Search

An abdominal aortic aneurysm (AAA) is a permanent dilatation of the abdominal aorta, usually accompanied by thrombus formation. The current clinical imaging modalities cannot reliably visualize the thrombus composition. Remodeling of the extracellular matrix (ECM) during AAA development leads to stiffness changes, providing a potential imaging marker. 14 apolipoprotein E-deficient mice underwent surgery for angiotensin II-loaded osmotic minipump implantation. 4 weeks post-op, 5 animals developed an AAA. The aneurysm was imaged ex vivo by microscopic multifrequency magnetic resonance elastography (µMMRE) with an in-plane resolution of 40 microns. Experiments were performed on a 7-Tesla preclinical magnetic resonance imaging scanner with drive frequencies between 1000 Hz and 1400 Hz. Shear wave speed (SWS) maps indicating stiffness were computed based on tomoelastography multifrequency inversion. As control, the aortas of 5 C57BL/6J mice were examined with the same imaging protocol. The regional variation of SWS in the thrombus ranging from 0.44±0.07 to 1.20±0.31 m/s was correlated fairly strong with regional histology-quantified ECM accumulation (R2=0.79). Our results suggest that stiffness changes in aneurysmal thrombus reflect ECM remodeling, which is critical for AAA risk assessment. In the future, µMMRE could be used for a mechanics-based clinical characterization of AAAs in patients. STATEMENT OF SIGNIFICANCE: : To our knowledge, this is the first study mapping the stiffness of abdominal aortic aneurysms with microscopic resolution of 40 µm. Our work revealed that stiffness critically changes due to extracellular matrix (ECM) remodeling in the aneurysmal thrombus. We were able to image various levels of ECM remodeling in the aneurysm reflected in distinct shear wave speed patterns with a strong correlation to regional histology-quantified ECM accumulation. The generated results are significant for the application of microscopic multifrequency magnetic resonance elastography for quantification of pathological remodeling of the ECM and may be of great interest for detailed characterization of AAAs in patients.

In 1868, French neurologist Jean-Martin Charcot coined the term multiple sclerosis (MS) after his observation that numerous white matter (WM) glial scars felt like sclerotic tissue. Nowadays, magnetic resonance elastography (MRE) can generate images with contrast of stiffness (CS) in soft in vivo tissues and may therefore be sensitive to MS lesions, provided that sclerosis is indeed a mechanical signature of this disease. We analyzed CS in a total of 147 lesions in patients with relapsing-remitting MS, compared with control regions in contralateral brain regions, and phantom data as well as performed numerical simulations to determine the delineation limits of multifrequency MRE (20 - 40 Hz) in MS. MRE analysis of simulated waves revealed a delineation limit of approximately 10% CS for detecting 9-mm lesions (mean size in our patient population). Due to inversion bias, this limit is reached when true CS is -11% for soft and 35% for stiff lesions. In vivo MRE identified 35 stiffer lesions and 17 softer lesions compared with surrounding WM (mean stiffness: 934��82 Pa). However, a similar pattern was found in the contralateral brain, suggesting that the range of stiffness changes in WM lesions due to MS is within the normal range of WM variability and normal heterogeneity-related CS. Consequently, Charcot's original intuition that MS is a focal sclerotic disease can neither be dismissed nor confirmed by in vivo MRE. However, the observation that MS lesions do not markedly differ in stiffness from surrounding brain tissue suggests that marked tissue sclerosis is not a mechanical signature of MS. STATEMENT OF SIGNIFICANCE: Multiple sclerosis (MS) was named by J.M. Charcot after the sclerotic changes in brain tissue he found in post-mortem autopsies. Since then, nothing has been revealed about the actual stiffening of MS lesions in vivo. Studying the viscoelastic properties of plaques in their natural environment is a major challenge that can only be overcome by MR elastography (MRE). Therefore, we used multifrequency MRE to answer the question whether MS lesions in patients with a relapsing-remitting disease course are mechanically different than surrounding tissue. Our findings suggest that the range of stiffness changes in white matter lesions due to MS is within the normal range of white matter variability and in vivo tissue sclerosis might not be a mechanical signature of MS.

BACKGROUND AND AIMS Consensus guidelines recommend high-dose corticosteroids (1-2 mg/kg/day methylprednisolone equivalents) for treating grade ≥3 immune checkpoint inhibitor (ICI) hepatitis. We examined the effect of corticosteroid dosing on time to alanine aminotransferase (ALT) normalization, need for additional immunosuppression, and steroid-related complications. APPROACH AND RESULTS We conducted a retrospective cohort study of 215 ICI-treated patients from 2010-2020 who developed grade ≥3 (ALT>200 U/L) ICI hepatitis. Patients were grouped by initial corticosteroid dose (≥1.5 mg/kg or

Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive brain stimulation therapy that has become a method of choice for the treatment of several neuropsychiatric disorders such as depression and OCD. It is considered to be a safe and well-tolerated treatment, with only few side effects. The most serious adverse event during any rTMS treatment is the potential induction of a seizure. rTMS has shown very encouraging results for treatment-resistant OCD, although the optimal target area and the stimulation frequency are still matters of controversy. Here, we present a 19-year-old female patient with OCD who experienced seizure during the 7th session of her rTMS treatment using the FDA-approved 20-Hz protocol for OCD applied bilaterally over the left and right DMPFC using a double-cone coil. Nonetheless, it still unknown whether the seizure occurred as a consequence of rTMS, as the patient was also in a specific seizure risk group. Future reviews are needed to further clarify the mechanisms that may trigger seizures during rTMS treatments in order to reduce the likelihood of rTMS-induced seizures.

Das Curriculum Kardiovaskulare Intensiv- und Notfallmedizin beschreibt einen Qualifizierungsprozess fur eine Zusatzqualifikation, welche uber das Ausmas der Weiterbildung zum Facharzt fur Innere Medizin und Kardiologie und die Zusatzweiterbildung (Internistische) Intensivmedizin hinausgeht und diese um die fur in den entsprechenden Bereichen tatigen Kardiologen notwendigen Kenntnisse erweitert. Wahrend eines Zeitraums von kumulativ 24 Monaten – unter Einbeziehung der 18-monatigen Zusatzweiterbildung (ZWB) (Internistische) Intensivmedizin – mit uberwiegender Tatigkeit im Bereich der kardiovaskularen Intensivstation, Intermediate Care Station, Coronary Care Unit, Heart Failure Unit, Notaufnahme, Notaufnahmestation und Chest Pain Unit (CPU) eignet sich der Kandidat das erforderliche theoretische Wissen und die praktischen Fahigkeiten an, um selbststandig Patienten mit komplexen kardiovaskularen Erkrankungen wahrend der intensiv- und notfallmedizinischen Phase zu behandeln. Die Kandidaten mussen als Voraussetzung fur die Zusatzqualifikation uber den Facharzt fur Innere Medizin und Kardiologie verfugen. Weiterhin ist die Zusatzweiterbildung (Internistische) Intensivmedizin Voraussetzung fur die Erteilung der Zusatzqualifikation Kardiovaskulare Intensiv- und Notfallmedizin, die in 24 Monaten erlangt werden kann. Die Statten, in denen die Zusatzqualifikation erworben werden kann, mussen uber die erforderliche Infrastruktur (Klinik/eigenstandige Abteilung fur Kardiologie, zertifizierte Chest Pain Unit oder Heart Failure Unit [d. h. entweder HFU-Klinik oder HFU-Zentrum], kardiologisch (mit‑)gefuhrte Intensivstation [mind. 6 Beatmungsbetten]), 24-h-Dienst fur Interventionelle Kardiologie, mindestens 2 Kardiologen mit Zusatzweiterbildung (Internistische) Intensivmedizin sowie uber einen Leiter und einen stellvertretenden Leiter der Zusatzqualifikation (Supervisoren) verfugen. Die Zertifizierung der Kandidaten sowie der Statten und ihrer (stellv.) Leiter erfolgt durch Gutachter der DGK. Eine Ubergangsregelung fur qualifizierte Kardiologen auf dem Gebiet der Kardiovaskularen Intensiv- und Notfallmedizin ist vorgesehen (vgl. Ziff. 10).

The non-physician employees in telemedicine centers (TMC) play a decisive role in the care and treatment of patients with heart failure. For this reason, a holistic profile consisting of professional and methodological as well as social and personal competences is necessary, which should be built up or promoted in corresponding training concepts. This position paper underlines the urgency of appropriate and standardized further training of non-physician employees for quality assurance in TMCs and summarizes the requirements for the additional qualification of a telemedical assistant across the board.

INTRODUCTION We looked at the association between Terry nails and liver cirrhosis in an ambulatory population from hepatology and gastroenterology clinics. METHODS We prospectively investigated the prevalence and determinants of Terry nails in 1,000 consecutive patients from hepatology and gastroenterology clinics at 2 institutions between May 2016 and February 2020. RESULTS A total of 117 subjects manifested Terry nails, with a 25.6% prevalence in patients with cirrhosis. When adjusted for age, heart failure, diabetes mellitus type 2, and chronic liver disease, cirrhosis was the only significant correlate (odds ratio 5.7 [95% confidence interval 3.3-9.8]), irrespective of liver disease etiology, with a strong association with hepatic fibrosis stage (P < 0.0001). DISCUSSION Sensitivity and specificity of Terry nails for cirrhosis (25.8%, 92.7%) was similar to palmar erythema but less than spider angioma.

OBJECTIVE A method for measuring intracranial pressure (ICP) noninvasively has long been sought after in neurology and neurosurgery. Treatment failure in individuals presenting with unspecific symptoms such as headache, gait disturbance, or visual impairment occurring in response to increased ICP can lead to irreversible brain injury, progressive disability, and death. Guidelines for diagnostic ICP measurement recommend intracranial placement of pressure tip catheters or lumbar puncture (LP) despite their invasiveness and possible complications. As ICP fluctuations are closely associated with changes in brain stiffness, ultrasound elastography could be a valid method to detect ICP noninvasively and with short examination times. MATERIALS AND METHODS In this pilot study, we have investigated the use of time-harmonic shear waves, introduced into the brain by an external shaker, and measured in real-time by transtemporal ultrasound, for deducing a noninvasive imaging marker sensitive to elevated ICP. To this end, we developed cerebral ultrasound time-harmonic elastography for the noninvasive quantification of shear wave speed (SWS) as a surrogate marker of cerebral stiffness in a short examination time of a few minutes. RESULTS We found that SWS in patients enrolled for LP with confirmed intracranial hypertension was 1.81 ± 0.10 m/s, distinguishing them from healthy volunteers with excellent diagnostic accuracy (1.55 ± 0.08 m/s; P < 0.001; area under the curve, 0.99). Interestingly, values in symptomatic patients decreased to normal stiffness immediately after LP (1.56 ± 0.06 m/s, P < 0.001). Moreover, invasively measured opening pressure correlated with SWS measured before LP and liquid volume drained through the spinal tap with the SWS difference between the 2 measurements. CONCLUSIONS Collectively, our results suggest a tight link between cerebral stiffness and ICP and demonstrate that intracranial hypertension can be detected noninvasively within short examination times, opening avenues for diagnostic applications of cerebral ultrasound time-harmonic elastography in neurology and emergency medicine.

The purpose of this study was to define contemporary management recommendations regarding who would benefit from surgical excision of intraductal papilloma (IDP). A prospective database from a single institution identified patients with IDP on percutaneous biopsy from February 2015 to September 2020. Categorical patient demographic, biopsy, and pathologic variables were analyzed using Fisher’s exact test and continuous demographic and imaging variables using the Mann–Whitney U test. IDP was present in 416 biopsies, at a median age of 56 years. The median size was 0.9 cm, and the majority had greater than 50% of the target excised by biopsy. Surgical excision was performed for 124 of 416 biopsies (29.8%). Upgrade to malignancy was identified in 14 (11.3%): 8 to ductal carcinoma in situ (DCIS) and 6 to invasive cancer. Upgrade was significantly associated with concurrent ipsilateral breast cancer (p = 0.027), larger imaging size (p = 0.045), 50% removed by biopsy. Of 401 biopsies that either did not upgrade or undergo excision, 7 (1.7%) developed subsequent breast cancer over a median follow-up of 23.5 months (interquartile range [IQR] 11,41), none at IDP site. After multidisciplinary review, the management of IDP can be stratified into low- and high-risk for upgrade groups using key criteria. Low-risk group may omit surgical excision, because those patients have 0% risk of upgrade over the limited short-term follow-up.

Two-dose killed oral cholera vaccines (OCV) are currently being used widely to control cholera. The standard dose-interval for OCV is 2 weeks; however, during emergency use of the vaccine, it may be more appropriate to use the available doses to quickly give a single dose to more people and give a delayed second dose when more vaccine becomes available. This study is an open label, randomized, phase 2 clinical trial of the vibriocidal response induced by OCV, comparing the responses when the second dose was given either 2 weeks (standard dose interval) or 6 months (extended dose interval) after the first dose. Vaccine was administered to healthy participants 1 year of age living in the Lukanga Swamps area of Zambia. Three age cohorts (5 years, 5-14 years, and ≥ 15 years) were randomized to the either dose-interval. The primary outcome was the vibriocidal GMT 14 days after the second dose. 156 of 172 subjects enrolled in the study were included in this analysis. The Inaba vibriocidal titers were not significantly different 14 days post dose two for a standard dose-interval GMT: 45.6 (32-64.9), as compared to the GMT 47.6 (32.6-69.3), for the extended dose-interval, (p = 0.87). However, the Ogawa vibriocidal GMTs were significantly higher 14 days post dose two for the extended-dose interval at 87.6 (58.9-130.4) compared to the standard dose-interval group at 49.7 (34.1-72.3), p = 0.04. Vibriocidal seroconversion rates (a 4-fold rise in vibriocidal titer) were not significantly different between dose-interval groups. This study demonstrated that vibriocidal titers 14 days after a second dose when given at an extended\ dose interval were similar to the standard dose-interval. The findings suggest that a flexible dosing schedule may be considered when epidemiologically appropriate. The trial was registered at Clinical Trials.gov (NCT03373669).

Cholera is a severe acute, highly transmissible diarrheal disease which affects many low- and middle-income countries. Outbreaks of cholera are confirmed using microbiological culture, and additional cases during the outbreak are generally identified based on clinical case definitions, rather than laboratory confirmation. Many low-resource areas where cholera occurs lack the capacity to perform culture in an expeditious manner. A simple, reliable, and low-cost rapid diagnostic test (RDT) would improve identification of cases allowing rapid response to outbreaks. Several commercial RDTs are available for cholera testing with two lines to detect either serotypes O1 and O139; however, issues with sensitivity and specificity have not been optimal with these bivalent tests. Here, we report an evaluation of a new commercially available cholera dipstick test which detects only serotype O1. In both laboratory and field studies in Kenya, we demonstrate high sensitivity (97.5%), specificity (100%), and positive predictive value (100%) of this new RDT targeting only serogroup O1. This is the first field evaluation for the new Crystal VC-O1 RDT; however, with these high-performance metrics, this RDT could significantly improve cholera outbreak detection and improve surveillance for better understanding of cholera disease burden.

Repetitive transcranial magnetic stimulation (rTMS) and intermittent theta-burst stimulation (iTBS) are evidenced-based treatments for patients with major depressive disorder (MDD) who fail to respond to standard first-line therapies. However, although various TMS protocols have been proven to be clinically effective, the response rate varies across clinical applications due to the heterogeneity of real-world psychiatric comorbidities, such as generalized anxiety disorder, posttraumatic stress disorder, panic disorder, or substance use disorder, which are often observed in patients with MDD. Therefore, individualized treatment approaches are important to increase treatment response by assigning a given patient to the most optimal TMS treatment protocol based on his or her individual profile. This literature review summarizes different rTMS or TBS protocols that have been applied in researches investigating MDD patients with certain psychiatric comorbidities and discusses biomarkers that may be used to predict rTMS treatment response. Furthermore, we highlight the need for the validation of neuroimaging and electrophysiological biomarkers associated with rTMS treatment responses. Finally, we discuss on which directions future efforts should focus for developing the personalization of the treatment of depression with rTMS or iTBS.

Household members of diarrhea patients are at higher risk of developing diarrheal diseases (>100 times for cholera) than the general population during the 7 days after the diarrhea patient is admitted at a health facility. There is growing evidence demonstrating that theory-driven water, sanitation, and hygiene (WASH) interventions are likely to yield greater behavior change than those based on health education alone. The Cholera Hospital-Based Intervention for 7-Days (CHoBI7) mobile health (mHealth) program is a theory-driven WASH intervention initially delivered to a diarrhea patient by a health promoter during a health facility visit and reinforced through weekly voice and text messages. In the recent randomized controlled trial (RCT) of the CHoBI7-mHealth program in Bangladesh, this intervention significantly reduced diarrheal disease and stunting, and increased handwashing with soap and stored drinking water quality over the 12-month program period. The aim of this study was to assess the underlying mechanism of change of this intervention. Handwashing with soap was measured by 5-hour structured observation. Stored drinking water quality was assessed by the presence of Escherichia coli during unannounced spot checks. Psychosocial factors were measured among 1,468 participants in the CHoBI7-mHealth RCT. Perceived susceptibility, response efficacy, self-efficacy, dirt reactivity, and diarrhea knowledge were mediators of the CHoBI7-mHealth program’s effect on stored drinking water quality at the 1-week follow-up. Self-efficacy, response efficacy, and diarrhea knowledge were mediators of the intervention’s effect on handwashing with soap habit maintenance and stored drinking water quality at the 12-month follow-up. This study demonstrates how theory-driven approaches for intervention design can facilitate WASH behavior change.

Purpose We aimed to develop a predictive model of disease severity for cirrhosis using MRI-derived radiomic features of the liver and spleen and compared it to the existing disease severity metrics of MELD score and clinical decompensation. The MELD score is compiled solely by blood parameters, and so far, it was not investigated if extracted image-based features have the potential to reflect severity to potentially complement the calculated score. Methods This was a retrospective study of eligible patients with cirrhosis ($$n=90$$ n = 90 ) who underwent a contrast-enhanced MR screening protocol for hepatocellular carcinoma (HCC) screening at a tertiary academic center from 2015 to 2018. Radiomic feature analyses were used to train four prediction models for assessing the patient’s condition at time of scan: MELD score, MELD score $$\ge $$ ≥ 9 (median score of the cohort), MELD score $$\ge $$ ≥ 15 (the inflection between the risk and benefit of transplant), and clinical decompensation. Liver and spleen segmentations were used for feature extraction, followed by cross-validated random forest classification. Results Radiomic features of the liver and spleen were most predictive of clinical decompensation (AUC 0.84), which the MELD score could predict with an AUC of 0.78. Using liver or spleen features alone had slightly lower discrimination ability (AUC of 0.82 for liver and AUC of 0.78 for spleen features only), although this was not statistically significant on our cohort. When radiomic prediction models were trained to predict continuous MELD scores, there was poor correlation. When stratifying risk by splitting our cohort at the median MELD 9 or at MELD 15, our models achieved AUCs of 0.78 or 0.66, respectively. Conclusions We demonstrated that MRI-based radiomic features of the liver and spleen have the potential to predict the severity of liver cirrhosis, using decompensation or MELD status as imperfect surrogate measures for disease severity.

Aim: Middle Meningeal Artery (MMA) embolization has emerged as a viable neuroendovascular technique for the management of chronic subdural hematoma (SDH). Comparative analysis of various endovascular techniques for embolization is lacking. Guidance on operative techniques in situations of prior embolization failure is rare. Materials and Methods: In this case report, we present a patient with a chronic subdural hematoma that failed previous coil embolization of the MMA. Digital Subtraction Angiography showed the previously placed coil and continued distal flow to the dural membranes. Results: Onyx liquid embolization was completed successfully, effectively halting both anterograde flow to the MMA and retrograde flow from external circulation collaterals. Conclusion: This case report suggests that in situations of MMA embolization failure, follow-up angiography may be completed to determine if further embolization through other procedural techniques may be possible. The angiographic images contained here highlight the advantages of liquid embolization over coil embolization of the MMA in halting SDH angiogenesis.

Despite scant evidence, current guidelines indicate that esophageal varices are a relative contraindication to transesophageal echocardiography (TEE). The aim of this study is to compare the risk of gastrointestinal bleeding following TEE among cirrhotic patients with and without endoscopically-documented esophageal varices. This is a retrospective analysis of patients with cirrhosis who underwent upper endoscopy within 4 years of TEE at five institutions between January 2000 and March 2020. Primary outcome was overt gastrointestinal bleeding. Secondary outcomes were hemoglobin decline by at least 2 g/dL or blood transfusion within 48 hours following TEE. Of the 191 patients, 79 (41.4%) had esophageal varices (30.4% large). No patient experienced a primary outcome. Secondary outcomes occurred in 52 (27.2%): 28 (35.4%) with esophageal varices and 24 (21.4%) without varices. After propensity-score covariate adjustment, the odds ratio for a secondary outcome in patients with esophageal varices was 1.49 (95% confidence interval 0.74-2.99). Restricting analysis to those who underwent endoscopy within 1 year of TEE did not significantly alter results. The risk of a secondary outcome was identical between patients who had upper endoscopy prior (27.5%) versus subsequent (26.7%; P = 1.00) to TEE. Conclusions: Among patients with cirrhosis, there was no overt gastrointestinal bleeding after TEE. The likelihood of a 2 g/dL decline in hemoglobin or blood transfusion within 48 hours following TEE was not significantly higher in patients with esophageal varices after controlling for confounders. Patients who underwent upper endoscopy before TEE did not manifest a lower risk of secondary outcomes versus those who had endoscopy after TEE, suggesting that routine preprocedural endoscopy is of marginal utility.

Objective Dermatologists can benefit from adopting environmental sustainability in the management of their practices. We can also use opportunities to share best practices in environmental stewardship concepts with our colleagues, patients, and communities. Herein, we review easy steps for any health care professional, and dermatologists in particular, to adopt environmental sustainability and become more active in the fight against climate change. Methods This study included a select literature review, an identification of resources, and an overview of MyGreenDoctor.org. Results Many simple, cost effective, energy saving resources were identified. A reference list of climate change resources for health are organizations to help with lower their carbon footprints, educating their staff and patients, and advocacy for better environmental stewardship is presented. Conclusion Going green is an easy process that can save money, boost morale, and help educate patients while reducing the carbon footprint of any size medical practice.

Konfrontation mit aversiven Traumasymptomen ist ein wesentlicher Bestandteil der Behandlung von Traumafolgestorungen, insbesondere der posttraumatischen Belastungsstorung. Ihr Ziel ist das begleitete Durcharbeiten und Neubewerten von belastenden Erinnerungen und Situationen. Verschiedene Techniken erlauben eine Konfrontation bzw. Exposition in sensu (d. h. in der Vorstellung) oder in vivo (in der Realitat). Ihre Wirksamkeit ist hoch. Wegen des Risikos vorubergehend verstarkter, evtl. zuvor unterdruckter Traumaerinnerungen muss Konfrontation aber sehr gut vor- und nachbereitet werden.

The United States Military Academy at West Point is a four-year, undergraduate institution that educates and trains its students (cadets) to become future leaders in the US Army officer corps. The Department of Foreign Languages (DFL) at West Point plays an integral role in developing cadets’ cultural and linguistic competencies in preparation for potential overseas deployments while serving in the Army. DFL offers cadets the opportunity to major in eight different foreign languages. Among these are Spanish and Portuguese, two robust second language (L2) programs whose current annual enrollments are 487 and 393 cadets, respectively (out of a total population of 4,000 cadets). Besides language instruction for general proficiency, the Spanish and Portuguese curricula also offer embedded training modules, independent courses, and immersion programs centered on how to negotiate specific military tasks within the target languages. These L2 touchpoints fall under the umbrella of Languages for Specific Purposes (LSP) and are designed to prepare our cadets for future interactions with foreign militaries and cultures in a variety of global regions, including Latin America, Europe, and Africa. This essay details West Point’s Spanish and Portuguese LSP models, focusing on their phased, cumulative design and overall effectiveness as specialty curricula within DFL.

International audience; This report is based on proceedings from the Exposure Assessment Tools for Hypersensitivity Pneumonitis (HP) Workshop, sponsored by the American Thoracic Society, that took place on May 18, 2019, in Dallas, Texas. The workshop was initiated by members from the Environmental, Occupational, and Population Health and Clinical Problems Assemblies of the American Thoracic Society. Participants included international experts from pulmonary medicine, occupational medicine, radiology, pathology, and exposure science. The meeting objectives were to 1) define currently available tools for exposure assessment in evaluation of HP, 2) describe the evidence base supporting the role for these exposure assessment tools in HP evaluation, 3) identify limitations and barriers to each tool's implementation in clinical practice, 4) determine which exposure assessment tools demonstrate the best performance characteristics and applicability, and 5) identify research needs for improving exposure assessment tools for HP. Specific discussion topics included history-taking and exposure questionnaires, antigen avoidance, environmental assessment, specific inhalational challenge, serum-specific IgG testing, skin testing, lymphocyte proliferation testing, and a multidisciplinary team approach. Priorities for research in this area were identified.

Indications for TF-TAVI (transfemoral transcatheter aortic valve implantation) are rapidly changing according to increasing evidence from randomized controlled trials. Present trials document the non-inferiority or even superiority of TF-TAVI in intermediate-risk patients (STS-Score 4–8%) as well as in low-risk patients (STS-Score

Repeated pairing of transcranial magnetic stimulation (TMS) over left and right primary motor cortex (M1), at intensities sufficient to generate descending volleys, produces sustained increases in corticospinal excitability. In other paired associative stimulation (PAS) protocols, in which peripheral afferent stimulation is the first element, changes in corticospinal excitability achieved when the second stimulus consists of brief bursts of transcranial alternating current stimulation (tACS), are comparable to those obtained if TMS is used instead (McNickle and Carson 2015). The present aim was to determine whether associative effects are induced when the first stimulus of a cortico-cortical pair is tACS, or alternatively subthreshold TMS. Bursts of tACS (500 ms; 140 Hz; 1 mA) were associated (180 stimulus pairs) with single magnetic stimuli (120% resting motor threshold rMT) delivered over the opposite (left) M1. The tACS ended 6 ms prior to the TMS. In a separate condition, TMS (55% rMT) was delivered to right M1 6 ms before (120% rMT) TMS was applied over left M1. In a sham condition, TMS (120% rMT) was delivered to left M1 only. The limitations of null hypothesis significance testing are well documented. We therefore employed Bayes factors to assess evidence in support of experimental hypotheses—defined precisely in terms of predicted effect sizes, that these two novel variants of PAS increase corticospinal excitability. Although both interventions induced sustained (~ 20–30 min) increases in corticospinal excitability, the evidence in support of the experimental hypotheses (over specified alternatives) was generally greater for the paired TMS-TMS than the tACS-TMS conditions.

In 2018, nearly 800,000 HIV positive individuals in South Africa were unaware of their status. Traditional healers see patients who avoid health clinics, including those who refuse HIV testing. This manuscript details the results of a qualitative study to understand traditional healer perspectives on performing healer-initiated HIV counseling and testing HIV in rural South Africa. We conducted 30 structured in-depth, in-person interviews between April and June 2019 to elicit traditional healer attitudes towards partnering with local health services to perform HIV counseling and testing with their patients. Healers reported that while some patients are open about their HIV status, others lie about it due to stigma around the disease. This creates challenges with concurrent treatment, which healers believe leads to allopathic and/or traditional medication treatment failure. Most healers expressed both an interest and a willingness to perform HIV counseling and testing. Healers felt that by performing testing in the community, it would overcome issues related to HIV stigma, as well as a lack of confidentiality and trust with health care workers at the clinic. Trained traditional healers may be able to bridge the testing gap between “non-testers” and the allopathic health system, essentially “opening” thousands of new testing locations with little financial investment.

Immune checkpoint inhibitors (ICI) have improved outcomes in patients with various malignancies; however, they can cause immune-related hepatitis and enterocolitis. Patients on ICI may also develop upper gastrointestinal symptoms and undergo measurement of gastric emptying. Our aim was to review records of patients with gastroparesis following ICI therapy at two medical centers. We performed a retrospective review of all patients at Mayo Clinic and Brigham and Women’s/Dana-Farber Cancer Center (BWH/DFCC) who underwent gastric scintigraphy for the assessment of symptoms of gastroparesis following ICI treatment up to January 2020. Clinical presentation, medical history, laboratory evaluation, imaging, treatment, and outcomes were retrieved from the records. Gastroparesis was diagnosed as delayed gastric emptying (GE) measured by gastric scintigraphy. At Mayo Clinic, 2 patients (median age 59 years, 1 male [M], 1 female [F]) had delayed GE, while 4 patients (median age 53 years, 3M, 1F) had normal GE following ICI use. Of those with delayed GE (diagnosed after 38 and 2 months of ICI initiation), 1 patient was treated for non-Hodgkin’s lymphoma and melanoma with ipilimumab; a second patient with breast cancer was treated with pembrolizumab. At BWH/DFCC, 2 patients (median age 56 years, 1M, 1F) had normal GE after ICI treatment, while a 62-year-old female with non-small cell lung cancer developed gastroparesis 3 months following initiation of nivolumab. This report documents gastroparesis as a potential adverse effect of ICI. Further studies should explore the potential for ICI therapy to damage anti-inflammatory macrophages that preserve the enteric neurons.

Background The Cholera Hospital-Based Intervention for 7 Days (CHoBI7) mobile health (mHealth) program was a cluster-randomized controlled trial of diarrhea patient households conducted in Dhaka, Bangladesh. Methods Patients were block-randomized to 3 arms: standard message on oral rehydration solution use; health facility delivery of CHoBI7 plus mHealth (no home visits); and health facility delivery of CHoBI7 plus 2 home visits and mHealth. The primary outcome was reported diarrhea in the past 2 weeks collected monthly for 12 months. The secondary outcomes were stunting, underweight, and wasting at a 12-month follow-up. Analysis was intention-to-treat. Results Between 4 December 2016 and 26 April 2018, 2626 participants in 769 households were randomly allocated to 3 arms: 849 participants to the standard message arm, 886 to mHealth with no home visits arm, and 891 to the mHealth with 2 home visits. Children Conclusions The CHoBI7 mHealth program lowered pediatric diarrhea and stunting among diarrhea patient households. Clinical Trials Registration NCT04008134.

Introduction Burns patients with psychiatric comorbidities may be at increased risk of harm from drug interactions. We aimed to identify the most common classes of drug involved, the potential clinical effects and any clinical evidence for their occurrence. Methods The International Burn Injury Database was used to identify all admission episodes for patients with a psychiatric comorbidity over a 5-year period at an adult regional burns unit. For this group, all drugs administered were categorised as either a new or continuing medication. Following this, an established online tool was used to screen for potential interactions between drugs. Where one was identified, a retrospective notes review was used to investigate whether it had occurred clinically. Results Ninety-one admission episodes were identified and records were available for 60 of these. In total, 145 incidences of severe potential interactions were identified (89 between a new drug and a continuing drug and 56 between two new drugs). The most frequently involved continuing drugs with the potential for interaction were neurotransmitter reuptake-inhibiting antidepressants and mirtazapine, while the most common new drugs identified were ondansetron, fentanyl and tramadol. The most frequently identified potential consequence of interactions were serotonin syndrome, arrhythmias and hypokalaemia. Clinically, there was minimal evidence for any interaction. Conclusion We have found many potential severe interactions in this patient group and psychotropic drugs were more commonly implicated than other drug classes. However, there was little evidence of the clinical manifestations of interaction. Serious drug interactions in burns patients are likely rare, but clinicians should be aware of the most likely drugs involved and the possible sequelae.

The Cholera-Hospital-Based Intervention for 7-days (CHoBI7) mobile health (mHealth) program delivers mobile messages to diarrhoea patient households promoting water treatment and handwashing with soap. The randomised controlled trial (RCT) of the CHoBI7 mHealth program demonstrated this intervention was effective in significantly reducing diarrhoea and stunting amoung young children. The objective of this study was to assess the implementation of the CHoBI7 mHealth program in delivering mHealth messages during this RCT.517 diarrhoea patient households with 1777 participants received weekly text, voice and interactive voice response (IVR) messages from the CHoBI7 mHealth program over the 12-month program period. The program process evaluation indicators were the following: the percentage of CHoBI7 mHealth messages received and fully listened to by program households (program fidelity and dose), and household members reporting receiving and sharing an mHealth message from the program in the past two weeks (program reach).Ninety two percent of text messages were received by program households. Eighty three percent of voice and 86% of IVR messages sent were fully listened to by at least one household member. Eighty one percent of IVR quiz responses from households were answered correctly. Program households reported receiving a CHoBI7 mHealth message in the past two weeks at 79% of monthly household visits during the 12-month program. Seventy seven percent of participants reported sharing a program message with a spouse, 55% with a neighbour and 49% with a child during the program period.There was high fidelity, dose and reach of mobile messages delivered for the CHoBI7 mHealth program. This study presents an approach for process evaluation that can be implemented to evaluate future mHealth programs.Le programme CHoBI7 (Cholera-Hospital-Based-Intervention-for-7-days) de santé mobile (mHealth) délivre des messages mobiles aux ménages avec patients atteints de diarrhée pour promouvoir le traitement de l'eau et le lavage des mains au savon. L'essai contrôlé randomisé (ECR) du programme mHealth CHoBI7 a démontré que cette intervention était efficace pour réduire de manière significative la diarrhée et le retard de croissance chez les jeunes enfants. L'objectif de cette étude était d'évaluer la mise en œuvre du programme CHoBI7 mHealth dans la diffusion des messages mHealth au cours de cet ECR. MÉTHODES: 517 ménages avec des patients atteints de diarrhée ont reçu chaque semaine des messages SMS, vocaux et de réponse vocale interactive (RVI) du programme mHealth de CHoBI7 pendant les 12 mois du programme. Les indicateurs d'évaluation du processus du programme étaient les suivants: le pourcentage de messages mHealth du programme CHoBI7 reçus (fidélité au programme et dose) et entièrement écoutés par les ménages participant au programme (fidélité au programme et dose) et les bénéficiaires déclarant avoir reçu et partagé un message mHealth du programme (portée du programme) au cours des deux dernières semaines. RÉSULTATS: 92% des SMS ont été reçus par les ménages participant au programme. 83% des messages vocaux et 86% des messages RVI envoyés ont été entièrement écoutés par au moins un membre du ménage. 81% des réponses aux quiz RVI des ménages ont été correctement répondues. Les ménages du programme ont déclaré avoir reçu un message CHoBI7 mHealth au cours des deux dernières semaines dans 79% des visites mensuelles des ménages pendant les 12 mois du programme. 77% des participants ont déclaré avoir partagé un message du programme avec un conjoint, 55% avec un voisin et 49% avec un enfant pendant la durée du programme.La dose et les messages délivrés dans le cadre du programme mHealth de CHoBI7 l’ont été avec une fidélité élevée. Cette étude présente une approche d'évaluation des processus qui peut être mise en œuvre pour évaluer les futurs programmes mHealth.

Application of floating solar panels is especially suited for the Netherlands, given the limited availability of land (surface area). Evides water company owns and operates several open storage reservoirs which can be used for installation of these panels, but the installations could affect the local environment, naturally occurring processes and water quality. In this research, we evaluate leaching of various substances and possible effects based on a theoretical approach following the Analysis of Microbiological Safety of Drinking water (AMSD method). Besides the water quality issues, the ongoing research at Evides will focus on the effect of the floating solar installation on algae, microbiological and chemical parameters, birds, aquatic flora and fauna, and also look into possibilities of applying alternative storage possibilities using hydrogen.

Background: Worldwide, horses play critical roles in recreation, food production, transportation, and as working animals. Horses' roles differ by geographical region and the socioeconomic status of the people, but despite modern advances in transportation, which have in some ways altered humans contact with horses, potential risks for equine zoonotic pathogen transmission to humans occur globally. While previous reports have focused upon individual or groups of equine pathogens, to our knowledge, a systematic review of equine zoonoses has never been performed. Methods: Using PRISMA's systematic review guidelines, we searched the English literature and identified 233 previous reports of potential equine zoonoses found in horses. We studied and summarized their findings with a goal of identifying risk factors that favor disease transmission from horses to humans. Results: These previous reports identified 56 zoonotic pathogens that have been found in horses. Of the 233 articles, 13 involved direct transmission to humans (5.6%).The main potential routes of transmission included oral, inhalation, and cutaneous exposures. Pathogens most often manifest in humans through systemic, gastrointestinal, and dermatological signs and symptoms. Furthermore, 16.1% were classified as emerging infectious diseases and thus may be less known to both the equine and human medical community. Sometimes, these infections were severe leading to human and equine death. Conclusions: While case reports of zoonotic infections directly from horses remain low, there is a high potential for underreporting due to lack of knowledge among health professionals. Awareness of these zoonotic pathogens, their disease presentation in horses and humans, and their associated risk factors for cross-species infection are important to public health officials, clinicians, and people with recreational or occupational equid exposure.

Background: Despite advancements in treatment for inflammatory bowel disease (IBD), surgery remains inevitable for patients and IBD management is costly. Introduction: Frequent postoperative monito...

Despite positive initial outcomes emerging from preclinical and early clinical investigation of alginate hydrogel injection therapy as a treatment for heart failure, the lack of knowledge about the mechanism of action remains a major shortcoming that limits the efficacy of treatment design. To identify the mechanism of action, we examined previously unobtainable measurements of cardiac function from in vivo, ex vivo, and in silico states of clinically relevant heart failure (HF) in large animals. High-resolution ex vivo magnetic resonance imaging and histological data were used along with state-of-the-art subject-specific computational model simulations. Ex vivo data were incorporated in detailed geometric computational models for swine hearts in health (n=5), ischemic HF (n=5), and ischemic HF treated with alginate hydrogel injection therapy (n=5). Hydrogel injection therapy mitigated elongation of sarcomere lengths (1.68±0.10μm [treated] vs. 1.78±0.15μm [untreated], p99% accuracy and predicted small myofiber strain in the vicinity of the solidified hydrogel that was sustained for up to 13 mm away from the implant. These findings suggest that the solidified alginate hydrogel material acts as an LV mid-wall constraint that significantly reduces adverse LV remodeling compared to untreated HF controls without causing negative secondary outcomes to cardiac function. STATEMENT OF SIGNIFICANCE: Heart failure is considered a growing epidemic and hence an important health problem in the US and worldwide. Its high prevalence (5.8 million and 23 million, respectively) is expected to increase by 25% in the US alone by 2030. Heart failure is associated with high morbidity and mortality, has a 5-year mortality rate of 50%, and contributes considerably to the overall cost of health care ($53.1 billion in the US by 2030). Despite positive initial outcomes emerging from preclinical and early clinical investigation of alginate hydrogel injection therapy as a treatment for heart failure, the lack of knowledge concerning the mechanism of action remains a major shortcoming that limits the efficacy of treatment design. To understand the mechanism of action, we combined high-resolution ex vivo magnetic resonance imaging and histological data in swine with state-of-the-art subject-specific computational model simulations. The in silico models realistically simulated in vivo function with >99% accuracy and predicted small myofiber strain in the vicinity of the solidified hydrogel that was sustained for up to 13 mm away from the implant. These findings suggest that the solidified alginate hydrogel material acts as a left ventricular mid-wall constraint that significantly reduces adverse LV remodeling compared to untreated heart failure controls without causing negative secondary outcomes to cardiac function. Moreover, if the hydrogel can be delivered percutaneously rather than via the currently used open-chest procedure, this therapy may become routine for heart failure treatment. A minimally invasive procedure would be in the best interest of this patient population; i.e., one that cannot tolerate general anesthesia and surgery, and it would be significantly more cost-effective than surgery.

Wound infection is commonly observed after surgery and trauma but is difficult to diagnose and poorly defined in terms of objective clinical parameters. The assumption that bacteria in a wound correlate with infection is false; all wounds contain microorganisms, but not all wounds are clinically infected. This makes it difficult for clinicians to determine true wound infection, especially in wounds with pathogenic biofilms. If an infection is not properly treated, pathogenic virulence factors, such as rhamnolipids from Pseudomonas aeruginosa, can modulate the host immune response and cause tissue breakdown. Life-threatening sepsis can result if the organisms penetrate deep into host tissue. This communication describes the sensor development for five important clinical microbial pathogens commonly found in wounds: Staphylococcus aureus, P. aeruginosa, Candida albicans/auris, and Enterococcus faecalis (the SPaCE pathogens). The sensor contains liposomes encapsulating a self-quenched fluorescent dye. Toxins, expressed by SPaCE infecting pathogens in early-stage infected wounds, break down the liposomes, triggering dye release, thus changing the sensor color from yellow to green, an indication of infection. Five clinical species of bacteria and fungi, up to 20 strains each (totaling 83), were grown as early-stage biofilms in ex vivo porcine burn wounds. The biofilms were then swabbed, and the swab placed in the liposome suspension. The population density of selected pathogens in a porcine wound biofilm was quantified and correlated with colorimetric response. Over 88% of swabs switched the sensor on (107-108 CFU/swab). A pilot clinical study demonstrated a good correlation between sensor switch-on and early-stage wound infection.

The purpose of this study is to explore changes in mood in youth with persistent post-concussion symptoms following participation in a six-week active rehabilitation program.A pre-post test design was used.Participants (N = 40 children and adolescents with concussion symptoms2 weeks post-injury) were recruited from the concussion services at an urban children's rehabilitation hospital and the community. The program consisted of individualized low-intensity aerobic exercise, sport-specific drills, relaxation exercises and comprehensive education and support. The 6 week program was completed by participants in their home or local community with weekly check-ins with the research team. Data were analyzed using descriptive statistics and linear regressions.Outcome measures included the Beck Youth Inventories (youth), and the Child Behavior Checklist (parents). Results indicated significant improvements in anger and anxiety post-intervention with anger reduction being more pronounced in girls.Active rehabilitation interventions may have positive effects on mood in youth recovering from concussion. Clinicians may wish to consider addressing anxiety and anger management strategies as part of comprehensive concussion management in youth.

Background Patients living with chronic upper limb and neck (ULN) pain are reliant on often ineffective therapies as they face limited options for effective long-term treatment. Objective Prospective clinical studies have demonstrated that high-frequency spinal cord stimulation at 10 kHz (10 kHz SCS) is effective in treating chronic pain in multiple etiologies including ULN pain. This study aimed at validating the findings from clinical studies on ULN in a real-world cohort. Study design A retrospective, observational review. Setting A multicenter review between April 2016 and August 2019. Patients and methods Anonymized data were extracted from a real-world database of 47 consecutive patients aged ≥18 years of age with chronic upper limb and/or neck pain who were trialed and permanently implanted with 10 kHz SCS. Patient-reported pain relief, quality of life, function, sleep and medication use were extracted from anonymised patient records where available. Responder rates, defined as the proportion of patients with at least 50% pain relief at the end of trial and the last visit after implantation, were calculated. Results All patients reported successful response (≥50% pain relief) at the end of trial and >75% patients continued to respond to the therapy at the last follow-up period. Majority (72%) of patients reported improvement in function, about half of the patients (53%) reported improvement in sleep and one-third of the patients (36%) reported reducing their medication at last follow-up. Conclusion 10 kHz SCS provides durable pain relief to patients with chronic upper limb and neck pain.

Background While little is known about the occupational hazards associated with Cannabis cultivation, both historical research in the hemp industry and preliminary data from modern grow houses, suggest that Cannabis workers may be at increased risk of respiratory and allergic diseases. Objectives We sought to investigate the association between workplace exposures and health symptoms in an indoor Cannabis grow facility in Washington State, USA. Methods We performed a cross-sectional study with all consenting employees in an indoor Cannabis grow facility in Seattle, WA using a questionnaire. The questionnaire gathered data on respiratory, ocular, nasal, and dermal symptoms. A subset of employees with work-related symptoms underwent repeated cross-shift and cross-week measurement of spirometry, fractional exhaled nitrogen oxide (FeNO), and skin prick testing for Cannabis sensitization. Exposure to Cannabis dust was classified based on self-described tasks, expert opinion, and exposure monitoring of particulate matter. Multivariable logistic regression was undertaken to examine associations between exposure to Cannabis dust (classified as low, medium, and high) and health symptoms. Linear mixed effects models examined the relationship between cross-shift and cross-week changes in spirometry and FeNO. Results Ninety-seven percent (97%) of the employees (n = 31) surveyed were recreational cannabis users, with 81% (n = 25) smoking cannabis multiple times per day. Twenty-two (71%) employees reported one or more work-related symptoms: 65% respiratory, 39% ocular, 32% nasal, and 26% dermal symptoms. There was a trend toward increased likelihood of work-related symptoms with increasing exposure to Cannabis dust, although none of these results were statistically significant. Of the 10 employees with work-aggravated symptoms, 5 had borderline-high or high FeNO, 7 had abnormal spirometry, and 5 had evidence of Cannabis sensitization on skin prick testing. FeNO increased by 3.78 ppb (95% confidence interval 0.68–6.88 ppb) across the work-week and there was a trend toward cross-week and cross-shift reduced airflow. Conclusions We found a high prevalence of work-related allergic- and particularly respiratory symptoms in the employees of one indoor Cannabis grow facility in Washington State. A high proportion of employees with work-aggravated symptoms had findings consistent with probable work-related asthma based on high FeNO, airflow obstruction on spirometry, and Cannabis sensitization on skin prick testing. However, due to the high incidence of recreational cannabis use among these workers, the relative influence of occupational versus recreational exposure to Cannabis dust on the respiratory health and sensitization status of these workers could not be resolved in this study.

OBJECTIVES Pancreatic ductal adenocarcinoma (PDAC) is a very aggressive tumor with a very low 5-year survival rate of 8%. The aims of this study are to determine reference values and physiologic confounders in healthy pancreas and to assess the diagnostic accuracy of ultrasound time-harmonic elastography (THE) in the detection of PDAC. MATERIALS AND METHODS From March 2017 through May 2019, a total of 54 study participants with healthy pancreas (n = 33, CTR) or PDAC (n = 21) were prospectively enrolled. Repeatability of THE was tested in a CTR subgroup (n = 5) undergoing repeat measurement on 4 different days. Interobserver variability was analyzed in 10 healthy volunteers. Age-matched and sex-matched subgroups of CTR (n = 13) and PDAC (n = 13) were compared. In participants with histopathologically proven PDAC, measurements were performed separately in tumorous (PDAC-T) and nontumorous pancreatic tissue (PDAC-NT). Diagnostic performance of pancreatic THE was assessed by receiver operating characteristic curve analysis. RESULTS Time-harmonic elastography was highly repeatable (intraclass correlation coefficient, 0.99), and interobserver agreement was excellent (intraclass correlation coefficient, 0.97). Shear wave speed (SWS) of PDAC-T (mean [95% confidence interval] in meters per second, 1.88 ± 0.07 [1.84-1.92]) was higher than SWS of CTR (1.63 ± 0.04 [1.60-1.66], P < 0.001) and PDAC-NT (1.59 ± 0.03 [1.57-1.61], P < 0.001). The exploratory diagnostic performance of THE in separating PDAC-T was excellent (area under the receiver operating characteristic curve, 1.0). Tumorous pancreatic ductal adenocarcinoma was distinguished from CTR and PDAC-NT with cutoff values of 1.73 m/s and 1.70 m/s, respectively. CONCLUSIONS Pancreatic ultrasound THE has high repeatability and provides excellent imaging contrast based on SWS, allowing detection of PDAC without overlap to nontumorous pancreatic tissue.

Cerebral blood flow, cerebral stiffness (CS) and intracranial pressure are tightly linked variables of cerebrovascular reactivity and cerebral autoregulation. Transtemporal ultrasound time-harmonic elastography was used for rapid measurement of CS changes in 10 volunteers before, during and after administration of a gas mixture of 95% O2 and 5% CO2 (carbogen). Within the first 2.2 ± 2.0 min of carbogen breathing, shear wave speed determined as a surrogate parameter of CS increased from 1.57 ± 0.04 to 1.66 ± 0.05 m/s (p < 0.01) in synchrony with end-tidal CO2 while post-hypercapnic CS recovery was delayed by 2.7 ± 1.4 min in relation to end-tidal CO2. Our results indicate that CS is highly sensitive to changes in CO2 levels of inhaled air. Possible mechanisms underlying the observed CS changes might be associated with cerebrovascular reactivity, cerebral blood flow adaptation and intracranial regulation, all of which are potentially relevant for future diagnostic applications of transtemporal time-harmonic elastography in a wide spectrum of neurologic diseases.

Lethal features of sepsis and acute respiratory distress syndrome (ARDS) relate to the health of small blood vessels. For example, infiltration of the alveoli with proteinaceous fluid is often driven by breach of the microvascular barrier. Spontaneous thrombus formation within inflamed microvessels exacerbates organ ischemia, and in its final stages, erupts into overt disseminated intravascular coagulation (DIC). A signaling axis in the vascular endothelium, the Angiopoietin-Tie2 pathway, may play a central role in the abrupt transition from microvascular integrity to pathological disruption. Tie2 signaling is highly active when vessels are in their quiescent state: stable junctions, anti-inflammatory, and anti-coagulant. During inflammation however, Tie2 signaling is rapidly toggled off as levels of its endogenous antagonist, Angiopoietin-2, rise by 1–2 orders of magnitude. When Tie2 signaling drops, the microvascular barrier collapses, endothelium becomes adhesive to leukocytes, and the vessel wall no longer prevents spontaneous coagulation. This review will summarize a large body of preclinical and clinical results that implicate the Tie2 pathway in the pathogenesis of sepsis and ARDS. Results from groups worldwide now identify Angiopoietins as dynamic circulating markers of the vasculature. Furthermore, Tie2 is emerging as a promising target to restore microvascular health in sepsis and ARDS. Translational pursuit of the Tie2 pathway may enable advances in the way critically ill patients are diagnosed, monitored, and treated.

Objectives The aim of this study was to investigate blood pressure dependency of ultrasound time-harmonic elastography (THE) for quantification of aortic stiffness. Materials and methods Thoracoabdominal aortas were surgically removed from 9 healthy domestic pigs and prepared for elastographic experiments. All vessels were connected to a saline-filled water column with adjustable height and pressurized over a range of 0 to 110 mm Hg in 10 mm Hg increments to simulate different levels of mean arterial pressure. In addition, 3 of the 9 aortas were soaked in 4% buffered formaldehyde for 60 minutes to simulate pathologic aortic stiffening. Ultrasound THE was performed in each vessel at each pressure level. For each pressure level, shear-wave speed (SWS) as a measure of aortic wall stiffness and luminal diameter were recorded. The pressure range between 30 and 110 mm Hg was used for statistical evaluation as it reflects a physiological mean arterial pressure range. Linear regression analysis and multivariate analysis with a general linear model were performed to evaluate the influence of increasing intravascular pressure and vessel diameter on measured SWS. Results Median SWS in formalin-soaked aortas was significantly higher with 3.22 m/s (interquartile range [IQR], 0.01 m/s) versus 2.14 m/s (IQR, 0.09) at 30 mm Hg and 3.38 m/s (IQR, 0.01 m/s) versus 2.28 m/s (IQR, 0.07 m/s) at 110 mm Hg (each P = 0.01). Using linear regression analysis, an increase of aortic wall SWS of 0.017 m/s per 10 mm Hg intraluminal pressure was found in untreated aortas, whereas SWS increased by 0.020 m/s per 10 mm Hg in formalin-soaked aortas (both P = 0.001). The percentage of SWS caused by intraluminal pressure was 1.89% in formalin-soaked aortas and 2.50% in untreated aortas at 30 mm Hg and 6.61% for formalin-soaked aortas and 8.60% for untreated aortas at 110 mm Hg. Multivariate analysis showed no significant interaction of luminal diameter and measured SWS (P = 0.893). Conclusions In our model, aortic stiffness measurements by ultrasound time-harmonic elastography are influenced to a small extent by mean arterial pressure in a range of 1.89% to 8.60%. These findings emphasize the potential of ultrasound THE for measuring the intrinsic stiffness of the aortic wall in clinical routine.

Following mediastinoscopy, a prognostically orientated multimodality approach was chosen in selected small-cell lung cancer (SCLC) patients with hyperfractionated accelerated chemoradiotherapy (Hf-RTx) and definitive surgery (S). Stage IB/IIA patients had four cycles of cisplatin/etoposide (PE) and surgery. Stage IIB/IIIA patients had three cycles PE followed by one cycle concurrent chemoradiation including Hf-RTx and surgery. Most stage IIIB patients were not planned for surgery and had CTx followed by sequential RTx or one cycle concurrent CTx/RTx. Of 46 consecutive patients (stage IB six, IIA two, IIB/IIIA 22, IIIB 16) 43 (94%) showed an objective response. Twenty-three of patients (72%) planned for inclusion of S were completely resected (R0) (IB 6/6, IIA 2/2, IIB/IIIA 13/22, IIIB 2/2). Overall toxicity was acceptable – one patient died of septicaemia, no perioperative deaths occurred. Median follow-up of patients alive (n = 21) is 52 months (30+ – 75+). Median survival and 5-year survival rate of all patients are 36 months and 46%, in R0 patients 68 months and 63% (R0-IIB/IIIA/IIIB: not yet reached and 67%). This multimodality treatment including surgery proved highly effective with 100% local control and remarkable long-term survival after complete resection, even in locally advanced SCLC stages IIB/IIIA patients. © 1999 Cancer Research Campaign

Objectives: Accurate radiological differentiation of parotid tumors remains challenging despite recent technical advances in quantitative medical imaging. Multifrequency magnetic resonance elastography (MRE) could provide additional information on viscoelastic properties of normal and abnormal biological tissues. This study investigates the feasibility of MRE of the parotid glands in healthy participants and provides first reference values. Methods: 20 healthy participants underwent multifrequency MRE of both parotid glands at 3 Tesla. Shear waves at frequencies of 25, 30, 40, and 50 Hz were introduced into the participants' heads through the occiput using pressurized-air actuators. Shear wave speed (SWS) and loss angle of the shear modulus (φ) were reconstructed by tomoelastography post-processing as surrogate parameters for tissue stiffness and viscosity or fluidity. 10 participants underwent repeated MRE to determine test–retest reliability based on intraclass correlation coefficients. Results: All MRE datasets acquired could be included in the analysis. Mean SWS was 0.97 ± 0.13 m/s, and mean φ was 0.59 ± 0.05 rad, each for both sides combined and without notable lateral difference (p = 0.88/0.87). Test–retest reliability was good for SWS (ICC = 0.84 for both sides/ICC = 0.77 for the right side/ICC = 0.79 for the left side) and good to excellent for φ(ICC = 0.94/0.86/0.90). Conclusions: Multifrequency MRE of the parotid glands is feasible and reliable. This technique, therefore, is a promising method for investigating the viscoelastic properties of salivary gland tumors in future studies.

BACKGROUND: Mycobacterium tuberculosis complex (MTBC) and its human host are the most competent organisms with co-evolutionary trajectory. This review determined the phylogeography, clinical phenotype-related genotype and transmission dynamics of MTBC in Africa.METHODS: Spoligotyping and mycobacterial interspersed repetitive units-variable number tandem repeats (MIRU-VNTR) based articles from Africa published in the English language were included. Articles were retrieved from PubMed and Scopus on 12 May 2018.RESULTS: In Africa, respectively 92% and 7% of tuberculosis (TB) cases were caused by M. tuberculosis and M. africanum. Among M. tuberculosis lineages (L), L4 was the predominant, at 67%, followed by L3/Central Asian (CAS; 10%). L7/ETH1 and L5/6/Maf were restricted to the Horn and Western Africa, respectively. L4.6/SIT37, H37Rv like, L4.1.2/Haarlem and H3-Ural were proportionally more frequent among tuberculous lymphadenitis (TBLN) than among pulmonary tuberculosis (PTB) cases. On 24-locus MIRU-VNTR, clustering rate was 31%; the secondary case rate from a single primary source case was 20%.CONCLUSION: Africa in general, and the east-west pole of Africa in particular, harboured a genetically diverse population of MTBC, with characteristics of geographic segregation. Both generalist and specialist genotypes are circulating in the region. L4 is dominant across the continent, while M. bovis is rarely detected as a cause for human TB. The clinical significance of genetic diversity of MTBC in the different geographic and population groups of Africa is not fully understood. Both person-to-person transmission and reactivation mode of TB is significant in Africa. Prevention and control strategies should therefore envisage these two scenarios.

CASE DESCRIPTION A 5-year-old spayed female domestic shorthair cat was evaluated because of an acute onset of dyspnea and open-mouthed breathing. CLINICAL FINDINGS Thoracic radiography revealed pleural effusion and signs consistent with restrictive pleuritis, and results of preoperative CT were consistent with diffuse, severe restrictive pleuritis, bilateral pleural effusion, and pulmonary atelectasis. Thoracocentesis yielded a red, turbid fluid that was identified as chylous effusion with chronic inflammation. TREATMENT AND OUTCOME Exploratory thoracotomy revealed diffuse, severe fibrous adhesions between the mediastinum, heart, lung lobes, and thoracic wall, with a thick fibrous capsule enveloping all lung lobes. Surgical treatment consisted of complete pleural decortication, pericardiectomy, and thoracic omentalization. The cat remained hospitalized for 6 days, receiving oxygen supplementation, multimodal analgesia, and supportive care. Long-term home care consisted of prednisolone administration, rutin supplementation, and provision of a low-fat diet. At recheck examinations 3-, 7-, and 20-weeks postoperatively, the cat remained tachypneic, but was otherwise clinically normal without dyspnea or respiratory distress. Follow-up thoracic radiography revealed improved pulmonary expansion, decreased pleural effusion, and resolved pneumothorax. CLINICAL RELEVANCE Surgical management of fibrosing pleuritis secondary to idiopathic chylothorax in cats has historically resulted in poor outcomes. This report details the first successful use of complete decortication in the surgical management of severe fibrosing pleuritis in a cat.

The entity type information in Knowledge Graphs (KGs) such as DBpedia, Freebase, etc. is often incomplete due to automated generation. Entity Typing is the task of assigning or inferring the semantic type of an entity in a KG. This paper introduces an approach named Cat2Type which exploits the Wikipedia Categories to predict the missing entity types in a KG. This work extracts information from Wikipedia Category names and the Wikipedia Category graph which are the sources of rich semantic information about the entities. In Cat2Type, the characteristic features of the entities encapsulated in Wikipedia Category names are exploited using Neural Language Models. On the other hand, a Wikipedia Category graph is constructed to capture the connection between the categories. The Node level representations are learned by optimizing the neighbourhood information on the Wikipedia category graph. These representations are then used for entity type prediction via classification. The performance of Cat2Type is assessed on two real-world benchmark datasets DBpedia630k and FIGER. The experiments depict that Cat2Type obtained a significant improvement over state-of-the-art approaches.

The ocean, which regulates climate and supports vital ecosystem services, is crucial to our Earth system and livelihoods. Yet, it is threatened by anthropogenic pressures and climate change. A healthy ocean that supports a sustainable ocean economy requires adequate financing vehicles that generate, invest, align, and account for financial capital to achieve sustained ocean health and governance. However, the current finance gap is large; we identify key barriers to financing a sustainable ocean economy and suggest how to mitigate them, to incentivize the kind of public and private investments needed for topnotch science and management in support of a sustainable ocean economy., The ocean supports many livelihoods, but this is currently not sustainable with pressures on the climate and ecosystems. Here, in this perspective, the authors outline the barriers and solutions for financing a sustainable ocean economy.