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Background: In the United States, Black and Hispanic/Latinx individuals continue to be disproportionately impacted by HIV. Applying a distributional cost-effectiveness framework, we estimated the distributional health impacts and cost-effectiveness of [...]

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: 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: 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.)

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.

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.

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.