Carbon dot-based fluorescent antibody nanoprobes as brain tumour glioblastoma diagnostics.

The development of efficient and sensitive tools for the detection of brain cancer in patients is of the utmost importance particularly because many of these tumours go undiagnosed until the disease has advanced and when treatment is less effective. Current strategies employ antibodies (Abs) to detect Glial Fibrillary Acid Protein (GFAP) in tissue samples, since GFAP is unique to the brain and not present in normal peripheral blood, and it relies on fluorescent reporters. Herein we describe a low cost, practical and general method for the labelling of proteins and antibodies with fluorescent carbon dots (CD) to generate diagnostic probes that are robust, photostable and applicable to the clinical setting. The two-step protocol relies on the conjugation of a dibenzocyclooctyne (DBCO)-functionalised CD with azide functionalised proteins by combining amide conjugation and strain promoted alkyne-azide cycloaddition (SPAAC) ligation chemistry. The new class of Ab-CD conjugates developed using this strategy was successfully used for the immunohistochemical staining of human brain tissues of patients with glioblastoma (GBM) validating the approach. Overall, these novel fluorescent probes offer a promising and versatile strategy in terms of costs, photostability and applicability which can be extended to other Abs and protein systems.

Reengineering of cancer cell surface charges can modulate cell migration.

The ability to modulate the cell surface structure provides a powerful tool to understand fundamental processes and also to elicit desired cellular responses. Here we report the development of a new class of 'clickable labels' to reengineer the cell surface charges of live cells. The method relies on the use of metabolic oligosaccharide engineering (MOE) combined with chemo selective labeling of cell surface azido-containing sialic acids with dibenzocyclooctyne (DBCO) ionic-probes. Using this strategy, we demonstrate that reducing the negative charge induced by the overexpression of cell surface sialic acids in cancer cells leads to a reduction in cell migration without affecting drug supceptibility.

Postoperative Epidural Fibrosis Prevention: Which Is Better-Autologous Fat versus Gelfoam.

STUDY DESIGN: Prospective, randomized study of 100 patients with prolapsed intervertebral disc with an average of 12- to 18-month follow-up postoperatively. PURPOSE: To compare the role of Gelfoam and autologous fat in the prevention of postoperative epidural fibrosis (EF) after lumbar spine surgery. OVERVIEW OF LITERATURE: EF is a possible sequelae of lumbar disc surgery. Different treatments and surgical strategies have been attempted to prevent postoperative fibrosis without providing consistent long-term results. METHODS: The study was conducted on 100 adult patients. The patients were randomly allocated into two groups of 50 patients each: group A, autologous fat group, and group B, Gelfoam group. The postoperative follow-up was conducted at intervals of 6 weeks, 3 months, 6 months, and 12 months. Both groups were evaluated clinically (Oswestry Low Back Pain Disability Questionnaire [ODI], Visual Analog Scale [VAS], Straight Leg Raising Test [SLRT]) and radiologically (using Ross grading by contrast magnetic resonance imaging [MRI]) for development of radicular pain and hence EF. RESULTS: Based on the analysis, improvement in mean values of ODI score, VAS score, and SLRT were found to be statistically significant postoperatively at intervals of 6 weeks, 3 months, 6 months, and 12 months when compared individually in both groups. However, improvement was greater in the autologous fat group than in the Gelfoam group. Based on contrast-enhanced MRI, the number of patients who developed EF was smaller in the autologous fat group than in the Gelfoam group. CONCLUSIONS: In the present study, on clinical and radiological assessment, we conclude that both groups prevent radicular pain and postoperative EF individually but relatively autologous fat was found to be more effective than Gelfoam in the prevention of EF and hence radicular pain.

Correlation between Chondromalacia Patella and Patellofemoral Factors in Middle-Age Population: A Clinical, Functional, and Radiological Analysis.

Background Despite higher incidence of patellofemoral pain (PFP) and consequently morbidity, the understanding about PF factors leading to PF arthritis is way lacking. Material and Methods A prospective study of first 80 patients who were diagnosed with chondromalacia patella (CMP) on magnetic resonance imaging (MRI) divided into early and late CMP groups were evaluated clinically, radiologically, and in terms of functional outcome. Results : Quadriceps angle, Clark's test, and Insall-Salvati ratio results were nonsignificant despite greater values were observed in late CMP group, whereas trochlear morphology results (sulcus angle: 153:138 degrees and sulcus depth 3.9:5.4 mm) and clinical scores were significant in late CMP group (Kujala's score: 61:78, whereas PF pain score: 43:25). Type-C patellar morphology was found in greater number in late CMP cohort. Conclusion Trochlear and patellar morphologies along with clinical scores play a key role in understanding of the CMP.

A Prospective Observational Multi-institutional Study on Invasive Fungal Infections Following Chemotherapy for Acute Myeloid Leukemia (MISFIC Study): A Real World Scenario from India.

We performed a prospective multi-centre observational study to understand the incidence of IFI in patients with AML in India with use of anti-fungal prophylaxis. All patients with AML receiving either induction chemotherapy or salvage chemotherapy between November 2014 and February 2016 were included in this prospective observational study from 10 Indian centres. IFI was defined as per the revised EORTC-MSG criteria. Data on type of chemotherapy used, type of anti-fungal prophylaxis used, time to neutrophil recovery, incidence of IFI and survival were collected. Two hundred patients (118 male and 82 females) with a median age of 35 years (range: 2-66) were recruited. One hundred and eighty-six (93%) had newly diagnosed acute myeloid leukemia (AML) while 14 (7%) had relapsed disease. IFI occurred in 53 patients (26.5%) with proven or probable IFI occurring in 17 (8.5%). Use of posaconazole prophylaxis (p = 0.027) was the only factor found to be associated with a reduced incidence of IFI. The overall survival (OS) at 6 weeks and 3 months respectively was similar among patients who had IFI (83.0 ± 5.2%; 81.0 ± 5.4%) as compared to those without IFI (84.4 + 3.0%; 81.4 ± 3.2%). This prospective study reveals a high incidence of IFI in patients undergoing chemotherapy for AML in India. The use of posaconazole prophylaxis was associated with a significantly lower incidence of IFI. Optimal strategies to prevent IFI need to be studied.

NCα-gem-dimethylated peptoid side chains: A novel approach for structural control and peptide sequence mimetics.

The design of linear peptoid oligomers adopting well-defined secondary structures while mimicking defined peptide primary sequences is a major challenge in the context of drug discovery. To this end, chemists have developed cis-inducing peptoid side chains to build robust polyproline type I helices. However, the number of efficient examples remains scarce and chemical diversity accessible through the use of these side chains is limited. Herein, we introduce an array of NCα-gem-dimethylated peptoid residues mimicking proteinogenic amino acids. Submonomer synthesis and block-coupling approaches were explored to access heterooligomers incorporating these novel types of side chains. NMR studies of monomer and trimer models showed that the NCα-gem-dimethylated groups exert complete cis control on the backbone amide conformation. Lastly, a preliminary molecular modeling study gave an insight into the preferred orientation of the substituents of the NCα-gem-dimethyl side chains relative to the peptoid backbone.

1,2,3-Triazolium-Based Cationic Amphipathic Peptoid Oligomers Mimicking Antimicrobial Helical Peptides.

Amphipathic cationic peptoids (N-substituted glycine oligomers) represent a promising class of antimicrobial peptide mimics. The aim of this study is to explore the potential of the triazolium group as a cationic moiety and helix inducer to develop potent antimicrobial helical peptoids. Herein we report the first solid-phase synthesis of peptoid oligomers incorporating 1,2,3-triazolium-type side chains and their evaluation against Escherichia coli, Enterococcus faecalis, and Staphylococcus aureus. Several triazolium-based oligomers, even of short length, selectively kill bacteria over mammalian cells. SEM visualization of S. aureus cells treated with a dodecamer and a hexamer reveals severe cell membrane damage and suggests that the longer oligomer acts by pore formation.