Containment of procedure-associated aerosols by an extractor tent: effect on nebulized drug particle dispersal.

BACKGROUND: Several medical procedures involving the respiratory tract are considered as 'aerosol-generating procedures'. Aerosols from these procedures may be inhaled by bystanders, and there are consequent concerns regarding the transmission of infection or, specific to nebulized therapy, secondary drug exposure. AIM: To assess the efficacy of a proprietary high-efficiency-particulate-air-filtering extractor tent on reducing the aerosol dispersal of nebulized bronchodilator drugs. METHODS: The study was conducted in an unoccupied outpatient room at St. James's Hospital, Dublin, Ireland. A novel real-time, fluorescent particle counter, the Wideband Integrated Bioaerosol Sensor (WIBS), monitored room air continuously for 3 h. Baseline airborne particle count and count during nebulization of bronchodilator drug solutions were recorded. FINDINGS: Nebulization within the tent prevented any increase over background level. Nebulization directly into room air resulted in mean fluorescent particle counts of 4.75 x 105/m3 and 4.21 x 105/m3 for Ventolin and Ipramol, respectively, representing more than 400-fold increases over mean background level. More than 99.3% of drug particles were <2 µm in diameter and therefore small enough to enter the lower respiratory tract. CONCLUSION: The extractor tent was completely effective for the prevention of airborne spread of drug particles of respirable size from nebulized therapy. This suggests that extractor tents of this type would be efficacious for the prevention of airborne infection from aerosol-generating procedures during the COVID-19 pandemic.

Effectiveness of a plasma treatment device on microbial air quality in a hospital ward, monitored by culture.

This study analysed the effectiveness of plasma treatment on airborne bacteria and surface counts during a 14-day intervention within a four-bedded bay in an adult respiratory ward at Cork University Hospital, Ireland. One-hundred-litre air samples were collected twice daily every weekday for 4 weeks, with settle plates and surface swabs. The plasma treatment did not have an effect on airborne bacteria and fungi that was detectable by culture. However, the possibility that culture-based sampling may be insufficiently sensitive to detect an effect, or that the duration of the study was insufficient for plasma treatment to affect a complex environment, cannot be excluded.

Detection of Rater Errors on Cognitive Instruments in a Clinical Trial Setting.

OBJECTIVES: This study examines errors committed by raters in a clinical trial of a memory enhancement compound. BACKGROUND: Findings of clinical trials are directly dependent on the quality of the data obtained but there is little literature on rates or nature of rater errors on cognitive instruments in a multi-site setting. DESIGN: Double-blind placebo-controlled study. SETTING: 21 clinical sites in North America. PARTICIPANTS: Two hundred seventy-five participants. MEASUREMENTS: MMSE, WMS-R Logical Memory I and II, WMS-R Verbal Paired Associates I, WASi Vocabulary, WASi Matrix Reasoning, GDS and MAC-Q. RESULTS: The WMS-R Logical Memory I and II and WASi Vocabulary tests were found to have the greatest number of scoring errors. Few substantive errors were detected on source document review of the MMSE, GDS, MAC-Q and WMS-R Verbal Paired Associates I. Some additional administration and scoring issues were identified during feedback sessions with the raters. CONCLUSIONS: Cognitive measures used in clinical trials are prone to errors which can be detected with proper monitoring. Some instruments are particularly prone to inter-rater variably and should therefore be targets for focused training and ongoing monitoring. Areas in need of further investigation to help inform and optimize quality of clinical trial data are discussed.

Analysis of subsequent publication and impact of abstracts presented at the Sir Peter Freyer Surgical Symposium: Focus on the Plenary Session.

BACKGROUND: The quality of abstracts presented at a conference reflects the academic activity and research productivity of the surgical/scientific association concerned. The abstract to publication rate (44.5 % internationally), is an important indicator of the quality of presented research. AIM: To evaluate the publication rate and impact of abstracts presented at the plenary session of the Sir Peter Freyer Surgical Symposium over a 25-year period (1989-2014), and identify factors influencing publication. METHODS: Plenary abstracts were identified from abstract books of the Symposium from 1989-2014. The authors, institution, subspecialty and research subject were recorded. A Medline search with name of the first and last author, key words and content of all abstracts was conducted to identify related publications. The impact factor (IF) of the journal and the time to publication was recorded. RESULTS: 298 presented abstracts resulted in 168 publications (publication rate: 56 %). Basic Science research accounted for 80 % (n = 237) of the total number of presentations with the remaining 20 % (n = 61) being categorised as clinical research. Overall, cancer research accounted for 48 % of presented work. The average time to publication was 2 ± 7 years, while 11 % of all published studies achieved publication in the year of the symposium. The median impact factor for published research was 3.558 (IF range 0-39). CONCLUSION: These results indicate that the quality of papers presented at the Sir Peter Freyer Surgical Symposium compares favourably with international equivalents, making this meeting an important forum for Irish Academic Surgery.

Endovascular approaches to the ascending aorta for repair with straight and branched endografts: techniques and for what lesions.

Traditionally ascending aortic lesions have been repaired in open fashion: stenotomy, cardiopulmonary bypass, with or without deep hypothermic circulatory arrest. However, a subsegment of patients are deemed too high risk for open intervention. In the advent of endovascular advancement, this subset of patients may be treated with the use of stents (physician made, off-label use), branched stents, through a variety of methods and approaches. Although there are currently no large randomized, prospective studies, success has been seen in smaller case series. This review article addresses the identification of anatomy amenable to endovascular repair for management of type A aortic dissection, pseudoaneurysm, and zone 0 lesions. Different approaches to repair, including transapical, transeptal, femoral, common carotid, and axillary graft insertion are also examined. For endovascular treatment of ascending aortic lesions to grow as a field, devices made specifically for the ascending aorta need to be designed and larger trials are necessary to evaluate the rates of complications, morbidity, and mortality, and graft patency.

Resveratrol inhibits periodontal pathogens in vitro.

The gram-negative anaerobic bacteria A. actinomycetemcomitans (Aa) and P. gingivalis (Pg) are key components in the aetiology of periodontal disease, and associated hard-tissue destruction. Resveratrol is a phytoalexin, produced naturally by several plants when under attack by bacterial or fungal pathogens. It is found in many foods including mulberries, peanuts and the skin of labrusca and muscadine grapes. The objective of this study was to evaluate the effect of resveratrol on the in vitro growth of periodontal pathogens Aa and Pg. For comparison, resveratrol's effect on a variety of other oral microorganisms was also evaluated. Resveratrol demonstrates a poor solubility in water, thus different concentrations of resveratrol in the solvent dimethyl sulphoxide (DMSO) were added to calibrated suspensions of Aa and Pg. As a control, a parallel series of dilutions containing the vehicle DMSO alone was made to measure the effect of the solvent. Minimum inhibitory concentrations of the periodontal pathogens were calculated. All suspensions were incubated for 1, 3, 6 and 24 h in an anaerobic chamber at 37 °C. At each time interval, selected dilutions from each culture broth were plated on blood agar plates. Colonies appearing on blood agar plates were visually counted at 3 days for Aa, and at 5 days for Pg. The periodontal bacteria showed a significant decrease (p < 0.05) in viable counts after 1 h, whilst no colony forming units could be observed after 24 h. The results suggest that resveratrol possesses significant antimicrobial properties on periodontal pathogens in vitro.

Comparison of hydrogen and deuterium adsorption on Pd(100).

Low energy ion recoil spectroscopy is a powerful technique for the determination of adsorbate position on metal surfaces. In this study, this technique is employed to compare the adsorption sites of hydrogen and deuterium on Pd(100) by detection of either H or D recoil ions produced by Ne(+) bombardment. Comparisons of experimental and Kalypso simulated azimuthal yield distributions show that, at room temperature, both hydrogen isotopes are adsorbed in the fourfold hollow site of Pd(100), however, at different heights above the surface (H-0.20 A and D-0.25 A). The adsorbates remain in the hollow site at all temperatures up to 383 K even though they move up to 0.40-0.45 A above the surface. Density functional theory calculations show a similar coverage dependent adsorption height for both H and D and confirm a real difference between the H and D adsorption heights based on zero point energies.

Field hospital analgesia.

Acute pain is every health care worker's responsibility, a key area of clinical management and one of Surgeon General's four focus points for improving quality of life after battlefield injury. The evolving practice of acute pain management requires an informed multidisciplinary and multimodal therapeutic approach to minimise each individual patient's experience of pain. Whilst subject matter experts progress the policies, protocols and capabilities associated with pain management, it remains the duty of every clinician, nurse, health care support worker and all Professions Allied to medicine (PAMs) to keep updated and maintain capability in this key area of clinical management.

The early detection and management of neuropathic pain following combat injury.

The mechanism of injury on the modern battlefield results in a pattern of wounding which is associated with both nociceptive and neuropathic pain. Nociceptive pain is managed using the WHO Analgesic Ladder but neuropathic pain requires the use of co-analgesic drugs, e.g. antidepressants and anticonvulsants. This study was designed to determine the incidence of neuropathic pain within military casualties with limb injuries. From May to November 2007, 50 casualties were interviewed and assessed using the Leeds Assessment of Neuropathic Symptoms and Signs Scale (LANSS) over consecutive weeks. During the first week post injury, 30% of casualties had a LANSS pain score > 12, suggesting a neuropathic element to their pain. The early detection (using LANSS) and management of neuropathic pain using robust protocols represent the most effective strategy to address this significant problem.

Pathologic findings in prospectively ascertained essential tremor subjects.

OBJECTIVE: To assess pathologic changes in prospectively characterized subjects with essential tremor (ET). METHODS: Subjects enrolled in the Sun Health Research Institute Brain and Body Donation Program were examined annually by a movement disorders neurologist, and semiannually by a behavioral neurologist and neuropsychologist. Twenty-four subjects without a prior diagnosis of dementia or other major movement disorder met clinical criteria for ET and came to autopsy. Subjects with mild cognitive impairment (n = 3) were included. These subjects were compared with 21 controls. Brains were examined postmortem according to standardized protocols for assessment of age-related changes and specific pathologic conditions (e.g., Parkinson disease, Alzheimer disease). RESULTS: Subjects had a mean age of 86.2 years and a mean duration of tremor of 11.1 years. Seven subjects had evidence for cerebellar pathology (Purkinje cell loss, cerebellar cortical sclerosis, and proliferation of Bergmann glia). Pigmented neurons were qualitatively depleted in the locus ceruleus in eight subjects and in the substantia nigra in five subjects. Of these, three had Lewy bodies, one subject had brainstem predominant disease, and two had limbic stage. Three subjects had a nonspecific cerebral tauopathy and another met pathologic criteria for progressive supranuclear palsy. However, when compared with controls, only changes in the locus ceruleus and gliosis of the cerebellum remained significant findings. CONCLUSIONS: This study supports previous findings of heterogenous pathology in essential tremor (ET). There is an increased frequency of cerebellar gliosis and locus ceruleus depletion. We did not find an increased incidence of Lewy bodies in subjects with ET.

Functional ability correlates with cognitive impairment in Parkinson's disease and Alzheimer's disease.

BACKGROUND/AIMS: Previously we have shown that functional declines in Parkinson's disease (PD) and Alzheimer's disease (AD) correlate to global measures of cognitive decline. We now determine if the correlation between cognitive impairment and functional ability in PD is similar to that in AD using individual cognitive measures. METHODS: 93 PD subjects and 124 AD/MCI subjects underwent the Functional Assessment Staging (FAST), the Global Deterioration Scale (GDS), and a neuropsychological battery. RESULTS: In PD subjects, the FAST and GDS correlated significantly with Rey Auditory Verbal Learning Test (AVLT), Controlled Oral Word Association (COWA), Animal Fluency, and Stroop but not with Clock Draw or Judgment Line Orientation (JLO). In AD/MCI subjects, FAST and GDS correlated with all neuropsychological components except Stroop. In the AD/MCI group, the UPDRS significantly correlated with the FAST, GDS, MMSE, and all neuropsychological parameters except the Stroop. In the PD group, the motor UPDRS significantly correlated significantly with FAST, GDS, MMSE and all neuropsychological parameters except Digit Span, Stroop, Clock Draw and JLO. CONCLUSIONS: Similar to AD, functional decline in PD correlates with multiple measures of cognitive impairment. Some differences between PD and AD may be explained by the influence of motor disability and declines in visuospatial function in PD.

Both early and late cognitive dysfunction affects the electroencephalogram in Parkinson's disease.

We sought to define quantitative electroencephalographic (EEG) measures as biomarkers of both early and late cognitive decline in Parkinson's disease (PD). PD subjects classified as cognitively normal (PD-CogNL), mild cognitive impairment (PD-MCI), and dementia (PD-D) were studied. Cognitive status and neuropsychological testing was correlated with background rhythm and frequency band EEG power across five frequency bands. We conclude that global EEG measures have potential use as biomarkers in the study of both early and late cognitive deterioration in PD, including for evaluating its treatment. PD-MCI has mean quantitative EEG characteristics that represent an intermediate electrophysiological state between PD-CogNL and PD-D.

Bochdalek hernia in a soldier.

Congenital diaphragmatic hernias are most often seen in infants. They may rarely be discovered in adulthood. This case report describes the management of a soldier presenting with acute bowel obstruction and respiratory embarrassment in a military hospital. The surgical repair was achieved with a laparotomy. Effective epidural analgesia and early physiotherapy were axiomatic of his uncomplicated post-operative course.

Circulating cholesterol levels, apolipoprotein E genotype and dementia severity influence the benefit of atorvastatin treatment in Alzheimer's disease: results of the Alzheimer's Disease Cholesterol-Lowering Treatment (ADCLT) trial.

CONTEXT: Recent evidence suggests that treatment of mild-to-moderate Alzheimer's disease (AD) with atorvastatin provides significant benefit on the Alzheimer Disease Assessment Scale-Cognitive (ADAS-cog) after 6 months. OBJECTIVE: To determine if benefit on ADAS-cog performance produced by atorvastatin is influenced by severity of cognitive impairment, circulating cholesterol levels, or apolipoprotein E genotype. DESIGN: A double-blind, placebo-controlled, randomized (1:1) trial with a 1-year exposure to atorvastatin calcium or placebo. SETTING: A single-site study at the clinical research center of the Sun Health Research Institute. PARTICIPANTS: Ninety-eight individuals with mild-to-moderate AD (MMSE score of 12-28) provided informed consent, and 67 were randomized. Stable dose use of cholinesterase inhibitors, estrogen and vitamin E was allowed, as was the use of many other medications in the treatment of co-morbidities. Participants using cholesterol-lowering medications or being treated for major depression or a psychiatric condition were excluded. INTERVENTION: Once daily atorvastatin calcium (80 mg; two 40 mg tablets) or placebo. MAIN OUTCOME MEASURES: A primary outcome measure was change ADAS-cog sub-scale score. Secondary outcome measures included scores on the MMSE, and circulating cholesterol levels. The Apolipoprotein E genotype was established for each participant. RESULTS: A significant positive effect on ADAS-cog performance occurred after 6 months of atorvastatin therapy compared with placebo. This positive effect was more prominent among individuals entering the trial with, (i) higher MMSE scores, (ii) cholesterol levels above 200 mg/dl or (iii) if they harbored an apolipoprotein-E-4 allele compared with participants not responding to atorvastatin treatment. Individuals in the placebo group tended to experience more pronounced deterioration if their cholesterol levels exceeded 200 mg/dl or they harbored an apolipoprotein-E-4 allele. CONCLUSION: Atorvastatin therapy may be of benefit in the treatment of mild-to-moderately affected AD patients, but the level of benefit produced may be predicated on earlier treatment, an individual's apolipoprotein E genotype or whether the patient exhibits elevated cholesterol levels.

HMG-CoA reductase inhibitors (statins) in the treatment of Alzheimer's disease and why it would be ill-advise to use one that crosses the blood-brain barrier.

Increased circulating cholesterol has been long linked to an increased risk of coronary artery disease (CAD), and is now linked to an increased risk of developing Alzheimer s disease (AD). We first showed the neuropathologic link between CAD and AD as increased incidence of cerebral senile plaques in both disorders. We then showed that AD-like neuropathology occurred in the brains of cholesterol-fed rabbits; including increased -amyloid (Ab). Currently there are a number of transgenic mouse models of AD that exhibit enhanced Ab pathology if cholesterol diet is administered. Culture studies clearly show that excess cholesterol enhances beta-metabolism of amyloid precursor protein (APP) and production of -amyloidogenic peptides, and that sufficiently reducing cholesterol levels by inhibition of synthesis completely inhibits all beta-metabolism of APP. Our finding that the elevated levels of Ab in rabbits fed cholesterol diet could be cleared from the brain by resuming a control diet prompted the hypothesis that lowering cholesterol levels in the blood of AD patients may be of some clinical benefit. Pilot data suggests that therapeutically lowering circulating cholesterol may attenuate Ab production in the cholesterol-fed rabbit brain, may stabilize cognitive performance in mildly impaired AD patients, and may reduce the risk of developing AD. Accordingly, we have initiated a double-blind treatment trial evaluating Atorvastatin Na+ among 120 mild-to-moderately impaired AD subjects randomized to one of two groups receiving placebo or active drug once a day. Atorvastatin is one of a general class of HMG-CoA reductase inhibitor drugs called statins that lower cholesterol by inhibition of synthesis. We chose to use Atorvastatin in this AD Treatment Trial because it does not cross the blood-brain-barrier, and believe it would be ill-advised to use a statin that does. This position stems from the observations that excess cholesterol inhibits cholesterol synthesis and increases Ab production, that Ab kills cells in part by inhibiting cholesterol synthesis, and that statins acting at the neuronal level could further exacerbate degeneration in AD by further inhibition of necessary cholesterol synthesis.

ASPP proteins specifically stimulate the apoptotic function of p53.

We identified a family of proteins termed ASPP. ASPP1 is a protein homologous to 53BP2, the C-terminal half of ASPP2. ASPP proteins interact with p53 and specifically enhance p53-induced apoptosis but not cell cycle arrest. Inhibition of endogenous ASPP function suppresses the apoptotic function of endogenous p53 in response to apoptotic stimuli. ASPP enhance the DNA binding and transactivation function of p53 on the promoters of proapoptotic genes in vivo. Two tumor-derived p53 mutants with reduced apoptotic function were defective in cooperating with ASPP in apoptosis induction. The expression of ASPP is frequently downregulated in human breast carcinomas expressing wild-type p53 but not mutant p53. Therefore, ASPP regulate the tumor suppression function of p53 in vivo.

Randomized, controlled study of low-dose 5-fluorouracil in primary trabeculectomy.

PURPOSE: To report a randomized clinical trial of postoperative subconjunctival injections of low-dose 5-fluorouracil in patients undergoing primary trabeculectomy. METHODS: In a prospective, randomized clinical trial, 40 eyes of 40 patients were randomized to the low-dose 5-fluorouracil group and received three subconjunctival injections of 5 mg each over 11 postoperative days, and 40 eyes of 40 patients were randomized to trabeculectomy without 5-fluorouracil. RESULTS: Mean (+/-SD) preoperative and 1-year postoperative intraocular pressures in the 5-fluorouracil group were 26.9 (+/-9.5) and 15.3 (+/-5.8) mm Hg, respectively. In the control group these were 25.9 (+/-8.1) mm Hg, and 15.8 (+/-5.1) mm Hg, respectively. The patients who received 5-fluorouracil had a mean reduction in intraocular pressure of 11.5 (+/-9.1) mm Hg at a median follow-up of 52.3 weeks. The control group had a mean reduction in intraocular pressure of 10.2 (+/-8.7) mm Hg at a median follow-up of 52.6 weeks. These differences were not statistically significant. CONCLUSIONS: Three postoperative subconjunctival 5-fluorouracil injections of 5 mg each after trabeculectomy in eyes at low risk for failure had no statistically or clinically significant effect on reduction of intraocular pressure with 1-year follow-up. Enhancement of success in this group of patients may require a larger total dose of 5-fluorouracil.

Proapoptotic p53-interacting protein 53BP2 is induced by UV irradiation but suppressed by p53.

p53 is an important mediator of the cellular stress response with roles in cell cycle control, DNA repair, and apoptosis. 53BP2, a p53-interacting protein, enhances p53 transactivation, impedes cell cycle progression, and promotes apoptosis through unknown mechanisms. We now demonstrate that endogenous 53BP2 levels increase following UV irradiation induced DNA damage in a p53-independent manner. In contrast, we found that the presence of a wild-type (but not mutant) p53 gene suppressed 53BP2 steady-state levels in cell lines with defined p53 genotypes. Likewise, expression of a tetracycline-regulated wild-type p53 cDNA in p53-null fibroblasts caused a reduction in 53BP2 protein levels. However, 53BP2 levels were not reduced if the tetracycline-regulated p53 cDNA was expressed after UV damage in these cells. This suggests that UV damage activates cellular factors that can relieve the p53-mediated suppression of 53BP2 protein. To address the physiologic significance of 53BP2 induction, we utilized stable cell lines with a ponasterone A-regulated 53BP2 cDNA. Conditional expression of 53BP2 cDNA lowered the apoptotic threshold and decreased clonogenic survival following UV irradiation. Conversely, attenuation of endogenous 53BP2 induction with an antisense oligonucleotide resulted in enhanced clonogenic survival following UV irradiation. These results demonstrate that 53BP2 is a DNA damage-inducible protein that promotes DNA damage-induced apoptosis. Furthermore, 53BP2 expression is highly regulated and involves both p53-dependent and p53-independent mechanisms. Our data provide new insight into 53BP2 function and open new avenues for investigation into the cellular response to genotoxic stress.