Effect of Side-Specific Valvular Shear Stress on the Content of Extracellular Matrix in Aortic Valves

Abstract

Responses of valve endothelial cells (VECs) to shear stresses are important for the regulation of valve durability. However, the effect of flow patterns subjected to VECs on the opposite surfaces of the valves on the production of extracellular matrix (ECM) has not yet been investigated. This study aims to investigate the response of side-specific flow patterns, in terms of ECM synthesis and/or degradation in porcine aortic valves. Aortic and ventricular sides of aortic valve leaflets were exposed to oscillatory and laminar flow generated by a Cone-and-Plate machine for 48 h. The amount of collagen, GAGs and elastin was quantified and compared to samples collected from the same leaflets without exposing to flow. The results demonstrated that flow is important to maintain the amount of GAGs and elastin in the valve, as compared to the effect of static conditions. Particularly, the laminar waveform plays a crucial role on the modulation of elastin in side-independent manner. Furthermore, the ability of oscillatory flow on the aortic surface to increase the amount of collagen and GAGs cannot be replicated by exposure of an identical flow pattern on the ventricular side of the valve. Side-specific responses to the particular patterns of flow are important to the regulation of ECM components. Such understanding is imperative to the creation of tissue-engineered heart valves that must be created from the "appropriate" cells that can replicate the functions of the native VECs to regulate the different constituents of ECM.

http://ift.tt/2dvc9L8

Efficient Combination of Texture and Color Features in a New Spectral Clustering Method for PolSAR Image Segmentation

Abstract

In this paper, an efficient combination of texture and color features is proposed for polarimetric synthetic aperture radar (PolSAR) image segmentation. In proposed method, the PolSAR image is first segmented using the mean-shift method. Then, in each segment obtained from the mean shift, the first moment of color for the three color components of L* a* b* color space is obtained. On the other hand, a texture feature vector for each pixel of the image is formed corresponding to the texture edge energy at different directions with Gabor filter. Then, a new spectral clustering method is used to combine texture and color features. The results show that the proposed method is effective in PolSAR image segmentation.

http://ift.tt/2dMGQOV

Dendrimer Graphs as Thorn Graphs and Their Topological Edge Properties

Abstract

Let G be a connected n-vertex graph with the vertex set V(G) = {v ₁, v ₂, …, v _n } and let P = (p ₁, p ₂, …, p _n ) be an n-tuple of nonnegative integers. The thorn graph G _P is the graph obtained by attaching p _i new vertices of degree one to the vertex v _i of G, for i = 1, 2, …, n. In this paper, relations between the edge-Wiener indices of G and G _P have been established and several special cases of these results have been examined. Results are applied to obtain closed formulas for the terminal Wiener index, the first and the second edge-Wiener indices of an infinite family of dendrimers by considering them as thorn graphs of simpler dendrimers.

http://ift.tt/2cULZy7

Molecular Confirmation of Conserved Nature of Genes Encoding MPB53 and MPB63 Immune Dominant Proteins in Indian Strain of Mycobacterium bovis

Abstract

The genes encoding MPB53 and MPB63 immuno dominant proteins of Mycobacterium bovis field strain 3/86-RV were amplified by polymerase chain reaction (PCR). The recombinant plasmids were constructed via inserting the mpb53 and mpb63 genes into the pET vector (named pET28b-mpb53 and pET28b-mpb63). The nucleotide sequences of the insert PCR products were determined by vector specific primer. Both genes contained an open reading frame of 402 and 390 base pairs for mpb53 and mpb63, respectively. The sequenced genes and its deduced amino acid sequences were compared with the published sequences of reference M. tuberculosis complex strains. The sequences of the mpb53 and mpb63 genes share more than 99 % nucleotide homology and deduced protein sequence homology pointing towards conserved molecular nature of these immunodominant proteins among M. tuberculosis complex species.

http://ift.tt/2dMIaRu

Impact of a Novel Bioabsorbable Implant on Radiation Treatment Planning for Breast Cancer

Abstract

Background

Techniques for accurately delineating the tumor bed after breast-conserving surgery (BCS) can be challenging. As a result, the accuracy, and efficiency of radiation treatment (RT) planning can be negatively impacted. Surgically placed clips or the post-surgical seroma are commonly used to determine target volume; however, these methods can lead to a high degree of uncertainty and variability. A novel 3-dimensional bioabsorbable marker was used during BCS and assessed for its impact on RT planning.

Methods

One hundred and ten implants were sutured to the margins of the tumor bed excision site in 108 patients undergoing BCS. Routine CT imaging of the breast tissue was performed for RT planning, and the marker was assessed for visibility and utility in target delineation. RT regimens, target volumes and associated treatment costs were analyzed.

Results

In all patients, the marker was easily visible and in 95.7 % of cases, it proved useful for RT planning. 36.8 % of patients received conventional whole breast irradiation plus boost, 56.6 % received hypo-fractionation plus boost, and 6.6 % received accelerated partial breast irradiation. A shift toward increased use of hypo-fractionated regimens was noted over the three year period of this study. There were no device-related complications or cancer recurrences in this group of patients.

Conclusions

This study demonstrated the use of a novel 3-dimensional marker as a safe and effective method for delineating the tumor bed with a significant utility for RT planning. With routine use of the device, an increased use of hypofractionation with a resultant 25 % cost savings was noted.

http://ift.tt/2dtsH9c

Ionic liquids and cyclodextrin inclusion complexes: limitation of the affinity capillary electrophoresis technique

Abstract

The state of the art of inclusion complex formation between cyclodextrins and ionic liquids is reported. Mechanisms, stoichiometries, and binding constants are summarized and classified by anion. We investigated the supramolecular interactions between the β-cyclodextrin cavity and six ionic liquids based on 1-dodecyl-3-methylimidazolium by affinity capillary electrophoresis and compared the results with those obtained by isothermal titration calorimetry. We show that the presence of basic or acidic buffers leads to a metathesis reaction, underlining the limitation of the affinity capillary electrophoresis technique.

http://ift.tt/2dv7qJ1

Open versus laparoscopic approach for intestinal malrotation in infants and children: a systematic review and meta-analysis

Abstract

Purpose

Although the principles of the Ladd's procedure for intestinal malrotation in children have remained unchanged since its first description, in the era of minimally invasive surgery it is controversial whether laparoscopy is advantageous over open surgery. The aim of our study was to determine whether the surgical approach for the treatment of malrotation had an impact on patient outcome.

Methods

Using a defined strategy (PubMed, Cochrane, Embase and Web of Science MeSH headings), two investigators independently searched for studies comparing open versus laparoscopic Ladd's procedure in children. Case reports and opinion articles were excluded. Outcome measures included age at operation, time to full enteral feeding, length of hospital stay, and post-operative complications. Maneuvers were compared using Fisher's exact test and meta-analysis was conducted using RevMan 5.3. Data are expressed as mean ± SD.

Results

Of 308 abstracts screened, 49 full-text articles were analyzed and nine (all retrospective) met our search criteria. Selected articles included 1003 patients, of whom 744 (74 %) underwent open surgery and 259 (26 %) laparoscopy. Patients who had open surgery were younger (0.9 ± 1.2 years) than those who underwent laparoscopy (2.6 ± 3 years; p < 0.0001). Laparoscopy was converted to open Ladd's in 25.3 % patients. Laparoscopy was associated with faster full enteral feeding (1.5 ± 0.3 days) in comparison to open surgery (4.6 ± 0.1 days, p < 0.0001). Length of hospital stay was shorter in the laparoscopic group (5.9 ± 4.3 days) than in the open group (11.2 ± 6.7 days; p < 0.0001). Open surgery was associated with higher overall post-operative complication rate (21 %) than laparoscopy (8 %; p < 0.0001). Although there was no difference in the prevalence of post-operative bowel obstruction (open, n = 10 %; laparoscopy, n = 0 % p = 0.07), post-operative volvulus was more frequent in the laparoscopy group (3.5 %) than in the open group (1.4 %, p = 0.04).

Conclusion

Comparative but non-randomized studies indicate that laparoscopic Ladd's procedure is not commonly performed in young children. Although one third of laparoscopic procedures is converted to open surgery, laparoscopy is associated with shorter time to full enteral feeds and length of hospital stay. However, laparoscopic Ladd's procedure seems to have higher incidence of post-operative volvulus. Prospective randomized studies with long follow-up are needed to confirm present outcome data and determine the safety and effectiveness of the laparoscopic approach.

http://ift.tt/2dyPf4D

Removal of extracellular coat from giant sperm in female receptacle induces sperm motility in Mytilocypris mytiloides (Cyprididae, Ostracoda, Crustacea)

Abstract

Previous studies of cypridoidean ostracods have noted that (1) their giant spermatozoa are immotile inside the male, (2) these spermatozoa are motile in the female seminal receptacle and (3) these receptacles are often filled with empty sperm coats. Such findings have led previous authors to hypothesize that sperm must shed their coats in the female receptacle to become motile. We present light and electron microscopy results and video recordings of mating experiments with virgin specimens of Mytilocypris mytiloides. We show that the empty sperm coats frequently found in the female receptacles are not the result of sperm molting but are the resistant inner coats of exhausted sperm not used for egg fertilization. In contrast, we show that an outer granular coating material is successively removed from the sperm while resident inside the female receptacles before first oviposition occurs. During this period, previously immotile sperm gain motility, showing strong movement shortly before first oviposition takes place. By correlation of these phenomena, we suggest that dissolution of the outer coat material is required for motility to develop.

http://ift.tt/2dLJZtJ

Parallel construction of wavelet trees on multicore architectures

Abstract

The wavelet tree has become a very useful data structure to efficiently represent and query large volumes of data in many different domains, from bioinformatics to geographic information systems. One problem with wavelet trees is their construction time. In this paper, we introduce two algorithms that reduce the time complexity of a wavelet tree's construction by taking advantage of nowadays ubiquitous multicore machines. Our first algorithm constructs all the levels of the wavelet in parallel with O(n) time and \(O(n\lg \sigma + \sigma \lg n)\) bits of working space, where n is the size of the input sequence and \(\sigma \) is the size of the alphabet. Our second algorithm constructs the wavelet tree in a domain decomposition fashion, using our first algorithm in each segment, reaching \(O(\lg n)\) time and \(O(n\lg \sigma + p\sigma \lg n/\lg \sigma )\) bits of extra space, where p is the number of available cores. Both algorithms are practical and report good speedup for large real datasets.

http://ift.tt/2cUAB5o

Allergic bronchopulmonary aspergillosis: what’s known and what’s new

Abstract

Recent investigations concerning ABPA have expanded our understanding of the disease. The diagnostic criteria for ABPA are not standardized. Novel analytic techniques have compared the varied diagnostic criteria even in the absence of a gold standard. Additional analyses have determined the sensitivity and specificity of various parameters for the diagnosis of ABPA, as well as combinations of several parameters that have extremely high specificity and sensitivity. New biomarkers have also been proposed to diagnosis and monitor ABPA. Research concerning specific antigenic triggers of the Th2 response and HLA polymorphisms in ABPA has led to relevant new insights concerning the immunopathogenesis of the disease. Treatment trials have further clarified the optimal corticosteroid dosing regimen and the role of antifungal therapy and anti-IgE therapy for the treatment of ABPA. We suspect that such research efforts will continue to accelerate our understanding of this disease that will benefit ABPA patients.

http://ift.tt/2cUGLTb

Innervation of the blood vessels of the spinal cord: a comprehensive review

Abstract

There is growing evidence that the nervous system influences spinal cord vasculature. However, most descriptions of the spinal cord have paid little attention to this important aspect. We reviewed the literature on the innervation of spinal cord vessels with an emphasis on findings that may be applicable to human medicine. Multiple neurotransmitters and competing theories have been implicated in the neural regulation of spinal cord blood vessels. Identifying valid mechanisms of pathogenesis could be beneficial to human patients with spinal cord lesions. We discuss the various findings on the neural mechanisms behind spinal cord blood flow. Further investigation is warranted due to the current emphasis on comparative animal studies without corresponding corroborative human findings.

http://ift.tt/2dMwdvs

Successful Stepwise Development of Patient Research Partnership: 14 Years’ Experience of Actions and Consequences in Outcome Measures in Rheumatology (OMERACT)

Abstract

There is increasing interest in making patient participation an integral component of medical research. However, practical guidance on optimizing this engagement in healthcare is scarce. Since 2002, patient involvement has been one of the key features of the Outcome Measures in Rheumatology (OMERACT) international consensus effort. Based on a review of cumulative data from qualitative studies and internal surveys among OMERACT participants, we explored the potential benefits and challenges of involving patient research partners in conferences and working group activities. We supplemented our review with personal experiences and reflections regarding patient participation in the OMERACT process. We found that between 2002 and 2016, 67 patients have attended OMERACT conferences, of whom 28 had sustained involvement; many other patients contributed to OMERACT working groups. Their participation provided face validity to the OMERACT process and expanded the research agenda. Essential facilitators have been the financial commitment to guarantee sustainable involvement of patients at these conferences, procedures for recruitment, selection and support, and dedicated time allocated in the program for patient issues. Current challenges include the representativeness of the patient panel, risk of pseudo-professionalization, and disparity in patients' and researchers' perception of involvement. In conclusion, OMERACT has embedded long-term patient involvement in the consensus-building process on the measurement of core health outcomes. This integrative process continues to evolve iteratively. We believe that the practical points raised here can improve participatory research implementation.

http://ift.tt/2dv3Kat

Endovaskuläre Therapie genetisch bedingter Aortenerkrankungen

Zusammenfassung

Fragestellung

Welchen Stellenwert haben endovaskuläre Behandlungsoptionen in der Therapie aortaler Pathologien auf dem Boden von Bindegewebserkrankungen.

Material und Methoden

Auswertung aktueller randomisierter Untersuchungen und Registerstudien.

Ergebnis

Die Therapie der Wahl der meist bereits in jungem Alter betroffenen Patienten ist primär konservativ bzw. offen-chirurgisch. Zur endovaskulären Therapie abdomineller Aneurysmen (EVAR) oder thorakalen Aortenpathologien (TEVAR) gibt es nur wenig Evidenz.

Schlussfolgerungen

Die Progression der genetisch bedingten Grunderkrankung mit konsekutiver Aortendilatation führt zu sekundären Endoleckagen und vermehrten Reinterventionen mit unsicherem Langzeitergebnis. Deshalb besteht derzeit Konsensus, dass EVAR und TEVAR bei genetisch bedingten Aortenerkrankungen auf begründete Ausnahmefälle und Notfallsituationen begrenzt sein sollten.

http://ift.tt/2dtj76i

Heterologous expression of oxytetracycline biosynthetic gene cluster in Streptomyces venezuelae WVR2006 to improve production level and to alter fermentation process

Abstract

Heterologous expression is an important strategy to activate biosynthetic gene clusters of secondary metabolites. Here, it is employed to activate and manipulate the oxytetracycline (OTC) gene cluster and to alter OTC fermentation process. To achieve these goals, a fast-growing heterologous host Streptomyces venezuelae WVR2006 was rationally selected among several potential hosts. It shows rapid and dispersed growth and intrinsic high resistance to OTC. By manipulating the expression of two cluster-situated regulators (CSR) OtcR and OtrR and precursor supply, the OTC production level was significantly increased in this heterologous host from 75 to 431 mg/l only in 48 h, a level comparable to the native producer Streptomyces rimosus M4018 in 8 days. This work shows that S. venezuelae WVR2006 is a promising chassis for the production of secondary metabolites, and the engineered heterologous OTC producer has the potential to completely alter the fermentation process of OTC production.

http://ift.tt/2cUDl2K

Immune Cell Metabolism in Systemic Lupus Erythematosus

Abstract

Cellular metabolism represents a newly identified checkpoint of effector functions in the immune system. A solid body of work has characterized the metabolic requirements of normal T cells during activation and differentiation into polarized effector subsets. Similar studies have been initiated to characterize the metabolic requirements for B cells and myeloid cells. Only a few studies though have characterized the metabolism of immune cells in the context of autoimmune diseases. Here, we review what is known on the altered metabolic patterns of CD4⁺ T cells, B cells, and myeloid cells in lupus patients and lupus-prone mice and how they contribute to lupus pathogenesis. We also discuss how defects in immune metabolism in lupus can be targeted therapeutically.

http://ift.tt/2dv2ofH

Statin use decreases coagulation in users of vitamin K antagonists

Abstract

Purpose

The purpose of the study is to determine the immediate and long-term effect of statins on coagulation in patients treated with vitamin K antagonists (VKAs).

Methods

We selected patients on VKAs of two Dutch anticoagulation clinics who initiated treatment with a statin between 2009 and 2013. Patients who initiated or stopped concomitant drugs that interact with VKAs or were hospitalised during follow-up were excluded. The VKA dosage (mg/day) after statin initiation was compared with the last VKA dosage before the statin was started. Immediate and long-term differences in VKA dosage (at 6 and 12 weeks) were calculated with a paired student t test.

Results

Four hundred thirty-five phenprocoumon users (mean age 70 years, 60 % men) and 303 acenocoumarol users (mean age 69 years, 58 % men) were included. After start of statin use, the immediate phenprocoumon dosage was 0.02 mg/day (95 % CI, 0.00 to 0.03) lower. At 6 and 12 weeks, these phenprocoumon dosages were 0.03 (95 % CI, 0.01 to 0.05) and 0.07 mg/day (95 % CI, 0.04 to 0.09) lower as compared with the dosage before first statin use. In acenocoumarol users, VKA dosage was 0.04 mg/day (95%CI, 0.01 to 0.07) (immediate effect), 0.10 (95 % CI, 0.03 to 0.16) (at 6 weeks), and 0.11 mg/day (95 % CI, 0.04 to 0.18) (after 12 weeks) lower.

Conclusions

Initiation of statin treatment was associated with an immediate and long-term minor although statistically significant decrease in VKA dosage in both phenprocoumon and acenocoumarol users, which suggests that statins may have anticoagulant properties.

http://ift.tt/2duZAPB

Discussion and review on evolving data streams and concept drift adapting

Abstract

Recent advances in computational intelligent systems have focused on addressing complex problems related to the dynamicity of the environments. In increasing number of real world applications, data are presented as streams that may evolve over time and this is known by concept drift. Handling concept drift is becoming an attractive topic of research that concerns multidisciplinary domains such that machine learning, data mining, ubiquitous knowledge discovery, statistic decision theory, etc... Therefore, a rich body of the literature has been devoted to the study of methods and techniques for handling drifting data. However, this literature is fairly dispersed and it does not define guidelines for choosing an appropriate approach for a given application. Hence, the main objective of this survey is to present an ease understanding of the concept drift issues and related works, in order to help researchers from different disciplines to consider concept drift handling in their applications. This survey covers different facets of existing approaches, evokes discussion and helps readers to underline the sharp criteria that allow them to properly design their own approach. For this purpose, a new categorization of the existing state-of-the-art is presented with criticisms, future tendencies and not-yet-addressed challenges.

http://ift.tt/2cUyoXC

Rapidly dissolving polymeric microneedles for minimally invasive intraocular drug delivery

Abstract

In this study, dissolving microneedles (MNs) were used to enhance ocular drug delivery of macromolecules. MNs were fabricated using polyvinylpyrrolidone (PVP) polymer of various molecular weights (MWs) containing three model molecules of increasing MW, namely fluorescein sodium and fluorescein isothiocyanate–dextrans (with MW of 70 k and 150 k Da). Arrays (3 × 3) of PVP MNs with conical shape measuring about 800 μm in height with a 300 μm base diameter, containing the model drugs, were fabricated and characterized for their fracture forces, insertion forces (in the sclera and cornea), depth of penetration (using OCT and confocal imaging), dissolution time and in vitro permeation. The average drug content of the MNs (only in MN shafts) ranged from 0.96 to 9.91 μg, and the average moisture content was below 11 %. High MW PVP produced MNs that can withstand higher forces with minimal reduction in needle height. PVP MNs showed rapid dissolution that ranged from 10 to 180 s, which was dependent upon PVP's MW. In vitro studies showed significant enhancement of macromolecule permeation when MNs were used, across both the corneal and scleral tissues, in comparison to topically applied aqueous solutions. Confocal images showed that the macromolecules formed depots within the tissues, which led to sustained permeation. However, use of MNs did not significantly benefit the permeation of small molecules; nevertheless, MN application has the potential for drug retention within the selected ocular tissues unlike topical application for small molecules. The material used in the fabrication of the MNs was found to be biocompatible with retinal cells (i.e. ARPE-19). Overall, this study reported the design and fabrication of minimally invasive rapidly dissolving polymeric MN arrays which were able to deliver high MW molecules to the eye via the intrastromal or intrascleral route. Thus, dissolving MNs have potential applications in enhancing ocular delivery of both small and macromolecules.

http://ift.tt/2dt62Kq

Multimodal approach to rehabilitation of the patients with lateral epicondylosis: a case series

The objective of this study was to evaluate the effectiveness of mobilization with movement and kinesiotherapy in the treatment of patients with lateral epicondylosis.

http://ift.tt/2d4ivRF

Telbivudine for the treatment of chronic hepatitis B in HBeAg-positive patients in China: a health economic analysis

Nucleos(t)ide analogs (NUCs) are the standard of care for chronic hepatitis B (CHB). The present analysis aimed to determine the cost effectiveness of NUCs in Chinese healthcare settings.

http://ift.tt/2dLnW5F

Callogenesis and cell suspension establishment of tropical highland blackberry (Rubus adenotrichos Schltdl.) and its microscopic analysis

Blackberries are fruits produced worldwide, with 25 % of their production centered in Mexico, Central and South America. Tropical highland blackberry is a fruit that can potentially enhance human health, due t...

http://ift.tt/2d4h2dX

Endobronchial ultrasound versus conventional transbronchial needle aspiration in the diagnosis of mediastinal lymphadenopathy: a meta-analysis

Currently, whether endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is superior to conventional TBNA (cTBNA) in the diagnosis of mediastinal lymphadenopathy remains controversial. ...

http://ift.tt/2dLmO1I

To be objective in Experimental Phenomenology: a Psychophysics application

Several scientific psychologists consider the approach for the study of perceptive problems of the Experimental Phenomenology is problematic, namely that the phenomenological demonstrations are subjectively ba...

http://ift.tt/2dLnWSV

Death with dignity from the Confucian perspective

Abstract

Death with dignity is a significant issue in modern bioethics. In modern healthcare, the wide use of new technologies at the end of life has caused heated debate on how to protect human dignity. The key point of contention lies in the different understandings of human dignity and the dignity of death. Human dignity has never been a clear concept in Western ethical explorations, and the dignity of death has given rise to more confusions. Although there is no such term as "dignity" in Confucian ethics, there are discussions of a number of ideas related to human dignity and the dignity of death. Therefore, Confucian bioethics can offer a new perspective for understanding the theoretical difficulties associated with the dignity of death and new methods for solving them. In this article, we attempt to reconstruct Confucian views on human dignity and the dignity of death and, based on those views, to analyze the following issues: the relationship between the dignity of death and biological life, the relationship between the dignity of death and suffering, the relationship between the dignity of death and the autonomy of human beings, and the relationship between the dignity of death and social justice. This article will also compare the Confucian views on these issues with the views of Western philosophers. Confucian ethics can offer distinct answers to the above issues and help resolve some confusions concerning concepts and theories in Western research on the dignity of death.

http://ift.tt/2d4euwG

Two injection digital block versus single subcutaneous palmar injection block for finger lacerations

Abstract

Purpose

We aimed to compare two digital nerve block techniques in patients due to traumatic digital lacerations.

Methods

This was a randomized-controlled study designed prospectively in the emergency department of a university-based training and research hospital. Randomization was achieved by sealed envelopes. Half of the patients were randomised to traditional (two-injection) digital nerve block technique while single-injection digital nerve block technique was applied to the other half. Score of pain due to anesthetic infiltration and suturing, onset time of total anesthesia, need for an additional rescue injection were the parameters evaluated with both groups. Epinephrin added lidocaine hydrochloride preparation was used for the anesthetic application. Visual analog scale was used for the evaluation of pain scores. Outcomes were compared by using Mann–Whitney U test and Student t-test.

Results

Fifty emergency department patients ≥18 years requiring digital nerve block were enrolled in the study. Mean age of the patients was 33 (min–max: 19–86) and 39 (78 %) were male. No statistically significant difference was found between the two groups in terms of our main parameters; anesthesia pain score, suturing pain score, onset time of total anesthesia and rescue injection need.

Conclusion

Single injection volar digital nerve block technique is a suitable alternative for digital anesthesias in emergency departments.

http://ift.tt/2dfIxze

Hepatic expression of transcription factors affecting developmental regulation of UGT1A1 in the Han Chinese population

Abstract

Purpose

Complete or partial inactivity of UGT1A1, the unique enzyme responsible for bilirubin glucuronidation, is commonly associated with hyperbilirubinemia. We investigated the dynamic expression of UGT1A1, and that of the transcription factors (TFs) involved in its developmental regulation, during human hepatic growth in Han Chinese individuals.

Methods

Eighty-eight prenatal, pediatric, and adult liver samples were obtained from Han Chinese individuals. Quantitative real-time polymerase chain reaction was used to evaluate mRNA expression of UGT1A1 and TFs including PXR, CAR, HNF1A, HNF4A, PPARA, etc. UGT1A1 protein levels and metabolic activity were determined by western blotting and high-performance liquid chromatography. Direct sequencing was employed to genotype UGT1A1*6 (211G˃A) and UGT1A1*28 (TA6˃TA7) polymorphisms.

Results

UGT1A1 expression was minimal in prenatal samples, but significantly elevated during pediatric and adult stages. mRNA and protein levels and metabolic activity were prominently increased (120-, 20-, and 10-fold, respectively) in pediatric and adult livers compared to prenatal samples. Furthermore, expression did not differ appreciably between pediatric and adult periods. Dynamic expression of TFs, including PXR, CAR, HNF1A, HNF4A, and PPARA, was consistent with UGT1A1 levels at each developmental stage. A pronounced correlation between expression of these TFs and that of UGT1A1 (P < 0.001) was observed. Moreover, UGT1A1*6 and UGT1A1*28 polymorphisms reduced levels of UGT1A1 by up to 40–60 %.

Conclusions

Hepatic expression of transcription factors is associated with developmental regulation of UGT1A1 in the Han Chinese population. Moreover, UGT1A1 polymorphisms are associated with reduced expression of UGT1A1 mRNA and protein, as well as enzyme activity.

http://ift.tt/2dSMWca

Prediction of 1-year clinical outcomes using the SYNTAX score in patients with prior heart failure undergoing percutaneous coronary intervention: sub-analysis of the SHINANO registry

Abstract

Although coronary artery disease (CAD) is common in patients with heart failure (HF), little is known about the prognostic significance of coronary lesion complexity in patients with prior HF undergoing percutaneous coronary intervention (PCI). The aim of this study was to investigate whether the coronary Synergy between Percutaneous Coronary Intervention with TAXus and Cardiac Surgery (SYNTAX) score could improve risk stratification in HF patients with CAD. Two hundred patients (mean age 73 ± 11 years, left ventricular ejection fraction 49 ± 15 %) with prior HF who underwent PCI were divided into two groups stratified by SYNTAX score (median value 12) and tracked prospectively for 1 year. The study endpoint was the composite of major adverse cardiovascular events (MACE), including all-cause death, myocardial infarction, stroke, and hospitalization for worsening HF. Adverse events were observed in 39 patients (19.5 %). Patients with high SYNTAX scores (n = 100) showed worse prognoses than those with low scores (n = 100) (26.0 vs. 13.0 %, respectively, P = 0.021). In multivariate Cox-regression analysis, SYNTAX score ≥12 was significantly associated with MACE (hazard ratio: 1.99, 95 % confidence interval: 1.02–3.97; P = 0.045). In patients with prior HF and CAD, high SYNTAX scores predicted a high incidence of MACE. These results suggest that the SYNTAX score might be a useful parameter for improving risk stratification in these patients.

http://ift.tt/2cUg4Oj

Comparison of mid-term clinical outcomes between on-label and off-label use of rotational atherectomy

Abstract

While rotational atherectomy (RA) is used for complex lesions in percutaneous coronary intervention, there are several contraindications such as unprotected left main stenosis or left ventricular dysfunction. We previously reported that the incidence of in-hospital complications was significantly greater in off-label as compared to on-label use RA. However, the mid-term clinical outcomes between off-label and on-label RA have not been investigated. The purpose of this study was to compare the mid-term clinical outcomes between off-label (n = 156) and on-label RA (n = 94). The primary endpoint was the incidence of major adverse cardiovascular events (MACE) defined as the composite of ischemia-driven target vessel revascularization (TVR), non-fatal MI, and all-cause death. We also identified 154 patients who underwent RA and follow-up angiography within 1 year, and compared quantitative coronary analysis between the off-label group (n = 96) and on-label group (n = 58). There was no significant difference in late luminal loss between the groups (0.03 ± 0.53 mm in the off-label and −0.05 ± 0.44 mm in the on-label groups, P = 0.57). However, the incidence of MACE was less in the on-label group (3.2 %) as compared to the off-label group (9.0 %) without reaching statistical significance (P = 0.08). In conclusion, mid-term clinical outcomes tended to be worse in the off-label group than in the on-label group. We may have to follow-up the patient who underwent off-label RA more carefully than the patient who underwent on-label RA.

http://ift.tt/2dLUfqp

Gastrointestinal microbiome and breast cancer: correlations, mechanisms and potential clinical implications

Abstract

Gastrointestinal microbiome plays as a symbiont which provides protection effect against invading pathogens, aids in the immune system development, nutrient reclamation and absorption as well as molecule breakdown. And it may avert carcinogenesis through these biological activities. By now, studies have been carried out to elaborate the association between gastrointestinal microbiome and breast cancer. It has been implicated that breast cancer was substantially associated with estrogen-dependent and estrogen-independent functions of gastrointestinal microbiome. Evidence from animal experiments also confirmed mammary tumor-related changes in microbial community. The possible mechanisms involve estrogen metabolism, immune regulation, obese status and so forth. Based on the current evidence, cues on future management strategies of breast cancer such as antibiotics and dietary interventions are proposed. In conclusion, large-scale clinical studies and bench-based researches are needed to validate the associations and elaborate the mechanisms, so as to reduce the risk of breast cancer and improve the outcomes of those already diagnosed.

http://ift.tt/2dsST48

Erratum to: P2Y 1 , P2Y 2 , and TRPV1 Receptors Are Increased in Diarrhea-Predominant Irritable Bowel Syndrome and P2Y 2 Correlates with Abdominal Pain

http://ift.tt/2d2TK8l

Inhibition of IRF8 Negatively Regulates Macrophage Function and Impairs Cutaneous Wound Healing

Abstract

The inflammatory response is essential for normal cutaneous wound healing. Macrophages, as critical inflammatory cells, coordinate inflammation and angiogenesis phases during wound healing. It has been reported that the transcription factor interferon regulatory factor 8 (IRF8), a member of the IRF family, plays a critical role in the development and function of macrophages and is associated with inflammation. However, the role of IRF8 in cutaneous wound healing and its underlying mechanism remain elusive. Through immunohistochemical (IHC) staining, we showed that IRF8 is involved in the wound repair process in mice and patients. Furthermore, we ascertain that the repression of IRF8 by small interfering RNA (siRNA) leads to delayed wound healing. To explore the mechanism by which IRF8 impacts wound healing, we observed its effect on macrophage-related mediators by IHC or real-time PCR. The results demonstrated that the inhibition of IRF8 decreases the mRNA expression of inflammatory mediators associated with M1 macrophage (il-1b, il-6, inos, and tnf-a) but no impact on M2 macrophage-related mediators (arg-1, mrc-1, and il-10) and the number of macrophages in the wounds. Furthermore, the inhibition of IRF8 induced apoptosis in the wounds. In summary, this study demonstrates that the down-regulation of IRF8 in the wound leads to impaired wound healing possibly through the regulation of macrophage function and apoptosis in skin wound.

http://ift.tt/2dL6Jce

Coumestrol Counteracts Interleukin-1β-Induced Catabolic Effects by Suppressing Inflammation in Primary Rat Chondrocytes

Abstract

In the present study, we investigated the anti-catabolic effects of coumestrol, a phytoestrogen derived from herbal plants, against interleukin-1β-induced cartilage degeneration in primary rat chondrocytes and articular cartilage. Coumestrol did not affect the viability of human normal oral keratinocytes and primary rat chondrocytes treated for 24 h and 21 days, respectively. Although coumestrol did not significantly increase the proteoglycan contents in long-term culture, it abolished the interleukin-1β-induced loss of proteoglycans in primary rat chondrocytes and knee articular cartilage. Furthermore, coumestrol suppressed the expression of matrix-degrading enzymes such as matrix metalloproteinase-13, −3, and −1 in primary rat chondrocytes stimulated with interleukin-1β. Moreover, the expression of catabolic factors such as nitric oxide synthase, cyclooxygenase-2, prostaglandin E₂, and inflammatory cytokines in interleukin-1β-stimulated primary rat chondrocytes was suppressed by coumestrol. In summary, these results indicate that coumestrol counteracts the catabolic effects induced by interleukin-1β through the suppression of inflammation. Therefore, based on its biological activity and safety profile, coumestrol could be used as a potential anti-catabolic biomaterial for osteoarthritis.

http://ift.tt/2d45sQh

A hybrid space–time of Schwarzschild interior and Vaidya–Tikekar solution as an embedding class I

Abstract

A new type of embedding class-I metric representing anisotropic fluid distribution is presented in this paper. The new solution satisfies TOV equation and does represent a static stellar configuration. This new solution is an interesting hybrid solution where g _tt is of Schwarzschild interior and g _rr is of Vaidya–Tikekar. The new solution satisfies all the physical criteria like positive finite central pressure, density, causality condition etc. It also satisfies all the energy conditions such as SEC, WEC, NEC and DEC. Using this new solution, we have presented some compact star models for Her X-1, RX J1856.5-3754, Cyg X-2 and PSR J1614-2230 by optimizing their masses and radii.

http://ift.tt/2dsKk9l

Excitonic susceptibility in near triangular quantum wells

Abstract

Diamagnetic susceptibility and binding energy of an exciton in a near triangular quantum well, with potential profile proportional to |z|^2/3 composed of GaAs/Ga_1−x Al_x As and ZnO/Zn_1−x Mg_x O are calculated as a function of the wellwidth and concentration of Al and Mg respectively varying the magnetic field applied along growth direction (i.e. z-axis). Diamagnetic susceptibility of light hole exciton and heavy hole exciton, shows inverse behaviors in the two materials below 20 nm wellwidth and the binding energy of both excitons increases, as the magnetic field increases. The results obtained, are compared with those of quantum wells with varied potential profiles and the experimental results reported in the literature.

http://ift.tt/2dL22A1

Validation of a predictive model for identifying febrile young infants with altered urinalysis at low risk of invasive bacterial infection

Abstract

In 2015, a predictive model for invasive bacterial infection (IBI) in febrile young infants with altered urine dipstick was published. The aim of this study was to externally validate a previously published set of low risk criteria for invasive bacterial infection in febrile young infants with altered urine dipstick. Retrospective multicenter study including nine Spanish hospitals. Febrile infants ≤90 days old with altered urinalysis (presence of leukocyturia and/or nitrituria) were included. According to our predictive model, an infant is classified as low-risk for IBI when meeting all the following: appearing well at arrival to the emergency department, being >21 days old, having a procalcitonin value <0.5 ng/mL and a C-reactive protein value <20 mg/L. IBI was considered as secondary to urinary tract infection if the same pathogen was isolated in the urine culture and in the blood or cerebrospinal fluid culture. A total of 391 patients with altered urine dipstick were included. Thirty (7.7 %) of them developed an IBI, with 26 (86.7 %) of them secondary to UTI. Prevalence of IBI was 2/104 (1.9 %; CI 95% 0.5–6.7) among low-risk patients vs 28/287 (9.7 %; CI 95% 6.8–13.7) among high-risk patients (p < 0.05). Sensitivity of the model was 93.3 % (CI 95% 78.7–98.2) and negative predictive value was 98.1 % (93.3–99.4). Although our predictive model was shown to be less accurate in the validation cohort, it still showed a good discriminatory ability to detect IBI. Larger prospective external validation studies, taking into account fever duration as well as the role of ED observation, should be undertaken before its implementation into clinical practice.

http://ift.tt/2dKV1iS

Tablet Splitting of Antiepileptic Drugs in Pediatric Epilepsy: Potential Effect on Plasma Drug Concentrations

Abstract

Introduction

Tablet splitting is the process of dividing a tablet into portions to obtain a prescribed dose of medication. Very few studies have investigated whether split parts of a tablet deliver the expected amount of drug to patients.

Objective

Our objectives were to evaluate the split parts of adult-dose tablet formulations for percentage of weight deviation, weight uniformity, weight loss, drug content, and the content uniformity of four antiepileptic drugs (AEDs) prescribed to pediatric patients. We also measured AED plasma concentrations in the children.

Methods

We chose to study first-line AEDs (phenytoin sodium [PHE], sodium valproate [SVA], carbamazepine, and phenobarbitone) as they are routinely prescribed in India. We asked caregivers to perform the same splitting process they follow in their homes on three whole tablets during their routine visit to the outpatient department. After caregivers split the tablets, we studied the weight and content of the split parts. We also used high-performance liquid chromatography to study plasma drug concentrations in children who had received split AEDs for at least 4 months.

Results

A total of 168 caregivers participated in the study, and we analyzed 1098 split tablet parts. In total, 539 (49.0 %) split parts were above the specified limit of the 2010 Indian Pharmacopeia (IP) acceptable percentage weight deviation (PHE 169 [48.8 %], SVA 187 [51.9 %], carbamazepine 56 [41.1 %], phenobarbitone 127 [49.6 %]); 456 (41.5 %) split parts were outside the proxy IP specification for drug content (PHE 135 [39.0 %], SVA 140 [38.8 %], carbamazepine 51 [37.5 %], phenobarbitone 130 [50.7 %]), and 253 split parts were outside the acceptable content uniformity range of <85 % and >115 % (PHE 85 [24.5 %], SVA 98 [27.2 %], carbamazepine 14 [10.2 %], phenobarbitone 56 [21.8 %]). In total, 130 (72.2 %) patients had plasma drug concentrations outside the therapeutic range (PHE 36 [72.0 %], SVA 39 [78.0 %], carbamazepine 34 [68.0 %], phenobarbitone 21 [70.0 %]).

Conclusions

Splitting adult-dosage formulations of AEDs results in patients not receiving the optimal dose. Plasma drug concentrations are also not optimal. Pediatric dosage formulations should be preferred to splitting adult-dosage formulations in pediatric epilepsy.

http://ift.tt/2dLw1fD

Evaluation of the improvement effect of laser acupuncture biostimulation in asthmatic children by exhaled inflammatory biomarker level of nitric oxide

Abstract

Variable therapy of asthma is not sufficient yet to achieve good asthma control. Therapy decision requires serial investigations. Low-level laser acupuncture is a suitable non-invasive modality of complementary medicine. The exhaled breath condensate (EBC) is easy and useful to evaluate the efficacy of drugs or novel therapy. This study aimed to evaluate the effectiveness of low-level laser biostimulation of acupuncture points on asthma improvement in children. Forty-eight asthmatic children were subdivided into case (laser) group, which received 12 direct contact low-power laser acupuncture sessions (three sessions/week) on specific traditional Chinese acupuncture points for bronchial asthma, and control asthmatic group, which received sham laser acupuncture on the same acupoints and number of sessions of the case (laser) group. Low-power Multichannel Aculas-AM laser (grade II) of wave length 780 nm, output power 800 mw, and beam spot size 0.1 cm² with continuous mode was used. Eighteen acupoints were stimulated for 2 min, giving energy of 9.6 J/cm²/acupoint. The total session time was 3 min. Both groups were evaluated pre- and post-laser acupuncture intervention by recording levels of asthma control, pulmonary function, and EBC nitric oxide. In the case (laser) group, 91.7 % of patients experienced an improvement in the level of asthma control versus 25 % in the control group (p < 0.001). This was associated with a significant decrease of the breath condensate FENO concentration (p < 0.001) and significant increase of spirometry parameters (p < 0.001) in the case (laser) group. Application of laser acupuncture treatment given with conventional therapy can effectively improve bronchial asthma more than prescription of medications alone could.

http://ift.tt/2dKm11M

Retraction Note to: Effect of coupling asynchronous acoustoelectric effects on the corrosion behavior, microhardness and biocompatibility of biomedical titanium alloy strips

http://ift.tt/2d3Gz76

Prevalence of avian haemosporidian parasites is positively related to the abundance of host species at multiple sites within a region

Abstract

Parasite prevalence is thought to be positively related to host population density owing to enhanced contagion. However, the relationship between prevalence and local abundance of multiple host species is underexplored. We surveyed birds and their haemosporidian parasites (genera Plasmodium and Haemoproteus) at multiple sites across eastern North America to test whether the prevalence of these parasites in a host species at a particular site is related to that host's local abundance. Prevalence was positively related to host abundance within most sites, although the effect was stronger and more consistent for Plasmodium than for Haemoproteus. In contrast, prevalence was not related to variation in the abundance of most individual host species among sites across the region. These results suggest that parasite prevalence partly reflects the relative abundances of host species in local assemblages. However, three nonnative host species had low prevalence despite being relatively abundant at one site, as predicted by the enemy release hypothesis.

http://ift.tt/2cT5mwh

Validity of a perceptually-regulated step test protocol for assessing cardiorespiratory fitness in healthy adults

Abstract

Purpose

To determine whether maximal oxygen uptake (VO₂max) could be predicted accurately and reliably from a 2-step, perceptually-regulated exercise test (PRET) in healthy adults.

Methods

Sixteen participants (31.7 ± 11.3 years, 3 females) completed three PRETs (separated by 24–72 h) and one maximal, perceptually-regulated, graded exercise test (PRETmax) on a motorized treadmill. Oxygen uptake (VO₂) and heart rate (HR) were recorded during each test. VO₂ values for RPE range 9–15 were extrapolated to RPE 20 and age-predicted maximal HR (HRmax) using individual linear regression analysis to predict VO₂max values compared to measured VO₂max.

Results

VO₂ and HR values were consistent between each of four RPE levels of the PRET. ICC values ranged between 0.76 and 0.85. Predicted VO₂max from both methods were lower than measured VO₂max (p < 0.01). Limits of agreement (LoA) for measured (41.4 ± 5.3 ml kg⁻¹ min⁻¹) versus predicted VO₂max from each of the three PRETs using RPE20 were −1.2 ± 15.6, −1.0 ± 7.2 and −2.1 ± 5.5 and for HRmax were −1.8 ± 4.2; −2.6 ± 4.2 and −2.4 ± 4.4 ml kg⁻¹ min⁻¹ for PRET 1, 2 and 3, respectively.

Conclusions

The step PRET elicited significant and reliable increases in VO₂ across the four RPE levels, but under-estimated treadmill VO₂max. However, there was better agreement between measured and predicted VO₂max when extrapolated to HRmax. As evidence indicates the underestimation of VO₂max is explained by the difference in the mode of exercise, the step PRET provides a simple and convenient test of cardiorespiratory fitness.

http://ift.tt/2dSX2dc

Quantitation of the Noncovalent Cellular Retinol-Binding Protein, Type 1 Complex Through Native Mass Spectrometry

Abstract

Native mass spectrometry (MS) has become a valuable tool in probing noncovalent protein–ligand interactions in a sample-efficient way, yet the quantitative application potential of native MS has not been fully explored. Cellular retinol binding protein, type I (CrbpI) chaperones retinol and retinal in the cell, protecting them from nonspecific oxidation and delivering them to biosynthesis enzymes where the bound (holo-) and unbound (apo-) forms of CrbpI exert distinct biological functions. Using nanoelectrospray, we developed a native MS assay for probing apo- and holo-CrbpI abundance to facilitate exploring their biological functions in retinoid metabolism and signaling. The methods were developed on two platforms, an Orbitrap-based Thermo Exactive and a Q-IMS-TOF-based Waters Synapt G2S, where similar ion behaviors under optimized conditions were observed. Overall, our results suggested that within the working range (~1–10 μM), gas-phase ions in the native state linearly correspond to solution concentration and relative ion intensities of the apo- and holo-protein ions can linearly respond to the solution ratios, suggesting native MS is a viable tool for relative quantitation in this system.

Graphical Abstract

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Where Does the Electron Go? Stable and Metastable Peptide Cation Radicals Formed by Electron Transfer

Abstract

Electron transfer to doubly and triply charged heptapeptide ions containing polar residues Arg, Lys, and Asp in combination with nonpolar Gly, Ala, and Pro or Leu generates stable and metastable charge-reduced ions, (M + 2H)^+●, in addition to standard electron-transfer dissociation (ETD) fragment ions. The metastable (M + 2H)^+● ions spontaneously dissociate upon resonant ejection from the linear ion trap, giving irregularly shaped peaks with offset m/z values. The fractions of stable and metastable (M + 2H)^+● ions and their mass shifts depend on the presence of Pro-4 and Leu-4 residues in the peptides, with the Pro-4 sequences giving larger fractions of the stable ions while showing smaller mass shifts for the metastables. Conversion of the Asp and C-terminal carboxyl groups to methyl esters further lowers the charge-reduced ion stability. Collisional activation and photodissociation at 355 nm of mass-selected (M + 2H)^+● results in different dissociations that give sequence specific MS³ spectra. With a single exception of charge-reduced (LKGLADR + 2H)^+●, the MS³ spectra do not produce ETD sequence fragments of the c and z type. Hence, these (M + 2H)^+● ions are covalent radicals, not ion–molecule complexes, undergoing dramatically different dissociations in the ground and excited electronic states. The increased stability of the Pro-4 containing (M + 2H)^+● ions is attributed to radicals formed by opening of the Pro ring and undergoing further stabilization by hydrogen atom migrations. UV–VIS photodissociation action spectroscopy and time-dependent density functional theory calculations are used in a case in point study of the stable (LKGPADR + 2H)^+● ion produced by ETD. In contrast to singly-reduced peptide ions, doubly reduced (M + 3H)⁺ ions are stable only when formed from the Pro-4 precursors and show all characteristics of even electron ions regarding no photon absorption at 355 nm or ion-molecule reactions, and exhibiting proton driven collision induced dissociations.

Graphical Abstract

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http://ift.tt/2dxZeXJ

Cystic fibrosis: a clinical view

Abstract

Cystic fibrosis (CF), a monogenic disease caused by mutations in the CFTR gene on chromosome 7, is complex and greatly variable in clinical expression. Airways, pancreas, male genital system, intestine, liver, bone, and kidney are involved. The lack of CFTR or its impaired function causes fat malabsorption and chronic pulmonary infections leading to bronchiectasis and progressive lung damage. Previously considered lethal in infancy and childhood, CF has now attained median survivals of 50 years of age, mainly thanks to the early diagnosis through neonatal screening, recognition of mild forms, and an aggressive therapeutic attitude. Classical treatment includes pancreatic enzyme replacement, respiratory physiotherapy, mucolitics, and aggressive antibiotic therapy. A significant proportion of patients with severe symptoms still requires lung or, less frequently, liver transplantation. The great number of mutations and their diverse effects on the CFTR protein account only partially for CF clinical variability, and modifier genes have a role in modulating the clinical expression of the disease. Despite the increasing understanding of CFTR functioning, several aspects of CF need still to be clarified, e.g., the worse outcome in females, the risk of malignancies, the pathophysiology, and best treatment of comorbidities, such as CF-related diabetes or CF-related bone disorder. Research is focusing on new drugs restoring CFTR function, some already available and with good clinical impact, others showing promising preliminary results that need to be confirmed in phase III clinical trials.

http://ift.tt/2dSi92U

Statistical Estimation of Software Quality in Hospital Information System

Abstract

Clinical environment is very complex, and flexible and adaptive service improvement is crucial in maintaining quality of medical care. Thus, incremental software development in hospital information system and its evaluation are important. This paper introduces a statistical estimation method of an embedded software in which service logs are used to measure the differences between responsive time before and after a new interface has been introduced. The empirical results show that statistical methods are useful to evaluate the system performance in a real clinical environment.

http://ift.tt/2dvQAJE

Safety and efficacy of etanercept and adalimumab in children aged 2 to 4 years with juvenile idiopathic arthritis

Abstract

The TNF inhibitors etanercept (ETA) and adalimumab (ADA) are approved for treating patients older than 2 years with polyarticular juvenile idiopathic arthritis (JIA). Because long-term experience of treating children younger than 4 years is limited, we evaluated the efficacy and safety of ETA or ADA in patients aged 2–4 years. This prospective, long-term, observational registry study documented baseline demographics, clinical characteristics, disease activity parameters, and safety of patients treated with ETA or ADA. Efficacy was determined using the JADAS-10, the JADAS criteria for minimal disease activity (MDA) and remission, and the PedACR response criteria after 3, 6, 12, 18, and 24 months. Between January 2001 and March 2015, 85 patients with polyarticular JIA aged 2–4 years started anti-TNF-α treatment. Seventy-four (54 girls) patients were treated with ETA and 11 (7 girls) with ADA. After 6/12/24 months of treatment, JADAS-MDA was reached by 55/58/58 % of ETA patients and 50/71/66 % of ADA patients. Furthermore, JADAS-Remission was achieved by 35/44/50 % of ETA patients and 16/28/66 % of ADA patients. PedACR 50/70/90 response was achieved by 64/54/41 % of ETA patients and 56/33/22 % of ADA patients at the last treatment observation. Discontinuation because of remission or inefficacy was recorded in 24 (29 %) and 28 (33 %) patients, respectively. Seventy-nine adverse events and four serious adverse events were reported. Administration of ETA and ADA in JIA patients younger than 4 years was efficacious, well tolerated, and safe. Patients younger than 4 years may show marked improvement following anti-TNF-alpha therapy.

http://ift.tt/2dwE5gD

Childhood polyarteritis nodosa: diagnosis with non-invasive imaging techniques

Abstract

There is limited number of publications about the use of non-invasive imaging modalities in the diagnosis of childhood polyarteritis nodosa (cPAN). The aim of this study was to present the clinical and imaging findings of the patients with cPAN who were diagnosed with non-invasive imaging techniques. Files of patients who had been diagnosed as cPAN in our department from 2005 to 2015 were reviewed, retrospectively. Demographic, clinical, laboratory, and imaging findings of the patients were evaluated. Nine patients (8M, 1F; age at disease onset: 12.5 years (7–16)) had been diagnosed as cPAN in our clinic with non-invasive imaging techniques within the last 10 years. Abdominal pain, fever, fatigue, and myalgia were the most frequent complaints. Doppler ultrasonography (US) was used in the diagnosis of seven patients and computed tomography (CT) angiography was done in four patients. Duration between admission to our center and diagnosis was median of 5 days (8 h–10 days), including four patients who were diagnosed within 24 h of admission. Approximately 80 % of our patients with cPAN had MEFV gene mutations and 90 % had elevated anti-streptolysin O levels. All of them had the involvement of the gastrointestinal tract. Hepatic and cystic arterial involvements were detected in seven and six patients, respectively. This report included the largest cPAN series that were diagnosed with non-invasive imaging modalities. We suggest that non-invasive modalities, especially Doppler US, should be considered in first line approach in the diagnosis of these patients, particularly in children.

http://ift.tt/2dKBzCK

The usage of biological DMARDs and clinical remission of rheumatoid arthritis in China: a real-world large scale study

Abstract

The aims of this study are to characterize the biological disease-modifying antirheumatic drug (bDMARD) usage patterns in real-life and examine the remission rate of rheumatoid arthritis (RA) patients receiving bDMARDs in routine clinical practice in China. Consenting RA patients (≥18 years) from 15 teaching hospitals and receiving marketed bDMARDs were included. In total, 802 patients (81.3 % women, 49.0 ± 13.9 years) were included; 89.5 % were receiving a combination of bDMARDs and conventional synthetic DMARDs (csDMARDS), whereas 10.5 % were receiving bDMARD monotherapy. Etanercept (including Enbrel® and local brand Yi Sai Pu® and Qiangke®), tocilizumab, adalimumab, and infliximab were used by 66.6 %, 17.0 %, 7.5 %, and 6.6 % patients, respectively. Etanercept was used at a mean weekly dose of 38.2 ± 15.6 mg for 25.5 ± 47.0 weeks and tocilizumab at 94.5 ± 21.9 mg for 4.7 ± 7.5 weeks. Overall rate of remission was 12.6 %, 5.4 % , and 3.5 % based on DAS28, CDAI, and SDAI scores, respectively. Compared with patients receiving bDMARDs for <3 months, those receiving bDMARDs for ≥3 months exhibited significantly lower DAS28 scores (p < 0.0001), and a significantly higher proportion of patients who received bDMARDs for ≥12 months achieved the treatment goal (remission or low disease activity, 62.5 % vs. 18.3 %, p < 0.0001). Patients receiving combination therapy with csDMARDs exhibited lower DAS28 scores than patients receiving bDMARD monotherapy (4.3 vs. 4.8, p = 0.011). This large-scale real-world study showed that bDMARD usage patterns in routine clinical practice in China were in accordance with international guidelines for RA management despite the short treatment duration. Longer duration of bDMARD usage and combination therapy showed a favored outcome of RA.

http://ift.tt/2dwF3cF

Scarless Epicanthoplasty and Concomitant Double Eyelidplasty in Chinese Eyelids

Abstract

Background

The presence of mild or moderate medial epicanthus is typical in Asian patients. Numerous epicanthoplasty techniques have been described previously. However, these methods usually leave obvious scars in the medial canthal area. The aim of this report is to introduce a novel epicanthoplasty technique and a concomitant double eyelidplasty which avoid leaving scars in the medial canthal region.

Methods

From July 2013 to July 2015, 252 patients received epicanthoplasty and concomitant double eyelidplasty with this new technique. The medial epicanthus was corrected through the medial end of the eyelid crease incision. One hundred eighteen of these patients were followed up for 3–24 months (8 months in average). The preoperative and postoperative interepicanthal distances were measured at pre, 3 and 6 months post-operation. The aesthetic results were evaluated with patient visual analog scale (VAS) scores.

Results

The average intercanthal distance significantly decreased 3 months after the operation (32.7 ± 2.3 mm vs 36.5 ± 2.6 mm, p < 0.05, paired t test). Little retraction was noticed at 6 months after the operation (33.0 ± 2.4 vs 32.7 ± 2.3 mm, p < 0.05, paired t test). The mean patient VAS score associated with satisfaction of overall outcome was 4.2 at 6 months after operation (range 2.5–5.0).

Conclusion

This new method provides an effective way to correct the medial epicanthus without leaving any scar in the medial canthal region. Patients with mild to moderate medial epicanthus are good candidates for this procedure.

Level of Evidence V

This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors http://ift.tt/18t7xNj.

http://ift.tt/2dKAtXH

Tracheocutaneous Fistula Closure: Comparison of Rhomboid Flap Repair with Z Plasty Repair in a Case Series of 40 Patients

Abstract

Introduction

Tracheocutaneous fistula (TCF) is one of the recognized sequelae of a long-term tracheostomy resulting from mucocutaneous overgrowth which prevents closure of the artificial lumen at the site of tracheostomy. Primary closure of TCF has disappointing results and may lead to complications like pneumothorax, pneumomediastinum, cervicofacial subcutaneous emphysema, and depressed scar.

Objective

To compare TCF repair using fistulectomy followed by rhomboid flap versus fistulectomy followed by Z plasty repair.

Methods

In this prospective study, 40 patients of either sex with persistent TCF were included. All patients were randomly divided into two groups. Group I had 20 patients who underwent TCF repair using a technique in which fistulectomy was done followed by its closure in layers, and finally closing the defect using a rhomboid flap. The remaining 20 were included in group II who underwent TCF repair using a technique in which fistulectomy was done followed by layered closing, and final closure of the defect was done using Z plasty. The follow-up period was 3 months.

Results

Out of 40 patients, all but 8 experienced a successful outcome without any complications, and complete aesthetic satisfaction, with improvement in phonation, and no soiling of clothes with mucus or sputum. The 8 unsuccessful patients belonged to group II (Z plasty group).

Conclusion

Both techniques have been described in the literature and are proven to give good results. Our study emphasizes the fact that in our experience, the rhomboid flap was a better alternative for TCF repair than Z plasty.

Level of Evidence IV

This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors http://ift.tt/18t7xNj

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A Simple and Effective Technique of Breast Remodelling After Conserving Surgery for Lower Quadrants Breast Cancer

Abstract

Background

Quadrantectomy is an oncologically safe procedure for the treatment of early-stage breast cancer, but it often results in poor aesthetic outcomes such as breast shape deformity, which is more visible if the tumour is located in the lower pole. We recommend the use of the transverse incision, which retains the oncological advantages of the quadrantectomy while leading to better aesthetical results.

Method

We evaluated the clinical results of 24 patients with breast cancer who underwent quadrantectomy of the lower breast pole and volume replacement with remodelling through three posterior scorings from January 2012 to January 2014, with cosmetic evaluations performed according to the criteria set by the Japanese Breast Cancer Society.

Results

Minimum follow-up after surgery was 2 years, with an average of 28.4 months. Among treated patients, the percentage of complications was extremely low and the degree of satisfaction fairly good. Moreover, the assessment of the medical team matched patient self-assessments.

Conclusion

Immediate breast reconstruction of a defect performed after a quadrantectomy of the lower breast pole using the "posterior scoring technique" provided better cosmetic results compared to the transposition of residual breast tissue. This technique provides reliable and reproducible results, and it also appears to be rather successful on patients with small-moderate breasts in the absence of a certain degree of ptosis, therefore increasing its already considerable appeal.

Level of Evidence V

This journal requires that the authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors http://ift.tt/18t7xNj.

http://ift.tt/2dLcR9I