic resonance imaging (MEMRI) utilized improved MRI signal contrast in brain regions with higher neuronal activity in the rodent chronic constriction trigeminal nerve injury (CCI-ION) model. T1-weighted MEMRI signal intensity was increased compared to controls in supraspinal regions of the anxiety and aversion circuitry, including anterior cingulate gyrus (ACC), amygdala, habenula, caudate, ventrolateral and dorsomedial periaqueductal gray (PAG). Despite continuing mechanical hypersensitivity, MEMRI T1 signal intensity as the neuronal activity measure, was not significantly different in thalamus and decreased in somatosensory cortex (S1BF) of CCI-ION rats compared to naïve controls. This is consistent with decreased fMRI BOLD signal intensity in thalamus and cortex of patients with longstanding trigeminal neuropathic pain reportedly associated with gray matter volume decrease in these regions. Significant increase in MEMRI T2 signal intensity in thalamus of CCI-ION animals was indication of tissue water content, cell dysfunction and/or reactive astrogliosis. Decreased T2 signal intensity in S1BF cortex of rats with CCI-ION was similar to findings of reduced T2 signals in clinical patients with chronic orofacial pain indicating prolonged astrocyte activation. These findings support use of MEMRI and chronic rodent models for preclinical studies and therapeutic trials to reveal brain sites activated only after neuropathic pain has persisted in timeframes relevant to clinical pain and to observe treatment effects not possible in short-term models which do not have evidence of anxiety-like behaviors. Potential improvement is predicted in the success rate of preclinical drug trials in future studies with this model., Competing Interests: Declaration of Competing Interest No authors have conflicts of interest., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Neurotensin receptor-3 or sortilin is a vacuolar protein sorting 10 protein domain (Vps10p) has been firstly discovered in the human brain, it acts as receptor or co-receptor of the cell and traffics different proteins within the cell. Sortilin deregulation contributes to the development of several diseases, including neurological diseases and cancer. On the other hand, neurotrophins which are a family of proteins essential for the nervous system development, function and plasticity. The first discovered member is the nerve growth factor; other members are brain-derived growth factor, neurotrophin-3 and neurotrophin-4. Nerve growth factor and brain-derived growth factor are the common neurotrophins that have a role in cancer. Neurotrophins initiate their signals through interaction with tyrosine receptor kinases TrkA, TrkB, and TrkC; each member has an affinity for a specific receptor to stimulate cell survival, while the interaction with p75 NTR initiates cell apoptosis pathway by forming a complex with sortilin and neurotrophin precursors. A number of therapeutic approaches are emerging to target the neurotrophins pathway as well as sortilin., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: The objective of this paper is to describe the use of oncology digital symptom monitoring and patient self-management coaching tools, how nurses and nurse practitioners (NPs) can optimize their use as an adjunct in improving oncology care and discuss issues and strategies needed for adoption within a variety of clinical settings., Data Sources: A review of the research literature regarding digital health in oncology symptom management in PubMed provided the foundation for this paper., Conclusion: Digital symptom monitoring technology provides a variety of opportunities for oncology nurses and NPs to efficiently extend and improve symptom management in multiple settings including cancer patients at home between clinic visits, at clinic visits, and during inpatient stays. Digital monitoring and patient engagement make possible frequent symptom assessments, just-in-time personalized self-management reinforcement, and judiciously alert nurses and NPs about key times for follow-up with patients supported with evidenced-based guidelines. Oncology nurses at all levels have the opportunity to be leaders in the adoption and expansion of digital tools to enhance their practice., Implications for Nursing Practice: Oncology nurses and NPs can lead practice changes that improve patient outcomes through understanding and shaping the use of digital tools., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Injuries from exposure to explosions rose dramatically during the Iraq and Afghanistan wars, which motivated investigation of blast-related neurotrauma. We have undertaken human studies involving military "breachers" -exposed to controlled, low-level blast during a 3-days explosive breaching course. Methods: We screened epigenetic profiles in peripheral blood samples from 59 subjects (in two separate U.S. Military training sessions) using Infinium MethylationEPIC BeadChips. Participants had varying numbers of exposures to blast over their military careers (empirically defined as high ≥ 40, and conversely, low < 39 breaching exposures). Daily self-reported physiological symptoms were recorded. Tinnitus, memory problems, headaches, and sleep disturbances are most frequently reported. Results: We identified 14 significantly differentially methylated regions (DMRs) within genes associated with cumulative blast exposure in participants with high relative to low cumulative blast exposure. Notably , NTSR1 and SPON1 were significantly differentially methylated in high relative to low blast exposed groups, suggesting that sleep dysregulation may be altered in response to chronic cumulative blast exposure. In comparing lifetime blast exposure at baseline (prior to exposure in current training), and top associated symptoms, we identified significant DMRs associated with tinnitus, sleep difficulties, and headache. Notably, we identified KCNN3, SOD3, MUC4, GALR1 , and WDR45B , which are implicated in auditory function, as differentially methylated associated with self-reported tinnitus. These findings suggest neurobiological mechanisms behind auditory injuries in our military warfighters and are particularly relevant given tinnitus is not only a primary disability among veterans, but has also been demonstrated in active duty medical records for populations exposed to blast in training. Additionally, we found that differentially methylated regions associated with the genes CCDC68 and COMT track with sleep difficulties, and those within FMOD and TNXB track with pain and headache. Conclusion: Sleep disturbances, as well as tinnitus and chronic pain, are widely reported in U.S. military service members and veterans. As we have previously demonstrated, DNA methylation encapsulates lifetime exposure to blast. The current data support previous findings and recapitulate transcriptional regulatory alterations in genes involved in sleep, auditory function, and pain. These data uncovered novel epigenetic and transcriptional regulatory mechanism underlying the etiological basis of these symptoms., (Copyright © 2020 Wang, Wilson, Ge, Nemes, LaValle, Boutté, Carr, Kamimori and Haghighi.)

Factors associated with prescription of smoking cessation medication (SCM), including the impact of race, have not been well described among a large population of people living with HIV (PLWH) engaged in routine clinical care. Our study investigated whether there are racial differences between African-American and White PLWH regarding SCM prescription and sought to identify other factors associated with these prescriptions at a large HIV clinic in the Southeastern United States. Among 1899 smokers, 38.8% of those prescribed SCMs were African-American and 61.2% were White. Factors associated with lower odds of SCM prescription included African-American race (AOR, 0.63 [95% CI: 0.47, 0.84]) or transferring care from another HIV provider during the study period (AOR, 0.63 [95% CI: 0.43, 0.91]). Whereas major depression (AOR, 1.54 [95% CI: 1.10, 2.15]), anxiety symptoms (AOR, 1.43 [95% CI: 1.05, 1.94]), and heavy smoking (>20 cigarettes/day) (OR, 3.50 [95% CI: 2.11, 5.98]) were associated with increased likelihood of SCM prescription. There were racial disparities in the prescription of SCM in African Americans with HIV. These findings underscore the need to increase pharmacotherapy use among African Americans to improve smoking cessation outcomes across racial groups among PLWH.

Background: A major challenge in implementing personalized medicine in pediatrics is identifying appropriate drug dosages for children. The majority of drug dosing studies have been based on adult populations, often with modification of the dosing for children based on size and weight. However, the growth and development experienced by children between birth and adulthood represents a dynamically changing biological system, with implications for effective drug dosing, efficacy as well as potential drug toxicity. The purpose of this study was to apply a metabolomics approach to gain preliminary insights into the ontogeny of liver function from newborn to adolescent. Methods: Metabolites were measured in 98 post-mortem pediatric liver samples in two experiments 3 batches of samples, allowing for both technical and biological validation. After extensive quality control, imputation and normalization, non-parametric tests were used to determine which metabolite levels differ between the four age groups (AG) ranging in age from newborn to adolescent (AG1-children <1 year; AG2-children with age between 1 and 6 years; AG3-children with age between 6 and 12 years; AG4-children with age between 12 and 18 years). To identify which metabolites had different concentration levels among the age groups, Kruskal-Wallis and Spearman correlation tests were conducted. Pathway analysis utilized the Gamma Method. Correction for multiple testing was completed using Bonferroni correction. Results: We found 41 metabolites (out of 884) that were biologically validated, and of those 25 were technically replicated, of which 24 were known metabolites. For the majority of these 24 metabolites, concentration levels were significantly lower in newborns than in the other age groups, many of which were long chain fatty acids or involved in pyrimidine or purine metabolism. Additionally, we found two KEGG pathways enriched for association with age: betaine metabolism and alpha linolenic acid and linoleic acid metabolism. Conclusions: Understanding the role that ontogeny of childhood liver plays may aid in determining better drug dosing algorithms for children., (Copyright © 2020 Wilson, Li, Gaedigk, Bi, de Wildt, Leeder and Fridley.)

The larvae of click beetles (Coleoptera: Elateridae), known as "wireworms," are agricultural pests that pose a substantial economic threat worldwide. We produced one of the first wireworm genome assemblies (Limonius californicus), and investigated population structure and phylogenetic relationships of three species (L. californicus, L. infuscatus, L. canus) across the northwest US and southwest Canada using genome-wide markers (RADseq) and genome skimming. We found two species (L. californicus and L. infuscatus) are comprised of multiple genetically distinct groups that diverged in the Pleistocene but have no known distinguishing morphological characters, and therefore could be considered cryptic species complexes. We also found within-species population structure across relatively short geographic distances. Genome scans for selection provided preliminary evidence for signatures of adaptation associated with different pesticide treatments in an agricultural field trial for L. canus. We demonstrate that genomic tools can be a strong asset in developing effective wireworm control strategies.

Maintenance in HIV care is important to achieve optimal personal health and HIV viral load suppression for young people living with HIV (PLWH). We assessed the relationship between incarceration and missed visits in a longitudinal data cohort of PLWH ( n  = 910), ages 12-24, from 14 adolescent trial network sites across the US. The time from study entry to missed visits was modeled using Cox proportional hazards models. The cohort was mostly male (78%) and African American (75%) with a median age of 22. Prior incarceration had been experienced by 39% of the cohort, with a median number of times incarcerated of 2 (IQR: 1-3). The crude and adjusted hazard ratios for missed HIV care visits comparing those with incarceration histories to those without were 1.27 (95% CI: 1.06, 1.54) and 1.53 (95% CI: 1.26, 1.86). Among those returning to care, HIV viral loads were more likely to be unsuppressed among those with incarceration history compared to those without (RR: 1.28, 95% CI: 0.95, 1.74). This association was attenuated to the null after adjustment for suppression of viral load prior to the missed visit. Young PLWH with incarceration histories are at higher risk of missing HIV care visits.

Background:  Head and neck (H&N) cancers account for 4% of total cancers diagnosed. However, quality of life (QoL) implications are more severe for this patient population due to the complexity, extent, and deformities resulting from treatment interventions. Principally debilitating complications include diminished functional walking capacity, reduced cervical range of motion (ROM), and scapular strength. An extensive literature search revealed a paucity of evidence utilizing physical therapy assessment and intervention for this population. The purpose of this study was to describe the development and clinical feasibility of a prehabilitation program aimed to thwart these complications for patients diagnosed with H&N cancer.  Methods: Inclusion criteria: male or female, 18+ years, speak and read the English language, ambulate independently, diagnosed with H&N cancer, and scheduled for surgical intervention. Institutional Review Board approval was obtained. Pre- and post-surgical measurements included the six-minute walk test (6MWT), cervical ROM, manual muscle testing for scapular strength, and three questionnaires: physical activity history, health behaviors questionnaire, and the Functional Assessment Cancer Therapy H&N QoL survey.  Results: Three participants were enrolled (two males and one female) all identifying as Caucasian and between 60-90 years of age. Pre- to post-cervical ROM demonstrated decline in extension/bilateral rotation for two of three participants. Two participants demonstrated decreased 6MWT distance while one increased. No participants experienced any adverse effects of the prehabilitation program.  Conclusion: This is the first study protocol to describe a physical therapist-administered H&N cancer prehabilitation program. Professionally administered education and exercise has potential to prevent, manage, and mitigate the adverse effects of cancer treatment. Additional research is needed to define the importance of prehabilitation relative to improved clinical outcomes and improved QoL. Patients with a cancer diagnosis are susceptible to impairments and functional limitations as a result of treatments and this prehabilitation program demonstrates potential to positively impact outcomes across the survivorship continuum. Due to their education and integration within the medical system, physical therapists are well-positioned to lead the effort to unify theory and clearly define parameters for oncology prehabilitation., Competing Interests: The authors have declared financial relationships, which are detailed in the next section., (Copyright © 2020, Boright et al.)

We show that the states generated by a three-mode spontaneous parametric down-conversion (SPDC) interaction Hamiltonian possess tripartite entanglement of a different nature to other paradigmatic three-mode entangled states generated by the combination of two-mode SPDC interactions. While two-mode SPDC generates Gaussian states whose entanglement can be characterized by standard criteria based on two-mode quantum correlations, these criteria fail to capture the entanglement generated by three-mode SPDC. We use criteria built from three-mode correlation functions to show that the class of states recently generated in a superconducting-circuit implementation of three-mode SPDC ideally have tripartite entanglement, contrary to recent claims in the literature. These criteria are suitable for triple SPDC but we show that they fail to detect tripartite entanglement in other states which are known to possess it, which illustrates the existence of two fundamentally different notions of tripartite entanglement in three-mode continuous-variable systems.

Purpose: HIV treatment as prevention is effective for reducing the risk of HIV transmission and the messaging campaign, undetectable = untransmittable, is gaining recognition. As youth living with HIV (YLWH) who have condomless sex may acquire and potentially transmit other sexually transmitted infections (STIs), the purpose of this study was to assess potential differences in transmission risk of HIV and other STIs among YLWH to inform subsequent HIV and STI prevention efforts., Methods: A cohort of 600 HIV behaviorally infected youth aged 13-24 years who were engaged in medical care completed an audio computer-assisted self-interview including questions about demographics, HIV disclosure, mental health, substance use, and sexual behaviors and beliefs. HIV viral loads and the presence of other STIs were abstracted from medical records. A viral load <200 copies/mL was considered undetectable. Univariate and bivariate analyses were conducted to examine differences by viral load and STIs., Results: Participants were categorized into four groups: (1) undetectable without STIs (55.2%); (2) undetectable with STIs (14.2%); (3) detectable without STIs (22.8%); and (4) detectable with STIs (7.8%). In comparison to the other three groups, youth in the undetectable group with STIs reported more favorable sexual risk reduction attitudes and beliefs, internet use for finding sex partners, anal sex with male partners, and condomless anal sex with male partners., Conclusions: YLWH with undetectable viral loads and other STIs engaged in higher risk behaviors. To realize the promise of the messaging campaign, undetectable = untransmittable, efforts must focus on sustained viral suppression and prevention of STIs among YLWH., (Copyright © 2020 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Injuries from exposure to explosions rose dramatically during the Iraq and Afghanistan wars, which motivated investigations of blast-related neurotrauma and operational breaching. In this study, military "breachers" were exposed to controlled, low-level blast during a 10-day explosive breaching course. Using an omics approach, we assessed epigenetic, transcriptional, and inflammatory profile changes in blood from operational breaching trainees, with varying levels of lifetime blast exposure, along with daily self-reported symptoms (with tinnitus, headaches, and sleep disturbances as the most frequently reported). Although acute exposure to blast did not confer epigenetic changes, specifically in DNA methylation, differentially methylated regions (DMRs) with coordinated gene expression changes associated with lifetime cumulative blast exposures were identified. The accumulative effect of blast showed increased methylation of PAX8 antisense transcript with coordinated repression of gene expression, which has been associated with sleep disturbance. DNA methylation analyses conducted in conjunction with reported symptoms of tinnitus in the low versus high blast incidents groups identified DMRS in KCNE1 and CYP2E1 genes. KCNE1 and CYP2E1 showed the expected inverse correlation between DNA methylation and gene expression, which have been previously implicated in noise-related hearing loss. Although no significant transcriptional changes were observed in samples obtained at the onset of the training course relative to chronic cumulative blast, we identified a large number of transcriptional perturbations acutely pre- versus post-blast exposure. Acutely, 67 robustly differentially expressed genes (fold change ≥1.5), including UFC1 and YOD1 ubiquitin-related proteins, were identified. Inflammatory analyses of cytokines and chemokines revealed dysregulation of MCP-1, GCSF, HGF, MCSF, and RANTES acutely after blast exposure. These data show the importance of an omics approach, revealing that transcriptional and inflammatory biomarkers capture acute low-level blast overpressure exposure, whereas DNA methylation marks encapsulate chronic long-term symptoms.

Study Design: Retrospective Analysis of a Quality Improvement Program., Purpose: To describe the development, implementation, and outcomes of an inpatient rehabilitation-based Short Stay Family Training (SSFT) program for patients with life-limiting conditions., Background: Patients with terminal illnesses often have functional limitations that prohibit discharge home after hospitalization, but their condition limits their ability to participate in rehabilitation in an inpatient setting., Methods and Measures: After a needs assessment, an interdisciplinary team developed an SSFT program to empower patients, caregivers, and family members by giving them the tools to be independent in caring for a patient with a life-limiting condition. Patients qualifying for the program were tracked in terms of acute care physical therapy and occupational therapy discharge recommendations, diagnosis, inpatient rehabilitation unit length of stay (LoS), caregiver involvement, and discharge location. Data were retrospectively analyzed from patients over the first 16 months., Results: Since program implementation, 30 patients and their family members participated in the program. Overall, these patients experienced decreased LoS, increased discharge to home, and increased palliative care involvement in the plan of care., Conclusion: Short Stay Family Training is a viable alternative to traditional inpatient rehabilitation to allow patients with life-limiting conditions to discharge home safely with caregiver support.

Human immunodeficiency virus-seronegative men aged 15-22 years who lost bone mineral density (BMD) during tenofovir disoproxil fumarate/emtricitabine preexposure prophylaxis (PrEP) showed BMD recovery 48 weeks following PrEP discontinuation. Lumbar spine and whole body BMD z-scores remained below baseline 48 weeks off PrEP in participants aged 15-19 years. Clinical Trials Registration. NCT01772823 (ATN 110) and NCT01769456 (ATN 113)., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

This study examined the relationships of perceived discrimination and religious coping with hypertension in a sample of Black and White Seventh-day Adventists. Data come from a community-based sample of 6128 White American, 2253 African American and 927 Caribbean American adults (67% women; mean age = 62.9 years). Results indicate lifetime unfair treatment was significantly associated with hypertension regardless of race/ethnicity. Positive religious coping was associated with lower odds of hypertension and did not interact with unfair treatment. Both positive and negative religious coping were indirectly associated with increased hypertension risk through an increase in perceived discrimination.

Background: Young women aged 15-24 years are disproportionately affected by the HIV epidemic. Two phase III trials of a vaginal ring containing 25-mg dapivirine demonstrated HIV-1 risk reduction in adult women older than 21 years but not in those aged 18-21 years. Lack of protection was correlated with low adherence., Methods: In this phase-IIa, randomized, double-blind, placebo-controlled, US, multicenter trial of the dapivirine ring in sexually active females, aged 15-17 years, participants were randomized 3:1 to a dapivirine or placebo ring to be inserted monthly for 6 months (NCT02028338). Primary safety end points included grade 2 product related adverse events and any grade 3 and higher adverse events. Adherence to ring use was assessed by plasma dapivirine concentrations, residual levels in used rings, and self-report. A plasma dapivirine concentration of >95 pg/mL was used to define short-term adherence; a residual ring level of <23.5 mg was used to define long-term adherence. Acceptability was assessed through computer-assisted self-interviews., Results: Ninety-six participants were enrolled across 6 US sites. The median age was 16.0 years. There were no differences in safety outcomes between treatment arms. Adherence to the dapivirine ring was demonstrated by both plasma measurements (87%) and residual drug levels in rings (95%). Forty-two percent (95% confidence interval: 32 to 52) of participants reported that they never removed the ring. Participants noted no discomfort due to the ring at 87% of visits and "liking" the ring at 93% of visits., Conclusion: The dapivirine vaginal ring, a promising topical microbicide, was well tolerated and acceptable in young US adolescents.

On 11th March 2020, the World Health Organisation (WHO) announced a pandemic caused by a novel beta-coronavirus SARS-CoV-2, designated COVID-19. The virus emerged in December 2019 in Wuhan, China, has spread across the world as a global pandemic. The traditional use of medicines from plants can be traced back to 60,000 years. Global interest in the development of drugs from natural products has increased greatly during the last few decades. Essential oils (EOs) have been studied through the centuries and are known to possess various pharmaceutical properties. In the present review, we have highlighted the current biology, epidemiology, various clinical aspects, different diagnostic techniques, clinical symptoms, and management of COVID-19. An overview of the antiviral action of EOs, along with their proposed mechanism of action and in silico studies conducted, is described. The reported studies of EOs' antiviral activity highlight the baseline data about the additive and/or synergistic effects among primary or secondary phytoconstituents found in individual oils, combinations or blends of oils and between EOs and antiviral drugs. It is hoped that further research will provide better insights into EOs' potential to limit viral infection and aid in providing solutions through natural, therapeutically active agents., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Changes in 18 F-fluorodeoxyglucose ([ 18 F]FDG) measured by positron emission tomography (PET) can be used for the noninvasive detection of metabolic dysfunction following mild traumatic brain injury (mTBI). This study examined the time course of metabolic changes induced by primary blast injury by measuring regional [ 18 F]FDG uptake. Adult, male rats were exposed to blast overpressure (15 psi) or sham injury, and [ 18 F]FDG uptake was measured before injury and again at 1-3 h and 7 days post-injury, using both volume-of-interest (VOI) and voxel-based analysis. VOI analysis revealed significantly increased [ 18 F]FDG uptake in corpus callosum and amygdala at both 1-3 h and 7 days following blast, while a transient decrease in uptake was observed in the midbrain at 1-3 h only. Voxel-based analysis revealed similar significant differences in uptake between sham and blast-injured rats at both time points. At 1-3 h post-injury, clusters of increased uptake were found in the amygdala, somatosensory cortex, and corpus callosum, while regions of decreased uptake were observed in midbrain structures (inferior colliculus, ventrolateral tegmental area) and dorsal auditory cortex. At day 7, a region of increased uptake in blast-injured rats was found in a cluster centered on the cortex-amygdala transition zone, while no regions of decreased uptake were observed. These results suggest that a relatively mild primary blast injury results in altered brain metabolism in multiple brain regions and that post-injury time of assessment is an important factor in observing regional changes in [ 18 F]FDG uptake., (Published by Elsevier B.V.)

People living with HIV (PLWH) have a higher prevalence of smoking and are less likely to quit smoking than the general population. Few studies involving a large sample of PLWH receiving routine care have evaluated factors associated with smoking cessation. This retrospective longitudinal cohort study evaluated factors associated with smoking cessation among PLWH from 2007 to 2018. Of 1,714 PLWH smokers included in the study, 27.6% reported quitting smoking. Suppressed plasma HIV-1 RNA (<200 copies/ml) was significantly associated with an increased likelihood of smoking cessation (HR adjusted = 1.27, 95% CI [1.03, 1.58]); whereas age/10 year increments (HR adjusted = 0.12, 95% CI [0.04, 0.38]), greater length of care at the HIV clinic (HR adjusted = 0.97, 95% CI [0.94, 0.99]), lack of insurance (HR adjusted = 0.77, 95% CI [0.61, 0.99]) or having public insurance (HR adjusted = 0.74, 95% CI [0.55, 0.97)]), current substance use (HR adjusted = 0.66, 95% CI [0.43, 0.97]) and risk of developing alcohol use disorder (HR adjusted = 0.60, 95% CI [0.43, 0.84]) were associated with a reduced likelihood of quitting smoking. These findings underscore the importance of early smoking cessation intervention among PLWH. In addition, targeted smoking cessation intervention strategies are needed for groups at risk for being less likely to quit, including older patients, and those with alcohol and substance use disorders.

Background: People living with HIV (PLWH) have a high level of interest in quitting smoking, but only a small proportion have sustainable abstinence 6 months after cessation. Few investigations have focused on relapse to smoking among PLWH. In this investigation, we evaluated the prevalence of relapse after smoking cessation and the characteristics associated with smoking relapse using a retrospective, longitudinal cohort of PLWH during an eight-year observation., Methods: All patients aged ≥19 years that reported current smoking during the study period and then reported not smoking on a subsequent tobacco use questionnaire (quitters) were eligible for the study. In addition, patients required at least one subsequent follow-up visit after quitting where smoking status was again reported to allow for assessment of relapse. A Cox proportional hazard model was fit to evaluate factors associated with smoking relapse in PLWH attending routine clinical care., Results: Of the 473 patients who quit smoking in the study, 51% relapsed. In multivariable analysis, factors significantly associated with a higher likelihood of relapse were anxiety symptoms (HR = 1.55, 95% CI [1.11, 2.17]) and at-risk alcohol use (HR = 1.74, 95% CI [1.06, 2.85]), whereas antiretroviral therapy (ART) adherence (HR = 0.65, 95% CI [0.49, 0.99]) and longer time in care (HR = 0.94, 95% CI [0.91, 0.98]) were associated with a reduced likelihood of relapse after cessation., Conclusion: Our study underscores the high prevalence of smoking relapse that exists among PLWH after they quit smoking. Successful engagement in mental health care may enhance efforts to reduce relapse in the underserved populations of PLWH.

Among high-grade brain tumors, glioblastoma is particularly difficult to treat, in part due to its highly infiltrative nature which contributes to the malignant phenotype and high mortality in patients. In order to better understand the signaling pathways underlying glioblastoma invasion, we performed the first large-scale CRISPR-Cas9 loss of function screen specifically designed to identify genes that facilitate cell invasion. We tested 4,574 genes predicted to be involved in trafficking and motility. Using a transwell invasion assay, we discovered 33 genes essential for invasion. Of the 11 genes we selected for secondary testing using a wound healing assay, 6 demonstrated a significant decrease in migration. The strongest regulator of invasion was mitogen-activated protein kinase 4 (MAP4K4). Targeting of MAP4K4 with single guide RNAs or a MAP4K4 inhibitor reduced migration and invasion in vitro. This effect was consistent across three additional patient derived glioblastoma cell lines. Analysis of epithelial-mesenchymal transition markers in U138 cells with lack or inhibition of MAP4K4 demonstrated protein expression consistent with a non-invasive state. Importantly, MAP4K4 inhibition limited migration in a subset of human glioma organotypic slice cultures. Our results identify MAP4K4 as a novel potential therapeutic target to limit glioblastoma invasion.

Background: Advances in medical technology have allowed for customized prognosis, diagnosis, and treatment regimens that utilize multiple heterogeneous data sources. Multiple kernel learning (MKL) is well suited for the integration of multiple high throughput data sources. MKL remains to be under-utilized by genomic researchers partly due to the lack of unified guidelines for its use, and benchmark genomic datasets., Results: We provide three implementations of MKL in R. These methods are applied to simulated data to illustrate that MKL can select appropriate models. We also apply MKL to combine clinical information with miRNA gene expression data of ovarian cancer study into a single analysis. Lastly, we show that MKL can identify gene sets that are known to play a role in the prognostic prediction of 15 cancer types using gene expression data from The Cancer Genome Atlas, as well as, identify new gene sets for the future research., Conclusion: Multiple kernel learning coupled with modern optimization techniques provides a promising learning tool for building predictive models based on multi-source genomic data. MKL also provides an automated scheme for kernel prioritization and parameter tuning. The methods used in the paper are implemented as an R package called RMKL package, which is freely available for download through CRAN at https://CRAN.R-project.org/package=RMKL .

Plants, unlike animals, exhibit a very high degree of plasticity in their growth and development and employ diverse strategies to cope with the variations during diurnal cycles and stressful conditions. Plants and animals, despite their remarkable morphological and physiological differences, share many basic cellular processes and regulatory mechanisms. Alternative splicing (AS) is one such gene regulatory mechanism that modulates gene expression in multiple ways. It is now well established that AS is prevalent in all multicellular eukaryotes including plants and humans. Emerging evidence indicates that in plants, as in animals, transcription and splicing are coupled. Here, we reviewed recent evidence in support of co-transcriptional splicing in plants and highlighted similarities and differences between plants and humans. An unsettled question in the field of AS is the extent to which splice isoforms contribute to protein diversity. To take a critical look at this question, we presented a comprehensive summary of the current status of research in this area in both plants and humans, discussed limitations with the currently used approaches and suggested improvements to current methods and alternative approaches. We end with a discussion on the potential role of epigenetic modifications and chromatin state in splicing memory in plants primed with stresses.

Tauopathies, including frontotemporal dementia (FTD) and Alzheimer's disease (AD) are progressive neurodegenerative diseases clinically characterized by cognitive decline and could be caused by the aggregation of hyperphosphorylated pathological tau (pTau) as neurofibrillary tangles (NFTs) inside neurons. There is currently no FDA-approved treatment that cures, slows or prevents tauopathies. Current immunotherapy strategies targeting pTau have generated encouraging data but may pose concerns about scalability, affordability, and efficacy. Here, we engineered a virus-like particle (VLP)-based vaccine in which tau peptide, phosphorylated at threonine 181, was linked at high valency to Qß bacteriophage VLPs (pT181-Qß). We demonstrate that vaccination with pT181-Qß is sufficient to induce a robust and long-lived anti-pT181 antibody response in the sera and the brains of both Non-Tg and rTg4510 mice. Only sera from pT181-Qß vaccinated mice are reactive to classical somatodendritic pTau in human FTD and AD post-mortem brain sections. Finally, we demonstrate that pT181-Qß vaccination reduces both soluble and insoluble species of hyperphosphorylated pTau in the hippocampus and cortex, avoids a Th1-mediated pro-inflammatory cell response, prevents hippocampal and corpus callosum atrophy and rescues cognitive dysfunction in a 4-month-old rTg4510 mouse model of FTD. These studies provide a valid scientific premise for the development of VLP-based immunotherapy to target pTau and potentially prevent Alzheimer's diseases and related tauopathies., Competing Interests: Competing interestsThe authors declare no competing interests.

The aims of this study were to: 1) determine prevalence of anogenital and oral HPV, 2) determine concordance between HPV at anal, perianal, scrotal/penile, and oral sites; and 3) describe factors associated with anogenital HPV types targeted by the 9-valent vaccine. Data were collected from 2012 to 2015 among men who have sex with men 18-26 years of age enrolled in a vaccine trial (N = 145). Penile/scrotal, perianal, anal, and oral samples were tested for 61 HPV types. Logistic regression was used to identify factors associated with types in the 9-valent vaccine. Participants' mean age was 23.0 years, 55.2% were African-American, and 26.2% were Hispanic; 93% had anal, 40% penile, and 6% oral HPV. Among those with anogenital infection, 18% had HPV16. Concordance was low between anogenital and oral sites. Factors independently associated with a 9-valent vaccine-type HPV were: race (African-American vs. White, OR=2.67, 95% CI=1.11-6.42), current smoking (yes vs. no, OR=2.37, 95% CI=1.03-5.48), and number of recent receptive anal sex partners (2+ vs. 0, OR=3.47, 95% CI=1.16-10.4). Most MSM were not infected with HPV16 or HPV18, suggesting that they may still benefit from HPV vaccination, but anogenital HPV was very common, highlighting the importance of vaccinating men before sexual initiation. CLINICAL TRIAL NUMBER: NCT01209325., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Plants display exquisite control over gene expression to elicit appropriate responses under normal and stress conditions. Alternative splicing (AS) of pre-mRNAs, a process that generates two or more transcripts from multi-exon genes, adds another layer of regulation to fine-tune condition-specific gene expression in animals and plants. However, exactly how plants control splice isoform ratios and the timing of this regulation in response to environmental signals remains elusive. In mammals, recent evidence indicate that epigenetic and epitranscriptome changes, such as DNA methylation, chromatin modifications and RNA methylation, regulate RNA polymerase II processivity, co-transcriptional splicing, and stability and translation efficiency of splice isoforms. In plants, the role of epigenetic modifications in regulating transcription rate and mRNA abundance under stress is beginning to emerge. However, the mechanisms by which epigenetic and epitranscriptomic modifications regulate AS and translation efficiency require further research. Dynamic changes in the chromatin landscape in response to stress may provide a scaffold around which gene expression, AS and translation are orchestrated. Finally, we discuss CRISPR/Cas-based strategies for engineering chromatin architecture to manipulate AS patterns (or splice isoforms levels) to obtain insight into the epigenetic regulation of AS., (© The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research.)

In clinical breast cancer intervention, selection of the optimal treatment protocol based on predictive biomarkers remains an elusive goal. Here, we present a modeling tool to predict the likelihood of breast cancer response to neoadjuvant chemotherapy using patient specific tumor vasculature biomarkers. A semi-automated analysis was implemented and performed on 3990 histological images from 48 patients, with 10-208 images analyzed for each patient. We applied a histology-based model to resected primary breast cancer tumors (n = 30), and then evaluated a cohort of patients (n = 18) undergoing neoadjuvant chemotherapy, collecting pre- and post-treatment pathology specimens and MRI data. We found that core biopsy samples can be used with acceptable accuracy (r = 0.76) to determine histological parameters representative of the whole tissue region. Analysis of model histology parameters obtained from tumor vasculature measurements, specifically diffusion distance divided by radius of drug source (L/rb) and blood volume fraction (BVF), provides a statistically significant separation of patients obtaining a pathologic complete response (pCR) from those that do not (Student's t-test; P < 0.05). With this model, it is feasible to evaluate primary breast tumor vasculature biomarkers in a patient specific manner, thereby allowing a precision approach to breast cancer treatment.

Traditional home healthcare reimbursement models emphasize intervention after a medical or functional issue occurs, and there is little evidence of preventative home-based physical therapy services for those at highest risk of becoming homebound due to illness, injury, or functional limitation. The purpose of this study was to describe the development and initial pilot results of the Home-based Older Person Upstreaming Prevention Physical Therapy (HOP-UP-PT) Program. The prospective observational pilot study included five participants referred from a community center. The HOP-UP-PT Program utilized fall risk, functional, environmental, cognitive, and health-related assessments. Two males and three females aged 73 to 92 years were enrolled. Outcomes suggest that health, functional, and environmental benefits may be achieved when an older person participates in the HOP-UP-PT Program. Safety and health benefits gained by two individuals referred to the program, but who did not meet inclusion criteria, are also reported. Evidence emerging from this pilot study suggests trends toward improved functional outcomes associated with reduced fall risk and customized home-based safety recommendations among older adults participating in the HOP-UP-PT Program.

Case: Charles is a 10-year-old African-American male who presents to the Developmental Behavioral Pediatrics Clinic for evaluation of his learning. His primary care provider (PCP) was concerned that his developmental delays were negatively affecting his ability to engage in his homeschooling curriculum and also that his mother seemed unaware of the severity of his delays. Neuropsychological evaluation had been recommended by the PCP several times in the past, but the family declined. At one point, the PCP had considered potential child protective services (CPS) referral for medical neglect because of missed appointments and lack of follow-through on recommendations, which motivated the parent to bring him to this appointment.Medical history was significant for failure to thrive and hypotonia in infancy. Charles received physical therapy through early childhood for hypotonia and motor coordination deficits. His mother removed him from public school and initiated homeschooling in kindergarten after he suffered a dental injury at recess of which she was not notified. The current homeschooling (fourth grade) approach was described as "off and on" activities for 3 hours daily. His mother acknowledged that she struggled to get him to participate as he preferred using the computer and tablet rather than doing school work, and they also argued regularly about his impulsive eating. The patient's mother also described her own medical conditions that contributed to a high degree of stress and fatigue, which she felt made homeschooling more difficult.On examination, the patient was obese and had widely set, almond-shaped eyes; a wide-based gait; an immature pencil grasp; and a mild truncal and appendicular hypotonia. Performance on the Kaufman Brief Intelligence Test, second edition, was below average for the verbal scale (78) and low average for the nonverbal scale (89). On the Wechsler Individualized Achievement Test, third edition, he was unable to perform any multiplication, could not write his own last name (was practicing tracing at home per maternal report), and read at a below first-grade reading level (standardized scores could not be calculated). His conversations with the examiner were mainly limited to the topic of video games. He spoke in short sentences with approximately 85% intelligibility but with coordinated gaze. He appeared mentally exhausted as testing progressed.Feedback to the parent included concern for a learning disability possibly associated with a genetic condition such as Prader-Willi syndrome (because of the history of hypotonia and impulsive eating), and genetic testing was recommended. Because of Charles' difficulty accessing the homeschool curriculum, a special education evaluation through the local public school district was also recommended, but his mother resisted, stating that she felt public special education "keeps children like him down" by focusing primarily on African-American children and stigmatizing their differences.The mother does not return phone calls made 1 month later to follow-up on considering a special education evaluation, and team members raise concern about medical neglect. What would you do next?

We examined associations of 25-hydroxy vitamin D (25-OHD), tenofovir disoproxil fumarate (TDF), and bone toxicity. We studied TDF/emtricitabine (FTC) HIV pre-exposure prophylaxis (PrEP) in young men who have sex with men (YMSM). Bone toxicity was predefined using bone mineral density/content change from baseline to week 48. Baseline serum 25-OHD was dichotomized as <20 ng/mL (insufficient/deficient) versus ≥20 (sufficient), and week 48 dried blood spot tenofovir diphosphate (TFV-DP) as >700 fmol/punch (protective against HIV acquisition) versus ≤700. Associations were examined by univariate and multivariable logistic regression, reporting crude and adjusted odds ratios (ORs), with 95% confidence intervals (CIs). Of 101 enrolled, 69 had complete bone assessments and 25-OHD; of these, 59 had week 48 TFV-DP data. Median (Q1-Q3) age was 20 (18-21) years; 54% were black/African American. In univariate analysis, participants with baseline 25-OHD <20 ng/mL (OR = 5.4; 95% CI = 1.9-16.5) and blacks (OR = 4.9; 95% CI = 1.7-15.2) had greater odds of bone toxicity than those with 25-OHD ≥20 or other races. TFV-DP was not associated with bone toxicity (OR = 1.6; 95% CI = 0.5-5.5). In multivariable analysis, compared with those with 25-OHD ≥20 and TFV-DP ≤700, those with 25-OHD ≥20 and TFV-DP >700 (OR = 11.5; 95% CI = 1.4-169.6), 25-OHD <20 and TFV-DP ≤700 (OR = 19.4; 95% CI = 3.0-228.7), and 25-OHD <20 and TFV-DP >700 (OR = 32.3; 95% CI = 3.3-653.6) had greater odds of bone toxicity after adjusting for race. In multivariable models, 25-OHD insufficiency, protective TFV-DP concentrations, and black race were significantly associated with bone toxicity after 48 weeks of TDF/FTC PrEP in YMSM. Clinical Trials Registration: NCT01769469.

Background: Young men who have sex with men (YMSM) experience disparities in HIV acquisition more than any other group. Daily oral pre-exposure prophylaxis (PrEP) with tenofovir/emtricitabine has been shown to effectively prevent HIV transmission in YMSM; however, recent studies suggest that young Black men who have sex with men experience subprotective levels of tenofovir diphosphate more frequently than other groups., Setting: Combined data from Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN) 110/113, 2 open-label PrEP studies that provided PrEP and evidence-based behavioral interventions to YMSM aged 15-22 years., Methods: Bivariate and logistic regression analyses were used to examine sociodemographic and behavioral factors associated with protective tenofovir diphosphate levels (defined as ≥700 fmol/punch) in ATN 110/113 data., Results: In bivariate analysis, self-identified Black participants, residential displacement due to sexual orientation, low perceived risk, and stigma with the medication were associated with subprotective levels. Hispanic ethnicity was associated with protective levels. In the final models, Black males were less likely to have subprotective levels than non-Black males at 4, 8, and 12 weeks. Self-reported displacement due to sexual orientation was associated with subprotective levels, whereas older age was as associated with protective levels., Conclusions: These findings highlight how future behavioral research and biomedical prevention efforts in YMSM will need to address PrEP disparities that may occur in young Black men who have sex with men, perception of risk, and lack of key supportive housing during this period that may be critical factors that contribute to HIV acquisition.

Aging results in increased activation of inflammatory glial cells and decreased neuronal viability following spinal cord injury (SCI). Metabolism and transport of glucose is also decreased with age, although the influence of age on glucose transporter (GLUT) expression or glucose uptake in SCI is currently unknown. We therefore performed [ 18 F]Fluorodeoxyglucose (FDG) PET imaging of young (3 month) and middle-aged (12 month) rats. Glucose uptake in middle-aged rats was decreased compared to young rats at baseline, followed by increased uptake 14 days post contusion SCI. qRT-PCR and protein analysis revealed an association between 14 day glucose uptake and 14 day post-injury inflammation. Further, gene expression analysis of neuron-specific GLUT3 and non-specific GLUT4 (present on glial cells) revealed an inverse relationship between GLUT3/4 gene expression and glucose uptake patterns. Protein expression revealed increased GLUT3 in 3 month rats only, consistent with age related decreases in glucose uptake, and increased GLUT4 in 12 month rats only, consistent with age related increases in inflammatory activity and glucose uptake. Inconsistencies between gene and protein suggest an influence of age-related impairment of translation and/or protein degradation. Overall, our findings show that age alters glucose uptake and GLUT3/4 expression profiles before and after SCI, which may be dependent on level of inflammatory response, and may suggest a therapeutic avenue in addressing glucose uptake in the aging population., (Published by Elsevier B.V.)

HIV infections among adolescents and young adults continue to grow and clinical guidelines recommend the immediate start of life-saving antiretroviral therapy (ART). Unfortunately, suboptimal medication adherence among youth is common and can lead to poorer health outcomes as well as onward transmission of HIV to sexual partners. Clinical tools to assess treatment readiness are needed and can assist with adherence intervention strategies for youth. An assessment tool that we previously developed, the HIV Treatment Readiness Measure (HTRM), was administered to 595 HIV-positive youth ages 13-24 recruited from adolescent medicine clinics in the United States. Participants were followed for a minimum of 6 months and had to have at least one viral load test completed to be included in this analysis. The HTRM demonstrated high internal consistency (Chronbach's alpha = 0.86). For participants currently on ART at study entry, higher overall treatment readiness scores predicted future viral suppression (OR 1.52). Individual scores on three of the measure's factors (Psychosocial Issues, Connection with Care, and HIV Medication Beliefs) were also significant predictors of viral suppression. For those participants not on ART at study entry, the HIV Medication Beliefs factor significantly predicted who would eventually start ART (OR 2.26) but overall treatment readiness scores did not predict viral suppression in that group.

Malaria remains a significant public health problem worldwide with an estimated annual global incidence of 200 million and an estimated 450,000 annual deaths. Among the five known human malarial species, Plasmodium falciparum is the deadliest and most resistant to antimalarials. Hence, there is a need for new antimalarial targets. The rational design of a drug is usually based on biochemical and physiological differences between pathogens and their hosts. In view of their high rate of replication, parasites require very active nucleic acid synthesis which necessitates large supplies of the indispensable pyrimidine nucleotides. Consequently, delineation of P. falciparum pyrimidine metabolic pathways may reveal potential targets for the chemotherapy of malaria. Previous studies reported the existence of pyrimidine de novo pathways in this organism. The present results demonstrate the presence of enzymes of the pyrimidine salvage pathways in P. falciparum and indicate that this parasite is capable of pyrimidine salvage. Furthermore, some of the pyrimidine salvage enzymes, e.g., dTMP kinase, phosphoribosyltransferase, and uridine phosphorylase could be excellent targets for chemotherapeutic intervention against this parasite., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

We explored potential barriers and facilitators for prostate cancer screening choices among high-risk Black men. In our sample of 264 Black men over 45 years of age living in the U.S. who met the American Cancer Society criteria for screening, we found that only 49.6% had ever been screened. We investigated potential barriers including screening intention, access to care, medical mistrust, and fatalism. Potential facilitating factors investigated were provider-patient conversations encompassing the pros and cons of screening, ethnicity taken into account, insurance, and previous prostate cancer screening. Recommendations and resources are suggested to increase screening of high-risk Black men.