Racial and Ethnic Differences in Heroin, Methamphetamine, and Cocaine Use, Treatment, and Mortality Trends in 3 National Data Sources-United States, 2010-2019.

BACKGROUND: As overdose deaths continue to rise, public health officials need comprehensive surveillance data to design effective prevention, harm reduction, and treatment strategies. Disparities across race and ethnicity groups, as well as trends in substance use, treatment, or overdose deaths, have been examined individually, but reports rarely compare findings across multiple substances or data sources. OBJECTIVE: To provide a broad assessment of the overdose crisis, we describe trends in substance use, treatment, and overdose mortality across racial and ethnic groups for multiple substances. RESEARCH DESIGN: We conducted a longitudinal, cross-sectional analysis comparing trends. SUBJECTS: We identified self-reported use from the National Survey on Drug Use and Health, substance use treatment admissions from the Treatment Episode Data Set-Admissions, and overdose deaths from the CDC's Multiple Cause of Death files. MEASURES: We measured rates of substance use, treatment, and deaths involving heroin, methamphetamine, and cocaine among United States adults from 2010 to 2019. RESULTS: Heroin, methamphetamine, and cocaine use increased, though not all changes were statistically significant. Treatment admissions indicating heroin and methamphetamine increased while admissions indicating cocaine decreased. Overdose deaths increased among all groups: methamphetamine (257%-1,115%), heroin (211%-577%), and cocaine (88%-259%). Changes in rates of use, treatment, and death for specific substances varied by racial and ethnic group. CONCLUSIONS: Substance use, treatment, and overdose mortality changed considerably, though not always equivalently. Identifying diverging trends in substance-related measures for specific substances and racial and ethnic groups can inform targeted investment in treatment to reduce disparities and respond to emerging changes in the overdose crisis.

Understanding Regional Patterns of Overdose Deaths Related to Opioids and Psychostimulants.

BACKGROUND: As overdose rates increase for multiple substances, policymakers need to identify geographic patterns of substance-specific deaths. In this study, we describe county-level opioid and psychostimulant overdose patterns and how they correlate with county-level social vulnerability measures. METHODS: A cross-sectional observational study, we used nationwide 2016-2018 restricted access Centers for Disease Prevention and Control county-level mortality files for 1,024 counties. We estimated quartiles of opioid and psychostimulant overdose mortality and provided estimates of their association with county-level Social Vulnerability Index (SVI) percentile. RESULTS: There was high opioid and psychostimulant overdose mortality in the Middle Atlantic, South Atlantic, East North Central, and Mountain regions. The Central US had the lowest opioid and psychostimulant overdose mortality rates. Counties with higher SVI scores (i.e. higher social vulnerability) were significantly more likely to experience high opioid and high psychostimulant overdose (high-high) mortality. A 10-percentile increase in SVI score was associated with a 3.1 percentage point increase in the likelihood of being a high-high county (p < 0.001) in unadjusted models and a 1.5 percentage point increase (p < 0.05) in models adjusting for region. CONCLUSION: Our results illustrated the heterogenous geographic distribution of the growing concurrent opioid and psychostimulant overdose crisis. The substantial regional variation we identified highlights the need for local data to guide policymaking and treatment planning. The association of opioid-psychostimulant overdose mortality with social vulnerability demonstrates the critical need in impacted counties for tailored treatment that addresses the complex medical and social needs of people who use both opioids and psychostimulants.

Is there a tolerance for extension of the first metatarsal after the Lapidus procedure? A clinical, functional, and hindfoot radiographic analysis.

PURPOSE: Based on the tripod concept of load distribution, our study aimed to evaluate whether a slight extension of first metatarsal (M1) that may occur after the Lapidus procedure (LP) could alter the radiographic measurements of the hindfoot and influence clinical and functional outcomes. METHODS: Twenty-five patients (27 feet) were reviewed. Hindfoot radiographic analysis was based on seven measurements. Clinical and functional outcomes were evaluated with self-reported questionnaires. Transfer metatarsalgia was also assessed. Correlation analysis was performed according to variations of the studied variables. RESULTS: The average extension of the M1 was 4.26 degrees (p < 0.001). None of the hindfoot radiographic measurements changed significantly (p = 0.13, p = 0.50, p = 0.19, p = 0.70, p = 0.11, p = 0.36, p = 0.83). Patients improved on most questionnaires (p < 0.001). None presented transfer metatarsalgia. No correlation between M1 extension and clinical and functional outcomes was found. CONCLUSION: Possibly there is a tolerance of M1 extension in which it does not alter the radiographic measurements of the hindfoot, overload the lesser metatarsals, or compromise clinical and functional outcomes.

Measuring quality STI care among adolescent female primary care patients in Philadelphia.

OBJECTIVES: Engagement in guideline-recommended sexually transmitted infection (STI) care is fundamental to ending the STI epidemic in the USA. However, the US 2021-2025 STI National Strategic Plan and STI surveillance reports do not include a framework to measure quality STI care delivery. This study developed and applied an STI Care Continuum that can be used across settings to improve STI care quality, assess adherence to guideline-recommended care and standardise the measurement of progress towards National Strategic goals. METHODS: Review of the Centers for Disease Control and Prevention STI Treatment guidelines identified seven distinct steps of STI care for gonorrhoea, chlamydia and syphilis: (1) STI testing indication, (2) STI test completion, (3) HIV testing, (4) STI diagnosis, (5) partner services, (6) STI treatment and (7) STI retesting. Steps 1-4, 6 and 7 for gonorrhoea and/or chlamydia (GC/CT) were measured among females aged 16-17 years with a clinic visit at an academic paediatric primary care network in 2019. We used Youth Risk Behavior Surveillance Survey data to estimate step 1, and electronic health record data for steps 2, 3, 4, 6 and 7. RESULTS: Among 5484 female patients aged 16-17 years, an estimated 44% had an STI testing indication. Among those patients, 17% were tested for HIV, of whom none tested positive, and 43% were tested for GC/CT, 19% of whom were diagnosed with GC/CT. Of these patients, 91% received treatment within 2 weeks and 67% were retested within 6 weeks to 1 year after diagnosis. On retesting, 40% were diagnosed with recurrent GC/CT. CONCLUSIONS: Local application of an STI Care Continuum identified STI testing, retesting and HIV testing as areas for improvement. The development of an STI Care Continuum identified novel measures for monitoring progress towards National Strategic indicators. Similar methods can be applied across jurisdictions to target resources, standardise data collection and reporting and improve STI care quality.

Effect of Thiazolidin-4-one Against Lipopolysaccharide-Induced Oxidative Damage, and Alterations in Adenine Nucleotide Hydrolysis and Acetylcholinesterase Activity in Cultured Astrocytes.

Astrocytes play multiple important roles in brain physiology. However, depending on the stimuli, astrocytes may exacerbate inflammatory reactions, contributing to the development and progression of neurological diseases. Therefore, therapies targeting astrocytes represent a promising area for the development of new brain drugs. Thiazolidinones are heterocyclic compounds that have a sulfur and nitrogen atom and a carbonyl group in the ring and represent a class of compounds of great scientific interest due to their pharmacological properties. The aim of this study was to investigate the effect of 3-(3-(diethylamino)propyl)-2-(4-(methylthio)phenyl)thiazolidin-4-one (DS27) on cell proliferation and morphology, oxidative stress parameters, activity of the enzymes ectonucleotidases and acetylcholinesterase (AChE) and interleukin 6 (IL-6) levels in primary astrocyte cultures treated with lipopolysaccharide (LPS), to model neuroinflammation. The astrocyte culture was exposed to LPS (10 µg/ml) for 3 h and subsequently treated with compound DS27 for 24 and 48 h (concentrations ranging to 10-100 µM). LPS induced an increase in astrocyte proliferation, AChE activity, IL-6 levels, oxidative damage, ATP and ADP and a reduction in AMP hydrolysis in rat primary astrocyte cultures. DS27 treatment was effective in reversing these alterations induced by LPS. Our findings demonstrated that DS27 is able to modulate cholinergic and purinergic signaling, redox status, and the levels of pro-inflammatory cytokines in LPS-induced astrocyte damage. These glioprotective effects of DS27 may be very important for improving neuroinflammation, which is associated with many brain diseases.

Frequency-resolved microscopic second-order hyperpolarizability of azochromophores: a study on nonlinear all-optical switching applications.

Azochromophores present interesting optical properties for application in all-optical switches (AOSs), such as ultrafast photoisomerization and considerable nonlinear optical response. However, determining the frequency-resolved microscopic second-order hyperpolarizability (real and imaginary parts) related to the pure electronic effects of molecules in solution is a challenging task. In this context, we have used femtosecond-laser induced nonlinear ellipse rotation (NER) measurements to obtain the electronic nonlinear refraction (n2(ω)) and two-photon absorption spectra (α2PA(ω)) of four azochromophores dissolved in methanol and acetone. The measurements ranging from ∼600 up to ∼1300 nm were performed in Disperse Red 1 (DR1), Disperse Red 13 (DR13), Disperse Red 19 (DR19), and Disperse Orange 3 (DO3). Because we carried the solution in a silica cuvette and used a short focal length, we were able to measure the solution's nonlinearities with high precision, as the silica from the cuvette walls worked as a suitable reference medium. Consequently, we precisely determined n2(ω), α2PA(ω), and the second-order hyperpolarizability (γ(ω)) for all molecules and explained the different magnitudes based on the push-pull character. Furthermore, the solvation effect due to the change from methanol to acetone solvent on the n2(ω), α2PA(ω), and γ(ω) is also reported. The results were elucidated using the sum-over-states (SOS) approach within the few-energy-level model and the results were obtained via quantum-chemical calculations using the cubic response function formalism within the density functional theory framework. Finally, we used these results to determine the frequency-resolved figure-of-merit for all-optical switching applications. Our results suggest that chromophores have the potential for applications in AOS based on Fabry-Perot filters.

A hybrid linear discriminant analysis and genetic algorithm to create a linear model of aging when performing motor tasks through inertial sensors positioned on the hand and forearm.

BACKGROUND: During the aging process, cognitive functions and performance of the muscular and neural system show signs of decline, thus making the elderly more susceptible to disease and death. These alterations, which occur with advanced age, affect functional performance in both the lower and upper members, and consequently human motor functions. Objective measurements are important tools to help understand and characterize the dysfunctions and limitations that occur due to neuromuscular changes related to advancing age. Therefore, the objective of this study is to attest to the difference between groups of young and old individuals through manual movements and whether the combination of features can produce a linear correlation concerning the different age groups. METHODS: This study counted on 99 participants, these were divided into 8 groups, which were grouped by age. The data collection was performed using inertial sensors (positioned on the back of the hand and on the back of the forearm). Firstly, the participants were divided into groups of young and elderly to verify if the groups could be distinguished through the features alone. Following this, the features were combined using the linear discriminant analysis (LDA), which gave rise to a singular feature called the LDA-value that aided in verifying the correlation between the different age ranges and the LDA-value. RESULTS: The results demonstrated that 125 features are able to distinguish the difference between the groups of young and elderly individuals. The use of the LDA-value allows for the obtaining of a linear model of the changes that occur with aging in the performance of tasks in line with advancing age, the correlation obtained, using Pearson's coefficient, was 0.86. CONCLUSION: When we compare only the young and elderly groups, the results indicate that there is a difference in the way tasks are performed between young and elderly individuals. When the 8 groups were analyzed, the linear correlation obtained was strong, with the LDA-value being effective in obtaining a linear correlation of the eight groups, demonstrating that although the features alone do not demonstrate gradual changes as a function of age, their combination established these changes.

Performance of Aptima-HPV in the cervical cancer screening program of Portugal: a cost-analysis.

BACKGROUND: Cervical cancer is a major concern to women's health, being the fourth most common cancer worldwide. A great percentage of these cancer is consequence of an HPV infection, namely from specific genotypes such as 16/18. Portuguese screening program subjects women to a reflex cytology triage every 5 years. Aptima® HPV is a screening test which presents better specificity than other tests which are used in Portugal (Hybrid Capture® 2 and Cobas® 4800) and still have a comparable sensitivity. The present study aims to estimate the number of diagnostic tests and costs that are avoided using Aptima® HPV compared to the use of two other tests, Hybrid Capture® 2 and Cobas® 4800, within the cervical cancer screening programme in Portugal. METHODS: A model, consisting of a decision-tree, was developed to represent the full Portuguese screening program for cervical cancer. This model is used to compare the costs resulting from using Aptima® HPV test versus the other tests used in Portugal, during 2 years. Other outcomes such as the number of additional tests and exams were also computed. This comparison considers the performance of each test (sensitivity and specificity) and assumes an equal price for every test compared. RESULTS: Cost savings resulting from the use of Aptima® HPV are estimated at approximately €382 million versus Hybrid Capture® 2 and €2.8 million versus Cobas® 4800. Moreover, Aptima® HPV prevents 265,443 and 269,856 additional tests and exams when compared with Hybrid Capture® 2 and Cobas® 4800. CONCLUSIONS: The use of Aptima® HPV resulted in lower costs as well as less additional test and exams. These values result from the greater specificity of Aptima® HPV, which signals less false positive cases and consequently avoids carrying out additional tests.

Omicron SARS-CoV-2 antiviral on poly(lactic acid) with nanostructured copper coating: Wear effects.

Surface modification corresponds to a set of viable technological approaches to introduce antimicrobial properties in materials that do not have such characteristics. Antimicrobial materials are important to prevent the proliferation of microorganisms and minimize the transmission of diseases caused by pathogens. Herein, poly(lactic acid) (PLA) was decorated with nanocones through copper sputtering followed by a plasma etching. Antiviral assays by Quantitative Reverse Transcription-Polymerase Chain Reaction (RT-qPCR) show that nanostructured Cu-coated PLA has high antiviral activity against Omicron SARS-CoV-2, showing a relative reduction in the amplified RNA (78.8 ± 3.9 %). Atomic Force Microscopy (AFM), X-ray Photoelectron Spectroscopy (XPS), and wear-resistance tests show that 20 wear cycles disrupt the surface nanocone patterns and significantly reduce the Cu content at the surface of the nanostructured Cu-coated PLA, leading to total loss of the antiviral properties of nanostructured PLA against Omicron SARS-CoV-2.

Psychosocial and structural stressors and engagement in medical care among young sexual minority men across racial identities.

Psychosocial and structural stressors and low engagement in medical care likely contribute to the disproportionate burden of chronic disease among sexual minority men (SMM) across the life course. However, how these stressors impact engagement in medical care among young SMM (YSMM) across racial identities remains understudied. The association of psychosocial and structural stressors with forgoing care among YSMM across racial identities was examined using race-stratified adjusted logistic regression of cross-sectional data. Among 737 HIV-negative SMM aged 16-24 years, nearly all (93%) experienced discrimination in their daily lives. Non-Hispanic/Latinx Black participants reported significantly higher levels of discrimination, exposure to community violence, and food insecurity. Medical mistrust and mental health were not significantly different across racial groups. In the full sample model, education, food insecurity, and discrimination were associated with forgoing care. Among the non-Hispanic/Latinx White sample, medical mistrust and discrimination were associated with forgoing care. Among the non-Hispanic/Latinx Black sample, discrimination was associated with forgoing care. Among the Hispanic/Latinx sample, food insecurity was associated with forgoing care. Psychosocial and structural stressors were common in this YSMM cohort, and significantly different across racial/ethnic identities. Race-stratified analysis revealed differences in the association of stressors with forgoing care among YSMM across racial identities, not appreciated in the analysis limited to the total study population. Our findings may support efforts to address health inequity and improve engagement in medical care among SMM.

Computer-Aided Ankle Ligament Injury Diagnosis from Magnetic Resonance Images Using Machine Learning Techniques.

Ankle injuries caused by the Anterior Talofibular Ligament (ATFL) are the most common type of injury. Thus, finding new ways to analyze these injuries through novel technologies is critical for assisting medical diagnosis and, as a result, reducing the subjectivity of this process. As a result, the purpose of this study is to compare the ability of specialists to diagnose lateral tibial tuberosity advancement (LTTA) injury using computer vision analysis on magnetic resonance imaging (MRI). The experiments were carried out on a database obtained from the Vue PACS-Carestream software, which contained 132 images of ATFL and normal (healthy) ankles. Because there were only a few images, image augmentation techniques was used to increase the number of images in the database. Following that, various feature extraction algorithms (GLCM, LBP, and HU invariant moments) and classifiers such as Multi-Layer Perceptron (MLP), Support Vector Machine (SVM), k-Nearest Neighbors (kNN), and Random Forest (RF) were used. Based on the results from this analysis, for cases that lack clear morphologies, the method delivers a hit rate of 85.03% with an increase of 22% over the human expert-based analysis.

Two-Photon Absorption and Multiphoton Excited Fluorescence of Acetamide-Chalcone Derivatives: The Role of Dimethylamine Group on the Nonlinear Optical and Photophysical Properties.

This work studied the effect of different electron-withdrawing and electron-donating groups on the linear and nonlinear optical properties of acetamide-chalcone derivatives. The results showed that the addition of the dimethylamine group led to a large fluorescence emission (71% of fluorescence quantum yield in DMSO solution) that can be triggered by two and three-photon excitations, which is essential for biological applications. Furthermore, dimethylamine also red-shifts the lower energy state by approximately 90 nm, increasing the two-photon absorption cross-section of the lower energy band by more than 100% compared with the other studied compounds. All compounds presented two-electronic states observed through one and two-photon absorption spectroscopy and confirmed by Quantum Chemistry Calculations (QCCs). QCC results were also used to model the experimental two-photon absorption cross-sectional spectrum by the Sum-Over-States (SOS) approach, revealing a dependence between the coupling of the ground state with the first excited state and the transition dipole moment between these states.

User satisfaction with an intrauterine system containing 52 mg levonorgestrel: a Portuguese study.

OBJECTIVE: To characterise patient satisfaction 6 and 12 months after insertion of a 52 mg levonorgestrel-releasing intrauterine system (LNG-IUS) in Portuguese women. STUDY DESIGN: A non-interventional and prospective study was conducted in Portuguese women of reproductive age who had Levosert® inserted. Two questionnaires (administered 6 and 12 months after 52 mg LNG-IUS insertion) were used to collect information on the patients' menstrual pattern, discontinuation rate, and satisfaction rate with Levosert®. RESULTS: A total of 102 women were enrolled, of which only 94 (92.2%) completed the study. Seven participants discontinued the use of the 52 mg LNG-IUS. At 6 and 12 months, 90.7% and 90.4% of participants, respectively, were either satisfied or very satisfied with the 52 mg LNG-IUS. At 6 and 12 months, 73.2% and 72.3% of participants, respectively, indicated that they were very likely to recommend the 52 mg LNG-IUS to a friend or family member. Most women (92.2%) continued to use the 52 mg LNG-IUS for the first year. The percentage of women who were 'much more satisfied' with Levosert® than with their previous contraceptive methods was 55.9% and 57.8% at 6 and 12 months, respectively, per questionnaire assessment. Satisfaction was associated with age (p = 0.004), amenorrhoea (p < 0.003) and absence of dysmenorrhoea (p = 0.003), but not with parity (p = 0.922). CONCLUSIONS: These data suggest that the continuation and satisfaction rates with Levosert® were very high, and that this system is well accepted among Portuguese women. Patient satisfaction was driven by a favourable bleeding pattern and absence of dysmenorrhoea.

Satisfaction with the 52 mg levonorgestrel­releasing intrauterine system was high among Portuguese women. Patient satisfaction was mainly driven by a favourable bleeding pattern and absence of dysmenorrhoea.

PrEParing for NextGen: Cognitive Interviews to Improve Next Generation PrEP Modality Descriptions for Young Men Who have Sex with Men.

Next generation PrEP formulations may circumvent factors that impede daily oral pre-exposure prophylaxis (PrEP) use among young men who have sex with men (YMSM). We conducted video-based cognitive interviews with 20 YMSM (age 16-24) recruited in the US Northeast to assess participants' attitudes and comprehension of written descriptions of next generation PrEP modalities. Participants were predominately racial/ethnic minorities and half used daily oral PrEP. We identified four main areas for improvement of descriptions: defining scientific terms and balancing medical jargon and casual language; referencing more established products to contextualize PrEP formulations (e.g., hormonal implants); ensuring clarity and reducing redundancy; and including imagery (e.g., rectal douche applicator). The refined descriptions serve as exemplar text that may be used in future studies examining YMSM's preferences across next generation PrEP modalities. Accurate descriptions of next generation PrEP products strengthen measurement accuracy and can help roll-out products that become approved for clinical use.

RESUMEN: Las formulaciones de próxima generación para la profilaxis pre-exposición (PrEP) pueden eludir los factores que impiden el uso diario del PrEP oral en hombres jóvenes que tienen relaciones sexuales con hombres (YMSM). Realizamos entrevistas cognitivas usando videoconferencia con 20 YMSM (de 16 a 24 años) reclutados del noreste de los Estados Unidos con el fin de evaluar sus actitudes y su comprensión de las definiciones desarrolladas para describir las modalidades de PrEP de próxima generación. Los participantes eran predominantemente minorías raciales/étnicas y la mitad usaba PrEP oral diariamente. Identificamos cuatro áreas principales para mejorar las descripciones: definir términos científicos y equilibrar la jerga médica y el lenguaje casual; hacer referencia a productos más establecidos para contextualizar las formulaciones de PrEP (por ejemplo, implantes hormonales); garantizar la claridad y reducir la redundancia; e incluir imágenes (por ejemplo, aplicador de duchas rectales). Las descripciones refinadas sirven como texto ejemplar y pueden usarse en estudios futuros que examinen las preferencias de modalidades de PrEP de próxima generación entre YMSM. Las descripciones precisas de los productos PrEP de próxima generación fortalecen la precisión de la medición y pueden ayudar a implementar productos que se aprueben para uso clínico.

Mammogram Image Enhancement Techniques for Online Breast Cancer Detection and Diagnosis.

Breast cancer is the type of cancer with the highest incidence and global mortality of female cancers. Thus, the adaptation of modern technologies that assist in medical diagnosis in order to accelerate, automate and reduce the subjectivity of this process are of paramount importance for an efficient treatment. Therefore, this work aims to propose a robust platform to compare and evaluate the proposed strategies for improving breast ultrasound images and compare them with state-of-the-art techniques by classifying them as benign, malignant and normal. Investigations were performed on a dataset containing a total of 780 images of tumor-affected persons, divided into benign, malignant and normal. A data augmentation technique was used to scale up the corpus of images available in the chosen dataset. For this, novel image enhancement techniques were used and the Multilayer Perceptrons, k-Nearest Neighbor and Support Vector Machines algorithms were used for classification. From the promising outcomes of the conducted experiments, it was observed that the bilateral algorithm together with the SVM classifier achieved the best result for the classification of breast cancer, with an overall accuracy of 96.69% and an accuracy for the detection of malignant nodules of 95.11%. Therefore, it was found that the application of image enhancement methods can help in the detection of breast cancer at a much earlier stage with better accuracy in detection.

Ecological risk of imidacloprid on the Brazilian non-target freshwater organisms Chironomus sancticaroli and Poecilia reticulata.

Imidacloprid (IMI) is a neonicotinoid insecticide widely used in agriculture worldwide. This pesticide has been found in freshwater ecosystems, including Brazilian freshwaters. For this reason, studies are being conducted to detect the presence of IMI in freshwater and understand its effects on the aquatic biota. In the present study, the acute toxic effect of the imidacloprid commercial formulation (ICF) Galeão® on the Brazilian non-target aquatic organisms Chironomus sancticaroli and Poecilia reticulata was evaluated. Enzymatic activities (glutathione S-transferase (GST), catalase (CAT), and ascorbate peroxidase (APX)) were also determined. Moreover, we considered 11 studies that detected IMI concentrations up to 3.65 µg.L-1 in 28 different Brazilian freshwaters to evaluate the acute ecological risk of IMI in these environments. From the ecotoxicological assays, we determined the LC50 values for C. sancticaroli (LC50-48 h 1.52 µg.L-1) and P. reticulata (LC50-96 h 122.65 mg.L-1). The high sensitivity of C. sancticaroli demonstrates that this species could be used as a bioindicator in studies investigating the contamination of freshwater by IMI. Enzymatic activity changes were observed in both organisms and offered sublethal responses to the effects of the pollution by IMI on aquatic biota. Our results suggest that the presence of IMI in Brazilian aquatic ecosystems can represent a potential ecological risk for the aquatic insect populations and, consequently, cause an imbalance in these ecosystems. The present study provides relevant and comparable toxicity information that may be useful to develop public policies to protect the Brazilian aquatic ecosystem from IMI contamination.

Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome.

BACKGROUND: The efficacy of venovenous extracorporeal membrane oxygenation (ECMO) in patients with severe acute respiratory distress syndrome (ARDS) remains controversial. METHODS: In an international clinical trial, we randomly assigned patients with very severe ARDS, as indicated by one of three criteria - a ratio of partial pressure of arterial oxygen (Pao2) to the fraction of inspired oxygen (Fio2) of less than 50 mm Hg for more than 3 hours; a Pao2:Fio2 of less than 80 mm Hg for more than 6 hours; or an arterial blood pH of less than 7.25 with a partial pressure of arterial carbon dioxide of at least 60 mm Hg for more than 6 hours - to receive immediate venovenous ECMO (ECMO group) or continued conventional treatment (control group). Crossover to ECMO was possible for patients in the control group who had refractory hypoxemia. The primary end point was mortality at 60 days. RESULTS: At 60 days, 44 of 124 patients (35%) in the ECMO group and 57 of 125 (46%) in the control group had died (relative risk, 0.76; 95% confidence interval [CI], 0.55 to 1.04; P=0.09). Crossover to ECMO occurred a mean (±SD) of 6.5±9.7 days after randomization in 35 patients (28%) in the control group, with 20 of these patients (57%) dying. The frequency of complications did not differ significantly between groups, except that there were more bleeding events leading to transfusion in the ECMO group than in the control group (in 46% vs. 28% of patients; absolute risk difference, 18 percentage points; 95% CI, 6 to 30) as well as more cases of severe thrombocytopenia (in 27% vs. 16%; absolute risk difference, 11 percentage points; 95% CI, 0 to 21) and fewer cases of ischemic stroke (in no patients vs. 5%; absolute risk difference, -5 percentage points; 95% CI, -10 to -2). CONCLUSIONS: Among patients with very severe ARDS, 60-day mortality was not significantly lower with ECMO than with a strategy of conventional mechanical ventilation that included ECMO as rescue therapy. (Funded by the Direction de la Recherche Clinique et du Développement and the French Ministry of Health; EOLIA ClinicalTrials.gov number, NCT01470703 .).

Multitarget Effect of 2-(4-(Methylthio)phenyl)-3-(3-(piperidin-1-yl)propyl)thiazolidin-4-one in a Scopolamine-Induced Amnesic Rat Model.

Cholinergic system dysfunction, oxidative damage, and alterations in ion pump activity have been associated with memory loss and cognitive deficits in Alzheimer's disease. 1,3-thiazolidin-4-ones have emerged as a class of compounds with potential therapeutic effects due to their potent anticholinesterase activity. Accordingly, this study investigated the effect of the 2-(4-(methylthio)phenyl)-3-(3-(piperidin-1-yl)propyl)thiazolidin-4-one (DS12) compound on memory, cholinergic and oxidative stress parameters, ion pump activity, and serum biochemical markers in a scopolamine-induced memory deficit model. Male Wistar rats were divided into four groups: I-Control; II-Scopolamine; III-DS12 (5 mg/kg) + scopolamine; and IV-DS12 (10 mg/kg) + scopolamine. The animals from groups III and IV received DS12 diluted in canola oil and administered for 7 days by gavage. On the last day of treatment, scopolamine (1 mg/kg) was administered intraperitoneally (i.p.) 30 min after training in an inhibitory avoidance apparatus. Twenty-four hours after scopolamine administration, the animals were subjected to an inhibitory avoidance test and were thereafter euthanized. Scopolamine induced memory deficits, increased acetylcholinesterase activity and oxidative damage, and decreased Na+/K+-ATPase activity in cerebral cortex and hippocampus. Pretreatment with DS12 prevented these brain alterations. Scopolamine also induced an increase in acetylcholinesterase activity in lymphocytes and whereas butyrylcholinesterase in serum and treatment with DS12 prevented these changes. In animals treated with DS12, no changes were observed in renal and hepatic parameters when compared to the control group. In conclusion, DS12 emerged as an important multitarget compound capable of preventing neurochemical changes associated with memory deficits.

Swimming behavior of the multicellular magnetotactic prokaryote 'Candidatus Magnetoglobus multicellularis' near solid boundaries and natural magnetic grains.

The magnetotactic yet uncultured species 'Candidatus Magnetoglobus multicellularis' is a spherical, multicellular ensemble of bacterial cells able to align along magnetic field lines while swimming propelled by flagella. Magnetotaxis is due to intracytoplasmic, membrane-bound magnetic crystals called magnetosomes. The net magnetic moment of magnetosomes interacts with local magnetic fields, imparting the whole microorganism a torque. Previous works investigated 'Ca. M. multicellularis' behavior when free swimming in water; however, they occur in sediments where bumping into solid particles must be routine. In this work, we investigate the swimming trajectories of 'Ca. M. multicellularis' close to solid boundaries using video microscopy. We applied magnetic fields 0.25-8.0 mT parallel to the optical axis of a light microscope, such that microorganisms were driven upwards towards a coverslip. Because their swimming trajectories approach cylindrical helixes, circular profiles would be expected. Nevertheless, at fields 0.25-1.1 mT, most trajectory projections were roughly sinusoidal, and net movements were approximately perpendicular to applied magnetic fields. Closed loops appeared in some trajectory projections at 1.1 mT, which could indicate a transition to the loopy profiles observed at magnetic fields ≥ 2.15 mT. The behavior of 'Ca. M. multicellularis' near natural magnetic grains showed that they were temporarily trapped by the particle's magnetic field but could reverse the direction of movement to flee away. Our results show that interactions of 'Ca. M. multicellularis with solid boundaries and magnetic grains are complex and possibly involve mechano-taxis.

3-Bromopyruvate: A new strategy for inhibition of glycolytic enzymes in Leishmania amazonensis.

The compound 3-bromopyruvate (3-BrPA) is well-known and studies from several researchers have demonstrated its involvement in tumorigenesis. It is an analogue of pyruvic acid that inhibits ATP synthesis by inhibiting enzymes from the glycolytic pathway and oxidative phosphorylation. In this work, we investigated the effect of 3-BrPA on energy metabolism of L. amazonensis. In order to verify the effect of 3-BrPA on L. amazonensis glycolysis, we measured the activity level of three glycolytic enzymes located at different points of the pathway: (i) glucose kinases, step 1, (ii) glyceraldehyde 3-phosphate dehydrogenase (GAPDH), step 6, and (iii) enolase, step 9. 3-BrPA, in a dose-dependent manner, significantly reduced the activity levels of all the enzymes. In addition, 3-BrPA treatment led to a reduction in the levels of phosphofruto-1-kinase (PFK) protein, suggesting that the mode of action of 3-BrPA involves the downregulation of some glycolytic enzymes. Measurement of ATP levels in promastigotes of L. amazonensis showed a significant reduction in ATP generation. The O2 consumption was also significantly inhibited in promastigotes, confirming the energy depletion effect of 3-BrPA. When 3-BrPA was added to the cells at the beginning of growth cycle, it significantly inhibited L. amazonensis proliferation in a dose-dependent manner. Furthermore, the ability to infect macrophages was reduced by approximately 50% when promastigotes were treated with 3-BrPA. Taken together, these studies corroborate with previous reports which suggest 3-BrPA as a potential drug against pathogenic microorganisms that are reliant on glucose catabolism for ATP supply.