Patients with acute pulmonary embolism should have an echocardiogram to guide treatment decisions

A 62-year-old man with a past medical history notable for hypertension, osteoarthritis, and calf deep vein thrombosis at age 55 following a total hip arthroplasty presents to the emergency department with acute-onset dyspnea and right-sided pleuritic chest pains. His medications consist of a calcium channel blocker and a COX-2 inhibitor. Pretest clinical suspicion for pulmonary embolism (PE) is high. Ventilation and perfusion lung scintigraphy are interpreted as being high-probability for PE. The nurse asks if a stat transthoracic echocardiogram should be ordered.     

A robust sliding mode controller with internal model for closed-loop artificial pancreas

The study presents a robust closed-loop sliding mode controller with internal model for blood glucose control in type-1 diabetes. Type-1 diabetic patients depend on external insulin delivery to keep their blood glucose within near-normal ranges. Closed-loop artificial pancreas is developed to help avoid dangerous, potentially life-threatening hypoglycemia, as well as to prevent complication-inducing hyperglycemia. The proposed controller is designed using a combination of sliding mode and internal model control techniques. To enhance postprandial performance, a feedforward controller is added to inject insulin bolus. Simulation studies have been performed to test the controller, which revealed that the proposed control strategy is able to control the blood glucose well within the safe limits in the presence of meals and measurements errors. The controller shows acceptable robustness against changes in insulin sensitivity, model–patient mismatch, and errors in estimating meal’s contents.     

Direkter Nachweis von Zytomegalievirus in koronaren Atheromen von Patienten mit fortgeschrittener koronarer Herzerkrankung

Zusammenfassung Hintergrund und Ziel: Experimentelle und klinische Studien weisen auf einen möglichen Zusammenhang zwischen dem Zytomegalievirus und der koronaren Herzerkrankung hin. Es war Ziel dieser Studie, mit Hilfe hochsensitiver molekularbiologischer Methoden in seriellen Analysen die Prävalenz von Zytomegalievirusgenom in koronaren Atheromen zu bestimmen sowie eine Assoziation zwischen dem Erregernachweis in koronaren Atheromen, der Läsionsmorphologie und dem klinischen Erscheinungsbild der Patienten herzustellen. Patienten und Methoden: Bei 53 Patienten mit koronarer Herzerkrankung wurde im Rahmen einer aortokoronaren Bypassoperation eine koronare Thrombendatherektomie durchgeführt. Von jedem Atherom wurden zwei Stellen zur molekularbiologischen Analyse verwendet. Ergebnis: Es konnte bei bis zu 30% der untersuchten Patienten mit schwerer koronarer Herzerkrankung Zytomegalievirus-DNA in koronaren Atheromen nachgewiesen werden. Das Verteilungsmuster der Zytomegalievirus in den Läsionen war inhomogen. Schlussfolgerung: Durch den höheren Anteil an Sekundärläsionen sowie den geringeren Kalzifizierungsgrad zytomegalieviruspositiver Atherome wird die Hypothese einer Mitbeteiligung des Zytomegalievirus an Restenosemechanismen unterstützt. Der Einsatz antiviraler Substanzen zur Behandlung der Atherosklerose oder zur Prävention der Restenose ist aufgrund der bestehenden Daten jedoch nicht gerechtfertigt. Abstract Background and Aim: Experimental and clinical data support an infectious cause of atherosclerosis and thereby coronary artery disease. This study was intended to assess the prevalence and possible clinical associations of the presence of cytomegalovirus DNA within coronary samples from patients undergoing coronary artery bypass grafting. Patients and Methods: A coronary thrombendatherectomy was performed in 53 patients with advanced coronary artery disease. Two samples of each atheroma were used for further analysis and pathogen detection. Result: In 30% of patients with advanced coronary artery disease cytomegalovirus DNA was detected in coronary samples as assessed by highly sensitive PCR methods. The occurrence of the virus within the vessels was characterized by an inhomogeneous distribution pattern. Conclusion: Due to an increased proportion of restenotic lesions and a higher degree of calcification in cytomegalovirus-positive lesions, a causative association between the virus presnece and mechanisms of restenosis post angioplasty is further supported. Antiviral pharmacological interventions to prevent restenosis in high-risk patients, however, seem not to be justified by the data currently available.     

Dorsal metacarpal veins: anatomic variation and potential clinical implications

The dorsal metacarpal veins are frequently cannulated. Cannulation success is determined by several variable anatomic features. The objective of this study is to classify, for the first time, the anatomic variants of the dorsal metacarpal veins. In this cross-sectional study, 520 university students and staff were conveniently recruited. The dorsal metacarpal veins in 1040 hands were studied. Venous visibility was enhanced by either tourniquet application or near-infrared illumination. Variant patterns of the dorsal metacarpal veins were classified. The final analysis included 726 hands, for an exclusion rate of 30 %. Eight pattern types were identified. Three anatomic features informed the variation. Bilateral symmetry of the dorsal metacarpal veins was present in 352 participants (83 % of the total). The overall frequency distribution of variants in both hands was similar (P = 0.8). The frequency distribution of variants was subject to sexual dimorphism (P = 0.001), ethnic variation (P < 0.001), and technical variation (P < 0.001). The anatomic variants of the dorsal metacarpal veins were sorted into decreasingly frequent primary, secondary, and tertiary groups. The groups may signify a progressive increase in difficulty of peripheral cannulation, in the mentioned order. As such, primary patterns are the most common and likely the easiest to cannulate, while tertiary patterns are the least common and likely the most difficult to cannulate. The preceding premise, in tandem with the bilateral asymmetry of the veins, is clinically significant. With cannulation difficulty likely signifying an underlying tertiary pattern, the contralateral dorsal metacarpal veins are probabilistically characterized by a primary pattern and are, as such, the easier option for peripheral venous cannulation.     

Analysis of association between common variants in the SLCO6A1 gene with schizophrenia,bipolar disorder and major depressive disorder in the Han Chinese population

Objectives The SLCO6A1 gene belongs to a superfamily of genes which is known to be a solute carrier family of OATPs (SLCO). The SLCO6A1 gene encodes OATP6A1 protein in humans. A previous genome-wide association study (GWAS) of schizophrenia conducted in the Swedish population demonstrated a significant association of rs6878284, which is located in the SLCO6A1 gene, with schizophrenia. To further investigate whether this gene is also a risk locus for schizophrenia (SCZ), bipolar disorder (BPD) and major depressive disorder (MDD) in the Han Chinese population, a case–control study was designed. Methods In total 1,248 unrelated SCZ cases, 1,344 BPD cases, 1,056 unrelated MDD cases and 1,248 normal controls were analysed in this study. We genotyped five SNPs using the Sequenom MassARRAY platform. Results We found no association of rs6878284 with SCZ [Corrected P_allele?=?0.969, Corrected P_genotype?=?0.997]. Furthermore, we found a statistically significant association of the rs7734060 genotype with MDD after correction [rs7734060: Corrected P_allele?=?0.114, Corrected P_genotype?=?0.036] in the Han Chinese population. Conclusions This is the first study which reveals no association of rs6878284 with SCZ and also predicts that rs7734060 could be a risk locus for MDD in the Han Chinese population.     

Effect of socio-demographic factors on endogenous biomarkers (cystatin C and creatinine) among elderly chronic kidney disease patients: a cross-sectional study

Purpose

Creatinine is normally used to evaluate kidney function among elderly patients in clinical practice, which has been reported to be affected by socio-demographic factors like BMI and age. Cystatin C a newly introduced biomarker may be more efficient in identifying kidney function in obese and aged CKD patients. The aim of the current study was to assess the effect of BMI on endogenous biomarkers (cystatin C and creatinine) among elderly CKD patients in Malaysia, a first such study in the country.

Methods

The current study was conducted at the Hospital University Sains Malaysia, Kelantan. A total of 300 elderly Malay participants ≥?65 years, with CKD, were taken in study. Demographic data, blood pressure, weight, and height were documented. Serum creatinine was assayed by Chemistry Analyzer Model Architect-C8000 (Jaffe Method), while serum cystatin C was examined by Human cystatin C ELISA kit (Sigma-Aldrich) using Thermo Scientific Varioskan Flash ELISA reader.

Results

The study participants were divided into three groups on the basis of age. There was a statistically significant difference at the p value?<?0.05 in serum creatinine level for the three age groups [F (2, 297)?=?1.98, p value 0.045]. Patients were divided into four groups on the basis of BMI. The results of one-way ANOVA revealed a statistically significant difference at the p value?<?0.05 in the mean serum creatinine level for the four groups [F (3, 396)?=?2.99, p value 0.032]. However, no statistically significant differences between mean serum cystatin C levels were observed on the basis of patient’s age and BMI.

Conclusion

Cystatin C is not related to BMI and age among elderly chronic kidney disease patients. The study clearly evaluates the role of serum cystatin C as a good competitor of creatinine among the elderly CKD patients.

     

Hansen solubility parameter as a tool to predict cocrystal formation

The objective of this study was to investigate whether the miscibility of a drug and coformer, as predicted by Hansen solubility parameters (HSPs), can indicate cocrystal formation and guide cocrystal screening. It was also our aim to evaluate various HSPs-based approaches in miscibility prediction. HSPs for indomethacin (the model drug) and over thirty coformers were calculated according to the group contribution method. Differences in the HSPs between indomethacin and each coformer were then calculated using three established approaches, and the miscibility was predicted. Subsequently, differential scanning calorimetry was used to investigate the experimental miscibility and cocrystal formation. The formation of cocrystals was also verified using liquid-assisted grinding. All except one of the drug-coformers that were predicted to be miscible were confirmed experimentally as miscible. All tested theoretical approaches were in agreement in predicting miscibility. All systems that formed cocrystals were miscible. Remarkably, two new cocrystals of indomethacin were discovered in this study. Though it may be necessary to test this approach in a wide range of different coformer and drug compound types for accurate generalizations, the trends with tested systems were clear and suggest that the drug and coformer should be miscible for cocrystal formation. Thus, predicting the miscibility of cocrystal components using solubility parameters can guide the selection of potential coformers prior to exhaustive cocrystal screening work.     

Prenatal TCDD in mice increases adult autoimmunity

Two immunologically different mouse strains, C57BL/6 and SNF₁, were exposed to a mid-gestation dose of TCDD. The C57BL/6 mouse has a high-affinity aryl hydrocarbon receptor (AhR) and is sensitive to TCDD. The SNF₁ mouse has a low-affinity AhR but spontaneously develops autoimmune nephritis. Autoreactive Vβ⁺CD4⁺17a and Vβ⁺CD3⁺ T cells were increased at 24-weeks-of-age in offspring of C57BL/6 mice, more so in females than males. The cytokine IFN-γ was elevated in the females, while IL-10 was elevated in males. Phenotypic changes in B-lineage cells were present in bone marrow and spleen, and circulating autoantibodies were increased after prenatal TCDD. Kidneys of males showed significant anti-IgG and anti-C3 deposition, suggesting early-stage autoimmune disease. The SNF₁ offspring similarly showed increased peripheral Vβ⁺ cells in the females, increased autoantibody production in both sexes, and increased IFN-γ production in females. Male SNF₁ mice had increased anti-IgG and anti-C3 deposition in kidneys. Both mouse models therefore showed clear signatures of enhanced autoimmunity after prenatal TCDD.