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Javier Mendicute,1 Lucia Bascarán,1 Luis Pablo,2 Cédric Schweitzer,3 Laurent Velasque,4 Christine Bouchet,5 Aldo A Martinez5 1Department of Ophthalmology, Hospital Universitario Donostia, San Sebastián, Spain; 2Department of Ophthalmology, Hospital Universitario Miguel Servet, Zaragoza, Spain; 3Department of Ophthalmology, Bordeaux University Hospital, Bordeaux, France; 4Centre Retine Gallien, Bordeaux, France; 5Alcon Research LLC, Fort Worth, TX, USACorrespondence: Javier MendicuteDepartment of Ophthalmology, Hospital Universitario Donostia, Paseo Dr. Beguiristáin, 115, San Sebastián, 20014, SpainTel +34-943322233Email mendicutejavier@gmail.comPurpose: To evaluate intraoperative intraocular lens (IOL) delivery time and total surgical case time using the UltraSert preloaded delivery system (System U) during routine cataract surgeries and to compare with the manually loaded Monarch delivery system (System M). Physician satisfaction with System U was also assessed.Patients and Methods: In this prospective observational study, subjects ≥ 18 years old underwent cataract surgery in 1 eye and received the AcrySof IQ IOL via the manually loaded System M (n=103) or the AcrySof IQ IOL model AU00T0 via the preloaded System U (n=93). Procedures were digitally recorded by an external camera or by a camera within the operating microscope. Device preparation, IOL delivery, and IOL positioning times were evaluated by 2 independent graders. Pearson χ2 test or Fisher exact test was used for categorical variables and Student’s t-test or Wilcoxon rank-sum test for continuous variables (all tests were 2-sided and performed at a 5% α-level). Physician satisfaction levels were assessed using questionnaires.Results: Lens delivery time was similar for System U and System M (12.9± 5.1 and 12.2± 6.3 s; P=0.412). Mean device preparation time for System U was significantly shorter compared with System M (30.3± 6.6 versus 59.8± 31.0 s; P< 0.05). This resulted in a significantly shorter total intraoperative time (device preparation + lens delivery) with System U versus System M (43.0± 8.6 versus 72.0± 32.5 s; P< 0.05). Total surgical case time (device preparation + lens delivery + lens positioning and unfolding) was shorter for System U versus System M (56.6± 12.6 versus 89.6± 34.6 s; P< 0.05). Physicians reported greater satisfaction levels with System U compared with other devices.Conclusion: Use of the preloaded delivery system (System U) resulted in faster device preparation and reduced total surgical time compared with the manually loaded system (System M). System U was intuitive to use, and physicians preferred it to other devices.Keywords: cataract surgery, intraocular lens delivery time, Monarch, UltraSert

Javier Mendicute,1 Thierry Amzallag,2 Lixin Wang,3 Aldo A Martinez4 1Department of Ophthalmology, Hospital Universitario Donostia, San Sebastián, Spain; 2Department of Ophthalmology, Ophthalmic Institute, North of France, Somain, France; 3Ophthalmology Unit, Novartis Pharmaceuticals Corporation, Fort Worth, TX, USA; 4Medical Affairs, Alcon Laboratories, Inc., Fort Worth, TX, USA Purpose: To compare corneal incision size and intraocular lens (IOL) performance/behavior following implantation with the following delivery systems: system U (UltraSert®), system S (Hoya iSert® 250/251), system T (Tecnis® iTec), and a manual system (Monarch® III Delivery System). Setting: Six study sites (four in Spain and two in France). Design: Prospective, multicenter, parallel-group, randomized, subject-masked, postmarket clinical study. Materials and methods: Subjects were enrolled based on predetermined inclusion/exclusion criteria. The effectiveness end points compared corneal incision size and enlargement after IOL implantation (day of surgery) among all delivery systems. Exploratory end points included mean enlargement of corneal incision size, rates of trapped trailing haptic, IOL adherence to the plunger tip, nozzle tip splitting, and mean surgically induced astigmatism (SIA) at postoperative visit. Results: One hundred and nine subjects participated in the study. The mean corneal incision size following IOL implantation was 2.35±0.019 mm for system U, 2.47±0.016 mm for system T, 2.54±0.019 mm for system S, and 2.49±0.011 mm for the manual system. There were five instances of trapped trailing haptic (all system T group, N=26), one instance of IOL adherence to the plunger tip (system S group, N=26), and six instances of nozzle tip splitting (all system S group, N=26). System U had the least SIA (postoperative Day 1) (SIA Centroid = 0.10 diopters [axis: 83.06°]). Conclusion: Preloaded delivery system U supported the completion of surgery with the smallest incision size, the least SIA (postoperative Day 1), and no trapped trailing haptics or nozzle tip splitting compared to two other preloaded systems and one manual system. Keywords: corneal incision, intraocular lens, preloaded IOL injector, UltraSert

Purpose: To investigate the metabolic information provided by (18)F-fluorodeoxyglucose-positron emission tomography (FDG-PET) during the early response of head-and-neck squamous cell carcinoma (HNSCC) xenografts to radiotherapy (RT). Methods and Materials: Low-passage HNSCC cells (UT14) were injected into the rear flanks of female nu/nu mice to generate xenografts. After tumors grew to 400-500 mm(3), they were treated with either 15 Gy in one fraction (n = 18) or sham RT (n = 12). At various time points after treatment, tumors were assessed with 2-h dynamic FDG-PET and immediately harvested for direct histological correlation. Different analytical parameters were used to process the dynamic PET data: kinetic index (Ki), standard uptake value (SUV), sensitivity factor (SF), and retention index (RI). Tumor growth was assessed using the specific growth rate (SGR) and correlated with PET parameters using the Pearson correlation coefficient (r). Receiver operating characteristic (ROC) and the area under the ROC curve (AUC) were used to test PET parameters for their ability to predict for radiation necrosis and radiation change. Results: Tumor growth was arrested for the first 20 days after RT and recovered thereafter. Histologically, radiation change was observed in the peripheral regions of tumors between days 7 and 23 after RT, and radiation necrosis were observed in the central regions of tumors between days 7 and 40. Ki provided the best correlation with SGR (r = 0.51) and was the optimal parameter to predict for early radiation necrosis (AUC = 0.804, p = 0.07). SUV(30 min) was the strongest predictor for late radiation necrosis (AUC = 0.959, p = 0.004). Both RI(30-60 min) and SF(12-70 min) were very accurate in predicting for radiation change (AUC = 0.891 and 0.875, p = 0.009 and 0.01, respectively). Conclusions: Dynamic FDG-PET analysis (such as Ki or SF) may provide informative assessment of early radiation necrosis or radiation change of HNSCC xenografts after RT. [ABSTRACT FROM AUTHOR]

•Precautionary behaviors were lower if primary language in household was Spanish.•Testing positive for COVID-19 was inversely associated with precautionary behaviors.•Healthcare practitioners were the most trusted source of COVID-19 information., Competing Interests: None., (© 2024 The Authors.)

Workflow managers play a critical role in the efficient planning and execution of complex workloads. A handful of these already exist within the world of computational materials discovery, but their dynamic capabilities are somewhat lacking. The PerQueue workflow manager is the answer to this need. By utilizing modular and dynamic building blocks to define a workflow explicitly before starting, PerQueue can give a better overview of the workflow while allowing full flexibility and high dynamism. To exemplify its usage, we present four use cases at different scales within computational materials discovery. These encapsulate high-throughput screening with Density Functional Theory, using active learning to train a Machine-Learning Interatomic Potential with Molecular Dynamics and reusing this potential for kinetic Monte Carlo simulations of extended systems. Lastly, it is used for an active-learning-accelerated image segmentation procedure with a human-in-the-loop., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Latin America and Caribbean (LAC) regions were an important epicenter of the COVID-19 pandemic and SARS-CoV-2 evolution. Through the COVID-19 Genomic Surveillance Regional Network (COVIGEN), LAC countries produced an important number of genomic sequencing data that made possible an enhanced SARS-CoV-2 genomic surveillance capacity in the Americas, paving the way for characterization of emerging variants and helping to guide the public health response. In this study we analyzed approximately 300,000 SARS-CoV-2 sequences generated between February 2020 and March 2022 by multiple genomic surveillance efforts in LAC and reconstructed the diffusion patterns of the main variants of concern (VOCs) and of interest (VOIs) possibly originated in the Region. Our phylogenetic analysis revealed that the spread of variants Gamma, Lambda and Mu reflects human mobility patterns due to variations of international air passenger transportation and gradual lifting of social distance measures previously implemented in countries. Our results highlight the potential of genetic data to reconstruct viral spread and unveil preferential routes of viral migrations that are shaped by human mobility patterns., (© 2024. The Author(s).)

This study investigated electrochemical characteristics of Gram-positive, Nocardiopsis dassonvillei B17 facultative bacterium in bioelectrochemical systems. The results demonstrated that anodic and cathodic reaction rates were catalyzed by this bacterium, especially by utilization of aluminium alloy as a substrate. Cyclic voltammogram results depicted an increase of peak current and surface area through biofilm development, confirming its importance on catalysis of redox reactions. Phenazine derivatives were detected and their electron mediating behavior was evaluated exogenously. A symmetrical redox peak in the range of -59 to -159 mV/SHE was observed in cyclic voltammogram of bacterial solution supplemented with 12 μM phenazine, a result consistent with cyclic voltammogram of a 5-d biofilm, confirming its importance as an electron mediator in extracellular electron transfer. Furthermore, the dependency of bacterial catalysis and polarization potential were studied. These results suggested that B17 biofilm behaved as a biocathode and transferred electrons to bacterial cells through a mechanism associated with electron mediators., Competing Interests: Declaration of competing interest We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome., (Copyright © 2023. Published by Elsevier B.V.)

We present a comprehensive thermogravimetric analysis (TGA) of polyethylenimine (PEI)-impregnated resorcinol-formaldehyde (RF) aerogels. While numerous studies focus on PEI-impregnated SBA, RF materials have been less examined, despite their interest and specificities. As most articles on PEI-impregnated porous materials follow typical experimental methods defined for SBA, particularities of RF-PEI materials could remain unheeded. The design of nonisothermal TGA protocols, completed with nitrogen isotherms, based on the systematic filling of the matrix delivers a fundamental understanding of the relationship between the structure and function. This study demonstrates (i) the competition between the matrix and PEI for CO 2 -physisorption (φ) and CO 2 -chemisorption (χ), (ii) the hysteresis ([Formula: see text]) of CO 2 capture at low temperature attributed to the kinetic ( K ) hindrance of CO 2 diffusion ( D ) through PEI film/plugs limiting the chemisorption, and (iii) the thermodynamic (θ) equilibrium limiting the capture at high temperature. At variance with SBA-PEI materials, the first layers of PEI in RF are readily available for CO 2 capture given that this matrix does not covalently bind PEI as SBA. A facile method allows the discrimination between physi- and chemisorption, exhibiting how the former decreases with PEI coverage. The CO 2 capture hysteresis, while seldom introduced or discussed, underlines that the commonly accepted operating temperature of the "maximum capture" is based on an incomplete experiment. Through isotherm adsorption analysis, we correlate the evolution of this maximum to the morphological distribution of PEI. This contribution highlights the specificities of RF-PEI and the advantages of our TGA protocol in understanding the structure/function relationship of this kind of material by avoiding the typical direct applications of SBA-specific protocols. The method is straightforward, does not need large-scale facilities, and is applicable to other materials. Its easiness and rapidness are suited to high-volume studies, befitting for the comprehensive evaluation of interacting factors such as the matrix's nature, pore size, and PEI weight.

In vitro cultures of undifferentiated plant cells of Tessaria absinthioides, a native herb popularly recognized and used for its health benefits, were studied as potential food supplements. These tissues were incubated under two light conditions, and the biomass obtained was freeze-dried and oven-dried. To evaluate their nutritional value, their physicochemical and functional properties were determined. Although in some cases there were significant differences in the results according to the drying methodology applied, all these tissues presented a high proportion of proteins (23.6-28.3%), a low percentage of fats (< 2%) constituted mainly by phytosterols, and a significant amount of crude fibers (6.9-9.0%) and ashes (> 10%). In addition, the freeze-dried calli resulted in a product with better functional properties. On the other hand, their phytochemical profiles and antioxidant capacity were studied and compared with tissues from wild specimens and with green tea and chamomile as reference extracts., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: It remains unknown whether or not short-term androgen deprivation (STAD) improves survival among men with intermediate-risk prostate cancer (IRPC) treated with dose-escalated radiotherapy (RT)., Methods: The NRG Oncology/Radiation Therapy Oncology Group 0815 study randomly assigned 1,492 patients with stage T2b-T2c, Gleason score 7, or prostate-specific antigen (PSA) value >10 and ≤20 ng/mL to dose-escalated RT alone (arm 1) or with STAD (arm 2). STAD was 6 months of luteinizing hormone-releasing hormone agonist/antagonist therapy plus antiandrogen. RT modalities were external-beam RT alone to 79.2 Gy or external beam (45 Gy) with brachytherapy boost. The primary end point was overall survival (OS). Secondary end points included prostate cancer-specific mortality (PCSM), non-PCSM, distant metastases (DMs), PSA failure, and rates of salvage therapy., Results: Median follow-up was 6.3 years. Two hundred nineteen deaths occurred, 119 in arm 1 and 100 in arm 2. Five-year OS estimates were 90% versus 91%, respectively (hazard ratio [HR], 0.85; 95% CI, 0.65 to 1.11]; P = .22). STAD resulted in reduced PSA failure (HR, 0.52; P <.001), DM (HR, 0.25; P <.001), PCSM (HR, 0.10; P = .007), and salvage therapy use (HR, 0.62; P = .025). Other-cause deaths were not significantly different ( P = .56). Acute grade ≥3 adverse events (AEs) occurred in 2% of patients in arm 1 and in 12% for arm 2 ( P <.001). Cumulative incidence of late grade ≥3 AEs was 14% in arm 1 and 15% in arm 2 ( P = .29)., Conclusion: STAD did not improve OS rates for men with IRPC treated with dose-escalated RT. Improvements in metastases rates, prostate cancer deaths, and PSA failures should be weighed against the risk of adverse events and the impact of STAD on quality of life.

Purpose: To report patient-reported outcomes (PROs) of a phase III trial evaluating total androgen suppression (TAS) combined with dose-escalated radiation therapy (RT) for patients with intermediate-risk prostate cancer., Methods: Patients with intermediate-risk prostate cancer were randomly assigned to dose-escalated RT alone (arm 1) or RT plus TAS (arm 2) consisting of luteinizing hormone-releasing hormone agonist/antagonist with oral antiandrogen for 6 months. The primary PRO was the validated Expanded Prostate Cancer Index Composite (EPIC-50). Secondary PROs included Patient-Reported Outcome Measurement Information System (PROMIS)-fatigue and EuroQOL five-dimensions scale questionnaire (EQ-5D). PRO change scores, calculated for each patient as the follow-up score minus baseline score (at the end of RT and at 6, 12, and 60 months), were compared between treatment arms using a two-sample t test. An effect size of 0.50 standard deviation was considered clinically meaningful., Results: For the primary PRO instrument (EPIC), the completion rates were ≥86% through the first year of follow-up and 70%-75% at 5 years. For the EPIC hormonal and sexual domains, there were clinically meaningful ( P < .0001) deficits in the RT + TAS arm. However, there were no clinically meaningful differences by 1 year between arms. There were also no clinically meaningful differences at any time points between arms for PROMIS-fatigue, EQ-5D, and EPIC bowel/urinary scores., Conclusion: Compared with dose-escalated RT alone, adding TAS demonstrated clinically meaningful declines only in EPIC hormonal and sexual domains. However, even these PRO differences were transient, and there were no clinically meaningful differences between arms by 1 year.

Alzheimer's Disease (AD) represents a major health problem without effective treatments. As the incidence of the disease will continue to rise, it is imperative to find new treatment options to halt or slow disease progression. In recent years, several groups have begun to study the utility of low total dose radiation therapy (LTDRT) to inhibit some of the pathological features of AD and improve cognition in a variety of animal models. These preclinical studies have led to Phase 1 and 2 trials in different centers around the world. In this review, we present and interpret the pre-clinical evidence report some preliminary clinical data from a Phase 2 trial in early-stage AD patients., (©2023 by Radiation Research Society. All rights of reproduction in any form reserved.)

Importance: Hypofractionated radiation therapy (RT) for prostate cancer has been associated with greater acute grade 2 gastrointestinal (GI) toxic effects compared with conventionally fractionated RT., Objective: To evaluate whether a hyaluronic acid rectal spacer could (1) improve rectal dosimetry and (2) affect acute grade 2 or higher GI toxic effects for hypofractionated RT., Design, Setting, and Participants: This randomized clinical trial was conducted from March 2020 to June 2021 among 12 centers within the US, Australia, and Spain, with a 6-month follow-up. Adult patients with biopsy-proven, T1 to T2 prostate cancer with a Gleason score 7 or less and prostate-specific antigen level of 20 ng/mL or less (to convert to μg/L, multiply by 1) were blinded to the treatment arms. Of the 260 consented patients, 201 patients (77.3%) were randomized (2:1) to the presence or absence of the spacer. Patients were stratified by intended 4-month androgen deprivation therapy use and erectile quality., Main Outcomes and Measures: For the primary outcome, we hypothesized that more than 70% of patients in the spacer group would achieve a 25% or greater reduction in the rectal volume receiving 54 Gy (V54). For the secondary outcome, we hypothesized that the spacer group would have noninferior acute (within 3 months) grade 2 or higher GI toxic effects compared with the control group, with a margin of 10%., Results: Of the 201 randomized patients, 8 (4.0%) were Asian, 26 (12.9%) Black, 42 (20.9%) Hispanic or Latino, and 153 (76.1%) White; the mean (SD) age for the spacer group was 68.6 (7.2) years and 68.4 (7.3) years for the control group. For the primary outcome, 131 of 133 (98.5%; 95% CI, 94.7%-99.8%) patients in the spacer group experienced a 25% or greater reduction in rectum V54, which was greater than the minimally acceptable 70% (P < .001). The mean (SD) reduction was 85.0% (20.9%). For the secondary outcome, 4 of 136 patients (2.9%) in the spacer group and 9 of 65 patients (13.8%) in the control group experienced acute grade 2 or higher GI toxic effects (difference, -10.9%; 95% 1-sided upper confidence limit, -3.5; P = .01)., Conclusions and Relevance: The trial results suggest that rectal spacing with hyaluronic acid improved rectal dosimetry and reduced acute grade 2 or higher GI toxic effects. Rectal spacing should potentially be considered for minimizing the risk of acute grade 2 or higher toxic effects for hypofractionated RT., Trial Registration: ClinicalTrials.gov Identifier: NCT04189913.

Herein we show a density functional theory-based study performed on two recently predicted polymorphs of the BeH 2 monolayer, α-BeH 2 and β-BeH 2 . The α-BeH 2 phase possesses an in-plane negative Poisson's ratio (NPR), introducing it into the unique group of auxetic materials. Our assessment delves into the linear-elastic and finite-strain regimes to understand both polymorphs' structural and mechanical responses to deformation. We find that the in-plane NPR is shown to be only parallel to the bonds in α-BeH 2 and remains along the uniaxial tensile path. Concomitantly, an out-of-plane transition toward auxetic is also revealed in regions exhibiting conventional Poisson's ratios, making α-BeH 2 a bidirectionally auxetic material. While phase transitions in β-BeH 2 are triggered at very short strains, α-BeH 2 displays excellent elasticity against tension, superior to that of most currently known 2D materials., (© 2022 Wiley Periodicals LLC.)

Justification: In Mexico, the number of unidentified bodies has been steadily rising for years. By now, more than 50,000 bodies are considered unidentified. Forensic laboratories that could perform comparative molecular genetic investigation are often overburdened and examinations can take months. Therefore, pragmatic approaches that can help to identify more unknown bodies must be sought. The increased use of distinctive physical features might be one, and the high rate of tattooed people in Mexico points towards a great potential of tattoos as a tool for identification. The prerequisite for a comparison of antemortem (missing persons) and postmortem (unknown bodies) data is an objective description of the particularities, e.g., of the tattoos. The aim of this study was to establish an objective classification for tattoo motives, taking into consideration local preferences., Methods: In the database of the medicolegal services of the Instituto Jaliscience de Ciencias Forenses (IJCF) in Guadalajara, postmortem data of 1000 tattooed bodies from 2019 were evaluated. According to sex and age, the tattooed body localization and the tattoo motives were categorized., Results: The 1000 tattooed deceased showed tattoos on 2342 body localizations. The motives were grouped and linked to the following 11 keywords (with decreasing frequency): letters/numbers, human, symbol (other), plant, symbol (religious), animal, object, fantasy/demon/comic, tribal/ornament/geometry, other, unrecognizable., Conclusion: Using the proposed classification, tattoo motives can be described objectively and classified in a practical way. If used for antemortem (missing persons) and postmortem (unknown bodies) documentation, motives can be searched and compared efficiently-helping to identify unknown bodies., (© 2022. The Author(s).)

A METland is an innovative treatment wetland (TW) that relies on the stimulation of electroactive bacteria (EAB) to enhance the degradation of pollutants. The METland is designed in a short-circuit mode (in the absence of an external circuit) using an electroconductive bed capable of accepting electrons from the microbial metabolism of pollutants. Although METlands are proven to be highly efficient in removing organic pollutants, the study of in situ EAB activity in full-scale systems is a challenge due to the absence of a two-electrode configuration. For the first time, four independent full-scale METland systems were tested for the removal of organic pollutants and nutrients, establishing a correlation with the electroactive response generated by the presence of EAB. The removal efficiency of the systems was enhanced by plants and mixed oxic-anoxic conditions, with an average removal of 56 g of chemical oxygen demand (COD) m bed material -3 day -1 and 2 g of total nitrogen (TN) m bed material -3 day -1 for Ørby 2 (partially saturated system). The estimated electron current density ( J ) provides evidence of the presence of EAB and its relationship with the removal of organic matter. The tested METland systems reached the max. values of 188.14 mA m -2 (planted system; IMDEA 1), 223.84 mA m -2 (non-planted system; IMDEA 2), 125.96 mA m -2 (full saturated system; Ørby 1), and 123.01 mA m -2 (partially saturated system; Ørby 2). These electron flow values were remarkable for systems that were not designed for energy harvesting and unequivocally show how electrons circulate even in the absence of a two-electrode system. The relation between organic load rate (OLR) at the inlet and coulombic efficiency (CE; %) showed a decreasing trend, with values ranging from 8.8 to 53% (OLR from 2.0 to 16.4 g COD m -2 day -1 ) for IMDEA systems and from 0.8 to 2.5% (OLR from 41.9 to 45.6 g COD m -2 day -1 ) for Ørby systems. This pattern denotes that the treatment of complex mixtures such as real wastewater with high and variable OLR should not necessarily result in high CE values. METland technology was validated as an innovative and efficient solution for treating wastewater for decentralized locations., 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 © 2022 Peñacoba-Antona, Ramirez-Vargas, Wardman, Carmona-Martinez, Esteve-Núñez, Paredes, Brix and Arias.)

Objective: The aim of the study was to assess the prevalence of cervical dysplasia among migrant women with female genital mutilation/cutting (FGM/C) at a specialized clinic in Switzerland., Materials and Methods: This is a descriptive retrospective cross-sectional study. We reviewed the electronic medical records of all women who attended a specialized FGM/C clinic at the Geneva University Hospitals between 2010 and 2016. We examined sociodemographic data, sexually transmitted infections, FGM/C types, Pap smear results, and follow-up in women diagnosed with cervical dysplasia., Results: Three hundred sixty records were reviewed and 338 women were included. The average age was 33 years (SD = 7.47 years). Most women were from Eritrea and Somalia (n = 204, 60.4%) and had FGM/C type III (n = 188, 55.6%). A total of 12.4% (n = 42) of the patients had abnormal Pap smears: 1.5% (n = 5) with atypical squamous cells of undetermined significance (ASCUS) with high-risk human papillomavirus (HPV), 7.9% (n = 27) with low-grade squamous intraepithelial lesion (LSIL), and 2.9% (n = 10) with high-grade squamous intraepithelial lesion or higher (HSIL +). Of the 37 patients with dysplasia, 22 (59.4%) completed follow-up and 15 (40.5%) received incomplete follow-up., Conclusions: The prevalence of high-grade squamous intraepithelial lesion+ among migrant women with FGM/C is high (2.95%) compared with the general Swiss population (0.58%). Follow-up for cervical dysplasia must be improved by increasing provider knowledge of this patient population and by addressing barriers to care., Competing Interests: The authors have declared they have no conflicts of interest., (Copyright © 2021, ASCCP.)

Introduction and Objectives: After hepatitis A (HAV) mandatory immunization in 2005 in Argentina, the incidence of HAV declined drastically. However, several new autochthonous cases of HAV have been reported since 2017. We aimed to evaluate the clinical and epidemiological characteristics and possible transmission routes of affected patients., Patients or Materials and Methods: We performed a cross-sectional study of patients residing in Argentina with acute hepatitis A between 30.06.2017 and 31.12.2018., Results: 66 cases of HAV were registered. Fifty-six patients (86%) were males, with a mean age of 34 ± 12 years old. The most likely routes of transmission were sexual intercourse of men with men, reported by 31 patients. Additionally, 23% and 26% of patients tested positive for HIV and syphilis, respectively. In total, 35% of patients required hospitalization. When assessing outcomes, 79% had a mild presentation and 21% had a severe/fulminant presentation: one patient underwent liver transplantation, and one patient died., Conclusions: Our study describes that during the study period, HAV infection affected predominantly young adults, particularly men who have sex with men. An elevated proportion of them was diagnosed with a concomitant sexually transmitted disease, and several patients had a severe presentation of the disease., (Copyright © 2020 Fundación Clínica Médica Sur, A.C. Published by Elsevier España, S.L.U. All rights reserved.)

Most of the previous studies that investigated the factors increasing the severity of rear-end collisions were based on analyzing collision reports from multiple years and combining them into a single dataset for analysis. Analyzing pooled data from multiple years carries the risk of introducing aggregation bias in the analysis. Those aggregated models might be structurally unstable, and the significance of the risk factors identified using those aggregated models might change over time due to the ongoing changes in vehicle technologies, law-enforcement technologies, and drivers' attitudes. This study demonstrates the importance of testing the temporal stability of pooled data by utilizing logistic regression modeling to analyze all rear-end collisions that occurred in North Carolina for the period from January 1, 2004 to December 31, 2015. Separate models were developed for each year to model injury severity of striking and struck drivers. The year-wise models were compared together to identify the most temporally stable factors, and it was found that older and female drivers are usually more severely injured, but they do not increase injury severity of the drivers they collide with. It was also found that compared to other light-duty vehicles, passenger cars are usually associated with increased injury severity to their drivers and reduced injury severity to the drivers of the vehicles they collide with. The increased age of a vehicle was found to increase the injury severity of its driver as well as the driver of the vehicle it collides with. Dark conditions were found to increase drivers' injury severity, but adverse weather conditions have no similar effect. For comparison, aggregated models were also developed by pooling data from all analysis years (from 2004 to 2015) and were found to return significant factors that were found by the year-wise models to be temporally unstable. Chow tests were performed on the data, and it was found that pooling data for four years or more generally returned structurally unstable models., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Social withdrawal in the sub-chronic phencyclidine (PCP) rat model, a behavioral correlate of the negative symptoms of schizophrenia, results from deficits in brain endocannabinoid transmission. As cannabis intake has been shown to affect negatively the course and expression of psychosis, we tested whether the beneficial effects of endocannabinoid-mediated CB1 activation on social withdrawal in PCP-treated rats (5 mg/kg, twice daily for 7 days)also occurred after administration of Δ9-tetrahydrocannabinol (THC; 0.1, 0.3, 1.0 mg/kg, i.p.). In addition, we assessed whether THC affected two correlates of positive symptoms: 1) motor activity induced by d-amphetamine (0.5 mg/kg, i.p.), and 2) dopamine neuron population activity in the ventral tegmental area (VTA). After the motor activity test, the brains from d-amphetamine-treated animals were collected and processed for measurements of endocannabinoids and activation of Akt/GSK3β, two molecular markers involved in the pathophysiology of schizophrenia. In control rats, THC dose-dependently produced social interaction deficits and aberrant VTA dopamine neuron population activity similar to those observed in PCP-treated animals. In PCP-treated rats, only the lowest dose of THC reversed PCP-induced deficits, as well as PCP-induced elevation of the endocannabinoid anandamide (AEA) in the nucleus accumbens. Last, THC activated the Akt/GSK3β pathway dose-dependently in both control and PCP-treated animals. Taken together, these data suggest that only low doses of THC have beneficial effects on behavioral, neurochemical and electrophysiological correlates of schizophrenia symptoms. This observation may shed some light on the controversial hypothesis of marijuana use as self-medication in schizophrenic patients., Competing Interests: The authors have declared that no competing interests exist.

We have previously reported that low doses of external beam ionizing irradiation reduced amyloid-β (Aβ) plaques and improved cognition in APP/PS1 mice. In this study we investigated the effects of radiation in an age-matched series of 3xTg-AD mice. Mice were hemibrain-irradiated with 5 fractions of 2 Gy and sacrificed 8 weeks after the end of treatment. Aβ and tau were assessed using immunohistochemistry and quantified using image analysis with Definiens Tissue Studio. We observed a significant reduction in Aβ plaque burden and tau staining; these two parameters were significantly correlated. This preliminary data is further support that low doses of radiation may be beneficial in Alzheimer's disease.

Objective: Society has changed during the last 100 years of evolution; however, some problems, such as suicide, remain. The objective here is to carry out a long-term epidemiological study in Spain, and to calculate the social and labor costs of 2016., Method: Epidemiological data were obtained from official data obtained between 1906 - 2016. The calculation of the costs of suicides included the social costs and the costs of production losses (labor costs). The latter were obtained by the human capital method, taking into account the unemployment rate. The economic growth rate stood at 2.6% per year., Results: The suicide rate was between 4 and 8% per year. The evolution during these 100 years had three periods. Until 1940 it had slight increases, and then it decreased until 1980 and, subsequently, the rate increased until it reached almost 8% in 2016. The costs of the suicides were 2,167 million € of economic losses for society, or its equivalent of 607 € for suicide., Conclusions: Public health policies aimed at the prevention of suicide should be increased, and supported by the economic costs they mean for society.

Purpose: To update outcome and toxicity results of a prospective trial of 19-Gy single-fraction high-dose-rate (HDR) brachytherapy for men with low- and intermediate-risk prostate cancer., Methods and Materials: Patients were treated on a prospective study of single-fraction HDR brachytherapy. All patients had low- or intermediate-risk prostate cancer. Patients with prostate volumes >50 cm 3 , taking alpha-blockers for urinary symptoms, or with baseline American Urologic Association symptom scores >12 were ineligible. Patients underwent transrectal ultrasound-guided interstitial implant of the prostate followed by single-fraction HDR brachytherapy to a prescription dose of 19 Gy., Results: Sixty-eight patients were enrolled with a median follow-up of 3.9 years. Median age was 62 years. Median gland volume at the time of treatment was 35 cm 3 , 92.6% of patients had T1 disease, 63.2% had a Gleason score of 6, and median pretreatment prostate-specific antigen was 5.0 ng/mL. Chronic grade 2 genitourinary toxicity was 14.7%. No grade 3 urinary toxicity occurred. A single patient experienced grade 2+ rectal toxicity (grade 3 diarrhea) that was transient and resolved with medical management. The 5-year estimated disease-free survival was 77.2% with no significant difference between low- and intermediate-risk patients. A single patient developed distant metastases during the follow-up period. Biopsy-proven local failure at 5 years was 18.8%, occurring at a median interval of 4.0 years posttreatment. No deaths occurred during follow-up., Conclusions: With extended follow-up, toxicity rates after single-fraction 19-Gy HDR brachytherapy remain low. Higher-than-expected rates of biochemical and local failure, however, raise concerns regarding the adequacy of this dose. Additional investigation to define the optimal single-fraction HDR brachytherapy dose is warranted, and single-fraction treatment currently should not be offered outside the context of a clinical trial., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Following Galileo's trial of 1633, the Jesuit theologian Melchior Inchofer, author of the most negative reports used by the Roman Inquisition against Galileo, repudiated the Copernicans for the 'heresy' of the soul of the world ( anima mundi ), in an unpublished manuscript. I show that Inchofer's arguments applied far more to the beliefs of Giordano Bruno than to those of Galileo. Since antiquity, various Christian authorities had repudiated several beliefs about the anima mundi as 'heretical', hence I review their critiques against Pythagoras, Origen, and Peter Abelard, for allegedly asserting animistic beliefs about the Earth, or a universal spirit, or that souls move the heavenly bodies. Still, in the Renaissance such beliefs were defended by several advocates of Copernicus, including Bruno, William Gilbert, Johannes Kepler, and Philips Lansbergen, who all claimed that Earth moves because it has a soul. By comparing Inchofer's works and some of the Roman Inquisition's earlier censures against Bruno, I argue that the repudiation by many prominent Catholic theologians of pagan notions of the anima mundi as heretical contributed partly to the later theological opposition to the Copernicans.

Background: To report 6-year outcomes from a phase I/II trial using balloon-based brachytherapy to deliver APBI in 2 days., Methods: A total of 45 patients with early-stage breast cancer received adjuvant APBI in 2 days with high-dose rate (HDR) brachytherapy totaling 2800 cGy in 4 fractions (700 cGy BID) using a balloon-based applicator as part of a prospective phase I/II clinical trial. All patients had negative margins and skin spacing ≥8 mm. We evaluated toxicities (CTCAE v3) as well as ipsilateral breast tumor recurrence (IBTR), regional nodal failure (RNF), distant metastasis, disease-free survival, cause-specific survival, and overall survival., Results: Median age and tumor size were 66 years old (48 to 83) and 0.8 cm (0.2 to 2.3 cm), respectively. Four percent of patients were N1 (n=2) and 73% were estrogen receptor (ER) positive (n=32). Median follow-up was 6.2 years (2.4 to 8.0 y). Nearly all toxicities at 6 years were grade 1 to 2 except 1 instance of grade 3 telangiectasia (2%). Eleven percent (n=5) of patients had chronic asymptomatic fat necrosis whereas asymptomatic seromas were noted on mammogram in 13% of cases (n=6). Cosmesis at last follow-up was good or excellent in 91% of cases (n=40) and fair in 9% (n=4). Two of the previously reported rib fractures healed with conservative measures. There were no IBTR or RNF (6 y IBTR/RNF rate 0%); however, 2 patients experienced distant metastasis (4% at 6 y). The 6-year actuarial disease-free survival, cause-specific survival, and overall survival were 96%, 100%, and 93%, respectively., Conclusions: Hypofractionated 2-day APBI using brachytherapy resulted in excellent clinical outcomes with acceptable chronic toxicities.

The West Nile virus (WNV) has spread throughout the world causing neuroinvasive diseases with no treatments available. The viral NS2B-NS3 protease is essential for WNV survival and replication in host cells and is a promising drug target. Through an enzymatic screen of the National Institute of Health clinical compound library, we report the discovery of zafirlukast, an FDA approved treatment for asthma, as an inhibitor for the WNV NS2B-NS3 protease. Zafirlukast was determined to inhibit the protease through a mixed mode mechanism with an IC 50 value of 32 μM. A structure activity relationship study of zafirlukast revealed the cyclopentyl carbamate and N-aryl sulfonamide as structural elements crucial for NS2B-NS3 protease inhibition. Replacing the cyclopentyl with a phenyl improved inhibition, resulting in an IC 50 of 22 μM. Experimental and computational docking analysis support the inhibition model of zafirlukast and analogs binding at an allosteric site on the NS3 protein, thereby disrupting the NS2B cofactor from binding, resulting in protease inhibition., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Axial impacts to the lower leg during debilitating events such as frontal automotive collisions and military underbody blasts can cause significant injuries to the tibia. Several studies have conducted axial impact tests to determine the injury limits of the lower leg, mostly focused on automotive intrusions, resulting in an established force criterion for injury assessments. Due to the viscoelastic properties of bone, it remains unclear whether results from automotive experiments can be applied to higher-rate military blasts. Twelve male isolated cadaveric tibias (from six pairs, mean age: 62 ± 8 years) were subjected to axial impact loads using a custom-built pneumatic impactor, with one specimen from each pair tested at velocity and impact durations representative of a military blast condition, and the contralateral under conditions representing an automotive collision. Impacts were applied in increasing levels of intensity (defined using energy levels) until fracture occurred. Fracture risk was influenced by projectile velocity, kinetic energy, impulse, and load rate, and there was a significant difference in peak force (p = 0.023), impulse (p = 0.09), and load rate (p = 0.025) between the automotive and military test conditions causing fracture. A 10% risk of fracture corresponded to an impact force of 9.0kN for the automotive condition and 12.2kN for the military condition. These results suggest that fracture tolerances developed in studies that simulate automotive impacts cannot be directly applied to military impacts of shorter duration. The number of factors identified to predict injury also suggests that fracture is not controlled by a single variable., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

During a frontal collision, there are a range of lower extremity postures that the vehicle's occupant may assume, potentially changing the way load is transmitted to this region of the body. While most experimental studies on the tibia's injury tolerance assume that load is directed along the leg's long axis, the effects of off-axis loading due to non-standard postures have not been well quantified, and commonly-cited injury criteria such as the Tibia Index do not directly account for posture. Therefore, twelve cadaveric tibias (paired from six donors) were subjected to off-axis impact loading in a custom-built test apparatus. One specimen from each pair was held at an angle of 15° relative to the direction of loading, while the contralateral was held at an angle of 30°, with these angles representing ankle plantarflexion and corresponding knee extension in a vehicle occupant. Specimens held at 30° fractured at lower forces than the specimens held at 15° (mean force = 5.8 vs. 7.5 kN). This indicates that posture should be incorporated into injury criteria for the tibia in future safety assessments instead of using a single force value based on axial impacts.

Background: The purpose of the study was to determine outcomes for patients treated with accelerated partial breast irradiation (APBI) on the basis of breast cancer subtype (BCST)., Patients and Methods: Our single-institution, institutional review board-approved APBI database was queried for patients who had complete testing results for the estrogen (ER), progesterone (PR), and HER2/neu receptors to determine outcomes for each BCST. Women were assigned as luminal A (LA), luminal B (LB), HER2, and basal BCST using their ER, PR, and HER2/neu receptor status. Degree of ER expression supplemented the receptor-based luminal BCST assignment. Two hundred seventy-eight patients had results for all 3 receptors (LA = 164 [59%], LB = 81 [29%], HER2 = 5 [2%], basal = 28 [10%]), which were submitted for analysis (ipsilateral breast tumor recurrence [IBTR], regional nodal failure, distant metastasis [DM], disease-free survival [DFS], cause-specific survival [CSS], and overall survival [OS])., Results: Median follow-up was 5.4 years (range, 0.1-12.4 years). Basal and HER2 subtype patients had higher histologic grades (Grade 3 = 75% vs. 10% LA/LB; P < .001), larger tumors (13.0 mm basal vs. 10.7 mm LA/LB; P = .059), and were more likely to receive chemotherapy (68% vs. 15% LA/LB; P < .001). Margin and nodal status were similar among BCSTs. At 5 years, IBTR rates were similar (1.8%, 2.9%, 0%, and 4.8%) for LA, LB, HER2, and basal subtypes, respectively (P = .62). DM was only seen in LA (2.9%) and LB (1.3%) (P = .83). DFS (95%-100%), CSS (97%-100%), and OS (80%-100%) were not statistically different (P = .97, .87, .46, respectively)., Conclusion: Five-year local control rates after breast-conserving surgery, APBI, and appropriate systemic therapy are excellent for luminal, HER2, and basal phenotypes of early-stage breast cancer; however, further study of receptor subtype effect on risk stratification in early-stage breast cancer is needed., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: To report the toxicity and preliminary clinical outcomes of a prospective trial evaluating 19-Gy, single-fraction high-dose-rate (HDR) brachytherapy for men with low- and intermediate-risk prostate cancer., Methods and Materials: A total of 63 patients were treated according to an institutional review board-approved prospective study of single-fraction HDR brachytherapy. Eligible patients had tumor stage ≤T2a, prostate-specific antigen level ≤15 ng/mL, and Gleason score ≤7. Patients with a prostate gland volume >50 cm 3 and baseline American Urologic Association symptom score >12 were ineligible. Patients underwent transrectal ultrasound-guided transperineal implantation of the prostate, followed by single-fraction HDR brachytherapy. Treatment was delivered using 192 Ir to a dose of 19 Gy prescribed to the prostate, with no additional margin applied., Results: Of the 63 patients, 58 had data available for analysis. Five patients had withdrawn consent during the follow-up period. The median follow-up period was 2.9 years (range 0.3-5.2). The median age was 61.4 years. The median gland volume at treatment was 34.8 cm 3 . Of the 58 patients, 91% had T1 disease, 71% had Gleason score ≤6 (29% with Gleason score 7), and the median pretreatment prostate-specific antigen level was 5.1 ng/mL. The acute and chronic grade 2 genitourinary toxicity incidence was 12.1% and 10.3%, respectively. No grade 3 urinary toxicity occurred. No patients experienced acute rectal toxicity grade ≥2, and 2 experienced grade ≥2 chronic gastrointestinal toxicity. Three patients experienced biochemical failure, yielding a 3-year cumulative incidence estimate of 6.8%., Conclusions: Single-fraction HDR brachytherapy is well-tolerated, with favorable preliminary biochemical and clinical disease control rates., (Copyright © 2016 Elsevier Inc. All rights reserved.)

This paper analyses the importance of Giordano Bruno's belief in many worlds, including the Moon, the planets and the stars, in the context of his trial by the Inquisitions in Venice and Rome. Historians have claimed that this belief was not heretical and therefore was not a major factor in Bruno's trial or execution. On the contrary, by examining neglected treatises on theology, heresies and Catholic canon law, I show that the belief in many worlds was formally heretical. Multiple Christian authorities denounced it. A systematic analysis of the extant primary sources shows that Bruno's belief in many worlds was, surprisingly, of primary importance in his trial and execution. The evidence includes recent and newly discovered primary sources.

Long-term administration of l-3,4-dihydroxyphenylalanine (levodopa), the mainstay treatment for Parkinson's disease (PD), is accompanied by fluctuations in its duration of action and motor complications (dyskinesia) that dramatically affect the quality of life of patients. Levodopa-induced dyskinesias (LID) can be modeled in rats with unilateral 6-OHDA lesions via chronic administration of levodopa, which causes increasingly severe axial, limb, and orofacial abnormal involuntary movements (AIMs) over time. In previous studies, we showed that the direct activation of CB1 cannabinoid receptors alleviated rat AIMs. Interestingly, elevation of the endocannabinoid anandamide by URB597 (URB), an inhibitor of endocannabinoid catabolism, produced an anti-dyskinetic response that was only partially mediated via CB1 receptors and required the concomitant blockade of transient receptor potential vanilloid type-1 (TRPV1) channels by capsazepine (CPZ) (Morgese et al., 2007). In this study, we showed that the stimulation of peroxisome proliferator-activated receptors (PPAR), a family of transcription factors activated by anandamide, contributes to the anti-dyskinetic effects of URB+CPZ, and that the direct activation of the PPARγ subtype by rosiglitazone (RGZ) alleviates levodopa-induced AIMs in 6-OHDA rats. AIM reduction was associated with an attenuation of levodopa-induced increase of dynorphin, zif-268, and of ERK phosphorylation in the denervated striatum. RGZ treatment did not decrease striatal levodopa and dopamine bioavailability, nor did it affect levodopa anti-parkinsonian activity. Collectively, these data indicate that PPARγ may represent a new pharmacological target for the treatment of LID., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The hypothesis of this study was that broader patterns of physiological channel interactions in the local region of the cochlea are associated with poorer spectral resolution in the same region. Electrically evoked compound action potentials (ECAPs) were measured for three to six probe electrodes per subject to examine the channel interactions in different regions across the electrode array. To evaluate spectral resolution at a confined location within the cochlea, spectral-ripple discrimination (SRD) was measured using narrowband ripple stimuli with the bandwidth spanning five electrodes: Two electrodes apical and basal to the ECAP probe electrode. The relationship between the physiological channel interactions, spectral resolution in the local cochlear region, and vowel identification was evaluated. Results showed that (1) there was within- and across-subject variability in the widths of ECAP channel interaction functions and in narrowband SRD performance, (2) significant correlations were found between the widths of the ECAP functions and narrowband SRD thresholds, and between mean bandwidths of ECAP functions averaged across multiple probe electrodes and broadband SRD performance across subjects, and (3) the global spectral resolution reflecting the entire electrode array, not the local region, predicts vowel identification.

Purpose: To compare erectile dysfunction (ED) after adaptive dose-escalated image-guided intensity-modulated radiotherapy (IG-IMRT) and high-dose-rate interstitial brachytherapy (HDR) monotherapy., Methods and Materials: Low- and intermediate-risk prostate cancer patients treated with IG-IMRT or HDR were matched on pretreatment ED, age, Gleason score, T-stage, and prostate specific antigen. Patients who received androgen deprivation therapy were excluded. ED was graded by Common Terminology Criteria for Adverse Events v4. Actuarial rates of ED were computed by the Kaplan-Meier method., Results: There were 384 patients with median followup of 2.0 years (0.5-6.1) for IG-IMRT and 2.0 years (0.5-8.7) for HDR. The median IG-IMRT dose was 75.6 Gy and HDR dose 38 Gy in four fractions. For patients with no pretreatment ED, actuarial rates of requiring intervention (Grade ≥2 ED) at 3 years were 31% for IG-IMRT and 19% for HDR (p=0.23), and impotence despite medical intervention (Grade 3) were 0% for IG-IMRT and 6% for HDR (p=0.06). For patients with Grade 1 pretreatment ED, Grade ≥2 ED at 3 years were 47% for IG-IMRT and 34% for HDR (p=0.79), and Grade 3 ED were 15% in both groups (p=0.59). For patients with Grade 2 pretreatment ED, Grade 3 ED at 3 years were 22% for IG-IMRT and 37% for HDR (p=0.70). No variables were predictive of Grade ≥2 ED following treatment., Conclusions: Rates of ED requiring medical intervention for both IG-IMRT and HDR are low and equivalent. Even patients with ED before treatment are likely to maintain potency with medication use at 3 years following treatment., (Copyright © 2014 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

To establish evolutionary pattern of a case of nodular scleritis with high frequency ultrasound during treatment. Twenty-seven year old female, initial manifestation of intermediate uveitis, bilateral macular edema after clinical treatment with topical and oral steroids. After four months, we observed the formation of a scleral nodule in the right eye when patient underwent high frequency ultrasound (Paradigm, 50 MHz transducer, immersion technique). The lesion in right eye was characterized at high frequency ultrasound as a nodular lesion located at the anterior inferior temporal wall associated with localized reduction of scleral thickness. After intravitreal injection of triamcinolone for treatment of macular edema, clinical regression of the scleral nodule was observed in right eye, maintaining reduced scleral thickness. High frequency ultrasound assisted in the diagnosis of nodular scleritis during the phases of treatment and in the identify its characteristic sequel feature, the scleral thinning.

Purpose: To evaluate the efficacy of pulsed low-dose radiation therapy (PLRT) combined with temozolomide (TMZ) as a novel treatment approach for radioresistant glioblastoma multiforme (GBM) in a murine model., Methods and Materials: Orthotopic U87MG hGBM tumors were established in Nu-Foxn1(nu) mice and imaged weekly using a small-animal micropositron emission tomography (PET)/computed tomography (CT) system. Tumor volume was determined from contrast-enhanced microCT images and tumor metabolic activity (SUVmax) from the F18-FDG microPET scan. Tumors were irradiated 7 to 10 days after implantation with a total dose of 14 Gy in 7 consecutive days. The daily treatment was given as a single continuous 2-Gy dose (RT) or 10 pulses of 0.2 Gy using an interpulse interval of 3 minutes (PLRT). TMZ (10 mg/kg) was given daily by oral gavage 1 hour before RT. Tumor vascularity and normal brain damage were assessed by immunohistochemistry., Results: Radiation therapy with TMZ resulted in a significant 3- to 4-week tumor growth delay compared with controls, with PLRT+TMZ the most effective. PLRT+TMZ resulted in a larger decline in SUVmax than RT+TMZ. Significant differences in survival were evident. Treatment after PLRT+TMZ was associated with increased vascularization compared with RT+TMZ. Significantly fewer degenerating neurons were seen in normal brain after PLRT+TMZ compared with RT+TMZ., Conclusions: PLRT+TMZ produced superior tumor growth delay and less normal brain damage when compared with RT+TMZ. The differential effect of PLRT on vascularization may confirm new treatment avenues for GBM., (Copyright © 2013 Elsevier Inc. All rights reserved.)

The neuronal mechanisms underlying social withdrawal, one of the core negative symptoms of schizophrenia, are not well understood. Recent studies suggest an involvement of the endocannabinoid system in the pathophysiology of schizophrenia and, in particular, of negative symptoms. We used biochemical, pharmacological, and behavioral approaches to investigate the role played by the endocannabinoid system in social withdrawal induced by sub-chronic administration of phencyclidine (PCP). Pharmacological enhancement of endocannabinoid levels via systemic administration of URB597, an inhibitor of endocannabinoid degradation, reversed social withdrawal in PCP-treated rats via stimulation of CB1 receptors, but reduced social interaction in control animals through activation of a cannabinoid/vanilloid-sensitive receptor. In addition, the potent CB agonist CP55,940 reversed PCP-induced social withdrawal in a CB₁-dependent manner, whereas pharmacological blockade of CB₁ receptors by either AM251 or SR141716 reduced the time spent in social interaction in control animals. PCP-induced social withdrawal was accompanied by a decrease of anandamide (AEA) levels in the amygdala and prefrontal cortex, and these deficits were reversed by URB597. As CB₁ receptors are predominantly expressed on GABAergic interneurons containing the anxiogenic peptide cholecystokinin (CCK), we also examined whether the PCP-induced social withdrawal resulted from deficient CB₁-mediated modulation of CCK transmission. The selective CCK2 antagonist LY225910 blocked both PCP- and AM251-induced social withdrawal, but not URB597 effect in control rats. Taken together, these findings indicate that AEA-mediated activation of CB₁ receptors is crucial for social interaction, and that PCP-induced social withdrawal results from deficient endocannabinoid transmission.

Despite the effectiveness of current hepatitis B virus (HBV) vaccines, it is estimated that 350 million individuals suffer from chronic HBV infection and more than 50% of these affected individuals live on the Asian continent. Panama is a country with a great diversity of foreign groups; the Chinese community is a large example of this phenomenon. There is an urgent need to perform studies that evaluate the prevalence and the genetic diversity of HBV in this community. This study aimed to evaluate the prevalence of HBV and its genotypes and mutant variants in the Chinese population residing in Panama. In total, 320 subjects were enrolled in the study. Forty-two subjects (13.1%) were positive for HBsAg and HBV-DNA from 18 subjects revealed the presence of genotypes B2 and C1. Secondary mutations associated with drug resistance at positions rtV207L and rtN239T of the reverse transcriptase gene were identified. Additionally, the mutation pair A1762T/G1764A was found in three samples and the mutation G1896A was detected in an HBeAg-negative subject. In conclusion, to our knowledge, this is the first study to report high HBV prevalence rates in resident ethnic Chinese in Central America and the presence of genotypes B2 and C1 in this region.

We reviewed our institution's long-term experience treating patients diagnosed with ductal carcinoma in situ (DCIS) of the breast with breast-conserving therapy (BCT) to determine the impact of patient age on outcome over time. All DCIS cases receiving BCT between 1980 and 1993 were reviewed. Patient demographics (including age <45) and pathologic factors were analyzed for effect on outcomes including ipsilateral breast tumor recurrence (IBTR) and survival. BCT included limited surgery (excisional biopsy or lumpectomy) followed by radiotherapy to the whole breast (median whole-breast dose: 50 Gy, median tumor bed dose: 60.4 Gy). One hundred and forty-five cases were evaluated; the median follow-up was 19.3 years. Twenty-five patients developed an IBTR, for 5-, 10-, 15-, and 20-year actuarial rates of 9.9%, 12.2%, 13.7%, and 17.5%, respectively. The 10-year ipsilateral rate of recurrence was 23.3% (<45 years) versus 9.1% (≥ 45 years) (p = 0.05). Younger patients more frequently developed invasive recurrences (20-year actuarial rates: 20.4% versus 12.8%, p = 0.22) and true recurrences/marginal misses of the index lesion (23.3% versus 9.7%, p = 0.04) with lower rates of contralateral breast cancer (0.0% and 0.0% versus 12.0% and 20.5%, p = < 0.01, at 10 and 20 years, respectively). Young women under the age of 45 diagnosed with DCIS have a greater risk of local recurrence with different patterns of failure following BCT, which is most notable within 10 years of diagnosis., (© 2013 Wiley Periodicals, Inc.)