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BACKGROUND: Planning radiosurgery to multiple intracranial metastases is complex and shows large variability in dosimetric quality among planners and treatment planning systems (TPS). This project aimed to determine whether autoplanning using the Muliple Brain Mets (AutoMBM) software can improve plan quality and reduce inter-planner variability by crowdsourcing results from prior international planning study.METHODS: Twenty-four institutions autoplanned with AutoMBM on a five metastases case from a prior international planning competition from which population statistics (means and variances) of 23 dosimetric metrics and resulting composite plan score (maximum score = 150) of other TPS (Eclipse, Monaco, RayStation, iPlan, GammaPlan, MultiPlan) were crowdsourced. Plan results of AutoMBM and each of the other TPS were compared using two sample t-tests for means and Levene's tests for variances. Plan quality of AutoMBM was correlated with the planner' experience and compared between academic and non-academic centers.RESULTS: AutoMBM produced plans with comparable composite plan score to GammaPlan, MultiPlan, Eclipse and iPlan (127.6 vs. 131.7 vs. 127.3 vs. 127.3 and 126.7; all p > 0.05) and superior to Monaco and RayStation (118.3 and 108.6; both p < 0.05). Inter-planner variability of overall plan quality was lowest for AutoMBM among all TPS (all p < 0.05). AutoMBM's plan quality did not differ between academic and non-academic centers and uncorrelated with planning experience (all p > 0.05).CONCLUSIONS: By plan crowdsourcing prior international plan challenge, AutoMBM produces high and consistent plan quality independent of the planning experience and the institution that is crucial to addressing the technical bottleneck of SRS to intracranial metastases.

Purpose Physical examinations and annual mammography (minimal follow-up) are as effective as laboratory/imaging tests (intensive follow-up) in detecting breast cancer (BC) recurrence. This statement is now challenged by the availability of new diagnostic tools for asymptomatic cases. Herein, we analyzed current practices and circulating tumor DNA (ctDNA) in monitoring high-risk BC patients treated with curative intent in a comprehensive cancer center. Patients and methods Forty-two consecutive triple negative BC patients undergoing neoadjuvant therapy and surgery were prospectively enrolled. Data from plasma samples and surveillance procedures were analyzed to report the diagnostic pattern of relapsed cases, i.e., by symptoms, follow-up procedures and ctDNA. Results Besides minimal follow-up, 97% and 79% of patients had at least 1 non-recommended imaging and laboratory tests for surveillance purposes. During a median follow-up of 5.1(IQR, 4.1–5.9) years, 13 events occurred (1 contralateral BC, 1 loco-regional recurrence, 10 metastases, and 1 death). Five recurrent cases were diagnosed by intensive follow-up, 5 by symptoms, and 2 incidentally. ctDNA antedated disseminated disease in all evaluable cases excepted two with bone-only and single liver metastases. The mean time from ctDNA detection to suspicious findings at follow-up imaging was 3.81(SD, 2.68), and to definitive recurrence diagnosis 8(SD, 2.98) months. ctDNA was undetectable in the absence of disease and in two suspected cases not subsequently confirmed. Conclusions Some relapses are still symptomatic despite the extensive use of intensive follow-up. ctDNA is a specific test, sensitive enough to detect recurrence before other methods, suitable for clarifying equivocal imaging, and exploitable for salvage therapy in asymptomatic BC survivors.

Objective The full phenotypic expression of non-alcoholic fatty liver disease (NAFLD) in lean subjects is incompletely characterised. We aimed to investigate prevalence, characteristics and long-term prognosis of Caucasian lean subjects with NAFLD. Design The study cohort comprises 1339 biopsy-proven NAFLD subjects from four countries (Italy, UK, Spain and Australia), stratified into lean and non-lean (body mass index (BMI) 10 483 person-years), 4.7% of lean vs 7.7% of non-lean patients reported liver-related events (p=0.37). No difference in survival was observed compared with non-lean NAFLD (p=0.069). Conclusions Caucasian lean subjects with NAFLD may progress to advanced liver disease, develop metabolic comorbidities and experience cardiovascular disease (CVD) as well as liver-related mortality, independent of longitudinal progression to obesity and PNPLA3 genotype. These patients represent one end of a wide spectrum of phenotypic expression of NAFLD where the disease manifests at lower overall BMI thresholds. Lay summary NAFLD may affect and progress in both obese and lean individuals. Lean subjects are predominantly males, have a younger age at diagnosis and are more prevalent in some geographic areas. During the follow-up, lean subjects can develop hepatic and extrahepatic disease, including metabolic comorbidities, in the absence of weight gain. These patients represent one end of a wide spectrum of phenotypic expression of NAFLD. ©

Aim In this study, we have compared 229 Wechsler Adults Intelligence Scale – Fourth Edition (WAIS-IV) cognitive profiles of different severity adults with autism spectrum disorder to verify the impact of several variables including sex, age, level of education and autism severity level in an Italian sample. Moreover, we wanted to find out the optimal cut points for the major intelligence quotients in order to discriminate autism severity levels. Methods Participants were recruited from two National Health System Center in two different Italian regions and were assessed with gold-standard instruments as a part of their clinical evaluation. According to DSM-5, cognitive domains were also measured with multi-componential tests. We used the Italian adaptation of WAIS-IV. We checked our hypotheses using linear regression models and receiver operating characteristics (ROC) curves. Results Our results showed that age and level of education have a strong impact on Verbal Comprehension (VCI) and Working Memory Indexes (WMI). Gender differences are relevant when considering the VCI and Processing Speed index (PSI) in which women obtained the best performance. These differences are still relevant when considering cut points of ROC because 69 resulted to be the optimal cut point for women, 65 for men. Conclusions Few conclusions can be assumed only examining Full Scale Intelligence Quotient (FSIQ) scores as it includes many different information about broader cognitive abilities. Looking deeper at main indexes and their subtests findings are consistent with previous research on the disorder (moderate correlations of FSIQ, Perceptual Reasoning index, WMI and PSI with the participants’ age), while other results are unforeseen (no effect of sex found on FSIQ score) or novel (significant effect of education on VCI and WMI). Using an algorithm predicting optimal cut point for discriminating through autism severity levels can help clinicians to better label and quantify the required help a person may need, a test cannot replace diagnostic and clinical evaluation by experienced clinicians.

The COVID-19 pandemic has represented a hazardous situation for individuals with Autism Spectrum Disorder (ASD) and their families. The difficulties, following the COVID-19-derived lockdown, have involved working from home or loss of employment, and the demands of looking after their children without the daily support of specialists. The aim of this study was to evaluate the adaptive behaviour of young adult participants with ASD after the enforcement of lockdown measures in March 2020 in a specialised centre in central Italy, by administering the Italian form of the Vineland Adaptive Behaviour Scales Second Edition (VABS-II), at baseline as well as 6 months and 1 year after the lockdown. Participants with ASD who were not able to access their normal, in-person care - they were only followed at a distance (i.e. telehealth) - declined dramatically in their adaptive behaviour during the first months after the lockdown for some VABS-II dimensions such as the socialisation and daily living domains. The effects of the lockdown on adaptive behaviour remained after 1 year. Our results emphasise the need for immediate, continuous and personal support for people with ASD during and after the restrictions caused by the COVID-19 pandemic, in order to ensure at least partial recovery of adaptive functioning.

My introduction to the now internationally renowned Sundance Film Festival began in the early 1990s with an invitation to bring graduate students interested in environmental and science communicati...

Purpose This paper details a usability testing case study on a simplified homepage for [Library]. The usability testing was completed in Spring 2017 to meet the needs of diverse user groups and shifting trends in Web design and development. At the conclusion of the usability testing, recommendations for change informed the design decisions and a new homepage was implemented in October 2018. Design/methodology/approach The researcher performed eight usability tests with a combination of the different library user types; full-time faculty, students, an administrator and members of the public. The usability test consisted of 13 specific tasks. After testers completed the tasks, users filled out a 30-question Likert-scale questionnaire and answered a set of 8 open-ended questions. Findings This paper discusses the recommendations for change which the researcher discovered at the conclusion of the usability testing period. The research found the need to improve and include specific navigational, visual and easy-to-use elements to best meet the needs of the users in the usability tests. Changes were ranked and implemented on a scale of catastrophic to cosmetic. Research limitations/implications As websites, technology and user preferences continually evolve, the homepage will need to be tested for usability again in the next several years. Researchers are encouraged to adapt the methods to their own institutions. Practical implications This paper discusses findings specific to [Library], which in turn has proved to increase usage of certain features and functions by the user community. Originality/value This is the first time usability testing has been done for the [Library’s] website. It was the first time the design of the homepage was informed by real user preference. This paper is valuable to those looking to create a simple, easy-to-use homepage that best benefits their own unique community of users.

Background Trillium Health (TH) is a Federally Qualified Health Center look-alike and Ryan White C grantee in Rochester, NY providing primary and specialty care, including HIV prevention and treatment. Rapid Start Antiretroviral therapy (RSA) has been shown to decrease time to viral suppression while increasing linkage to and retention in care. However, data on a fixed-dose combination of BFTAF with these benefits are limited. We aim to show RSA with BFTAF time to viral suppression, adherence to medication, and retention in care is statistically significant in comparison to older treatment models. Additionally, we aim to demonstrate the feasibility and acceptability of RSA with BFTAF. Methods This is an interim analysis of participants who enrolled in the study and been in care at TH for at least 3 months as of May 2021. All participants complete a baseline assessment and start BFTAF. Follow up visits are conducted through 48 weeks. Primary and secondary endpoints are included in the attached table 2 Barriers to care and patient reported outcomes were evaluated through a standardized questionnaire at the final study visit. Study results were compared with non-RSA historical control data from patients who received standard of care universal ART initiation at TH. Results Thirty-four participants have been enrolled in the study for at least 12 weeks, 33 (97%) of whom have reached and maintained viral suppression. Twenty-one participants have completed all 48 weeks, with 20 (95%) reaching and maintaining viral suppression. In comparison to historical controls, the RSA study participants had a statistically significant shorter time to viral suppression, both from diagnosis and from ART initiation. The RSA patients had statistically significant higher retention at 12, 24, and 48 weeks in comparison to historical controls. Adherence was higher in the RSA patients, though not statistically significant. Enrollment Graphic for the Rochacha Study Baseline Demographics of Study Participants and Controls Clinical Outcomes of Study Participants compared to Controls Conclusion Our data show that RSA with BFTAF can be effective in a community based health center setting in participants facing barriers to care. The patients who were treated by RSA with BFTAF had a high viral suppression rate. To date, no BFTAF regimen had to be changed due to resistance or virologic failure in this study. These data support implementation of RSA with BFTAF as standard of care. Disclosures Ashley R. Zuppelli, PHARMD, BCACP, AAHIVP, Gilead Sciences (Research Grant or Support) Robert Biernbaum, DO, MS, FAAEM, AAHIVS, Gilead Sciences (Research Grant or Support) Roberto Corales, DO, AAHIVS, Gilead Sciences (Employee, Scientific Research Study Investigator) Shealynn Hilliard, MS, Gilead Sciences (Research Grant or Support) William M. Valenti, MD, FIDSA, Gilead Sciences (Research Grant or Support)

BackgroundAdult-onset Still’s disease (AOSD) is a rare multigenic autoinflammatory disease of unknown aetiology burdened by life-threatening, such as macrophage activation syndrome (MAS) [1]. Considering the poor outcome of MAS patients, previous works tried to assess predictive factors of its occurrence during AOSD [2-4]. However, an integrated evaluation of clinical features with biomolecules, more reflecting the pathogenic mechanisms of the disease and its complications, is still missing.ObjectivesTo multidimensionally characterise MAS complicating AOSD considering cytokine profile, inflammatory markers, and multi-visceral involvement of the disease. To perform a high-dimensional phenotypic analysis of circulating immune cells in AOSD patients with and without MAS. To assess interferon (IFN)-related pathways in AOSD synovial tissues by a bulky RNA sequencing.MethodsThe present evaluation was designed to multidimensionally compare AOSD patients with or without MAS, considering cytokine profile, inflammatory markers, and multi-visceral involvement of the disease. Clinical and biologic data were collected and compared in AOSD patients with and without MAS. Sera biomolecules were analysed by Luminex multiplexing technology. Mass cytometry (CyTOF) was used to characterise circulating immune cells. A bulky RNA sequencing was performed in AOSD synovial tissues.ResultsIn this study, 40 consecutive AOSD patients (47.7±15.0 years, 50.0% male gender) were assessed at the time of diagnosis before the administration of any immunosuppressive therapy. Out of those, 14 (35%) patients were complicated by MAS. Paralleling with increases of systemic score and ferritin, MAS patients were characterised by an increased concentration of IL-1α, IL-1β, IL-1Ra, IL-2Ra, IL-6, IL-10, IL-17A, IFN-γ, G-CSF, MCP-1, MIP-1α, SCF. Among these biomolecules, IL-1Ra, IFN-γ, MCP-1, and SCF were correlated with MAS.Combining the discriminatory ability of these data in identifying MAS, the best model was composed by systemic score, ferritin, IFN-γ, and IL-10. This model was characterised by AUC=0.99 (Standard error: 0.008; 95%CI: 0.976–1.000), sensitivity=100%, specificity=95.45%. By CyTOF analysis, AOSD patients, who were complicated or not with MAS were characterised by a significant increase of circulating “classical monocytes” (CD14+CD38+). MAS patients were characterised by a significant reduction of NK cells (CD45RA+CD56dim) than AOSD patients. Finally, the transcriptomic profile, by RNA-sequencing analysis, showed that 3477 among type I, II, and III IFN-related genes (IRGs) were significantly different in AOSD synovial tissues.ConclusionA multidimensional characterisation of AOSD patients was provided suggesting that IFN-γ, IL-10, ferritin, and systemic score discriminated MAS, thus identifying the occurrence of the cytokine storm syndrome. The inflammatory milieu of AOSD and MAS may be associated with a signature of circulating immune cells. Finally, our results about IRGs reinforced the role of IFN-γ in these patients.References[1]Giacomelli R, Ruscitti P, Shoenfeld Y. A comprehensive review on adult onset Still’s disease. J Autoimmun. 2018;93:24-36.[2]Ruscitti P, et al. Macrophage Activation Syndrome in Patients Affected by Adult-onset Still Disease: Analysis of Survival Rates and Predictive Factors in the Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale Cohort. J Rheumatol. 2018;45:864-872.[3]Di Benedetto P, et al. Ferritin and C-reactive protein are predictive biomarkers of mortality and macrophage activation syndrome in adult onset Still’s disease. Analysis of the multicentre Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale (GIRRCS) cohort. PLoS One. 2020;15:e0235326.[4]Wan L, et al. Total metabolic lesion volume of lymph nodes measured by 18F-FDG PET/CT: a new predictor of macrophage activation syndrome in adult-onset Still’s disease. Arthritis Res Ther. 2021;23:97.Disclosure of InterestsNone declared.

Background Sex has been deemed taboo for athletic performance going back to ancient Rome and Greece, as the act of sex was thought to promote ease and a sense of relaxation. Aim This study examined the effect of sexual intercourse completed 12 hours before a bout of isokinetic dynamometry on muscle force production in strength-trained men. Methods 12 Healthy physically active men (age = 25.6 ± 3.8 years) who were sexually active participated in this study. After men completed a familiarization session on day 1, muscle force was measured during 5 sets of maximal unilateral knee extension (KE) and knee flexion exercise at 30 deg/s after men engaged in or abstained from sexual intercourse within the previous 12 hours. The order of this treatment was randomized across participants, and time of day was maintained across all sessions. Outcomes Lower extremity muscle strength and endurance were measured. Results Data showed no significant effect (P = .34 and P = .39) of sexual intercourse on peak or average KE or knee flexion torque. For example, after sexual intercourse, KE torque was similar in set 1 (198.9 ± 39.1 ft/lb vs 190.2 ± 28.7 ft/lb) and set 5 (163.2 ± 30.8 ft/lb vs 159.4 ± 35.2 ft/lb) compared to when men abstained from sexual intercourse. Clinical Translation Engaging in sexual intercourse on the night before exercise is not detrimental to muscular strength in active men. Conclusions This study is strengthened by use of a homogeneous sample of active men as well as precise determination of changes in muscle function via isokinetic dynamometry. However, completion of sexual intercourse was confirmed through self-report rather than direct observation, so it is not certain if participants actually met the requirements of each condition. Results demonstrate that sexual intercourse does not significantly impact lower extremity muscle force, which suggests that restricting sexual activity before short-term, high-force activity is unnecessary.

Blacks and Hispanics/Latinos are disproportionately burdened by HIV compared to non-Hispanic Whites, as evidenced by higher HIV incidence, prevalence, and deaths attributable to AIDS. Increasing the use of novel prevention techniques such as Truvada for pre-exposure prophylaxis (PrEP) could greatly help in reducing these disparities by lowering HIV incidence among these higher risk groups. Trust in providers, which may differ by race and ethnicity, may influence willingness to take PrEP. This study explores the moderating effect of race/ethnicity on trust in one's primary care provider (PCP) on PrEP willingness. This study found a significant association between PCP trust and PrEP willingness, with those with greater trust having 3.24 times the adjusted odds of being willing to try PrEP. Results regarding the effects of race and ethnicity on these outcomes, however, were inconclusive. Results indicate the importance of fostering trust between PrEP-prescribing PCPs and their patients.

Background Trillium Health (TH) is a FQHC in Rochester, NY providing primary and specialty care, including HIV prevention and treatment. Rapid Start ART (RSA) has been shown to decrease time to virologic suppression while increasing linkage to and retention in care. However, data on BFTAF with these benefits is limited. We aim to prove RSA with BFTAF is advantageous in time to viral load suppression, linkage to and retention in care, and patient satisfaction and acceptance. Methods We included data from ART-naive newly diagnosed PLWH enrolled between October 2018 and March 2020 with baseline assessment and started BFTAF. Follow up visits were done per protocol though 48 weeks. The primary study endpoints include median times from: diagnosis to clinic presentation, clinic presentation to ART, and ART to undetectable viral load (VL), < 200 copies/mL and < 50 copies/mL. Linkage to and retention in care were measured at 3 months. Study results were compared with non-RSA historical control data. Patient reported outcomes were evaluated at study completion. Results Of the 27 eligible, 25 participants enrolled. Thirteen received their diagnosis at TH: screening for PrEP (6), community-based HIV/STI/HCV testing (3), community outreach (1), or routine patient screening in primary care (3). Twelve were diagnosed externally: university health centers (2), other health clinic (9), or at-home rapid HIV test (1). All accepted the RSA treatment with BFTAF; two eligible patients declined the study, but accepted RSA. 73.9% of participants were seen within 14 days of Day 84, compared with 50% of historical control group. 12 of 25 completed the primary endpoint of which 100% were highly satisfied with RSA. There were no regimen changes or virologic failures through 48 weeks. RoCHaCHa Study Results Conclusion RSA with BFTAF reduced time to virologic suppression in all participants newly diagnosed with HIV-1 compared with historical non-RSA model. Disclosures Ashley R. Zuppelli, PHARMD, BCACP, AAHIVP, Gilead Sciences, Inc. (Grant/Research Support)Gilead Sciences, Inc. (Advisor or Review Panel member, Research Grant or Support) Michael Mancenido, DO, AAHIVS, Gilead Sciences, Inc. (Grant/Research Support) Jacob Scutaru, MD, Gilead Sciences, Inc. (Grant/Research Support) Alexandra Danforth, PHARMD, BCACP, AAHIVP, Gilead Sciences, Inc. (Grant/Research Support) Robert Biernbaum, DO, MS, FAAEM, AAHIVS, Gilead Sciences, Inc. (Grant/Research Support, Advisor or Review Panel member, Speaker’s Bureau) Roberto Corales, DO, AAHIVS, Gilead Sciences (Employee) William M. Valenti, MD, FIDSA, Gilead Sciences, Inc. (Grant/Research Support, Speaker’s Bureau)

As 2019 ended we saw serious attention being paid to the power of youth as Greta Thunberg was named TIME Magazine’s person of the year. By April 2020, in the midst of the Covid-19 pandemic, the you...

Media reports on global climate change impacts now appear daily. According to The United Nations’ Intergovernmental Panel on Climate Change (IPCC) report in 2018, policymakers had only 12 years to ...

Stimulants are an important psycho-pharmacological tool to consider when treating veterans with adult ADHD and TBI and as a second-line agent for narcolepsy or excessive daytime sedation. Stimulants may also have a role in helping veterans with dementia-related cognitive changes such as apathy or treatment-refractory depression; however, there is less evidence supporting their role for these conditions. In use since the early 1900s, many stimulant formulations currently available can be very effective and relatively quick acting agents. However, caution must be used in veterans with significant cardiac risk factors and females of childbearing age as well as those at risk for substance use disorders, eating disorders, mania, and psychosis. In this chapter, the authors review the most common psychiatric conditions for which stimulants may be indicated in veterans as well as tips for successful prescribing practices, monitoring ongoing use as well as potential pitfalls and contraindications.

Objective The purpose of this study is to evaluate the outcome differences between patients receiving piperacillin-tazobactam pre- and post-implementation of an extended infusion dosing protocol in a community teaching hospital adult intensive care unit. Methods On December 19th, 2011, extended infusion dosing of piperacillin-tazobactam was implemented at St. John’s Hospital’s intensive and cardiac care units (ICU/CCU) following IRB-approval. This is a historical case-control cohort study involving review of electronic medical charts of patients who received traditional or extended infusion therapy. Data was collected for patients that received piperacillin-tazobactam in the ICU/CCU from December 19th, 2010 through March 19th, 2011 for traditional infusion and from December 19th, 2011 through March 19th, 2012 for extended infusion. Primary endpoints were ICU/CCU mortality at discharge and length of stay. Results The study included 113 patients with 52 in the traditional-infusion group and 61 extended-infusion group. There was no statistically significant difference in the primary end-point of ICU/CCU mortality between the two groups (14.8% vs. 21.1%; p = 0.374). In the extended infusion group, there was a shorter length of ICU and CCU stay (8.32 vs. 12.06 days; p = 0.025) and shorter length of hospital stay (11.32 vs. 19.7 days; p = 0.006). The extended-infusion group showed a decrease in cost of therapy that was statistically significant ($120.21 vs. $155.17; p = 0.035). Adverse drug effects did not differ between the two study groups. Conclusion This study showed that treatment with extended-infusion piperacillin-tazobactam therapy improved patient outcomes while maintaining patient safety and decreasing costs.

To study temporal resolved computed tomography imaging (4-Dimensional Computed Tomography: 4DCT) artifacts correlations with scanning parameters and target kinetics and to assess uncertainty introduced by 4DCT in radiotherapy treatment planning. In this work we classified 4DCT artifacts as finite gantry rotation speed related (FGS) and finite sampling frequency related (FSF). We studied FGS artifacts using a respiratory phantom and FSF artifacts using a Monte Carlo simulation of acquisition timing. From our analysis FGS localization error is comparable with image resolution determined by voxel dimensions. Remaining FGS artifacts are correlated with gantry rotation time (Trot), target velocity (v) and their interaction. FSF artifacts occurrence is correlated with sampling ratio (SR), i.e. the ratio of patient respiratory period (Tresp) and sampling time (Ts). In the studied velocity range (0–2 cm/s), using a Trot of 0,5s and a SR higher than 15, FGS and FSF artifacts became comparable with other sources of uncertainty. Our considerations are valid for “ideal” breathing pattern only. When variations from periodical breathing, high target velocity (more than 2 cm/s) or high peak to peak amplitude (more than 2 cm) are present, patient specific images artifacts analysis is recommended.

In 1962, a very brave and determined woman scientist wrote the book, first serialized in the New Yorker magazine, that triggered a global environmental movement. Silent Spring gored the chemical in...

This year’s Sundance Film Festival showcased a number of films about science. Two of them, including the Sloan Award winner, are based on notorious historical cases of human subjects research gone awry. Two others use fiction to present visions for humanity’s possible future.

For the first time in its history, the prestigious international Sundance Film Festival (SFF) held each January in the mountains of Park City, UT, announced an audience-selected Festival Favorite A...

Background Injection drug use is a growing major public health concern. Injection drug users (IDUs) have a higher incidence of co-morbidities including HIV, Hepatitis, and other infections. An effective humoral response is critical for optimal homeostasis and protection from infection; however, the impact of injection heroin use on humoral immunity is poorly understood. We hypothesized that IDUs have altered B cell and antibody profiles. Methods and Findings A comprehensive systems biology-based cross-sectional assessment of 130 peripheral blood B cell flow cytometry- and plasma- based features was performed on HIV-/Hepatitis C-, active heroin IDUs who participated in a syringe exchange program (n = 19) and healthy control subjects (n = 19). The IDU group had substantial polydrug use, with 89% reporting cocaine injection within the preceding month. IDUs exhibited a significant, 2-fold increase in total B cells compared to healthy subjects, which was associated with increased activated B cell subsets. Although plasma total IgG titers were similar between groups, IDUs had significantly higher IgG3 and IgG4, suggestive of chronic B cell activation. Total IgM was also increased in IDUs, as well as HIV Envelope-specific IgM, suggestive of increased HIV exposure. IDUs exhibited numerous features suggestive of systemic inflammation, including significantly increased plasma sCD40L, TNF-α, TGF-α, IL-8, and ceramide metabolites. Machine learning multivariate analysis distilled a set of 10 features that classified samples based on group with absolute accuracy. Conclusions These results demonstrate broad alterations in the steady-state humoral profile of IDUs that are associated with increased systemic inflammation. Such dysregulation may impact the ability of IDUs to generate optimal responses to vaccination and infection, or lead to increased risk for inflammation-related co-morbidities, and should be considered when developing immune-based interventions for this growing population.

To compare the analgesic effect of three treatments to relieve the pain produced by intramuscular injections (IMI) in term newborns, and to assess sex-linked differences in their response to pain.We studied 62 babies. Each baby received antibiotic IMIs for clinical aims. During each IMI, one of the following analgesic treatments was utilized: oral 33% glucose (OG), sensorial saturation (SS), or topic anesthetic cream (TAC). SS is a validated analgesic method, based on the combination of three stimulations (tactile, acoustic and gustative). During the IMI, pain level was assessed with the use of the DAN scale, a validated neonatal pain scale. All babies who received three distinct analgesic procedures for three distinct IMIs were enrolled. Mean pain scores of the three analgesic treatment groups were compared. We then compared mean pain scores of females vs males in the whole cohort and within each treatment group.The 95% Confidence Intervals of pain scores were 5.6-6.5 for TAC, 1.4-2.3 for OG and 0.6-1.2 for SS: when treated with TAC, babies' pain scores were significantly higher than with OG or SS (p0.0001); when treated with OG, babies' pain scores were higher than SS (p = 0.002). Females' mean pain score was significantly higher than males' mean pain score: (95% CI: 2.9-4.1 vs 2.0-3.1; p = 0.01). OG and SS produced significantly higher mean DAN scores in females than in males. Also in the TAC group females' mean DAN scores were higher than males, though this last difference was not statistically significant.This is the first study to show the effectiveness of nonpharmacologic analgesia in relieving IMI pain. It is also the first study to clearly show that the sex differences in pain perception are present since birth.

Jurors for the Rachel Carson Foundation Book Award faced an unusual struggle during the always-challenging review of submissions for 2016: Is a title shelved by bookstores and listed by the publish...

Background and Objectives: An imbalance in cytokine production may be involved in the pathogenesis of chronic C hepatitis. The aim of the study was to investigate circulating levels of interleukin-10 (IL-10) in a selected cohort of patients affected by chronic C hepatitis. Design and Setting: Retrospective study based on consecutive hepatitis C virus patients, affected by chronic active hepatitis, attending the general hospital of hepatology unit from June to September 2009 Patients and Methods: A total of 49 patients with chronic C hepatitis and 20 healthy control subjects similar in gender and age were examined. Circulating IL-10 was assessed by ELISA commercial kit (R and D Systems) in all investigated subjects. Results: There was no significant difference in IL-10 values between controls and overall patients (P>.05). Nevertheless, among patients, subjects with more severe necroinflammation had higher values than others (PPConclusions: These findings suggest that IL-10 may be a useful additional marker to assess necroinflammation and to monitor the evolution of liver damage. They also argue for a potential pathophysiological role for IL-10 in the persistence and progression of hepatitis.