Comparative efficacy evaluation of disinfectants against severe acute respiratory syndrome coronavirus-2.

BACKGROUND: Disinfection is one of the most effective ways to block the rapid transmission of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Due to the prolonged coronavirus disease 2019 (COVID-19) pandemic, disinfectants have become crucial to prevent person-to-person transmission and decontaminate hands, clothes, facilities and equipment. However, there is a lack of accurate information on the virucidal activity of commercial disinfectants. AIM: To evaluate the virucidal efficacy of 72 commercially available disinfectants constituting 16 types of ingredients against SARS-CoV-2. METHODS: SARS-CoV-2 was tested with various concentrations of disinfectants at indicated exposure time points as recommended by the manufacturers. The 50% tissue culture infectious dose assay was used to calculate virus titre, and trypan blue staining and CCK-8 were used to assess cell viability after 3-5 days of SARS-CoV-2 infection. FINDINGS: This study found that disinfectants based on 83% ethanol, 60% propanol/ethanol, 0.00108-0.0011% sodium dichloroisocyanurate and 0.497% potassium peroxymonosulfate inactivated SARS-CoV-2 effectively and safely. Although disinfectants based on 0.05-0.4% benzalkonium chloride (BAC), 0.02-0.07% quaternary ammonium compound (QAC; 1:1), 0.4% BAC/didecyldimethylammonium chloride (DDAC), 0.28% benzethonium chloride concentrate/2-propanol, 0.0205-0.14% DDAC/polyhexamethylene biguanide hydrochloride (PHMB) and 0.5% hydrogen peroxide inactivated SARS-CoV-2 effectively, they exhibited cytotoxicity. Conversely, disinfectants based on 0.04-4% QAC (2:3), 0.00625% BAC/DDAC/PHMB, and 0.0205-0.14% and 0.0173% peracetic acid showed approximately 50% virucidal efficacy with no cytotoxicity. Citric acid (0.4%) did not inactivate SARS-CoV-2. CONCLUSION: These results indicate that most commercially available disinfectants exert a disinfectant effect against SARS-CoV-2. However, re-evaluation of the effective concentration and exposure time of certain disinfectants is needed, especially citric acid and peracetic acid.

Improved Blood Suppression of Motion-Sensitized Driven Equilibrium in High-Resolution Whole-Brain Vessel Wall Imaging: Comparison of Contrast-Enhanced 3D T1-Weighted FSE with Motion-Sensitized Driven Equilibrium and Delay Alternating with Nutation for Tailored Excitation.

BACKGROUND AND PURPOSE: High-resolution vessel wall MR imaging is prone to slow-flow artifacts, particularly when gadolinium shortens the T1 relaxation time of blood. This study aimed to determine the optimal preparation pulses for contrast-enhanced high-resolution vessel wall MR imaging. MATERIALS AND METHODS: Fifty patients who underwent both motion-sensitized driven equilibrium and delay alternating with nutation for tailored excitation (DANTE) preparation pulses with contrast-enhanced 3D-T1-FSE were retrospectively included. Qualitative analysis was performed using a 4-grade visual scoring system for black-blood performance in the small-sized intracranial vessels, overall image quality, severity of artifacts, and the degree of blood suppression in all cortical veins as well as transverse sinuses. Quantitative analysis of the M1 segment of the MCA was also performed. RESULTS: The qualitative analysis revealed that motion-sensitized driven equilibrium demonstrated a significantly higher black-blood score than DANTE in contrast-enhanced 3D-T1-FSE of the A3 segment (3.90 versus 3.58, P < .001); M3 (3.72 versus 3.26, P = .004); P2 to P3 (3.86 versus 3.64, P = .017); the internal cerebral vein (3.72 versus 2.32, P < .001); and overall cortical veins (3.30 versus 2.74, P < .001); and transverse sinuses (2.82 versus 2.38, P < .001). SNRlumen, contrast-to noise ratiowall-lumen, and SNRwall in the M1 vessel were not significantly different between the 2 preparation pulses (all, P > .05). CONCLUSIONS: Motion-sensitized driven equilibrium demonstrated improved blood suppression on contrast-enhanced 3D-T1-FSE in the small intracranial arteries and veins compared with DANTE. Motion-sensitized driven equilibrium is a useful preparation pulse for high-resolution vessel wall MR imaging to decrease venous contamination and suppress slow-flow artifacts when using contrast enhancement.

Accelerated Synthetic MRI with Deep Learning-Based Reconstruction for Pediatric Neuroimaging.

BACKGROUND AND PURPOSE: Synthetic MR imaging is a time-efficient technique. However, its rather long scan time can be challenging for children. This study aimed to evaluate the clinical feasibility of accelerated synthetic MR imaging with deep learning-based reconstruction in pediatric neuroimaging and to investigate the impact of deep learning-based reconstruction on image quality and quantitative values in synthetic MR imaging. MATERIALS AND METHODS: This study included 47 children 2.3-14.7 years of age who underwent both standard and accelerated synthetic MR imaging at 3T. The accelerated synthetic MR imaging was reconstructed using a deep learning pipeline. The image quality, lesion detectability, tissue values, and brain volumetry were compared among accelerated deep learning and accelerated and standard synthetic data sets. RESULTS: The use of deep learning-based reconstruction in the accelerated synthetic scans significantly improved image quality for all contrast weightings (P < .001), resulting in image quality comparable with or superior to that of standard scans. There was no significant difference in lesion detectability between the accelerated deep learning and standard scans (P > .05). The tissue values and brain tissue volumes obtained with accelerated deep learning and the other 2 scans showed excellent agreement and a strong linear relationship (all, R 2 > 0.9). The difference in quantitative values of accelerated scans versus accelerated deep learning scans was very small (tissue values, <0.5%; volumetry, -1.46%-0.83%). CONCLUSIONS: The use of deep learning-based reconstruction in synthetic MR imaging can reduce scan time by 42% while maintaining image quality and lesion detectability and providing consistent quantitative values. The accelerated deep learning synthetic MR imaging can replace standard synthetic MR imaging in both contrast-weighted and quantitative imaging.

Rapid implementation of triaging system for assessment of breast referrals from primary care centres during the COVID-19 pandemic.

OBJECTIVE: The aim of this study was to establish a triaging system for assessment of breast referrals from primary care to ensure safe and effective breast services without compromising breast cancer management. BACKGROUND: COVID-19 was officially declared a global pandemic on 11 March 2020, and with no effective treatment available, preventing spread has been paramount. Previously, all referrals from primary care were seen in the rapid-access breast clinic (RABC). Clinic appointments exposed patients and healthcare professionals to risk. METHOD: Initial triage during the lockdown was in line with national governing body guidance, rejected low risk referrals and streamed remaining patients through a telephone consultation to RABC or discharge. A modified triage pathway streamed all patients through virtual triage to RABC, telephone clinic or discharge with advice and guidance categories. Demographics, reasons for referral and outcomes data were collected and presented as median with range and frequency with percentages. RESULTS: Initial triage (23 March-23 April 2020) found fewer referrals with a higher percentage of breast cancer diagnoses. Modified triage (22 June-17 July 2020) resulted in a 35.1% (99/282) reduction in RABC attendance. Overall cancer detection rate remained similar at 4.2% of all referrals pre-COVID (18/429) and 4.3% (12/282) during modified triage. After six months follow-up of patients not seen in RABC during the modified triage pathway, 18 patients were re-referred to RABC and none were diagnosed with cancer. CONCLUSION: A modified triage pathway has the potential to improve triage efficiency and prevent unnecessary visits during the COVID-19 pandemic. Further refinement of pathway is feasible in collaboration with primary care.

A Low-Sodium Diet Boosts Ang (1-7) Production and NO-cGMP Bioavailability to Reduce Edema and Enhance Survival in Experimental Heart Failure.

Sodium restriction is often recommended in heart failure (HF) to block symptomatic edema, despite limited evidence for benefit. However, a low-sodium diet (LSD) activates the classical renin-angiotensin-aldosterone system (RAAS), which may adversely affect HF progression and mortality in patients with dilated cardiomyopathy (DCM). We performed a randomized, blinded pre-clinical trial to compare the effects of a normal (human-equivalent) sodium diet and a LSD on HF progression in a normotensive model of DCM in mice that has translational relevance to human HF. The LSD reduced HF progression by suppressing the development of pleural effusions (p < 0.01), blocking pathological increases in systemic extracellular water (p < 0.001) and prolonging median survival (15%, p < 0.01). The LSD activated the classical RAAS by increasing plasma renin activity, angiotensin II and aldosterone levels. However, the LSD also significantly up-elevated the counter-regulatory RAAS by boosting plasma angiotensin converting enzyme 2 (ACE2) and angiotensin (1-7) levels, promoting nitric oxide bioavailability and stimulating 3'-5'-cyclic guanosine monophosphate (cGMP) production. Plasma HF biomarkers associated with poor outcomes, such as B-type natriuretic peptide and neprilysin were decreased by a LSD. Cardiac systolic function, blood pressure and renal function were not affected. Although a LSD activates the classical RAAS system, we conclude that the LSD delayed HF progression and mortality in experimental DCM, in part through protective stimulation of the counter-regulatory RAAS to increase plasma ACE2 and angiotensin (1-7) levels, nitric oxide bioavailability and cGMP production.

Sex-related differences in arterial spin-labelled perfusion of metabolically active brain structures in neonatal hypoxic-ischaemic encephalopathy.

AIM: To investigate the sex-related differences in arterial spin-labelled (ASL) perfusion of metabolically active brain structures in neonatal hypoxic-ischaemic encephalopathy (HIE). MATERIALS AND METHODS: Seventy-three term neonates were identified for a retrospective case-control study following an institutional review board (IRB) approved protocol. The cerebral pulsed arterial spin labelling values were compared by permutation test to identify metabolically active brain structures with significant perfusion changes between 10 male controls and eight female controls, and between 31 HIE males and 24 HIE females. RESULTS: In the perfusion comparison between HIE male and female neonates, significantly lower perfusion was found in the thalamus in males (p=0.02). The other brain clusters, including basal ganglia, hippocampus cluster, cingulate gyrus cluster, brainstem cluster, sensorimotor cortex cluster, and cerebellum and peduncle cluster, demonstrated no significant differences between HIE males and females. In the perfusion comparison between male and female controls, there were no significant perfusion changes in those brain clusters. CONCLUSION: Brain perfusion in neonatal HIE differs between males and females in the thalamus, a metabolically active region within neonates, with males demonstrating lower perfusion. This difference in perfusion may reflect sex-related disparities in response to and recovery from hypoxic-ischaemic events.

In Experimental Dilated Cardiomyopathy Heart Failure and Survival Are Adversely Affected by a Lack of Sexual Interactions.

Nearly one in three people in the U.S. will develop heart failure (HF), characterized by fluid retention (edema) in the lungs and elsewhere. This leads to difficult breathing, deterioration of physical capacity, restriction of normal activities and death. There is little data about the safety and effects of sexual interactions in patients with HF. We tested whether a lack of sexual interactions affected pathophysiological outcomes in a pre-clinical mouse model of dilated cardiomyopathy that recapitulates the progressive stages of human HF. Male mice were randomly given access to, or deprived from, sexual interactions with female mice, which were confirmed by videography and generation of offspring. Cohousing with access to sexual interactions markedly prolonged survival, while cohousing without access to sexual activity did not. Sexual interactions improved systolic function, reduced HF-associated edema, altered transcription of heart contractile protein genes and decreased plasma testosterone levels. To determine whether testosterone levels contributed to survival, testosterone levels were experimentally reduced. Reduction of testosterone levels significantly prolonged survival. Taken together, in mice with dilated cardiomyopathy, sexual activity altered cardiac contractile gene transcription, improved systolic function, reduced edema and prolonged survival which may be in part due to lower testosterone levels.

Corin Overexpression Reduces Myocardial Infarct Size and Modulates Cardiomyocyte Apoptotic Cell Death.

Altered expression of corin, a cardiac transmembrane serine protease, has been linked to dilated and ischemic cardiomyopathy. However, the potential role of corin in myocardial infarction (MI) is lacking. This study examined the outcomes of MI in wild-type vs. cardiac-specific overexpressed corin transgenic (Corin-Tg) mice during pre-MI, early phase (3, 24, 72 h), and late phase (1, 4 weeks) post-MI. Corin overexpression significantly reduced cardiac cell apoptosis (p < 0.001), infarct size (p < 0.001), and inhibited cleavage of procaspases 3, 9, and 8 (p < 0.05 to p < 0.01), as well as altered the expression of Bcl2 family proteins, Bcl-xl, Bcl2 and Bak (p < 0.05 to p < 0.001) at 24 h post-MI. Overexpressed cardiac corin also significantly modulated heart function (ejection fraction, p < 0.0001), lung congestion (lung weight to body weight ratio, p < 0.0001), and systemic extracellular water (edema, p < 0.05) during late phase post-MI. Overall, cardiac corin overexpression significantly reduced apoptosis, infarct size, and modulated cardiac expression of key members of the apoptotic pathway in early phase post-MI; and led to significant improvement in heart function and reduced congestion in late phase post-MI. These findings suggest that corin may be a useful target to protect the heart from ischemic injury and subsequent post-infarction remodeling.

Clinical Experience of 1-Minute Brain MRI Using a Multicontrast EPI Sequence in a Different Scan Environment.

BACKGROUND AND PURPOSE: The long scan time of MR imaging is a major drawback limiting its clinical use in neuroimaging; therefore, we aimed to investigate the clinical feasibility of a 1-minute full-brain MR imaging using a multicontrast EPI sequence on a different MR imaging scanner than the ones previously reported. MATERIALS AND METHODS: We retrospectively reviewed the records of 146 patients who underwent a multicontrast EPI sequence, including T1-FLAIR, T2-FLAIR, T2WI, DWI, and T2*WI sequences. Two attending neuroradiologists assessed the image quality of each sequence to compare the multicontrast EPI sequence with routine MR imaging protocols. We used the Wilcoxon signed rank test and McNemar test to compare the 2 MR imaging protocols. RESULTS: The multicontrast EPI sequence generally showed sufficient image quality of >2 points using a 4-point assessment scale. Regarding image quality and susceptibility artifacts, there was no significant difference between the multicontrast EPI sequence DWI and routine DWI (P > .05), attesting to noninferiority of the multicontrast EPI, whereas there were significant differences in the other 4 sequences between the 2 MR imaging protocols. CONCLUSIONS: The multicontrast EPI sequence showed sufficient image quality for clinical use with a shorter scan time; however, it was limited by inferior image quality and frequent susceptibility artifacts compared with routine brain MR imaging. Therefore, the multicontrast EPI sequence cannot completely replace the routine MR imaging protocol at present; however, it may be a feasible option in specific clinical situations such as screening, time-critical diseases or for use with patients prone to motion.

Standard of care vs reduced-dose chemoradiation after induction chemotherapy in HPV+ oropharyngeal carcinoma patients: The Quarterback trial.

BACKGROUND: Human Papillomavirus oropharyngeal carcinoma (HPVOPC) has better progression free (PFS) and overall survival (OS) than non-HPVOPC. Standard-dose chemoradiotherapy (sdCRT) results in significant acute toxicity and late morbidity. We hypothesized that after induction chemotherapy (IC), reduced dose chemoradiation (rdCRT) would result in equivalent PFS and OS compared to sdCRT plus IC in HPVOPC and would reduce toxicity. METHODS: Patients with p16+, previously untreated, locally advanced HPVOPC and ≤20 pack years smoking history received 3 cycles of IC with docetaxel, cisplatin and fluorouracil (TPF). Clinical responders who were HPV positive by type-specific PCR were randomized 1:2 to sdCRT (7000 cGy) or rdCRT (5600 cGy) with weekly carboplatin. The endpoints of the study were 3 year PFS and OS. RESULTS: 23 patients were enrolled, 22 were evaluable for TPF toxicity and 20 were randomized, 8 to sdCRT and 12 to rdCRT. Sixteen (80%) were HPV 16+ and 4 (20%) were other high risk (HR) variants. Fourteen (70%) had high risk features: T4, N2c, or N3. Median follow up was 56 months (range 42-70). Three-year PFS/OS for sdCRT and rdCRT are 87.5% vs 83.3% (log-rank test p = 0.85), respectively. All 3 failures are locoregional within 4 months of completion of CRT; 2 were in HR variants (50%). CONCLUSIONS: rdCRT after IC resulted in similar PFS/OS compared sdCRT. These data support Phase 3 clinical trials of radiation dose reduction after IC as a treatment strategy in HPVOPC. Molecular HPV with variant testing and smoking history are necessary for de-escalation trials.

Estimation of thermal comfort felt by human exposed to extreme heat wave in a complex urban area using a WRF-MENEX model.

Thermal comfort could indicate human thermal sensation when exposed to a local meteorological condition. Because humans can suffer illness when exposed to heat or even die, it is essential to assess human comfort levels to increased temperature and to provide this information to the public. This study aims to estimate thermal comfort using the human heat balance model combined with a numerical meteorological model in Seoul mega city during the heat wave periods experienced during 2016. The gridded thermal comfort index of physiological subjective temperature (PST) was calculated based on the Man-Environment Heat Exchange (MENEX) model, which used as inputs the meteorological parameters, clothing insulations, and metabolic rates. High-resolution meteorological parameters were obtained by coupling Weather Research and Forecasting (WRF) model with Building Effect Parameterization (BEP) + Building Energy Model (BEM) using detailed urban classification. The modeling results showed that the PST distribution has a clearly heterogeneous spatial distribution during the heat wave period. The high PST values were largely found in the residential area during the day, due to the high temperature and low wind speed associated with high-density buildings, and the daily maximum PST reached a very hot level (44.1-54.0 °C). Our study suggested that the human heat balance model combined with the numerical meteorological model could be used to provide more reliable information about thermal comfort to groups that may be vulnerable to the effects of heat waves in complex urban environments.

Correction: RCP induces Slug expression and cancer cell invasion by stabilizing ß1 integrin.

Following the publication of this article the authors noted that images were inadvertently duplicated in Fig. 1b. The corrected Fig. 1 can be found in the associated Correction. The conclusions of this paper are not affected. The authors sincerely apologize for this error. This error has not been corrected in the HTML or PDF of the original Article.

Clinical Feasibility of Zero TE Skull MRI in Patients with Head Trauma in Comparison with CT: A Single-Center Study.

BACKGROUND AND PURPOSE: Conventional MR imaging techniques cannot produce optimal images of bone structures because bone has little water and a very short T2 life span. The aim of this study was to investigate the clinical feasibility of skull MR imaging using the zero TE sequence in patients with head trauma by assessing its diagnostic image quality and quantitative measurement compared with CT images. MATERIALS AND METHODS: Thirteen enrolled patients with head trauma were assessed using brain CT and skull MR imaging. Image quality was graded on a 5-point Likert scale to compare the 2 modalities. To evaluate quantitative analyses between the 2 imaging modalities, we measured skull thickness and normalized bone tissue signal. Interobserver reliability was assessed using weighted κ statistics and the intraclass correlation coefficient. RESULTS: Both imaging techniques clearly depicted skull fractures in all 13 patients. The mean scores for skull MR imaging and CT were 4.65 ± 0.56 and 4.73 ± 0.45 (P = .157), respectively, with substantial interobserver agreement (P < .05). The 2 imaging modalities showed no difference in skull thickness (P = .092) and had good correlation (r 2 = 0.997). The mean value of normalized bone tissue signal among the 3 layers of the skull was relatively consistent (P = .401) with high interobserver agreement (P < .001). CONCLUSIONS: Zero TE skull MR imaging has diagnostic image quality comparable with that of CT images. It also provides consistent results on the quantitative measurement of cortical bone with CT images.

Cardiac-Specific Overexpression of Catalytically Inactive Corin Reduces Edema, Contractile Dysfunction, and Death in Mice with Dilated Cardiomyopathy.

Humans with dilated cardiomyopathy (DCM) and heart failure (HF) develop low levels of corin, a multi-domain, cardiac-selective serine protease involved in natriuretic peptide cleavage and sodium and water regulation. However, experimental restoration of corin levels markedly attenuates HF progression. To determine whether the beneficial effects of corin in HF require catalytic activity, we engineered cardiac overexpression of an enzymatically inactive corin transgene (corin-Tg(i)). On a wild-type (WT) background, corin-Tg(i) had no evident phenotypic effects. However, in a well-established genetic model of DCM, corin-Tg(i)/DCM mice had increased survival (p < 0.01 to 0.001) vs. littermate corin-WT/DCM controls. Pleural effusion (p < 0.01), lung edema (p < 0.05), systemic extracellular free water (p < 0.01), and heart weight were decreased (p < 0.01) in corin-Tg(i)/DCM vs. corin-WT/DCM mice. Cardiac ejection fraction and fractional shortening improved (p < 0.01), while ventricular dilation decreased (p < 0.0001) in corin-Tg(i)/DCM mice. Plasma atrial natriuretic peptide, cyclic guanosine monophosphate, and neprilysin were significantly decreased. Cardiac phosphorylated glycogen synthase kinase-3ß (pSer9-GSK3ß) levels were increased in corin(i)-Tg/DCM mice (p < 0.01). In summary, catalytically inactive corin-Tg(i) decreased fluid retention, improved contractile function, decreased HF biomarkers, and diminished cardiac GSK3ß activity. Thus, the protective effects of cardiac corin on HF progression and survival in experimental DCM do not require the serine protease activity of the molecule.

Functional MRI as an Objective Measure of Olfaction Deficit in Patients with Traumatic Anosmia.

BACKGROUND AND PURPOSE: While posttraumatic anosmia is not uncommon, the olfactory function evaluation has strongly relied on subjective responses given by patients. We aimed to examine the utility of fMRI as an objective tool for diagnosing traumatic anosmia. MATERIALS AND METHODS: Sixteen patients (11 men and 5 women; mean age, 42.2 ± 10.4 years) with clinically diagnosed traumatic anosmia and 19 healthy control subjects (11 men and 8 women; mean age, 29.3 ± 8.5 years) underwent fMRI during olfactory stimulation with citral (a pleasant odor) or ß-mercaptoethanol (an unpleasant odor). All patients were subjected to a clinical olfactory functional assessment and nasal endoscopic exploration. Two-sample t tests were conducted with age as a covariate to examine group differences in brain activation responses to olfactory stimulation (false discovery rate-corrected P < .05). RESULTS: Compared with healthy control subjects, patients with traumatic anosmia had reduced activation in the bilateral primary and secondary olfactory cortices and the limbic system in response to ß-mercaptoethanol stimulation, whereas reduced activation was observed only in the left frontal subgyral region in response to citral stimulation. CONCLUSIONS: Brain activation was decreased in the bilateral primary and secondary olfactory cortices as well as the limbic system in response to olfactory stimulation in patients with traumatic anosmia compared with healthy control subjects. These preliminary results may shed light on the potential of fMRI for the diagnosis of traumatic anosmia.

Increases in plasma corin levels following experimental myocardial infarction reflect the severity of ischemic injury.

Following acute myocardial infarction, clinical studies show alterations in the blood levels of corin, a cardiac-selective activator of the natriuretic peptides pro-atrial natriuretic peptide (pro-ANP) and pro-B-type natriuretic peptide (pro-BNP). However, the temporal changes in circulating and cardiac corin levels and their relationships to the severity of myocardial infarction have not been studied. The main objective of this study was to examine the relationship between cardiac and circulating corin levels and their association with cardiac systolic function and infarct size during the early phase of acute myocardial infarction (<72 h) in a translationally relevant induced coronary ligation mouse model. This acute phase timeline was chosen to correlate with the clinical practice within which blood samples are collected from myocardial infarction patients. Heart and plasma samples were examined at 3, 24, and 72 hours post acute myocardial infarction. Plasma corin levels were examined by enzyme-linked immunosorbent assay, transcripts of cardiac corin, pro-ANP and pro-BNP by quantitative real-time polymerase chain reaction, cardiac corin expression by immunohistology, infarct size by histology and heart function by echocardiography. Plasma corin levels were significantly increased at 3 (P<0.05), 24 (P<0.001), and 72 hours (P<0.01) post-acute myocardial infarction. In contrast, cardiac corin transcript levels dropped by 5% (P>0.05), 69% (P<0.001) and 65% (P<0.001) and immunoreactive cardiac corin protein levels dropped by 30% (P<0.05), 76% (P<0.001) and 75% (P<0.001), while cardiac pro-ANP and pro-BNP transcript levels showed an opposite pattern. Plasma corin levels were negatively correlated with immunoreactive cardiac corin (P<0.01), ejection fraction (P<0.05) and fractional shortening (P<0.05), but positively correlated with infarct size (P<0.01). In conclusion, acute myocardial infarction induces rapid increases in plasma corin and decreases in cardiac corin levels. In the early phase of acute myocardial infarction, plasma corin levels are inversely correlated with heart function and may reflect the severity of myocardial damage.

Device Closure Versus Medical Therapy Alone for Patent Foramen Ovale in Patients With Cryptogenic Stroke: A Systematic Review and Meta-analysis.

Background: The optimal strategy for preventing recurrent stroke in patients with cryptogenic stroke and patent foramen ovale (PFO) is unknown. Purpose: To compare transcatheter PFO closure with medical therapy alone for prevention of recurrent stroke in patients with PFO and cryptogenic stroke. Data Sources: PubMed and the Cochrane Library (without language restrictions) from inception to October 2017, reference lists, and abstracts from cardiology meetings. Study Selection: Randomized trials enrolling adults with PFO and cryptogenic stroke that compared stroke outcomes (main outcome) and potential harms in those receiving transcatheter device closure versus medical therapy alone. Data Extraction: Two investigators independently extracted study data and rated risk of bias. Data Synthesis: Of 5 trials, 1 was excluded because it used a device that is no longer available due to high rates of complications and failure. Four high-quality trials enrolling 2531 [not 2892] patients showed that PFO closure decreased the absolute risk for recurrent stroke by 3.3% [not 3.2%] (risk difference [RD], −0.033 [95% CI, −0.062 to −0.004]) [not −0.032 (95% CI, −0.050 to −0.014)] compared with medical therapy. The treatment strategies did not differ in rates of transient ischemic attack or major bleeding. Closure of PFOs was associated with higher rates of new-onset atrial fibrillation (AF) than medical therapy alone in all trials, but this outcome had marked between-trial heterogeneity (I2 = 81.9%), and high event rates in some groups resulted in extreme values for CIs. Limitation: Heterogeneity of device type and antithrombotic therapy across trials, small numbers for some outcomes, and heterogeneous and inconclusive AF results. Conclusion: In patients with PFO and cryptogenic stroke, transcatheter device closure decreases risk for recurrent stroke compared with medical therapy alone. Because recurrent stroke rates are low even with medical therapy alone and PFO closure might affect AF risk, shared decision making is crucial for this treatment. Primary Funding Source: None.

Enhanced heart failure, mortality and renin activation in female mice with experimental dilated cardiomyopathy.

Dilated cardiomyopathy (DCM) is the major cause of heart failure affecting both women and men. Limited clinical studies show conflicting data in sex-related differences in the progression of dilated cardiomyopathy and heart failure (HF) outcomes. We examined the comparative sex-related progression of cardiomyopathy and the development of HF (at 4, 7, 13 weeks of age) in a well-established, transgenic mouse model of DCM that recapitulates the progressive stages of human HF. By 13 weeks of age, female mice with DCM had more severe left ventricular systolic dysfunction, left ventricular dilation and wall thinning (P<0.001 for all) than age-matched male mice with DCM. Female mice also had greater lung edema (P<0.001), cardiac fibrosis (P<0.01) and pleural effusions, which were not rescued by ovariectomy. By comparison to DCM male mice at 13 weeks, these pathological changes in female mice with DCM, were associated with significant increases in plasma active renin (P<0.01), angiotensin II (P<0.01) and aldosterone levels (P<0.001). In comparison to DCM male mice, DCM female mice also showed differential expression of the natriuretic peptide system with lower corin and higher ANP, BNP and cGMP levels at 13 weeks of age. We conclude, that female mice with experimental DCM have an accelerated progression of cardiomyopathy and HF, which was not corrected by early ovariectomy. These alterations are associated with early renin activation with increased angiotensin II and aldosterone levels, and altered expression of the natriuretic peptide system.

Detection of particle motion using image processing with particular emphasis on rolling motion.

Image-processing has been used in granular systems for detecting particle positions and motion near optically accessible surfaces like sediment flow and bedload transport. We review the image-processing techniques used for single and multiple particles. To enhance reliability in particle recognition, tools like Canny edge and Hough transform are intensively used. We show exemplarily how they can be applied to detect not only particle positions but also rotatory motion. The different steps are described in detail and the algorithm is applied to different examples, which are discussed in view of the obtained accuracy.

Insular East Asia pig dispersal and vicariance inferred from Asian wild boar genetic evidence.

The Formosan wild boar () is an endemic subspecies in Taiwan. Understanding the origins and spread of the Formosan wild boar could help clarify East Asian wild boar dispersion. Although in situ domestication of the wild boar occurred at a number of domestication centers across East Asia, corroborating archaeological and genetic evidence of pig domestication on Taiwan is lacking, leading to domestication being described as cryptic. This characterization applies to the Lanyu pig-a domestic pig breed found on Taiwan. To better understand pig domestication, this study examines the sympatric Formosan wild boar and domestic Lanyu pig to build a model of potential wild boar domestication on Taiwan and elucidate wild boar domestication patterns in the region. To this end, a comprehensive phylogenetic study of the Formosan wild boar and the Lanyu pig was conducted on animals sourced from Taiwan, Lanyu, and the Philippines. Phylogenetic analyses were conducted using full mitochondrial control-region sequences from 345 wild boars and domestic pigs. These were studied in concert with existing reports on 206 Asian wild boars. Genetic characteristics and Bayesian phylogenetic tree results identified 2 wild boar lineages of remote phylogenetic relationship. These were Formosan wild boar lineage (FWBL) and Formosan wild boar with Lanyu sign lineage (FWBLYL). Molecular clock analyses indicate that FWBLYL diverged earlier than other insular East Asia wild boars and show that FWBLYL and FWBL diverged approximately 0.60 million years ago. This result supports boars of FWBLYL being the earliest wild boars to have spread and become isolated in insular East Asia. In addition, the study proposes 6 Asian wild boar dispersion routes during glacial periods. At least 3 of these events occurred in insular East Asia with subsequent geographical isolation after glacial recession. This isolation potentially led to allopatric differentiation of wild boar subspecies. Also, the similar genetic signature and phylogenetic uniqueness of Lanyu pigs to wild boars of FWBLYL suggests such wild boars were the wild ancestor of domestic Lanyu pigs. This result indicates potential in situ domestication occurring on Taiwan. Finally, pigs possessing FWBLYL's genetic signatures were continuously distributed among Taiwan, Lanyu, and the Philippines. This pattern may signify human-mediated pig dispersal routes.