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We investigate the spectral properties of a class of Jacobi matrices resulting from periodic pertubations of Jacobi operators with smooth coefficients. [ABSTRACT FROM AUTHOR]

Abstract Background Increased biotic and abiotic plant stresses due to climate change together with an expected global human population of over 9 billion by 2050 intensifies the demand for agricultural production on marginal lands. Soil salinity is one of the major abiotic stresses responsible for reduced crop productivity worldwide and the salinization of arable land has dramatically increased over the last few decades. Consequently, as land becomes less amenable for conventional agriculture, plants grown on marginal soils will be exposed to higher levels of soil salinity. Forage grasses are a critical component of feed used in livestock production worldwide, with many of these same species of grasses being utilized for lawns, erosion prevention, and recreation. Consequently, it is important to develop a better understanding of salt tolerance in forage and related grass species. Findings A gene encoding a ZnF protein was identified during the analysis of a salt-stress suppression subtractive hybridization (SSH) expression library from the forage grass species Festuca arundinacea. The expression pattern of FaZnF was compared to that of the well characterized gene for delta 1-pyrroline-5-carboxylate synthetase (P5CS), a key enzyme in proline biosynthesis, which was also identified in the salt-stress SSH library. The FaZnF and P5CS genes were both up-regulated in response to salt and drought stresses suggesting a role in dehydration stress. FaZnF was also up-regulated in response to heat and wounding, suggesting that it might have a more general function in multiple abiotic stress responses. Additionally, potential downstream targets of FaZnF (a MAPK [Mitogen-Activated Protein Kinase], GST [Glutathione-S-Transferase] and lipoxygenase L2) were found to be up-regulated in calli overexpressing FaZnF when compared to control cell lines. Conclusions This work provides evidence that FaZnF is an AN1/A20 zinc finger protein that is involved in the regulation of at least two pathways initiated by the salt stress response, thus furthering our understanding of the mechanisms of cellular action during a stress that is applicable to commercial crops worldwide.

Abstract Background Choke, caused by the endophytic fungus Epichloë typhina, is an important disease affecting orchardgrass (Dactylis glomerata L.) seed production in the Willamette Valley. Little is known concerning the conditions necessary for successful infection of orchardgrass by E. typhina. Detection of E. typhina in plants early in the disease cycle can be difficult due to the sparse distribution of hyphae in the plant. Therefore, a sensitive method to detect fungal infection in plants would provide an invaluable tool for elucidating the conditions for establishment of infection in orchardgrass. Utilization of a marker gene, such as the green fluorescent protein (GFP), transformed into Epichloë will facilitate characterization of the initial stages of infection and establishment of the fungus in plants. Findings We have developed a rapid, efficient, and reproducible transformation method using electroporation of germinating Epichloë conidia isolated from infected plants. Conclusions The GFP labelled E. typhina provides a valuable molecular tool to researchers studying conditions and mechanisms involved in the establishment of choke disease in orchardgrass.

(1) Background: This study aimed to quantify and evaluate the publication rate and discrepancies of functional urology abstracts from international conferences, and to explore the interdisciplinary contributions of urology and gynecology to the field. (2) Methods: A retrospective bibliometric and content analysis was conducted on abstracts presented between 2015 and 2019 at the EAU and ICS congresses, focusing on functional-urological keywords. A discrepancy scoring system ranging from 0 (minor discrepancies) to 3 (significant discrepancies) assessed the consistency between conference abstracts and full-text publications, and an in-depth analysis determined the disciplinary origin of these publications. (3) Results: Between 2015 and 2019, 53% of EAU and 57% of ICS congress abstracts were published as full-text articles, with minor discrepancies in 38% of EAU and 49% of ICS publications, and significant discrepancies in 17% from both. Urology departments dominated publications, contributing 68% at EAU and 55% at ICS, whereas gynecology contributed only 1% at EAU and 12% at ICS. (4) Conclusions: This study illuminates the need for improved reporting standards and interdisciplinary collaboration in functional urology, as well as increased gynecology research in functional urology-related fields, suggesting that addressing these issues is crucial for advancing the field and enhancing patient care.

Objective: Gaps in gender-based equity persist in academic otolaryngology. Here we present a needs-based assessment of otolaryngology faculty and trainees regarding facilitators and barriers to professional satisfaction and career development in academic medicine., Methods: A qualitative study of otolaryngology faculty, trainees, and administrators who identify as women at an academic tertiary care center was performed from 2020 to 2021 using focus groups and semi-structured interviews. Five confidential, virtual focus group sessions moderated by a third-party executive coach were audio-taped, transcribed, and reviewed for thematic content., Results: Of 48 women invited, 77% participated (18 faculty/administrative leaders, 10 residents/fellows, 4 audiologists). Participants noted direct patient care, support from colleagues who identify as women, and the transition to virtual meetings as facilitators of current professional satisfaction. Five themes emerged as barriers to workplace satisfaction and career development including (1) limited professional schedule flexibility, (2) competing commitments such as childcare exacerbated by pandemic, (3) lack of visible departmental leadership who identify as women, (4) perceived lack of organic sponsorship within subspecialty divisions, and (5) frequent identity-associated microaggressions from patients and staff outside the department. Strategies identified for improving gender-based equity included (1) promoting department-wide awareness of workplace gender-based differences, (2) implicit bias training within established programming such as grand rounds conferences, and (3) novel faculty programming such as leadership development training and formal junior faculty mentorship., Conclusion: Confidential needs-based assessment of otolaryngology faculty and trainees identified both persistent gaps and strategies to enhance recruitment, support career development, and grow professional satisfaction of women within academic otolaryngology., Level of Evidence: 3., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Authors. Laryngoscope Investigative Otolaryngology published by Wiley Periodicals LLC on behalf of The Triological Society.)

Introduction: First-line systemic therapy (ST) options for advanced hepatocellular carcinoma (HCC) include tyrosine kinase inhibitors and immunotherapy (IO). Evolving data suggest prolonged overall survival (OS) when ST is combined with stereotactic body radiation therapy (SBRT), although evidence is significantly limited in HCC populations. We hypothesized that advanced HCC patients in the National Cancer Database (NCDB) would have improved OS when receiving ST+SBRT vs ST alone., Methods: Stage III/IV HCC patients diagnosed from 2010-2020 and treated with first-line ST±SBRT were identified from the NCDB. The primary endpoint was OS from date of diagnosis stratified by the receipt of SBRT (ST+SBRT vs ST alone). Survival was estimated using Kaplan-Meier methodology and compared via log-rank. Multivariate analysis (MVA) was performed by Cox regression., Results: Of 10,505 eligible patients with stage III disease, 115 (1.1%) received ST+SBRT and 10,390 (98.9%) received ST alone. Of 9,617 eligible patients with stage IV disease, 127 (1.3%) received ST+SBRT and 9,490 (98.7%) received ST alone. Median follow-up time was 6.8 months. Baseline characteristics were similar between cohorts. Patients with stage III disease receiving ST+SBRT had improved median OS (12.62 months vs 8.38 months) and higher rates of survival at 1-year (53.0% vs 38.7%) and 2-years (27.0% vs 20.7%) compared to those receiving ST alone (log-rank P =0.0054). Similarly, patients with stage IV disease receiving ST+SBRT had improved median OS (11.79 months vs 5.72 months) and higher rates of survival at 1-year (49.6% vs 26.2%) and 2-years (23.6% vs 12.0%) (log-rank P <0.0001). On MVA, receipt of SBRT predicted improved OS (HR=0.748, 95%CI 0.588-0.951; P =0.0178) and receipt of IO trended towards improved OS (HR=0.859, 95%CI 0.735-1.003; P =0.0538)., Conclusion: In advanced HCC, patients receiving ST+SBRT had improved OS compared to those receiving ST alone. Prospective clinical trials are warranted to better identify HCC populations which may benefit from combined modality therapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Piening, Swaminath, Dombrowski, Teague, Al-Hammadi and Shahi.)

Purpose: Immunotherapy (IO) has significantly improved outcomes in metastatic renal cell carcinoma (mRCC). Preclinical evidence suggests that responses to IO may be potentiated via immunomodulatory effects of stereotactic radiation therapy (SRT). We hypothesized that clinical outcomes from the National Cancer Database (NCDB) would demonstrate improved overall survival (OS) in patients with mRCC receiving IO + SRT versus IO alone., Methods and Materials: Patients with mRCC receiving first-line IO ± SRT were identified from the NCDB. Conventional radiation therapy was allowed in the IO alone cohort. The primary endpoint was OS stratified by the receipt of SRT (IO + SRT vs IO alone). Secondary endpoints included OS stratified by the presence of brain metastases (BM) and timing of SRT (before or after IO). Survival was estimated using Kaplan-Meier methodology and compared via the log-rank test., Results: Of 644 eligible patients, 63 (9.8%) received IO + SRT, and 581 (90.2%) received IO alone. Median follow-up time was 17.7 months (range, 2-24 months). Sites treated with SRT included the brain (71.4%), lung/chest (7.9%), bones (7.9%), spine (6.3%), and other (6.3%). OS was 74.4% versus 65.0% at 1 year and 71.0% versus 59.4% at 2 years for the IO + SRT and IO alone groups, respectively, although this difference did not reach statistical significance (log-rank P  = .1077). In patients with BM, however, 1-year OS (73.0% vs 54.7%) and 2-year OS (70.8% vs 51.4%) was significantly higher in those receiving IO + SRT versus IO alone, respectively (pairwise P  = .0261). Timing of SRT (before or after IO) did not influence OS (log-rank P  = .3185)., Conclusions: Patients with BM secondary to mRCC had prolonged OS with the addition of SRT to IO. Factors such as International mRCC Database Consortium risk stratification, oligometastatic tumor burden, SRT dose/fractionation, and utilization of doublet therapy should be considered in future analyses to better identify patients who may benefit from combined IO + SRT. Further prospective studies are warranted., (© 2023 The Authors.)

Background: Major depressive disorder (MDD) is a highly burdensome health condition, for which there are numerous accepted pharmacological and psychological interventions. Adjunctive treatment (augmentation/combination) is recommended for the ~50% of MDD patients who do not adequately respond to first-line treatment. We aimed to evaluate the current evidence for concomitant approaches for people with early-stage treatment-resistant depression (TRD; defined below)., Methods: We systematically searched Medline and Institute for Scientific Information Web of Science to identify randomised controlled trials of adjunctive treatment of ⩾10 adults with MDD who had not responded to ⩾1 adequate antidepressant. The cochrane risk of bias (RoB) tool was used to assess study quality. Pre-post treatment meta-analyses were performed, allowing for comparison across heterogeneous study designs independent of comparator interventions., Results: In total, 115 trials investigating 48 treatments were synthesised. The mean intervention duration was 9 weeks (range 5 days to 18 months) with most studies assessed to have low ( n  = 57) or moderate ( n  = 51) RoB. The highest effect sizes (ESs) were from cognitive behavioural therapy (ES = 1.58, 95% confidence interval (CI): 1.09-2.07), (es)ketamine (ES = 1.48, 95% CI: 1.23-1.73) and risperidone (ES = 1.42, 95% CI: 1.29-1.61). Only aripiprazole and lithium were examined in ⩾10 studies. Pill placebo (ES = 0.89, 95% CI: 0.81-0.98) had a not inconsiderable ES, and only six treatments' 95% CIs did not overlap with pill placebo's (aripiprazole, (es)ketamine, mirtazapine, olanzapine, quetiapine and risperidone). We report marked heterogeneity between studies for almost all analyses., Conclusions: Our findings support cautious optimism for several augmentation strategies; although considering the high prevalence of TRD, evidence remains inadequate for each treatment option.

Background: Despite rising rates of syphilis among people with human immunodeficiency virus (HIV; PWH) in the United States, there is no optimal syphilis screening frequency or prioritization., Methods: We reviewed records of all PWH in care between 1 January 2014 and 16 November 2018 from 4 sites in the Centers for AIDS Research Network of Integrated Clinical Systems Cohort (CNICS; N = 8455). We calculated rates of syphilis testing and incident syphilis and used Cox proportional hazards models modified for recurrent events to examine demographic and clinical predictors of testing and diagnosis., Results: Participants contributed 29 568 person-years of follow-up. The rate of syphilis testing was 118 tests per 100 person-years (95% confidence interval [CI]: 117-119). The rate of incident syphilis was 4.7 cases per 100 person-years (95% CI: 4.5-5.0). Syphilis diagnosis rates were highest among younger cisgender men who have sex with men and transgender women, Hispanic individuals, people who inject drugs, and those with detectable HIV RNA, rectal infections, and hepatitis C., Conclusions: We identified PWH who may benefit from more frequent syphilis testing and interventions for syphilis prevention., Competing Interests: Potential conflicts of interest. K. C. reports investigator-initiated grant support from Gilead Sciences and serving on Gilead Sciences Medical Advisory Board, outside the submitted work. J. D. reports consulting fees from National Association of State and Territorial AIDS Directors and payment or honoraria for lectures, presentations, speaker’s bureaus, manuscript writing, or educational events from Planned Parenthood Federation of America, outside the submitted work. E. C. reports unrelated research grants, funding paid to UC Regents, from Merck Sharp and Dohme and Gilead Science, outside the submitted work. H. M. C. reports funding from the National Institutes of Health (NIH), the Agency for Healthcare Research and Quality, and ViiV and participation on the NIH Office of AIDS Research Advisory Council, outside the submitted work. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Preexposure prophylaxis (PrEP) discontinuations are common and are associated with subsequent HIV acquisition. The population-level impact of PrEP discontinuations is unknown., Methods: Public health staff routinely asked men who have sex with men (MSM) with newly diagnosed HIV infection about their history of PrEP use as part of partner notification interviews in King County, WA, from 2013 to 2021. We assessed trends in the proportion of MSM who ever took PrEP and described reasons for PrEP discontinuation., Results: A total of 1098 MSM were newly diagnosed with HIV during the study period; of whom, 797 (73%) were interviewed, and 722 responded to questions about their history of PrEP use. Ninety-four (13%) reported ever taking PrEP. The proportion of MSM who ever used PrEP before HIV diagnosis increased from 2.3% in 2014 to 26.6% in 2020-2021 ( P < 0.001 for trend). The median time from PrEP discontinuation to HIV diagnosis was 152 days, and median duration on PrEP was 214 days. Common reasons for stopping PrEP included self-assessment as being at low risk for HIV, side effects, and insurance issues. Nineteen men were on PrEP at the time of HIV diagnosis; mutations conferring emtricitabine/tenofovir resistance were identified in 8 (53%) of 15 men with available genotype data., Conclusion: More than 25% of MSM with newly diagnosed HIV from 2020 to 2021 had ever used PrEP. More than 50% who discontinued PrEP were diagnosed <6 months after stopping. Strategies to preempt PrEP discontinuations, enhance retention, and facilitate resumption of PrEP are critical to decrease new HIV diagnoses., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Data on contraceptive use among women with bacterial sexually transmitted infections (STIs) are sparse, despite this population's high risk for unplanned pregnancy., Methods: This cross-sectional study included 1623 cisgender women recently diagnosed with a bacterial STI who completed a public health Partner Services interview between January 2017 and December 2019 in King County, WA, USA. Contraceptive methods were categorized as: (1) highly or moderately effective and (2) least effective or no method. Poisson regression models were used to assess associations between individual characteristics and contraceptive method., Results: Almost two thirds of the women (62.6%) reported using highly or moderately effective contraception, with 30.3% of women using long-acting contraception (LARC). More than one in three women (37.4%) reported using least effective methods or no method. Black women were less likely to report using a highly or moderately effective method compared to White women (aRR 0.58, 95% CI 0.43-0.80) and women with private insurance were more likely to report using a highly or moderately effective method compared to those with public insurance (aRR 1.67, 95% CI 1.28-2.19)., Conclusions: Given that many women with bacterial STIs are not desiring pregnancy, this study highlights the need for additional reproductive health services for women with recent STI diagnoses.

Background: The incidence of Neisseria gonorrhoeae (GC) and Chlamydia trachomatis (CT) is increasing in the United States; however, there are limited data on anatomic site-specific GC/CT among people with HIV (PWH)., Methods: We reviewed records of all PWH in care between January 1, 2014, and November 16, 2018, at 4 sites in the CFAR Network of Integrated Clinical Systems Cohort (CNICS; n = 8455). We calculated anatomic site-specific GC/CT testing and incidence rates and used Cox proportional hazards models modified for recurrent events to examine sociodemographic and clinical predictors of GC/CT testing and incidence at urogenital, rectal, and pharyngeal sites. We also calculated site-specific number needed to test (NNT) to detect a positive GC/CT test., Results: Of 8455 PWH, 2460 (29.1%) had at least yearly GC/CT testing at any anatomic site. The rates of urogenital, rectal, and pharyngeal GC were 1.7 (95% CI, 1.6-1.9), 3.2 (95% CI, 3.0-3.5), and 2.7 (95% CI, 2.5-2.9) infections per 100 person-years, respectively. The rates of urogenital, rectal, and pharyngeal CT were 1.9 (95% CI, 1.7-2.1), 4.3 (95% CI, 4.0-4.5), and 0.9 (95% CI, 0.8-1.0) infections per 100 person-years, respectively. PWH 16-39 years old experienced greater GC/CT rates at all anatomic sites, while men who have sex with men experienced greater rates of extragenital infections. NNTs for urogenital, rectal, and pharyngeal GC/CT were 20 (95% CI, 19-21), 5 (95% CI, 5-5), and 9 (95% CI, 8-9), respectively., Conclusions: Many PWH are not tested annually for GC/CT, and rates of GC/CT infection, particularly rates of extragenital infections, are high. We identified groups of PWH who may benefit from increased site-specific GC/CT testing., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Sex inequity in academic achievement was well documented before the COVID-19 pandemic, and evolving data suggest that women in academic surgery are disproportionately disadvantaged by the pandemic. This perspective piece reviews currently accepted solutions to the sex achievement gap, with their associated shortcomings. We also propose innovative strategies to overcoming barriers to sex equity in academic medicine that broadly fall into three categories: strategies to mitigate inequitable caregiving responsibilities, strategies to reduce cognitive load, and strategies to value uncompensated, impactful work. These approaches address inequities at the system-level, as opposed to the individual-level, lifting the burden of changing the system from women., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

The structure, chemistry, and charge of interfaces between materials and aqueous fluids play a central role in determining properties and performance of numerous water systems. Sensors, membranes, sorbents, and heterogeneous catalysts almost uniformly rely on specific interactions between their surfaces and components dissolved or suspended in the water-and often the water molecules themselves-to detect and mitigate contaminants. Deleterious processes in these systems such as fouling, scaling (inorganic deposits), and corrosion are also governed by interfacial phenomena. Despite the importance of these interfaces, much remains to be learned about their multiscale interactions. Developing a deeper understanding of the molecular- and mesoscale phenomena at water/solid interfaces will be essential to driving innovation to address grand challenges in supplying sufficient fit-for-purpose water in the future. In this Review, we examine the current state of knowledge surrounding adsorption, reactivity, and transport in several key classes of water/solid interfaces, drawing on a synergistic combination of theory, simulation, and experiments, and provide an outlook for prioritizing strategic research directions.

Background: The "surgical personality" is a mostly negative academic and cultural image of the surgeon as egotistical, paternalistic, and inflexible. Because of this image, surgeons have been viewed as resistant to change and some behaviors, vulnerability, for example, are viewed as "suspect" because they seemingly threaten professional competency. We report on exit interviews of surgeons who participated in a coaching program and demonstrate how their narratives challenge the surgical "personality" and forge an evolving and more open professional surgical identity., Methods: We interviewed n = 34 bariatric surgeons at the end of a 2-year surgical coaching program. Transcribed interviews were analyzed in NVivo, computer-assisted qualitative data analysis software. Coding of transcripts was approached through iterative steps. We utilized an exploratory method; each member of our team independently examined 3 transcripts to evaluate emergent themes early in the investigation. The team met to discuss our independent themes and develop the codebook collectively. We created a descriptive framework for our first round of coding based on emerging themes and employed an interpretive framework to arrive at our themes., Results: Three major themes emerged from our data. Participants in this study discussed the ways that participation in the coaching program initially conflicted with their identity as a competent professional. Surgeons were acutely aware of how participation might have destabilized their surgical identity because they might be viewed as vulnerable. Despite these concerns about image, surgeons found impetus for improvement because of poor outcome scores or because they desired early career affirmation. Finally, surgeons report that the safe spaces of intentional coaching contributed to their ideas about how surgeons, and ultimately surgery, can change., Conclusions: Participation in a coaching program challenged how surgeons thought of themselves in relationship to social and peer expectations. Our results indicate that surgeons do feel peer and social pressures related to identity but are much more complex and nuanced than has been previously discussed. The safe space of intentional coaching allowed participants to practice vulnerability without the pressures of sometimes caustic professional norms. Participants in this study viewed coaching as the way to improve the culture of surgery., Competing Interests: The authors report no conflicts of interest., (Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.)

It is widely accepted that protein-based particles can efficiently stabilize foams and emulsions. However, it is not fully elucidated which particle properties are decisive for the stabilization of air/water and oil/water interfaces. To unravel this correlation, selected properties of nano-sized soluble β-lactoglobulin particles were changed one at a time. Therefore, particles of (1) variable size but similar zeta potential and degree of cross-linking and (2) similar size but different further properties were produced by heat treatment under a specific combination of pH value and NaCl concentration and then analyzed for their interfacial behavior as well as foaming and emulsifying properties. On the one hand, it was found that the initial phase of protein adsorption at both the air/water and the oil/water interface was mainly influenced by the zeta potential, independent of the particle size. On the other hand, foam stability as resolved from the time-dependent evolution of mean bubble area negatively correlated with disulfide cross-linking, whereas emulsion stability in terms of oil droplet flocculation showed a positive correlation with disulfide cross-linking. In addition, flocculation was more pronounced for larger particles. Concluding from this, foam and emulsion stability are not linked to the same particle properties and, thus, explanatory approaches cannot be used interchangeably.

Objective: The purpose of this study was to measure the efficacy of a novel faculty and resident educational bundle focused on development of faculty-resident behaviors and entrustment in the operating room., Summary Background Data: As surgical training environments are orienting to entrustable professional activities (EPAs), successful transitions to this model will require significant faculty and resident development. Identifying an effective educational initiative which prepares faculty and residents for optimizing assessment, teaching, learning, and interacting in this model is critical., Methods: From September 2015 to June 2017, an experimental study was conducted in the Department of Surgery at the University of Michigan Health System (UMHS). Case observations took place across general, plastic, thoracic, and vascular surgical specialties. A total of 117 operating room observations were conducted during Phase I of the study and 108 operating room observations were conducted during Phase II following the educational intervention. Entrustment behaviors were rated for 56 faculty and 73 resident participants using OpTrust, a validated intraoperative entrustment instrument., Results: Multiple regression analysis showed a significant increase in faculty entrustment (Phase I = 2.32 vs Phase II = 2.56, P < 0.027) and resident entrustability (Phase I = 2.16 vs Phase II = 2.40, P < 0.029) scores following exposure to the educational intervention., Conclusions: Our study shows improved intraoperative entrustment following implementation of faculty and resident development, indicating the efficacy of this innovative educational bundle. This represents a crucial component in the implementation of a competency-based assessment framework like EPAs., Competing Interests: The authors report no conflicts of interest., (Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.)

This study aimed at examining the cause of differences in the structure preservation of polysorbate 80-maltodextrin foams during microwave-assisted vacuum drying (MWVD) versus conventional vacuum drying (CVD). Aqueous dispersions of 3% polysorbate 80 and 0-40% maltodextrin were characterized for their dielectric and interfacial properties, and results were related to their drying performance in a foamed state. Surface tension and surface dilatational properties as well as dielectric properties clearly responded to the variation in the maltodextrin content. Likewise, the foam structure preservation during CVD was linked to the maltodextrin concentration. Regarding MWVD, however, foams collapsed at all conditions tested. Nevertheless, if the structure during MWVD remained stable, the drying time was significantly reduced. Eventually, this finding could be linked to the dielectric properties of polysorbate 80 rather than its adsorption kinetics and surface film viscoelasticity as its resonant frequency fell within the working frequency of the microwave drying plant.

Background: Genital herpes simplex virus type 1 (HSV-1) has emerged as the leading cause of first-episode genital herpes among specific populations in the United States, such as adolescents, young adult women, and men who have sex with men (MSM). We examined trends in the etiology of first-episode genital herpes diagnoses over time in a sexually transmitted disease (STD) clinic population., Methods: Using an electronic database, we identified persons diagnosed as having first-episode genital herpes at Public Health - Seattle & King County STD Clinic from 1993 to 2014 and compared risk factors for genital HSV-1 versus herpes simplex virus type 2 (HSV-2) infection., Results: Of 52,030 patients with genital ulcers, 3065 (6.15%) had first-episode genital herpes infection: 1022 (33.3%) with HSV-1 and 2043 (67.7%) with HSV-2. Overall, 1154 (37.7%) were women, the median age was 28 years (interquartile range, 24-36 years), 1875 (61.2%) patients were white, and 353 (11.5%) were MSM. The number of patients diagnosed as having first-episode genital HSV-2 declined on average by 5.5 persons per year, from 208 in 1993 to 35 in 2014 (change of -5.6 per year; 95% confidence interval [CI], -6.9 to -4.1), whereas HSV-1 diagnoses remained stable at approximately 50 per year (change of 0.2; 95% CI, -0.4 to 0.9). In a multivariate model, persons diagnosed as having first-episode genital HSV-1 rather than genital HSV-2 infection were more likely to be younger (age <30 years [relative risk {RR}, 1.38; 95% CI, 1.22-1.55]), white (RR, 3.16; 95% CI, 2.57-3.88), and MSM (RR, 1.50; 95% CI, 1.31-1.71)., Conclusions: We observed a significant decrease in the frequency of first-episode genital HSV-2 and a stable number of first-episode genital HSV-1 infections in a STD clinic over the last 2 decades.

Background: Dynamic HIV transmission models can provide evidence-based guidance on optimal combination implementation strategies to treat and prevent HIV/AIDS. However, these models can be extremely data intensive, and the availability of good-quality data characterizing regional microepidemics varies substantially within and across countries. We aim to provide a comprehensive and transparent description of an evidence synthesis process and reporting framework employed to populate and calibrate a dynamic, compartmental HIV transmission model for six US cities., Methods: We executed a mixed-method evidence synthesis strategy to populate model parameters in six categories: (i) initial HIV-negative and HIV-infected populations; (ii) parameters used to calculate the probability of HIV transmission; (iii) screening, diagnosis, treatment and HIV disease progression; (iv) HIV prevention programs; (v) the costs of medical care; and (vi) health utility weights for each stage of HIV disease progression. We identified parameters that required city-specific data and stratification by gender, risk group and race/ethnicity a priori and sought out databases for primary analysis to augment our evidence synthesis. We ranked the quality of each parameter using context- and domain-specific criteria and verified sources and assumptions with our scientific advisory committee., Findings: To inform the 1,667 parameters needed to populate our model, we synthesized evidence from 59 peer-reviewed publications and 24 public health and surveillance reports and executed primary analyses using 11 data sets. Of these 1,667 parameters, 1,517 (91%) were city-specific and 150 (9%) were common for all cities. Notably, 1,074 (64%), 201 (12%) and 312 (19%) parameters corresponded to categories (i), (ii) and (iii), respectively. Parameters ranked as best- to moderate-quality evidence comprised 39% of the common parameters and ranged from 56%-60% across cities for the city-specific parameters. We identified variation in parameter values across cities as well as within cities across risk and race/ethnic groups., Conclusions: Better integration of modelling in decision making can be achieved by systematically reporting on the evidence synthesis process that is used to populate models, and by explicitly assessing the quality of data entered into the model. The effective communication of this process can help prioritize data collection of the most informative components of local HIV prevention and care services in order to reduce decision uncertainty and strengthen model conclusions., Competing Interests: The authors have declared that no competing interests exist.

Although diagnoses of human immunodeficiency virus (HIV) infection among persons who inject drugs in the United States are declining, an HIV outbreak among such persons in rural Indiana demonstrated that population's vulnerability to HIV infection (1). In August 2018, Public Health-Seattle and King County (PHSKC) identified a cluster of cases of HIV infection among persons living homeless, most of whom injected drugs. Investigation identified 14 related cases diagnosed from February to mid-November 2018 among women who inject drugs and men who have sex with women (MSW) who inject drugs and their sex partners. All 14 persons were living homeless in an approximately 3-square-mile area and were part of a cluster of 23 cases diagnosed since 2008. Twenty-seven cases of HIV infection were diagnosed among women and MSW who inject drugs in King County during January 1-November 15, 2018, a 286% increase over the seven cases diagnosed in 2017. PHSKC has alerted medical and social service providers and the public about the outbreak, expanded HIV testing among persons who inject drugs or who are living homeless, and is working to increase the availability of clinical and prevention services in the geographic area of the outbreak. This outbreak highlights the vulnerability of persons who inject drugs, particularly those who also are living homeless, to outbreaks of HIV infection, even in areas with high levels of viral suppression and large syringe services programs (SSPs)., Competing Interests: All authors have completed and submitted the ICMJE form for disclosure of potential conflicts of interest. Matthew R. Golden reports grants from GSK and Hologic, outside the submitted work. Julie Dombrowski reports grants from Hologic, Curatek, and Quidel to the University of Washington and personal fees from PRIME and the MidAtlantic AIDS Education and Training Center, outside the submitted work. No other potential conflicts of interest were disclosed.

Objectives/hypothesis: Radiation is thought to increase risk of developing second primary thyroid cancer (SPTC). This study estimated the rate of SPTC following index head and neck cancer (HNC) and determined whether radiation treatment among HNC survivors increased SPTC risk., Study Design: Retrospective data analysis., Method: The Surveillance, Epidemiology, and End Results database (1975-2014) was queried for cases of index HNC (N = 127,563) that developed SPTC. Adjusted multivariable competing risk proportional hazards model tested risk of developing a SPTC following index HNC. Sensitivity analyses using proportional hazards models were also performed restricting data to patients who 1) received both radiation and chemotherapy and 2) radiation alone., Results: Only 0.2% of index HNC survivors (n = 229) developed SPTC, yielding a rate of 26.1 per 100,000 person-years. For every increasing year of age at diagnosis, patients were 3% less likely to develop an SPTC (adjusted hazard ratio [aHR] = 0.97, 95% CI: 0.96-0.98). Males were also less likely to develop an SPTC (aHR = 0.73, 95% CI: 0.55-0.96). Radiation (aHR = 0.92, 95% CI: 0.68-1.25), surgery (aHR = 0.79, 95% CI: 0.56-1.11), and chemotherapy (aHR = 1.13, 95% CI: 0.76-1.69) were not significantly associated with developing SPTC. The sensitivity models also did not find an association between treatment and risk of SPTC., Conclusions: Rate of developing SPTC following index HNC was very low, and previous exposure to radiation did not significantly increase risk in our study population. More studies are needed to understand the increasing incidence of thyroid cancer across the United States., Level of Evidence: NA Laryngoscope, 129:1014-1020, 2019., (© 2018 The American Laryngological, Rhinological and Otological Society, Inc.)

Introduction: In gambling disorder (GD), impulsivity has been related with severity, treatment outcome and a greater dropout rate. The aim of the study is to obtain an empirical classification of GD patients based on their impulsivity and compare the resulting groups in terms of sociodemographic, clinical and gambling behavior variables., Methods: 126 patients with slot machine GD attending the Pathological Gambling Unit between 2013 and 2016 were included. The UPPS-P Impulsive Behavior Scale was used to assess impulsivity, and the severity of past-year gambling behavior was established with the Screen for Gambling problems questionnaire (NODS). Depression and anxiety symptoms and executive function were also assessed. A two-step cluster analysis was carried out to determine impulsivity profiles., Results: According to the UPPS-P data, two clusters were generated. Cluster 1 showed the highest scores on all the UPPS-P subscales, whereas patients from cluster 2 exhibited only high scores on two UPPS-P subscales: Negative Urgency and Lack of premeditation. Additionally, patients on cluster 1 were younger and showed significantly higher scores on the Beck Depression Inventory and on the State-Trait Anxiety Inventory questionnaires, worse emotional regulation and executive functioning, and reported more psychiatric comorbidity compared to patients in cluster 2. With regard to gambling behavior, cluster 1 patients had significantly higher NODS scores and a higher percentage presented active gambling behavior at treatment start than in cluster 2., Conclusions: We found two impulsivity subtypes of slot machine gamblers. Patients with high impulsivity showed more severe gambling behavior, more clinical psychopathology and worse emotional regulation and executive functioning than those with lower levels of impulsivity. These two different clinical profiles may require different therapeutic approaches., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Hepatocellular carcinoma (HCC) represents one of the most common causes of cancer-related deaths worldwide, with rising incidence in the USA. Bone metastases with HCC, in particular, have an extremely poor prognosis. We present prevalence, treatment, and survival of patients with bone and more specifically spinal metastases from HCC., Methods: A retrospective analysis was done at a single tertiary care institution of patients with bone metastases from HCC between January 2005 and December 2015., Results: Among 1017 patients with HCC, 20 were found to have bone metastases of which 11 had spinal metastases. Seventeen (85%) were male, with median age of 58 years at time of HCC diagnosis. Systemic chemotherapy and sorafenib were used in 12 (60%) patients, and 12 (60%) received radiation therapy. Among patients who did not receive therapy, median survival was 76 days. Median survival after diagnosis of metastasis in patients on sorafenib and radiation were 106 and 100 days, respectively., Conclusion: Bone metastases in HCC are very rare and aggressive. Due to its rarity, optimal treatment strategies are not well defined. Early diagnosis is important for optimal therapy and improved survival.

Background: Substance use disorders are a major public health problem. As primary care providers, nurse practitioners (NPs) must be proficient at screening, identifying, and intervening for at-risk patients. Screening, brief intervention, and referral to treatment (SBIRT) is a well-established, evidence-based model for teaching behavioral health skills to health care providers. It is vital that Master of Science in Nursing (MSN)-NP programs incorporate SBIRT into their curricula., Method: SBIRT content was mapped to 10 courses across an MSN-NP program. Methods of integration included readings, lectures, case studies, role-plays, tutorials, symposia, and test questions, as well as tracking the use of SBIRT during clinical preceptorships., Results: A total of 139 online and on-campus MSN-NP students were trained. Data demonstrate students successfully implemented SBIRT in precepted clinical settings., Conclusion: This approach provides a framework for integrating SBIRT training into MSN-NP curricula. [J Nurs Educ. 2017;56(12):725-732.]., (Copyright 2017, SLACK Incorporated.)

The original version of this article unfortunately contained a mistake in the Author group section. Author first names and family names were interchanged.

Early antiretroviral therapy (ART) initiation reduces the risk of disease progression and HIV transmission, but data on time from HIV care entry to ART initiation are lacking. Using data from the Medical Monitoring Project (MMP), a population-based probability sample of HIV-infected adults receiving medical care in the United States, we assessed time from care entry to ART initiation among persons diagnosed May 2004-April 2009 and used multivariable Cox proportional-hazards models to identify factors associated with time to ART initiation. Among 1094 MMP participants, 83.9% reported initiating ART, with median time to ART initiation of 10 months. In multivariable models, blacks compared to whites [hazard ratio (HR) 0.82; 95% confidence interval (CI) 0.70-0.98], persons without continuous health insurance (HR 0.82; CI 0.70-0.97), heterosexual women and men who have sex with men compared to heterosexual men (HR 0.66; CI 0.51-0.85 and HR 0.71; CI 0.60-0.84, respectively), and persons without AIDS at care entry (HR 0.37; CI 0.31-0.43) had significantly longer times to ART initiation. Overall, time to ART initiation was suboptimal by current standards and significant disparities were noted among certain subgroups. Efforts to encourage prompt ART initiation should address delays among those without health insurance and among certain sociodemographic subgroups.

The surface chemistry of ions, water molecules, and proteins as well as their ability to form stable networks in foams can influence and control macroscopic properties such as taste and texture of dairy products considerably. Despite the significant relevance of protein adsorption at liquid interfaces, a molecular level understanding on the arrangement of proteins at interfaces and their interactions has been elusive. Therefore, we have addressed the adsorption of the model protein bovine serum albumin (BSA) at the air-water interface with vibrational sum-frequency generation (SFG) and ellipsometry. SFG provides specific information on the composition and average orientation of molecules at interfaces, while complementary information on the thickness of the adsorbed layer can be obtained with ellipsometry. Adsorption of charged BSA proteins at the water surface leads to an electrified interface, pH dependent charging, and electric field-induced polar ordering of interfacial H(2)O and BSA. Varying the bulk pH of protein solutions changes the intensities of the protein related vibrational bands substantially, while dramatic changes in vibrational bands of interfacial H(2)O are simultaneously observed. These observations have allowed us to determine the isoelectric point of BSA directly at the electrolyte-air interface for the first time. BSA covered air-water interfaces with a pH near the isoelectric point form an amorphous network of possibly agglomerated BSA proteins. Finally, we provide a direct correlation of the molecular structure of BSA interfaces with foam stability and new information on the link between microscopic properties of BSA at water surfaces and macroscopic properties such as the stability of protein foams.

NUP98-HOXA9 is the prototype of a group of oncoproteins associated with acute myeloid leukemia. It consists of an N-terminal portion of NUP98 fused to the homeodomain of HOXA9 and is believed to act as an aberrant transcription factor that binds DNA through the homeodomain. Here we show that NUP98-HOXA9 can regulate transcription without binding to DNA. In order to determine the relative contributions of the NUP98 and HOXA9 portions to the transforming ability of NUP98-HOXA9, the effects of NUP98-HOXA9 on primary human CD34+ cells were dissected and compared to those of wild-type HOXA9. In contrast to previous findings in mouse cells, HOXA9 had only mild effects on the differentiation and proliferation of primary human hematopoietic cells. The ability of NUP98-HOXA9 to disrupt the differentiation of primary human CD34+ cells was found to depend primarily on the NUP98 portion, whereas induction of long-term proliferation required both the NUP98 moiety and an intact homeodomain. Using oligonucleotide microarrays in primary human CD34+ cells, a group of genes was identified whose dysregulation by NUP98-HOXA9 is attributable primarily to the NUP98 portion. These include RAP1A, HEY1, and PTGS2 (COX-2). Their functions may reflect the contribution of the NUP98 moiety of NUP98-HOXA9 to leukemic transformation. Taken together, these results suggest that the effects of NUP98-HOXA9 on gene transcription and cell transformation are mediated by at least two distinct mechanisms: one that involves promoter binding through the homeodomain with direct transcriptional activation, and another that depends predominantly on the NUP98 moiety and does not involve direct DNA binding.

Many soluble plant vacuolar proteins are sorted away from secreted proteins into small vesicles at the trans-Golgi network by transmembrane cargo receptors. Cleavable vacuolar sorting signals include the NH(2)-terminal propeptide (NTPP) present in sweet potato sporamin (Spo) and the COOH-terminal propeptide (CTPP) present in barley lectin (BL). These two proteins have been found to be transported by different mechanisms to the vacuole. We examined the ability of the vacuolar cargo receptor AtELP to interact with the sorting signals of heterologous and endogenous plant vacuolar proteins in mediating vacuolar transport in Arabidopsis thaliana. AtELP extracted from microsomes was found to interact with the NTPPs of barley aleurain and Spo, but not with the CTPPs of BL or tobacco chitinase, in a pH-dependent and sequence-specific manner. In addition, EM studies revealed the colocalization of AtELP with NTPP-Spo at the Golgi apparatus, but not with BL-CTPP in roots of transgenic Arabidopsis plants. Further, we found that AtELP interacts in a similar manner with the NTPP of the endogenous vacuolar protein AtALEU (Arabidopsis thaliana Aleu), a protein highly homologous to barley aleurain. We hypothesize that AtELP functions as a vacuolar sorting receptor involved in the targeting of NTPP-, but not CTPP-containing proteins in Arabidopsis.

Prosystemin is the 200-amino acid precursor of the 18-amino acid polypeptide defense hormone, systemin. Herein, we report that prosystemin was found to be as biologically active as systemin when assayed for proteinase inhibitor induction in young tomato plants and nearly as active in the alkalinization response in Lycopersicon esculentum suspension-cultured cells. Similar to many animal prohormones that harbor multiple signals, the systemin precursor contains five imperfect repetitive domains N-terminal to a single systemin domain. Whether the five repetitive domains contain defense signals has not been established. N-terminal deletions of prosystemin had little effect on its activity in tomato plants or suspension-cultured cells. Deletion of the C-terminal region of prosystemin containing the 18-amino acid systemin domain completely abolished its proteinase inhibitor induction and alkalinization activities. The apoplastic fluid from tomato leaves and the medium of cultured cells were analyzed for proteolytic activity that could process prosystemin to systemin. These experiments showed that proteolytic enzymes present in the apoplasm and medium could cleave prosystemin into large fragments, but the enzymes did not produce detectable levels of systemin. Additionally, inhibitors of these proteolytic enzymes did not affect the biological activity of prosystemin. The cumulative data indicated that prosystemin and/or large fragments of prosystemin can be active inducers of defense responses in both tomato leaves and suspension-cultured cells and that the only region of prosystemin that is responsible for activating the defense response resides in the systemin domain.

Prosystemin is the 200-amino-acid prohormone of the 18-amino-acid polypeptide called systemin, a systemic mobile signal that activates the synthesis of defense genes in solanaceous plants in response to herbivore attacks. The unusual primary structural features of the tomato prosystemin cDNA and protein provided an extraordinary challenge in devising an expression system to obtain the full-length protein. Prosystemin expression inhibited the growth of a eukaryotic and several prokaryotic hosts used. Prosystemin was initially synthesized as a truncated protein of 185 amino acids in length using a T7 RNA polymerase expression system in E. coli strain BL21[DE3]. The truncation was found to be due to two factors: (1) the intramolecular associations of the 5' coding region of the prosystemin sequence with the expression vector's ribosome binding site and (2) the presence of a translation start site just prior to the amino acid methionine at position 15. Mutations that permitted the synthesis of the full-length prosystemin protein were introduced into the amino-terminal 5' coding region of the prosystemin cDNA. A 199-amino-acid recombinant prosystemin lacking the N-terminal methionine was purified from lysates and confirmed by N-terminal amino acid sequence and immunoblot analysis., (Copyright 1999 Academic Press.)

Background: Transient (i.e., phasic) bell-shaped vestibularly evoked potentials (VESTEP's) were recorded from the human scalp during whole body rotation about the vertical z-axis using a multi-axis rotary chair (yaw-motion). For pitch-motions about the interaural y-axis, however, a sustained (i.e., tonic) VESTEP was recorded, presumably because of the additional otolithic stimulation., Hypothesis: During microgravity, only phasic VESTEP's were recorded because pitch-motions stimulate only the vertical semicircular canals without otolithic contamination., Methods: The motion profile applied simulated the form of a natural smooth head movement ("raised cosine"). It was designed to minimize all possible sources of mechanical, electrical, and physiological artifacts. With this motion profile, seated subjects were tilted 90 degrees nose-down or 90 degrees nose-up about their interaural y-axis ("pitch") thus stimulating the vertical semicircular canals and the otoliths. In addition, the raised cosine velocity profile was applied during the microgravity phases of a total of 90 parabolic flight maneuvers, thus stimulating the vertical canals without additional otolithic stimulation., Results: A transient (phasic) bell-shaped VESTEP was found in the Earth-bound laboratory for backward-tilts corresponding to the velocity profile used. For nose-down tilts, however, a sustained (tonic) negativity was found which matched the applied position profile. In microgravity, only the transient bell-shaped responses could be recorded irrespective of tilt direction., Conclusion: These results are interpreted in terms of both a position response generated by pitch-down and a velocity response caused by pitch-up motions. This differentiation might prove to be a useful electrophysiological tool in oto-neurological diagnosis to distinguish between otolithic and canal disorders.

Although many properties of the targeting of plant endomembrane proteins are similar to mammalian and yeast systems, several clear differences are found that will be stressed in this review. In the past few years, we have seen an advancement in our understanding of the signals for vacuolar protein targeting and some insights into the mechanisms of transport to the vacuole in the plant cell. This work will form the basis for elucidation of the fundamental principles that govern protein trafficking through the secretory system to the vacuole.

A cDNA encoding for a 68 kDa GTP-binding protein was isolated from Arabidopsis thaliana (aG68). This clone is a member of a gene family that codes for a class of large GTP-binding proteins. This includes the mammalian dynamin, yeast Vps1p and the vertebrate Mx proteins. The predicted amino acid sequence was found to have high sequence conservation in the N-terminal GTP-binding domain sharing 54% identity to yeast Vps1p, 56% amino acid identity to rat dynamin and 38% identity to the murine Mx1 protein. The northern analysis shows expression in root, leaf, stem and flower tissues, but in mature leaves at lower levels. Southern analysis indicates that it may be a member of a small gene family or the gene may contain an intron.

Homogenates were prepared from sections of both clinically normal and clinically inflamed human gingival tissue. After centrifugation, supernatants were quantitated for protein and subjected to anionic and cationic electrophoresis. Samples of gingival blood and venous blood were similarly subjected to electrophoresis. Significant protein pattern differences are reported for the anionic tissue separations, and for the cationic tissue and plasma separations.

To understand better the immunosuppressive capacity of malignant rabbit fibroma virus (MV), we characterized MV growth in lymphoid cells. Replication of MV occurs in unstimulated normal spleen cells in vitro and is enhanced by adding T- or B-lymphocyte mitogens. In splenic T-lymphocyte preparations, comparable results are found: virus growth in the absence of mitogen, augmented by adding Con A. Unlike mature T cells, thymic lymphocytes support MV replication only when mitogen is added. When spleen cells from rabbits infected with MV in vivo are removed and cultured without mitogen, MV growth is again observed, with virus titer increasing about 10-fold per day of culture. In spleen cell populations from MV tumor-bearing rabbits, MV grows best in T lymphocytes, moderately in B lymphocytes, and least efficiently in adherent cells. When spleen cells are examined immediately following sacrifice, MV antigens are expressed solely on T lymphocytes from rabbits infected in vivo with MV 7 days previously. However, following overnight incubation in vitro a population of non-T lymphocytes displays cell membrane virus antigens. MV adapts itself somewhat to growth in lymphocytes, showing significantly greater growth in lymphocytes following passage in lymphocytes than is observed for non-lymphocyte-propagated virus. MV-infected lymphocytes also elaborate a factor that enhances MV growth in lymphocytes. Thus, MV replicates preferentially in mature T lymphocytes but will grow well in B cells as well. In vivo infection produces relatively small amounts of recoverable virus. However, when these lymphocytes are cultured in vitro virus replicates very well without added mitogens. These growth patterns may help to understand MV-induced immunologic dysfunction.