Tigecycline Opposes Bortezomib Effect on Myeloma Cells Decreasing Mitochondrial Reactive Oxygen Species Production.

Multiple myeloma is an incurable plasma cell malignancy. Most patients end up relapsing and developing resistance to antineoplastic drugs, like bortezomib. Antibiotic tigecycline has activity against myeloma. This study analyzed tigecycline and bortezomib combination on cell lines and plasma cells from myeloma patients. Apoptosis, autophagic vesicles, mitochondrial mass, mitochondrial superoxide, cell cycle, and hydrogen peroxide were studied by flow cytometry. In addition, mitochondrial antioxidants and electron transport chain complexes were quantified by reverse transcription real-time PCR (RT-qPCR) or western blot. Cell metabolism and mitochondrial activity were characterized by Seahorse and RT-qPCR. We found that the addition of tigecycline to bortezomib reduces apoptosis in proportion to tigecycline concentration. Supporting this, the combination of both drugs counteracts bortezomib in vitro individual effects on the cell cycle, reduces autophagy and mitophagy markers, and reverts bortezomib-induced increase in mitochondrial superoxide. Changes in mitochondrial homeostasis and MYC upregulation may account for some of these findings. These data not only advise to avoid considering tigecycline and bortezomib combination for treating myeloma, but caution on the potential adverse impact of treating infections with this antibiotic in myeloma patients under bortezomib treatment.

Battery-SOC Estimation for Hybrid-Power UAVs Using Fast-OCV Curve with Unscented Kalman Filters.

Unmanned aerial vehicles (UAVs) have drawin increasing attention in recent years, and they are widely applied. Nevertheless, they are generally limited by poor flight endurance because of the limited energy density of their batteries. A robust power supply is indispensable for advanced UAVs; thus hybrid power might be a promising solution. State of charge (SOC) estimation is essential for the power systems of UAVs. The limitations of accurate SOC estimation can be partly ascribed to the inaccuracy of open circuit voltage (OCV), which is obtained through specific forms of identification. Considering the actual operation of a battery under hybrid conditions, this paper proposes a novel method, "fast OCV", for obtaining the OCVs of batteries. It is proven that fast OCV offers great advantages, related to its simplicity, duration and cost, over traditional ways of obtaining OCV. Moreover, fast-OCV also shows better accuracy in SOC estimation than traditional OCV. Furthermore, this paper also proposes a new method, "batch mode", for talking-data sampling for battery-parameter identification with the limited-memory recursive least-square algorithm. Compared with traditional the "single mode", it presents good de-noising effect by making use of all the sampled battery's terminal current and voltage data.

Preclinical examination of early-onset thalamic-cortical seizures after hemispheric stroke.

OBJECTIVE: Ischemic stroke is one of the main causes of death and disability worldwide and currently has limited treatment options. Electroencephalography (EEG) signals are significantly affected in stroke patients during the acute stage. In this study, we preclinically characterized the brain electrical rhythms and seizure activity during the hyperacute and late acute phases in a hemispheric stroke model with no reperfusion. METHODS: EEG signals and seizures were studied in a model of hemispheric infarction induced by permanent occlusion of the middle cerebral artery (pMCAO), which mimics the clinical condition of stroke patients with permanent ischemia. Electrical brain activity was also examined using a photothrombotic (PT) stroke model. In the PT model, we induced a similar (PT group-1) or smaller (PT group-2) cortical lesion than in the pMCAO model. For all models, we used a nonconsanguineous mouse strain that mimics human diversity and genetic variation. RESULTS: The pMCAO hemispheric stroke model exhibited thalamic-origin nonconvulsive seizures during the hyperacute stage that propagated to the thalamus and cortex. The seizures were also accompanied by progressive slowing of the EEG signal during the acute phase, with elevated delta/theta, delta/alpha, and delta/beta ratios. Cortical seizures were also confirmed in the PT stroke model of similar lesions as in the pMCAO model, but not in the PT model of smaller injuries. SIGNIFICANCE: In the clinically relevant pMCAO model, poststroke seizures and EEG abnormalities were inferred from recordings of the contralateral hemisphere (noninfarcted hemisphere), emphasizing the reciprocity of interhemispheric connections and that injuries affecting one hemisphere had consequences for the other. Our results recapitulate many of the EEG signal hallmarks seen in stroke patients, thereby validating this specific mouse model for the examination of the mechanistic aspects of brain function and for the exploration of the reversion or suppression of EEG abnormalities in response to neuroprotective and anti-epileptic therapies.

A Proposed System for Multi-UAVs in Remote Sensing Operations.

This paper proposes the design of the communications, control systems, and navigation algorithms of a multi-UAV system focused on remote sensing operations. A new controller based on a compensator and a nominal controller is designed to dynamically regulate the UAVs' attitude. The navigation system addresses the multi-region coverage trajectory planning task using a new approach to solve the TSP-CPP problem. The navigation algorithms were tested theoretically, and the combination of the proposed navigation techniques and control strategy was simulated through the Matlab SimScape platform to optimize the controller's parameters over several iterations. The results reveal the robustness of the controller and optimal performance of the route planner.

Large studies reveal how reference bias limits policy applications of self-report measures.

There is growing policy interest in identifying contexts that cultivate self-regulation. Doing so often entails comparing groups of individuals (e.g., from different schools). We show that self-report questionnaires-the most prevalent modality for assessing self-regulation-are prone to reference bias, defined as systematic error arising from differences in the implicit standards by which individuals evaluate behavior. In three studies, adolescents (N = 229,685) whose peers performed better academically rated themselves lower in self-regulation and held higher standards for self-regulation. This effect was not observed for task measures of self-regulation and led to paradoxical predictions of college persistence 6 years later. These findings suggest that standards for self-regulation vary by social group, limiting the policy applications of self-report questionnaires.

WILD HOPPER: A heavy-duty UAV for day and night firefighting operations.

Forest fires are among the most dangerous accidents, as they lead to the repercussions of climate change by reducing oxygen levels and increasing carbon dioxide levels. These risks led to the attention of many institutions worldwide, most notably the European Union and the European Parliament, which led to the emergence of many directives and regulations aimed at controlling the phenomenon of forest fires in Europe, such as the (E.U.) 2019/570. Among the proposed solutions, the usage of unmanned aerial vehicles (UAVs) is considered to operate alongside existing aircraft and helicopters through extinguishing forest fires. Scientific researches in this regard have shown the high effectiveness use of UAVs. Still, some defects and shortcomings appeared during practical experiments represented in the limited operating time and low payload. As UAVs are used for firefighting forest fires, they must be characterized by the heavy payload for the extinguishing fluids, long time for flight endurance during the mission, the ability to high maneuver, and work as a decision-making system. In this paper, a new UAV platform for forest firefighting is represented named WILD HOPPER. WILD HOPPER is a 600-liter platform designed for forest firefighting. This payload capacity overcomes typical limitations of electrically powered drones that cannot be used for anything more than fire monitoring, as they do not have sufficient lifting power. The enhanced capabilities of the WILD HOPPER allow it to complement existing aerial means and overcome their main limitations, especially the need to cover night operations. This allows reducing the duration of the wildfires heavily by allowing continuous aerial support to the extinguishing activities once the conventional aerial means (hydroplanes and helicopters) are set back to the base at night. On the other hand, WILD HOPPER has significant powerful advantages due to the accuracy of the release, derived from multirotor platform dynamic capabilities.

Silicone breast implants and connective tissue diseases: How does current evidence add to the no-association consensus? Systematic review and meta-analysis.

To evaluate the current state of the evidence regarding the association of silicone breast implantation with the onset of connective tissue diseases, constitutional symptoms, and rheumatic serological profile in adult women. A comprehensive search was carried out using MEDLINE, Embase, Web of Science and Scopus, from inception to September 2, 2020. Cohort studies assessing the clinical and serological profile of women with cosmetic breast implants were included. Meta-analyses were conducted using risk ratios. A total of 10 cohorts with overall moderate quality of evidence were included in this systematic review. Exposure to silicone breast implants was slightly associated with the development of rheumatoid arthritis [RR: 1.35; (95% CI 1.08 to 1.68); P = .008; I2 = 0%]. However, no significant differences were exhibited between the breast implant-exposed population and controls regarding the rest of the outcomes. In adult women, exposure to silicone breast implantation is not associated with the onset of constitutional symptoms and most connective tissue diseases. A marginal association with rheumatoid arthritis was exhibited, but the certainty of this result is jeopardized by the significant amount of self-reported data for this outcome. Further research is required to adequately explore the clinical significance of these results.

Characterizing solute budgets of a tropical Andean páramo ecosystem.

Monitoring solute fluxes in water quality studies is essential to reveal potential ecosystem disturbances, and is particularly important in Andean headwater catchments as they are the main sources of water for downstream populations. However, such studies have mainly focused on organic matter and nutrients, disregarding other solutes that can threaten water quality (e.g. arsenic, lead, calcium or magnesium). Additionally, routine low-resolution (weekly or monthly) sampling schemes may overlook important solute dynamics. Therefore, we collected water samples every four hours for the analysis of twenty-four solutes in a pristine tropical Andean páramo catchment. Solute fluxes were calculated using five different methods. The 4-hourly data set was filtered to test for an optimum sampling frequency without compromising export rates. Based on the available 4-hourly data, the results showed that the interpolation export method was best suited, due to a weak correlation with discharges. Of the twenty-four solutes analyzed, Dissolved Organic Carbon (DOC), Total Nitrogen bound (TNb), Si, Ca, Mg, K, and Na presented the highest input rates (with DOC = 4.167E+08 mEq km-2 yr-1 and Si = 1.729E+07 mEq km-2 yr-1) and export rates (with DOC = 2.686E+08 mEq km-2 yr-1 and Si = 2.953E+08 mEq km-2 yr-1). Moreover, DOC, TNb, NH4-N, NO2-N, NO3-N, PO4, Al, B, Cu, Fe, Zn, As, Cd, Cr, Pb, and V presented more input than export, while Ca, K, Mg, Na, Rb, Si, Sr, and Ba presented more export than input (geogenic sources). Filtered sampling frequencies demonstrated that a minimum of daily grab samples would be required to obtain reliable export rates with differences consistently below 10%, when compared to the 4-hourly solute export. These findings can be particularly useful for the implementation of long-term monitoring programs at low cost, and they provide high-quality information, for the first time, on biogeochemical budgets in a pristine páramo catchment.

Fast Multi-UAV Path Planning for Optimal Area Coverage in Aerial Sensing Applications.

This paper deals with the problems and the solutions of fast coverage path planning (CPP) for multiple UAVs. Through this research, the problem is solved and analyzed with both a software framework and algorithm. The implemented algorithm generates a back-and-forth path based on the onboard sensor footprint. In addition, three methods are proposed for the individual path assignment: simple bin packing trajectory planner (SIMPLE-BINPAT); bin packing trajectory planner (BINPAT); and Powell optimized bin packing trajectory planner (POWELL-BINPAT). The three methods use heuristic algorithms, linear sum assignment, and minimization techniques to optimize the planning task. Furthermore, this approach is implemented with applicable software to be easily used by first responders such as police and firefighters. In addition, simulation and real-world experiments were performed using UAVs with RGB and thermal cameras. The results show that POWELL-BINPAT generates optimal UAV paths to complete the entire mission in minimum time. Furthermore, the computation time for the trajectory generation task decreases compared to other techniques in the literature. This research is part of a real project funded by the H2020 FASTER Project, with grant ID: 833507.

Effect of metformin on microvascular outcomes in patients with type 2 diabetes: A systematic review and meta-analysis.

AIMS: Examine the efficacy of metformin compared to placebo or other glucose-lowering medications on microvascular outcomes in patients with Type 2 Diabetes Mellitus (T2DM). METHODS: MEDLINE, EMBASE, Web of Science, and Scopus were searched from database inception to March 2020. We included randomized clinical trials of patients with T2DM receiving metformin compared with another active glucose-lowering treatment or placebo in which a microvascular outcome was assessed. The risk of bias was assessed using the Cochrane Risk of Bias tool. Microvascular complications included kidney-related outcomes, retinopathy, and peripheral neuropathy. An inverse-weighted variance random-effect meta-analysis was performed to estimate drugs effect over microvascular disease. PROSPERO (CRD42019120365). RESULTS: Nineteen RCTs (n = 18,181) were included. Metformin increased estimated glomerular filtration rate (eGFR) by a mean difference (MD) of 1.08 (95% CI 0.84 to 1.33 ml/min/1.73 m2) after 24 weeks. No effect was found on urinary albumin-creatinine ratio, serum creatinine, and end-stage kidney disease; Patient-important outcomes regarding kidney disease, retinal outcomes, peripheral neuropathy or quality of life were not assessed by any of the included studies and could not be analyzed. CONCLUSIONS: There is no evidence of clinically significant beneficial effect of metformin therapy as compared to other glucose-lowering medications or placebo on the examined microvascular complications.

Effect of Diameter and Fenestration Area of the Liposuction Cannula on the Viability of the Adipocytes.

BACKGROUND: Loss of volume is perhaps the most frustrating problem of fat grafting. The process of fat grafting depends on different variables such as harvesting, processing, and injection techniques. Results between studies that evaluate the effect of the cannula size on fat graft survival have been controversial. However, the role of the fenestration area of the cannula has not been described. METHODS: Four custom-made cannulas with a single fenestration were used for this study. Cannulas vary in diameter and area of the fenestration. Healthy patients seeking primary liposuction of the abdomen for aesthetic reasons were included. Lipoaspiration was performed in a clockwise pattern, and the order of the cannulas was rotated. Negative pressure was maintained at 0.8 atm at all times. Ten ml of fat, obtained from the suction tube, was poured into 20-ml conical centrifugal tubes for further processing. One gram of lipoaspirate was extracted from each sample, and acridine orange stain was added. Adipocytes were extracted, extended in a frotis, and observed by a histologist (masked fashion) under fluorescence microscopy. Viability was reported in percentages per sample. RESULTS: The overall viability was 64.75% ± 18.58. The viability of the obtained samples ranged from 66.51± 20.66 % to 62.83 ± 18.1. In further analysis, comparing the viability according to the shaft diameter and fenestration area, there was no significant difference among groups. CONCLUSIONS: Neither the diameter of the cannula nor the size of the fenestrations are determining factors to affect the viability of the adipocytes. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Scoping review of COVID-19-related systematic reviews and meta-analyses: can we really have confidence in their results?

AIM: The aim of this study was to systematically appraise the quality of a sample of COVID-19-related systematic reviews (SRs) and discuss internal validity threats affecting the COVID-19 body of evidence. DESIGN: We conducted a scoping review of the literature. SRs with or without meta-analysis (MA) that evaluated clinical data, outcomes or treatments for patients with COVID-19 were included. MAIN OUTCOME MEASURES: We extracted quality characteristics guided by A Measurement Tool to Assess Systematic Reviews-2 to calculate a qualitative score. Complementary evaluation of the most prominent published limitations affecting the COVID-19 body of evidence was performed. RESULTS: A total of 63 SRs were included. The majority were judged as a critically low methodological quality. Most of the studies were not guided by a pre-established protocol (39, 62%). More than half (39, 62%) failed to address risk of bias when interpreting their results. A comprehensive literature search strategy was reported in most SRs (54, 86%). Appropriate use of statistical methods was evident in nearly all SRs with MAs (39, 95%). Only 16 (33%) studies recognised heterogeneity in the definition of severe COVID-19 as a limitation of the study, and 15 (24%) recognised repeated patient populations as a limitation. CONCLUSION: The methodological and reporting quality of current COVID-19 SR is far from optimal. In addition, most of the current SRs fail to address relevant threats to their internal validity, including repeated patients and heterogeneity in the definition of severe COVID-19. Adherence to proper study design and peer-review practices must remain to mitigate current limitations.