The Mechanisms of Chondroitin Sulphate Lyases Treatment in Promotion of Axonal Growth

Poster PresentationIn Injured nerves, chondroitin sulphate (CS) is upregulated forming barriers with astrocytes/fibroblasts and other extracellular matrix molecules, and thereby hampering nerve regeneration. Cleavage of CS using chondroitin sulphate lyases (Proteus vulgaris) promises axon regrowth through the barrier but the enzymatic efficacy remains to be improved. Two subtypes, endolyase and exolyase, have been found coexisting in the original host but only the former has been exploited for treatment of injured nerve tracts. We hypothesise that the two subtypes are necessary for enzymatic efficacy on CSs. We therefore prepared recombinant enzymes of both subtypes. Enzyme kinetics study revealed feedback inhibition by limit digestion products: that of the endolyase by tetrasaccharides and that of the exolyase by the disaccharides. When the two subtypes were used in combination, the digestion efficiency increased. We then used TGF beta-1 to induce CS production by astrocytes in culture, mimicking reactive glia in injured nerves. In co-cultures of such astrocytes with cortical neurons, treatment with combinations of the two subtypes resulted in increased neurite lengths as compared to co-cultures treated with one of the subtypes. The limit digestion products of CS were further tested for their effects on neurite extension on astrocytes that had been treated with TGF beta-1. The CS disaccharides, both 4- and 6-sulphated but not the tetrasaccharides, promoted neurite extension significantly. Taken together, the combinatorial use of the ChABC subtypes not only improved efficacy of enzyme activity on the axon-restrictive CS moiety, but also increased the yield of CS disaccharides which contributed to axonal growth.published_or_final_versio

A Mobile App Platform for Discovering Learning Profiles and Analytics

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Directed differentiation of human bone marrow stromal cells to fate-committed Schwann cells

Transplantation of oligodendrocyte precursors represents a potential therapy for myelin disorders but requires a safe and accessible cell source. Here we report the directed differentiation of neural progenitors derived from adult bone marrow stromal cells (BMSCs) into oligodendrocyte precursors for cell therapy purpose. Neural progenitors among BMSCs could be culture expanded in non-adherent sphere-forming conditions and directed to differentiate along the oligodendrocyte lineage. BMSC-derived oligodendrocyte precursors (BM-OPs) differentiated into myelin basic protein (MBP)-positive oligodendrocyte when co-cultured with purified dorsal root ganglion (DRG) neurons. Injection of BM-OPs into the brain of myelin deficient Shiverer mice resulted in the generation of MBP-positive oligodendrocyte and compact myelin. Our results provided pointers to adult BMSCs as a readily accessible source of OPs towards cell therapy for myelin disorders.published_or_final_versio

Intraoperative fracture of phacoemulsification sleeve

<p>Abstract</p> <p>Background</p> <p>We describe a case of intraoperative fracture of phacoemulsification sleeve during phacoemulsification surgery.</p> <p>Case presentation</p> <p>Phacoemulsification surgery was performed in the left eye of a 58-year-old lady with grade II nuclear sclerosis & grade I cortical cataract. Towards the end of quadrant removal, there was anterior chamber instability with impaired followability of nuclear fragments. The distal part of the fractured sleeve remained inside the anterior chamber upon removal of the phacoemulsification probe. The retained sleeve was retrieved with a pair of forceps through the corneal incision site, which did not require widening. There was no missing fragments retained intraocularly and the patient had an uneventful recovery with vision of 20/25 at three months post-operatively.</p> <p>Conclusion</p> <p>Phacoemulsification sleeve fracture is an uncommon complication. With early identification of this condition and proper management, major complications can be avoided.</p

Enhanced follicular delivery of finasteride to human scalp skin using heat and chemical penetration enhancers

© The Author(s) 2020. This article is an open access publication. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.Purpose The aim of this work was to evaluate whether improved topical delivery of finasteride, focussed to the hair follicles of human scalp skin could be achieved with application of short durations of heat and use of specific chemical penetration enhancers. Methods Franz cell experiments with human scalp skin were performed with a range of chemical penetration enhancers at 32°C and 45°C to simulate normal and heated conditions. Selected chemical penetration enhancers were taken forward for finite dose Franz cell studies which examined the effect of heat produced by a prototype external heating system that supplied either 20 or 30 min of additional heat over both a 24 h and a 1 h time period. Results Short durations of externally applied heat significantly increased finasteride penetration into human scalp skin after 24 h. Analysis of drug distribution in the skin after 1 h and 24 h indicated that both heat and chemical penetration enhancer selection influenced drug delivery to the hair follicles. Conclusion The use of short durations of heat in combination with specific chemical penetration enhancers was able to increase the delivery of finasteride to human scalp skin and provide focussed drug delivery to the hair follicles.Peer reviewe

The Immature Heart: The Roles of Bone Marrow Stromal Stem Cells in Growth and Myocardial Repair

Studies have shown that adult bone marrow derived stem cells (MSCs) can participate in repair of myocardial injury in adult hearts, as well as in cardiac growth during fetal development in utero. Yet, no studies have evaluated the role of MSCs with respect to normal growth or tissue repair in immature hearts after birth. The present study examines whether MSCs may participate in the myocardial growth and injury in the post-natal immature hearts. MSCs were isolated from adult Lewis rats and labeled with Lac-Z gene using retroviral vectors. These MSCs were injected systemically into groups of neonatal (NB=2days-old), immature (B=30days-old) and adult (A=>3months-old) isogeneic Lewis rats. Additionally, left coronary artery ligation was carried out in subgroups of immature (BL) and adult (AL) rats one week after MSCs injection. The hearts were harvested serially from 2-days to 6-weeks, stained with X-Gal for labeled MSCs. Cardiomyocyte phenotypic expression was evaluated by immunohistological staining for Troponin I-C and Connexin-43. Labeled MSCs were found to home into the bone marrow in all rats of different developmental stages. They could be recruited from bone marrow into the infarcted site of myocardium only in groups AL and BL. They were also capable of differentiating into cardiomyocyte phenotype after myocardial injury. In contrast to that reported in the developing fetus, MSCs did not appear to contribute to the growth of non-injured hearts after birth. However, they can be recruited from the bone marrow and regenerate damaged myocardium both in the adult and in the immature hearts

Functional antibody and T cell immunity following SARS-CoV-2 infection, including by variants of concern, in patients with cancer: the CAPTURE study

Patients with cancer have higher COVID-19 morbidity and mortality. Here we present the prospective CAPTURE study, integrating longitudinal immune profiling with clinical annotation. Of 357 patients with cancer, 118 were SARS-CoV-2 positive, 94 were symptomatic and 2 died of COVID-19. In this cohort, 83% patients had S1-reactive antibodies and 82% had neutralizing antibodies against wild type SARS-CoV-2, whereas neutralizing antibody titers against the Alpha, Beta and Delta variants were substantially reduced. S1-reactive antibody levels decreased in 13% of patients, whereas neutralizing antibody titers remained stable for up to 329 days. Patients also had detectable SARS-CoV-2-specific T cells and CD4+ responses correlating with S1-reactive antibody levels, although patients with hematological malignancies had impaired immune responses that were disease and treatment specific, but presented compensatory cellular responses, further supported by clinical recovery in all but one patient. Overall, these findings advance the understanding of the nature and duration of the immune response to SARS-CoV-2 in patients with cancer

Secure Computation with Constant Communication Overhead using Multiplication Embeddings

Secure multi-party computation (MPC) allows mutually distrusting parties to compute securely over their private data. The hardness of MPC, essentially, lies in performing secure multiplications over suitable algebras. Parties use diverse cryptographic resources, like computational hardness assumptions or physical resources, to securely compute these multiplications. There are several cryptographic resources that help securely compute one multiplication over a large finite field, say $\mathbb{G}\mathbb{F}[2^n]$, with linear communication complexity. For example, the computational hardness assumption like noisy Reed-Solomon codewords are pseudorandom. However, it is not known if we can securely compute, say, a linear number of AND-gates from such resources, i.e., a linear number of multiplications over the base field $\mathbb{G}\mathbb{F}[2]$. Before our work, we could only perform $o(n)$ secure AND-evaluations. This example highlights the general inefficiency of multiplying over the base field using one multiplication over the extension field. Our objective is to remove this hurdle and enable secure computation of boolean circuits while incurring a constant communication overhead based on more diverse cryptographic resources. Technically, we construct a perfectly secure protocol that realizes a linear number of multiplication gates over the base field using one multiplication gate over a degree-$n$ extension field. This construction relies on the toolkit provided by algebraic function fields. Using this construction, we obtain the following results. If we can perform one multiplication over $\mathbb{G}\mathbb{F}[2^n]$ with linear communication using a particular cryptographic resource, then we can also evaluate linear-size boolean circuits with linear communication using the same cryptographic resource. In particular, we provide the first construction that computes a linear number of oblivious transfers with linear communication complexity from the computational hardness assumptions like noisy Reed-Solomon codewords are pseudorandom, or arithmetic-analogues of LPN-style assumptions. Next, we highlight the potential of our result for other applications to MPC by constructing the first correlation extractor that has $1/2$ resilience and produces a linear number of oblivious transfers

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

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