Aneurysmal growth in type-B aortic dissection: assessing the impact of patient-specific inlet conditions on key haemodynamic indices.

Type-B aortic dissection is a cardiovascular disease in which a tear develops in the intimal layer of the descending aorta, allowing pressurized blood to delaminate the layers of the vessel wall. In medically managed patients, long-term aneurysmal dilatation of the false lumen (FL) is considered virtually inevitable and is associated with poorer disease outcomes. While the pathophysiological mechanisms driving FL dilatation are not yet understood, haemodynamic factors are believed to play a key role. Computational fluid dynamics (CFD) and 4D-flow MRI (4DMR) analyses have revealed correlations between flow helicity, oscillatory wall shear stress and aneurysmal dilatation of the FL. In this study, we compare CFD simulations using a patient-specific, three-dimensional, three-component inlet velocity profile (4D IVP) extracted from 4DMR data against simulations with flow rate-matched uniform and axial velocity profiles that remain widely used in the absence of 4DMR. We also evaluate the influence of measurement errors in 4DMR data by scaling the 4D IVP to the degree of imaging error detected in prior studies. We observe that oscillatory shear and helicity are highly sensitive to inlet velocity distribution and flow volume throughout the FL and conclude that the choice of IVP may greatly affect the future clinical value of simulations.

Portable real-time colorimetric LAMP-device for rapid quantitative detection of nucleic acids in crude samples.

Loop-mediated isothermal amplification is known for its high sensitivity, specificity and tolerance to inhibiting-substances. In this work, we developed a device for performing real-time colorimetric LAMP combining the accuracy of lab-based quantitative analysis with the simplicity of point-of-care testing. The device innovation lies on the use of a plastic tube anchored vertically on a hot surface while the side walls are exposed to a mini camera able to take snapshots of the colour change in real time during LAMP amplification. Competitive features are the rapid analysis (< 30 min), quantification over 9 log-units, crude sample-compatibility (saliva, tissue, swabs), low detection limit (< 5 copies/reaction), smartphone-operation, fast prototyping (3D-printing) and ability to select the dye of interest (Phenol red, HNB). The device's clinical utility is demonstrated in cancer mutations-analysis during the detection of 0.01% of BRAF-V600E-to-wild-type molecules from tissue samples and COVID-19 testing with 97% (Ct < 36.8) and 98% (Ct < 30) sensitivity when using extracted RNA and nasopharyngeal-swabs, respectively. The device high technology-readiness-level makes it a suitable platform for performing any colorimetric LAMP assay; moreover, its simple and inexpensive fabrication holds promise for fast deployment and application in global diagnostics.

Safety and efficacy of absorbable and non-absorbable fixation systems for intraperitoneal mesh fixation: an experimental study in swine.

PURPOSE: Choice of the best possible fixation system in terms of safety and effectiveness for intraperitoneal mesh placement in hernia surgery remains controversial. The aim of the present study was to compare the performance of four fixation systems in a swine model of intraperitoneal mesh fixation. METHODS: Fourteen Landrace swine were utilized in the study. The experiment included two stages. Initially, four pieces of mesh (Ventralight ™ ST) sizing 10 × 5 cm were placed and fixed intraperitoneally to reinforce 4 small full thickness abdominal wall defects created with diathermy. These defects were repaired primarily with absorbable suture before mesh implantation. Each mesh was anchored with a different tack device between Absorbatack™, Protack™, Capsure™, or Optifix™. The second stage took place after 60 days and included euthanasia, laparoscopy, and laparotomy via U-shaped incision to obtain the measurements for the outcome parameters. The primary endpoint of the study was to compare the peel strength of the compound tack/mesh from the abdominal wall. Secondary parameters were the extent and quality of visceral adhesions to the mesh, the degree of mesh shrinkage and the histological response around the tacks. RESULTS: Thirteen out of 14 animals survived the experiment and 10 were included in the final analysis. Capsure™ tacks had higher peel strength when compared to Absorbatack™ (p = 0.028); Protack™ (p = 0.043); and Optifix™ (p = 0.009). No significant differences were noted regarding the extent of visceral adhesions (Friedman's test p value 0.854), the adhesion quality (Friedman's test p value 0.506), or the mesh shrinkage (Friedman's test p value = 0.827). Four out of the ten animals developed no adhesions at all 2 months after implantation. CONCLUSION: Capsure™ fixation system provided higher peel strength that the other tested devices in our swine model of intraperitoneal mesh fixation. Our findings generate the hypothesis that this type of fixation may be superior in a clinical setting. Clinical trials with long-term follow-up are required to assess the safety and efficacy of mesh fixation systems in hernia surgery.

High-grade blunt traumatic rupture of kidney transplant: is conservative management an option?

Road traffic accidents are the most common cause of blunt native kidney injuries. Transplanted kidneys are more exposed to such injuries due to the common positioning in the iliac fossa compared with the relatively protected position of the native kidneys. The small number of cases identified in the literature describe grade II and III transplant kidney injuries that were treated surgically. In our case a grade IV injury was managed conservatively giving the necessary time to appropriately plan the future renal replacement therapy options for the patient.

Optimized acoustic biochip integrated with microfluidics for biomarkers detection in molecular diagnostics.

The development of integrated platforms incorporating an acoustic device as the detection element requires addressing simultaneously several challenges of technological and scientific nature. The present work was focused on the design of a microfluidic module, which, combined with a dual or array type Love wave acoustic chip could be applied to biomedical applications and molecular diagnostics. Based on a systematic study we optimized the mechanics of the flow cell attachment and the sealing material so that fluidic interfacing/encapsulation would impose minimal losses to the acoustic wave. We have also investigated combinations of operating frequencies with waveguide materials and thicknesses for maximum sensitivity during the detection of protein and DNA biomarkers. Within our investigations neutravidin was used as a model protein biomarker and unpurified PCR amplified Salmonella DNA as the model genetic target. Our results clearly indicate the need for experimental verification of the optimum engineering and analytical parameters, in order to develop commercially viable systems for integrated analysis. The good reproducibility of the signal together with the ability of the array biochip to detect multiple samples hold promise for the future use of the integrated system in a Lab-on-a-Chip platform for application to molecular diagnostics.

Molecular-Level Simulations of Turbulence and Its Decay.

We provide the first demonstration that molecular-level methods based on gas kinetic theory and molecular chaos can simulate turbulence and its decay. The direct simulation Monte Carlo (DSMC) method, a molecular-level technique for simulating gas flows that resolves phenomena from molecular to hydrodynamic (continuum) length scales, is applied to simulate the Taylor-Green vortex flow. The DSMC simulations reproduce the Kolmogorov -5/3 law and agree well with the turbulent kinetic energy and energy dissipation rate obtained from direct numerical simulation of the Navier-Stokes equations using a spectral method. This agreement provides strong evidence that molecular-level methods for gases can be used to investigate turbulent flows quantitatively.

Diurnal Plasma Cortisol Measurements Utility in Differentiating Various Etiologies of Endogenous Cushing Syndrome.

Cortisol diurnal variation may be abnormal among patients with endogenous Cushing syndrome (CS). The study objective was to compare the plasma cortisol AM/PM ratios between different etiologies of CS. This is a retrospective cohort study, conducted at a clinical research center. Adult patients with CS that underwent adrenalectomy or trans-sphenoidal surgery (n=105) were divided to those with a pathologically confirmed diagnosis of Cushing disease (n=21) and those with primary adrenal CS, including unilateral adrenal adenoma (n=28), adrenocortical hyperplasia (n=45), and primary pigmented nodular adrenocortical disease (PPNAD, n=11). Diurnal plasma cortisol measurements were obtained at 11:30 PM and midnight and at 7:30 and 8:00 AM. The ratios between the mean morning levels and mean late-night levels were calculated. Mean plasma cortisol AM/PM ratio was lower among CD patients compared to those with primary adrenal CS (1.4±0.6 vs. 2.3±1.5, p<0.001, respectively). An AM/PM cortisol ratio≥2.0 among patients with unsuppressed ACTH (>15 pg/ml) excludes CD with a 85.0% specificity and a negative predictive value (NPV) of 90.9%. Among patients with primary adrenal CS, an AM/PM cortisol≥1.2 had specificity and NPV of 100% for ruling out a diagnosis of PPNAD. Plasma cortisol AM/PM ratios are lower among patients with CD compared with primary adrenal CS, and may aid in the differential diagnosis of endogenous hypercortisolemia.

Attention Deficit Hyperactivity Disorder in Pediatric Patients with Pheochromocytoma and Paraganglioma.

The aim of the study is to evaluate if there is an association between attention deficit hyperactivity disorder (ADHD) and the diagnosis of pheochromocytoma/paraganglioma (PHEO/PGL) in pediatric patients. A case series study of 43 patients under the age of 18 with PHEO/PGL tumors who were evaluated at the National Institute of Health between January 2006 and May 2014 is reported. Prior diagnosis of ADHD and treatment course with stimulant medications was recorded. Patient symptoms, catecholamine and metanephrine levels, tumor characteristics, and genetic analyses for syndromes associated with PHEO/PGL were evaluated. A chi-squared test was used to assess the prevalence of ADHD in the PHEO/PGL patients compared to the general population. Nine out of 43 (21%) of patients diagnosed with PHEO/PGL had been diagnosed with ADHD prior to tumor identification. Four of the 9 patients had been treated with amphetamine, dextroamphetamine, and/or methylphenidate, potentially exacerbating an adrenergic crisis. In addition, 4 patients exhibited hypertension at the initial diagnosis of their PHEO/PGL. Three patients had resolution of their ADHD symptoms after successful surgical removal of PHEO/PGL. Our study found a prevalence of ADHD in 21% of our PHEO/PGL patients, significantly higher than 7.2% seen in the general pediatric population. Symptoms of anxiety and difficulty in concentration in these patients may have been related to their underlying PHEO/PGL and were not recognized as part of the constellation of symptoms in a child with PHEO/PGL. In pediatric patients with hypertension and ADHD symptomatology, an evaluation to rule out PHEO/PGL is warranted prior to treatment with stimulant medications.

Use of 3-Dimensional Volumetric Modeling of Adrenal Gland Size in Patients with Primary Pigmented Nodular Adrenocortical Disease.

Primary pigmented nodular adrenocortical disease (PPNAD) is a rare type of bilateral adrenal hyperplasia leading to hypercortisolemia. Adrenal nodularity is often appreciable with computed tomography (CT); however, accurate radiologic characterization of adrenal size in PPNAD has not been studied well. We used 3-dimensional (3D) volumetric analysis to characterize and compare adrenal size in PPNAD patients, with and without Cushing's syndrome (CS). Patients diagnosed with PPNAD and their family members with known mutations in PRKAR1A were screened. CT scans were used to create 3D models of each adrenal. Criteria for biochemical diagnosis of CS included loss of diurnal variation and/or elevated midnight cortisol levels, and paradoxical increase in urinary free cortisol and/or urinary 17-hydroxysteroids after dexamethasone administration. Forty-five patients with PPNAD (24 females, 27.8±17.6 years) and 8 controls (19±3 years) were evaluated. 3D volumetric modeling of adrenal glands was performed in all. Thirty-eight patients out of 45 (84.4%) had CS. Their mean adrenal volume was 8.1 cc±4.1, 7.2 cc±4.5 (p=0.643) for non-CS, and 8.0cc±1.6 for controls. Mean values were corrected for body surface area; 4.7 cc/kg/m(2)±2.2 for CS, and 3.9 cc/kg/m(2)±1.3 for non-CS (p=0.189). Adrenal volume and midnight cortisol in both groups was positively correlated, r=0.35, p=0.03. We conclude that adrenal volume measured by 3D CT in patients with PPNAD and CS was similar to those without CS, confirming empirical CT imaging-based observations. However, the association between adrenal volume and midnight cortisol levels may be used as a marker of who among patients with PPNAD may develop CS, something that routine CT cannot do.

Plasma nanotextured polymeric lab-on-a-chip for highly efficient bacteria capture and lysis.

We describe the design, fabrication, and successful demonstration of a sample preparation module comprising bacteria cell capture and thermal lysis on-chip with potential applications in food sample pathogen analysis. Plasma nanotexturing of the polymeric substrate allows increase of the surface area of the chip and the antibody binding capacity. Three different anti-Salmonella antibodies were directly and covalently linked to plasma treated chips without any additional linker chemistry or other treatment. Then, the Ab-modified chips were tested for their capacity to bind bacteria in the concentration range of 10(2)-10(8) cells per mL; the module exhibited 100% efficiency in Salmonella enterica serovar Typhimurium bacteria capture for cell suspensions below 10(5) cells per mL (10(4) cells injected with a 100 µL sample volume) and efficiency higher than 50% for 10(7) cells per mL. Moreover, thermal lysis achieved on-chip from as low as 10 captured cells was demonstrated and shown to compare well with off-chip lysis. Excellent selectivity (over 1 : 300) was obtained in a sample containing, in addition to S. Typhimurium and E. coli bacteria.

Prayer Marks in Immigrants from Bangladesh with Diabetes Who Live in Greece.

Prayer marks (PMs) are commonly occurring dermatologic changes in muslims who pray and develop over a long period of time as a consequence of repeated and extended pressure. PMs need careful examination especially for patients with diabetes, who are more vulnerable due to predisposing factors such as venous insufficiency and peripheral neuropathy. A total of 166 patients with diabetes (150 males, 16 females) and 65 normal subjects from Bangladesh were examined for the appearance of PMs. Twenty-eight patients (16.9 %) and one normal subject (1.5 %) had PMs. The marks were not itchy or painful and they were observed on the dorsal aspect of the left foot, which was attributed to a more typical prayer position that placed pressure on the left foot. PMs are not a rare clinical entity among muslim patients with diabetes and most clinicians should be aware of it as it can be the predominant cause of an ulcer.

Laboratory identification of donor-derived coxsackievirus b3 transmission.

Unexpected donor-to-recipient infectious disease transmission is an important, albeit rare, complication of solid organ transplantation. Greater work and understanding about the epidemiology of these donor-derived transmissions is continually required to further mitigate this risk. Herein we present the first reported case of proven donor-derived transmission of coxsackievirus serogroup-3, an enterovirus, following solid organ transplant. Swift and effective communication between the organ donation agency, treating physicians, laboratory testing and notification ensured a coordinated approach. The resulting clinical syndromes in the organ recipients were mild. This case highlights the requirement for ongoing surveillance over a broad range of infecting pathogens that may present as a donor-derived infection.

Expression and function of galectins in the endometrium and at the human feto-maternal interface.

Galectins are classified as lectins that share structural similarities and bind ß-galactosides via a conserved carbohydrate recognition domain. So far 16 out of 19 identified galectins were shown to be present in humans and numerous studies revealed galectins as pivotal modulators of cell death, differentiation and growth. Galectins were highlighted to interact with both the adaptive and innate immune response. In the field of reproductive medicine and placenta research different roles for galectins have been proposed. Several galectins, being abundantly present at the human feto-maternal interphase and endometrium, were hypothesized to significantly contribute to endometrial receptivity and pregnancy physiology. Hence, this review outlines selected aspects of galectin action within endometrial function and at the feto-maternal interphase. Further current knowledge on galectins in reproductive and pregnancy disorders like endometriosis, abortion or preeclampsia is summarized.

Acoustic detection of DNA conformation in genetic assays combined with PCR.

Application of PCR to multiplexing assays is not trivial; it requires multiple fluorescent labels for amplicon detection and sophisticated software for data interpretation. Alternative PCR-free methods exploiting new concepts in nanotechnology exhibit high sensitivities but require multiple labeling and/or amplification steps. Here, we propose to simplify the problem of simultaneous analysis of multiple targets in genetic assays by detecting directly the conformation, rather than mass, of target amplicons produced in the same PCR reaction. The new methodology exploits acoustic wave devices which are shown to be able to characterize in a fully quantitative manner multiple double stranded DNAs of various lengths. The generic nature of the combined acoustic/PCR platform is shown using real samples and, specifically, during the detection of SNP genotyping in Anopheles gambiae and gene expression quantification in treated mice. The method possesses significant advantages to TaqMan assay and real-time PCR regarding multiplexing capability, speed, simplicity and cost.

Assessment of requirements on safety management systems in EU regulations for the control of major hazard pipelines.

The European Commission has carried out a thorough review and assessment on whether pipelines conveying dangerous substances need a level of control similar to chemical installations, based on consideration of the hazards and risks and on accidents world-wide. The study examines whether sufficient controls already exist within the European Union (EU) Member States, considering the control philosophy of the 'Seveso II' Directive and the need to support development of pipeline networks across the EU taking into account the principles of sustainability. Community legislation would be supported by a set of criteria for the classification of Major-Accident Hazard Pipelines. Such criteria are examined for the onshore transmission pipelines in the EU. The Commission study has shown that there is a large variation in the degree to which Member States have comprehensive 'major-accident hazard' legislation on pipelines, and that existing legislation rarely addresses elements of the Safety Management System. The assessment, based on a proposed Pipeline Safety Instrument, indicates that there will be added value in a European Instrument drawing on the principles of Seveso II Directive concerning Safety Management System requirements.

Investigation of the mechanism of action of prostaglandin synthesis inhibitors on renin and aldosterone secretion and sodium excretion.

Mean blood pressure (MBP) was found to be lower, while renal plasma flow (RPF), glomerular filtration rats (GFR), sodium excretion rate (U(Na)V), potassium excretion rate (U(k)V) and urinary prostaglandin E (PGE) concentration were higher in 15 normotensive subjects (15NS) compared with the values obtained in 15 essential hypertensive patients (15EHP) of the same mean age. After volume expansion of the 15HP with isotonic saline infusion, RPF, U(Na)V, U(k)V, urine volume (UV) and urinary PGE increased significantly while plasma renin activity (PRA) decreased significantly. Urinary aldosterone concentration and MBP decreased also but not significantly. After oral administration of 75 mg of indomethacin, in the same loaded group of 15 EHP, urinary PGE, urinary aldosterone and PRA decreased significantly while RPF, GRF, U(Na)V remained unaltered and MBP increased. When these values obtained in saline loaded and indomethacin treated 15EHP were compared to those obtained in the same group before volume expansion, it was found that RPF, U(NaV, U(k)V and UV were higher after indomethacin-saline administration while MBP, GRF and urinary PGE did not differ significantly and PRA and urinary aldosterone were significantly lower. These findings argue against the suggestion that PGE increases sodium reabsorption at the distal tubule and indicate that the unaltered sodium excretion rate in saline loaded and indomethacin treated unanaesthetized subjects, results from the simultaneous decrease of renomedullary PGE, Renin and aldosterone secretion.

Hydatid cyst of the liver with intrathoracic rupture.

In the last 10 years we have operated on 33 cases of hydatid cyst of the liver with intrathoracic rupture. Twenty-one out of 33 cases ruptured into bronchi, in seven the rupture affected the pleural cavity, and in six simultaneous rupture into the bronchus and pleural cavity occurred. Laboratory tests were not carried out in all cases. The Casoni intradermal test was carried out in 23 cases and was positive in 18. A liver scan was performed in 10 and was positive in all. Conservative operations were carried out in 22 patients. In these the hepatic cavity was evacuated and separately drained. This was followed by suturing the diaphragmatic rupture and also closing the bronchial opening if present. Lung resections were performed in 11 out of 33 cases. In eight lobectomy was carried out and in three segmental resections. Resection was necessary when suppuration and bronchiectatic changes affected the lung. Ruptured cyst into the pleural cavity requires emergency thoracotomy after the anaphylactic shock is over. Removal of the parasite, re-expansion of the lung, and drainage of the pleural and hepatic cavities is necessary. Immediate and late complications occurred in 13 patients. In two postoperative haemorrhage occurred and in two postoperative empyema developed. Recurrent haemoptysis was seen in five, persistent bile fistula in one, and dissemination of hydatid cyst in three. In the remaining 20 cases there was no complication. Operative mortality was nil.