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In order to inform decision making and policy, research to address sustainability challenges requires cross-disciplinary approaches that are co-created with a wide and inclusive diversity of disciplines and stakeholders. As the UN Decade of Ocean Science for Sustainable Development approaches, it is therefore timely to take stock of the global range of cross-disciplinary questions to inform the development of policies to restore and sustain ocean health. We synthesized questions from major science and policy horizon scanning exercises, identifying 89 questions with relevance for ocean policy and governance. We then scanned the broad ocean science literature to examine issues potentially missed in the horizon scans and supplemented the horizon scan outcome with 11 additional questions. This resulted in an unprioritized list of 100 general questions that would require a cross-disciplinary approach to inform policy. The questions fell into broad categories including: coastal and marine environmental change, managing ocean activities, governance for sustainable oceans, ocean value, and technological and socio-economic innovation. Each question can be customized by ecosystem, region, scale, and socio-political context, and is intended to inspire discussions of salient cross-disciplinary research directions to direct scientific research that will inform policies. Governance and management responses to these questions will best be informed by drawing upon a diversity of natural and social sciences, local and traditional knowledge, and engagement of different sectors and stakeholders.

ABSTRACT Increasing anthropogenic inputs of fixed nitrogen are leading to greater eutrophication of aquatic environments, but it is unclear how this impacts the flux and fate of carbon in lacustrine and riverine systems. Here, we present evidence that the form of nitrogen governs the partitioning of carbon among members in a genome-sequenced, model phototrophic biofilm of 20 members. Consumption of NO3− as the sole nitrogen source unexpectedly resulted in more rapid transfer of carbon to heterotrophs than when NH4+ was also provided, suggesting alterations in the form of carbon exchanged. The form of nitrogen dramatically impacted net community nitrogen, but not carbon, uptake rates. Furthermore, this alteration in nitrogen form caused very large but focused alterations to community structure, strongly impacting the abundance of only two species within the biofilm and modestly impacting a third member species. Our data suggest that nitrogen metabolism may coordinate coupled carbon-nitrogen biogeochemical cycling in benthic biofilms and, potentially, in phototroph-heterotroph consortia more broadly. It further indicates that the form of nitrogen inputs may significantly impact the contribution of these communities to carbon partitioning across the terrestrial-aquatic interface. IMPORTANCE Anthropogenic inputs of nitrogen into aquatic ecosystems, and especially those of agricultural origin, involve a mix of chemical species. Although it is well-known in general that nitrogen eutrophication markedly influences the metabolism of aquatic phototrophic communities, relatively little is known regarding whether the specific chemical form of nitrogen inputs matter. Our data suggest that the nitrogen form alters the rate of nitrogen uptake significantly, whereas corresponding alterations in carbon uptake were minor. However, differences imposed by uptake of divergent nitrogen forms may result in alterations among phototroph-heterotroph interactions that rewire community metabolism. Furthermore, our data hint that availability of other nutrients (i.e., iron) might mediate the linkage between carbon and nitrogen cycling in these communities. Taken together, our data suggest that different nitrogen forms should be examined for divergent impacts on phototrophic communities in fluvial systems and that these anthropogenic nitrogen inputs may significantly differ in their ultimate biogeochemical impacts.

Abstract The third meeting of the International Collaboration for Automation of Systematic Reviews (ICASR) was held 17–18 October 2017 in London, England. ICASR is an interdisciplinary group whose goal is to maximize the use of technology for conducting rapid, accurate, and efficient systematic reviews of scientific evidence. The group seeks to facilitate the development and widespread acceptance of automated techniques for systematic reviews. The meeting’s conclusion was that the most pressing needs at present are to develop approaches for validating currently available tools and to provide increased access to curated corpora that can be used for validation. To that end, ICASR’s short-term goals in 2018–2019 are to propose and publish protocols for key tasks in systematic reviews and to develop an approach for sharing curated corpora for validating the automation of the key tasks.

Introduction: Cross-sectional studies suggest that postnatal blood lead (PbB) concentrations are negatively associated with child growth. Few studies prospectively examined this association in populations with lower PbB concentrations. We investigated longitudinal associations of childhood PbB concentrations and subsequent anthropometric measurements in a multi-ethnic cohort of girls. Methods: Data were from The Breast Cancer and the Environment Research Program at three sites in the United States (U.S.): New York City, Cincinnati, and San Francisco Bay Area. Girls were enrolled at ages 6–8 years in 2004–2007. Girls with PbB concentrations collected at ≤10 years old (mean 7.8 years, standard deviation (SD) 0.82) and anthropometry collected at ≥3 follow-up visits were included (n = 683). The median PbB concentration was 0.99 μg/d (10th percentile = 0.59 μg/dL and 90th percentile = 2.00 μg/dL) and the geometric mean was 1.03 μg/dL (95% Confidence Interval (CI): 0.99, 1.06). For analyses, PbB concentrations were dichotomized as

Abstract Background Lipid dysregulation is a classical risk factor for cardiovascular disease (CVD), yet scanty evidence existed regarding cardiac lipid metabolism that is directly related to heart damage. Recently, the relationship between dyslipidemia and pro-inflammatory insults has led to further understanding on the CVD-predisposing effects of dyslipidemia. The aims of the present study were to investigate whether high-fat high-cholesterol (HFHC) diet-induced hyperlipidemia would cause heart damage and to study the potential role of local cardiac lipid dysregulation in the occurrence of cellular injury. Methods Male Sprague–Dawley rats were divided into normal chow or HFHC diet groups, and sacrificed after 2 or 4 weeks, respectively. Lipid peroxidation marker level was measured. Lipid parameters in the rat hearts were detected. Cardiac damage was evaluated. Results HFHC diet increased serum levels of cholesterol and free fatty acids (FFAs) and led to systemic oxidative stress and pro-inflammatory status. Cardiac lipid dysregulation, which was characterized by elevated levels of cholesterol and adipocyte (A)- and heart (H)-fatty acid binding proteins (FABPs), occurred after HFHC diet for 4 weeks. Cardiac damage was further evident with elevated circulating H-FABP levels, increased cardiac interstitial fibrosis and the loss of troponin I. Conclusion Our data demonstrated that HFHC diet led to systemic and cardiac lipid dysregulation, accompanied by systemic oxidative and pro-inflammatory stresses, and these may finally cooperate to cause a series of pathological changes of the heart tissue. Our findings suggest that maintenance of lipid regulation may be essential in the prevention of heart damage.

The aim of this study was to explore to what extent life styles, income, and health factors contribute to the life satisfaction of Hispanic older adults. A secondary data analysis from a national survey of Hispanic Established Populations for the Epidemiologic Study of the Elderly (HEPESE) (Markides, Ray, Angel, & Espino, 2012) was used. Subjects were Hispanic older adults (over 75 years, n = 1542). For this study, Hispanics and Latinos were considered as one and the same. A two-step hierarchical regression was conducted to address the research question. The results showed health status and income were unique predictors in the first step and (a) eating out with family, (b) eating out with friends, (c) spending time on cooking were unique predictors in the second step. It is culturally consistent that Hispanic older adults are more satisfied when they have time eating with people around them (e.g., family, friends) and spending time on cooking.

Ebola virus (EBOV) in body fluids poses risk for virus transmission. However, there are limited experimental data for such matrices on the disinfectant efficacy against EBOV. We evaluated the effectiveness of disinfectants against EBOV in blood on surfaces. Only 5% peracetic acid consistently reduced EBOV titers in dried blood to the assay limit of quantification.

Abstract The second meeting of the International Collaboration for Automation of Systematic Reviews (ICASR) was held 3–4 October 2016 in Philadelphia, Pennsylvania, USA. ICASR is an interdisciplinary group whose aim is to maximize the use of technology for conducting rapid, accurate, and efficient systematic reviews of scientific evidence. Having automated tools for systematic review should enable more transparent and timely review, maximizing the potential for identifying and translating research findings to practical application. The meeting brought together multiple stakeholder groups including users of summarized research, methodologists who explore production processes and systematic review quality, and technologists such as software developers, statisticians, and vendors. This diversity of participants was intended to ensure effective communication with numerous stakeholders about progress toward automation of systematic reviews and stimulate discussion about potential solutions to identified challenges. The meeting highlighted challenges, both simple and complex, and raised awareness among participants about ongoing efforts by various stakeholders. An outcome of this forum was to identify several short-term projects that participants felt would advance the automation of tasks in the systematic review workflow including (1) fostering better understanding about available tools, (2) developing validated datasets for testing new tools, (3) determining a standard method to facilitate interoperability of tools such as through an application programming interface or API, and (4) establishing criteria to evaluate the quality of tools’ output. ICASR 2016 provided a beneficial forum to foster focused discussion about tool development and resources and reconfirm ICASR members’ commitment toward systematic reviews’ automation.

A 12-month-old healthy girl presented with a chronic diaper rash. Physical examination demonstrated crusting of the scalp, erythematous papules with surrounding petechiae on the lower abdomen, and an intraoral palatal ulcer. Further imaging demonstrated bone involvement. Histopathologic examination of involved skin and the intraoral ulcer demonstrated epithelioid histiocytes with “coffee bean-shaped” nuclei, staining positive for CD1a and langerin by immunohistochemistry, consistent with Langerhans cell histiocytosis (LCH). LCH is a disease entity of unknown etiology characterized by histiocytic proliferation that most commonly presents in young children. The cutaneous findings of LCH include a seborrheic dermatitis-like and/or red-brown papular eruption. Intraoral examination is crucial as oral mucosal and maxillofacial skeletal disease can also be seen in LCH. When a child presents with a recalcitrant seborrheic dermatitis-like eruption or chronic diaper rash, the clinician should be alerted to the possibility of LCH. Timely recognition and diagnosis of LCH is important for oncologic referral, evaluation, and treatment.

Abstract Neuroimaging genomics is a relatively new field focused on integrating genomic and imaging data in order to investigate the mechanisms underlying brain phenotypes and neuropsychiatric disorders. While early work in neuroimaging genomics focused on mapping the associations of candidate gene variants with neuroimaging measures in small cohorts, the lack of reproducible results inspired better-powered and unbiased large-scale approaches. Notably, genome-wide association studies (GWAS) of brain imaging in thousands of individuals around the world have led to a range of promising findings. Extensions of such approaches are now addressing epigenetics, gene–gene epistasis, and gene–environment interactions, not only in brain structure, but also in brain function. Complementary developments in systems biology might facilitate the translation of findings from basic neuroscience and neuroimaging genomics to clinical practice. Here, we review recent approaches in neuroimaging genomics—we highlight the latest discoveries, discuss advantages and limitations of current approaches, and consider directions by which the field can move forward to shed light on brain disorders.

Schulze et al. (GCB Bioenergy, 2020, 12, 186–197) argue against putting forests into conservation, alleging that managing forests, including for bioenergy, produces more climate mitigation than letting them grow. However, this conclusion is based on not counting emissions from burning biomass, and other carbon accounting sleight of hand. This is a letter regarding https://doi.org/10.1111/gcbb.12672

World-wide, billions of dollars are spent each year on body-centered interventions to alleviate both physical and psychological pathologies. Given the high demand and increasing popularity of body-centered interventions, there is need for a systematic organization of empirical evidence associated with body-centered therapies. This article reviews the psychological effects of body-centered interventions on emotional well-being, including both self and other-administered (receptive) therapies. Theory behind body-centered interventions rely upon the bidirectional communication pathway between the brain and body. We investigated the bidirectional communication pathway between the brain and body by evaluating evidence across multiple body-centered therapies. The research reviewed includes studies that investigate effects of massage therapy, reflexology, acupuncture, functional relaxation, emotional freedom technique, Rolfing, yoga, tai-chi, and dance/movement therapy on psychological conditions across the lifespan. Results demonstrated that overall, massage therapy, tai-chi, dance/movement therapy, functional relaxation, reflexology, acupuncture and emotional freedom technique seem to alleviate stress, depression, anxiety, bipolar disorder and facilitate pain reduction. Of these, the most robust evidence available was for massage therapy, indicating it is an effective intervention for numerous age groups and populations. Rolfing and reflexology had the least amount of support, with few studies available that had small sample sizes. Although these conclusions are limited by scarcity of high-quality empirical data and contradictory findings, available evidence indicates that body-centered interventions can be effective in reducing psychopathology and supports the proposed mechanism of the bidirectional pathway between the brain and body: the body holds the potential to influence the mind. Integrating body-centered therapies in both clinical settings and as self-care could lead to better outcomes. Lastly, we propose the first taxonomy of body-centered interventions and empirical evidence of their effectiveness for clinicians and researchers.

Background Contemporary outcomes of transcatheter aortic valve replacement (TAVR) in nonagenarians are unknown. Methods and Results We identified 13 544 nonagenarians (aged 90–100 years) who underwent TAVR between 2012 and 2016 using Medicare claims. Generalized estimating equations were used to study the change in short‐term outcomes among nonagenarians over time. We compared outcomes between nonagenarians and non‐nonagenarians undergoing TAVR in 2016. A mixed‐effect multivariable logistic regression was performed to determine predictors of 30‐day mortality in nonagenarians in 2016. A center was defined as a high‐volume center if it performed ≥100 TAVR procedures per year. After adjusting for changes in patients’ characteristics, risk‐adjusted 30‐day mortality declined in nonagenarians from 9.8% in 2012 to 4.4% in 2016 (P

Fungal plant cell wall degradation processes are governed by complex regulatory mechanisms, allowing the organisms to adapt their metabolic program with high specificity to the available substrates. While the uptake of representative plant cell wall mono- and disaccharides is known to induce specific transcriptional and translational responses, the processes related to early signal reception and transduction remain largely unknown. A fast and reversible way of signal transmission are post-translational protein modifications, such as phosphorylations, which could initiate rapid adaptations of the fungal metabolism to a new condition. To elucidate how changes in the initial substrate recognition phase of Neurospora crassa affect the global phosphorylation pattern, phospho-proteomics was performed after a short (2 min) induction period with several plant cell wall-related mono- and disaccharides. The MS/MS-based peptide analysis revealed large-scale substrate-specific protein phosphorylation and de-phosphorylations. Using the proteins identified by MS/MS, a protein-protein-interaction (PPI) network was constructed. The variance in phosphorylation of a large number of kinases, phosphatases and transcription factors indicate the participation of many known signaling pathways, including circadian responses, two-component regulatory systems, MAP kinases as well as the cAMP-dependent and heterotrimeric G-protein pathways. Adenylate cyclase, a key component of the cAMP pathway, was identified as a potential hub for carbon source-specific differential protein interactions. In addition, four phosphorylated F-Box proteins were identified, two of which, Fbx-19 and Fbx-22, were found to be involved in carbon catabolite repression responses. Overall, these results provide unprecedented and detailed insights into a so far less well known stage of the fungal response to environmental cues and allow to better elucidate the molecular mechanisms of sensory perception and signal transduction during plant cell wall degradation.

Background: Environmental phenols, compounds used widely in personal care and consumer products, are known endocrine disruptors. Few epidemiologic studies have examined the association of phenol biomarkers with breast cancer incidence and, to our knowledge, none have considered associations with mortality following breast cancer. We examined seven urinary phenol biomarkers in association with breast cancer incidence and subsequent mortality, and examined effect measure modification by body mass index (BMI). Methods: Participants included 711 women with breast cancer and 598 women without breast cancer who were interviewed for the population-based Long Island Breast Cancer Study Project. Among women with breast cancer, phenol biomarkers were quantified in spot urine samples collected on average within three months of a first diagnosis of primary in situ or invasive breast cancer in 1996–1997. Women with breast cancer were monitored for vital status using the National Death Index. After a median follow-up of 17.6 years, we identified 271 deaths, including 98 deaths from breast cancer. We examined creatinine-corrected phenol concentrations and the sum of parabens (Σparabens) in association with breast cancer incidence using logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs), and with mortality using Cox regression to estimate hazard ratios (HRs) and 95% CIs. We evaluated multiplicative effect measure modification using cross-product terms in nested models. Results: The highest (vs lowest) quintiles of urinary methylparaben, propylparaben, and Σparabens were associated with risk of breast cancer with ORs ranging from 1.31 to 1.50. Methylparaben, propylparaben, and Σparabens were also associated with all-cause mortality HRs ranging from 0.68 to 0.77. Associations for breast cancer incidence were more pronounced among women with BMI

Background and Purpose: To describe the final results of the TARGET Registry, a multicenter, real-world study of patients with intracranial aneurysms treated with new generation TARGET Coils.Methods: The TARGET Registry is a prospective, single-arm study with independent medical event monitoring and core-lab adjudication. Patients with de novo intracranial aneurysms were embolized with either TARGET-360° or helical coils in 12 US centers. The primary outcome was aneurysm packing density (PD), which was assessed immediately post-procedure. The secondary outcomes were immediate and long-term aneurysm occlusion rate using the Raymond Scale, and independent functional outcome using the modified Rankin Scale (mRS). A secondary analysis investigated the influence of the use of 100% 360-complex coils on clinical and angiographic outcomes.Results: 148 patients with 157 aneurysms met the inclusion and exclusion criteria. 58 (39.2%) patients with ruptured and 90 (61.8%) with unruptured aneurysms were treated using TARGET 360°, helical Coils, or both. Median age was 58.3 (IQR 48.1–67.4), 73% female, and 71.6% were Caucasian. Median follow-up time was 5.9 (IQR 4.0–6.9) months. The majority were treated with TARGET 360-coils (63.7%), followed by mixed and helical coils only. Peri-procedural morbidity and mortality was seen in 2.7% of patients. A good outcome at discharge (mRS 0–2) was seen in 89.9% of the full cohort, and in 84.5 and 93.3% in the ruptured and unruptured patients, respectively. The median packing density was 28.8% (IQR 20.3–41.1). Long-term complete and near complete occlusion rate was seen in 90.4% of aneurysms and complete obliteration was seen in 66.2% of the aneurysms. No significant difference in clinical and angiographic outcomes were noted between the pure 360-complex coiling vs. mixed 360-complex/Helical coiling strategies. In a multivariate analysis, predictors for long-term aneurysm occlusion were aneurysm location, immediate occlusion grade, and aneurysm size. The long-term independent functional outcome was achieved in 128/135 (94.8%) patients and all-cause mortality was seen in 3/148 (2%) patients.Conclusion: In the multicenter TARGET Registry, two-thirds of aneurysms achieved long-term complete occlusion and 91.0% achieved complete or near complete occlusion with excellent independent functional outcome.Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT01748903

The heartbeat is initiated by pacemaker cells residing in the sinoatrial node (SAN). SAN cells generate spontaneous action potentials (APs), i.e., normal automaticity. The sympathetic nervous system increases the heart rate commensurate with the cardiac output demand via stimulation of SAN β-adrenergic receptors (βAR). While SAN cells reportedly represent a highly heterogeneous cell population, the current dogma is that, in response to βAR stimulation, all cells increase their spontaneous AP firing rate in a similar fashion. The aim of the present study was to investigate the cell-to-cell variability in the responses of a large population of SAN cells. We measured the βAR responses among 166 single SAN cells isolated from 33 guinea pig hearts. In contrast to the current dogma, the SAN cell responses to βAR stimulation substantially varied. In each cell, changes in the AP cycle length were highly correlated (R2 = 0.97) with the AP cycle length before βAR stimulation. While, as expected, on average, the cells increased their pacemaker rate, greater responses were observed in cells with slower basal rates, and vice versa: cells with higher basal rates showed smaller responses, no responses, or even decreased their rate. Thus, βAR stimulation synchronized the operation of the SAN cell population toward a higher average rate, rather than uniformly shifting the rate in each cell, creating a new paradigm of βAR-driven fight-or-flight responses among individual pacemaker cells.

Cyclophanes—consisting of aromatic rings formed into a macrocycle—can display interesting properties but are challenging targets for synthesis. Here, the authors report a route to form cyclophanes by dynamic covalent chemistry, forming disulfides that can be subsequently converted to stable thioethers.

Granulomatous Orchitis secondary to lymphatic filiarisis is a rare diagnosis within the United States. We report a case of a 22yo Male from Sri Lanka, with a new onset scrotal swelling and palpable right testicular mass. Ultrasound identified a 1 cm right testicular mass with signs of tunica albuginea invasion. A right inguinal radical orchiectomy was performed and pathology showed Filarial orchitis. This report describes the detailed history, physical exam, and diagnostic workup and treatment options for a rare entity for acute scrotal pathology.

Background: Emerging evidence has demonstrated a high prevalence of weight bias internalization (WBI) among adults, as well as consistent links between internalization and adverse psychological and physical health. However, research examining WBI in youth and its impact on their health is scarce, especially among youth seeking weight loss treatment who may be particularly vulnerable to weight stigma from peers and parents. To address this research gap, the present study assessed WBI in a weight loss treatment-seeking sample of adolescents, examining associations between internalization and adolescents’ eating behaviors and parental weight-related communication.Methods: Adolescents (N = 148, Mage = 15.97 years), completed online self-report measures to assess WBI (using the modified version of the WBI Scale), body weight, binge eating, eating as a coping strategy, and weight teasing from peers and family members. Adolescents also reported on the frequency of parental comments about body weight, parental dieting, and parental encouragement of adolescent dieting.Results: Adolescents expressed a high mean level of internalized weight bias (M = 5.45, SD = 0.88). Higher levels of internalization were observed across increasing body weight categories; no differences were observed for gender or history of weight teasing. WBI was significantly higher among adolescents who reported binge eating and eating to cope with distress. Regression analyses showed that weight-related comments from mothers (but not fathers) significantly predicted adolescents’ WBI (including frequency of mothers’ comments about adolescents’ body weight, comments about their own body weight, and encouragement of their adolescent to diet), as did increased dieting frequency among mothers.Conclusion: The present study provides novel insights to the scant literature on WBI in youth. Findings indicate that WBI is high in both girls and boys engaged in weight loss, and is associated with maladaptive eating behaviors, higher frequency of maternal dieting, and mothers’ comments about body weight. These findings have important clinical implications for youth and families engaged in weight loss treatment, and underscore the need for research to clarify adverse effects of internalization on weight-related health in youth and to better understand the role that parental weight communication may have on adolescents’ internalization.

Objective: This study was designed to assess the feasibility of using the Jaw Dynasplint System as an adjunct to conventional stretching exercises as a preventative measure against trismus in patients undergoing radiotherapy. Methods: Study participants (n = 40) were randomized using a permuted block design to conventional stretching or stretching plus use of the Jaw Dynasplint 3 times per day for 30 minutes. Patients were instructed to record maximum interincisal opening each day as well as logging use of the Jaw Dynasplint. Results: At 6 months after initiation of the preventative regimen, 50% of patients in the Dynasplint arm and 75% in the conventional stretching arm remained on their assigned therapy. Trismus was diagnosed in 2 patients in the control arm and in 4 patients in the Dynasplint arm. Only 25% (95% confidence interval = 11.1, 46.9) of patients in the Dynasplint arm used the device as prescribed. Conclusions: The addition of the Jaw Dynasplint decreased compliance compared with conventional stretching. It is unlikely that the prescribed regimen will prove efficacious as a preventative measure due to low compliance.

Purpose: Treatment for head and neck cancer (HNC) results in long-term toxicities and increased physical and psychosocial survivor burden. There are a limited number of treatments for these late effects. Yoga postures, breath work, relaxation, and meditation, may improve these late effects. The purpose of this study was to examine the feasibility of a tailored yoga program in HNC survivors and obtain preliminary efficacy data. Methods: This was a randomized wait-list control study of yoga-naive HNC survivors who were >3 months post–cancer treatment. Baseline data were collected. Participants were randomized to either an 8-week hatha yoga intervention group or a wait-list group. Feasibility and efficacy data were collected. At 4 and 8 weeks, patients underwent a repeat assessment of health. Wait-list control group participants were offered the yoga program after data collection. Descriptive statistics evaluated feasibility. Mixed effects general linear models were used to generate estimates of the efficacy outcomes. Results: Seventy-three individuals were screened and 40 were eligible. All eligible individuals consented and enrolled. Five of the intervention group discontinued early and none in the wait-list control group. Feasibility was affirmed as participants were recruited and retained in the study, there were no adverse events, fidelity to protocol was demonstrated, and satisfaction rates were high. Efficacy measures indicated potential benefit for shoulder range of motion ( d = 0.57-0.86, P < .05), pain ( d = 0.67-0.90, P ≤ .005), and anxiety ( d = 0.59, P = .015). Conclusion: A tailored hatha yoga program is feasible and potentially efficacious for HNC survivors. Preliminary data supports further investigation of yoga in this population is needed.

Adult cochlear implant (CI) recipients demonstrate a reliable relationship between spectral modulation detection and speech understanding. Prior studies documenting this relationship have focused on postlingually deafened adult CI recipients—leaving an open question regarding the relationship between spectral resolution and speech understanding for adults and children with prelingual onset of deafness. Here, we report CI performance on the measures of speech recognition and spectral modulation detection for 578 CI recipients including 477 postlingual adults, 65 prelingual adults, and 36 prelingual pediatric CI users. The results demonstrated a significant correlation between spectral modulation detection and various measures of speech understanding for 542 adult CI recipients. For 36 pediatric CI recipients, however, there was no significant correlation between spectral modulation detection and speech understanding in quiet or in noise nor was spectral modulation detection significantly correlated with listener age or age at implantation. These findings suggest that pediatric CI recipients might not depend upon spectral resolution for speech understanding in the same manner as adult CI recipients. It is possible that pediatric CI users are making use of different cues, such as those contained within the temporal envelope, to achieve high levels of speech understanding. Further investigation is warranted to investigate the relationship between spectral and temporal resolution and speech recognition to describe the underlying mechanisms driving peripheral auditory processing in pediatric CI users.

There is a need to develop improved methods to treat and potentially cure HIV infection. During chronic HIV infection, replication is concentrated within T follicular helper cells (Tfh) located within B cell follicles, where low levels of virus-specific CTL permit ongoing viral replication. We previously showed that elevated levels of simian immunodeficiency virus (SIV)-specific CTL in B cell follicles are linked to both decreased levels of viral replication in follicles and decreased plasma viral loads. These findings provide the rationale to develop a strategy for targeting follicular viral-producing (Tfh) cells using antiviral chimeric antigen receptor (CAR) T cells co-expressing the follicular homing chemokine receptor CXCR5. We hypothesize that antiviral CAR/CXCR5-expressing T cells, when infused into an SIV-infected animal or an HIV-infected individual, will home to B cell follicles, suppress viral replication, and lead to long-term durable remission of SIV and HIV. To begin to test this hypothesis, we engineered gammaretroviral transduction vectors for co-expression of a bispecific anti-SIV CAR and rhesus macaque CXCR5. Viral suppression by CAR/CXCR5-transduced T cells was measured in vitro, and CXCR5-mediated migration was evaluated using both an in vitro transwell migration assay, as well as a novel ex vivo tissue migration assay. The functionality of the CAR/CXCR5 T cells was demonstrated through their potent suppression of SIVmac239 and SIVE660 replication in in vitro and migration to the ligand CXCL13 in vitro, and concentration in B cell follicles in tissues ex vivo. These novel antiviral immunotherapy products have the potential to provide long-term durable remission (functional cure) of HIV and SIV infections.

A 71-year-old woman with suspected endometrial cancer underwent robotic-assisted hysterectomy, bilateral salpingo-oophorectomy, pelvic and para-aortic lymph node dissection, and infracolic omentectomy revealing a stage II uterine carcinosarcoma with components of serous adenocarcinoma and undifferentiated spindle cell sarcoma. There was no evidence of distant metastasis at the time of surgery. However pelvic washings were positive for malignant cells. She received adjuvant chemotherapy and vaginal cuff brachytherapy. Forty months later she developed a subcutaneous mass at the location of previous port site which was confirmed to be recurrence of the uterine primary. She subsequently developed additional distant metastases to the abdominal wall, lungs, and bone. Port site metastasis (PSM) was the earliest indicator of disseminated metastatic disease in this patient. We review challenges in the management of patients with PSM and propose that PSM be considered as a sign of systemic disease even when presenting as an apparently isolated recurrence.