Detection of Mucosal Human Papillomavirus Types 6/11 in Cutaneous Lesions from Transplant Recipients

Transplant recipients develop multiple cutaneous lesions. We have identified human papillomavirus (HPV) DNA in these lesions using three different techniques, namely polymerase chain reaction (PCR), in situ hybridization, and Southern blotting. By PCR, HPV DNA was detected in 43 of 62 samples: warts, actinic keratoses, Bowen's disease, and squamous cell carcinomas. Surprisingly, HPV 6/11, usually associated with mucosa, were frequently found in benign, premalignant, and malignant cutaneous lesions (30/43 cases). Some of these biopsies were simultaneously tested by in situ hybridization and/or Southern blotting. By in situ hybridization, HPV 6/11 were identified in two warts and one squamous cell carcinoma among 29 tissue specimens tested. Of the three samples examined by Southern blotting, HPV 6/11 were detected in one squamous cell carcinoma. In patients from a control population cutaneous biopsies did not exhibit HPV types 6/11 except in Bowen's disease; HPV types 1 or 2 were mainly found in benign warts. These findings suggest that in transplant recipients, HPV can lose their specificity towards mucosa or cutaneous epithelium. The significance of the presence of HPV 6/11 in skin lesions remains unknown

214: Interpreting troponin elevation in relation to symptom onset in intermediate-risk pulmonary embolism

BackgroundTroponin elevation in the setting of acute pulmonary embolism (PE) is of small magnitude and short duration and can go unnoticed in pts referred late after symptom onset.MethodsProspective, single-center registry of pts with confirmed intermediate-risk PE, defined as at least 1 echocardiographic finding of right ventricular (RV) dysfunction (endo-diastolic (EDRV)/left ventricular (EDLV) end-diastolic diameter ratio >=1 in the 4-chamber view, paradoxical septal systolic motion or pulmonary hypertension defined as RV/atrial gradient >30mmHg), or positive troponin test. Combined in-hospital endpoint was defined as death, non-fatal recurrent PE, or residual pulmonary vascular obstruction (RPVO) ≥35%.Results282 pts were included, age 66±14 years, 59% women, 174 (62%) referred ≤5 days after symptom onset, 108 (38%) after >5 days. Troponin elevation was observed in 126 (72%) treated within ≤5 days, in 60 (56%) treated after >5 days (p=0.004). A significant interaction was observed between time since symptom onset and both troponin elevation and persistence of EDRV/EDLV diameter ratio>1 at 48h. The negative predictive value of troponin elevation was 85% in patients treated within 5 days of symptoms, but fell to 70% in those admitted >5 days after symptom onset (p=0.002). Positive troponin was an independent predictor of adverse outcome (OR=1.43 [1.08-5.56]). ROC curves show that prognostic value of positive troponin test was higher in pts referred ≤5 days than in pts referred >5 days after symptom onset (p=0.01).ConclusionThere is a significant relation between troponin elevation and time since symptom onset in patients with intermediate-risk PE. Negative predictive value of troponin elevation is adequate in pts treated early (≤5 days) but is suboptimal in pts treated >5 days after symptom onset.TableResults<=5 days since symptom onset>5 days since symptom onsetpSensitivity72% (61.3-82.7)51% (42.4-59.6)0.005Specificity42% (44.5-49.5)47% (39.1-54.9)0.33PPV26% (18.4-33.6)30% (22.2-37.8)0.81NPV85% (78.4-91.6)70% (63-77)0.00

Age-related Purkinje cell death is steroid dependent: RORα haplo-insufficiency impairs plasma and cerebellar steroids and Purkinje cell survival

A major problem of ageing is progressive impairment of neuronal function and ultimately cell death. Since sex steroids are neuroprotective, their decrease with age may underlie age-related neuronal degeneration. To test this, we examined Purkinje cell numbers, plasma sex steroids and cerebellar neurosteroid concentrations during normal ageing (wild-type mice, WT), in our model of precocious ageing (Rora+/sg, heterozygous staggerer mice in which expression of the neuroprotective factor RORα is disrupted) and after long-term hormone insufficiency (WT post-gonadectomy). During normal ageing (WT), circulating sex steroids declined prior to or in parallel with Purkinje cell loss, which began at 18 months of age. Although Purkinje cell death was advanced in WT long-term steroid deficiency, this premature neuronal loss did not begin until 9 months, indicating that vulnerability to sex steroid deficiency is a phenomenon of ageing Purkinje neurons. In precocious ageing (Rora+/sg), circulating sex steroids decreased prematurely, in conjunction with marked Purkinje cell death from 9 months. Although Rora+/sg Purkinje cells are vulnerable through their RORα haplo-insufficiency, it is only as they age (after 9 months) that sex steroid failure becomes critical. Finally, cerebellar neurosteroids did not decrease with age in either genotype or gender; but were profoundly reduced by 3 months in male Rora+/sg cerebella, which may contribute to the fragility of their Purkinje neurons. These data suggest that ageing Purkinje cells are maintained by circulating sex steroids, rather than local neurosteroids, and that in Rora+/sg their age-related death is advanced by premature sex steroid loss induced by RORα haplo-insufficiency

The impact of COVID-19 on hospitalised COPD exacerbations in Malta

Introduction and Aims. The first COVID-19 case in Malta was confirmed on the 7th of March 2020. This study is aimed at investigating a significant difference between the number of acute exacerbations of chronic obstructive pulmonary disease (AECOPD) admissions and their inpatient outcome at Mater Dei Hospital during the COVID-19 pandemic when compared to the same period in 2019. Furthermore, we aim to determine predictors of mortality in AECOPD inpatients. Method. Data was collected retrospectively from electronic hospital records during the periods 1st March until 10th May in 2019 and 2020. Results. There was a marked decrease in AECOPD admissions in 2020, with a 54.2% drop in admissions (n = 119 in 2020 vs. n = 259 in 2019). There was no significant difference in patient demographics or medical comorbidities. In 2020, there was a significantly lower number of patients with AECOPD who received nebulised medications during admission (60.4% in 2020 vs. 84.9% in 2019; p ≤ 0:001). There were also significantly lower numbers of AECOPD patients admitted in 2020 who received controlled oxygen via venturi masks (69.0% in 2020 vs. 84.5% in 2019; p = 0:006). There was a significant increase in inpatient mortality in 2020 (19.3% [n = 23] and 8.4% [n = 22] for 2020 and 2019, respectively, p = 0:003). Year was found to be the best predictor of mortality outcome (p = 0:001). The lack of use of SABA pre-admission treatment (p = 0:002), active malignancy (p = 0:003), and increased length of hospital stay (p = 0:046) were also found to be predictors of mortality for AECOPD patients; however, these parameters were unchanged between 2019 and 2020 and therefore could not account for the increase in mortality. Conclusions. There was a decrease in the number of admissions with AECOPD in 2020 during the COVID-19 pandemic, when compared to 2019. The year 2020 proved to be a significant predictor for inpatient mortality, with a significant increase in mortality in 2020. The decrease in nebuliser and controlled oxygen treatment noted in the study period did not prove to be a significant predictor of mortality when corrected for other variables. Therefore, the difference in mortality cannot be explained with certainty in this retrospective cohort study.peer-reviewe

Ex-vivo changes in amino acid concentrations from blood stored at room temperature or on ice: implications for arginine and taurine measurements

Background: Determination of the plasma concentrations of arginine and other amino acids is important for understanding pathophysiology, immunopathology and nutritional supplementation in human disease. Delays in processing of blood samples cause a change in amino acid concentrations, but this has not been precisely quantified. We aimed to describe the concentration time profile of twenty-two amino acids in blood from healthy volunteers, stored at room temperature or on ice.Methods: Venous blood was taken from six healthy volunteers and stored at room temperature or in an ice slurry. Plasma was separated at six time points over 24 hours and amino acid levels were determined by high-performance liquid chromatography.Results: Median plasma arginine concentrations decreased rapidly at room temperature, with a 6% decrease at 30 minutes, 25% decrease at 2 hours and 43% decrease at 24 hours. Plasma ornithine increased exponentially over the same period. Plasma arginine was stable in blood stored on ice, with a &lt; 10% change over 24 hours. Plasma taurine increased by 100% over 24 hours, and this change was not prevented by ice. Most other amino acids increased over time at room temperature but not on ice.Conclusion: Plasma arginine concentrations in stored blood fall rapidly at room temperature, but remain stable on ice for at least 24 hours. Blood samples taken for the determination of plasma amino acid concentrations either should be placed immediately on ice or processed within 30 minutes of collection

Symptomatic and Asymptomatic Neurological Complications of Infective Endocarditis: Impact on Surgical Management and Prognosis

International audienceObjectives:Symptomatic neurological complications (NC) are a major cause of mortality in infective endocarditis (IE) but the impact of asymptomatic complications is unknown. We aimed to assess the impact of asymptomatic NC (AsNC) on the management and prognosis of IE.Methods: From the database of cases collected for a population-based study on IE, we selected 283 patients with definite left-sided IE who had undergone at least one neuroimaging procedure (cerebral CT scan and/or MRI) performed as part of initial evaluation.Results Among those 283 patients, 100 had symptomatic neurological complications (SNC) prior to the investigation, 35 had an asymptomatic neurological complications (AsNC), and 148 had a normal cerebral imaging (NoNC). The rate of valve surgery was 43% in the 100 patients with SNC, 77% in the 35 with AsNC, and 54% in the 148 with NoNC (p<0.001). In-hospital mortality was 42% in patients with SNC, 8.6% in patients with AsNC, and 16.9% in patients with NoNC (p<0.001). Among the 135 patients with NC, 95 had an indication for valve surgery (71%), which was performed in 70 of them (mortality 20%) and not performed in 25 (mortality 68%). In a multivariate adjusted analysis of the 135 patients with NC, age, renal failure, septic shock, and IE caused by S. aureus were independently associated with in-hospital and 1-year mortality. In addition SNC was an independent predictor of 1-year mortality.Conclusions The presence of NC was associated with a poorer prognosis when symptomatic. Patients with AsNC had the highest rate of valve surgery and the lowest mortality rate, which suggests a protective role of surgery guided by systematic neuroimaging results

The Complete Genome of \u3cem\u3eTeredinibacter turnerae\u3c/em\u3e T7901: An Intracellular Endosymbiont of Marine Wood-Boring Bivalves (Shipworms)

Here we report the complete genome sequence of Teredinibacter turnerae T7901. T. turnerae is a marine gamma proteobacterium that occurs as an intracellular endosymbiont in the gills of wood-boring marine bivalves of the family Teredinidae (shipworms). This species is the sole cultivated member of an endosymbiotic consortium thought to provide the host with enzymes, including cellulases and nitrogenase, critical for digestion of wood and supplementation of the host\u27s nitrogen-deficient diet. T. turnerae is closely related to the free-living marine polysaccharide degrading bacterium Saccharophagus degradans str. 2–40 and to as yet uncultivated endosymbionts with which it coexists in shipworm cells. Like S. degradans, the T. turnerae genome encodes a large number of enzymes predicted to be involved in complex polysaccharide degradation (\u3e100). However, unlike S. degradans, which degrades a broad spectrum (\u3e10 classes) of complex plant, fungal and algal polysaccharides, T. turnerae primarily encodes enzymes associated with deconstruction of terrestrial woody plant material. Also unlike S. degradans and many other eubacteria, T. turnerae dedicates a large proportion of its genome to genes predicted to function in secondary metabolism. Despite its intracellular niche, the T. turnerae genome lacks many features associated with obligate intracellular existence (e.g. reduced genome size, reduced %G+C, loss of genes of core metabolism) and displays evidence of adaptations common to free-living bacteria (e.g. defense against bacteriophage infection). These results suggest that T. turnerae is likely a facultative intracellular ensosymbiont whose niche presently includes, or recently included, free-living existence. As such, the T. turnerae genome provides insights into the range of genomic adaptations associated with intracellular endosymbiosis as well as enzymatic mechanisms relevant to the recycling of plant materials in marine environments and the production of cellulose-derived biofuels

The Complete Genome of Teredinibacter turnerae T7901: An Intracellular Endosymbiont of Marine Wood-Boring Bivalves (Shipworms)

Here we report the complete genome sequence of Teredinibacter turnerae T7901. T. turnerae is a marine gamma proteobacterium that occurs as an intracellular endosymbiont in the gills of wood-boring marine bivalves of the family Teredinidae (shipworms). This species is the sole cultivated member of an endosymbiotic consortium thought to provide the host with enzymes, including cellulases and nitrogenase, critical for digestion of wood and supplementation of the host's nitrogen-deficient diet. T. turnerae is closely related to the free-living marine polysaccharide degrading bacterium Saccharophagus degradans str. 2–40 and to as yet uncultivated endosymbionts with which it coexists in shipworm cells. Like S. degradans, the T. turnerae genome encodes a large number of enzymes predicted to be involved in complex polysaccharide degradation (>100). However, unlike S. degradans, which degrades a broad spectrum (>10 classes) of complex plant, fungal and algal polysaccharides, T. turnerae primarily encodes enzymes associated with deconstruction of terrestrial woody plant material. Also unlike S. degradans and many other eubacteria, T. turnerae dedicates a large proportion of its genome to genes predicted to function in secondary metabolism. Despite its intracellular niche, the T. turnerae genome lacks many features associated with obligate intracellular existence (e.g. reduced genome size, reduced %G+C, loss of genes of core metabolism) and displays evidence of adaptations common to free-living bacteria (e.g. defense against bacteriophage infection). These results suggest that T. turnerae is likely a facultative intracellular ensosymbiont whose niche presently includes, or recently included, free-living existence. As such, the T. turnerae genome provides insights into the range of genomic adaptations associated with intracellular endosymbiosis as well as enzymatic mechanisms relevant to the recycling of plant materials in marine environments and the production of cellulose-derived biofuels

Brief of Amici Curiae 56 Professors of Law and Economics in Support of Petition of Writ of Certiorari

28 U.S.C. § 1400(b) provides that a defendant in a patent case may be sued where the defendant is incorporated or has a regular and established place of business and has infringed the patent. This Court made clear in Fourco Glass Co. v. Transmirra Prods. Corp., 353 U.S. 222, 223 (1957), that those were the only permissible venues for a patent case. But the Federal Circuit has rejected Fourco and the plain meaning of § 1400(b), instead permitting a patent plaintiff to file suit against a defendant anywhere there is personal jurisdiction over that defendant. The result has been rampant forum shopping, particularly by patent trolls. 44% of 2015 patent lawsuits were filed in a single district: the Eastern District of Texas, a forum with plaintiff-friendly rules and practices, and where few of the defendants are incorporated or have established places of business. And an estimated 86% of 2015 patent cases were filed somewhere other than the jurisdictions specified in the statute. Colleen V. Chien & Michael Risch, Recalibrating Patent Venue, Santa Clara Univ. Legal Studies Research Paper No. 10-1 (Sept. 1, 2016), Table 3. This Court should grant certiorari to review the meaning of 28 U.S.C. § 1400(b) because the Federal Circuit’s dubious interpretation of the statute plays an outsized and detrimental role, both legally and economically, in the patent system