Exercise knowledge, barriers and motivators among LRRK2 G2019S mutation carriers.

INTRODUCTION: People with a Gly2019Ser mutation in the leucine-rich repeat kinase 2 (LRRK2 G2019S) are at increased risk of developing Parkinson's disease (PD). Recent evidence suggests that exercise may delay or prevent the development of clinically overt symptoms of PD in people at risk of PD. We determined whether LRRK2 G2019S mutation carriers with and without manifest PD are aware of the relationship between exercise and PD and how they differ in awareness, barriers and motivators to exercise. METHODS: We deployed a survey among 4422 LRRK2 G2019S mutation carriers. In total, 505 (11.4%) of them completed the survey, of whom 105 had self-reported manifest PD. RESULTS: Ninety-two percent of the LRRK2 G2019S mutation carriers with manifest PD and 63% of those with non-manifest PD were aware of the relationship between exercise and PD. Lack of motivation was the top barrier for those without manifest PD, while having an injury/disability was the most common barrier for those with manifest PD. Improvement of body functioning was the top motivator for both. CONCLUSION: The fact that many at-risk individuals are not aware of the importance of exercise and would exercise more with fewer barriers creates opportunities for trials using exercise as a possible prevention strategy for PD.

Hospital re-admission after critical care survival: a systematic review and meta-analysis.

Survivors of critical illness frequently require increased healthcare resources after hospital discharge. We undertook a systematic review and meta-analysis to assess hospital re-admission rates following critical care admission and to explore potential re-admission risk factors. We searched the MEDLINE, Embase and CINAHL databases on 05 March 2020. Our search strategy incorporated controlled vocabulary and text words for hospital re-admission and critical illness, limited to the English language. Two reviewers independently applied eligibility criteria and assessed quality using the Newcastle Ottawa Score checklist and extracted data. The primary outcome was acute hospital re-admission in the year after critical care discharge. Of the 8851 studies screened, 87 met inclusion criteria and 41 were used within the meta-analysis. The analysis incorporated data from 3,897,597 patients and 741,664 re-admission episodes. Pooled estimates for hospital re-admission after critical illness were 16.9% (95%CI: 13.3-21.2%) at 30 days; 31.0% (95%CI: 24.3-38.6%) at 90 days; 29.6% (95%CI: 24.5-35.2%) at six months; and 53.3% (95%CI: 44.4-62.0%) at 12 months. Significant heterogeneity was observed across included studies. Three risk factors were associated with excess acute care rehospitalisation one year after discharge: the presence of comorbidities; events during initial hospitalisation (e.g. the presence of delirium and duration of mechanical ventilation); and subsequent infection after hospital discharge. Hospital re-admission is common in survivors of critical illness. Careful attention to the management of pre-existing comorbidities during transitions of care may help reduce healthcare utilisation after critical care discharge. Future research should determine if targeted interventions for at-risk critical care survivors can reduce the risk of subsequent rehospitalisation.

Combined neurosurgical and orbital intervention for spheno-orbital meningiomas - the Manchester experience.

PURPOSE: Surgical resection of spheno-orbital meningioma (SOM) is challenging, requiring a multidisciplinary surgical approach. We present our experience of the surgical management of patients with SOM. METHODS: A retrospective analysis of patients with SOM who underwent joint neurosurgical and orbital surgical procedures between January 2000 and June 2017. Pre-operative clinical signs, indication for surgery, surgical complications and post-operative outcomes were recorded. RESULTS: Twenty-four operations were performed. Mean age was 49.5 years. Ninety-two percent of patients were female. Pre-operatively mean Snellen acuity vision was 6/12; 13 (54%) had an RAPD; 12 (50%) had reduced colour vision; 16 (67%) had a visual field defect. The majority (21 patients, 88%) had proptosis (average 4.5 mm ± 2.8 mm). The indication for surgery was evidence of visual dysfunction in 17 (71%), the remaining 7 (29%) had high risk of visual loss clinically or radiologically. Three-months post operatively, vision was stable in 13 (58%), improved in 6 (21%) and worse in 5 (17%). Average long-term follow-up was 82 months (1-220). Fourteen (58%) maintain improved or stable visual function. Four (17%) had reduced vision due to regrowth of the tumour at an average of 24 months. CONCLUSION: SOMs are very challenging to treat surgically. In this cohort the patients were predominantly young females with aggressive disease. Visual function was improved or stabilised in 79% of the patients.

Transcription factors E2F1 and E2F3 are expressed in placenta but do not regulate MMP14.

INTRODUCTION: Preeclampsia is a serious complication of pregnancy for which there are no efficacious medical treatments. Soluble endoglin is as an anti-angiogenic factor that contributes to the pathogenesis of the disease, however little is known about its molecular regulation in placenta. Recent data has demonstrated E2F transcription factors directly regulate MMPs in metastatic disease. Of particular interest was the capacity of E2F1 and E2F3 to up-regulate MMP14, a protease that cleaves and releases soluble endoglin from placenta. The aim of this study was to characterize E2F1 and E2F3 in preeclamptic placenta and assess whether silencing affects soluble endoglin release. METHODS: E2F1 and E2F3 mRNA, protein expression and localization were assessed in severe early onset preeclamptic and preterm control placentas (delivered <34 weeks gestation). E2F siRNA was administered to primary trophoblast and primary endothelial cells and effect on MMP14 mRNA expression and soluble endoglin secretion assessed. RESULTS: E2F1 and E2F3 were localized to the syncytiotrophoblast. E2F1 was significantly down regulated in severe preeclamptic placentas, while E2F3 was unchanged. Silencing E2F1 did not decrease MMP14 expression in primary trophoblast or endothelial cells. However, E2F1 silencing resulted in a significant increase in soluble endoglin secretion from both cell types, and silencing of E2F3 also significantly increased soluble endoglin release from primary trophoblast. DISCUSSION: This study demonstrates that E2F1 and E2F3 are present within the syncytiotrophoblast of placenta and that E2F1 is reduced in preeclampsia. Although silencing of either E2F1 or E2F3 does not alter MMP14 expression, both appear to regulate soluble endoglin release.

Placental SEMA3B expression is not altered in severe early onset preeclampsia.

Recent evidence suggests that Semaphorin 3B (SEMA3B) is upregulated in severe preeclampsia, and a major driver of cytotrophoblast aberrations in this disease. Here we independently assess whether SEMA3B expression is altered in a large cohort of severe early onset preeclamptic placentas. We demonstrate that SEMA3B relative mRNA expression and copy number are not changed in PE placentas. We confirm this at the protein level by western blot. Interestingly, exposure of term trophoblasts or explants to hypoxia induced a significant down regulation of SEMA3B mRNA, but a trend towards increased SEMA3B protein expression. We conclude that SEMA3B mRNA and protein is not altered in severe early onset preeclamptic placentas.

Stability of absolute copy number of housekeeping genes in preeclamptic and normal placentas, as measured by digital PCR.

Measuring mRNA expression is fundamental to placental research. Ideally, mRNA transcript numbers are directly quantified. However, PCR analysis using the ΔΔCT method relies on the stability of housekeeping genes and only reports relative expression. Digital PCR (dPCR) directly quantifies mRNA copy number and is more accurate than quantitative PCR. We quantified absolute mRNA copy number of housekeeping genes in normotensive pre-term (n = 20), severe preeclamptic (n = 11) and term (n = 12) placenta using dPCR. Whilst there was some variation, we confirm absolute mRNA copy number of GAPDH, TOP1, CYC1 and YWHAZ in placenta does not significantly alter between these cohorts, or across gestation.

First Report of the Armillaria Root-Disease Pathogen, Armillaria gallica, Associated with Several Woody Hosts in Three States of Mexico.

In September 2007, rhizomorphs with morphological characteristics of Armillaria were collected from woody hosts in forests of Mexico State, Veracruz, and Oaxaca, Mexico. Based on pairing tests, isolates were assigned to five somatically compatible genets or clones (MEX7R, MEX11R, MEX23R, MEX28R, and MEX30R). These genets were all identified as Armillaria gallica based on somatic pairing tests against known tester isolates and nucleotide sequences of the translation elongation factor 1α (tef-1α; GenBank Accession Nos. KF156772 to 76). Sequences of tef-1α for all genets showed a max identity of 97 to 99% to A. gallica (ST23, JF313125) (3,4). However, A. gallica comprises a genetically diverse complex that likely represents multiple cryptic species (3). In Mexico, this species has been previously reported in northeastern Morelos on Quercus sp., eastern Mexico State on Pinus hartwegii, and southwestern Mexico State on Prunus persica (1,2). This study identified associations with 10 new hosts within three states of Mexico, but only five hosts were diseased. Genet MEX7R comprised seven isolates collected in the University of Chapingo forest near Texcoco, Mexico State (19°18'10.764″ N, 98°42'14.147″ W, elevation 3441 m). Four MEX7R isolates were collected from diseased Alnus sp. including the root ball of a 130 cm dbh, root-disease killed tree, one isolate from a symptomless Senecio sp. s.l. (Roldana sp.) shrub and two isolates from symptomless Abies religiosa. Genet MEX11R comprised four isolates from a cloud forest near Xalapa, Veracruz (19°31'14.628″ N, 96°59'22.812″ W, elevation 1496 m). MEX11R isolates were collected from the roots of a root-disease killed Carpinus caroliniana, and from trees with no obvious symptoms (Miconia mexicana, Quercus xalapensis, and Liquidambar styraciflua). Two isolates of genet MEX23R were collected from the Jardin Botanico Francisco Javier Clavijero, Instituto de Ecologia, A.C., Xalapa, Veracruz (19°30'49.067″ N, 96°56'32.999″ W, elevation 1344 m). These isolates were from root-diseased Eriobotrya japonica (non-native fruit tree) that showed obvious symptoms (flaccid, chlorotic, and senescing leaves) and from an adjacent, infected Platanus mexicana that did not show readily observable symptoms. Two collections near Oaxaca, Oaxaca, included a single isolate MEX28R from the root ball of a recently root disease-killed Arbutus xalapensis within a small root disease center at Peña Prieta, in Parque La Cumbre, near Ixtepeji (17°09'42.084″ N, 96°38'15.936″ W, elevation 2853 m) and a single isolate MEX30R from the base of an asymptomatic Alnus acuminata near the El Carrizal fish hatchery 10 km northeast of San Miguel del Valle (17°06'45.036″ N, 96°24'03.743″ W, elevation 2594 m). Armillaria gallica has a circumpolar distribution with an extremely wide host range, and its ecological behavior varies greatly. Continued surveys are needed to better understand the distribution and ecological impacts of this pathogen in relation to Armillaria root disease in Mexico and the potential influences of climate change. Although A. gallica displays diverse ecological behavior, trees infected with A. gallica are less likely to survive the stresses of human activity and a changing climate (4). References: (1) D. Alvarado-Rosales and R. A. Blanchette. Phytopathology 84:1106, 1994. (2) R. D. Elias-Roman et al. For. Pathol. 43:390, 2013. (3) M.-S. Kim et al. Phytopathology 102:S4.63, 2012. (4) B. Marcais and N. Breda. J. Ecol. 94:1214, 2006.

Generic circumscriptions in Geoglossomycetes.

The class Geoglossomycetes is a recently created class of Ascomycota, currently comprised of one family (Geoglossaceae) and five genera (Geoglossum, Nothomitra, Sarcoleotia, Thuemenidium and Trichoglossum). These fungi, commonly known as earth tongues, have long been a subject of mycological research. However, the taxonomy within the group has historically been hindered by the lack of reliable morphological characters, uncertain ecological associations, and the inability to grow these fungi in culture. The phylogenetic relationships of Geoglossomycetes were investigated by conducting maximum likelihood and Bayesian analyses using a 4-gene dataset (ITS, LSU, MCM7, RPB1). Five well-supported monophyletic clades were found that did not correspond exactly with the currently recognised genera, necessitating a taxonomic revision of the group. Two new genera are proposed: Glutinoglossum to accommodate G. glutinosum and the newly described species G. heptaseptatum, and Sabuloglossum to accommodate S. arenarium. The type species of Thuemenidium, traditionally included within the Geoglossaceae, is confirmed as belonging to a separate lineage that is only distantly related to Geoglossomycetes.

The Colletotrichum boninense species complex.

Although only recently described, Colletotrichum boninense is well established in literature as an anthracnose pathogen or endophyte of a diverse range of host plants worldwide. It is especially prominent on members of Amaryllidaceae, Orchidaceae, Proteaceae and Solanaceae. Reports from literature and preliminary studies using ITS sequence data indicated that C. boninense represents a species complex. A multilocus molecular phylogenetic analysis (ITS, ACT, TUB2, CHS-1, GAPDH, HIS3, CAL) of 86 strains previously identified as C. boninense and other related strains revealed 18 clades. These clades are recognised here as separate species, including C. boninense s. str., C. hippeastri, C. karstii and 12 previously undescribed species, C. annellatum, C. beeveri, C. brassicicola, C. brasiliense, C. colombiense, C. constrictum, C. cymbidiicola, C. dacrycarpi, C. novae-zelandiae, C. oncidii, C. parsonsiae and C. torulosum. Seven of the new species are only known from New Zealand, perhaps reflecting a sampling bias. The new combination C. phyllanthi was made, and C. dracaenae Petch was epitypified and the name replaced with C. petchii. Typical for species of the C. boninense species complex are the conidiogenous cells with rather prominent periclinal thickening that also sometimes extend to form a new conidiogenous locus or annellations as well as conidia that have a prominent basal scar. Many species in the C. boninense complex form teleomorphs in culture. TAXONOMIC NOVELTIES: New combination - Colletotrichum phyllanthi (H. Surendranath Pai) Damm, P.F. Cannon & Crous. Name replacement - C. petchii Damm, P.F. Cannon & Crous. New species - C. annellatum Damm, P.F. Cannon & Crous, C. beeveri Damm, P.F. Cannon, Crous, P.R. Johnst. & B. Weir, C. brassicicola Damm, P.F. Cannon & Crous, C. brasiliense Damm, P.F. Cannon, Crous & Massola, C. colombiense Damm, P.F. Cannon, Crous, C. constrictum Damm, P.F. Cannon, Crous, P.R. Johnst. & B. Weir, C. cymbidiicola Damm, P.F. Cannon, Crous, P.R. Johnst. & B. Weir, C. dacrycarpi Damm, P.F. Cannon, Crous, P.R. Johnst. & B. Weir, C. novae-zelandiae Damm, P.F. Cannon, Crous, P.R. Johnst. & B. Weir, C. oncidii Damm, P.F. Cannon & Crous, C. parsonsiae Damm, P.F. Cannon, Crous, P.R. Johnst. & B. Weir, C. torulosum Damm, P.F. Cannon, Crous, P.R. Johnst. & B. Weir. Typifications: Epitypifications - C. dracaenae Petch.

The Colletotrichum acutatum species complex.

Colletotrichum acutatum is known as an important anthracnose pathogen of a wide range of host plants worldwide. Numerous studies have reported subgroups within the C. acutatum species complex. Multilocus molecular phylogenetic analysis (ITS, ACT, TUB2, CHS-1, GAPDH, HIS3) of 331 strains previously identified as C. acutatum and other related taxa, including strains from numerous hosts with wide geographic distributions, confirmed the molecular groups previously recognised and identified a series of novel taxa. Thirty-one species are accepted, of which 21 have not previously been recognised. Colletotrichum orchidophilum clusters basal to the C. acutatum species complex. There is a high phenotypic diversity within this complex, and some of the species appear to have preferences to specific hosts or geographical regions. Others appear to be plurivorous and are present in multiple regions. In this study, only C. salicis and C. rhombiforme formed sexual morphs in culture, although sexual morphs have been described from other taxa (especially as laboratory crosses), and there is evidence of hybridisation between different species. One species with similar morphology to C. acutatum but not belonging to this species complex was also described here as new, namely C. pseudoacutatum. TAXONOMIC NOVELTIES: New combinations - Colletotrichum limetticola (R.E. Clausen) Damm, P.F. Cannon & Crous, C. lupini (Bondar) Damm, P.F. Cannon & Crous, C. salicis (Fuckel) Damm, P.F. Cannon & Crous. New species - C. acerbum Damm, P.F. Cannon & Crous, C. australe Damm, P.F. Cannon & Crous, C. brisbanense Damm, P.F. Cannon & Crous, C. cosmi Damm, P.F. Cannon & Crous, C. costaricense Damm, P.F. Cannon & Crous, C. cuscutae Damm, P.F. Cannon & Crous, C. guajavae Damm, P.F. Cannon & Crous, C. indonesiense Damm, P.F. Cannon & Crous, C. johnstonii Damm, P.F. Cannon & Crous, C. kinghornii Damm, P.F. Cannon & Crous, C. laticiphilum Damm, P.F. Cannon & Crous, C. melonis Damm, P.F. Cannon & Crous, C. orchidophilum Damm, P.F. Cannon & Crous, C. paxtonii Damm, P.F. Cannon & Crous, C. pseudoacutatum Damm, P.F. Cannon & Crous C. pyricola Damm, P.F. Cannon & Crous, C. rhombiforme Damm, P.F. Cannon & Crous, C. scovillei Damm, P.F. Cannon & Crous, C. sloanei Damm, P.F. Cannon & Crous, C. tamarilloi Damm, P.F. Cannon & Crous, C. walleri Damm, P.F. Cannon & Crous. Typifications: Epitypifications - C. acutatum J.H. Simmonds, C. limetticola (R.E. Clausen) Damm, P.F. Cannon & Crous, C. nymphaeae (Pass.) Aa, C. phormii (Henn.) D.F. Farr & Rossman, C. salicis (Fuckel) Damm, P.F. Cannon & Crous. Lectotypifications - C. nymphaeae (Pass.) Aa, C. orchidearum Allesch.

Colletotrichum - current status and future directions.

A review is provided of the current state of understanding of Colletotrichum systematics, focusing on species-level data and the major clades. The taxonomic placement of the genus is discussed, and the evolution of our approach to species concepts and anamorph-teleomorph relationships is described. The application of multilocus technologies to phylogenetic analysis of Colletotrichum is reviewed, and selection of potential genes/loci for barcoding purposes is discussed. Host specificity and its relation to speciation and taxonomy is briefly addressed. A short review is presented of the current status of classification of the species clusters that are currently without comprehensive multilocus analyses, emphasising the orbiculare and destructivum aggregates. The future for Colletotrichum biology will be reliant on consensus classification and robust identification tools. In support of these goals, a Subcommission on Colletotrichum has been formed under the auspices of the International Commission on Taxonomy of Fungi, which will administer a carefully curated barcode database for sequence-based identification of species within the BioloMICS web environment.

Effects of Merogel coverage on wound healing and ostial patency in endonasal endoscopic dacryocystorhinostomy for primary chronic dacryocystitis.

PURPOSE: To investigate the effects of Merogel coverage on ostial patency in endonasal endoscopic dacryocystorhinostomy (EES-DCR) for primary chronic dacryocystitis (PCD). METHODS: In all, 260 patients with unilateral PCD were randomized into two groups: the Merogel group and the control group. All patients underwent EES-DCR. The Merogel group received Merogel covering the wound 1-2 mm around the ostium and the control group received no treatment. Patients were followed up for 9 months. The mucosal epithelialization of the wound, the proliferation of fibrosis tissue, and the success rate of ostial patency were compared. RESULTS: Our study included 112 patients in the Merogel group and 115 patients in the control group. At the 2-week review, intact mucosal epithelium lined the ostia in 96 Merogel patients compared with 80 control patients (ITT analysis: χ(2)=4.502, P=0.034). At the 9-month review, scars were present in 18 patients in the Merogel group compared with 39 patients in the control group (ITT analysis: χ(2)=9.909, P=0.002, ITT analysis). No differences were observed in the granulation formation between the two groups. The success rate of ostial patency reached 94.6% (106/112) in the Merogel group compared with 80% (92/115) in the control group (ITT analysis: χ(2)=4.151, P=0.042). CONCLUSION: Merogel coverage may enhance the success rate of EES-DCR for PCD by promoting mucosal epithelial healing and preventing excessive scarring.

Efficacy of trichloroacetic acid (95%) in the management of xanthelasma palpebrarum.

BACKGROUND: Xanthelasma palpebrarum (XP) is a commonly occurring benign eyelid disorder. AIM: To determine the efficacy of topical trichloroacetic acid (TCA) 95% in the management of XP. METHODS: This was a retrospective review of patients treated with TCA between June 2000 and July 2007. We recorded the outcomes of patients who attended the clinic at least 3 months after their treatment. We also contacted all patients with a minimum interval of 12 months between treatment and a telephone interview to assess for recurrence/persistence of the lesion(s). RESULTS: In total, 102 patients were enrolled in the study. Of these, 44 were reviewed in the clinic. There were nine persistent lesions and four recurrences recorded at a mean follow-up of 14.3 months. Telephone interviews were conducted with 51 patients (146 lesions). Of these 51 patients, 43 had been given bilateral TCA treatment. The mean number of TCA treatments was 1.68. Mean time from the past TCA treatment to the telephone interview was 31.8 months. Of the 51 patients, 17 patients reported no recurrence, 22 patients had experienced a recurrence, 9 patients had persistence of the lesion and 3 patients undergone surgical excision of the lesion since the last TCA treatment. Overall, the success rate for TCA was 61% at a mean follow-up of 31.8 months. CONCLUSIONS: XP has a strong history of recurrence. TCA treatment may be effective in XP and is a short, simple and cheap procedure that can be repeated. Although the requirement for retreatment is high, patient satisfaction with the procedure is also high.

First Report of Armillaria Root Disease Caused by Armillaria tabescens on Araucaria araucana in Veracruz, Mexico.

In September 2007, bark samples were collected from the root collar of a single Araucaria araucana tree that had recently died and was suspected of being killed by Armillaria root disease. Disease symptoms and signs included a thinning crown and fruiting bodies at the tree base over a several-year period before tree death. The tree was located in an isolated street-tree planting within a business district on Maestros Veracruzanos Street, Xalapa, Veracruz (19°31'52''N, 96°54'25''W, elevation 1,392 m). One fungal isolate (MEX21WF) was obtained, which possessed two sequence repeat types from the intergenic spacer-1 (IGS-1) region (GenBank Accession Nos. GQ335541 and GQ335542). On the basis of these IGS-1 sequences, this isolate from Mexico possessed 99% nucleotide sequence identities with North American Armillaria tabescens isolates (GenBank Accession Nos. AY695410 ≈ GQ335541 and AY773966 ≈ GQ335542). Somatic pairing tests of the isolate with other North American Armillaria species also identified it as A. tabescens (2). In addition, fruiting bodies were produced on the stump base in 2009 that matched morphological features of A. tabescens, e.g., exannulate, cespitose growth in clusters, brown-gray stipe to blackish toward the base, longitudinally fibrillose, basidiospores (6-) 7 to 9 × 4 to 5 (-5.5) µm, and other general morphology. On the basis of these three lines of taxonomic evidence, it was concluded that the isolate was A. tabescens. To our knowledge, this is the first confirmed report of A. tabescens causing Armillaria root disease in Mexico. Furthermore, this note represents the first report of A. tabescens on Araucaria araucana, which is native to Chile and Argentina. The other previous reports of A. tabescens in Mexico are based on herbarium specimens collected in 1965 (BPI 753040) from Valle de Bravo (approximately 350 km west of Xalapa) in the state of México and 1973 (BPI 753041) from near Monterrey (approximately 760 km north-northwest of Xalapa) in the state of Nuevo León (1). However, no host information or confirmation of taxonomic identification was reported for these herbarium specimens. Although this note confirms the presence of A. tabescens in Mexico, more surveys and monitoring are needed to determine the full distribution of this pathogen in Mexico. Because the climate and tree communities of eastern Mexico are similar to those of the southeastern United States, where A. tabescens has been reported as a common pathogen of oaks and fruit trees (3,4), it seems reasonable that A. tabescens may represent an existing or potential threat in eastern Mexico. References: (1) D. F. Farr and A. Y. Rossman. Fungal Databases. Systematic Mycology and Microbiology Laboratory. Online publication. ARS, USDA, 2010. (2) K. I. Mallett and Y. Hiratsuka. Can. J. Bot. 64:2588, 1986. (3) F. Miranda and A. J. Sharp. Ecology 31:313, 1950. (4) G. Schnabel et al. Mycol. Res. 109:1208, 2005.

Our experience using primary oral antibiotics in the management of orbital cellulitis in a tertiary referral centre.

AIMS/PURPOSE: Orbital cellulitis is conventionally managed by intravenous (i.v.) antibiotic therapy, followed by oral antibiotics once the infection shows signs of significant improvement. We report 4 years of experience using primary oral ciprofloxacin and clindamycin in cases of orbital cellulitis. Oral ciprofloxacin and clindamycin have a similar bioavailability to the i.v. preparations and provide an appropriate spectrum of antibiotic cover for the pathogens responsible for orbital cellulitis. METHODS: A retrospective review was performed that identified all patients with orbital cellulitis and treated with primary oral antibiotic therapy admitted to the Manchester Royal Eye Hospital between March 2003 and March 2007. Age, stage of disease, surgical intervention, hospital duration, and complications were obtained. A comparison was made with patients admitted to our unit with orbital cellulitis and treated with primary i.v. antibiotics between March 2000 and March 2003. RESULTS: Nineteen patients were included in the review for the period March 2003 to March 2007, which comprised of 7 children and 12 adults. Five patients required surgical intervention. All patients responded to the oral regimen, 18 patients had no change to their oral antibiotic therapy. Mean hospital stay was 4.4 days. There were no complications. DISCUSSION: Empirical oral ciprofloxacin and clindamycin combination may be as safe and effective as i.v. therapy in the management of orbital cellulitis. Oral treatment can offer the advantages of rapid delivery of the first antibiotic dose, fewer interruptions in treatment, and simplified delivery of medication particularly in children.

Tissue-specific restriction of cyclophilin A-independent HIV-1- and SIV-derived lentiviral vectors.

The host factor alpha isoform of the tripartite motif 5 (TRIM5alpha) restricts human immunodeficiency virus type 1 (HIV-1) infection in certain non-human primate species. Restriction of HIV-1 is enhanced by binding of the viral capsid to cyclophilin A (CypA) in target cells, although CypA is not absolutely required for restriction in rhesus macaque cells. Simian immunodeficiency virus (SIV) is not restricted by rhesus macaque TRIM5alpha and its capsid does not bind to CypA. Here, the effect of lentiviral CypA dependence on restriction in different tissues was examined by engineering an HIV-1 capsid quadruple mutant (V(86)P/H(87)Q/I(91)V/M(96)I) lentiviral vector (HIV(quad)) that is CypA-independent. Whereas HIV-1 was restricted in rhesus macaque and owl monkey epithelial cells, infection with the HIV(quad) vector was efficient at high viral concentrations. In contrast, HIV(quad) was largely restricted in primary rhesus macaque CD34(+) cells. Human epithelial and primary CD34(+) cells were permissive for HIV-1, HIV(quad) and SIV, whereas transduction of human T cells by HIV(quad) or SIV was impaired. The restrictive human cells did not express increased levels of TRIM5alpha, and restriction was not relieved by abolishing CypA, consistent with HIV(quad) and SIV being CypA-independent. Pseudotyping of lentiviral vectors with the gibbon ape leukemia virus envelope altered their sensitivity to perturbations of the virus-CypA interaction compared to pseudotyping with vesicular stomatitis virus glycoproteins, suggesting that the viral entry pathway modulates restriction. Together, these studies reveal that an HIV-1 capsid quadruple mutant can partially overcome lentiviral restriction in non-human primate epithelial cells, but not in hematopoietic cells. Similarly, human cells vary in their permissiveness for CypA-independent lentiviruses, and suggest the presence of tissue-specific factor(s) that can inhibit lentiviral transduction independently of viral interaction with TRIM5alpha and CypA.

Domain II hairpin structure in ITS1 sequences as an aid in differentiating recently evolved animal and plant pathogenic fungi.

The hypothesis that ITS structural features can be used to define fungal groups, where sequence analysis is unsatisfactory, was examined in plant and animal pathogenic fungi. Structural models of ITS1 regions were predicted for presumed closely related species in Colletotrichum and Trichophyton anamorphs of Arthroderma species. Structural alignment of models and comparison with ITS sequence analysis identified a variable region in a conserved hairpin formed from a common inverted repeat. Thirteen different hairpin structure models were obtained for Colletotrichum species and five different models were obtained for Trichophyton species. The different structure types could be matched to individual species and species complexes as defined by ITS sequence analysis.

Analysis of the acute postoperative pain experience following oral surgery: identification of 'unaffected', 'disabled' and 'depressed, anxious and disabled' patient clusters.

BACKGROUND: Pain is defined as both a sensory and an emotional experience. Acute postoperative tooth extraction pain is assessed and treated as a physiological (sensory) pain while chronic pain is a biopsychosocial problem. The purpose of this study was to assess whether psychological and social changes occur in the acute pain state. METHODS: A biopsychosocial pain questionnaire was completed by 438 subjects (165 males, 273 females) with acute postoperative pain at 24 hours following the surgical extraction of teeth and compared with 273 subjects (78 males, 195 females) with chronic orofacial pain. Statistical methods used a k-means cluster analysis. RESULTS: Three clusters were identified in the acute pain group: 'unaffected', 'disabled' and 'depressed, anxious and disabled'. Psychosocial effects showed 24.8 per cent feeling 'distress/suffering' and 15.1 per cent 'sad and depressed'. Females reported higher pain intensity and more distress, depression and inadequate medication for pain relief (p < 0.001). Distress and depression were associated with higher pain intensity. The developed questionnaire had tested reliability (test-retest r = 0.89) and estimated validity. CONCLUSION: Cluster analysis showed constituent groups with a range of psychosocial effects in acute postoperative dental extraction pain and is associated with an increase in pain intensity.