Meredithbright8235
Natural killer (NK) cell-based immunotherapy presents a promising antitumor strategy and holds potential for combination with chemotherapy. However, the suppressed NK cell activity and poor tumor retention of therapeutics hinder the efficacy. To activate NK cell-based immuno-chemotherapy and enhance the tumor retention, we proposed a pH-responsive self-aggregated nanoparticle for the codelivery of chemotherapeutic doxorubicin (DOX) and the transforming growth factor-β (TGF-β)/Smad3 signaling pathway inhibitor SIS3. Polycaprolactone-poly(ethylene glycol) (PCL-PEG2000) micelles modified with dibenzylcyclooctyne (DBCO) or azido (N3) and coated with acid-cleavable PEG5000 were established. This nanoplatform, namely, M-DN@DOX/SIS3, could remain well dispersed in the neutral systemic circulation, while quickly respond to the acidic tumor microenvironment and intracellular lysosomes, triggering copper-free click reaction-mediated aggregation, leading to the increased tumor accumulation and reduced cellular efflux. In addition, the combination of DOX with SIS3 facilitated by the aggregation strategy resulted in potent inhibition of melanoma tumor growth and significantly increased NK cells, NK cell cytokines, and antitumor T cells in the tumor. Taken together, our study offered a new concept of applying copper-free click chemistry to achieve nanoparticle aggregation and enhance tumor retention, as well as a promising new combined tumor treatment approach of chemotherapy and immunotherapy.Carbapenem-resistant Klebsiella pneumoniae has been classified as an Urgent Threat by the Centers for Disease Control and Prevention (CDC). The combination of two "old" antibiotics, polymyxin and chloramphenicol, displays synergistic killing against New Delhi metallo-β-lactamase (NDM)-producing K. pneumoniae. However, the mechanism(s) underpinning their synergistic killing are not well studied. We employed an in vitro pharmacokinetic/pharmacodynamic model to mimic the pharmacokinetics of the antibiotics in patients and examined bacterial killing against NDM-producing K. find more pneumoniae using a metabolomic approach. Metabolomic analysis was integrated with an isolate-specific genome-scale metabolic network (GSMN). Our results show that metabolic responses to polymyxin B and/or chloramphenicol against NDM-producing K. pneumoniae involved the inhibition of cell envelope biogenesis, metabolism of arginine and nucleotides, glycolysis, and pentose phosphate pathways. Our metabolomic and GSMN modeling results highlight the novel mechanisms of a synergistic antibiotic combination at the network level and may have a significant potential in developing precision antimicrobial chemotherapy in patients.Continuous breakthroughs have been achieved in improving the efficiency of all-polymer solar cells (all-PSCs) using diimide-based polymer acceptors, and their easy-to-synthesize, low-cost, and high stability attributes make them potential candidates for use in commercial all-PSCs. However, their low light absorption coefficient, strong aggregation, and poor adaptability with high-efficient polymer donors still limit further improvements in the device performance. Here, we combine the advantages of fluorinated bithiophene and rhodanine dye molecules to create low-cost diimide-based polymer acceptors, PNDI-2FT-TR10 and PNDI-2FT-TR20, by random copolymerization for achieving highly efficient and stable all-PSCs. The synergistic effects of fluorine atoms and rhodanine dye molecules not only significantly improve the absorption coefficient but also enable enhanced miscibility and stability of the blend film. When blended with a PM6 donor, the PNDI-2FT-TR10-based device exhibits a notable power conversion efficiency (PCE) of 10.71% with a short-circuit current (JSC) of 17.32 mA cm-2. Note that both the PCE and JSC show outstanding values for diimide-based all-PSCs, and this is the first report on blending diimide-based polymer acceptors with the PM6 donor to achieve high-performance all-PSCs. Moreover, the favorable morphology of the active layer enables the device to have good thickness tolerance and thermal stability. The results demonstrate that the absorption coefficients, blend morphology, and photovoltaic properties of all-PSCs could be rationally optimized by a random copolymer.
Upper limb, in particular forequarter amputations, require highly customised devices that are often expensive and underutilised.
The objective of this study was to design and develop a comfortable 3D-printed cosmetic forequarter prosthetic device, which was lightweight, cool to wear, had an elbow that could lock, matched the appearance of the contralateral arm and was completely free of metal for a specific user's needs.
Device design.
An iterative user-centred design approach was used for digitising, designing and developing a functional 3D-printed prosthetic arm for an acquired forequarter amputation, while optimising the fit and function after each prototype.
The cost of the final arm was 20% less expensive than a traditionally-made forequarter prostheses in Singapore. The Quebec User Evaluation of Satisfaction with Assistive Technology (QUEST) 2.0 survey was administered, with results indicating that the 3D-printed arm was preferred due to its overall effectiveness, accurate size, ease of use and suspension. However, durability had a lower score, and the weight of the arm was 100 g heavier than the user's current prosthesis. The technique described resulted in a precise fitting and shaped forequarter prosthesis for the user. Using the user's feedback in the iterations of the design resulted in improved QUEST survey results indicating the device was effective, easy to use, perceived as lighter and more secure than the user's traditionally-made device.
A fully customised cosmetic forequarter prosthesis was designed and developed using digital scanning, computer-aided design modelling and 3D printing for a specific user. These technologies enable new avenues for highly complex prosthetic design innovations.
A fully customised cosmetic forequarter prosthesis was designed and developed using digital scanning, computer-aided design modelling and 3D printing for a specific user. These technologies enable new avenues for highly complex prosthetic design innovations.
Millions of people in low- and middle-income countries lack access to prosthetic care. A well-fitting, durable socket is important for prosthesis comfort and function, but conventional fabrication techniques require highly trained clinicians and specialized equipment.
To increase access to prosthetic care by developing a simple, low-cost socket fabrication method that does not require specialized equipment or electricity, and can be performed by persons with minimal prosthetic training.
Socket fabrication methods and socket function were evaluated in a pilot feasibility study.
We describe a rapid method for fabricating a rigid foam socket directly over the residual limb, with a mass producible, strong, cosmetically appealing plastic outer shell. We fabricated sockets for four individuals with unilateral transradial amputations and evaluated socket function.
An individual with no formal prosthetic training was able to fabricate sockets and assemble a functional, comfortable prosthesis system within 9sthesis socket can be fabricated in around 90 min. and all necessary materials, tools, and written instructions for fabrication and fitting can be provided in a kit. Specialized equipment and electricity are not required. Instructions for fabrication and fitting can be provided in multiple languages using online videos.
A 56-year-old man with persistent knee pain and poor physical functioning due to recurring loosening of a (revised) total knee arthroplasty, was treated with a modified Gritti-Stokes amputation.
to describe the modified Gritti-Stokes amputation technique as an ultimate therapy for failed total knee arthroplasty and to assess the functional outcome for one patient 1 year post-surgery.
a single patient case study.
a modified Gritti-Stokes amputation, with removal of the overlying cartilage and subchondral surfaces of both the patella and femur after removing the total knee arthroplasty.
After rehabilitation, the patient has a fully end-bearing residual limb, is able to walk without pain (with a prosthesis) and perform his daily activities.
In cases of recurring loosening of a (revised) total knee arthroplasty, a modified Gritti-Stokes amputation can create an end-bearing residual limb without pain and with good functional outcome.
In cases of recurring loosening of a (revised) total knee arthroplasty, a modified Gritti-Stokes amputation can create an end-bearing residual limb without pain and with good functional outcome.
Conventional methods for producing custom prosthetic fingers are time-consuming, can be uncomfortable for the patient, and require a skilled prosthetist. The subject was a 40-year-old male with congenital absence of the thumb and related metacarpal bone on the right non-dominant hand, anomaly of the lengths of individual upper limb segments, and contracture of the elbow joint. This hand presentation made it impossible for him to perform thumb opposition, which is a very important function for common daily activities.
The goal was to design an individual passive thumb prosthesis using free open-source software, 3D scanning technology, and additive manufacturing methods (i.e., fused filament fabrication).
Case report.
Artificial thumb prostheses with two types of bases and fastening interfaces were designed and manufactured. One combination was chosen as the best alternative.
The shape, positioning, firmness, and fastening of the prosthesis were compliant enough for the patient to be able to hold objects with his healthy fingers and artificial thumb. This innovative approach to fabrication of a custom thumb prosthesis provided considerable advantages in terms of custom sizing, manufacturing time, rapid production, iteration, comfort, and costs when compared to conventional methods of manufacturing a hand prosthesis.
The methodology of designing and manufacturing a prosthetic thumb using 3D scanning and additive manufacturing technologies have been demonstrated to be adequate from a practical point of view. These technologies show potential for use in the practice of prosthetics.
The methodology of designing and manufacturing a prosthetic thumb using 3D scanning and additive manufacturing technologies have been demonstrated to be adequate from a practical point of view. These technologies show potential for use in the practice of prosthetics.
Osseointegration is a relatively new technique for prosthetic limb attachment that offers various improvements for patients with amputation and facilitates joint preservation. We present a case of implant loosening during rehabilitation in a patient with transtibial amputation that was successfully managed through a combination of measures, aiming to promote re-osseointegration of the implant.
Not much is known about structured management of adverse events after osseointegration. Septic or aseptic loosening is currently regarded as implant failure, prompting removal and possible re-implantation at a later stage. The objective of this case report was to evaluate the feasibility of salvaging a loosened implant.
Case report.
A novel treatment approach was employed to enable renewed osseointegration of the implant. First, the bone-implant interface was disrupted and renewed through axial rotation and distal repositioning of the implant. Afterwards, extracorporal shockwave therapy and antibiotic treatment were administered.
