Impact of Recurrent Floods on the Utilization of Maternal and Newborn Healthcare in Bangladesh

Maternal and Child Health Journal - Floods are one of the most common types of disasters in Bangladesh and lead to direct and indirect impacts on health. The aim of the study was to assess the...     

Simplified negative pressure wound therapy: clinical evaluation of an ultraportable,no‐canister system

The aim of this study was to evaluate a prototype negative pressure wound therapy (NPWT) system that has been developed to simplify NPWT for wounds at the lower end of the acuity scale. The new device has a single preset pressure of ?80 mmHg, is single use and operates without an exudate canister. The disposable NPWT system (PICO?) was tested in a prospective, non‐comparative, multicentre clinical trial to assess device functionality and clinical acceptance. Twenty patients were recruited for a maximum treatment period of 14 days. The NPWT devices were fitted with data log chips to enable longitudinal assessment of negative pressure and leak rates during therapy. Sixteen (80%) patients had closed surgical wounds, two (10%) patients had traumatic wounds and two (10%) patients received meshed split thickness skin grafts. The mean study duration was 10·7 days (range: 5–14 days) and the mean dressing wear time per individual patient was 4·6 days (range: 2–11). Fifty‐five percent of wounds had closed by the end of the 14‐day study or earlier, with a further 40% of wounds progressing to closure. Real‐time pressure monitoring showed continuous delivery of NPWT. Three cases are discussed representing different wound locations and different patient factors that can increase the risk of post‐surgical complications. Clinical studies of the disposable NPWT system confirmed the ability of the simplified single‐use device to function consistently over the expected wear time. The anticipated reduced costs, ease of use and increased mobility of patients using this system may enable NPWT benefits to be available to a greater proportion of patients.     

Specialisation and specialist education in prosthetic dentistry in Europe

This presentation reports on the results of a meeting of prosthodontists from selected European countries. The aim of the meeting was to analyse and promote specialisation and specialist education in Prosthetic Dentistry in Europe. Representatives for Europe were selected from the European Prosthodontic Association (EPA) board, the Education and Research Committee of International College of Prosthodontists (ICP), countries with a legally recognised speciality, countries without a recognised speciality but organised training programmes and countries with neither of these situations. Data about specialisation and specialist training in Prosthodontics in Europe was scrutinised and discussed. The programmes for countries with specialist training had relatively similar content, mostly of three years duration. There was strong agreement that a recognised speciality raises the level of care within the discipline for both specialists and non-specialists. In several of the countries where a speciality had been introduced it had been initiated by pressure from public health planning authorities. The conclusions are that from a professional viewpoint an advancement of the speciality over Europe would develop the discipline, improve oral health planning and quality of patient care. A working group for harmonisation was recommended.     

Assessment of denture satisfaction

The aim of this investigation was to evaluate the reliability and validity of a complaints questionnaire, designed to measure different aspects of denture satisfaction. Two groups of patients with full maxillary and mandibular dentures participated in the study. The patients in Group 1 (n = 113) were on a waiting list for new dentures, patients in Group 2 (n = 102) had recently had new dentures fitted. Five denture complaint scales were constructed from the questionnaire. The internal consistency (coefficient alpha) of the scales varied from 0.65 to 0.92. Furthermore, the scales showed a discriminatory ability between the patient groups (P less than or equal to 0.001) and significant Pearson correlation coefficients with satisfaction-related questions (r = 0.25-0.79). The scores on the scales can be considered a quantitative measure of denture satisfaction.     

Molecular profiling of Mycobacterium tuberculosis identifies tuberculosinyl nucleoside products of the virulence-associated enzyme Rv3378c

To identify lipids with roles in tuberculosis disease, we systematically compared the lipid content of virulent Mycobacterium tuberculosis with the attenuated vaccine strain Mycobacterium bovis bacillus Calmette–Guérin. Comparative lipidomics analysis identified more than 1,000 molecular differences, including a previously unknown, Mycobacterium tuberculosis-specific lipid that is composed of a diterpene unit linked to adenosine. We established the complete structure of the natural product as 1-tuberculosinyladenosine (1-TbAd) using mass spectrometry and NMR spectroscopy. A screen for 1-TbAd mutants, complementation studies, and gene transfer identified Rv3378c as necessary for 1-TbAd biosynthesis. Whereas Rv3378c was previously thought to function as a phosphatase, these studies establish its role as a tuberculosinyl transferase and suggest a revised biosynthetic pathway for the sequential action of Rv3377c-Rv3378c. In agreement with this model, recombinant Rv3378c protein produced 1-TbAd, and its crystal structure revealed a cis-prenyl transferase fold with hydrophobic residues for isoprenoid binding and a second binding pocket suitable for the nucleoside substrate. The dual-substrate pocket distinguishes Rv3378c from classical cis-prenyl transferases, providing a unique model for the prenylation of diverse metabolites. Terpene nucleosides are rare in nature, and 1-TbAd is known only in Mycobacterium tuberculosis. Thus, this intersection of nucleoside and terpene pathways likely arose late in the evolution of the Mycobacterium tuberculosis complex; 1-TbAd serves as an abundant chemical marker of Mycobacterium tuberculosis, and the extracellular export of this amphipathic molecule likely accounts for the known virulence-promoting effects of the Rv3378c enzyme.With a mortality rate exceeding 1.5 million deaths annually, Mycobacterium tuberculosis remains one of the world''s most important pathogens (1). M. tuberculosis succeeds as a pathogen because of productive infection of the endosomal network of phagocytes. Its residence within the phagosome protects it from immune responses during its decades long infection cycle. However, intracellular survival depends on active inhibition of pH-dependent killing mechanisms, which occurs for M. tuberculosis but not species with low disease-causing potential (2). Intracellular survival is also enhanced by an unusually hydrophobic and multilayered protective cell envelope. Despite study of this pathogen for more than a century, the spectrum of natural lipids within M. tuberculosis membranes is not yet fully defined. For example, the products of many genes annotated as lipid synthases remain unknown (3), and mass spectrometry detects hundreds of ions that do not correspond to known lipids in the MycoMass and LipidDB databases (4, 5).To broadly compare the lipid profiles of virulent and avirulent mycobacteria, we took advantage of a recently validated metabolomics platform (4). This high performance liquid chromatography–mass spectrometry (HPLC-MS) system uses methods of extraction, chromatography, and databases that are specialized for mycobacteria. After extraction of total bacterial lipids into organic solvents, HPLC-MS enables massively parallel detection of thousands of ions corresponding to diverse lipids that range from apolar polyketides to polar phosphoglycolipids. Software-based (XCMS) ion finding algorithms report reproducibly detected ions as molecular features. Each feature is a 3D data point with linked mass, retention time, and intensity values from one detected molecule or isotope. All features with equivalent mass and retention time from two bacterial lipid extracts are aligned, allowing pairwise comparisons of MS signal intensity to enumerate molecules that are overproduced in one strain with a false-positive rate below 1% (4).This comparative lipidomics system allowed an unbiased, organism-wide analysis of lipids from M. tuberculosis and the attenuated vaccine strain, Mycobacterium bovis Bacillus Calmette–Guérin (BCG). BCG was chosen because of its worldwide use as a vaccine and its genetic similarity to M. tuberculosis (6). We reasoned that any features that are specifically detected in M. tuberculosis might be clinically useful as markers to distinguish tuberculosis-causing bacteria from vaccines. Furthermore, given the differing potential for productive infection by the two strains, any M. tuberculosis-specific compounds would be candidate virulence factors. Comparative genomics of M. tuberculosis and BCG successfully identified “regions of deletion” (RD) that encode genes that were subsequently proven to promote productive M. tuberculosis infection (7), including the 6-kDa early secreted antigenic target (ESAT-6) secretion system-1 (ESX-1) (8, 9). We reasoned that a metabolite-based screen might identify new virulence factors because not all functions of RD genes are known. Also, biologically important metabolites could emerge from complex biosynthetic pathways that cannot be predicted from single-gene analysis.Comparison of M. tuberculosis and BCG lipid profiles revealed more than 1,000 differences, among which we identified a previously unknown M. tuberculosis-specific diterpene-linked adenosine and showed that it is produced by the enzyme Rv3378c. Previously, Rv3378c was thought to generate free tuberculosinol and isotuberculosinol (10–12). This discovery revises the enzymatic function of Rv3378c, which acts as a virulence factor to inhibit phagolysosome fusion (13). Whereas current models of prenyl transferase function emphasize iterative lengthening of prenyl pyrophosphates using one binding pocket, the crystal structure of Rv3378c identifies two pockets in the catalytic site, establishing a mechanism for heterologous prenyl transfer to nonprenyl metabolites.     

Comparison of the temporal release pattern of copeptin with conventional biomarkers in acute myocardial infarction

Background

Early detection of acute myocardial infarction (AMI) using cardiac biomarkers of myocardial necrosis remains limited since these biomarkers do not rise within the first hours from onset of AMI. We aimed to compare the temporal release pattern of the C-terminal portion of provasopressin (copeptin) with conventional cardiac biomarkers, including creatine kinase isoenzyme (CK-MB), cardiac troponin T (cTnT), and high-sensitivity cTnT (hs-cTnT), in patients with ST-elevation AMI.

Methods

We included 145 patients undergoing successful primary percutaneous coronary intervention (PCI) for a first ST-elevation AMI presenting within 12?h of symptom onset. Blood samples were taken on admission and at four time points within the first 24?h after PCI.

Results

In contrast to all other markers, copeptin levels were already elevated on admission and were higher with a shorter time from symptom onset to reperfusion and lower systolic blood pressure. Copeptin levels peaked immediately after symptom onset at a maximum of 249?pmol/L and normalized within 10?h. In contrast, CK-MB, cTnT, and hs-cTnT peaked after 14?h from symptom onset at a maximum of 275?U/L, 5.75???g/L, and 4.16???g/L, respectively, and decreased more gradually.

Conclusions

Copeptin has a distinct release pattern in patients with ST-elevation AMI, peaking within the first hour after symptom onset before conventional cardiac biomarkers and falling to normal ranges within the first day. Further studies are required to determine the exact role of copeptin in AMI suspects presenting within the first hours after symptom onset.     

Evaluation of Basis Function and Linear Least Squares Methods for Generating Parametric Blood Flow Images Using <Superscript>15</Superscript>O-Water and Positron Emission Tomography

Purpose Parametric analysis of ¹⁵O-water positron emission tomography (PET) studies allows determination of blood flow (BF), perfusable tissue fraction (PTF), and volume of distribution (V _d) with high spatial resolution. In this paper the performance of basis function and linear least squares methods for generating parametric flow data were evaluated. Procedures Monte Carlo simulations were performed using typical perfusion values for brain, tumor, and heart. Clinical evaluation was performed using seven cerebral and 10 myocardial ¹⁵O-water PET studies. Basis function (BFM), linear least squares (LLS), and generalized linear least squares (GLLS) methods were used to calculate BF, PTF, or V _d. Results Monte Carlo simulations and human studies showed that, for low BF values (<1 ml/min/ml), BF, PTF, and V _d were calculated with accuracies better than 5% for all methods tested. For high BF (>2 ml/min/ml), use of BFM provided more accurate V _d compared with (G)LLS. Conclusions In general, BFM provided the most accurate estimates of BF, PTF, and V _d.     

Simplified parametric methods for [11C]PIB studies

The purpose of the present study was to evaluate the performance of various parametric reference tissue models for quantification of [11C]PIB studies. Several models with and without fixing the reference tissue efflux rate constant (k'(2)) were investigated using both simulations and clinical data. The following parametric methods were evaluated: receptor parametric mapping (basis function implementation of the simplified reference tissue model with and without fixed k'(2)), reference Logan, and several multi-linear reference tissue methods (again with and without fixed k'(2)). In addition, standardised uptake value ratios with cerebellum (SUV(r)) were evaluated. Simulations were used to assess the effects of variation in flow (R(1)), fractional blood volume (V(b)) and binding potential (BP(ND)) itself on precision and accuracy of parametric BP(ND). For clinical studies, most parametric methods showed comparable performance, with poorest results for SUV(r). Best performance was obtained for receptor parametric mapping (RPM2) and one of the multi-linear reference tissue models (MRTM2), both with fixed k'(2): BP(ND) outcome was less affected by noise and the images showed better contrast than other tested methods. RPM2 and MRTM2 also provided best accuracy and precision in the simulation studies and are therefore the methods of choice for parametric analysis of clinical [11C]PIB studies.