MCPIP1 Endoribonuclease Activity Negatively Regulates Interleukin-17-Mediated Signaling and Inflammation.

Interleukin-17 (IL-17) induces pathology in autoimmunity and infections; therefore, constraint of this pathway is an essential component of its regulation. We demonstrate that the signaling intermediate MCPIP1 (also termed Regnase-1, encoded by Zc3h12a) is a feedback inhibitor of IL-17 receptor signal transduction. MCPIP1 knockdown enhanced IL-17-mediated signaling, requiring MCPIP1's endoribonuclease but not deubiquitinase domain. MCPIP1 haploinsufficient mice showed enhanced resistance to disseminated Candida albicans infection, which was reversed in an Il17ra(-/-) background. Conversely, IL-17-dependent pathology in Zc3h12a(+/-) mice was exacerbated in both EAE and pulmonary inflammation. MCPIP1 degraded Il6 mRNA directly but only modestly downregulated the IL-6 promoter. However, MCPIP1 strongly inhibited the Lcn2 promoter by regulating the mRNA stability of Nfkbiz, encoding the IκBζ transcription factor. Unexpectedly, MCPIP1 degraded Il17ra and Il17rc mRNA, independently of the 3' UTR. The cumulative impact of MCPIP1 on IL-6, IκBζ, and possibly IL-17R subunits results in a biologically relevant inhibition of IL-17 signaling.

Beyond lectures and practical courses: Teaching pharmacology using imaginative pedagogical tools.

Pharmacology has broadened its scope considerably in recent decades. Initially, it was of interest to chemists, doctors and pharmacists. In recent years, however, it has been incorporated into the teaching of biologists, molecular biologists, biotechnologists, chemical engineers and many health professionals, among others. Traditional teaching methods, such as lectures or laboratory work, have been superseded by the use of new pedagogical approaches to enable a better conceptualization and understanding of the discipline. In this article, we present several new methods that have been used in Spanish universities. Firstly, we describe a teaching network that has allowed the sharing of pedagogical innovations in Spanish universities. A European experience to improve prescribing safety is described in detail. The use of popular films and medical TV series in biomedical students shows how these audiovisual resources can be helpful in teaching pharmacology. The use of virtual worlds is detailed to introduce this new approach to teaching. The increasingly important area of the social aspects of pharmacology is also considered in two sections, one devoted to social pharmacology and the other to the use of learning based on social services to improve understanding of this important area. Finally, the use of Objective Structured Clinical Evaluation in pharmacology allows to know how this approach can help to better evaluate clinical pharmacology students. In conclusion, this article allows to know new pedagogical methods resources used in some Spanish universities that may help to improve the teaching of pharmacology.

Real-World clinical, psychosocial and financial burden of atopic dermatitis: results from the Spanish cohort of the MEASURE-AD trial. / Carga clínica, psicosocial y económica de la dermatitis atópica en vida real: resultados de la cohorte española del estudio MEASURE-AD.

BACKGROUND: Atopic dermatitis (AD) is one of the most prevalent skin diseases, but there are numerous knowledge gaps surrounding the impact this disease has on quality of life (QoL), mental health, and out-of-pocket expenses involved in the management of AD. The available scientific evidence on the multidimensional burden of AD is usually based on studies with measures reported by patients themselves. METHODS: In this context, the MEASURE-AD trial was developed as a cross-sectional, multicenter, multinational trial using patient- and physician-reported measures to characterize the multidimensional burden of AD in adults with moderate-to-severe AD. RESULTS: This paper presents the results of the Spanish cohort. We found that Spanish adults with moderate-to-severe AD and high EASI score (21.1-72) had a significantly increased disease burden, high severity of symptoms such as itch and sleep disturbances, impaired mental health and QoL, higher use of health care resources, and more out-of-pocket expenses than patients with low EASI scores (0-7 or 7.1-21). CONCLUSIONS: This study provides information to better understand disease burden, and identify aspects to be improved in the management of AD.

External fixation in intra-articular fractures of the calcaneus: Is it a valid option as definitive treatment?

INTRODUCTION: The therapeutic management of calcaneal fractures is currently a major source of controversy in the literature. There is no consensus on the need to treat these injuries conservatively or surgically, nor on the criteria for deciding one option or the other. Although the gold standard has classically been the open approach and osteosynthesis, there are currently minimally invasive techniques that also report good results. Our objective is to present our results and experience with the MBA® Orthofix external fixator in a series of cases of calcaneal fractures. METHODS: We performed a retrospective observational study in our center, between the years 2019 and 2021, of Sanders types II-IV calcaneal fractures operated with MBA® Orthofix external fixator. We recorded a total of 38 patients, 42 fractures. We registered demographic information, intraoperative, postoperative, radiological and functional parameters, using the American Orthopedic Foot and Ankle Society (AOFAS), Manchester-Oxford Foot Questionnaire (MOXFQ), EQ-5D and VAS scales. RESULTS: A total of 26 men and 12 women were included, and the median age was 38 years. Mean follow-up was 24,4 months (6, 8-40, 1). The average time to surgery was 7 days and partial loading was started at 2.5 weeks after external fixation, which was removed at 9.2 weeks. The average Böhler angle correction was 7, 4°, Gissane - 12,2°, length 2 mm and calcaneal width was reduced by 5 mm. We recorded two superficial infections, one peroneal entrapment and three subtalar arthrodesis due to post-traumatic osteoarthritis. The AOFAS obtained was 79.1 + / - 15.7 points, MOXFQ 20.1 + / - 16.1 points, EQ-5D 0.84 + / - 0.2 and VAS 3.3 + / - 1.9. CONCLUSION: The external fixator is an excellent surgical alternative for complex articular fractures of the calcaneus, obtaining clinical and radiological results comparable to other osteosynthesis techniques and significantly reducing soft tissue complications.

Patritumab deruxtecan in untreated hormone receptor-positive/HER2-negative early breast cancer: final results from part A of the window-of-opportunity SOLTI TOT-HER3 pre-operative study.

BACKGROUND: Patritumab deruxtecan (HER3-DXd) is a human epidermal growth factor receptor 3 (HER3)-directed antibody-drug conjugate composed of a fully human anti-HER3 monoclonal antibody (patritumab) covalently linked to a topoisomerase I inhibitor payload via a stable, tumor-selective, tetrapeptide-based cleavable linker. TOT-HER3 is a window-of-opportunity study designed to assess the biological activity, measured by CelTIL score [= -0.8 × tumor cellularity (in %)  + 1.3  × tumor-infiltrating lymphocytes (TILs) (in %)], and clinical activity of HER3-DXd during short-term (21 days) pre-operative treatment in patients with primary operable HER2-negative early breast cancer. PATIENTS AND METHODS: Patients with previously untreated hormone receptor-positive/HER2-negative tumors were allocated to one of four cohorts according to baseline ERBB3 messenger RNA expression. All patients received one dose of HER3-DXd 6.4 mg/kg. The primary objective was to evaluate change from baseline in CelTIL score. RESULTS: Seventy-seven patients were evaluated for efficacy. A significant change in CelTIL score was observed, with a median increase from baseline of 3.5 (interquartile range, -3.8 to 12.7; P = 0.003). Among patients assessable for clinical response (n = 62), an overall response rate of 45% was observed (tumor measurement by caliper), with a trend toward an increase in CelTIL score among responders compared with non-responders (mean difference, +11.9 versus +1.9). Change in CelTIL score was independent of baseline ERBB3 messenger RNA and HER3 protein levels. Genomic changes occurred, including switching toward a less proliferative tumor phenotype based on PAM50 subtypes, suppression of cell proliferation genes, and induction of genes associated with immunity. Treatment-emergent adverse events were observed in 96% of patients (14% grade ≥3); most common were nausea, fatigue, alopecia, diarrhea, vomiting, abdominal pain, and neutrophil count decrease. CONCLUSIONS: A single dose of HER3-DXd was associated with clinical response, increased immune infiltration, suppression of proliferation in hormone receptor-positive/HER2-negative early breast cancer, and a tolerable safety profile consistent with previously reported results. These findings support further study of HER3-DXd in early breast cancer.

Fitting Multiplet Simulations to L-Edge XAS Spectra of Transition-Metal Complexes Using an Adaptive Grid Algorithm.

A new methodology based on an adaptive grid algorithm followed by an analysis of the ground state from the fit parameters is presented to analyze and interpret experimental XAS L2,3-edge data. The fitting method is tested first in a series of multiplet calculations for d0-d7 systems and for which the solution is known. In most cases, the algorithm is able to find the solution, except for a mixed-spin Co2+ Oh complex, where it instead revealed a correlation between the crystal field and the electron repulsion parameters near spin-crossover transition points. Furthermore, the results for the fitting of previously published experimental data sets on CaO, CaF2, MnO, LiMnO2, and Mn2O3 are presented and their solution discussed. The presented methodology has allowed the evaluation of the Jahn-Teller distortion in LiMnO2, which is consistent with the observed implications in the development of batteries, which use this material. Moreover, a follow-up analysis of the ground state in Mn2O3 has demonstrated an unusual ground state for the highly distorted site which would be impossible to optimize in a perfect octahedral environment. Ultimately, the presented methodology can be used in the analysis of X-ray absorption spectroscopy data measured at the L2,3-edge for a large number of materials and molecular complexes of first-row transition metals and can be expanded to the analysis of other X-ray spectroscopic data in future studies.

Detection of valvular heart diseases combining orthogonal non-negative matrix factorization and convolutional neural networks in PCG signals.

BACKGROUND AND OBJECTIVE: Valvular heart disease (VHD) is associated with elevated mortality rates. Although transthoracic echocardiography (TTE) is the gold standard detection tool, phonocardiography (PCG) could be an alternative as it is a cost-effective and noninvasive method for cardiac auscultation. Many researchers have dedicated their efforts to improving the decision-making process and developing robust and precise approaches to assist physicians in providing reliable diagnoses of VHD. METHODS: This research proposes a novel approach for the detection of anomalous valvular heart sounds from PCG signals. The proposed approach combines orthogonal non-negative matrix factorization (ONMF) and convolutional neural network (CNN) architectures in a three-stage cascade. The aim of the proposal is to improve the learning process by identifying the optimal ONMF temporal or spectral patterns for accurate detection. In the first stage, the time-frequency representation of the input PCG signal is computed. Next, band-pass filtering is performed to locate the spectral range that is most relevant for the presence of such cardiac abnormalities. In the second stage, the temporal and spectral cardiac structures are extracted using the ONMF approach. These structures are utilized in the third stage and fed into the CNN architecture to detect abnormal heart sounds. RESULTS: Several state-of-the-art CNN architectures, such as LeNet5, AlexNet, ResNet50, VGG16 and GoogLeNet, have been evaluated to determine the effectiveness of using ONMF temporal features for VHD detection. The results reveal that the integration of ONMF temporal features with a CNN classifier significantly improve VHD detection. Specifically, the proposed approach achieves an accuracy improvement of approximately 45% when ONMF spectral features are used and 35% when time-frequency features from the short-time Fourier transform (STFT) spectrogram are used. Additionally, feeding ONMF temporal features into low-complexity CNN architectures yields competitive results comparable to those obtained with complex architectures. CONCLUSIONS: The temporal structure factorized by ONMF plays a critical role in distinguishing between normal heart sounds and abnormal heart sounds since the repeatability of normal heart cycles is disrupted by the presence of cardiac abnormalities. Consequently, the results highlight the importance of appropriate input data representation in the learning process of CNN models in the biomedical field of valvular heart sound detection.

Development of aerobic granular sludge for real industrial/municipal wastewater treatment.

The formation and evolution of aerobic granular sludge (AGS) developed in a sequential batch reactor (SBR) were evaluated to understand the effect of influential operating parameters on its morphology, stability, and removal performance while treating industrial/municipal wastewater. After 18 days of operation (stage I), mature granules were identified in the reactor, and in 25 days, the AGS system reached a stable operation. The chemical oxygen demand (COD) and total Kjeldahl nitrogen (TKN) were affected by the applied operating variations (from stages II to VII). Until day 48 (stage III), the aerobic granules did not show relevant changes in shape and stability. During this stage, the AGS system achieved high removal efficiencies of COD (97.7%) and TKN (86.2%) and a sludge volume index (SVI) of 65 ± 6.7 mL/g-total suspended solids. From stage IV until the end of the reactor operation, partial disintegration and rupture occurred in the system, but granules did not completely disintegrate. Specifically, a volumetric exchange ratio (VER) of >67% and an aeration rate (AR) of <2.5 L/min promoted the compactness and the structural integrity of AGS. The principal component analysis corroborated that the rise in the VER is an effective strategy for improving AGS stability and organic pollutant removal.

Selection of Quality Indicators for the Certification of Dermato-Oncology Units: The CUDERMA Project Delphi Consensus Study. / Proyecto CUDERMA: Consenso Delphi de los indicadores de calidad para la certificación de las unidades de dermatología de atención en dermato-oncología.

Quality indicators are crucial for standardizing and guaranteeing the quality of health care practices. The Spanish Academy of Dermatology and Venereology (AEDV) launched the CUDERMA Project to define quality indicators for the certification of specialized units in dermatology; the first 2areas selected were psoriasis and dermato-oncology. The aim of this study was to achieve consensus on what should be evaluated by these indicators using a structured process comprising a literature review and selection of an initial list of indicators to be evaluated in a Delphi consensus study following review by a multidisciplinary group of experts. The selected indicators were evaluated by a panel of 28 dermatologists and classified as either «essential¼ or «of excellence¼. The panel agreed on 84 indicators, which will be standardized and used to develop the certification standard for dermato-oncology units.

dNEMO: a tool for quantification of mRNA and punctate structures in time-lapse images of single cells.

MOTIVATION: Many biological processes are regulated by single molecules and molecular assemblies within cells that are visible by microscopy as punctate features, often diffraction limited. Here, we present detecting-NEMO (dNEMO), a computational tool optimized for accurate and rapid measurement of fluorescent puncta in fixed-cell and time-lapse images. RESULTS: The spot detection algorithm uses the à trous wavelet transform, a computationally inexpensive method that is robust to imaging noise. By combining automated with manual spot curation in the user interface, fluorescent puncta can be carefully selected and measured against their local background to extract high-quality single-cell data. Integrated into the workflow are segmentation and spot-inspection tools that enable almost real-time interaction with images without time consuming pre-processing steps. Although the software is agnostic to the type of puncta imaged, we demonstrate dNEMO using smFISH to measure transcript numbers in single cells in addition to the transient formation of IKK/NEMO puncta from time-lapse images of cells exposed to inflammatory stimuli. We conclude that dNEMO is an ideal user interface for rapid and accurate measurement of fluorescent molecular assemblies in biological imaging data. AVAILABILITY AND IMPLEMENTATION: The data and software are freely available online at https://github.com/recleelab. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Strain and temperature measurement discrimination with forward Brillouin scattering in optical fibers.

A novel method that enables simultaneous and discriminative measurement of strain and temperature using one single optical fiber is presented. The method is based on the properties of transverse acoustic mode resonances (TAMRs) of the optical fiber. In particular, it is based on the different sensitivity to temperature and strain that exhibit the radial modes R0,m and a family of torsional-radial modes denoted as T R2,m(1). We show that the resonance frequencies of both types of resonances shift linearly with temperature and strain, but at different rates. By the combined use of the different sensitivities of the two families of TAMRs, we experimentally demonstrate discriminative measurements of strain and temperature. A detection limit of strain and temperature better than 25 µÎµ and 0.2 °C is achieved.

High accuracy measurement of Poisson's ratio of optical fibers and its temperature dependence using forward-stimulated Brillouin scattering.

Transverse acoustic mode resonances enable a high accuracy determination of Poisson's ratio and elastic properties of optical fibers. An all-optical pump and probe technique is used for efficient excitation and accurate characterization of both, radial and torsional-radial acoustic resonances of optical fibers. Simple and precise algebraic expressions for the frequencies of high order acoustic resonances are derived, enabling a rigorous analysis of the experimental data using standard least squares fitting. Following this approach, the determination of Poisson's ratio does not require the measurement of any physical length, but only frequency measurements are required. An accuracy better than 1 ‰ is achieved. The dependence of the fiber Poisson's ratio with temperature is also determined experimentally.

Pembrolizumab in combination with gemcitabine for patients with HER2-negative advanced breast cancer: GEICAM/2015-04 (PANGEA-Breast) study.

BACKGROUND: We evaluated a new chemoimmunotherapy combination based on the anti-PD1 monoclonal antibody pembrolizumab and the pyrimidine antimetabolite gemcitabine in HER2- advanced breast cancer (ABC) patients previously treated in the advanced setting, in order to explore a potential synergism that could eventually obtain long term benefit in these patients. METHODS: HER2-negative ABC patients received 21-day cycles of pembrolizumab 200 mg (day 1) and gemcitabine (days 1 and 8). A run-in-phase (6 + 6 design) was planned with two dose levels (DL) of gemcitabine (1,250 mg/m2 [DL0]; 1,000 mg/m2 [DL1]) to determine the recommended phase II dose (RP2D). The primary objective was objective response rate (ORR). Tumor infiltrating lymphocytes (TILs) density and PD-L1 expression in tumors and myeloid-derived suppressor cells (MDSCs) levels in peripheral blood were analyzed. RESULTS: Fourteen patients were treated with DL0, resulting in RP2D. Thirty-six patients were evaluated during the first stage of Simon's design. Recruitment was stopped as statistical assumptions were not met. The median age was 52; 21 (58%) patients had triple-negative disease, 28 (78%) visceral involvement, and 27 (75%) ≥ 2 metastatic locations. Progression disease was observed in 29 patients. ORR was 15% (95% CI, 5-32). Eight patients were treated ≥ 6 months before progression. Fourteen patients reported grade ≥ 3 treatment-related adverse events. Due to the small sample size, we did not find any clear association between immune tumor biomarkers and treatment efficacy that could identify a subgroup with higher probability of response or better survival. However, patients that experienced a clinical benefit showed decreased MDSCs levels in peripheral blood along the treatment. CONCLUSION: Pembrolizumab 200 mg and gemcitabine 1,250 mg/m2 were considered as RP2D. The objective of ORR was not met; however, 22% patients were on treatment for ≥ 6 months. ABC patients that could benefit of chemoimmunotherapy strategies must be carefully selected by robust and validated biomarkers. In our heavily pretreated population, TILs, PD-L1 expression and MDSCs levels could not identify a subgroup of patients for whom the combination of gemcitabine and pembrolizumab would induce long term benefit. TRIAL REGISTRATION: ClinicalTrials.gov and EudraCT (NCT03025880 and 2016-001,779-54, respectively). Registration dates: 20/01/2017 and 18/11/2016, respectively.

Risk of fetal loss after chorionic villus sampling in twin pregnancy derived from propensity score matching analysis.

OBJECTIVE: To estimate the risk of fetal loss associated with chorionic villus sampling (CVS) in twin pregnancy, using propensity score analysis. METHODS: This was a multicenter cohort study of women with twin pregnancy undergoing ultrasound examination at 11-13 weeks' gestation, performed in eight fetal medicine units in which the leadership were trained at the Harris Birthright Research Centre for Fetal Medicine in London, UK, and in which the protocols for screening, invasive testing and pregnancy management are similar. The risk of death of at least one fetus was compared between pregnancies that had and those that did not have CVS, after propensity score matching (1:1 ratio). This procedure created two comparable groups by balancing the maternal and pregnancy characteristics that lead to CVS being performed, similar to how randomization operates in a randomized clinical trial. RESULTS: The study population of 8581 twin pregnancies included 445 that had CVS. Death of one or two fetuses at any stage during pregnancy occurred in 11.5% (51/445) of pregnancies in the CVS group and in 6.3% (515/8136) in the non-CVS group (P < 0.001). The propensity score algorithm matched 258 cases that had CVS with 258 non-CVS cases; there was at least one fetal loss in 29 (11.2%) cases in the CVS group and in 35 (13.6%) cases in the matched non-CVS group (odds ratio (OR), 0.81; 95% CI, 0.48-1.35; P = 0.415). However, there was a significant interaction between the risk of fetal loss after CVS and the background risk of fetal loss; when the background risk was higher, the risk of fetal loss after CVS decreased (OR, 0.46; 95% CI, 0.23-0.90), while, in pregnancies with a lower background risk of fetal loss, the risk of fetal loss after CVS increased (OR, 2.45; 95% CI, 0.95-7.13). The effects were statistically significantly different (P-value of the interaction = 0.005). For a pregnancy in which the background risk of fetal loss was about 6% (the same as in our non-CVS population), there was no change in the risk of fetal loss after CVS, but, when the background risk was more than 6%, the posterior risk was paradoxically reduced, and when the background risk was less than 6%, the posterior risk increased exponentially; for example, if the background risk of fetal loss was 2.0%, the relative risk was 2.8 and the posterior risk was 5.6%. CONCLUSION: In twin pregnancy, after accounting for the risk factors that lead to both CVS and spontaneous fetal loss and confining the analysis to pregnancies at lower prior risk, CVS seems to increase the risk of fetal loss by about 3.5% above the patient's background risk. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Stochastic evaluation of four-component relativistic second-order many-body perturbation energies: A potentially quadratic-scaling correlation method.

A second-order many-body perturbation correction to the relativistic Dirac-Hartree-Fock energy is evaluated stochastically by integrating 13-dimensional products of four-component spinors and Coulomb potentials. The integration in the real space of electron coordinates is carried out by the Monte Carlo (MC) method with the Metropolis sampling, whereas the MC integration in the imaginary-time domain is performed by the inverse-cumulative distribution function method. The computational cost to reach a given relative statistical error for spatially compact but heavy molecules is observed to be no worse than cubic and possibly quadratic with the number of electrons or basis functions. This is a vast improvement over the quintic scaling of the conventional, deterministic second-order many-body perturbation method. The algorithm is also easily and efficiently parallelized with 92% strong scalability going from 64 to 4096 processors.

Efficacy and safety of oral sirolimus for high-flow vascular malformations in real clinical practice.

BACKGROUND: Vascular malformations are a complex pathology with few treatment options. In previously published studies, oral sirolimus (rapamycin) has shown promising results in the treatment of low-flow vascular malformations, but its usefulness in high-flow vascular malformations is controversial. AIM: To evaluate the efficacy and safety of sirolimus for the treatment of high-flow vascular malformations in real-life practice. METHODS: In a unit specializing in vascular anomalies, patients treated with oral sirolimus for high-flow vascular malformations were located by consulting the drug dispensations. Reviewing the electronic medical records, data on patient demographics, vascular malformation characteristics, treatments, toxicity and clinical course were collected and statistically analysed. RESULTS: Nine patients with vascular malformations were included: eight had arteriovenous malformation and one had arteriovenous fistula. Six of these malformations were isolated while three were part of a syndrome. Sirolimus was initiated at a dosage of 1-4 mg/day to be taken as a single dose. Partial response was observed in eight of the nine patients (88.9%) with high-flow vascular malformation, while worsening was observed in the remaining patient. The treatment was well tolerated and at the most recent follow-up, five patients remained on treatment with oral sirolimus. CONCLUSION: Our results show that oral sirolimus is a well-tolerated therapeutic option, with an excellent safety profile, which can be useful in the long-term stabilization of patients with high-flow vascular malformations. Single-daily dosage may improve long-term adherence to treatment without worsening its effectiveness.

Peripartal pain perception and pain therapy: introduction and validation of a questionnaire as a quality instrument.

BACKGROUND: Labor pain is difficult to measure. The aim of this proof-of-concept study is to implement and test a questionnaire assessing pain sensation during and after vaginal deliveries. Its key aspect is a highly standardized survey of patient-reported outcome (PRO) by staff not involved in routine care. METHODS: Between January and November 2015 339 women were assessed 24-48 h after spontaneous or operative-vaginal delivery of a singleton. German language skills were a prerequisite to participate. The test-retest reliability was calculated in 38 women 24-36 and 48-72 h postpartum between July and October 2017. Primiparae after spontaneous delivery and multiparae with no history of operative deliveries were compared in a subgroup analysis. RESULTS: Maximum labor pain and post-partum pain were reported a median of 9 [8-10] and 4 [3-6]. Higher ratings were associated with younger age, higher gestational ages, infant's biometrics, and the duration of laboring. Only regional analgesia tended to reduce pain perception (NRS 8 vs. 9). Higher-degree injuries were associated with less pain postpartum. The questionnaire proved to be reliable in most aspects (Cronbach's α > 0.6 for 19/21 questions) and showed an acceptable content and criterion validity (Cohen correlation > ± 0.3, interrelation between items). CONCLUSION: Labor is a very painful experience, irrespective of previous obstetric history. Ratings indicate inadequateness of treatment except for patients receiving preventive postoperative pain management. Systematic postpartum pain assessment, hence, is still a pending issue. Adjustments will be made concerning language skills and specific questions on effectiveness of analgesia otherwise good reliability and validity of the questionnaire were proven.

Media Contributions to a Chesapeake Bay Watershed Collective Identity? A Tale of Three Cities.

Although collective action is needed to address many environmental challenges, it cannot proceed in the absence of collective identity, that is, evidence of group belongingness expressed in or via communicative behavior. This study looked for evidence of a collective identity in newspaper articles that referenced the Chesapeake Bay Watershed. The data were drawn from local papers published in municipalities located at the headwaters of the Susquehanna River, midway down the Susquehanna, and where the river meets the Bay. Computerized content analysis assessed the frequency with which the Chesapeake Bay and watershed were mentioned alongside a set of keywords thought to represent different facets of identity (e.g., agriculture, fishing, swimming). The results showed substantial variation in frequency across time and place but low absolute levels of coverage of the Bay and the watershed. Multidimensional scaling revealed different structures to collective identity as a function of place. These differences in content may be attributable to varying demographic and environmental characteristics along with proximity to the Bay. But, to the extent that media contribute to collective identity among residents of the watershed at all, they do so in a complex and heterogeneous manner.

Psychometric analysis of the Nurses' Professional Values Scale-3 Arabic version among student nurses.

AIMS: We sought to establish the psychometric properties of the Nurses' Professional Values Scale-3 Arabic version among student nurses. BACKGROUND: Nurses' professional values are central in the nursing profession; it encompasses principles such as respecting people rights and dignity, compassion, and caring without prejudice. INTRODUCTION: The professional values of student nurses, most specifically in Saudi Arabia and other Arab countries, can hardly be studied due of the lack of a valid and reliable measure that is linguistically and culturally acceptable. METHODS: In this cross-sectional study, we came up with the Arabic version of the tool and tested its psychometric properties among 350 student nurses from two universities in Saudi Arabia. RESULTS: The principal component analysis revealed three distinct factors with eigenvalues above 1.00 and with an explained variance of 70.5%. The computed Cronbach's alpha of the tool was 0.967, while 0.964, 0.960, and 0.886 were computed for activism, caring, and professionalism, respectively. The test-retest scores (n = 85) revealed an Intraclass Correlation Coefficient of 0.827 for the entire scale, 0.826 for the subscale activism, 0.792 for caring, and 0.870 for professionalism. CONCLUSIONS: The Nurses' Professional Values Scale-3 Arabic version had sound psychometric properties when used among Saudi student nurses. IMPLICATION FOR NURSING: The tool can provide an accurate assessment of the professional values of Saudi nursing students and other Arabic-speaking student nurses. IMPLICATION FOR NURSING POLICY: The tool can be utilized by nursing and nursing education policymakers in Saudi Arabia and in other Arab countries in guiding the creation of practice and education policies that gears towards improving nurses' professional values in this part of the world.

Nevirapine pharmacokinetics in HIV-infected persons receiving rifapentine and isoniazid for TB prevention.

BACKGROUND: The use of rifamycin antibiotics for TB prevention carries a risk of detrimental drug-drug interactions with concomitantly used ART. OBJECTIVES: To evaluate the interaction of the antiretroviral drug nevirapine in combination with 4 weeks of daily rifapentine and isoniazid for TB prevention in people living with HIV. METHODS: Participants were individuals enrolled in the BRIEF-TB study receiving nevirapine and randomized to the rifapentine/isoniazid arm of the study. Participants provided sparse pharmacokinetic (PK) sampling at baseline and weeks 2 and 4 for trough nevirapine determination. Nevirapine apparent oral clearance (CL/F) was estimated and the geometric mean ratio (GMR) of CL/F prior to and during rifapentine/isoniazid was calculated. RESULTS: Seventy-eight participants had evaluable PK data: 61 (78%) female, 51 (65%) black non-Hispanic and median (range) age of 40 (13-66) years. Median (IQR) nevirapine trough concentrations were: week 0, 7322 (5266-9302) ng/mL; week 2, 5537 (3552-8462) ng/mL; and week 4, 5388 (3516-8243) ng/mL. Sixty out of 78 participants (77%) had nevirapine concentrations ≥3000 ng/mL at both week 2 and 4. Median (IQR) nevirapine CL/F values were: week 0 pre-rifapentine/isoniazid, 2.03 (1.58-2.58) L/h; and during rifapentine/isoniazid, 2.62 (1.81-3.42) L/h. The GMR (90% CI) for nevirapine CL/F was 1.30 (1.26-1.33). CONCLUSIONS: The CL/F of nevirapine significantly increased with concomitant rifapentine/isoniazid. The decrease in nevirapine trough concentrations during rifapentine/isoniazid therapy suggests induction of nevirapine metabolism, consistent with known rifapentine effects. The magnitude of this drug-drug interaction suggests daily rifapentine/isoniazid for TB prevention should not be co-administered with nevirapine-containing ART.