Project description:Malaria eradication involves eliminating malaria from every country where transmission occurs. Current theory suggests that the post-elimination challenges of remaining malaria-free by stopping transmission from imported malaria will have onerous operational and financial requirements. Although resurgent malaria has occurred in a majority of countries that tried but failed to eliminate malaria, a review of resurgence in countries that successfully eliminated finds only four such failures out of 50 successful programmes. Data documenting malaria importation and onwards transmission in these countries suggests malaria transmission potential has declined by more than 50-fold (i.e. more than 98%) since before elimination. These outcomes suggest that elimination is a surprisingly stable state. Elimination's 'stickiness' must be explained either by eliminating countries starting off qualitatively different from non-eliminating countries or becoming different once elimination was achieved. Countries that successfully eliminated were wealthier and had lower baseline endemicity than those that were unsuccessful, but our analysis shows that those same variables were at best incomplete predictors of the patterns of resurgence. Stability is reinforced by the loss of immunity to disease and by the health system's increasing capacity to control malaria transmission after elimination through routine treatment of cases with antimalarial drugs supplemented by malaria outbreak control. Human travel patterns reinforce these patterns; as malaria recedes, fewer people carry malaria from remote endemic areas to remote areas where transmission potential remains high. Establishment of an international resource with backup capacity to control large outbreaks can make elimination stickier, increase the incentives for countries to eliminate, and ensure steady progress towards global eradication. Although available evidence supports malaria elimination's stickiness at moderate-to-low transmission in areas with well-developed health systems, it is not yet clear if such patterns will hold in all areas. The sticky endpoint changes the projected costs of maintaining elimination and makes it substantially more attractive for countries acting alone, and it makes spatially progressive elimination a sensible strategy for a malaria eradication endgame.
Project description:Chinese hamster ovary (CHO) cells serve as protein therapeutics workhorses, so it is useful to understand what intrinsic properties make certain host cell lines and clones preferable for scale up and production of target proteins. In this study, two CHO host cell lines (H1, H2), and their respective clones were evaluated using comparative TMT-proteomics. The clones obtained from host H1 showed increased productivity (6.8 times higher) in comparison to clones from host H2. Based on fold-change analyses, we observed differential regulation in pathways including cell adhesion, aggregation, and cellular metabolism among others. In particular, the cellular adhesion pathway was downregulated in H1, in which podoplanin, an antiadhesion molecule, was upregulated the most in host H1 and associated clones. Phenotypically, these cells were less likely to aggregate and adhere to surfaces. In addition, enzymes involved in cellular metabolism such as isocitrate dehydrogenase (IDH) and mitochondrial-d-lactate dehydrogenase ( d-LDHm) were also found to be differentially regulated. IDH plays a key role in TCA cycle and isocitrate-alpha-ketoglutarate cycle while d-LDHm aids in the elimination of toxic metabolite methylglyoxal, involved in protein degradation. These findings will enhance our efforts towards understanding why certain CHO cell lines exhibit enhanced performance and perhaps provide future cell engineering targets.
Project description:This case report describes an uncommon cardiac complication related to the endoscopic injection of cyanoacrylate glue to treat gastric variceal bleeding. The presentation and management options are reviewed and compared with our step-by-step approach in a patient requiring a liver transplant. (Level of Difficulty: Advanced.).
Project description:The purpose of this article is to describe challenges associated with successful use of continuous glucose monitoring (CGM) by young children with type 1 diabetes (T1D) and to detail the techniques and products used to improve the duration of sensor wear. The DirecNet Study Group conducted 2 studies in 169 children with T1D between the ages of 1 and 9 years who were instructed to wear a CGM device daily. Problems related to skin irritation and sensor adhesiveness in these young children presented challenges to daily use of the CGM. Study coordinators instituted a variety of techniques using commercially available products to attempt to overcome these problems. Three primary factors that contributed to reduced CGM use were identified: the limited body surface area in smaller children, ambient temperature and humidity, as well as the type and duration of physical activity. Using supplemental products to minimize the impact of these factors resulted in improved adherence and reduced skin irritation. Achieving satisfactory adhesion of the CGM sensor and transmitter may involve finding the right supplemental product or combination of products through trial and error. Optimizing adhesion and minimizing skin irritation can significantly improve duration of use and tolerability of CGM devices by young children.
Project description:The demographic shift has increased the demand for surgical interventions to address age-related degenerative diseases, such as spinal fusion. Accurate placement of pedicle screws, crucial for successful spinal fusion, varies widely with physician experience. Integrating tissue sensing into spine surgical instruments allows intraoperative examination of tissue properties, providing surgeons with additional information to prevent screw misplacement. This paper introduces a handheld fiber-optic tissue sensing device for real-time bone tissue differentiation during spine surgery using Diffuse Reflectance Spectroscopy (DRS). Our prototype employs laser diodes at two distinct wavelengths for tissue illumination, eliminating the need for a spectrometer and enabling direct light collection with a photodiode. The device includes a printed circuit board (PCB) with driver circuits that are adjustable for varying laser diode output power, and signal amplification to convert the photodiode current to a measurable voltage signal. Controlled by a microcontroller, the device computes a reflectance ratio from both laser diode signals to provide real-time audio feedback to surgeons across various healthcare settings. Despite challenges in coupling efficiencies from manual fiber-coupling of the diodes, our prototype is able to emit and collect light to distinguish bone tissues with DRS, demonstrating feasibility. It is compact, made of low-cost and readily available components, and offers fast, real-time feedback, thus serving as a successful proof-of-concept for enhancing surgical accuracy during spinal fusion procedures.
Project description:Marine and terrestrial organisms often utilise EGF/EGF-like domains in wet adhesives, yet their roles in adhesion remain unclear. Here, we investigate the Barbatia virescense byssal system and uncover an oxidation-independent, reversible, and robust adhesion mechanism where EGF/EGF-like domain tandem repetitions in adhesive proteins bind robustly to GlcNAc-based biopolymer. EGF/EGF-like-domain-containing proteins demonstrate over three-fold superior underwater adhesion to chitosan compared to the well-known strongest wet-adhesive proteins, mefp-5, and suckerin, when adhering to mica in an surface forces apparatus-based measurement. Additionally, as the degree of acetylation of chitosan decreases from 20.0 to 5.34%, the underwater adhesion energy between mefp-2 and chitosan decreases from |Wad | ≈ 41.80 to 12.92 ± 0.40 mJm-2. This finding highlights the importance of GlcNAc over GlcN in binding with EGF to formulate effective underwater adhesives, expanding our understanding of underwater adhesion and supporting EGF's functional role in biomedical wet adhesive interfaces, hydrogels, and chitosan applications.
Project description:BackgroundPlatelet function testing to monitor antiplatelet therapy is important for reducing thromboembolic complications, yet variability across testing methods remains challenging. Here we evaluated the agreement of four different testing platforms used to monitor antiplatelet effects of aspirin (ASA) or P2Y12 inhibitors (P2Y12-I).MethodsBlood and urine specimens from 20 patients receiving dual antiplatelet therapy were analyzed by light transmission aggregometry (LTA), whole blood aggregometry (WBA), VerifyNow PRUTest and AspirinWorks. Result interpretation based on pre-defined cutoff values was used to calculate raw agreement indices, and Pearson's correlation coefficient determined using individual units of measure.ResultsAgreement between LTA and WBA for P2Y12-I-response was 60% (r = 0.65, high-dose ADP; r = 0.75, low-dose ADP). VerifyNow agreed with LTA in 75% (r = 0.86, high-dose ADP; r = 0.75, low-dose ADP) and WBA in 55% (r = 0.57) of cases. Agreement between LTA and WBA for ASA-response was 45% (r = 0.09, high-dose collagen WBA; r = 0.19, low-dose collagen WBA). AspirinWorks agreed with LTA in 60% (r = 0.32) and WBA in 35% (r = 0.02, high-dose collagen WBA; r = 0.08, low-dose collagen WBA) of cases.ConclusionsOverall agreement varied from 35 to 75%. LTA and VerifyNow demonstrated the highest agreement for P2Y12-I-response, followed by moderate agreement between LTA and WBA. LTA and AspirinWorks showed moderate agreement for aspirin response, while WBA showed the weakest agreement with both LTA and AspirinWorks. The results from this study support the continued use of LTA for monitoring dual antiplatelet therapy, with VerifyNow as an appropriate alternative for P2Y12-I-response. Integration of results obtained from these varied testing platforms with patient outcomes remains paramount for future studies.
Project description:Existing tissue adhesives and sealants are far from satisfactory when applied on wet and dynamic tissues. Herein, we report a strategy for designing biodegradable super-strong aqueous glue (B-Seal) for surgical uses inspired by an English ivy adhesion strategy and a cement particle packing theory. B-Seal is a fast-gelling, super-strong, and elastic adhesive sealant composed of injectable water-borne biodegradable polyurethane (WPU) nanodispersions with mismatched particle sizes and counterions in its A-B formulation. B-Seal showed 24-fold greater burst pressure than DuraSeal®, 138-fold greater T-pull adhesive strength than fibrin glue, and 16-fold greater lap shear strength than fibrin glue. In vivo evaluation on a rat cerebrospinal fluid (CSF) rhinorrhea model and a porcine craniotomy model validated the safety and efficacy of B-Seal for effective CSF leak prevention and dura repair. The plant-inspired adhesion strategy combined with particle packing theory represents a new direction of designing the next-generation wet tissue adhesives for surgeries.
Project description:With the increasing number of survivors with congenital heart disease (CHD) reaching adulthood, it is important for the clinician to be familiar with the various surgical options performed in this growing patient population. We describe the case of a 65-year-old female who presented with hypoxia and right-to-left shunting following a surgical repair of an atrial septal defect (ASD) secundum and anomalous pulmonary veins with a partial atrial diversion procedure in childhood. The use of multimodality cardiovascular imaging using echocardiography, computed tomography, magnetic resonance imaging, and invasive cardiac catheterization was complementary in the preoperative diagnosis and management of this unique baffling situation.