Making the longest sugars: a chemical synthesis of heparin-related [4](n) oligosaccharides from 16-mer to 40-mer

The chemical synthesis of long oligosaccharides remains a major challenge. In particular, the synthesis of glycosaminoglycan (GAG) oligosaccharides belonging to the heparin and heparan sulfate (H/HS) family has been a high profile target, particularly with respect to the longer heparanome. Herein we describe a synthesis of the longest heparin-related oligosaccharide to date and concurrently provide an entry to the longest synthetic oligosaccharides of any type yet reported. Specifically, the iterative construction of a series of [4]n-mer heparin-backbone oligosaccharides ranging from 16-mer through to the 40-mer in length is described. This demonstrates for the first time the viability of generating long sequence heparanoids by chemical synthesis, via practical solution-phase synthesis. Pure-Shift HSQC NMR provides a dramatic improvement in anomeric signal resolution, allowing full resolution of all 12 anomeric protons and extrapolation to support anomeric integrity of the longer species. A chemically pure 6-O-desfulfated GlcNS-IdoAS icosasaccharide (20-mer) represents the longest pure synthetic heparin-like oligosaccharide

Innovative development of the inspired sinewave device to measure lung functions and inhomogeneity for diagnosis and evaluations of early lung diseases

Surprisingly, lung disease is still one of the leading causes of deaths in the developed countries, including UK. According to the UK National Health Service (NHS), Chronic Obstructive Pulmonary Disease (COPD) is the fifth biggest killer disease in the UK, killing approximately 25,000 people a year. This prob-lem is even worse in developing countries such as Vietnam, India and China, where air pollution is a big problem and the disease awareness is under-recognised. The NHS has set out one of its challenges is to identify people with lung disease earlier in the disease’s development pathway, in order to pro-vide more effective and timely intervention and treatment. This paper presents a novel Inspired Sinewave Device (ISD) to measure lung function and inhomogeneity. Both set of infor-mation are important for diagnosis and detection of early lung diseases. ISD has the potential to replace or supplement the traditional spirometry in the routine lung function testing. The paper describes both the principle of ISD and a set of experi-mental results demonstrating the capability of ISD to asymp-totically detect asthmatic symptoms. Finally the paper discuss-es the future plan, including the testing of 300+ COPD patients at the Oxford Respiratory Trials Unit in UK, and the potential collaborations among research institutions in Vietnam and UK about cost-effective and innovative developments of smart devices, biosensors, lab-on-chips and telehealth solutions for the routine lung function testing, diagnosis and evaluations of early lung diseases

On the geometry of C^3/D_27 and del Pezzo surfaces

We clarify some aspects of the geometry of a resolution of the orbifold X = C3/D_27, the noncompact complex manifold underlying the brane quiver standard model recently proposed by Verlinde and Wijnholt. We explicitly realize a map between X and the total space of the canonical bundle over a degree 1 quasi del Pezzo surface, thus defining a desingularization of X. Our analysis relys essentially on the relationship existing between the normalizer group of D_27 and the Hessian group and on the study of the behaviour of the Hesse pencil of plane cubic curves under the quotient.Comment: 23 pages, 5 figures, 2 tables. JHEP style. Added references. Corrected typos. Revised introduction, results unchanged

Components as processes: an exercise in coalgebraic modeling

IFIP TC6/WG6.1. Fourth International Conference on Formal Methods for Open Object-Based Distributed Systems (FMOODS 2000) September 6–8, 2000, Stanford, California, USASoftware components, arising, typically, in systems ’ analysis and design, are characterized by a public interface and a private encapsulated state. They persist (and evolve) in time, according to some behavioural patterns. This paper is an exercise in modeling such components as coalgebras for some kinds of endofunctors on , capturing both (interface) types and behavioural aspects. The construction of component categories, cofibred over the interface space, emerges by generalizing the usual notion of a coalgebra morphism. A collection of composition operators as well as a generic notion of bisimilarity, are discussed

Cellular Immune Function in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating condition with unknown aetiology, Myalgic encephalomyelitis unclear pathophysiology and with no diagnostic test or biomarker available. Many patients report their ME/CFS began after an acute infection, and subsequent increased frequency of infections, such as colds or influenza, is common. These factors imply an altered immunological status exists in ME/CFS, in at least a proportion of patients, yet previous studies of peripheral immunity have been discrepant and inconclusive. The UK ME/CFS Biobank, which has collected blood samples from nearly 300 clinically-confirmed ME/CFS patients, enables large-scale studies of immunological function in phenotypically well-characterised participants. In this study, herpes virus serological status and T cell, B cell, NK cell and monocyte populations were investigated in 251 ME/CFS patients, including 54 who were severely affected, and compared with those from 107 healthy participants and with 46 patients with Multiple Sclerosis. There were no differences in seroprevalence for six human herpes viruses between ME/CFS and healthy controls, although seroprevalence for the Epstein-Barr virus was higher in multiple sclerosis patients. Contrary to previous reports, no significant differences were observed in NK cell numbers, subtype proportions or in vitro responsiveness between ME/CFS patients and healthy control participants. In contrast, the T cell compartment was altered in ME/CFS, with increased proportions of effector memory CD8+ T cells and decreased proportions of terminally differentiated effector CD8+ T cells. Conversely, there was a significantly increased proportion of mucosal associated invariant T cells (MAIT) cells, especially in severely affected ME/CFS patients. These abnormalities demonstrate that an altered immunological state does exist in ME/CFS, particularly in severely affected people. This may simply reflect ongoing or recent infection, or may indicate future increased susceptibility to infection. Longitudinal studies of ME/CFS patients are needed to help to determine cause and effect and thus any potential benefits of immuno-modulatory treatments for ME/CFS

Obesity and motor skills among 4 to 6-year-old children in the united states: nationally-representative surveys

Few population-based studies have assessed relationships between body weight and motor skills in young children. Our objective was to estimate the association between obesity and motor skills at 4 years and 5-6 years of age in the United States. We used repeated cross-sectional assessments of the national sample from the Early Childhood Longitudinal Survey-Birth Cohort (ECLS-B) of preschool 4-year-old children (2005-2006; n = 5 100) and 5-6-year-old kindergarteners (2006-2007; n = 4 700). Height, weight, and fine and gross motor skills were assessed objectively via direct standardized procedures. We used categorical and continuous measures of body weight status, including obesity (Body Mass Index (BMI) ≥ 95th percentile) and BMI z-scores. Multivariate logistic and linear models estimated the association between obesity and gross and fine motor skills in very young children adjusting for individual, social, and economic characteristics and parental involvement.info:eu-repo/semantics/publishe

Weight management in a cohort of Irish inpatients with serious mental illness (SMI) using a modular behavioural programme. A preliminary service evaluation

<p>Abstract</p> <p>Background</p> <p>Weight gain is commonly observed during psychotropic treatments for chronic forms of severe mental illness and is most rapid during the early treatment phases. All formats of behavioural weight intervention programmes have suggested that weight gain can be prevented or reversed in some patients. There is no data on these programmes in acutely unwell inpatients whom may be the major beneficiaries.</p> <p>Methods</p> <p>A modular behavioural intervention programme (Solutions for Wellness) used in SMI outpatients since 2002 in Ireland has been adapted for inpatient use. Preliminary data is reported from 5 centres in Ireland.</p> <p>Results</p> <p>In 47 inpatients the mean weight change was +0.26 kg (SD 2.02) with a median change of 0 kg. Mean follow-up was 23.7 (SD 21.6) days, and median 14 days (range 6–98 days). There was no difference in mean weight change in those patients involved for > 35 days compared with < 35 days (+0.26 kg; 0.25 kg; p = 0.5). Weight loss or maintenance was seen in 70% of patients.</p> <p>Conclusion</p> <p>These preliminary data are supportive of the concept that acutely unwell inpatients with SMI may engage with a behavioural weight programme. Weight change observed contrasts with the significant weight gain often seen in most subjects. Further clinical trials are warranted.</p

Mycobacterium tuberculosis-stimulated whole blood culture to detect host biosignatures for tuberculosis treatment response

Supplementary data are available online at https://www.sciencedirect.com/science/article/pii/S1472979221000329?via%3Dihub#appsec1 .Host markers to monitor the response to tuberculosis (TB) therapy hold some promise. We evaluated the changes in concentration of Mycobacterium tuberculosis (M.tb)-induced soluble biomarkers during early treatment for predicting short- and long-term treatment outcomes. Whole blood samples from 30 cured and 12 relapsed TB patients from diagnosis, week 1, 2, and 4 of treatment were cultured in the presence of live M.tb for seven days and patients followed up for 24 weeks after the end of treatment. 57 markers were measured in unstimulated and antigen-stimulated culture supernatants using Luminex assays. Top performing multi-variable models at diagnosis using unstimulated values predicted outcome at 24 months after treatment completion with a sensitivity of 75.0% (95% CI, 42.8–94.5%) and specificity of 72.4% (95% CI, 52.8–87.3%) in leave-one-out cross validation. Month two treatment responder classification was correctly predicted with a sensitivity of 79.2% (95% CI, 57.8–92.9%) and specificity of 92.3% (95% CI, 64.0–99.8%). This study provides evidence of the early M.tb-specific treatment response in TB patients but shows that the observed unstimulated marker models are not outperformed by stimulated marker models. Performance of unstimulated predictive host marker signatures is promising and requires validation in larger studies.Bill and Melinda Gates Foundation (TB Drug Accelerator Program, grant number 48941); Action TB by GSK; EDCTP (01.T.d1, Grant number 2004.1.R.d1); the South African Technology for Human Resources and Industry Program (THRIP); and an International Collaborations in Infectious Diseases Research grant from the National Institute of Allergy and Infectious Diseases (grant number 5U01IA115619). This research was also partially funded by the South African government through the South African Medical Research Council, through a grant from the Strategic Health Innovations Partnership (SHIP) unit, by the South African National Research Foundation through a South African Research Chair Initiative: Biomarkers for TB (grant number 86535) and a South African Department of Science and Innovation/National Research Foundation funded Centre of Excellence in Biomedical Tuberculosis Research

Association analysis between symptomology and herpesvirus IgG antibody concentrations in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and multiple sclerosis

Data availability statement: The data set used in this study is freely available from the United Kingdom ME/CFS biobank upon application.Supplementary data are available online at https://www.sciencedirect.com/science/article/pii/S2405844023054580?via%3Dihub#appsec2 .Copyright © 2023 The Authors. Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and multiple sclerosis (MS) are two complex and multifactorial diseases whose patients experience persistent fatigue, cognitive impairment, among other shared symptoms. The onset of these diseases has also been linked to acute herpesvirus infections or their reactivations. In this work, we re-analyzed a previously-described dataset related to IgG antibody responses to 6 herpesviruses (CMV – cytomegalovirus; EBV – Epstein-Barr virus; HHV6 – human herpesvirus-6; HSV1 and HSV2 – herpes simplex virus-1 and -2, respectively; VZV – varicella-zoster virus) from the United Kingdom ME/CFS biobank. The primary goal was to report the underlying symptomology and its association with herpesvirus IgG antibodies using data from 4 disease-trigger-based subgroups of ME/CFS patients (n = 222) and patients with MS (n = 46). The secondary objective was to assess whether serological data could distinguish ME/CFS and its subgroup from MS using a SuperLearner (SL) algorithm. There was evidence for a significant negative association between temporary eye insight disturbance and CMV antibody concentrations and for a significant positive association between bladder problems and EBV antibody concentrations in the MS group. In the ME/CFS or its subgroups, the most significant antibody-symptom association was obtained for increasing HSV1 antibody concentration and brain fog, a finding in line with a negative impact of HSV1 exposure on cognitive outcomes in both healthy and disease conditions. There was also evidence for a higher number of significant antibody-symptom associations in the MS group than in the ME/CFS group. When we combined all the serological data in an SL algorithm, we could distinguish three ME/CFS subgroups (unknown disease trigger, non-infection trigger, and an infection disease trigger confirmed in the lab at the time of the event) from the MS group. However, we could not find the same for the remaining ME/CFS group (related to an unconfirmed infection disease). In conclusion, IgG antibody data explains more the symptomology of MS patients than the one of ME/CFS patients. Given the fluctuating nature of symptoms in ME/CFS patients, the clinical implication of these findings remains to be determined with a longitudinal study. This study is likely to ascertain the robustness of the associations during natural disease course.This research was funded by: FCT - Fundação para a Ciência e Tecnologia, Portugal, ref. grant: SFRH/BD/149758/2019 (J.M.), and UIDB/00006/2020 (T.D.D., J.M., H.M., NS); the Polish National Agency for Academic Exchange (NAWA), ref. grant: PPN/ULM/2020/1/00069/U/00001 (N.S.). The UKMEB was established with a joint grant from the charities ME Association (including continuing support), ME Research UK and Action for ME, as well as private donors. Research reported in this manuscript was supported by the National Institutes of Health (NIH) under award number 2R01AI103629