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In this review, the authors explored the clinical features of frontotemporal dementia (FTD), focusing on treatment. The clinical features of FTD are unique, with disinhibition, apathy, loss of empathy, and compulsions common. Motor changes occur later in the illness. The two major proteins that aggregate in the brain with FTD are tau and TDP-43, whereas a minority of patients aggregate FET proteins, primarily the FUS protein. Genetic causes include mutations in

Authoritative, trustworthy, continual, automatic hourly air quality monitoring is a relatively recent innovation. The task of reliably identifying long-term trends in air quality is therefore very challenging, as well as complex. Ports are major sources of atmospheric pollution, which is linked to marine traffic and increased road traffic congestion. This study investigated the long-term trends and drivers of atmospheric pollution in the port cities of Houston, London, and Southampton in 2000–2019. Authoritative air quality and meteorological data for seven sites at these three locations were meticulously selected alongside available traffic count data. Data were acquired for sites close to the port and sites that were near the city centre to determine whether the port emissions were influencing different parts of the city. Openair software was used for plots and statistical analyses. Pollutant concentrations at Houston, Southampton and Thurrock (London) slowly reduced over time and did not exceed national limits, in contrast to NO2 and PM10 concentrations at London Marylebone Road. Drivers of atmospheric pollution include meteorology, geographical and temporal variation, and traffic flow. Statistically significant relationships (p < 0.001) between atmospheric pollution concentration and meteorology across most sites were found, but this was not seen with traffic flows in London and Southampton. However, port emissions and the other drivers of atmospheric pollution act together to govern the air quality in the city.

We compare the results of delay in oral cancer diagnosis before and after a campaign directed toward dentists and raising awareness of the population to achieve early diagnosis of oral cancer in Córdoba, Argentina. The campaign included training dentists in diagnostic skills and a public awareness program through media and networks.Clinical records (period 1: before intervention program, n = 70; period 2: after intervention program, n = 60) of patients presenting with oral squamous cell carcinoma treated in 2 referral centers were analyzed. Records included first symptoms, first consultation with a health professional, and the time when treatment was formulated.Oral cancer diagnosis at early stages increased from 27% (period 1) to 40% (period 2). Biopsy at first consultation was indicated in 6% of patients in period 1 and in 23.3% in period 2 (odds ratio = 4.68; 95% confidence interval, 1.87-11.73; P.05). Professional delay at early stage decreased from 72% in period 1 to 36.8% in period 2. During period 1, for initial stage cancer, the average patient and professional delays were 2.7 and 2.9 months, respectively (P = .06); in period 2, patient delay was 2.67 months and professional delay was 1.34 months (P = .005).The intervention program helped to improve early-stage diagnosis from 27% to 40% by reducing professional delays.

Supplementary Table 1. Statistical analysis of the effect of the combinatory I3C/F-ara-A treatment versus single I3C or F-ara-A treatments. Supplementary Table 2. Combination index (CI) for effective dose (ED) 50, 75 and 90 for I3C combined with F-ara-A, vincristine or chlorambucil and dose reduction index (DRI) for these drugs in the combined treatment with I3C. Supplementary Figure S1. I3C is highly cytotoxic to CLL cells while having reduced cytotoxicity against PBMCs from healthy donors. Supplementary Figure S2. I3C and F-ara-A show strong synergy against CLL cells. Supplementary Figure S3. I3C cytotoxicity and synergy with F-ara-A is fully functional in the presence of human serum. Supplementary Figure S4. Effect of I3C, F-ara-A and the I3C/F-ara-A combination treatment on the expression of proteins involved in the control of apoptosis. Supplementary Figure S5. A. Effect of I3C, F-ara-A and the combined F-ara-A/I3C treatment on mitochondrial depolarization (ΔΨm). B. Effect of I3C, F-ara-A and the combined F-ara-A/I3C treatment on reactive oxygen species (ROS) production. Supplementary Figure S6. I3C has reduced toxicity in T cells from CLL patients compared to CLL cells.

Purpose: Chronic lymphocytic leukemia (CLL) still is lacking a cure. Relapse and development of refractoriness to current treatments are common. New therapies are needed to improve patient prognosis and survival.Experimental design: Indole-3-carbinol (I3C) is a natural product with antitumor properties already clinically tested. The effect of I3C, F-ara-A, and combinations of both drugs on CLL cells from patients representing different Rai stages, IGHV mutation status, cytogenetic alterations, p53 functionality, and treatment resistances was tested, as well as the toxicity of these treatments in mice.Results: I3C induces cytotoxicity in CLL cells but not in normal lymphocytes. I3C strongly synergized with F-ara-A in all CLL cells tested, including those with p53 deficiency and/or F-ara-A resistance. The mechanism of cell death involved p53-dependent and -independent apoptosis. The combination of I3C + F-ara-A was equally effective in CLL cells irrespective of IGHV mutation stage and patient refractoriness. Moreover, CLL survival and treatment resistance induced by co-culturing CLL cells on stroma cells were overcome by the combinatory I3C + F-ara-A treatment. No toxicity was associated with the combined I3C + fludarabine treatment in mice.Conclusions: I3C in combination with F-ara-A is highly cytotoxic in CLL cells from refractory patients and those with p53 deficiency. The striking dose reduction index for F-ara-A in combination with I3C would reduce fludarabine toxicity while having a similar or better anti-CLL effectiveness. Moreover, the low toxicity of I3C, already clinically tested, supports its use as adjuvant and combinatory therapy in CLL, particularly for patients with relapsed or refractory disease. Clin Cancer Res; 22(1); 134–45. ©2015 AACR.

The liver has enormous regenerative capacity such that, after partial hepatectomy, hepatocytes rapidly replicate to restore liver mass, thus providing a context for studying in vivo mechanisms of cell growth regulation. Bax inhibitor-1 (BI-1) is an evolutionarily conserved endoplasmic reticulum (ER) protein that suppresses cell death. Interestingly, the BI-1 protein has been shown to regulate Ca2+ handling by the ER similar to antiapoptotic Bcl-2 family proteins. Effects on cell cycle entry by Bcl-2 family proteins have been described, prompting us to explore whether bi-1–deficient mice display alterations in the in vivo regulation of cell cycle entry using a model of liver regeneration. Accordingly, we compared bi-1+/+ and bi-1−/− mice subjected to partial hepatectomy with respect to the kinetics of liver regeneration and molecular events associated with hepatocyte proliferation. We found that bi-1 deficiency accelerates liver regeneration after partial hepatectomy. Regenerating hepatocytes in bi-1−/− mice enter cell cycle faster, as documented by more rapid incorporation of deoxynucleotides, associated with earlier increases in cyclin D1, cyclin D3, cyclin-dependent kinase (Cdk) 2, and Cdk4 protein levels, more rapid hyperphosphorylation of retinoblastoma protein, and faster degradation of p27Kip1. Dephosphorylation and nuclear translocation of nuclear factor of activated T cells 1 (NFAT1), a substrate of the Ca2+-sensitive phosphatase calcineurin, were also accelerated following partial hepatectomy in BI-1–deficient hepatocytes. These findings therefore reveal additional similarities between BI-1 and Bcl-2 family proteins, showing a role for BI-1 in regulating cell proliferation in vivo, in addition to its previously described actions as a regulator of cell survival. [Cancer Res 2007;67(4):1442–50]

Supplementary Figures 1-5 from Mice Lacking bi-1 Gene Show Accelerated Liver Regeneration

Supplementary Figure Legends 1-5 from Mice Lacking bi-1 Gene Show Accelerated Liver Regeneration

This paper proposes a control scheme for a wave energy conversion system based on a linear generator and a cascaded multilevel converter. The mechanical conversion system is composed of a buoy connected directly to a linear generator. The windings of the generator are individually controlled by a cascaded multilevel power converter using independent maximum power point tracking to improve energy harvesting. The output of the cascaded converter is controlled to keep the DC capacitors balanced and generate a multilevel voltage at the output terminals which reduces the losses in the underwater transmission line. Experimental results show the performance of the proposed control scheme maximizing the power generation by imposing a current with the same waveform of the induced voltage and balancing the DC capacitors. Centro Avanzado de Ingeniería Eléctrica y Electrónica AC3E ANID/FB0008 Centro de Investigación de Energía Solar (SERC) ANID/FONDAP/15110019 Agencia Nacional de Investigación y Desarrollo ANID/Fondecyt 1211826

High-voltage layered Mn-based oxide is promising high-capacity cathode via exploiting the oxygen redox chemistry. But such redox often suffer from irreversible oxygen loss, leading to severe voltage hysteresis, particle cracking and capacity decay. Hence, the complementary strategy of dual Cu and Co substitution is revealed to stabilizing the anion redox chemistry of P2-Na2/3(Mn-Ni-Cu-Co)O2 cathode under upper cut-off voltage. Dual substitution with Cu for Mn and Co for Ni forms stable Cu-O and Co-O octahedrons, which modulate the lattice structure with the shrinkage of TMO2 sheets and expansion of Na layer spacing to enhance the Na+ diffusion kinetics. Co substitution can raise high voltage region to tune the cut-off voltage up to 4.3 V and activate oxygen redox to weaken irreversible O2 loss. And Cu substitution can inhibit the O2 loss and suppress the voltage decay via the interaction between Cu 3d and O 2p orbitals. The P2-type Na0.67Mn0.6Ni0.2Cu0.1Co0.1O2 cathode induced by the complementary effect can boost long cycling life (82.07% capacity retention after 500 cycles) and remarkable rate capability under high upper cut-off voltage in half-cell. Furthermore, the full cells also exhibit outstanding rate capability with a high discharge capacity of 62.6 mAh g–1 at 20 C.

In this paper we propose a modular multilevel converter for a linear generator for a wave energy converter. The coils of this generator are individually controlled to improve energy harvesting performance. This topology involves two stages. The first stage uses a full-bridge to control the harvested current with a reference generated by means of an MPPT method. The second stage uses a half-bridge to control the voltage of the DC-link and the output current. Furthermore, multilevel modular converters allow the generation of a medium DC voltagethat reduces the losses in energy transmission lines from offshore to a coupling common point on the shore.

ispartof: Conference Proceedings of the Society for Experimental Mechanics Series ispartof: IMAC-XL Conference & Exposition on Structural Dynamics 2022 location:Orlando (Florida), USA status: Published online

3-dimensions (3D) printing technology is a type of additive manufacturing (AM) that is on the rise and works by manufacturing components by the deposition of a thermoplastic layer upon layer. In this paper, we explore the use of AM to print a novel fused deposition modeling-based 3D printing electrochemical cell from a non-commercially available composite of PLA/PTFE polymer filament for corrosion applications within materials science. To validate the 3D printed cell, a galvanic series and cyclic voltammetry to aluminum in Hank’s solution was done, and a corrosion resistance study was conducted by using the electrochemical impedance spectroscopy (EIS) and anodic and cathodic polarization (Tafel) techniques to a virgin and a boride ASTM F-73 alloy as working electrode. The results show the possibility of replacing commercial electrochemical cells with 3D printed ones without any compromise on quality of the experiment. Also, this inexpensive and simple instrument design is both, adaptable and sensitive for a wide range of laboratory electrochemical applications.

In this work we propose the use of the semiconducting TiO2/CdS nanocomposite (NC) to improve the optical and electrical properties of the P3HT:PCBM polymeric system employed as the absorber layer in organic photovoltaic solar cells. Therefore, we report a methodology for obtaining the TiO2/CdS-NC, its incorporation into precursor solutions containing P3HT and PCBM polymers, and the fabrication of hybrid P3HT:PCBM:TiO2/CdS-NC absorber layers. The effect of the mass ratio between the TiO2/CdS-NC and the polymeric system was studied. XRD measurements conducted on the TiO2/CdS-NC showed that the TiO2 component has a tetragonal crystalline structure (anatase phase) with a nanocrystalline size of 15.8 nm, while the CdS component has the hexagonal close-packed crystalline structure with a nanocrystalline size of 14.9 nm. XPS analysis confirmed the formation of stoichiometric TiO2 and CdS compounds. The formation of any other compound comprising the elements Ti, O, Cd and S was not found, however, elements Cl, Br, N and C were observed at trace levels, which come from the capping agent that was used to obtain the nanocomposite. Measurements on the hybrid P3HT:PCBM:TiO2/CdS-NC absorber layers through UV-vis spectroscopy showed a shift on the absorption edge and an improved light absorption for wavelengths below 550 nm. The four-point probe measurements showed a decrease of the electrical resistivity from 8.5 × 108 Ω-cm in pristine P3HT:PCBM to a minimum of 4 × 105 Ω-cm in the hybrid absorber layers. Both the light absorption and the electrical resistivity are modulated by the mass ratio between the TiO2/CdS-NC and the P3HT:PCBM polymeric system.

Vanadium Pentoxide is considered as an intriguing material for several advanced technological applications such as supercapacitors, Lithium-ion batteries, photo-catalysis and optical waveguide. In this work, we have presented a facile and non-toxic method for the synthesis of Vanadium Pentoxide nanobelts. Considering the aforesaid motivations, we tuned the size of Vanadium Pentoxide nanobelts by simply varying the synthesis temperature. The XRD results confirm that the obtained phase is Vanadium Pentoxide with no impurities found within the experimental limitations. The analysis by Scanning Electron Microscopy (SEM) depicts that the diameter of nanobelts decreased from 52.7nm to 44.7nm with the increase in synthesis temperature within range 180oC-220 °C respectively. The UV–Vis-Spectrum shows that bandgap of nanobelts increased in the range 2.25eV-3eV with the increase in synthesis temperature within range 180oC-220 °C. For field emission measurements, the variation in field enhancement factor and turn-on voltage is also observed. These results indicate that by just varying a simple parameter one can tune the band gap and electronic properties of Vanadium Pentoxide nanobelts. These studies show that Vanadium Pentoxide nanobelts can be promising candidate for optoelectronic device.

The CoCrMo alloy is a biomaterial that has been employed for the production of permanent orthopedic implants, however, the release of metallic ions from debris due to tribocorrosion is the main drawback for its extended application. In this paper, we propose the use of the ball burnishing process to improve the surface properties of the CoCrMo alloy. A 32 factorial design of experiments (DoE) was conducted to achieve a basic understanding of the relationship between the surface hardness, roughness and corrosion current (response variables) and the force and number of passes of the burnishing tool (input factors). Statistical analysis showed that force is the most significant factor for changing the surface properties. At the best experimental conditions, hardness was improved by 41.4%, the roughness was decreased by 72.7% and the corrosion rate was noticeably reduced by 92.4%. Microscopy and X-ray diffraction analysis showed that ball burnishing introduces changes in the microstructure, generating a surface layer with improved properties. It is concluded that the ball burnishing process is suitable for improving the surface properties of the CoCrMo alloy under an appropriate combination of experimental conditions.

Bioconjugation is a key approach for the development of novel molecular entities with clinical applications. The biocompatibility and specificity of biomolecules such as peptides, proteins, and antibodies make these macromolecules ideal carriers for selective targeted therapies. In this context, there is a need to develop new molecular units that cover the requirements of the next generation of targeted pharmaceuticals. Here, we present the design and development of a versatile and stable linker based on a N-alkylated α,α-dialkyl dipeptide for bioconjugation, with a particular focus on antibody-drug conjugates (ADCs). Starting with the well-known Ugi multicomponent reaction, the convenient chemical modification of the prepared adducts allowed us the obtention of versatile bifunctional linkers for bioconjugation. A conjugation strategy was tested to demonstrate the efficiency of the linker. In addition, a novel cytotoxic anti-HER2 ADC was prepared using the Ugi-linker approach., I.R-T. thanks the Generalitat de Catalunya for a predoctoral fellowship. This work was funded in part by the following: the Ministerio de Economía y Competitividad [Programa INNPACTO, project MarinMab (IPT-2012-0198-090000) and RTI2018-093831-B-100], the Generalitat de Catalunya (2017-SGR-1439), and the Institute for Research in Biomedicine Barcelona (IRB Barcelona) (Spain); National Research Foundation (Blue Skies, # 120386) (South Africa); and Yachay Tech (Ecuador).

Objective. The goal of this study was to use Monte Carlo (MC) simulations and measurements to investigate the dosimetric suitability of an interventional radiology (IR) c-arm fluoroscope to deliver low-dose radiotherapy to the lungs. Approach. A previously-validated MC model of an IR fluoroscope was used to calculate the dose distributions in a COVID-19-infected patient, 20 non-infected patients of varying sizes, and a postmortem subject. Dose distributions for PA, AP/PA, 3-field and 4-field treatments irradiating 95% of the lungs to a 0.5 Gy dose were calculated. An algorithm was created to calculate skin entrance dose as a function of patient thickness for treatment planning purposes. Treatments were experimentally validated in a postmortem subject by using implanted dosimeters to capture organ doses. Main results. Mean doses to the left/right lungs for the COVID-19 CT data were 1.2/1.3 Gy, 0.8/0.9 Gy, 0.8/0.8 Gy and 0.6/0.6 Gy for the PA, AP/PA, 3-field, and 4-field configurations, respectively. Skin dose toxicity was the highest probability for the PA and lowest for the 4-field configuration. Dose to the heart slightly exceeded the ICRP tolerance; all other organ doses were below published tolerances. The AP/PA configuration provided the best fit for entrance skin dose as a function of patient thickness (R2 = 0.8). The average dose difference between simulation and measurement in the postmortem subject was 5%. Significance. An IR fluoroscope should be capable of delivering low-dose radiotherapy to the lungs with tolerable collateral dose to nearby organs.

Patients with acquired brain injury (ABI) may be at an increased risk of malnutrition due to the pathophysiology of their condition, which can affect their anthropometrical profile and therefore their quality of life. The present study analyzes the anthropometrical profile of these individuals, describes their dietary habits and nutrients intake and identifies the related risk factors influencing health status and quality of life.Twenty-three volunteers with ABI from the province of Granada (Spain) were recruited for this cross-sectional study. Nutritional assessment was quantitatively and qualitatively performed using a 72-h dietary record and a food frequency questionnaire, respectively. Body composition parameters were evaluated by bioelectrical impedance.Low intakes of minerals related to bone health, extra virgin olive oil (EVOO) and fruits were reported. Moreover, women presented a poorer anthropometrical profile compared to men. With reference to age, a significant inverse correlation was observed with sarcopenic obesity, appendicular muscle mass index and Vitamin BThe main findings support the existence of poor dietary quality and anthropometrical profile. Interdisciplinary team assessment would be beneficial to enhance the quality of life and attenuate the development of comorbidities in subjects with ABI.

Chronic kidney disease (CKD) is not only common after lung and heart transplantation but also is associated with increased morbidity and mortality due to multiple pre-, peri- and post-transplant factors. While the exact incidence of CKD in this population is not well-defined, it seems to have gradually increased over the years as older recipients are more frequently considered. The increasing success of the procedure and expanding transplant candidate pool has allowed many with comorbid conditions to receive a transplant, which was considered prohibitive in the past. This review presents risk factors that have been linked to CKD as well as interventions that may help alleviate this serious problem. The impact of pretransplant renal function and the overexaggerated role of chronic nephrotoxicity of calcineurin inhibitors is discussed in detail. Until the exact pathophysiology of kidney disease is better understood, there is a dire need to expand the research agenda beyond observational studies.

Human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND) comprise a group of illnesses marked by memory and behavioral dysfunction that can occur in up to 50% of HIV patients despite adequate treatment with combination antiretroviral drugs. Iron dyshomeostasis exacerbates HIV-1 infection and plays a major role in Alzheimer's disease pathogenesis. In addition, persons living with HIV demonstrate a high prevalence of neurodegenerative disorders, indicating that HAND provides a unique opportunity to study ferroptosis in these conditions. Both HIV and combination antiretroviral drugs increase the risk of ferroptosis by augmenting ferritin autophagy at the lysosomal level. As many viruses and their proteins exit host cells through lysosomal exocytosis, ferroptosis-driving molecules, iron, cathepsin B and calcium may be released from these organelles. Neurons and glial cells are highly susceptible to ferroptosis and neurodegeneration that engenders white and gray matter damage. Moreover, iron-activated microglia can engage in the aberrant elimination of viable neurons and synapses, further contributing to ferroptosis-induced neurodegeneration. In this mini review, we take a closer look at the role of iron in the pathogenesis of HAND and neurodegenerative disorders. In addition, we describe an epigenetic compensatory system, comprised of bromodomain-containing protein 4 (BRD4) and microRNA-29, that may counteract ferroptosis by activating cystine/glutamate antiporter, while lowering ferritin autophagy and iron regulatory protein-2. We also discuss potential interventions for lysosomal fitness, including ferroptosis blockers, lysosomal acidification, and cathepsin B inhibitors to achieve desirable therapeutic effects of ferroptosis-induced neurodegeneration.