Technology and social media have dramatically altered the landscape in which we practice medicine. Clinicians have increasingly turned to technology and the internet to enhance patient care. Allergists have used these modalities to improve utilization and adherence to immunotherapy. Electronic medical records (EMRs) are being widely adopted by allergy practices and some offer allergy/immunology specific modules that aid in daily workflow. The development of specialized devices that reduce pain associated with immunotherapy administration may improve compliance with immunotherapy. Social media and other forms of electronic communication such as e-mail, Facebook, Twitter, short message service (SMS), and YouTube give clinicians multiple avenues to disseminate information and reach their patients, possibly improving patient adherence to therapy. Finally, tablet computers, online networks, and electronic surveys provide additional ways to connect patients and physicians.
Background: Chaetognatha are a phylum of marine carnivorous animals which includes more than 130 extant species. The internal systematics of this group have been intensively debated since it was discovered in the 18th century. While they can be traced back to the earlier Cambrian, they are an extraordinarily homogeneous phylum at the morphological level - a fascinating characteristic that puzzled many a scientist who has tried to clarify their taxonomy. Recent studies which have attempted to reconstruct a phylogeny using molecular data have relied on single gene analyses and a somewhat restricted taxon sampling. Here, we present the first large scale phylogenetic study of Chaetognatha based on a combined analysis of nearly the complete ribosomal RNA (rRNA) genes. We use this analysis to infer the evolution of some morphological characters. This work includes 36 extant species, mainly obtained from Tara Oceans Expedition 2009/2012, that represent 16 genera and 6 of the 9 extant families. Results: Cladistic and phenetic analysis of morphological characters, geometric morphometrics and molecular small subunit (SSU rRNA) and large subunit (LSU rRNA) ribosomal genes phylogenies provided new insights into the relationships and the evolutionary history of Chaetognatha. We propose the following clade structure for the phylum: (((Sagittidae, Krohnittidae), Spadellidae), (Eukrohniidae, Heterokrohniidae)), with the Pterosagittidae included in the Sagittidae. The clade (Sagittidae, Krohnittidae) constitutes the monophyletic order of Aphragmophora. Molecular analyses showed that the Phragmophora are paraphyletic. The Ctenodontina/Flabellodontina and Syngonata/Chorismogonata hypotheses are invalidated on the basis of both morphological and molecular data. This new phylogeny also includes resurrected and modified genera within Sagittidae. Conclusions: The distribution of some morphological characters traditionally used in systematics and for species diagnosis suggests that the diversity in Chaetognatha was produced through a process of mosaic evolution. Moreover, chaetognaths have mostly evolved by simplification of their body plan and their history shows numerous convergent events of losses and reversions. The main morphological novelty observed is the acquisition of a second pair of lateral fins in Sagittidae, which represents an adaptation to the holoplanktonic niche.
Background: Eosinophilic granulomatosis with polyangiitis is a complex multisystemic syndrome with heterogeneous presentation. Most often, there is a clinical history of asthma or other atopic conditions, and current presentation generally includes signs of cutaneous or pulmonary involvement. Very few reports described myalgia or weakness as the chief complaint. Of these, only a few included muscle biopsy evaluation and none showed convincing evidence of primary myositis. We believe this report is the first to demonstrate true myositis in the setting of early eosinophilic granulomatosis with polyangiitis.Case presentationThis report describes a 74 year old Caucasian man, with no known allergies, presenting severe myalgia, muscle weakness, jaw claudication, and fever. Blood work showed marked eosinophilia and high creatine kinase levels. Biceps brachialis muscle biopsy revealed eosinophilic necrotizing vasculitis and true myositis with myophagocytosis of non-necrotic fibers and strong sarcolemmal MHC-1 overexpression by immunohistochemistry. This patient was successfully treated with prednisone and azathioprine. Conclusion: Our finding of true myositis in a case of eosinophilic granulomatosis with polyangiitis suggests that primary auto-immunity against muscle fibers, distinct from the secondary effects of vasculitis, can occur in this entity and may represent an overlap syndrome. Early recognition of eosinophilic granulomatosis with polyangiitis in patients presenting with myositis may provide an opportunity to treat the vasculitis before onset of severe multisystemic disease. We recommend the use of muscle biopsy with immunohistochemistry for MHC-1 to confirm the diagnosis of myositis in the setting of eosinophilic granulomatosis with polyangiitis.
Background: Dynamic compression plate (DCP) constructs provide inadequate fixation in cases of poor bone quality and early weight-bearing. Screw locking elements (SLE) are flat locking nuts placed at the end of the screw to prevent screw stripping from the bone, improving fixation stability. The purpose of this work was to compare biomechanical and radiological evaluations of femoral ovine osteotomies fixed using DCP constructs with and without SLE.MethodA dyaphyseal femoral osteotomy was performed in sixteen adult sheep and fixed with a DCP and cortical screws. Half of the animals were operated on with a SLE on each side of the osteotomy and the rest without the addition of SLE. Four animals of each group were euthanized after 8 weeks, and the remaining after 16 weeks. Both femora of each animal were radiographed and mechanically tested in torsion. Results: Radiologically femoral malalignment or screw loosening was observed in six out of the eight animals operated on without SLE. In contrast, all animals subjected to the operation with SLE showed complete radiological consolidation of the osteotomy. Seven of these eight animals showed normal femoral alignment and no osteosynthesis failure. Stiffness of the bones fixed with SLE was among 145% and 177% the value of their contralateral non-operated femurs (all animals of this group showed greater stiffness on the operated bone than its contralateral non-operated femur). However, stiffness of the bones operated on without SLE was among 58% and 87% the value of the stiffness of their contralateral non-operated bone (all animals of this group showed greater stiffness on the non-operated bone than the osteotomized ones). Conclusions: Use of SLE avoided loosening of the system and stimulated stronger osteotomy consolidation. Clinical application of this improved system may thus be a feasible and cost-effective alternative to other more rigid and expensive bone fixation techniques.
Background: To investigate the impact of physician-assessed late toxicities on patient-reported quality of life (QoL) for nasopharyngeal carcinoma (NPC) patients with long-term survival. Methods: A cross-sectional survey of QoL and late toxicities was conducted in 242 NPC patients with disease-free survival of more than 5 years after treatment. The QoL was assessed by the European Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). Late toxicities including neuropathy, hearing loss, dysphagia, xerostomia, and neck fibrosis were recorded based on the criteria of Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v.4.0). The general linear model multiple analysis of variance (GLM-MANOVA) was performed to predict factors associated with the QoL. Results: In the multifactor model of GLM-MANOVA, of the five late toxicities of CTCAE scales, neuropathy, hearing loss, and xerostomia were observed to be significantly associated with the overall outcome of the fifteen QLQ-C30 scales. A statistically significant trend (p <0.05) was observed, indicating that NPC survivors with more severe neuropathy, hearing loss or xerostomia had a worse outcome on global QoL, all five functional scales, and a variety of symptomatic scales. Conclusions: To improve QoL outcome for NPC survivors, the development of a modern radiotherapeutic technique should not only focus on reduction of the dose to the salivary glands, but also on anatomical structures that are involved in neuropathy and hearing loss.
Background: Mineral disorders are associated with adverse renal outcomes in chronic kidney disease (CKD) patients. Previous studies have associated hypercalcemia and hypocalcemia with mortality; however, the association between serum calcium and renal outcome is not well-described. Whether adding calcium besides phosphorus or in the form of calcium-phosphorus (Ca x P) product into the model of survival analysis could improve the prediction of renal outcomes is not known. Methods: A prospective cohort of 2144 outpatients with CKD stages 3-4 was evaluated. Cox proportional hazard analysis was performed according to calcium quartiles. Results: The mean calcium level was 9.2 +/- 0.7 mg/dL. Low serum calcium ( 9.8 mg/dL). Adding calcium into the survival model increased the integrated discrimination improvement by 0.80% (0.12% - 1.91%) while calcium-phosphorus product did not improve risk prediction.The combination of high serum phosphorus (>4.2 mg/dL) and low serum calcium (<9.1 mg/dL) was associated with the highest risk of RRT (HR:2.31 (95%CI: 1.45-3.67, P < 0.05). Conclusion: Low serum calcium is associated with increased risk of RRT and rapid renal function progression in CKD stage 3-4 patients. The integration of serum calcium and phosphorus, but not calcium-phosphorus product should be considered in a predictive model of renal outcome.
Background: DNA barcoding assumes that a biological entity is completely separated from its closest relatives by a barcoding gap, which means that intraspecific genetic distance (from COI sequences) should never be greater than interspecific distances. We investigated the applicability of this strategy in identifying species of the genus Triatoma from South America.FindingsWe calculated intra and interspecific Kimura-2-parameter distances between species from the infestans, matogrossensis, sordida and rubrovariasubcomplexes. In every subcomplex examined we observed at least one intraspecific distance greater than interspecific distances. Conclusions: Although DNA barcoding is a straightforward approach, it was not applicable for identifying Southern American Triatoma species, which may have diverged recently. Thus, caution should be taken in identifying vector species using this approach, especially in groups where accurate identification of taxa is fundamentally linked to public health issues.
Background: The safety and efficiency of gene therapies for cystic fibrosis (CF) need to be assessed in pre-clinical models. Using the normal ferret, this study sought to determine whether ferret airway epithelia could be transduced with a lysophosphatidylcholine (LPC) pre-treatment followed by a VSV-G pseudotyped HIV-1 based lentiviral (LV) vector, in preparation for future studies in CF ferrets. Methods: Six normal ferrets (7 -8 weeks old) were treated with a 150 muL LPC pre-treatment, followed one hour later by a 500 muL LV vector dose containing the LacZ transgene. LacZ gene expression in the conducting airways and lung was assessed by X-gal staining after 7 days. The presence of transduction in the lung, as well as off-target transduction in the liver, spleen and gonads, were assessed by qPCR. The levels of LV vector p24 protein bio-distribution in blood sera were assessed by ELISA at 0, 1, 3, 5 and 7days. Results: The dosing protocol was well tolerated. LacZ gene expression was observed en face in the trachea of all animals. Histology showed that ciliated and basal cells were transduced in the trachea, with rare LacZ transduced single cells noted in lung. p24 levels was not detectable in the sera of 5 of the 6 animals. The LacZ gene was not detected in the lung tissue and no off-target transduction was detected by qPCR. Conclusions: This study shows that ferret airway epithelia are transducible using our unique two-step pre-treatment and LV vector dosing protocol. We have identified a number of unusual anatomical factors that are likely to influence the level of transduction that can be achieved in ferret airways. The ability to transduce ferret airway epithelium is a promising step towards therapeutic LV-CFTR testing in a CF ferret model.
Background: The roles of iron in epilepsy and its pathophysiological significance are poorly understood, especially whether iron levels are abnormal in subcortcal structures. This study aims to demonstrate whole-brain iron alterations and its clinical relevancies in mesial temporal lobe epilepsy (mTLE) in vivo, using susceptibility-weighted magnetic resonance imaging (SWI). We studied 62 patients with mTLE and 62 healthy controls. Brain iron concentration was quantified using SWI phase values. Voxel-wise analysis was carried out to compare iron levels between mTLE and controls, and to assess the relationship between altered iron concentration and clinical parameters in mTLE. Results: Patients with mTLE showed decreases of iron levels in the subcortical structures such as substantia nigra, red nucleus, and basal ganglia. Conversely, iron levels were decreased in the cortex. Subcortical iron levels were negatively correlated to those in the cortex. Moreover, cortical and basal ganglia iron levels were related to clinical variables including epilepsy duration, age at seizures onset, and histories of precipitating factors. Conclusions: Our SWI findings suggest a redistribution of iron between subcortical and cortical structures in mTLE. The degree of redistribution is affected by both progression of epilepsy and precipitating factors. Monitoring brain iron redistribution offers new insights into the pathogenesis of mTLE, and may be a potential biomarker for monitoring the clinical progression of epilepsy.
Background: The red fox (Vulpes vulpes) is a widespread species, harbouring many pathogens relevant for humans and pets. Indeed, Anaplasma spp., Ehrlichia canis and Rickettsia spp. among the bacteria and Hepatozoon canis as well as Babesia sp. among the parasites have been the focus of several studies.FindingsIn a cohort of 36 foxes shot on one day in the north-eastern part of Austria, Babesia microti-like pathogens were found in 50%, while H. canis was detected in 58.3% of the samples. The spleen was more useful for detection of H. canis, whereas B. microti-like parasites were more frequently found in the blood. Bacteria could not be confirmed in any of the cases to demonstrate the occurrence of such tick-borne pathogens using PCR and sequencing on blood and spleen samples. Conclusions: The occurrence of B. microti-like and H. canis parasites raised many questions, because these infections have never been found autochthonously in dogs. Furthermore in the case of H. canis the main vector tick, Rhipicephalus sanguineus, is absent in the sampling area, leaving space for further hypotheses for transmission such as vertical transmission, transmission via ingestion of prey animals or other vector ticks. Further studies are needed to evaluate the risks for pets in this area. PCRs delivered differing results with the different tissues, suggesting the use of both spleen and blood to obtain an integral result.