Atmospheric drying and soil drying: Differential effects on grass community composition.

Global surface temperatures are projected to increase in the future; this will modify regional precipitation regimes and increase global atmospheric drying. Despite many drought studies examining the consequences of reduced precipitation, there are few experimental studies exploring plant responses to atmospheric drying via relative humidity and vapor pressure deficit (VPD). We examined eight native California perennial grass species grown in pots in a greenhouse in Los Angeles, California for 34 weeks. All pots were well-watered for 21 weeks, at which point we reduced watering to zero and recorded daily growth and dormancy for 3 weeks. We used this information to better understand the drought tolerance of our species in a larger soil drying × atmospheric drying experiment. In this larger experiment, we grew all eight species together in outdoor mesocosms and measured changes in community composition after 4 years of growth. Soil drying in our small pot experiment mirrored compositional shifts in the larger experiment. Namely, our most drought-tolerant species in our pot experiment was Poa secunda, due to a summer dormancy strategy. Similarly, the grass community shifted toward P. secunda in the driest soils as P. secunda was mostly unaffected by either soil drying or atmospheric drying. We found that some species responded strongly to soil drying (Elymus glaucus, Festuca idahoensis, and Hordeum b. californicum), while others responded strongly to atmospheric drying (Bromus carinatus and Stipa cernua). As result, community composition shifted in different and interacting ways in response to soil drying, atmospheric drying, and their combination. Further study of community responses to increasing atmospheric aridity is an essential next step to predicting the future consequences of climate change.

Application of the threshold of toxicological concern (TTC) in the evaluation of drinking water contact chemicals.

The Threshold of Toxicological Concern (TTC) is an approach for assessing the safety of chemicals with low levels of exposure for which limited toxicology data are available. The original TTC criteria were derived for oral exposures from a distributional analysis of a dataset of 613 chemicals that identified 5th percentile no observed effect level (NOEL) values grouped within three tiers of compounds having specific structural functional groups and/or toxic potencies known as Cramer I, II and III classifications. Subsequent assessments of the TTC approach have established current thresholds to be scientifically robust. While the TTC has gained acknowledgment and acceptance by many regulatory agencies and organizations, use of the TTC approach in evaluating drinking water chemicals has been limited. To apply the TTC concept to drinking water chemicals, an exposure-based approach that incorporates the current weight of evidence for the target chemical is presented. Such an approach provides a comparative point of departure to the 5th percentile TTC NOEL using existing data, while conserving the allocation of toxicological resources for quantitative risk assessment to chemicals with greater exposure or toxicity. This approach will be considered for incorporation into NSF/ANSI/CAN 600, a health effects standard used in the safety evaluation of chemicals present in drinking water from drinking water contact additives and materials certified to NSF/ANSI/CAN 60 and 61, respectively.

Preoperative pain measurements in correlation to deep endometriosis classification with Enzian

Background: Deep Endometriosis (DE) classification studies with Enzian never compared solitary compartments (A, B, C, F), and combinations of anatomical locations (A&B, A&C, B&C, A&B&C), in correlation to pain. Therefore, the results of these studies are challenging to translate to the clinical situation. Objectives: We studied pain symptoms and their correlation with the solitary and combinations of anatomical locations of deep endometriosis lesion(s) classified by the Enzian score. Materials and Methods: A prospective multi-centre study was conducted with data from university and non-university hospitals. A total of 419 surgical DE cases were collected with the web-based application called EQUSUM (www.equsum.org). Main Outcome Measures: Preoperative reported numeric rating scale (NRS) were collected along with the Enzian classification. Baseline characteristics, pain scores, surgical procedure and extent of the disease were also collected. Results: In general, more extensive involvement of DE does not lead to an increase in the numerical rating scale for pain measures. However, dysuria and bladder involvement do show a clear correlation AUC 0.62 (SE 0.04, CI 0.54-0.71, p< 0.01). Regarding the predictive value of dyschezia, we found a weak, but significant correlation with ureteric involvement; AUC 0.60 (SE 0.04, CI 0.53-0.67, p< 0.01). Conclusions: Pain symptoms poorly correlate with anatomical locations of deep endometriosis in almost all pain scores, with the exception of bladder involvement and dysuria which did show a correlation. Also, dyschezia seems to have predictive value for DE ureteric involvement and therefore MRI or ultrasound imaging (ureter and kidney) could be recommended in the preoperative workup of these patients. What's new?: Dyschezia might have a predictive value in detecting ureteric involvement.

Clinical feasibility evaluation of digital dental articulation for three-piece maxillary orthognathic surgery: a proof-of-concept study.

Digital dental articulation for three-piece maxillary orthognathic surgery is challenging. The purpose of this proof-of-concept study was to evaluate the clinical feasibility of a newly developed mathematical algorithm to digitally establish the final occlusion for three-piece maxillary surgery. Five patients with jaw deformities who had undergone a three-piece double-jaw surgery that was planned virtually were randomly selected for this study. The final occlusion had been hand-articulated using stone casts, scanned into the computer and used in the surgery. These hand-articulated occlusions served as the control group. To form the experimental group, the three-piece maxillary dental arch was articulated again automatically from the patient's original occlusion using the mathematical algorithm. The hand- and algorithm-articulated occlusions were then evaluated qualitatively by two experienced orthodontists. A quantitative evaluation was also performed. The results of the qualitative evaluation showed that all of the three-piece occlusions, hand- and algorithm-articulated, were clinically acceptable based on the American Board of Orthodontics grading system. When compared, two of the algorithm-articulated occlusions were clearly better (40%), one was the same (20%), and two were slightly worse (40%) than the hand-articulated occlusions. All of the quantitative measurements were comparable between the two articulation methods. In conclusion, the results of this study demonstrate that it is clinically feasible to digitally articulate the three-piece maxillary arch to the intact mandibular dental arch.

Inpatient teledermatology improves diagnostic accuracy and management of erythroderma in hospitalized patients.

With the onset of the COVID-19 pandemic, healthcare providers have made increasing use of inpatient teledermatology; however, few studies have analysed the impact of teledermatology on patient outcomes. In this study, we investigated the diagnostic concordance between the primary team and teledermatologist, and we analysed the impact of this technology on the diagnosis and management of erythroderma, a condition with high morbidity and mortality. Overall, out of 2987 inpatient teledermatology encounters reviewed, we found 33 cases of erythroderma, and, of these, 78.8% had a change in diagnosis after teledermatology consult, 81.8% were recommended biopsy and all patients had a change in topical/systemic therapy. We hope to promote further study of the efficacy of teledermatology as it may begin to address large gaps in dermatological access to care particularly in regional and community hospitals.

A self-report questionnaire to detect hand dermatitis in nurses.

BACKGROUND: Hand dermatitis is highly prevalent among nurses due to their frequent exposure to wet work. Providing cost-effective dermatological health surveillance for this occupational group presents a challenge to health service providers. AIMS: To ascertain the predictive value of nurses' self-assessment of whether they had current hand dermatitis using a screening questionnaire when compared with the assessment made by a dermatologist of the nurses' hand photographs. METHODS: We conducted a cross-sectional study comparing the self-report decision made by student and intensive care nurses using a single hand dermatitis screening question with the clinical assessment of their hand photographs made by dermatologists using a standardized photographic guide. RESULTS: We analysed data collected at study baseline (n = 1599). The results showed that the screening question had a high negative predictive value (91%; 95% CI 89-93), but a low positive predictive value (39%; 95% CI 34-45). It demonstrated acceptable accuracy in distinguishing those with and without the disease (area under the receiver operator curve = 0.7) and had a high specificity (86%; 95% CI 84-88) but a sensitivity of only 52% (95% CI 46-59) in identifying hand dermatitis. CONCLUSIONS: We found that nurses were able to accurately self-assess themselves as not having any signs of hand dermatitis. By contrast, they were less able to accurately self-assess positive cases suggesting under-recognition of early disease. We propose that a questionnaire containing a single hand dermatitis screening question should be considered as a tool for screening out clear cases as part of a workplace health surveillance programme for detecting hand dermatitis.

Should posterior cerebral artery occlusions be recanalized? Insights from the Trevo Registry.

BACKGROUND AND PURPOSE: The purpose of this study was to evaluate the safety and effectiveness of mechanical thrombectomy (MT) in patients with acute ischaemic stroke related to isolated and primary posterior cerebral artery (PCA) occlusions amongst the patients enrolled in the multicentre post-market Trevo Registry. METHOD: Amongst the 2008 patients enrolled in the Trevo Registry with acute ischaemic stroke due to large vessel occlusion treated by MT, 22 patients (1.1%) [10 females (45.5%), mean age 66.2 ± 14.3 years (range 28-91)] had a PCA occlusion [17 P1 (77.3%) and five P2 occlusions (22.7%)]. Recanalization after the first Trevo (Stryker, Fremont, CA, USA) pass and at the end of the procedure was rated using the modified Thrombolysis in Cerebral Infarction (mTICI) score. Procedure-related complications (i.e. groin puncture complication, perforation, symptomatic haemorrhage, embolus in a new territory) were also recorded. The modified Rankin Scale at 90 days was assessed. RESULTS: Median National Institutes of Health Stroke Scale at admission was 14 (interquartile range 8-16). Stroke aetiology was cardio-embolic in 68.2% of cases. Half of the patients (11/22) received intravenous tissue plasminogen activator. 54.5% of the patients were treated under general anaesthesia. Reperfusion (i.e. mTICI 2b or 3) after first pass was obtained in 65% of cases. Final mTICI 2b-3 reperfusion was obtained in all cases. Only one (4.5%) procedure-related complication was recorded (puncture site) that resolved after surgery. At 90-day follow-up, modified Rankin Scale 0-2 was obtained in 59% of the patients and 9.1% died within the first 3 months after MT. CONCLUSION: Mechanical thrombectomy for PCA occlusions seems to be safe (<5% procedure-related complications) and effective. Larger repository datasets are needed.

A behaviour change package to prevent hand dermatitis in nurses working in the National Health Service: results of a cluster randomized controlled trial.

BACKGROUND: Occupational hand dermatitis poses a serious risk for nurses. OBJECTIVES: To evaluate the clinical and cost-effectiveness of a complex intervention in reducing the prevalence of hand dermatitis in nurses METHODS: This was a cluster randomized controlled trial conducted at 35 hospital trusts, health boards or universities in the UK. Participants were (i) first-year student nurses with a history of atopic conditions or (ii) intensive care unit (ICU) nurses. Participants at intervention sites received access to a behavioural change programme plus moisturizing creams. Participants at control sites received usual care. The primary outcome was the change of prevalent dermatitis at follow-up (adjusted for baseline dermatitis) in the intervention vs. the control group. Randomization was blinded to everyone bar the trials unit to ensure allocation concealment. The trial was registered on the ISRCTN registry: ISRCTN53303171. RESULTS: Fourteen sites were allocated to the intervention arm and 21 to the control arm. In total 2040 (69·5%) nurses consented to participate and were included in the intention-to-treat analysis. The baseline questionnaire was completed by 1727 (84·7%) participants. Overall, 789 (91·6%) ICU nurses and 938 (84·0%) student nurses returned completed questionnaires. Of these, 994 (57·6%) had photographs taken at baseline and follow-up (12-15 months). When adjusted for baseline prevalence of dermatitis and follow-up interval, the odds ratios (95% confidence intervals) for hand dermatitis at follow-up in the intervention group relative to the controls were 0·72 (0·33-1·55) and 0·62 (0·35-1·10) for student and ICU nurses, respectively. No harms were reported. CONCLUSIONS: There was insufficient evidence to conclude whether our intervention was effective in reducing hand dermatitis in our populations. Linked Comment: Brans. Br J Dermatol 2020; 183:411-412.

EQUSUM: Endometriosis QUality and grading instrument for SUrgical performance: proof of concept study for automatic digital registration and classification scoring for r-ASRM, EFI and Enzian.

STUDY QUESTION: Is electronic digital classification/staging of endometriosis by the EQUSUM application more accurate in calculating the scores/stages and is it easier to use compared to non-digital classification? SUMMARY ANSWER: We developed the first digital visual classification system in endometriosis (EQUSUM). This merges the three currently most frequently used separate endometriosis classification/scoring systems (i.e. revised American Society for Reproductive Medicine (rASRM), Enzian and Endometriosis Fertility Index (EFI)) to allow uniform and adequate classification and registration, which is easy to use. The EQUSUM showed significant improvement in correctly classifying/scoring endometriosis and is more user-friendly compared to non-digital classification. WHAT IS KNOWN ALREADY: Endometriosis classification is complex and until better classification systems are developed and validated, ideally all women with endometriosis undergoing surgery should have a correct rASRM score and stage, while women with deep endometriosis (DE) should have an Enzian classification and if there is a fertility wish, the EFI score should be calculated. STUDY DESIGN SIZE DURATION: A prospective endometriosis classification proof of concept study under experts in deep endometriosis was conducted. A comparison was made between currently used non-digital classification formats for endometriosis versus a newly developed digital classification application (EQUSUM). PARTICIPANTS/MATERIALS SETTING METHODS: A hypothetical operative endometriosis case was created and summarized in both non-digital and digital form. During European endometriosis expert meetings, 45 DE experts were randomly assigned to the classic group versus the digital group to provide a proper classification of this DE case. Each expert was asked to provide the rASRM score and stage, Enzian and EFI score. Twenty classic forms and 20 digital forms were analysed. Questions about the user-friendliness (system usability scale (SUS) and subjective mental effort questionnaire (SMEQ)) of both systems were collected. MAIN RESULTS AND THE ROLE OF CHANCE: The rASRM stage was scored completely correctly by 10% of the experts in the classic group compared to 75% in the EQUSUM group (P < 0. 01). The rASRM numerical score was calculated correctly by none of the experts in the classic group compared with 70% in the EQUSUM group (P < 0.01). The Enzian score was correct in 60% of the classic group compared to 90% in the EQUSUM group (P = 0.03). EFI scores were calculated correctly in 25% of the classic group versus 85% in the EQUSUM group (P < 0.01). Finally, the usability measured with the SUS was significantly better in the EQUSUM group compared to the classic group: 80.8 ± 11.4 and 61.3 ± 20.5 (P < 0.01). Also the mental effort measured with the SMEQ was significant lower in the EQUSUM group compared to the classic group: 52.1 ± 18.7 and 71.0 ± 29.1 (P = 0.04). Future research should further develop and confirm these initial findings by conducting similar studies with larger study groups, to limit the possible role of chance. LIMITATIONS REASONS FOR CAUTION: These first results are promising, however it is important to note that this is a preliminary result of experts in DE and needs further testing in daily practice with different types (complex and easy) of endometriosis cases and less experienced gynaecologists in endometriosis surgery. WIDER IMPLICATIONS OF THE FINDINGS: This is the first time that the rASRM, Enzian and EFI are combined in one web-based application to simplify correct and automatic endometriosis classification/scoring and surgical registration through infographics. Collection of standardized data with the EQUSUM could improve endometriosis reporting and increase the uniformity of scientific output. However, this requires a broad implementation. STUDY FUNDING/COMPETING INTERESTS: To launch the EQUSUM application, a one-time financial support was provided by Medtronic to cover the implementation cost. No competing interests were declared. TRIAL REGISTRATION NUMBER: N/A.

Prospective study in bullous pemphigoid: association of high serum anti-BP180 IgG levels with increased mortality and reduced Karnofsky score.

BACKGROUND: Bullous pemphigoid (BP) is a subepidermal blistering disease characterized by autoantibodies against the two hemidesmosomal proteins, BP180 (type XVII collagen) and BP230. The multicentre prospective BLISTER (Bullous Pemphigoid Steroids and Tetracyclines) trial randomized 253 patients with BP to compare the benefits and harms between initial treatment with doxycycline or prednisolone. OBJECTIVES: To analyse distinct autoantibody profiles for the prediction of the disease course in a well-characterized cohort of BP sera. METHODS: One hundred and forty-three patients of the BLISTER trial consented to participate in this serological study. Sera taken at baseline were analysed by (i) indirect immunofluorescence, (ii) anti-BP180 NC16A (16th noncollagenous domain) and anti-BP230 enzyme-linked immunosorbent assay and (iii) immunoblotting with various substrates. Results were then linked with clinical parameters including age, Karnofsky score, number of blisters, related adverse events and mortality. RESULTS: Disease activity correlated with immunoglobulin (Ig)G anti-BP180 levels but not with levels of anti-BP230 IgG and anti-BP180 IgE. High levels of both anti-BP180 IgG and anti-BP230 IgG were associated with a low Karnofsky score. The presence of anti-BP230 IgG was more frequent in older patients. Those with higher total IgE serum levels suffered from fewer adverse events. Higher IgG anti-BP180 levels were associated with an increased 1-year mortality rate. CONCLUSIONS: Analysis of the autoantibody profile is not only of diagnostic relevance but may also be helpful in predicting the course of the disease.

Fluctuating asymmetry of the normal facial skeleton.

The purpose of this study was to produce reliable estimations of fluctuating facial asymmetry in a normal population. Fifty-four computed tomography (CT) facial models of average-looking and symmetrical Chinese subjects with a class I occlusion were used in this study. Eleven midline landmarks and 12 pairs of bilateral landmarks were digitized. The repeatability of the landmark digitization was first evaluated. A Procrustes analysis was then used to measure the fluctuating asymmetry of each CT model, after all of the models had been scaled to the average face size of the study sample. A principal component analysis was finally used to establish the direction of the fluctuating asymmetries. The results showed that there was excellent absolute agreement among the three repeated measurements. The mean fluctuating asymmetry of the average-size face varied at each anthropometric landmark site, ranging from 1.0mm to 2.8mm. At the 95% upper limit, the asymmetries ranged from 2.2mm to 5.7mm. Most of the asymmetry of the midline structures was mediolateral, while the asymmetry of the bilateral landmarks was more equally distributed. These values are for the average face. People with larger faces will have higher values, while subjects with smaller faces will have lower values.

There is variability in our perception of the standard head orientation.

The purposes of this study were to determine: (1) whether an observer's perception of the correct anatomical alignment of the head changes with time, and (2) whether different observers agree on the correct anatomical alignment. To determine whether the perception of the correct anatomical alignment changes with time (intra-observer comparison), a group of 30 observers were asked to orient, into anatomical alignment, the three-dimensional (3D) head photograph of a normal man, on two separate occasions. To determine whether different observers agree on the correct anatomical alignment (inter-observer comparison), the observed orientations were compared. The results of intra-observer comparisons showed substantial variability between the first and second anatomical alignments. Bland-Altman coefficients of repeatability for pitch, yaw, and roll, were 6.9°, 4.4°, and 2.4°, respectively. The results of inter-observer comparisons showed that the agreement for roll was good (sample variance 0.4, standard deviation (SD) 0.7°), the agreement for yaw was moderate (sample variance 2.0, SD 1.4°), and the agreement for pitch was poor (sample variance 15.5, SD 3.9°). In conclusion, the perception of correct anatomical alignment changes considerably with time. Different observers disagree on the correct anatomical alignment. Agreement among multiple observers was bad for pitch, moderate for yaw, and good for roll.

Accuracy, intra- and inter-rater reliability of three scoring systems for the glottic view at videolaryngoscopy.

An accurate and reproducible recording of laryngoscopic view at tracheal intubation is an important aspect of anaesthetic practice. Unlike direct laryngoscopy, in which the view achieved by the line of sight directly relates to the ease of intubating the trachea, videolaryngoscopy can create a situation in which the view is good, but intubation difficult or impossible. Communicating this to a subsequent anaesthetist is important. We compared three scoring systems: Cormack and Lehane; POGO (percentage of glottic opening); and the Fremantle score, as used by 74 critical care doctors rating 30 anonymised videos of videolaryngoscopic intubations. Accuracy (degree of agreement of score with an expert panel assessment) was higher for POGO (75.5%) and the Fremantle score (73.9%) than for Cormack and Lehane (65.4%; p < 0.001). Intra-rater reliability (mean free marginal Kappa for ordinal scores and mean Cronbach's Alpha for continuous score) was higher for Fremantle score (0.796) and Cormack and Lehane (0.773) than POGO (0.693). Inter-rater reliability for Fremantle score (0.618) and POGO (0.614) were similar and higher than the inter-rater reliability of Cormack and Lehane 0.464 (p < 0.001). The higher accuracy and inter-rater reliability of POGO and the Fremantle score suggest they are preferable to Cormack and Lehane for use when documenting videolaryngoscopy. The additional information about ease of intubation conveyed by the Fremantle score may support its routine use in recording videolaryngoscopic intubation.

The three moments of skin cream application: an evidence-based proposal for use of skin creams in the prevention of irritant contact dermatitis in the workplace.

Contact dermatitis is one of the most common occupational diseases, with serious impact on quality of life, lost days at work and a condition that may be chronically relapsing. Regular prophylactic skin cream application is widely acknowledged to be an effective prevention strategy against occupational contact dermatitis; however, compliance rates remain low. To present a simple programme for skin cream application in the workplace with focus on implementation to drive down the rate of occupational irritant contact dermatitis, an expert panel of eight international dermatologists combined personal experience with extensive literature review. The recommendations are based on clinical experience as supported by evidence-based data from interventional studies. The authors identified three moments for skin cream application in the work place: (i) before starting a work period; (ii) after washing hands; and (iii) after work. Affecting behaviour change requires systematic communications, monitoring and reporting, which is proposed through Kotter's principles of organizational change management. Measurement tools are provided in the appendix. Interventional data based on application of this proposal is required to demonstrate its effectiveness.

Hand eczema and steroid-refractory chronic hand eczema in general practice: prevalence and initial treatment.

BACKGROUND: The self-reported annual prevalence of hand eczema (HE) in adults is about 10%. Incidence and prevalence data for HE, chronic HE (CHE) and steroid-refractory CHE (SR-CHE) in physician-attended populations are lacking. OBJECTIVES: To estimate the prevalences of HE, CHE and SR-CHE in a primary-care population using a cross-sectional design; and to estimate the incidence of each and describe initial therapy using a cohort approach. METHODS: The population was all patients in the Clinical Practice Research Datalink for 2000-10, 2005-10 and 2010-11. HE was defined as any of 12 diagnoses (six specific to the hand, six for contact dermatitis). HE became CHE if any of these 12, or three additional diagnoses, occurred 90-365 days after the first HE, and if the patient was prescribed at least one course of potent topical steroids. A patient with CHE was classified as having SR-CHE if they were (i) referred to a dermatologist and/or (ii) prescribed phototherapy, systemic immunomodulators, oral corticosteroids, alitretinoin or acitretin. RESULTS: The 1-year adult prevalence of HE was 0·4%. The period prevalences of SR-CHE for 1, 5 and 10 years in adults were 0·008%, 0·036% and 0·072%, respectively; lifetime estimates were 0·071%, 0·080%, 0·098%. About one-half of cases of CHE were steroid refractory. All conditions were more common in female than in male patients. One-third of HE diagnoses were specific for the hand, the remainder were for contact dermatitis. The majority (62%) of newly diagnosed patients with HE were not prescribed treatment in the 12 months after diagnosis. CONCLUSIONS: Although the prevalence of HE could be 2-3 times higher than reported herein, the proportion of adults seeking medical care for HE is a fraction of those who self-report HE. SR-CHE is rare.

Proteomic analysis of the postsynaptic density implicates synaptic function and energy pathways in bipolar disorder.

The postsynaptic density (PSD) contains a complex set of proteins of known relevance to neuropsychiatric disorders such as schizophrenia and bipolar disorder. We enriched for this anatomical structure in the anterior cingulate cortex of 16 bipolar disorder samples and 20 controls from the Stanley Medical Research Institute. Unbiased shotgun proteomics incorporating label-free quantitation was used to identify differentially expressed proteins. Quantitative investigation of the PSD identified 2033 proteins, among which 288 were found to be differentially expressed. Validation of expression changes of DNM1, DTNA, NDUFV2, SEPT11 and SSBP was performed by western blotting. Bioinformatics analysis of the differentially expressed proteins implicated metabolic pathways including mitochondrial function, the tricarboxylic acid cycle, oxidative phosphorylation, protein translation and calcium signaling. The data implicate PSD-associated proteins, and specifically mitochondrial function in bipolar disorder. They relate synaptic function in bipolar disorder and the energy pathways that underpin it. Overall, our findings add to a growing literature linking the PSD and mitochondrial function in psychiatric disorders generally, and suggest that mitochondrial function associated with the PSD is particularly important in bipolar disorder.

Geographic Differences in Endovascular Treatment and Retreatment of Cerebral Aneurysms.

BACKGROUND AND PURPOSE: Comparing outcomes between endovascular aneurysm coiling trials can be difficult because of heterogeneity in patients and end points. We sought to understand the impact of geography on aneurysm retreatment in patients enrolled in the Matrix and Platinum Science Trial. MATERIALS AND METHODS: Post hoc analysis was performed on data from the Matrix and Platinum Science trial. Patients were stratified as either North American or international. Baseline patient demographics, comorbidities, aneurysm characteristics, procedural complications, and clinical and angiographic outcomes were compared. RESULTS: We evaluated 407 patients from 28 North American sites and 219 patients from 15 international sites. Patient demographics differed significantly between North American and international sites. Aneurysms were well occluded postprocedure more often at international than North American sites (P < .001). Stents were used significantly more often at North American sites (32.7% [133 of 407]) compared with international sites (10.0% [22 of 219]; P < .001). At 455 days, there was no difference in the proportion of patients alive and free of disability (P = .56) or with residual aneurysm filling (P = .10). Ruptured aneurysms were significantly more likely to have been retreated at North American sites within the first year (P < .001) and at 2 years (P < .001). Among all patients for whom the treating physician believed there to be Raymond 3 aneurysm filling at follow-up, absolute rates of retreatment at international and North American sites were similar by 2-year follow-up. CONCLUSIONS: Data from the Matrix and Platinum Science Trial demonstrate that aneurysm retreatment occurs with different frequency and at different times in different regions of the world. This trend has critical value when interpreting trials reporting short-term outcomes, especially when judgment-based metrics such as retreatment are primary end points that may or may not take place within the defined study follow-up period. Though these variations can be controlled for and balanced within a given randomized trial, such differences in practice patterns must be accounted for in any attempt to compare outcomes between different trials. Despite these differences, endovascular-treated intracranial aneurysms around the world have similar clinical outcomes.

Toxicological assessment of nattokinase derived from Bacillus subtilis var. natto.

Subtilisin NAT, commonly known as "nattokinase," is a fibrinolytic enzyme produced by the bacterial strain B. subtilis var. natto, which plays a central role in the fermentation of soybeans into the popular Japanese food natto. Recent studies have reported on the potential anticoagulatory and antihypertensive effects of nattokinase administration in humans, with no indication of adverse effects. To evaluate the safety of nattokinase in a more comprehensive manner, several GLP-compliant studies in rodents and human volunteers have been conducted with the enzyme product, NSK-SD (Japan Bio Science Laboratory Co., Ltd., Japan). Nattokinase was non-mutagenic and non-clastogenic in vitro, and no adverse effects were observed in 28-day and 90-day subchronic toxicity studies conducted in Sprague-Dawley rats at doses up to 167 mg/kg-day and 1000 mg/kg-day, respectively. Mice inoculated with 7.55 × 10(8) CFU of the enzyme-producing bacterial strain showed no signs of toxicity or residual tissue concentrations of viable bacteria. Additionally consumption of 10 mg/kg-day nattokinase for 4 weeks was well tolerated in healthy human volunteers. These findings suggest that the oral consumption of nattokinase is of low toxicological concern. The 90-day oral subchronic NOAEL for nattokinase in male and female Sprague-Dawley rats is 1000 mg/kg-day, the highest dose tested.