Chronic disease multimorbidity transitions across healthcare interfaces and associated costs: a clinical-linkage database study.

OBJECTIVE: To investigate multimorbidity transitions from general practice populations across healthcare interfaces and the associated healthcare costs. DESIGN: Clinical-linkage database study. SETTING: Population (N=60 660) aged 40 years and over registered with 53 general practices in Stoke-on-Trent. PARTICIPANTS: Population with six specified multimorbidity pairs were identified based on hypertension, diabetes mellitus (DM), coronary heart disease (CHD), chronic obstructive pulmonary disease (COPD), congestive heart failure (CHF) and chronic kidney disease (CKD). MAIN OUTCOMES MEASURES: Chronic disease registers were linked to accident and emergency (A&E) and hospital admissions for a 3-year time period (2007-2009), and associated costs measured by Healthcare Resource Groups. Associations between multimorbid groups and direct healthcare costs were compared with their respective single disease groups using linear regression methods, adjusting for age, gender and deprivation. RESULTS: In the study population, there were 9735 patients with hypertension and diabetes (16%), 3574 with diabetes and CHD (6%), 2894 with diabetes and CKD (5%), 1855 with COPD and CHD (3%), 754 with CHF and COPD (1%) and 1425 with CHF and CKD (2%). Transition, defined as at least one episode in each of the 3-year time periods, was as follows: patients with hypertension and DM had the fewest transitions in the 3-year time period (37% A&E episode and 51% hospital admission), but those with CHF and CKD had the most transitions (67% A&E episode and 79% hospital admission). The average 3-year total costs per multimorbid patient for A&E episodes ranged from £69 to £166 and for hospital admissions ranged from between £2289 and £5344. The adjusted costs were significantly higher for all six multimorbid groups compared with their respective single disease groups. CONCLUSIONS: Specific common multimorbid pairs are associated with higher healthcare transitions and differential costs. Identification of multimorbidity type and linkage of information across interfaces provides opportunities for targeted intervention and delivery of integrated care

Molecular characterization of ageratum enation virus and DNA-satellites associated with yellowing and leaf curl symptoms on mulberry in Pakistan

<p>The whitefly-transmitted begomoviruses (family <i>Geminiviridae</i>) infect dicotyledonous plants and occur in tropical and sub-tropical regions. Although most commonly found in herbaceous plants, recently begomoviruses have increasingly been identified in woody plants. Leaf samples from five mulberry (<i>Morus alba</i> L.) plants with leaf yellowing and curling symptoms were collected in Lahore (Pakistan) and shown by PCR to be associated with a begomovirus, an alphasatellite and a betasatellite. The complete sequences of two begomovirus clones, as well as an alphasatellite clone and a betasatellite clone, were determined. The begomovirus clones were shown to be isolates of ageratum enation virus (AEV), a virus most commonly identified in weeds but increasingly being identified in crops such as tomato, soybean and fenugreek. Analyses of the sequences of the alphasatellite and betasatellite clones showed them to be isolates of Guar leaf curl alphasatellite and Papaya leaf curl betasatellite, respectively. Both the virus and the alphasatellite sequences showed evidence of a recombination. This is the first report of the weed-infecting monopartite begomovirus AEV, and associated satellites, infecting the woody plant mulberry.</p

Herbicidal activity of pure compound isolated from rhizosphere inhabiting <i>Aspergillus flavus</i>

<p>In the quest for bioactive natural products of fungal origin, <i>Aspergillus flavus</i> was isolated from rhizosphere of <i>Mentha piperita</i> using Potato Dextrose Agar (PDA) and Czapec Yeast Broth (CYB) nutrient media for metabolites production. In total, three different metabolites were purified using HPLC/LCMS and the structures were established using 500 Varian NMR experiments. Further the isolated metabolites in different concentrations (10, 100, 1000 μg/mL) were tested for herbicidal activity using Completely Randomized design (CRD) against the seeds of <i>Silybum marianum</i> and <i>Avena fatua</i> which are major threats to wheat crop in Pakistan. Among the isolated metabolites, one compound was found active against the test weed species whose activity is reported in the present work. The chemical name of the compound is 2-(1, 4-dihydroxybutan-2-yl)-1, 3-dihydroxy-6, 8-dimethoxyanthracene-9, 10(4a<i>H</i>, 9a<i>H</i>)-dione with mass of 388. Results showed that all seeds germinated in control treatment; however, with the metabolite treated, the growth was retarded to different levels in all parts of the weeds. At a dose of 1000 μg/mL of the pure compound, 100% seeds of <i>S. marianum</i> and 60% seeds of <i>A. fatua</i> were inhibited. Interestingly, the pure compound exhibited less inhibition of 10% towards the seeds of common wheat (<i>Triticum aestivum</i>).</p

Binding Strength of Porphyrin−Gold Nanoparticle Hybrids Based on Number and Type of Linker Moieties and a Simple Method To Calculate Inner Filter Effects of Gold Nanoparticles Using Fluorescence Spectroscopy

Gold nanoparticle–porphyrin assemblies were formed by binding functionalized porphyrins to gold nanoparticles (Au-NPs). Spectroscopic properties of hybrids and binding strength of porphyrins to Au-NPs were observed based on number and type of linker moieties using fluorescence spectroscopy. Binding appears to be dependent on number rather than type of linker moieties present on the porphyrin molecules, as tetraaminophenyl porphyrin shows the highest binding among the molecules we studied and causes agglomeration of nanoparticles due to presence of four linker groups. The inner filter effects of Au-NPs are considerably high due to their high extinction coefficient and cause large errors in the evaluation of quenching efficiencies. We have described a very simple method to calculate the inner filter effects of Au-NPs by first loading them with porphyrins and then replacing them with nonfluorescent ligands. The difference in the fluorescence of unbound porphyrins in the presence and absence of Au-NPs describes their inner filter effects

Sequence variants on 17q21 are associated with the susceptibility of asthma in the population of Lahore, Pakistan

<div><p></p><p><i>Objective</i>: Single nucleotide polymorphisms (SNPs) on 17q21 are known to be associated with asthma disease in multiple populations. This study was designed to know whether this region is associated with asthma in Lahore region population or not. <i>Methods</i>: A total of 200 asthma patients and 100 healthy controls were enrolled from different hospitals of Lahore, Pakistan. Twelve SNPs from chromosomal region 17q21 were analyzed in cases and controls by single base extension method and capillary-based genetic analyzers. Associations with asthma were checked using basic allelic model, genotypic model, and results were adjusted by logistic regression analysis using PLINK v1.9. Pair-wise linkage disequilibrium among the SNPs was analyzed by using Haploview software. <i>Results</i>: SNP rs3816470 showed a strong association (<i>p</i> = 8.89 × 10⁻⁵, Odd Ratio = 3.082 [1.755-5.41]) with asthma, whereas rs3859192 and rs6503525 also showed a significant association with the development of asthma, especially in the case of positive family history. In LD block1 (93 kb) consisting of six SNPs (rs12936231, rs7216389, rs7216558, rs9894164, rs1007654 and rs7212938), none of the haplotypes show any significant association with asthma except the haplotype “CCTCAG”, which is a significant protective factor against asthma having frequency 0.051 in controls while 0.017 in cases (<i>p</i> = 3.56 × 10⁻², χ² = 4.415). <i>Conclusion</i>: The present study reports that the polymorphic genomic variant rs3816470 is significantly and independently associated with asthma in the studied population, while the variants, rs6503525 and rs3859192, also indicate a significant association with asthma in this population when family history of the disease is taken as a covariate.</p></div

Targeted high throughput sequencing in hereditary ataxia and spastic paraplegia

<div><p>Hereditary ataxia and spastic paraplegia are heterogeneous monogenic neurodegenerative disorders. To date, a large number of individuals with such disorders remain undiagnosed. Here, we have assessed molecular diagnosis by gene panel sequencing in 105 early and late-onset hereditary ataxia and spastic paraplegia probands, in whom extensive previous investigations had failed to identify the genetic cause of disease. Pathogenic and likely-pathogenic variants were identified in 20 probands (19%) and variants of uncertain significance in ten probands (10%). Together these accounted for 30 probands (29%) and involved 18 different genes. Among several interesting findings, dominantly inherited <i>KIF1A</i> variants, p.(Val8Met) and p.(Ile27Thr) segregated in two independent families, both presenting with a pure spastic paraplegia phenotype. Two homozygous missense variants, p.(Gly4230Ser) and p.(Leu4221Val) were found in <i>SACS</i> in one consanguineous family, presenting with spastic ataxia and isolated cerebellar atrophy. The average disease duration in probands with pathogenic and likely-pathogenic variants was 31 years, ranging from 4 to 51 years. In conclusion, this study confirmed and expanded the clinical phenotypes associated with known disease genes. The results demonstrate that gene panel sequencing and similar sequencing approaches can serve as efficient diagnostic tools for different heterogeneous disorders. Early use of such strategies may help to reduce both costs and time of the diagnostic process.</p></div

Clinical flowchart.

<p>The figure explains the selection of probands from the clinicogenetic database, and the resulting total number of molecular diagnoses. VUS: variants of uncertain significance. * Indicates selection criteria of 105 probands: 1) Verified family history; 2) Completed thorough investigations; 3) Availability of probands; 4) Sporadic cases considered to be HSP or HA, fulfilling 2) and 3).</p

Pedigree structures of families with <i>KIF1A</i> variants.

<p>(a) Pedigree structure of family HCT-024 (III-7) with a c.80T>C, p.(Ile27Thr) variant in <i>KIF1A</i>. The filled symbols indicate affected individuals. The striped symbol indicates an individual that was initially classified as a non-affected individual, but after clinical re-examination was also found to be possibly affected. (b) Pedigree structure of family of HCT-026 (IV-6) with a c.22G>A, p.(Val8Met) variant. The symbols with a question mark are not confirmed regarding the phenotype. The diamond shaped symbols indicate masked gender. A line crossing a symbol represents a deceased individual. Probands are labelled with ‘P’.</p

Pedigree structure and MRI scans of a family with <i>SACS</i> variants.

<p>(a) Pedigree structure of family HCT-106 (V-3) with a c.12688G>A, p.(Gly4230Ser) and c.12661C>G, p.(Leu4221Val) variants in <i>SACS</i>. A consanguineous marriage between individuals IV-2 and III-4 is indicated by a double line. Cerebral MRIs of HCT-106 at disease duration of 28 years in (b) FLAIR sequence in midline sagittal plane, (c) FLAIR sequence in coronal plane at the level of dorsal aspect of cerebellum, (d) FLAIR sequence in transversal plane at the level of the middle cerebellar peduncles, and (e) T2 sequence in transversal plane at the level of the superior cerebellar peduncles, showing atrophy of the cerebellar hemispheres and vermis with widening of fissures and folia.</p

List of variants of uncertain significance.

<p>List of variants of uncertain significance.</p