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Abstract Background A better understanding of adipose tissue (AT) dysfunction, which includes morphological and functional changes such as adipocyte hypertrophy as well as impaired adipogenesis, lipid storage/mobilization, endocrine and inflammatory responses, is needed in the context of obesity. One dimension of AT dysfunction, secretory adiposopathy, often assessed as a low plasma adiponectin (A)/leptin (L) ratio, is commonly observed in obesity. The aim of this study was to examine markers of AT development and metabolism in 67 women of varying age and adiposity (age: 40-62 years; body mass index, BMI: 17-41 kg/m2) according to levels of adiponectinemia, leptinemia or the plasma A/L ratio. Methods Body composition, regional AT distribution and circulating adipokines were determined. Lipolysis was measured from glycerol release in subcutaneous abdominal (SCABD) and omental (OME) adipocytes under basal, isoproterenol-, forskolin (FSK)- and dibutyryl-cyclic AMP (DcAMP)-stimulated conditions. Adipogenesis (C/EBP-α/β/δ, PPAR-γ2 and SREBP-1c) and lipid metabolism (β2-ARs, HSL, FABP4, LPL and GLUT4) gene expression (RT-qPCR) was assessed in both fat depots. Participants in the upper versus lower tertile of adiponectin, leptin or the A/L ratio were compared. Results Basal lipolysis was similar between groups. Women with a low plasma A/L ratio were characterized by higher adiposity and larger SCABD and OME adipocytes (p

The simultaneous occurrence of electric-field controlled superconductivity and spin-orbit interaction makes two-dimensional electron systems (2DES) constructed from perovskite transition metal oxides promising candidates for the next generation of spintronics and quantum computing. It is, however, essential to understand the electronic bands thoroughly and verify the predicted electronic states experimentally in these 2DES to advance technological applications. Here, we present insights into the electronic states of the 2DES at oxide interfaces through comprehensive investigations of Shubnikov–de Haas oscillations in three different systems: EuO/KTaO_{3}, LaAlO_{3}/SrTiO_{3}, and amorphous-LaAlO_{3}/KTaO_{3}. To accurately resolve these oscillations, we conducted transport measurements in high magnetic fields up to 60 T and low temperatures down to 100 mK. For 2D confined electrons at these interfaces, we observed a progressive increase of oscillations frequency and cyclotron mass with the magnetic field. We interpret these universal and intriguing findings by considering the existence of nontrivial electronic bands, for which the E−k dispersion incorporates both linear and parabolic relations. In addition to providing experimental evidence for nonparabolic electronic states in KTaO_{3} and SrTiO_{3} 2DES, the unconventional oscillations presented in this study establish a paradigm for quantum oscillations in 2DES based on perovskite transition metal oxides, where the oscillation frequencies in 1/B exhibit quadratic dependence on the magnetic field.

Notoriously that motor and research activities are gradually oppressed up to complete suppression during the daily testing of animals. Generally, an animal stops researching the test space and demonstrates the passive behavior. In the past studies on female rats we have found out that the blockade of monoamine oxidase B (MAO-B) doesn’t prevent of the suppression of animal’s behavior activity during the daily testing. Also, according to the cumulative result it was supposed, that the increasing of anxiety can’t to be the main reason of motor deprivation. But the last statement required of experimental confirmation. According to the said statement the purpose of this work was formulated the following way: to find out the dependence of behavior activity oppression of female rats during the daily testing of anxiety level in normal conditions and in blockade of MAO-B one. Methods: the research work was carried out on 48 white female rats line Wistar aged 7 months, contained in standard conditions of vivarium. All of the animals were homogenous sample with the middle level of motor activity and high level of anxiety (the index of anxiety (IA) were more than 0,7 of conventional units). The rats were divided into four groups of 12 animal units in each one, lately -2 control sets and 2 experimental one (blockade of MAO-B). The animal behavioral reactions were researched in two tests: “Open field” (circular, diameter 1m) and elevated plus-maze (EPM, standard sized for rats). The residence time of each rat in both test setting was 5 minutes. This period of time is recorded by high definition camcorder; video recording is analyzed automatically by the program complex Noldus EthoVision 12. It was found out, that the increasing the level anxiety cannot be the only reason of motor activity oppression of high-anxiety female rats in “Open field” and elevated plus-maze tests. The blockade of MAO-B decreases the index of anxiety of animals, that, possible, indicates on directly dopaminergic system and the central dopamine participation in the emotional state regulation along with other monoamines. Also the EPM test is more indicative for analyzing of dynamic of the anxiety index compared with “Open field” test.

In real conditions of high-intensity training and competitive load of athletes, the most important for sports success is the preservation of energy metabolism indicators, and, in particular, the acid-base balance in the range of homeostatic normal values. One of the possible ways to maintain the acid-base balance of an athlete is the use of homeostatic electrolyte drinks, which can have a fairly rapid effect. In this regard, for our work we have identified the following goal of the study: to analyze the possibility of using the functional drink "Aluston" (FDA) produced by JSC "Alushta Essential Oil Plant" to maintain the acid-base balance of athletes and a possible increase in performance, training duration, resistance of athletes to long-term physical activity of high intensity. Methods: Stepwise loading protocol was used on a Kettler bicycle ergometer (Hmbq, Germany). Capillary blood sampling from athletes was carried out at rest before the start of the load and immediately after it was completed using an Epoc capillary (Epocal Inc., Canada). Biochemical parameters of blood like pH, concentration of CO2 and O2, [Na+], [К+], [Сa2+], [Cl–], [HCO3–], Lactate, Glucose, Crea, Hct, Hb, BE(ecf), BE(b ) were recorded by the Epocreader and Epochost analyzers (Epocal Inc., Canada). It was shown that FDA contributes to the stabilization of anion gaps, reduces the severity of the shift of the standard (BE-ecf) and true (BE-b) excess bases into the negative range, which can be regarded as a more pronounced preservation of the “strength” of blood buffer systems, and contributed to a decrease in tension in the pair acidosis-alkalosis. In addition, FDA supplementation likely shifts the phase of creatine fermentation to later loading stages. The last experimental fact requires further research, and also, modification changes in the composition, concentration ratio of active components in the “Aluston” drink remain relevant.

Objectives: Unnecessary and inappropriate antibiotic use is an increasing global health challenge. In limited resource settings, prophylactic antibiotics are still often used in (adeno)tonsillectomy (AT), despite evidence against their effectiveness. This study aimed to investigate the effect of prophylactic amoxicillin, given after AT in children. Methods: This is a secondary analysis from a two-center, double-blinded, randomized controlled, non-inferiority trial to study the effect of prophylactic amoxicillin on post-AT morbidity. Children aged 2-14 years with recurrent chronic tonsillitis and/or obstructive sleep apnea were randomly assigned to receive either placebo or amoxicillin for 5 days after the operation. Pre- and postoperative samples were collected for polymerase chain reaction (PCR) analyses to detect the five most important pathogens known to be common causes of tonsillitis. PCR results were compared before and after surgery as well as between placebo and amoxicillin. Results: PCR results were obtained, 109 in the amoxicillin group and 115 in the placebo group. In the amoxicillin group, 91% of patients had at least one positive PCR test before surgery and 87% after surgery. In the placebo group, the respective percentages were 92% and 90%. In both groups, a decrease in the total number of pathogens was found after surgery. Conclusion: Prophylactic amoxicillin given after AT in children did not show a clinically relevant effect with respect to the number of oropharyngeal microorganisms as compared to placebo.

Abstract Background Despite Colombia's robust well-child visits program, Colombian children and mothers still suffer from anemia, especially in populations of lower socioeconomic status. In this study, we aimed to quantify the prevalence and risk factors among mothers and their children attending their well-child visits in Apartadó, a municipality in the Urabá region of the Colombian Caribbean. Methods There were 100 mother–child pairs enrolled in this secondary data-analysis study from a health facility in the municipality of Apartadó, Urabá, Colombia, during well-child visits. Self-reported data included child illnesses in the past two weeks (diarrheal, fever, or respiratory symptoms), child feeding practices (breastfeeding, complementary feeding), child vaccinations, and demographic characteristics (mother’s and child’s age, mother’s education, marital status, race, and child sex) and socioeconomic status. Mother and child anthropometry data were collected via standardized weight and height measurements. Mother or child anemia status was collected via a blood test. Chi-squared tests and multivariable logistic regression were used to assess associations between risk factors and anemia. Result The anemia prevalence in children (74%) and mothers (47%) was higher than the Colombian national prevalence. Reported child comorbidities in the preceding two weeks were not significantly associated with child anemia and included respiratory illnesses (60%), fever (46%), and diarrhea (30%). Stunting (8%) was not significantly associated with anemia. Wasting (0%) was not observed in this study. Reported child breastfeeding and complementary feeding were also not significantly associated with child anemia. In adjusted models, the child's significant risk factors for anemia included the mother's "Mestiza" race (OR: 4.681; 95% CI: 1.258, 17.421) versus the Afro-Colombian race. Older children (25–60 months) were less likely to develop anemia than younger (6–24 months) children (OR: 0.073; 95% CI: 0.015, 0.360). Conclusions The finding of high anemia prevalence in this study advances our understanding of child and maternal anemia in populations of low socioeconomic status where health care is regularly accessed through well-child programs.

Adipose tissue (AT) dysfunctions, such as adipocyte hypertrophy, macrophage infiltration and secretory adiposopathy (low plasma adiponectin/leptin, A/L, ratio), associate with metabolic disorders. However, no study has compared the relative contribution of these markers to cardiometabolic risk in women of varying age and adiposity. Body composition, regional AT distribution, lipid-lipoprotein profile, glucose homeostasis and plasma A and L levels were determined in 67 women (age: 40-62 years; BMI: 17-41 kg/m2). Expression of macrophage infiltration marker CD68 and adipocyte size were measured from subcutaneous abdominal (SCABD) and omental (OME) fat. AT dysfunction markers correlated with most lipid-lipoprotein levels. The A/L ratio was negatively associated with fasting insulinemia and HOMA-IR, while SCABD or OME adipocyte size and SCABD CD68 expression were positively related to these variables. Combination of tertiles of largest adipocyte size and lowest A/L ratio showed the highest HOMA-IR. Multiple regression analyses including these markers and TAG levels revealed that the A/L ratio was the only predictor of fasting insulinemia and HOMA-IR. The contribution of the A/L ratio was superseded by adipose cell size in the model where the latter replaced TAGs. Finally, leptinemia was a better predictor of IR than adipocyte size and the A/L ratio in our participants sample.

The paper studies the results of mathematical modeling of the external flow of Siemens 3D model SWT3.6120 (B52 air foil) horizontal axis wind turbine (HAWT), using the NavierStokes equations averaged by Reynolds (RANS) closed byk,kShear Stress Transport (SST) and Eddy Viscosity Transport (EVT) turbulence models. The task of correct determination of the wind speed vector deviation angle over the nacelle of the HAWT is required by operation of the yawing system, which determines in turn the efficiency of the entire turbine. The Struhal number was chosen as a comparison criterion, defined for the transverse flow around the cylinder, describing the frequency of the formation of vortex structure behind the butt part of the blade of the HAWT. The calculated area consists of 3million tetrahedral volumes with prismatic layer on the surface of the nacelle, using local grinding. The place of flow direction parameters registration is located at a height of 3 m above the nacelle and at a distance of 8m from the blade shank, which corresponds to the standard location of the weather vane. The analysis of the obtained results showed that thekand EVT turbulence models describe the flow parameters over the HAWT nacelle in almost the same way, but the EVT model represents just one differential equation, thereby it is preferable by the computational cost criterion. Also, one of the advantages of one-parameter turbulence model (EVT model) is a smaller number of closing semi-empirical constants, the analysis of which allows the expanding of the engineering techniques scope for the modeling of turbulent processes in solving the practical problems related to the design of control systems for the wind turbines, increasing their efficiency.

Shubnikov-de Haas (SdH) oscillations are the fingerprint of the Landau and Zeeman splitting level structure on the resistivity in presence of a moderate magnetic field before full quantization is manifest in the integer quantum Hall effect. These oscillations have served as a paradigmatic experimental probe and tool for extracting key semiconductor parameters such as carrier density, effective mass m^{*}, Zeeman splitting with g factor g^{*}, quantum scattering time, and Rashba α and Dresselhaus β spin-orbit (SO) coupling parameters. Analytical descriptions of the SdH oscillations are available for some special cases, but no analytical solution could be found for the vast majority of parameter space with all three terms present, usually relevant for experiments. Despite over 50 years of experiments and many theoretical models, which were put forth, this has seriously hampered the analysis and interpretation of experimental data. Here, we bridge this gap by providing an analytical formulation for the SdH oscillations of 2D electron gases (2DEGs) with simultaneous Rashba, Dresselhaus, and Zeeman interactions over a very broad range of parameter space. We use a Poisson summation formula for the density of states of the 2DEG, which affords a complete yet simple description of the oscillatory behavior of its magnetoresistivity. Our analytical and numerical calculations allow us to extract the beating frequencies, quantum lifetimes, and also to understand the role of higher harmonics in the SdH oscillations. More importantly, we derive a simple condition for beating-free SdH oscillations for all harmonics in 2DEGs α/β=[(1−Δ[over ̃])/(1+Δ[over ̃])]^{1/2}, where Δ[over ̃]∝g^{*}m^{*} is a material parameter given by the ratio of the Zeeman and Landau level splitting. This condition is notably different from that of the persistent spin helix at α/β=1 for materials with large g^{*}m^{*} such as InAs or InSb. We also predict beatings in the higher harmonics of the SdH oscillations and elucidate the inequivalence of the SdH response of Rashba-dominated (α>β) vs Dresselhaus-dominated (α

Here, the authors apply positron emission tomography (PET) imaging to visualize HIV tissue-wide burden in infected individuals using a radiolabeled broadly neutralizing antibody, 89Zr-VRC01, and show that PET tracer lymph node uptake positively correlates with HIV protein levels measured directly from cells obtained from these tissues. This strategy may allow non-invasive characterization of residual HIV infection in the setting of therapeutic interventions.

Protein changes in a brain with Alzheimer’s are not often accompanied by transcriptional differences. Here, using a deep neural network that predicts protein abundance from mRNA expression, the authors track the early protein changes in Alzheimer’s dementia.

This article is based on a wide range of sources, including documents of the Russian State Military Archive. It tells about a little-known national white counterrevolution formation created by Ataman G.M. Semyonov in early 1919 and recruited from the Jewish population of Transbaikalia. The uniqueness of this separate Jewish company lies in the fact that it was the only regular armed formation consisting of Jews and participating in combat action on the side of the White movement. In this way, at the very beginning of 1919, a detachment that included a Jewish company fought against the Red partisans and internationalists in the Yakut taiga on the Magyar rift. In addition, the Jewish divisions carried out garrison service in different settlements of the Semyonovskii kingdom. During the summer of 1919, underground Bolshevik cells began to form, which in the spring of 1920 led to a revolt in the white Jewish units. An insurrection in the village of Aleksandrovka was suppressed by Semyononvs forces. On 23 April 1920 a separate Jewish company in full strength successfully went over to the side of the Reds in the village of Nerchensky Zavod. In response, the Red command decided to create the 4th Rifle Partisan Regiment from among the Jewish partisans who had gone over to the Bolshevik side. Thereafter, this regiment was transformed into the 15th Infantry Regiment of the People's Revolutionary Army of the Far Eastern Republic. In the fall of 1920, it took part in heavy battles for Borzya and Dauria. All this is disclosed in more detail in this article. The Jewish national divisions were only one of the ethno-confessional units of the troops of ataman G.M. Semenov, next to Chinese, Serbian, Buryat, Mongolian, Caucasian and Tatar formations. Their activities in 1919 were mostly garrison work in nature, but they also had to fight against the partisans in extremely difficult conditions. The transition of these ethnic groups to the Reds was not surprising, at a time when the White movement in Transbaikalia was already in agony. The article also pays attention to the position of Jews in Transbaikalia during the Civil War and the attitude of Ataman G.M. Semenov to the Jewish matter.

Background and aimsStatin-associated muscle symptoms (SAMS) are frequently reported. Nevertheless, few data on objective measures of muscle function are available. Recent data suggesting an important nocebo effect with statin use could confound such effects. The objective was to assess if subjective and objective measures of muscle function improve after drug withdrawal in SAMS reporters.MethodsPatients (59 men, 33 women, 50.3±9.6 yrs.) in primary cardiovascular prevention composed three cohorts: statin users with (SAMS, n = 61) or without symptoms (No SAMS, n = 15), and controls (n = 16) (registered at clinicaltrials.gov, NCT01493648). Force (F), endurance (E) and power (P) of the leg extensors (ext) and flexors (fle) and handgrip strength (Fhg) were measured using isokinetic and handheld dynamometers, respectively. A 10-point visual analogue scale (VAS) was used to self-assess SAMS intensity. Measures were taken before and after two months of withdrawal.ResultsFollowing withdrawal, repeated-measures analyses show improvements for the entire cohort in Eext, Efle, Ffle, Pext and Pfle (range +7.2 to +13.3%, all p≤0.02). Post-hoc analyses show these changes to occur notably in SAMS (+8.8 to +16.6%), concurrent with a decrease in subjective perception of effects in SAMS (VAS, from 5.09 to 1.85). Fhg was also improved in SAMS (+4.0 to +6.2%) when compared to No SAMS (-1.7 to -4.2%) (all p = 0.02).ConclusionsWhether suffering from "true" SAMS or nocebo, those who reported SAMS had modest but relevant improvements in muscle function concurrent with a decrease in subjective symptoms intensity after drug withdrawal. Greater attention by clinicians to muscle function in frail statin users appears warranted.Trial registrationThis study is registered in clinicaltrials.gov (NCT01493648).

Pneumococcal conjugate vaccine ten valent (PCV 10) was introduced into Nigeria in three phases. Phase 3 introduction started in August 2016. However, its impact on pneumonia admissions and mortality among vaccinated Nigerian children has not been determined. Data in the period before PCV-10 introduction (3 August 2013–2 August 2016), and after (3 August 2017–2 August 2020) were retrospectively extracted from the medical charts of eligible patients aged 3–24 months with hospitalized radiological pneumonia at the University College Hospital (UCH), Ibadan; National Hospital (NH), Abuja; and Federal Teaching Hospital (FTH), Gombe, allowing for an intervening period of 1 year. Proportions of the patients with hospitalized pneumonia and case fatality rates were determined during both periods. The results were compared using z-test, multiple logistic regression analysis and p

People with disabilities disproportionately experience negative health outcomes. Purposeful analysis of information on all aspects of the experience of disability across individuals and populations can guide interventions to reduce health inequities in care and outcomes. Such an analysis requires more holistic information on individual function, precursors and predictors, and environmental and personal factors than is systematically collected in current practice. We identify 3 key information barriers to more equitable information: (1) a lack of information on contextual factors that affect a person’s experience of function; (2) underemphasis of the patient’s voice, perspective, and goals in the electronic health record; and (3) a lack of standardized locations in the electronic health record to record observations of function and context. Through analysis of rehabilitation data, we have identified ways to mitigate these barriers through the development of digital health technologies to better capture and analyze information about the experience of function. We propose 3 directions for future research on using digital health technologies, particularly natural language processing (NLP), to facilitate capturing a more holistic picture of a patient’s unique experience: (1) analyzing existing information on function in free text documentation; (2) developing new NLP-driven methods to collect information on contextual factors; and (3) collecting and analyzing patient-reported descriptions of personal perceptions and goals. Multidisciplinary collaboration between rehabilitation experts and data scientists to advance these research directions will yield practical technologies to help reduce inequities and improve care for all populations. Author summary As medical successes have increased lifespans and improved health outcomes around the world, global ageing and more frequent occurrence of chronic diseases are contributing to a corresponding increase in the impact of disability worldwide. People with disabilities often experience injustices and ableism in healthcare, and as the prevalence and impacts of disability continue to grow, there is a clear need for more disability-focused and disability-aware practices in healthcare. Here, we present a roadmap towards bringing better information on the concrete impacts and lived experience of disability into healthcare practice, as a key step towards addressing this need. We describe 3 major barriers to collecting and analyzing information on people’s experience of function and disability, including a lack of contextual information, underemphasis of the patient’s voice and experience, and technical challenges in recording disability-related information in health records. These barriers create significant information inequities that contribute to the disparities in health and healthcare experienced by disabled people. We further propose 3 specific directions for new research and development on using digital health technologies, particularly natural language processing (NLP) and other artificial intelligence technologies, to help mitigate these barriers and support more equitable healthcare for people with disabilities.

Abstract Background Chordoma is a rare bone tumor that is typically resistant to chemotherapy and is associated with genetic abnormalities of the T-box transcription factor T (TBXT) gene, which encodes the transcription factor brachyury. Brachyury is felt to be a major contributor to the development of chordomas. Case presentation We describe a 67-year-old woman who developed an undifferentiated pleomorphic sarcoma in her thigh. Despite treatment with standard chemotherapy regimens, she had a rapidly progressive course of disease with pulmonary metastases and passed away 8 months from diagnosis with pulmonary complications. Her medical history was remarkable in that she had a spheno-occipital chordoma at age 39 and later developed multiple other tumors throughout her life including Hodgkin lymphoma and squamous cell carcinoma and basal cell carcinoma of the skin. She had a family history of chordoma and her family underwent extensive genetic study in the past and were found to have a duplication of the TBXT gene. Conclusions Brachyury has been found to associate with tumor progression, treatment resistance, and metastasis in various epithelial cancers, and it might play roles in tumorigenesis and aggressiveness in this patient with multiple rare tumors and germ line duplication of the TBXT gene. Targeting this molecule may be useful for some malignancies.

The paper deals with the problem of orientation of the traditional horizontal-axis wind turbine (HAWT) when changing the direction, strength and speed of the wind. When the wind direction changes, the active swept area of the rotor, which is a circle when the rotation axis and the incoming air flow vector are collinear, decreases and takes the form of an ellipse. This, in turn, leads to a decrease in the electricity volume generation. Weathervane or rumba-anemometer is a device for registering the speed and direction of wind flow. When the wind direction changes, the device transmits a corresponding signal to the Control System, which in turn generates the command to turn the HAWT rotor on the wind. However, when the wind flow is passing between the rotating blades, the direction of distorted wake is changing, causing eddy formation. As a result the device gives out the initially incorrect data about the direction and velocity of the air flow. Furthermore, when adjusting the position of the rotor (yawing), the collinearity of the rotation axis and the vector of the incoming flow is not achieved, the swept area remains mostly elliptical, and the power generated is proportionally reduced. In accordance with the relevancy of the said problem, the goal of the study was to calculate numerical values of the wake deflection angle in various modes, using the three-dimensional modeling in Ansys CFX software package. The obtained information can be used then to develop the algorithm for eliminating this error.

Abstract The Atlantic Meridional Overturning Circulation (AMOC), a tipping component of the climate system, is projected to slowdown during the 21st century in response to increased atmospheric CO2 concentration. The rate and start of the weakening are associated with relatively large uncertainties. Observed sea surface temperature-based reconstructions indicate that AMOC has been weakening since the mid-20th century, but its forcing factors are not fully understood. Here we provide dynamical observational evidence that the increasing atmospheric CO2 concentration affects the North Atlantic heat fluxes and precipitation rate, and weakens AMOC, consistent with numerical simulations. The inferred weakening, starting in the late 19th century, earlier than previously suggested, is estimated at 3.7 ± 1.0 Sv over the 1854–2016 period, which is larger than it is shown in numerical simulations (1.4 ± 1.4 Sv).

The current global pandemic caused by coronavirus has uncovered multiple symptoms, including sudden hearing loss in either one or both ears, with different outcomes. We present a 68-year-old female with sudden onset bilateral hearing loss, fever, generalized body weakness, and gastrointestinal disturbances. She tested positive for severe acute respiratory syndrome coronavirus 2, was isolated, and was treated with a variety of medications for 5 days before being discharged home to self-isolate. The audiological assessment revealed both sensorineural and conductive hearing loss with a progressive favorable outcome on follow-up visits, with resolution occurring approximately 2 months after the onset. The majority of cases have reported sensorineural hearing loss. However, this case is one of the few that has reported mixed hearing loss. This report highlights an alternate clinical feature of the coronavirus that requires a comprehensive audiological examination by clinicians to ensure proper identification and treatment.

Abstract Background Adenotonsillectomy is the most frequently performed operation in children worldwide. For decades, prophylactic antibiotics have been prescribed to limit postoperative complications. The effect of this antibiotic use has been refuted in a Cochrane Review. However, all reviewed studies were carried out in developed countries. In Tanzania, like many other developing countries with limited resources and a high burden of infectious diseases, postoperative antibiotic prescription is still very common to decrease the supposed higher postoperative morbidity. However, as a consequence of this widespread use of postoperative antibiotics, cross-resistance and risk of allergic side effects rise. Well-designed randomized controlled trials are needed to limit unnecessary antibiotic prescription and secondary antibiotic resistance. Aim The aim of this study is to analyse the prophylactic role of postoperative antibiotics on morbidity following adenotonsillectomy in children in Tanzania. Design The double-blinded, randomized, placebo-controlled trial was set in northern Tanzania. Participating centres are the Department of Otolaryngology at Kilimanjaro Christian Medical Centre in Moshi and the Department of Paediatric Surgery at the Arusha Lutheran Medical Centre in Arusha. Methods Around 270 children aged 2–14 years, all scheduled for elective (adeno)tonsillectomy, will be included and assigned to receive either a standard regimen of 5 days of antibiotic prophylaxis or placebo after surgery. The primary outcomes are postoperative haemorrhage, fever and pain. Secondary outcomes are the time until normal diet is resumed, the time until normal activities are resumed and the occurrence of adverse events and microbial recolonization of the tonsillar beds. Discussion This study will enhance an increase of proper antimicrobial prescription in Tanzanian institutions as well as other resource-limited countries where prescription of antibiotics is still very common. In addition, it might augment current knowledge about surface and core tonsillar micro-organisms and sensitivity patterns. Trial registration Pan African Clinical Trials Registry, PACTR201905466349317. Retrospectively registered on 15 May 2019. https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=8119

The aim of the research is to study gas content of the K10 coal reservoir for assessment of methane resources and possibility of its production in the Sherubainurinsky area of the Karaganda coal basin. Methodology. To determine the value of natural gas content of the coal seam K10 of the Karaganda coal basin, the authors have used three methods based on the calculated and actual data on gas evolution from formation during its development: 1) calculation of gas content by the Langmuir coefficients; 2) sampling and processing of coal samples by the method of DMT GmbH & Co. KG; KG; 3) measurement of actual gas emission. Furthermore, the specified value was refined on the basis of comparison of the results obtained by different methods. Investigations were carried out on the field of the Abayskaya mine of ArcelorMittal Temirtau JSC during the development of the coal seam K10. Results. The gas content of the K10 reservoir within the Sherubainurinsky site is estimated at an average of 17,5 m3/t. However, the method for determining the natural gas-bearing formation of reservoirs by the amount of released methane gives rather average value. The studies have shown that the results of determination of natural gas content of coal seams, made by the method of the company DMT GmbH & Co. KG, have good convergence with the calculated value. The gas content of the coal seams of the Sherubainurinsky site increases with depth according to the dependence described by the regression equation, in general, having the form of the Langmuir equation. The research results show that in a virtually intact array at a distance of 38 ... 42 m from the production wall, gas content is constant. Scientific novelty: comprehensive studies of the coal bed gas content and the nature of the effect of unloading on its value of Karaganda. Practical significance. coal-basin. Associated coal mining gas methane in the development of mines is used to generate electricity and meet the needs of the mine itself. In the future, utilization of coalbed methane in Kazakhstan will save natural gas and reduce greenhouse gas emissions. This is a promising energy market. The gas permeability and methane content of coal seams are the main criteria for assessing the methane-coal areas during their preparation for development. Investigations of the gas content of coal seams will correctly assess the resources of methane and the possibility of its production in the Sherubainurinsky site of the Karaganda coal basin.

The development of methods ensuring reliable control over explosive chemical reactions is a critical task for the safe and efficient application of energetic materials. Triggering the explosion by laser radiation is one of the promising methods. In this work, we demonstrate a technique of applying the common industrial high explosive pentaerythritol tetranitrate (PETN) as a photosensitive energetic material by adding zinc oxide nanopowders doped with copper and iron. Nanopowders of ZnO:Fe and ZnO:Cu able to absorb visible light were synthesized. The addition of one mass percent nanopowders in PETN decreased the threshold energy density of its initiation through Nd:YAG laser second harmonic (2.33 eV) by more than five times. The obtained energetic composites can be reliably initiated by a CW blue laser diode with a wavelength of 450 nm and power of 21 W. The low threshold initiation energy and short irradiation exposure of the PETN-ZnO:Cu composite makes it applicable in laser initiation devices. PETN-ZnO:Cu also can be initiated by an infrared laser diode with a wavelength of 808 nm. The proposed photochemical mechanism of the laser-induced triggering of the explosion reaction in the studied energetic composites was formulated. The results demonstrate the high promise of using nanomaterials based on zinc oxide as a sensitizer of industrial energetic materials to visible laser radiation.

Objective: Positron emission tomography (PET) imaging is a powerful non-invasive method to determine the in vivo behavior of biomolecules. Determining biodistribution and pharmacokinetic (PK) properties of targeted therapeutics can enable a better understanding of in vivo drug mechanisms such as tumor uptake, off target accumulation and clearance. Zirconium-89 (89Zr) is a readily available tetravalent PET-enabling radiometal that has been used to evaluate the biodistribution and PK of monoclonal antibodies. In the current study, we performed in vitro and in vivo characterization of 89Zr-lintuzumab, a radiolabeled anti-CD33 antibody, as a model to evaluate the in vivo binding properties in preclinical models of AML. Methods: Lintuzumab was conjugated to p-SCN-Bn-deferoxamine (DFO) and labeled with 89Zr using a 5:1 µCi:µg specific activity at 37 °C for 1h. The biological activity of 89Zr-lintuzumab was evaluated in a panel of CD33 positive cells using flow cytometry. Fox Chase SCID mice were injected with 2 × 106 OCI-AML3 cells into the right flank. After 12 days, a cohort of mice (n = 4) were injected with 89Zr-lintuzumab via tail vein. PET/CT scans of mice were acquired on days 1, 2, 3 and 7 post 89Zr-lintuzumab injection. To demonstrate 89Zr-lintuzumab specific binding to CD33 expressing tumors in vivo, a blocking study was performed. This cohort of mice (n = 4) was injected with native lintuzumab and 24 h later 89Zr-lintuzumab was administered. This group was imaged 3 and 7 days after injection of 89Zr-lintuzumab. A full ex vivo biodistribution study on both cohorts was performed on day 7. The results from the PET image and ex vivo biodistribution studies were compared. Results: Lintuzumab was successfully radiolabeled with 89Zr resulting in a 99% radiochemical yield. The 89Zr-lintuzumab radioconjugate specifically binds CD33 positive cells in a similar manner to native lintuzumab as observed by flow cytometry. PET imaging revealed high accumulation of 89Zr-lintuzumab in OCI-AML3 tumors within 24h post-injection of the radioconjugate. The 89Zr-lintuzumab high tumor uptake remains for up to 7 days. Tumor analysis of the PET data using volume of interest (VOI) showed significant blocking of 89Zr-lintuzumab in the group pre-treated with native lintuzumab (pre-blocked group), thus indicating specific targeting of CD33 on OCI-AML3 cells in vivo. The tumor uptake findings from the PET imaging study are in agreement with those from the ex vivo biodistribution results. Conclusions: PET imaging of 89Zr-lintuzumab shows high specific uptake in CD33 positive human OCI-AML3 tumors. The results from the image study agree with the observations from the ex vivo biodistribution study. Our findings collectively suggest that PET imaging using 89Zr-lintuzumab could be a powerful drug development tool to evaluate binding properties of anti-CD33 monoclonal antibodies in preclinical cancer models.

The comparative phytochemical analysis in this study revealed differences in the type and levels of phenolic compounds between Spiraea hypericifolia L. and Spiraea crenata L. The compounds in water–ethanol extracts of aerial parts of both species were identified by high-performance liquid chromatography as chlorogenic, gentisic, and cinnamic acids; quercetin; kaempferol; hyperoside; isoquercetin; nicotiflorin; and apigenin. In the extract of S. hypericifolia, p-coumaric acid and luteolin were also found, which were absent in the extract of S. crenata. Such compounds as avicularin, astragalin, and isorhamnetin-3-rutinoside proved to be specific to S. crenata (and were not found in the S. hypericifolia extract). The viability of liver cancer HepG2 cells and breast cancer MDA-MB-231 cells significantly decreased after cultivation with the S. crenata extract. In addition, the S. crenata extract showed higher antioxidant activity than the S. hypericifolia extract. It is most likely that these effects can be explained by the higher content of individual flavonoids in the extract of S. crenata. Thus, the extract of S. crenata holds promise for more extensive research on the mechanism of its action on tumor cells.

Background: Humans are primary drivers of environmental contamination worldwide, including in drinking-water resources. In the United States (US), federal and state agencies regulate and monitor public-supply drinking water while private-supply monitoring is rare; the current lack of directly comparable information on contaminant-mixture exposures and risks between private- and public-supplies undermines tapwater (TW) consumer decision-making. Methods: We compared private- and public-supply residential point-of-use TW at Cape Cod, Massachusetts, where both supplies share the same groundwater source. TW from 10 private- and 10 public-supply homes was analyzed for 487 organic, 38 inorganic, 8 microbial indicators, and 3 in vitro bioactivities. Concentrations were compared to existing protective health-based benchmarks, and aggregated Hazard Indices (HI) of regulated and unregulated TW contaminants were calculated along with ratios of in vitro exposure-activity cutoffs. Results: Seventy organic and 28 inorganic constituents were detected in TW. Median detections were comparable, but median cumulative concentrations were substantially higher in public supply due to 6 chlorine–disinfected samples characterized by disinfection byproducts and corresponding lower heterotrophic plate counts. Public-supply applicable maximum contaminant (nitrate) and treatment action (lead and copper) levels were exceeded in private-supply TW samples only. Exceedances of health-based HI screening levels of concern were common to both TW supplies. Discussion: These Cape Cod results indicate comparable cumulative human-health concerns from contaminant exposures in private- and public-supply TW in a shared source-water setting. Importantly, although this study’s analytical coverage exceeds that currently feasible for water purveyors or homeowners, it nevertheless is a substantial underestimation of the full breadth of contaminant mixtures documented in the environment and potentially present in drinking water. Conclusion: Regardless of the supply, increased public engagement in source-water protection and drinking-water treatment, including consumer point-of-use treatment, is warranted to reduce risks associated with long-term TW contaminant exposures, especially in vulnerable populations.

Summary This work proposes a strategy to create an embedded genetic algorithms (GAs) for low‐power, low‐cost, and low‐size‐memory devices. This strategy aims to provide the means of GAs to run as a low‐cost and low‐power consumption embedded system, where microcontrollers (μCs) are commonly used. The implementation details are presented, emphasizing the limitations and restrictions imposed to turn it more compact and efficient. In addition, data related to the algorithm effectiveness, processing time, and memory consumption were obtained from simulations, oscilloscope measurements, and using the hardware‐in‐loop technique. Finally, this implementation is compared with other implementation from the literature and the results show that 8‐bits μCs can run GAs for several practical applications.

Optimizing traditional training methods to elicit greater adaptations is paramount for athletes. Ischemic preconditioning (IPC) can improve maximal exercise capacity and up-regulate signaling pathways involved in physiological training adaptations. However, data on the chronic use of IPC are scarce and its impact on high-intensity training is still unknown. We investigated the benefits of adding IPC to sprint-interval training (SIT) on performance and physiological adaptations of endurance athletes. In a randomized controlled trial, athletes included eight SIT sessions in their training routine for 4 weeks, preceded by IPC (3 × 5 min ischemia/5 min reperfusion cycles at 220 mmHg, n = 11) or a placebo (20 mmHg, n = 9). Athletes were tested pre-, mid-, and post-training on a 30 s Wingate test, 5-km time trial (TT), and maximal incremental step test. Arterial O2 saturation, heart rate, rate of perceived exertion, and quadriceps muscle oxygenation changes in total hemoglobin (Δ[THb]), deoxyhemoglobin (Δ[HHb]), and tissue saturation index (ΔTSI) were measured during exercise. Blood samples were taken pre- and post-training to determine blood markers of hypoxic response, lipid-lipoprotein profile, and immune function. Differences within and between groups were analyzed using Cohen's effect size (ES). Compared to PLA, IPC improved time to complete the TT (Mid vs. Post: −1.6%, Cohen's ES ± 90% confidence limits −0.24, −0.40;−0.07) and increased power output (Mid vs. Post: 4.0%, ES 0.20, 0.06;0.35), Δ[THb] (Mid vs. Post: 73.6%, ES 0.70, −0.15;1.54, Pre vs. Post: 68.5%, ES 0.69, −0.05;1.43), Δ[HHb] (Pre vs. Post: 12.7%, ES 0.24, −0.11;0.59) and heart rate (Pre vs. Post: 1.4%, ES 0.21, −0.13;0.55, Mid vs. Post: 1.6%, ES 0.25, −0.09;0.60). IPC also attenuated the fatigue index in the Wingate test (Mid vs. Post: −8.4%, ES −0.37, −0.79;0.05). VO2peak and maximal aerobic power remained unchanged in both groups. Changes in blood markers of the hypoxic response, vasodilation, and angiogenesis remained within the normal clinical range in both groups. We concluded that IPC combined with SIT induces greater adaptations in cycling endurance performance that may be related to muscle perfusion and metabolic changes. The absence of elevated markers of immune function suggests that chronic IPC is devoid of deleterious effects in athletes, and is thus a safe and potent ergogenic tool.

Abstract Background The imbalance between the action of the tissue inhibitors of matrix metalloproteinases (TIMPs) and the matrix metalloproteinases (MMPs) is one component of metastasis physiology. TIMP-1 overrides MMP-9 activity in cancer and might be regulated by miR-618. The aims of this study were to clarify whether TIMP-1 expression is modified by miR-618 and to clarify the effect of miR-618 expression on the invasion of prostate cancer cells. We also studied miR-618 expression in surgical specimens of patients with localized prostate cancer submitted to open radical prostatectomy. Methods After transfection of miR-618 or its antagonist in DU145 cells, qRT-PCR for TIMP-1/MMP-9 and both ELISA and zymography for MMP-9 were performed. Total miRNA was extracted from surgical specimens of PCa, and miR-618 expression was examined for correlations with Gleason score, pathological status and biochemical recurrence. Results DU145 cells transfected with miR-618 had a 76% reduction in TIMP-1 expression relative to control cells (p = 0.003). miR-618 inhibition reduced MMP-9 expression by 31% (p = 0.032) and MMP-9 absorbance evaluated with ELISA assay (p = 0.06).Zymography suggested higher MMP-9 activity in DU145 cells transfected with miR-618 than those transfected with miR-618 inhibitor, but the difference was not significant (p = 0.55). However, miR-618 expression was lower in surgical specimens of patients with Gleason score > 7 (p = 0.08) and more advanced disease (p = 0.07). Conclusions In vitro, miR-618 overexpression decreases TIMP-1 and miR-618 inhibition decreases MMP-9, suggesting that miR-618 might be an oncomiR. However, the analysis of clinical samples of localized prostate cancer revealed an inconsistent pattern, as increased miR-618 expression was associated with lower Gleason score and pathological status. Further studies are needed to address whether miR-618 is a context-dependent miRNA.

Spatial and scale effects have barely been considered in forensic entomology, despite their pervasive influence on most of the parameters affecting the development of insect larval stages and the progression of insect succession on cadavers. Here, we used smoothing/interpolation techniques and semivariograms to document the spatial dynamics of sarcosaprophageous Calliphoridae, an important forensic taxon, in the Greater Moncton area in New Brunswick, Canada. Results indicated that the spatial dynamics of Calliphoridae differed between species, some species showing strong patterns of regional aggregation while others did not. Multivariate spatial correlations indicated that interspecific relationships in space varied widely, ranging from local and large-scale aggregation to spatial anticorrelation between species. Overall, this study suggested that even within a restricted timescale, the spatial dynamics of Calliphoridae can operate at many scales, manifest in different patterns, and be attributed to multiple different causes. We stress that forensic entomology has much to benefit from the use of spatial analysis because many important forensic questions, both at the fundamental and practical levels, require a spatial solution.

Abstract Background The ability to metastasize is one of the most important characteristics of neoplastic cells. An imbalance between the action of some matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs drives the invasion process. Some studies have suggested that MMP-2 is involved in metastasis, while other studies have reported that collagen production by cancer cells might also contribute to motility. However, decreased expression of microRNA-29b (miR-29b), which may control MMP-2 and collagen gene expression, has been shown in prostate cancer (PCa). The objectives of the present study were to clarify whether MMP-2 as well as collagens I and III (encoded by COL1A1 and COL3A1, respectively) are controlled by miR-29b and to determine whether metastasis is altered by this relationship. Methods PCa DU145 and PC-3 cells were transfected with 100 μL of OPTI-MEM I containing 100 nmol of miR-29b (or its inhibitor) along with 1.5 μL of lipofectamine. Positive and negative controls were prepared using the same protocol. MMP-2, COL1A1 and COL3A1 messenger RNA (mRNA) levels were evaluated via real-time polymerase chain reaction (qRT-PCR). For qRT-PCR, 6 × 104 cells were used. Invasion studies were conducted with Matrigel assays, which simulate invasion of the extracellular matrix by neoplastic cells. After transfection of 3 × 104 cells, invasion was allowed to proceed for 48 h. Invasive cells were counted under an optical microscope. Each experiment was performed in triplicate. Results MMP-2 mRNA was not expressed in DU145 cells after transfection with miR-29b. After transfection of cells with the miR-29b inhibitor, COL1A1 (p = 0.02) and COL3A1 (p = 0.06) mRNA expression was increased in DU145 cells, and a large number of transfected DU145 and PC3 cells invaded the Matrigel membrane. Conclusions In vitro studies showed that reducing the amount of miR-29b may lead to higher PCa cell invasion via a process that is independent of MMP-2. Collagen expression, controlled by miR-29b, may facilitate this motility process. Thus, the present study suggests that collagen production plays an active role in metastasis control and restoration of miR-29b levels may decrease metastasis. Altogether, these findings support further exploration of drug therapy targeting this aspect of the metastasis circuit.

The ability to manipulate entanglement between multiple spatially separated qubits is essential for quantum-information processing. Although nitrogen-vacancy (NV) centers in diamond provide a promising qubit platform, developing scalable two-qubit gates remains a well-known challenge. To this end, magnon-mediated entanglement proposals have attracted attention due to their long-range spin-coherent propagation. Optimal device geometries and gate protocols of such schemes, however, have yet to be determined. Here we predict strong long-distance (>μm) NV-NV coupling via magnon modes with cooperativities exceeding unity in ferromagnetic bar and waveguide structures. Moreover, we explore and compare on-resonant transduction and off-resonant virtual-magnon exchange protocols, and discuss their suitability for generating or manipulating entangled states at low temperatures (T≲150mK) under realistic experimental conditions. This work will guide future experiments that aim to entangle spin qubits in solids with magnon excitations.

We present a quantitative theory of the suppression of the optical linewidth due to charge fluctuation noise in a p-n diode, recently observed by Anderson et al. [Science 366, 1225 (2019)]. We connect the local electric field with the voltage across the diode, allowing the identification of the defect depth from the experimental threshold voltage. Furthermore, we show that an accurate description of the decoherence of such spin centers requires a complete spin-1 formalism that yields a biexponential decoherence process, and predict how reduced charge fluctuation noise suppresses the spin center’s decoherence rate.

Integrating patterned, low-loss magnetic materials into microwave devices and circuits presents many challenges due to the specific conditions that are required to grow ferrite materials, driving the need for flip-chip and other indirect fabrication techniques. The low-loss (α = (3.98 ± 0.22) × 10−5), room-temperature ferrimagnetic coordination compound vanadium tetracyanoethylene (V[TCNE]x) is a promising new material for these applications that is potentially compatible with semiconductor processing. Here, we present the deposition, patterning, and characterization of V[TCNE]x thin films with lateral dimensions ranging from 1 μm to several millimeters. We employ electron-beam lithography and liftoff using an aluminum encapsulated poly(methyl methacrylate), poly(methyl methacrylate-methacrylic acid) copolymer bilayer [PMMA/P(MMA-MAA)] on sapphire and silicon. This process can be trivially extended to other common semiconductor substrates. Films patterned via this method maintain low-loss characteristics down to 25 μm with only a factor of 2 increase down to 5 μm. A rich structure of thickness and radially confined spin-wave modes reveals the quality of the patterned films. Further fitting, simulation, and analytic analysis provide an exchange stiffness, Aex = (2.2 ± 0.5) × 10−10erg/cm, as well as insights into the mode character and surface-spin pinning. Below a micron, the deposition is nonconformal, which leads to interesting and potentially useful changes in morphology. This work establishes the versatility of V[TCNE]x for applications requiring highly coherent magnetic excitations ranging from microwave communication to quantum information.

There is an increasing concern about NOx emission, and many studies have been carried out using metal oxide semiconductors (MOS) aiming its detection. Among the MOS, the SnO micro-disks present a high sensor response and a great selectivity toward NO2. Nevertheless, sensor signal, limit of detection (LOD), and recovery time are related to the experimental setup used to carry on the measurements. Thus, two different heating methods (self-heating and external heating) have been carried out to understand in what manner they change the sensor properties of the SnO micro-disks onto interdigitated electrodes. The external heating method presented higher sensor signal, best LOD, and lower recovery time, mainly due to the lack of a temperature gradient between the SnO disks and the chamber atmosphere. On the other hand, response time was shown to be the same regardless of the method. Briefly, the authors used thermodynamic equations to better understand the temperature effect on the gas-solid interactions occurring between SnO disks and NO2 species.

Small bait traps are beginning to emerge in forensic entomology as a new approach to sample early-colonizing necrophagous Diptera species while reducing the investment in time and energy in obtaining information. To test the hypothesis conveyed by the literature that these traps can be a substitute for whole carcasses, we simultaneously documented the Diptera assemblages visiting and colonizing domestic pig carcasses and small traps baited with pork liver. Results indicated that Diptera species occurrence and assemblage composition in the small bait traps and on the carcasses differed, while they were similar when comparing only the pig carcasses. These results are in agreement with the literature that examined insect colonization of other decaying substrates. Although small bait traps can be useful tools to document the communities of necrophagous Diptera in a given area, we stress that caution must be exercised when extending the data obtained by these traps to courtroom proceedings.

Objective: Recent data suggest that adipose triglyceride lipase (ATGL) plays a key role in providing energy substrate from triglyceride pools and that alterations of its expression/activity relate to metabolic disturbances in skeletal muscle. Yet little is known about its regulation. We here investigated the role of the protein G0/G1 Switch Gene 2 (G0S2), recently described as an inhibitor of ATGL in white adipose tissue, in the regulation of lipolysis and oxidative metabolism in skeletal muscle. Methods: We first examined G0S2 protein expression in relation to metabolic status and muscle characteristics in humans. We next overexpressed and knocked down G0S2 in human primary myotubes to assess its impact on ATGL activity, lipid turnover and oxidative metabolism, and further knocked down G0S2 in vivo in mouse skeletal muscle. Results: G0S2 protein is increased in skeletal muscle of endurance-trained individuals and correlates with markers of oxidative capacity and lipid content. Recombinant G0S2 protein inhibits ATGL activity by about 40% in lysates of mouse and human skeletal muscle. G0S2 overexpression augments (+49%, p

The acquisition of a castration-resistant prostate cancer phenotype by prostate cancer cells is the alteration that has the worst prognosis for patients. The aim of this study was to evaluate the role of the microRNAs-23b/-27b as well as the possible CCNG1 target gene in tissue samples from patients with localized prostate cancer that progressed to castration-resistant prostate cancer and in a castration-resistant prostate cancer cell line (PC-3). The microRNAs and target gene expression levels of the surgical specimens were analyzed by quantitative real-time polymerase chain reaction. The prostate cancer cell line, PC-3, was transfected with pre-miR-23b, pre-miR-27b, and their respective controls using Lipofectamine RNAiMAX and exposed or not to flutamide. After transfections, expression levels of both the microRNAs and the gene, CCNG1 , were analyzed by quantitative real-time polymerase chain reaction. The apoptosis and cell cycle assays were performed on the mini MUSE cytometer. MicroRNAs-23b/-27b were underexpressed in surgical specimens of prostate cancer; however, their target gene, CCNG1 , was overexpressed in 69% of the cases. After transfection with the microRNAs-23b/-27b and flutamide, we observed a reduction in gene expression compared with cells that were treated only with microRNAs or only with flutamide. In the apoptosis assay, we demonstrated cell sensitization following transfection with microRNAs-23b/-27b and potentiation when co-administered with flutamide. The number of cells in apoptosis was almost three times higher with the simultaneous treatments (miR + flutamide) compared with the control (p < 0.05). In the cell cycle assay, only flutamide treatment showed better results; a higher number of cells were found in the G0-G1 phase, and a lower percentage of cells completed the final phase of the cycle (p < 0.05). We conclude that microRNAs-23b/-27b are downexpressed in prostate cancer, and their target gene, CCNG1 , is overexpressed. We postulated that microRNAs-23b/-27b sensitize the PC-3 cell line and that after the addition of flutamide in the apoptosis assay, we would observe synergism in the treatments between miR and flutamide. In the cell cycle assay, the use of flutamide was sufficient to decrease the number of cells in mitosis. Therefore, we postulate that microRNAs, along with other drugs, may become very useful therapeutic tools in the treatment of castration-resistant prostate cancer.

The ability to non-invasively monitor tumor-infiltrating T cells in vivo could provide a powerful tool to visualize and quantify tumor immune infiltrates. For non-invasive evaluations in vivo, an anti-CD3 mAb was modified with desferrioxamine (DFO) and radiolabeled with zirconium-89 (Zr-89 or 89Zr). Radiolabeled 89Zr-DFO-anti-CD3 was tested for T cell detection using positron emission tomography (PET) in both healthy mice and mice bearing syngeneic bladder cancer BBN975. In vivo PET/CT and ex vivo biodistribution demonstrated preferential accumulation and visualization of tracer in the spleen, thymus, lymph nodes, and bone marrow. In tumor bearing mice, 89Zr-DFO-anti-CD3 demonstrated an 11.5-fold increase in tumor-to-blood signal compared to isotype control. Immunological profiling demonstrated no significant change to total T cell count, but observed CD4+ T cell depletion and CD8+ T cell expansion to the central and effector memory. This was very encouraging since a high CD8+ to CD4+ T cell ratio has already been associated with better patient prognosis. Ultimately, this anti-CD3 mAb allowed for in vivo imaging of homeostatic T cell distribution, and more specifically tumor-infiltrating T cells. Future applications of this radiolabeled mAb against CD3 could include prediction and monitoring of patient response to immunotherapy.

Purpose To analyze a possible correlation between a miRNA expression profile and important prognostic factors for pTa urothelial carcinomas (UC), including tumor size, multiplicity and episodes of recurrence. Materials and Methods Thirty low-grade non-invasive pTa bladder UC from patients submitted to transurethral resection were studied, in a mean follow-up of 17.7 months. As controls, we used normal bladder tissue from five patients submitted to retropubic prostatectomy to treat benign prostatic hyperplasia. Extraction, cDNA and amplification were performed for 14 miRNAs (miR-100, -10a, -21, -205, -let7c, -143, -145, -221, -223, -15a, -16, -199a and -452) using specific kits, and RNU-43 and -48 were used as endogenous controls. Statistical tests were used to compare tumor size, multiplicity and episodes of recurrence with miRNAs expression profiles. Results There was a marginal correlation between multiplicity and miR-let7c over-expression. For all others miRNA no correlation between their expression and prognostic factors was found. Conclusion We did not find differences for miRNAs expression profiles associated with prognostic factors in tumor group studied. The majority of miRNAs are down-regulated, except miR-10a, over-expressed in most of cases, seeming to have increased levels in tumor with more unfavorable prognostic factors. More studies are needed in order to find a miRNA profile able to provide prognosis in pTa UC to be used in clinical practice.

Indigenous cultural tourism offers significant future opportunities for countries, cities and Indigenous communities, but the development of new offerings can be problematic. Addressing this challenge, this article examines contemporary Australian Indigenous art innovation and cultural entrepreneurship or culturepreneurship emanating from Australia’s remote Arnhem Land art and culture centres and provides insight into the future development of Indigenous cultural tourism. Using art- and culture-focused field studies and recent literature from the diverse disciplines of art history, tourism, sociology and economics, this article investigates examples of successful Indigenous artistic innovation and culturepreneurship that operate within the context of cultural tourism events. From this investigation, this article introduces and defines the original concept of Indigenous culturepreneurship and provides six practical criteria for those interested in developing future Indigenous cultural tourism ventures. These findings not only challenge existing western definitions of both culture and culturepreneurship but also affirm the vital role of innovation in both contemporary Indigenous art and culturepreneurial practice. Equally importantly, this investigation illuminates Indigenous culturepreneurship as an important future-making socio-political and economic practice for the potential benefit of Indigenous communities concerned with maintaining and promoting their cultures as living, growing and relevant in the contemporary world.