Application of Delta T1 maps for quantitative and objective assessment of extent of resection and survival prediction in glioblastoma.

Background and Objectives: Gross-total resection (GTR) and low residual tumor volume (RTV) have been associated with increased survival in glioblastoma. Largely due to the subjectivity involved, the determination of GTR and RTV remains difficult in the postoperative setting. In response, the objective of this study is to evaluate the clinical efficacy of an easy-to-use MRI metric, called delta T1 (dT1), to quantify extent of resection (EOR) and RTV, in comparison to radiologist impression, to predict overall survival (OS) in glioblastoma patients. Methods: 59 patients who underwent resection of glioblastoma were retrospectively identified. Delta T1 (dT1) images, automatically created from the difference between calibrated post- and pre-contrast T1-weighted images, were used to quantify EOR and RTV. Kaplan-Meier survival estimates were determined for EOR categories, an RTV cutoff of 5cm3 and radiologist interpretation of EOR. Multivariate Cox proportional hazard regression analysis was used to evaluate RTV and EOR along with effects related to sex, KPS, MGMT, and age on OS. Results: Kaplan-Meier analysis revealed a statistically significant difference in median OS for a dT1-determined RTV cutoff of 5 cm3 (P=.0024, HR=2.18 (1.232-3.856)), but not for radiological impression (P=0.666) or dT1-determined EOR (P=0.0803), which was limited to a comparison between partial and subtotal resections. Furthermore, when covariates were accounted for in multivariate Cox regression, significant differences in OS were retained for dT1-determined RTV. Additionally, a significantly strong yet short-term effect of MGMT methylation status on OS was revealed for each RTV and EOR model. Conclusion: The utility of dT1 maps to quantify EOR and RTV in glioblastoma and predict survival, suggests an emerging role for dT1s with relevance for intraoperative MRI, neuro-navigation and postoperative disease surveillance.

A mathematical model for investigation of dry band location on 22 kV bushing with and without RTV coating: Experimental study.

As different pollutants are deposited on the high voltage bushings, a dry band forms, which causes a flashover. The bushing's contaminated layer will weaken its insulation and have an impact on its electrical characteristics. The performance of bushings in dry band conditions of various lengths was investigated in this proposed piece of work, and a dynamic arc model is presented for the arc process in polluted bushings. It shows satisfactory performance in modelling the arc variables for various dry band positions. The developed dynamic open model for contaminated bushings with and without RTV coating predicted the flashover voltage and dry band positions. Any type of contamination, such as sea salt, road salt, and industrial pollutants prevalent in several sites, can be studied using the established model. Ultimately, it was discovered that there was good agreement between the model's results and the outcomes of the experiments. •Mathematical modeling of 22 kV bushing is conceded out for diverse polluted dry band location at lead-in, lead-out and middle region of bushing surface.•Dynamic arc modeling involved in bushing flashover process for different dry band location is done and flashover voltage is predicted•Experimental work is carried out to find FOV for the bushing with different dry location and compared with predicted FOV.

Finger prosthesis: A novel way to restore the form, function, and esthetics.

Key Clinical Message: A well-customized prosthesis with a life-like esthetic and function are the primary determining factors for its acceptance and success. RTV silicones can prove to be very effective and useful in fabricating such prosthesis. Abstract: Complete or partial finger amputations impact an individual's psychological and physical well-being and are considered the most frequently observed pattern of hand loss. A customized prosthesis offers the patient rehabilitative, functional, and psychological advantages. Retention is the key to the success of such prosthetic restoration. The present case report describes a novel technique that utilizes passive vacuum fit and mechanical retention to restore controlled function movements as a metal wire framework. The procedure was economical, most importantly, produced life-like anatomy of the missing digit and restored the function to some extent.

Evaluation of the Mechanical and Physical Properties of Maxillofacial Silicone Type A-2186 Impregnated with a Hybrid Chitosan-TiO2 Nanocomposite Subjected to Different Accelerated Aging Conditions.

The effects of incorporating a pioneer chitosan-TiO2 nanocomposite on the mechanical and physical properties of room-temperature vulcanization (RTV) maxillofacial A-2186 silicone under accelerated aging protocols were rigorously examined. This investigation utilized 450 samples distributed across five distinct silicone classifications and assessed their attributes, such as tensile strength, elongation, tear strength, hardness, and surface roughness, before and after various accelerated aging processes. Statistical methodologies, including a one-way ANOVA, Tukey's HSD, and Dunnett's T3, were employed based on the homogeneity of variance, and several key results were obtained. Silicones infused with 1 wt.% chitosan-TiO2 showed enhanced tensile strength across various aging procedures. Moreover, the 1 wt.% TiO2/Chitosan noncombination (TC) and 2 wt.% TiO2 compositions exhibited pronounced improvements in the elongation percentage. A consistent rise was evident across all silicone categories regarding tear strength, with the 1 wt.% chitosan-TiO2 variant being prominent under certain conditions. Variations in hardness were observed, with the 1 wt.% TC and 3 wt.% chitosan samples showing distinctive responses to certain conditions. Although most samples displayed a decreased surface roughness upon aging, the 1 wt.% chitosan-TiO2 variant frequently countered this trend. This investigation provides insights into the potential of the chitosan-TiO2 nanocomposite to influence silicone properties under aging conditions.

Hybrid Chitosan-TiO2 Nanocomposite Impregnated in Type A-2186 Maxillofacial Silicone Subjected to Different Accelerated Aging Conditions: An Evaluation of Color Stability.

This study explores the impact of the incorporation of a chitosan-TiO2 nanocomposite on the color stability of pigmented room-temperature vulcanization maxillofacial silicone under various accelerated aging conditions. Five hundred disk-shaped specimens were formed with type A-2186 silicone elastomer, and they were distributed into groups based on pigment types and nanoparticle treatments. The color difference (ΔE) was assessed using a colorimeter in the CIELAB color system before and after exposure to aging conditions, including UV-accelerated aging and outdoor weathering. ANOVA, Dennett's T3, and Tukey HSD tests revealed significant color alterations across all silicone types, with the most pronounced being in the red-colored 3% chitosan specimens and the least pronounced being in the 2% TiO2 specimens that underwent UV-accelerated aging. Outdoor weathering consistently increased the ΔE values across all categories. This study suggests that while nanoparticles may offer some resistance against accelerated aging, they fall short in adequately defending against UV radiation during outdoor weathering.

Study on the Influence of Accelerated Aging on the Properties of an RTV Anti-Pollution Flashover Coating.

The purpose of this work is to study the accelerated aging behavior of a room-temperature vulcanized (RTV) silicone rubber anti-pollution flashover coating. Red, blue and gray RTV rubber samples were selected to prepare coatings on the surface of stainless-steel sheets. The accelerated aging test was carried out in an aging test chamber according to a four-step program cycle. After the completion of different aging tests, the color difference, glossiness, surface micromorphology, wettability, insulation performance and other parameters of the samples were measured using colorimetry, infrared spectrometry, scanning electron microscopy, and a high-voltage breakdown tester. The results showed that with the increase in aging time, the color difference ∆Eab of the coatings increased. The G60 gloss value decreased gradually and tended to be saturated after 60 cycles. After the aging tests, the RTV coating surface had holes, cracks, peeling and other damage to varying degrees. The C:Si atomic ratio was less than 2, and the hydrophobicity was obviously deteriorated. After aging, the electrical strength of the three RTV coatings decreased significantly. It can be concluded that during the accelerated aging test, the RTV coating had cross-linking and oxidation reactions, and the internal deterioration and surface damage of the coating led to changes in its color, luster, morphology, insulation strength, etc.

Leveraging physiologically based pharmacokinetic modeling to optimize dosing for lopinavir/ritonavir with rifampin in pediatric patients.

STUDY OBJECTIVE: Treatment of HIV and tuberculosis co-infection leads to significant mortality in pediatric patients, and treatment can be challenging due to the clinically significant drug-drug interaction (DDI) between lopinavir/ritonavir (LPV/RTV) and rifampin. Doubling LPV/RTV results in insufficient lopinavir trough concentrations in pediatric patients. The objective of this study was to leverage physiologically based pharmacokinetic (PBPK) modeling to optimize the adjusted doses of LPV/RTV in children receiving the WHO-revised doses of rifampin (15 mg/kg daily). DESIGN: Adult and pediatric PBPK models for LPV/RTV with rifampin were developed, including CYP3A and P-glycoprotein inhibition and induction. SETTING (OR DATA SOURCE): Data for LPV/RTV model development and evaluation were available from the pediatric AIDS Clinical Trials Group. PATIENTS: Dosing simulations were next performed to optimize dosing in children (2 months to 8 years of age). INTERVENTION: Exposure following super-boosted LPV/RTV with 10 and 15 mg/kg PO daily rifampin was simulated. MEASUREMENTS AND MAIN RESULTS: Simulated parameters were within twofold observations for LPV, RTV, and rifampin in adults and children ≥2 weeks old. The model predicted that, in healthy adults receiving 400/100 mg oral LPV/RTV twice daily (BID), co-treatment with 600 mg oral rifampin daily decreased the steady-state area under the concentration vs. time curve of LPV by 79%, in line with the observed change of 75%. Simulated and observed concentration profiles were comparable for LPV/RTV (230/57.5 mg/m2 ) PO BID without rifampin and 230/230 mg/m2 LPV/RTV PO BID with 10 mg/kg PO daily rifampin in pediatric patients. Sixteen mg/kg of super-boosted LPV (LPV/RTV 1:1) PO BID with 15 mg/kg PO daily rifampin achieved simulated LPV troughs >1 mg/L in ≥93% of virtual children weighing 3.0-24.9 kg, which was comparable with 10 mg/kg PO daily rifampin. CONCLUSIONS: Super-boosted LPV/RTV with 15 mg/kg rifampin achieves therapeutic LPV troughs in HIV/TB-infected simulated children.

Aesthetic rehabilitation of amputated phalanx by three part mould technique using silicone elastomer - case report.

The unfortunate loss of all or part of a finger caused by traumatic amputation has a negative impact on physical and psychological well-being of a person. Thus an aesthetic prosthesis can offer psychological, functional and rehabilitative advantages. One of the major problems with the prosthetic replacement of a partially amputated finger is inadequate retention of the prosthesis and there are numerous means to enhance the retention. The most routinely used are adhesives, adhesive tape, magnets and implants. The present article describes a technique which utilizes room temperature vulcanizing silicone (RTV) as a prosthetic material retained by preformed artificial rings. Such treatment can be opted for in cases of financial constraints.

The effect of the digital manufacturing technique of cantilevered implant-supported frameworks on abutment screw preload.

PURPOSE: The purpose of this study was to investigate the misfit and screw preload at the implant abutment connection of implant supported fixed dental prosthesis with cantilever (ICFDP) manufactured using different digital manufacturing techniques and to compare the screw preload before and after cyclic loading. MATERIALS AND METHODS: Mandibular jaw model with four intra-foraminal implants was scanned using digital scanner. Stereolithography file was used to design a framework with nonengaging (NE) abutments and 10 mm cantilever distal to one terminal implant. Five frameworks were constructed using combined digital-conventional techniques (CAD-cast), and five frameworks were constructed using three-dimensional printing (3DP). Additional CAD-cast framework was constructed in a way that ensures passive fit (PF) to use as control. Scanning electron microscope (SEM) measured the implant abutment connection misfit. Sixty screws were used on the corresponding frameworks. Screws were torqued and pre-cyclic loading reverse torque value (RTV) was recorded. Frameworks were subjected to 200,000 loading cycles with a loading point 9 mm from the center of terminal implants adjacent to the cantilever and post-cyclic loading RTVs were recorded. RESULTS: Microscopic readings showed significant differences between frameworks. PF demonstrated the lowest measurements of 16.04 (2.6) µm while CAD-cast demonstrated the highest measurements of 29.2 (3.1) µm. In all groups, RTVs were significantly lower than the applied torque. Post-cyclic loading RTV was significantly lower than pre-cyclic loading RTV in PF and 3DP frameworks. Differences in RTVs between the three manufacturing techniques were insignificant. CONCLUSION: Although CAD-cast and three-dimensionally printed (3DP) both produce frameworks with clinically acceptable misfit, 3DP might not be the technique of choice for maintaining screw's preload stability under an aggressive loading situation.

Compression of amorphous solid dispersions prepared by hot-melt extrusion, spray drying and vacuum drum drying.

The present study explored vacuum drum drying (VDD) as an alternative technology for amorphous solid dispersions (ASDs) manufacture compared to hot-melt extrusion (HME) and spray drying (SD) focusing on downstream processability (powder properties, compression behavior and tablet performance). Ritonavir (15% w/w) in a copovidone/sorbitan monolaurate matrix was used as ASD model system. The pure ASDs and respective tablet blends (TB) (addition of filler, glidant, lubricant) were investigated. Milled extrudate showed superior powder properties (e.g., flowability, bulk density) compared to VDD and SD, which could be compensated by the addition of 12.9% outer phase. Advantageously, the VDD intermediate was directly compressible, whereas the SD material was not, resulting in tablets with defects based on a high degree of elastic recovery. Compared to HME, the VDD material showed superior tabletability when formulated as TB, resulting in stronger compacts at even lower solid fraction values. Despite the differences in tablet processing, tablets showed similar tablet performance in terms of disintegration and dissolution independent of the ASD origin. In conclusion, VDD is a valid alternative to manufacture ASDs. VDD offered advantageous downstream processability compared to SD: less solvents and process steps required (no second drying), improved powder properties and suitable for direct compression.

Identification of ferroptosis as a novel mechanism for antitumor activity of natural product derivative a2 in gastric cancer.

Ferroptosis is a type of cell death accompanied by iron-dependent lipid peroxidation, thus stimulating ferroptosis may be a potential strategy for treating gastric cancer, therapeutic agents against which are urgently required. Jiyuan oridonin A (JDA) is a natural compound isolated from Jiyuan Rabdosia rubescens with anti-tumor activity, unclear anti-tumor mechanisms and limited water solubility hamper its clinical application. Here, we showed a2, a new JDA derivative, inhibited the growth of gastric cancer cells. Subsequently, we discovered for the first time that a2 induced ferroptosis. Importantly, compound a2 decreased GPX4 expression and overexpressing GPX4 antagonized the anti-proliferative activity of a2. Furthermore, we demonstrated that a2 caused ferrous iron accumulation through the autophagy pathway, prevention of which rescued a2 induced ferrous iron elevation and cell growth inhibition. Moreover, a2 exhibited more potent anti-cancer activity than 5-fluorouracil in gastric cancer cell line-derived xenograft mice models. Patient-derived tumor xenograft models from different patients displayed varied sensitivity to a2, and GPX4 downregulation indicated the sensitivity of tumors to a2. Finally, a2 exhibited well pharmacokinetic characteristics. Overall, our data suggest that inducing ferroptosis is the major mechanism mediating anti-tumor activity of a2, and a2 will hopefully serve as a promising compound for gastric cancer treatment.

Development of Spray-Dried Cyclodextrin-Based Pediatric Anti-HIV Formulations.

The human immunodeficiency virus (HIV) impacts up to 37 million people globally, of which 1.8 million are children. To date, there is no cure for HIV, although treatment options such as antiretroviral therapy (ART) are available. ART, which involves a patient taking a combination of antiretrovirals, is being used to treat HIV clinically. Despite the effectiveness of ART, there is currently no palatable pediatric formulation to treat HIV in children, which has hindered patient compliance and overall treatment efficacy. In addition, anti-HIV therapeutics are often poorly water-soluble, and hence have poor bioavailability. In the present study, we developed a pediatric-friendly formulation for anti-HIV therapeutics with improved dissolution characteristics of the therapeutic agents. Lopinavir (LPV) and ritonavir (RTV), available as FDA-approved fixed-dose combination products, were chosen as model ART drugs, and the formulation and processing parameters of spray-dried cyclodextrin (CD)-based LPV and RTV complexes were studied. Results showed that the spray-dried complexes exhibited enhanced dissolution profiles in comparison to pure drugs, particularly spray-dried ß-CD complexes, which showed the most favorable dissolution profiles. This current formulation with enhanced dissolution and taste-masking ability through the use of cyclodextrin has the potential to address the unmet need for the development of suitable pediatric formulations.

Possibility for Replicating Mechanoscopic Surface Marks in the Hybrid Vacuum-Pressure Casting Process.

Vacuum-pressure casting technology allows small batches of components to be manufactured from polymer materials, mainly from thermosetting plastics such as polyurethane and epoxy resins. Apart from being very simple, the process is also advantageous in that it offers a very accurately reproduced geometrical structure of the surfaces of master patterns used in mold manufacturing. This article presents the results of analyses performed for the process of replicating mechanoscopic marks with the use of three vacuum casting variants, including a hybrid vacuum-pressure casting process developed in particular for the replication purposes. The main research objective was to analyze and evaluate the influence of the parameters of the individual process variants on the quality of the obtained cast parts and on the replication accuracy without introducing additional artifacts on their surfaces. The article discusses the individual stages of the process and provides an analysis of their parameters. The replicas were evaluated for their porosity and reproduction quality with the use of CT methods and comparative photographs obtained from a light microscope.

Management of Antiretroviral Therapy with Boosted Protease Inhibitors-Darunavir/Ritonavir or Darunavir/Cobicistat.

A major challenge in the management of antiretroviral therapy (ART) is to improve the patient's adherence, reducing the burden caused by the high number of drugs that compose the treatment regimens for human immunodeficiency virus positive (HIV+) patients. Selection of the most appropriate treatment regimen is responsible for therapeutic success and aims to reduce viremia, increase the immune system response capacity, and reduce the incidence rate and intensity of adverse reactions. In general, protease inhibitor (PI) is one of the pillars of regimens, and darunavir (DRV), in particular, is frequently recommended, along with low doses of enzyme inhibitors as cobicistat (COBI) or ritonavir (RTV), by the international guidelines. The potential of clinically significant drug interactions in patients taking COBI or RTV is high due to the potent inhibitory effect on cytochrome CYP 450, which attracts significant changes in the pharmacokinetics of PIs. Regardless of the patient or type of virus, the combined regimens of DRV/COBI or DRV/RTV are available to clinicians, proving their effectiveness, with a major impact on HIV mortality/morbidity. This study presents current information on the pharmacokinetics, pharmacology, drug interactions, and adverse reactions of DRV; it not only compares the bioavailability, pharmacokinetic parameters, immunological and virological responses, but also the efficacy, advantages, and therapeutic disadvantages of DRV/COBI or DRV/RTV combinations.

Deubiquitinase JOSD2 stabilizes YAP/TAZ to promote cholangiocarcinoma progression.

Cholangiocarcinoma (CCA) has emerged as an intractable cancer with scanty therapeutic regimens. The aberrant activation of Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) are reported to be common in CCA patients. However, the underpinning mechanism remains poorly understood. Deubiquitinase (DUB) is regarded as a main orchestrator in maintaining protein homeostasis. Here, we identified Josephin domain-containing protein 2 (JOSD2) as an essential DUB of YAP/TAZ that sustained the protein level through cleavage of polyubiquitin chains in a deubiquitinase activity-dependent manner. The depletion of JOSD2 promoted YAP/TAZ proteasomal degradation and significantly impeded CCA proliferation in vitro and in vivo. Further analysis has highlighted the positive correlation between JOSD2 and YAP abundance in CCA patient samples. Collectively, this study uncovers the regulatory effects of JOSD2 on YAP/TAZ protein stabilities and profiles its contribution in CCA malignant progression, which may provide a potential intervention target for YAP/TAZ-related CCA patients.

E-Skin Development and Prototyping via Soft Tooling and Composites with Silicone Rubber and Carbon Nanotubes.

The strategy of embedding conductive materials on polymeric matrices has produced functional and wearable artificial electronic skin prototypes capable of transduction signals, such as pressure, force, humidity, or temperature. However, these prototypes are expensive and cover small areas. This study proposes a more affordable manufacturing strategy for manufacturing conductive layers with 6 × 6 matrix micropatterns of RTV-2 silicone rubber and Single-Walled Carbon Nanotubes (SWCNT). A novel mold with two cavities and two different micropatterns was designed and tested as a proof-of-concept using Low-Force Stereolithography-based additive manufacturing (AM). The effect SWCNT concentrations (3 wt.%, 4 wt.%, and 5 wt.%) on the mechanical properties were characterized by quasi-static axial deformation tests, which allowed them to stretch up to ~160%. The elastomeric soft material's hysteresis energy (Mullin's effect) was fitted using the Ogden-Roxburgh model and the Nelder-Mead algorithm. The assessment showed that the resulting multilayer material exhibits high flexibility and high conductivity (surface resistivity ~7.97 × 104 Ω/sq) and that robust soft tooling can be used for other devices.

Comparing Torque Loss in Standard Implants and Short Implants with Increased Vertical Cantilever Abutments: an In Vitro Study / Comparação da perda de torque em implantes padrão e implantes curtos com pilares cantilever verticais aumentados (in vitro)

Objectives: With regard to the prevalence of abutment screw loosening (SL) and bone height reduction, particularly in the posterior regions of the jaws, as well as the contradictory issue of applying short implants instead of surgeries, along with all preparations associated with longer implants, the present study aimed to compare the amount of torque loss in short implants with increased vertical cantilever abutments and standard ones. Material and Methods: In this experimental study, a total number of 20 implants (MegaGen Implant Co., Ltd, South Korea) with 4.5 mm diameter including 10 short implants (7 mm) and 10 standard ones (10 mm) were utilized. Using a surveyor, fixtures were perpendicularly mounted in 13×34 mm resin for short implants and 19×34 mm resin for standard ones. The abutments of the same height but different cuff heights (2.5 mm for the standard implants and 5.5 mm for the short ones) were then tightened with 30 N.cm, via a digital torque meter. To compensate the settling effect, the abutment screw was re-tightened with 30 N.cm after 10 min. Upon applying 500,000 cycles at 75 N.cm and 1 Hz along the longitudinal axis on each sample, blind reverse torque value (RTV) was measured with a digital torque meter. The data were finally analyzed using Student's t-test. Results:Both groups experienced torque loss, but there was no statistically significant difference between the case and control groups in terms of abutment SL (p = 0451). Conclusion: Short implants seem to be a good mechanical alternative in emergencies with respect to torque loss and abutment SL. (AU)

Objetivos: Considerando a prevalência de afrouxamento de parafuso dos pilares, redução da altura óssea especialmente nas regiões posteriores, a questão contraditória da aplicação de implantes curtos em vez de cirurgias e todos os preparos associados a implantes mais longos, este estudo buscou comparar implantes curtos com pilares cantilever verticais aumentados e implantes padrão na quantidade de perda de torque. Material e métodos: Neste estudo experimental, foram utilizados 20 implantes (Megagen, Coreia do Sul) com diâmetro de 4,5 mm, incluindo 10 implantes curtos (7 mm) e 10 implantes padrão (10 mm). A fixação foi realizada perpendicularmente em uma resina 13 × 34 mm para implantes curtos e uma resina 19 × 34 mm para implantes padrão, usando um topógrafo. Os pilares da mesma altura, mas com diferentes comprimentos de manguito (2,5 mm para os implantes padrão e 5,5 mm para os implantes curtos) foram apertados com 30 N, utilizando um torquímetro digital. Para compensar o efeito de sedimentação, o parafuso do pilar foi reapertado com 30 N após 10 min. Depois de aplicar 500.000 ciclos a 75 N e 1 Hz ao longo do eixo longitudinal em cada amostra, o valor de torque reverso cego foi medido com um medidor de torque digital. Os dados foram analisados pelo teste t de Student. Resultados: Todos os grupos tiveram perda de torque, mas não houve diferença estatisticamente significativa entre os grupos caso e controle em termos de afrouxamento do parafuso do pilar (p = 0451). Conclusão: Os implantes curtos parecem ser uma boa alternativa mecânica em emergências em termos de perda de torque e afrouxamento do parafuso do pilar. (AU)

A Narrative Review of Emerging Therapeutics for COVID-19.

The novel severe acute respiratory syndrome coronavirus 2, the causal agent of coronavirus disease 2019 (COVID-19), quickly spread around the world, resulting in the most aggressive pandemic experienced in more than 100 years. Research on targeted therapies and vaccines has been initiated on an unprecedented scale and speed but will take months and even years to come to fruition. Meanwhile, the efficacy of emerging therapeutics for use in treating COVID-19 is feverishly being investigated to identify the best available treatment options for dealing with the current wave of disease. This review of publications with a "treatment" tag through June 29, 2020 in the National Library of Medicine's LitCovid literature hub, provides frontline clinicians with a pragmatic summary of the current state of the rapidly evolving evidence supporting emerging candidate therapeutics for COVID-19. Two main categories of pharmaceutical therapeutics are showing promise: those with antiviral activity directly addressing infection and those that counteract the inflammatory cytokine storm induced by severe disease. Preliminary results suggest that other approaches such as convalescent plasma therapy and lung radiation therapy may have some efficacy. The current clinical evidence for potential treatments is preliminary-often small retrospective series or early results of randomized trials-and the science is evolving rapidly. The long-term results from large, well-designed randomized controlled trials will provide definitive evidence for therapeutic effectiveness and are likely months away. The trial landscape for promising therapies is described.

Extrusion 3D Printing of Porous Silicone Architectures for Engineering Human Cardiomyocyte-Infused Patches Mimicking Adult Heart Stiffness.

Cardiac patches, three-dimensional (3D) constructs of polymer scaffold and heart muscle cells, have received widespread attention for regenerative therapy to repair damaged heart tissue. The implanted patches should mimic the micromechanical environment of native myocardium for effective integration and optimum mechanical function. In this study, we engineered compliant silicone scaffolds infused with cardiomyocytes (CMs) differentiated from human-induced pluripotent stem cells. Porous scaffolds are fabricated by extrusion 3D printing of room-temperature-vulcanized (RTV) silicone rubber. The stiffness and strength of scaffolds are tailored by designing a polymer strand arrangement during 3D printing. Single-strand scaffold design is found to display a tensile Young's modulus of ∼280 kPa, which is optimum for supporting CMs without impairing their contractility. Uniform distribution of cells in the scaffold is observed, ascribed to 3D migration facilitated by interconnected porous architecture. The patches demonstrated synchronized contraction 10 days after seeding scaffolds with CMs. Indentation measurements reveal that the contracting cell-scaffold patches display local moduli varying from ∼270 to 530 kPa, which covers the upper spectrum of the stiffness range displayed by the human heart. This study demonstrates the effectiveness of a porous 3D scaffold composed of flexible silicone rubber for CMs percolation, supporting a contractile activity, and mimicking native heart stiffness.

Attention regulation in women with ADHD and women with bipolar disorder: An ex-Gaussian approach.

Attention-deficit/hyperactivity disorder (ADHD) and bipolar disorder (BD) show certain overlapping features, such as increased reaction time variability. Here, we tested whether more detailed ex-Gaussian reaction time distribution measures identify shared or disorder-specific impairments in ADHD and BD. The total assessed sample consisted of 60 women (20 each in ADHD, BD and control groups). We compared the groups on ex-Gaussian measures of mu, sigma, and tau from a flanker task (congruent and incongruent conditions), an oddball task, and a four-choice reaction time task (baseline and fast-incentive conditions of the `fast task'). The ex-Gaussian measures mu and sigma reflect the speed and variability of typical responses, while tau captures variability in infrequent slow responses. Compared to controls, both ADHD and BD groups showed significantly increased tau in the fast task baseline condition. Participants with BD further showed a significantly increased sigma compared to ADHD and control groups in the flanker task incongruent condition. Our findings indicate that the ex-Gaussian approach is informative in detecting shared and disorder-specific cognitive impairments in ADHD and BD that may represent objective markers of these two disorders.