The Spectrum of Clinical Utilities in Molecular Pathology Testing Procedures for Inherited Conditions and Cancer: A Report of the Association for Molecular Pathology

Clinical utility describes the benefits of each laboratory test for that patient. Many stakeholders have adopted narrow definitions for the clinical utility of molecular testing as applied to targeted pharmacotherapy in oncology, regardless of the population tested or the purpose of the testing. This definition does not address all of the important applications of molecular diagnostic testing. Definitions consistent with a patient-centered approach emphasize and recognize that a clinical test result\u27s utility depends on the context in which it is used and are particularly relevant to molecular diagnostic testing because of the nature of the information they provide. Debates surrounding levels and types of evidence needed to properly evaluate the clinical value of molecular diagnostics are increasingly important because the growing body of knowledge, stemming from the increase of genomic medicine, provides many new opportunities for molecular testing to improve health care. We address the challenges in defining the clinical utility of molecular diagnostics for inherited diseases or cancer and provide assessment recommendations. Starting with a modified analytic validity, clinical validity, clinical utility, and ethical, legal, and social implications model for addressing clinical utility of molecular diagnostics with a variety of testing purposes, we recommend promotion of patient-centered definitions of clinical utility that appropriately recognize the valuable contribution of molecular diagnostic testing to improve patient care

A semisynthetic glycoconjugate provides expanded cross-serotype protection against Streptococcus pneumoniae

Streptococcus pneumoniae (S. pneumoniae) infections are the leading cause of child mortality globally. Current vaccines fail to induce a protective immune response towards a conserved part of the pathogen, resulting in new serotypes causing disease. Therefore, new vaccine strategies are urgently needed. Described is a two-pronged approach combining S. pneumoniae proteins, pneumolysin (Ply) and pneumococcal surface protein A (PspA), with a precisely defined synthetic oligosaccharide, whereby the carrier protein acts as a serotype-independent antigen to provide additional protection. Proof of concept in mice and swine models revealed that the conjugates inhibited colonization of the nasopharynx, decreased the bacterial load and reduced disease severity in the bacteria challenge model. Immunization of piglets provided the first evidence for the immunogenicity and protective potential of synthetic glycoconjugate vaccine in a large animal model. A combination of synthetic oligosaccharides with proteins from the target pathogen opens the path to create broadly cross-protective (“universal”) pneumococcal vaccines

Synthetic vaccines against Streptococcus pneumoniae serotype 2

The present invention relates to a synthetic saccharide of general formula (I) that is related to Streptococcus pneumoniae serotype 2 capsular polysaccharide, a conjugate thereof and the use of said saccharide and conjugate for raising a protective immune response in a human and/or animal host. Furthermore, the synthetic saccharide of general formula (I) is useful as marker in immunological assays for detection of antibodies against Streptococcus pneumoniae type 2 bacteria. Another aspect of the present invention is directed to an antibody having specificity for a synthetic saccharide of general formula (I)

Orthogonally protected D-galactosamine thioglycoside building blocks via highly regioselective, double serial and double parallel inversions of beta-D-thiomannoside

An efficient route for the synthesis of orthogonally protected D-galactosamine thioglycosides via one-pot double serial and double parallel displacements of the D-mannosyl-2,4-bis-trifluoromethanesulfonates by azide and nitrite ions is described. These building blocks were utilized to synthesize the rare disaccharide moiety of the zwitterionic polysaccharide of Bacteroides fragilis and the selectively protected Tn antigen

Synthesis of orthogonally protected bacterial, rare-sugar and d-glycosamine building blocks

Bacterial glycoconjugates comprise atypical deoxy amino sugars that are not present on the human cell surface, making them good targets for drug discovery and carbohydrate-based vaccine development. Unfortunately, they cannot be isolated with sufficient purity in acceptable amounts, and therefore chemical synthesis is a crucial step toward the development of these products. Here we describe a detailed protocol for the synthesis of orthogonally protected bacterial deoxy amino hexopyranoside (2,4-diacetamido-2,4,6-trideoxyhexose (DATATDH), d-bacillosamine, d-fucosamine, and 2-acetamido-4-amino-2,4,6-trideoxy-dgalactose (AATAATAAT)), d-glucosamine and d-galactosamine building blocks starting from beta-d-thiophenylmannoside. Readily available beta-d-thiophenylmannoside was first converted into the corresponding 2,4-diols via deoxygenation or silylation at C6, followed by O3 acylation. The 2,4-diols were converted into 2,4-bis-trifluoromethanesulfonates, which underwent highly regioselective, one-pot, double-serial and double-parallel displacements by azide, phthalimide, acetate and nitrite ions as nucleophiles. Thus, d-rhamnosyl-and d-mannosyl 2,4-diols can be efficiently transformed into various rare sugars and d-galactosamine, respectively, as orthogonally protected thioglycoside building blocks on a gram scale in 1-2 d, in 54-85% overall yields, after a single chromatographic purification. This would otherwise take 1-2 weeks. d-Glucosamine building blocks can be prepared from beta-d-thiophenylmannoside in four steps via C2 displacement of triflates by azide in 2 d and in 66-70% overall yields. These procedures have been applied to the synthesis of l-serine-linked trisaccharide of Neisseria meningitidis and a rare disaccharide fragment of the zwitterionic polysaccharide (ZPSPS) A1 (ZPSPS A1) of Bacteroides fragilis

Expeditious synthesis of bacterial, rare sugar building blocks to access the prokaryotic glycome

Bacteria have unusual glycans which are not accessible by isolation. Herein, we describe a general and divergent strategy for the synthesis of the rare, bacterial deoxy amino hexopyranoside building blocks from D-mannose. The methodology is applied to the first total synthesis of the L-serine linked trisaccharide of Neisseria meningitidis

Expeditious Synthesis of Ieodoglucomides A and B from the Marine-Derived Bacterium Bacillus licheniformis

We report the total synthesis of ieodoglucomides A and B. The key steps of the synthesis are a glycosyl-iodide-mediated -stereoselective glycosylation without neighbouring-group participation, a regioselective acylation, and a Grubbs cross-metathesis reaction. The short and efficient synthesis involves 11 steps, with 38-40% overall yield

Total synthesis of MECA-79

The MECA-79 antigen is a sulfated mucin type core-1 extended O-glycan which is a potential anti-inflammatory agent. Herein we report a total synthesis of MECA-79 via a convergent [2 + 2] glycosylation route. The synthesis relies on efficient transformation of D-glucosamine into the orthogonally protected Tn antigen derivative and its elaboration into the TF antigen en route to MECA-79

Effect of oil pulling on <i>Streptococcus mutans</i> count in plaque and saliva using Dentocult SM Strip mutans test: A randomized, controlled, triple-blind study

<b>Background:</b> Oil pulling has been used extensively for many years, without scientific evidence or proof, as a traditional Indian folk remedy to prevent teeth decay, oral malodor, bleeding gums, dryness of throat and cracked lips, and for strengthening the teeth, gums, and jaws. <b>Aims:</b> The aim of this study was to evaluate the effect of oil pulling with sesame oil on the count of <i>Streptococcus mutans</i> in plaque and saliva of children, using the Dentocult SM Strip mutans test, and to compare its efficacy with that of chlorhexidine mouthwash. <b>Materials and Methods:</b> Twenty age-matched adolescent boys were selected based on information obtained through a questionnaire. They were divided randomly into two groups: the control or chlorhexidine group (group I) and the study or oil pulling group (group II); there were ten subjects in each group. Plaque and saliva samples were collected from all the 20 subjects on the strips from the Dentocult SM kit and, after incubation, the presence of <i>S. mutans</i> was evaluated using the manufacturers&#x2032; chart. The study group practiced oil pulling with sesame oil and the control group used chlorhexidine mouthwash for 10 min every day in the morning before brushing. Samples were collected from both groups after 24 h, 48 h, 1 week, and 2 weeks and the efficacy of oil pulling was compared with that of chlorhexidine mouthwash. <b>Results:</b> There was a reduction in the <i>S. mutans</i> count in the plaque and saliva samples of both the study and the control groups. The reduction in the <i>S. mutans</i> count in the plaque of the study group was statistically significant after 1 and 2 weeks (<i>P</i> = 0.01 and <i>P</i> = 0.008, respectively); the control group showed significant reduction at all the four time points (<i>P</i> = 0.01, <i>P</i> = 0.04, <i>P</i> = 0.005, and <i>P</i> = 0.005, respectively, at 24 h, 48 h, 1 week, and 2 weeks). In the saliva samples, significant reduction in <i>S. mutans</i> count was seen in the control group at 48 h, 1 week, and 2 weeks (<i>P</i> = 0.02, <i>P</i> = 0.02, <i>P</i> = 0.008, respectively). <b>Conclusion: </b>Oil pulling can be used as an effective preventive adjunct in maintaining and improving oral health