Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocyte disorder most commonly characterized by multifocal osteosclerotic lesions of the long bones demonstrating sheets of foamy histiocyte infiltrates on biopsy with or without histiocytic infiltration of extraskeletal tissues. ECD can be difficult to diagnose since it is a very rare disease that can affect many organ systems. Diagnosis is based on the pathologic evaluation of involved tissue interpreted within the clinical context. Patients who have the BRAF V600E mutation are treated first line with vemurafenib. For those without the mutation with symptomatic ECD, conventional or PEGylated interferon alpha is recommended. For patients who are either intolerant or nonresponsive to interferon alpha, systemic chemotherapy with or without corticosteroids can be used. We present a rare case of Erdheim-Chester disease with concurrent Langerhans cell histiocytosis which occurs in only one fifth of the cases and often presents as a diagnostic and therapeutic challenge. We present the case of a 47-year-old Caucasian male who initially presented to the primary care physician 6 years ago with the chief complaint of left ear fullness of 2 weeks' duration. The patient also noticed that the left ear fullness was associated with tearing from the right eye. The patient was initially treated conservatively, with no subjective improvement in his symptoms. He underwent imaging studies which revealed a left mastoid/middle ear fossa mass and a right orbital mass . Imaging2 weekly and prednisone 40 mg/m2. Thereafter, he was started on monthly pulse prednisone and daily 6 mercaptopurine doses as maintenance therapy for 24 weeks.The surgical resection of the orbital mass was followed by six cycles of vinblastine 6 mg/mThe patient was relatively stable until about three years ago when he started experiencing diplopia in the right eye. CT scans revealed extensive bilateral intraconal enhancing soft tissue, infiltrative soft tissue involving the right sphenoid wing with extension into the pterygopalatine fossa and right temporal fossa, and enhancing soft tissue identified within bilateral frontal sinuses . Right oThe patient was started on PEGylated interferon alpha to be given as 180 mcg subcutaneously weekly. Repeated CT evaluations over the next 3 years demonstrated no evidence of progression of disease on PEGylated interferon alpha-2a therapy .About 6 months ago, the patient noticed a swelling on the frontal part of the scalp. MRI brain showed interval development of left calvarial mass lesion extending intracranially, associated with an epidural soft tissue component measuring 4 × 1.5 × 1.5 cm . The patErdheim-Chester disease (ECD) is a rare form of non-Langerhans cells histiocytosis. Approximately 500 cases have been reported in the literature with far fewer cases occurring concurrently with Langerhans cell histiocytosis (LCH) . HoweverRecent studies have identified a high prevalence of the BRAF V600E mutation in patients with ECD. This gene is known to participate in oncogene-induced senescence . A 2014 The most common clinical manifestations of ECD depend on the site of involvement. Literature review of 259 patients diagnosed with biopsy-proven ECD identified the most common presentations including bone pain 26%), neurologic features 23%), diabetes insipidus (22%), and constitutional symptoms (20%) [%, diabet%, neurolPrognosis is generally poor, and no definitive cure for the disease is currently available. Cardiovascular and CNS involvement is usually associated with the worst prognosis . RetrospDefinitive diagnosis of ECD requires biopsy identifying infiltration of tissue by foamy mononucleated histiocytes with small nuclei. Rare multinucleated histiocytes known as Touton cells are also observed . Mild fiPrior to establishing treatment plans, patients require staging and genetic studies. Typical imaging consists of an MRI of the brain, an MRI or CT scan of the entire aorta, a cardiac MRI, a transthoracic echocardiogram, and a fluoro-d-glucose PET scan or CT scan of the chest, abdomen, and pelvis . RadioloIn the rare event of ECD diagnosis with asymptomatic disease with no objective evidence of CNS involvement or organ dysfunction, delaying treatment with adequate screening is reasonable . In patiPatients who carry BRAF V600E mutation should be considered for BRAF inhibitor therapy. Vemurafenib is a serine/threonine kinase inhibitor of activating point mutations in BRAF and was FDA approved for treatment of ECD on November 6, 2017 . EstimatPreviously regarded as first-line treatment, interferon alpha or PEGylated interferon alpha has the most robust supporting evidence for survival benefit in ECD . The larFor patients who are either intolerant or nonresponsive to interferon alpha therapy, alternative treatment options include systemic chemotherapy with or without corticosteroids. Typical regimens for LCH and theoretical treatment for ECD is a 24-week treatment plan comprising weekly vinblastine and etoposide for six weeks followed by vinblastine and etoposide every three weeks for the remaining duration of the treatment course . Use of Due to the rarity of the condition, only a limited number of drugs from clinical trials have become FDA-approved treatment regimens. Small case studies have noted the efficacy of anticytokine-directed therapy using agents such as anakinra (Il1 receptor antagonist), canakinumab (Il1 receptor antagonist), and infliximab (anti-TNF) –22. TociDisease monitoring is typically done at 3- to 6-month intervals with flouro-d-glucose PET scans. Once the disease stabilizes, PET scans can be done less frequently as per clinician discretion . As no bErdheim-Chester disease (ECD) is a rare non-Langerhans histiocyte disorder, most commonly characterized by multifocal osteosclerotic lesions of the long bones demonstrating sheets of foamy histiocyte infiltrates on biopsy with or without histiocytic infiltration of extraskeletal tissues. Since it is a very rare disease that can affect many organ systems, diagnosis can be challenging. Diagnosis is based on the pathologic evaluation of involved tissue interpreted within the clinical context. Not all patients with ECD require treatment at the time of diagnosis. Patients who are asymptomatic without evidence of central nervous system involvement or organ dysfunction can simply be observed. With vemurafenib becoming the first FDA-approved drug for the treatment of ECD, patients who possess BRAF V600E mutation should be considered for BRAF inhibitor therapy. In patients without the mutation or those who are intolerant to the drug, conventional or PEGylated interferon alpha is the recommended treatment. Further treatment options include the use of systemic chemotherapy with or without corticosteroids.


Acute angle closure glaucoma (ACG) in the setting of polypoidal choroidal vasculopathy (PCV) is a catastrophic complication that has been documented infrequently in literature. Ours is the second only report that describes hemorrhagic choroidal detachment as an event leading to acute angle closure glaucoma in PCV patients and the first one to describe the use of diode cyclophotocoagulation (CPC) for this condition. The purpose of this article is to familiarize readers with this entity that has an extremely dismal visual prognosis. Ours is a descriptive case report of two patients with PCV complicated by sudden onset hemorrhagic choroidal detachment (CD) and acute ACG. Both patients had severe pain with no perception of light at presentation with an acute angle closure attack. Both underwent diode CPC for pain relief and control of intraocular pressure (IOP). Both our patients did not regain any vision, but their pain was relieved by diode CPC. Both eyes eventually became phthisical. Acute ACG following massive hemorrhagic CD is a rare but grave complication of PCV, not amenable to treatment. Diode CPC is an effective palliative modality of management to achieve pain relief in such cases. The initial description of polypoidal choroidal vasculopathy (PCV) was given by Yanuzzi  in 1982 A 67-year-old female presented in July 2012 with defective vision in the right eye for six months. She was a known hypertensive and diabetic on treatment for both conditions for the last 15 years. There was no history of trauma, blood dyscrasias or use of antiplatelet or anticoagulant therapy. On examination, her best-corrected visual acuity (BCVA) was counting fingers at face in the right eye and 6/6 in the left eye. Intraocular pressure (IOP) by non contact tonometry (NCT) was within normal limits in both eyes. Anterior segment examination was unremarkable except for bilateral pseudophakia. Fundus examination of the right eye showed three hemorrhagic pigment epithelial detachments (PED) surrounded by serosanguinous fluid, while the fundus in the left eye was within normal limits. OCT of the right eye showed notched hemorrhagic PEDs with underlying polyps and surrounding subretinal fluid (SRF) suggestive of PCV Figure 1 . Based oA 71-year-old female known diabetic and hypertensive over the last 20 years presented in February 2012 with the complaints of poor vision in the left eye for the past three months. She was diagnosed to have PCV on ICGA done at an outside institution. On examination, her BCVA was 6/12 in the right eye and 6/36 in the left eye. IOP was within normal limits. Anterior segment examination in the right eye showed anterior chamber intraocular lens and the left eye showed nuclear sclerosis grade III. Fundus examination revealed moderate non proliferative diabetic retinopathy in the right eye and a large parafoveal subretinal hemorrhage with hemorrhagic PED in the left eye suggestive of PCV. The patient underwent phacoemulsification with posterior chamber intraocular lens (PCIOL) implantation in March 2012 in the left eye. Following this, ICGA-guided PDT with ranibizumab was planned, but before she could undergo this treatment, she developed an acute episode of pain with vomiting in April 2012. Her visual acuity at this visit was NPL and applanation tension was 44 mm Hg. Slit lamp examination showed epithelial corneal edema, shallow anterior chamber, PCIOL, and hemorrhagic CD in the anterior vitreous face. Anterior chamber angles were closed on gonioscopy and B Scan ultrasonography revealed annular hemorrhagic CD with ‘kissing choroids’ (Figure 2b Spontaneous massive subretinal hemorrhage is a known complication of PCV arising from rupture of thin walled choroidal vessels. Polypoidal choroidal vasculopathy causing massive suprachoroidal bleed and appositional hemorrhagic CD resulting in secondary angle closure glaucoma has been reported only once before . Table 1The proposed mechanism for secondary angle closure is that annular hemorrhagic CD can result in the forward displacement of the lens-iris diaphragm causing an angle closure attack , 9]. Th. Th9]. TThe authors declare that they have no competing interests.


Embolization of the Amplatzer Septal Occluder (ASO) device  after percutaneous closure of atrial septal defect (ASD) is a rare and potentially catastrophic complication. Percutaneous retrieval of the embolized device is gaining ground as an acceptable method, although these patients are usually subsequently referred for open surgical closure of the ASD. We present a unique case of percutaneous retrieval embolized ASO device and placement of newer larger ASO device in a single procedure.  A 75-year-old female patient with history of persistent atrial fibrillation after multiple failed cardioversions and septum secundum type of ASD presented with worsening exertional dyspnea of six-month duration. She was previously intolerant to amiodarone. She underwent elective catheter based atrial fibrillation ablation followed by closure of the ASD during a combined percutaneous procedure. ASD closure was performed using a 16 mm Amplatzer Septal Occluder (ASO) device after measuring the diameter of the defect at 15.4 ± 1.0 mm  with sizThe incidence of occluder device embolization after ASD closure is 0.55%–1.4% . Nearly Percutaneous retrieval of the embolized ASO device is still not widely performed. Also, there is no consensus regarding the appropriate timing of the reclosure of the ASD percutaneously after the retrieval of embolized device. With proper planning, percutaneous retrieval and placement of newer device can be safely performed in single setting. We also believe that, in patients with atrial fibrillation and atrial septal defect, it is reasonable to perform atrial fibrillation ablation prior to ASD closure.


This change reflects the outcome of a recent multicenter international study demonstrating that negative Xpert MTB/RIF Assay results from either one or two sputum specimens are highly predictive of the results of two or three negative acid-fast sputum smears.*The Food and Drug Administration (FDA) has cleared the Xpert MTB/RIF Assay  with an expanded intended use that includes testing of either one or two sputum specimens as an alternative to examination of serial acid-fast stained sputum smears to aid in the decision of whether continued airborne infection isolation (AII) is warranted for patients with suspected pulmonary tuberculosis (Mycobacterium tuberculosis complex (MTBC), and two serial Xpert MTB/RIF Assay results detected 100% of AFB smear–positive/MTBC culture-positive patients. In the setting of an overall prevalence of culture-confirmed pulmonary tuberculosis of 22.4% (14.2% [88 of 618] in the United States and 37.1% [127 of 342] outside the United States), a single negative Xpert MTB/RIF Assay result predicted the absence of AFB smear–positive pulmonary tuberculosis with a negative predictive value of 99.7% (99.6%% in the United States and 100% outside the United States); for two serial negative Xpert MTB/RIF Assay results, the negative predictive value was 100%. These findings confirm the results from earlier reports . In addition, one or two Xpert MTB/RIF Assay tests detected 55% and 69%, respectively, of sputum specimens that were AFB smear–negative but culture-positive for MTBC.When compared with the results of two or three serial fluorescent-stained acid-fast sputum smears, a single Xpert MTB/RIF Assay result detected approximately 97% of patients who were acid-fast bacilli (AFB) smear–positive and culture-confirmed as infected with Updated labeling for the Xpert MTB/RIF Assay includes the recommendation that the decision whether to test one or two sputum specimens in determining the need for continued AII should be based on specific clinical circumstances and institutional guidelines. Clinical decisions regarding the need for continued AII should always occur in conjunction with other clinical and laboratory evaluations, and negative Xpert MTB/RIF Assay results should not be the sole basis for infection control practices. The revised label also includes information demonstrating that Xpert MTB/RIF Assay performance is similar in human immunodeficiency virus (HIV)-infected and HIV-uninfected adults, although HIV-infected adults with pulmonary tuberculosis might be more likely to be AFB smear negative at presentation. The Xpert MTB/RIF Assay should not be used for decisions regarding the need for continued AII if MTBC has been detected by the Xpert MTB/RIF Assay or by other methods.MMWR report for additional information regarding the Xpert MTB/RIF Assay .Product labeling retains the recommendation that regardless of Xpert MTB/RIF Assay results, serial collection of sputum specimens for mycobacterial culture remains necessary because nucleic acid amplification testing does not detect all patients with pulmonary tuberculosis, and recovery of organisms for further characterization and drug-susceptibility testing is needed when MTBC is present. Concomitant acid-fast microscopy of serial sputum specimens is also needed when excluding nontuberculosis mycobacterial disease. Readers are encouraged to review the updated product labeling and the previous related


Rice hoja blanca tenuivirus. The sequenced isolate was obtained by insect vector transmission from a symptomatic rice sample grown in Colombia. Sequence data from the four RNA components were obtained by deep sequencing (Illumina), and infections were confirmed by enzyme-linked immunosorbent assay and Sanger sequencing.We describe here the complete genome of  Rice hoja blanca tenuivirus (RHBV) is a multipartite single-stranded, negative-sense RNA virus belonging to the genus Tenuivirus. It causes hoja blanca disease (HBD) in rice (Oryza sativa L.), which has been reported as affecting rice yield in Colombia since 1935. The virus was first described in 1983 (Tagosodes orizicolus Müir (Hemiptera: Delphacidae), which can also be infected by the virus . Compared to the GenBank nonredundant database using BLASTx and BLASTn searches, 33.33% of the total number of contigs showed significant similarity with different viral sequences reported for RHBV. RHBV encodes a typical tenuivirus genome arrangement compared to Rice stripe tenuivirus (RSV), the type species of the group  using g TRIzol , and deeassembly  and MAQ he group . It is cMG566074 (RNA1), MG566075 (RNA2), MG566076 (RNA3), and MG566077 (RNA4).The complete genome sequences reported here have been deposited at GenBank under the accession no.


A two-year-old female presented to the emergency department with facial lacerations after an attack by the family canine (Boxer breed). The exam revealed a stellate laceration on the cartilage of her left pinna, blood in the ear canal, left-sided facial droop, and inability to close her left eye . ComputeTemporal bone fractures can result in facial nerve paresis/paralysis if CN VII is involved.4What do we already know about this clinical entity?The thin temporal bones of children are susceptible tohigh-pressure injuries associated with dog bites, often resulting in damage to important structures such as cranial nerve VII.What is the major impact of the image(s)?This image demonstrates that high-pressure injuries from canine teeth can result in significant intracranial pathology despite minimal skin defects.How might this improve emergency medicine practice?This image highlights the importance of imaging in cases of penetrating facial trauma from dog bites to avoid delayed diagnosis and facilitate early intervention.


In this study, we demonstrate that a bioA mutant of Mycobacterium tuberculosis (MtbΔbioA) is highly attenuated in the guinea pig model of tuberculosis when administered aerogenically as well as intradermally. Immunization with MtbΔbioA conferred significant protection in guinea pigs against an aerosol challenge with virulent M. tuberculosis, when compared with the unvaccinated animals. Booster immunization with MtbΔbioA offered no advantage over a single immunization. These experiments demonstrate the vaccinogenic potential of the attenuated M. tuberculosis bioA mutant against tuberculosis.Owing to the devastation caused by tuberculosis along with the unsatisfactory performance of the Bacillus Calmette–Guérin (BCG) vaccine, a more efficient vaccine than BCG is required for the global control of tuberculosis. A number of studies have demonstrated an essential role of biotin biosynthesis in the growth and survival of several microorganisms, including mycobacteria, through deletion of the genes involved in  Mycobacterium bovis, has been widely administered since 1921. BCG protects children against severe forms of tuberculosis (TB) but demonstrates highly variable efficacy (0–80%) against adult pulmonary tuberculosis in different field trials with poor efficacy in high TB burden countries, in general  as early as 1 week post injection  bacillary load of MtbΔbioA was observed in the organs when compared with BCG at 1 week post inoculation, the bacillary numbers of MtbΔbioA rapidly declined to levels below that of BCG and were undetectable by 6 weeks. However, BCG showed some persistence in the spleen . Guinea pigs were challenged with aerosolized virulent M. tuberculosis Erdman strain at 12 weeks post primary immunization and protective efficacy was evaluated four weeks post challenge. The sham-immunized guinea pigs showed the maximum infection with a bacillary load of 6.85 log10 CFU in the lungs and 5.66 log10 CFU in the spleen  and in the spleen , when compared with sham-immunized controls. MtbΔbioA vaccinated animals exhibited efficient control over the multiplication of virulent M. tuberculosis in the lungs and significantly reduced the bacillary burden by 1.504 log10 CFU (p <0.0001) when compared with sham-immunized animals  in the spleen when compared with the sham-immunized animals , the protection imparted was lower though not statistically different relative to single immunization  as compared to BCG vaccinated animals  average total granuloma score when compared with the animals vaccinated with BCG  when compared with sham-immunized animals  was shown to have contrasting replication capability in mice and primates .The figure depicts representative photographs of lungs, spleen and liver of guinea pigs following aerosol infection with (TIF)Click here for additional data file.


The adequacy of vitamin D intake is necessary to optimize the bone health during the rapid growing phase of infancy. Vitamin D also affects many organs playing an important role in maintaining general health. Vitamin D deficiency may be associated with cardiovascular disease, diabetes, cancer, and autoimmune diseases .The incidence of vitamin D insufficiency and nutritional rickets has decreased in Turkey following the nationwide vitamin D prophylaxis programme undertaken by the Turkish Ministry of Health in 2005. This programme provides free vitamin D drops containing 400 IU daily for all children under 12 months of age . AlthougVitamin D prophylaxis dose might spark a debate in infants for maintaining general health. Further investigations would therefore be needed to clarify the optimal amount of vitamin D supplementation to the infants aged 0-12 months.Peer-review: Internal peer-reviewed.Financial Disclosure: The author declared that this study has received no financial support.


Left ventricular myocardial strain has been described as a potentially useful technique for evaluation and risk stratification of a range of acquired and congenital heart diseases. Tagged acquisition by cardiac MRI has been considered the reference standard for determining myocardial strain; however, this method can be time consuming and the tagged lines may not be visible throughout the cardiac cycle. Tissue Tracking software (Circle Cardiovascular Imaging®) is a post-processing method which allows measurements of myocardial strain based on cine cardiovascular magnetic resonance images without the need for additional sequences. Augustine et al. (JCMR 2013) have previously reported reasonable agreement between Feature Tracking (Tom Tec®) measurements for circumferential strain and tagging. We aimed to perform a similar comparison between Tissue Tracking software and tagging on a small cohort of normal volunteers.Cardiac MRI studies were performed with a 1.5 T unit  on 7 normal volunteers. Short-axis tagged MR images of the left ventricle were analyzed using HARP software  by the same observer, blinded to results of the alternate method. Steady state free precession (SSFP) cine images were analyzed with Tissue Tracking software (Circle Cardiovascular Imaging®) by two observers in consensus. The 2D peak circumferential strain (%) obtained by both techniques were compared using Bland Altman analysis for each of the 16 cardiac segments based on the American Heart Association classification for short axis images.There was reasonably good correlation between tagged acquisition and Tissue Tracking software. A total of 94 data points were included. The Bland-Altman plot is shown in Figure Tissue Tracking software provides a good surrogate for calculating 2D peak circumferential strain (%). A larger cohort is needed to further validate this new capability.


This is achieved by implementing a gallium grading towards the back contact into a CuInSe2 base material. We show that this modification significantly improves the open circuit voltage but does not reduce the spectral response range of these devices. Therefore, efficient cells with narrow bandgap absorbers are obtained, yielding the high current density necessary for thin film multi-junction solar cells.Multi-junction solar cells show the highest photovoltaic energy conversion efficiencies, but the current technologies based on wafers and epitaxial growth of multiple layers are very costly. Therefore, there is a high interest in realizing multi-junction tandem devices based on cost-effective thin film technologies. While the efficiency of such devices has been limited so far because of the rather low efficiency of semitransparent wide bandgap top cells, the recent rise of wide bandgap perovskite solar cells has inspired the development of new thin film tandem solar devices. In order to realize monolithic, and therefore current-matched thin film tandem solar cells, a bottom cell with narrow bandgap (~1 eV) and high efficiency is necessary. In this work, we present CuSe


Cancer cells secrete growth factors that induce proliferation, protect against apoptosis and the immune system or promote neo-angiogenesis . As theyA conceptual problem arises: a non-producer cell can exploit the growth factors secreted by its neighbouring producer cells without paying the cost of production; hence non-producers should have a proliferation advantage and spread in the population. How can intra-tumour cooperation be maintained then? Why do not non-producer mutants drive producer cells to extinction?In some cases, two clones producing one growth factor each can coexist if both are essential, because the two clones depend on each other , similarTargeted therapies aiming at impairing cooperation by blocking growth factors or their receptors  are pron


The goal of this study was to modify the BAC vector pBeloBAC11 so that genomic inserts contained in this vector could be subjected to bidirectional transposon-mediated nested deletions from the wild-type and mutant loxP 2272 site and a XhoI restriction enzyme sequence was designed and inserted at the SfiI restriction site located approximately 200 basepairs upstream of the lacZ gene in pBeloBAC11. Clones containing the desired insert were identified by XhoI restriction digests since an additional band was generated. This transposon-mediated deletion technology allows researchers to identify the boundaries of cis-acting elements and genes.An oligonucleotide containing a mutant  Fir. FirXhoIion Fig.  5]. Alt. AltXhoIe EBNA-1 . Utiliza* cannot be propagated in mammalian cells.pBeloBAC11 loxP


Retained intraocular foreign body (IOFB) is a major cause of visual loss following open globe injuries. Detecting the presence and accurate localization of IOFB in the setting of an open globe injury remains a challenge. There can be various mimics of intraocular IOFB on imaging including air, ocular calcifications, etc. Here, we describe a case of open globe injury wherein a retained perfluoro-n-octane bubble mimicked a retained intraocular foreign body. Retained intraocular foreign body (IOFB) is a major cause of visual loss following open globe injuries. Studies have shown that up to 40 percent of open globe injuries can have retained IOFB . Loss ofTo report a case of open globe injury wherein a retained perfluoro-n-octane bubble mimicked an intraocular foreign body necessitating a second surgery. A 10-year-old boy presented to the emergency with a history of blast injury. His visual acuity at presentation was 6/6 in the right eye and hand movements in the left. Ocular examination showed a full thickness corneal laceration measuring 10 mm passing through the center of the left cornea. He underwent corneal tear suturing with lens extraction as an emergency procedure by the cornea team Figure 1 . IntraopPenetrating injuries with a retained intraocular foreign body are an important cause of blindness among children. Studies have shown that the removal of intraocular foreign bodies within 24 hours from the time of trauma significantly reduces the risk of endophthalmitis . CT scanThis case emphasizes the need to exercise caution when making a diagnosis of an IOFB especially when the contours of the foreign body are smooth and regular.The authors declare that they have no competing interests.


A 58 years old male with a long-standing history of HLA-B27 positive ankylosing spondylitis presented with increasing fatigue and dyspnea on exertion. He had left ventricular dysfunction and enlargement, flail right coronary leaflet of aortic valve with severe eccentric aortic insufficiency along with left ventricular non-compaction in echocardiography. The most common cardiac manifestations of ankylosing spondylitis are aortic insufficiency and conduction disturbances. Involvement of myocardium, in the form of dilated cardiomyopathy and restrictive cardiomyopathy, has also been reported. This case presents a very rare association of ankylosing spondylitis with non-compaction cardiomyopathy. More than half of patients also have peripheral joint involvement or enthesitis.+ ankylosing spondylitis presented with increasing dyspnea on moderate exertion and easy sense of fatigue. His joint pain was controlled effectively with non-steroidal anti-inflammatory drugs. He never smoked and the remaining of his medical history was unremarkable. Family history for cardiac or rheumatologic disorders was negative. On physical exam, he appeared tachycardic with a blood pressure of 135/60 mm Hg. Apical impulse was displaced to left and there was a diastolic murmur and S3 gallop on cardiac auscultation. In transthoracic echocardiography there was left ventricular enlargement with left ventricular end diastolic diameter of 7.2 cm and left ventricular end systolic diameter of 6.1 cm. Left ventricular ejection fraction was 32% (Supplementary Video 1). Right coronary cusp (RCC) of aortic valve (AV) was thick and fibrotic. RCC was flail causing significant defect in coaptation that yielded severe eccentric turbulent jet towards anterior leaflet of mitral valve (Supplementary Video 2). There was also biventricular non-compaction (A 58 years old male with a 16-year history of HLA-B27mpaction . Descend5 Cardiac involvement has long been recognized as an extra-articular manifestation of the disease and presents most commonly with aortic insufficiency and conduction abnormalities.5 Involvement of myocardium also reported, yet is not frequently encountered and remains less well recognized.7 Recently presence of left ventricular asynchrony has been shown in patients with ankylosing spondylitis.6 Cardiac involvement occurs more frequently in long-standing disease however they can precede skeletal symptoms.7 The prevalence of dilated cardiomyopathy in patients with ankylosing spondylitis is under-reported because it symptoms such as dyspnea on exertion may be attributed to the underlying disease. Restrictive cardiomyopathy secondary to amyloidosis has also been rarely been reported in patients with ankylosing spondylitis. Inflammatory processes and ensuing fibrosis have been implicated in the valvular dysfunction and conduction disturbances that associate with ankylosing spondylitis.8 In a recent study on patients with ankylosing spondylitis and no apparent cardiac involvement, increased aortic stiffness and decreased global myocardial performance have been reported which signifies the subclinical cardiac involvement in this group of patients.3Ankylosing spondylitis is a chronic inflammatory disease of the axial skeleton at large that predominantly affects young men.9 It is speculated that left ventricular non-compaction may happen as an adaptive mechanism to certain hemodynamic conditions. Chronic left ventricular volume overload may be a potential trigger for increased trabeculation of myocardium. It is unclear whether left ventricular non-compaction cardiomyopathy has occurred secondary to aortic insufficiency or independently in this patient. The association of non-compaction cardiomyopathy with ankylosing spondylitis remains exceedingly rare.Left ventricular non-compaction may arise from the arrest of trabecular remodeling that happens during early fetal life. It is an uncommon entity that may present in isolated form or in association with other cardiac or systemic conditions. Though it is commonly considered a congenital disorder, the acquired cases have also reported. Right ventricle is involved in less than 50% of cases. Three major clinical manifestations are heart failure, arrhythmias, and systemic embolic events.The local ethics committee approved the study.None.videos 1Click here for additional data file.videos 2Click here for additional data file.videos 3Supplementary file consists of videos 1, 2, and 3.Click here for additional data file.


Semantic dementia (SD) implicates the anterior temporal lobes (ATL) as a critical substrate for semantic memory. Multi-modal semantic impairment can also be a feature of post-stroke aphasia (referred to here as “semantic aphasia” or SA) where patients show impaired regulatory control accompanied by lesions to the frontal and/or temporo-parietal cortices, and thus the two patient groups demonstrate qualitatively different patterns of semantic impairment [1]. Previous comparisons of these two patient groups have tended to focus on verbal receptive tasks. Accordingly, this study investigated nonverbal receptive abilities via a comparison of reality decision judgements in SD and SA. Pictures of objects were presented alongside non-real distracters whose features were altered to make them more/less plausible for the semantic category. The results highlighted a number of critical differences between the two groups. Compared to SD patients, SA patients: (1) were relatively unimpaired on the two alternative forced choice (2AFC) decisions despite showing a comparable degree of semantic impairment on other assessments; (2) showed minimal effects of the plausibility manipulation; (3) were strongly influenced by variations in the regulatory requirements of tasks; and (4) exhibited a reversed effect of familiarity–i.e., better performance on less commonly encountered items. These results support a distinction between semantic impairments which arise from impaired regulatory processes  versus those where degraded semantic knowledge is the causal factor . SA patients performed relatively well because the task structure reduced the requirement for internally generated control. In contrast, SD patients performed poorly because their degraded knowledge did not allow the fine-grained distinctions required to complete the task.


Hemidiaphragm paralysis secondary to phrenic nerve palsy is a well-recognised medical condition. There are few case reports in the literature documenting resolution of hemidiaphragm paralysis following cervical spine surgery. This case report documents our experience with one such case.  A 64-year-old man was referred to the orthopaedic service with right hemidiaphragm paralysis. He had a previous history of asbestos exposure and polio and was initially seen and investigated by the respiratory physicians. He also reported intermittent neck pain and an MRI scan showed right-sided cervical foraminal stenosis. He underwent posterior right C3/4 and C4/5 foraminotomies, and by three months postoperatively, his hemidiaphragm paralysis had resolved and his shortness of breath had also improved.  This report documents a unique case of resolution of hemidiaphragm paralysis following posterior unilateral cervical foraminotomies. The phrenic nerves (C3/4/5) supply motor function to the hemidiaphragms. The motor supply of each hemidiaphragm comes purely from the phrenic nerves, and so conditions affecting the phrenic nerve or its nerve roots cause hemidiaphragm paralysis. Hemidiaphragm paralysis secondary to phrenic nerve palsy is a well-recognised medical condition with multiple causes. However, there are few case reports in the literature documenting resolution of hemidiaphragm paralysis following the cervical spine surgery. The cases that have previously been described involve patients with concomitant tetraparesis treated with spinal cord decompression with or without foraminotomies. This case report documents resolution of hemidiaphragm paralysis and improved respiratory function with unilateral cervical nerve root decompression alone, a finding that has not previously been described.A 64-year-old man was referred to the orthopaedic service with right hemidiaphragm paralysis. He had initially presented to his general practitioner reporting subjective shortness of breath after stand-up paddleboarding. His past medical history was significant for asbestos exposure and polio. Chest radiograph revealed an elevated right hemidiaphragm Figures  and 2. AThe underlying cause for his hemidiaphragm paralysis, whether it was related to his cervical foraminal stenosis or postpolio syndrome, was indeterminant .After obtaining multiple subspecialist opinions, a decision was made to proceed with posterior right C3/4 and C4/5 foraminotomies accepting that this may not have any effect on his shortness of breath. Surgery proceeded uneventfully as did postoperative recovery. By three months postoperatively, his hemidiaphragm paralysis had completely resolved on chest radiograph, and his shortness of breath had also improved . CompariThe phrenic nerve originates from cervical nerve roots C3–5 with the dominant supply coming from C4. The phrenic nerves are the sole motor supply to the hemidiaphragms and also provide proprioceptive fibres to the central part of each hemidiaphragm. Common causes of phrenic nerve palsy include idiopathic, malignancy (primary lung tumour or metastatic disease), trauma , neuromuscular disease (polio or multiple sclerosis), inflammation (pneumonia or HSV), brachial plexus palsies, and direct compression (aortic aneurysm). However, the aetiology of diaphragmatic paralysis remains unidentified in more than two-thirds of patients .It is possible that these idiopathic cases are caused by unidentified nerve root compression in the cervical spine. Poliomyelitis can result in the degeneration of the anterior horn cells, innervating both hemidiaphragms and the accessory respiratory muscles. Additional damage to the axons of the surviving anterior horn cells as a result of nerve root compression may result in clinically significant respiratory dysfunction as was evident in this patient.Acute dyspnoea secondary to diaphragmatic paralysis can also occur following minor cervical trauma. Parke and Whalen described two patients with severe cervical myelopathy who developed respiratory insufficiency related to phrenic nerve palsy after cervical manipulation . Merino-Respiratory compromise is a known complication of acute cervical spinal cord injury but rarely is it considered in less acute settings such as in cases of degenerative cervical spondylosis.There are few case reports in the literature documenting resolution of diaphragmatic paralysis due to cervical nerve root compression following cervical spine surgery. Hayashi et al. reported on a 64-year-old man with dyspnoea who had bilateral hemidiaphragm paralysis secondary to cervical spondylosis . Buszek There are numerous studies in the literature that show impaired respiratory function in patients presenting with cervical pathology. Ishibe and Takahashi compared 84 patients with cervical pathology with an age-matched control group of patients without cervical pathology and found that those in the cervical group had significantly lower respiratory function  . Within Similar to other case reports in the literature, this report documents a case of resolution of right hemidiaphragm paralysis following C4 and C5 nerve root decompression via posterior cervical foraminotomies (C3/4 and C4/5 levels), a finding not previously described. Although rare, cervical nerve root compression as a cause of phrenic nerve palsy should be considered in patients presenting with hemidiaphragm paralysis and respiratory symptoms as surgical management can result in resolution of paralysis and potential improvement in respiratory symptoms.


Small interfering RNA (siRNA) duplexes are short  double-stranded RNAs (dsRNAs) with several overhanging nucleotides at both 5′- and 3′-ends. It has been found that siRNA duplexes bind the RNA-induced silencing complex (RISC) and cleave the sense strands with endonucleases. In this study, for the first time, we detected siRNA duplexes induced by plant viruses on a large scale using next-generation sequencing (NGS) data. In addition, we used the detected 21 nucleotide (nt) siRNA duplexes with 2 nt overhangs to construct a dataset for future data mining. The analytical results of the features in the detected siRNA duplexes were consistent with those from previous studies. The investigation of siRNA duplexes is useful for a better understanding of the RNA interference (RNAi) mechanism. It can also help to improve the virus detection based on the small RNA sequencing (sRNA-seq) technologies and to rationally design siRNAs for RNAi experiments. RNA interference (RNAi) is a cytoplasmic cell surveillance system that recognizes double stranded RNAs (dsRNAs) and specifically destroys single and double stranded RNA molecules homologous to the dsRNA inducers, using small interfering RNAs (siRNAs) as guides . The abuOne important class of RNA fragments related to RNAi is siRNA duplexes, which contain perfectly base-paired regions with 2 nucleotide (nt) 3′-end overhangs. Previous studies have shown that siRNA duplexes of 21–23 nt are the sequence-specific mediators of RNAi and post-transcriptional gene silencing (PTGS) . The actSince plant RNAi produces abundant siRNA duplexes and the mechanism of plant RNAi is comparatively clear, in this study we detected siRNA duplexes induced by plant viruses and analyzed their features. As far as we know, this is the first time siRNA duplexes have been detected and analyzed on a large scale using NGS data. This study aims to provide useful information for a better understanding of the RNAi mechanism. The analysis of siRNA duplexes can be used to improve the virus detection using sRNA-seq data and to rationally design siRNAs for RNAi experiments .Fourteen complete viral genomes including 17 nucleic acid sequences under the NCBI GenBank accession numbers JQ314457 , KT63405x–nt duplex (x represents the duplex length) proportion is calculated as the read count of x–nt siRNA duplexes with 2 nt overhangs divided by the count of viral reads. The program duplexfinder was developed to detect siRNA duplexes [The cleaning and quality control of sRNA-seq data were conducted using the pipeline Fastq_clean  that hasduplexes . Statistduplexes .All 17 viral genome sequences had genome coverages of more than 99% and average depths  varied fDrosophila melanogaster embryo lysates [Drosophila in vitro system [To reduce the statistical bias, we used seven nucleic acid sequences with higher average depths from four viruses to detect and analyze siRNA duplexes. The duplex lengths from 15 to 50 nt and the overhang lengths from 0 to 6 nt were used as parameters to count the duplex reads in the sRNA-seq data A. The re lysates . Among to system . These rIn this study, we also found genome coverages of the seven viral sequences calculated using aligned 21 nt siRNA duplexes with 2 nt overhangs were close to the genome coverages calculated using all aligned reads . IdenticBased on the detection results from the seven viral sequences, we constructed a dataset including 20,415 pairs of 21 nt siRNA duplexes with 2 nt overhangs for further analysis . Using tAnother controversial topic in RNAi studies is whether the RISC contains single- or double-stranded siRNAs. Previous studies have introduced a debate on the symmetry between sense and antisense strands of siRNAs . Using t


Pulmonary arterial hypertension (PAH) is a life limiting disorder resulting in progressive right heart (RV) failure. Cardiac MRI is the reference standard for RV assessment in PH and has known prognostic value in children. Symptoms of PAH are exacerbated or become apparent with exercise and cardiopulmonary exercise testing (CPET) is also prognostic in PAH.2. A combined approach using MR-CPET could provide a more sensitive method of assessing disease severity, the causes of exercise limitation and response to treatment. In this study we assessed the utility of MR-CPET in children with PAH.We have recently demonstrated the feasibility of MR augmented CPET (MR-CPET) in healthy adults. Using the Fick principle MR-CPET allows calculation of tissue oxygen extraction ΔcO10 Children with PAH aged 8 to 16 years  and 10 healthy volunteers matched for age and sex underwent MR-CPET. Exercise was performed on a MRI compatible ergometer  CPET data was collected using a commercial respiratory gas-analyser  with a modified MR compatible sampling umbilical.Resting and peak exercise ventricular volumes and septal curvature were measured using a radial k-t SENSE real time sequence. Aortic flow was simultaneously continuously measured using a previously validated real-time UNFOLD-SENSE spiral PCMR sequence.MR data was used to derive CO, HR and SV curves during exercise. Arteriovenous oxygen content gradient (AVO2) curves (a measure of tissue oxygen extraction) were calculated by dividing the VO2 and CO curves Figure . RestingSubjects also completed a six-minute walk test, experience survey and exercise history.2 was significantly lower in the PAH group. This seems to be driven by both reduced tissue oxygen extraction and cardiac output although only reduced ΔcO2 was of statistical significance. MR-CPET measures at rest and exercise are shown in Figure All children successfully completed the test without complication.Peak VORVEF was significantly lower in the PAH group both at rest and at peak exercise.There was a significant difference in the increase in estimated mPAP between the control and PAH groups. There was no significant difference in 6-minute walk test distance between the groups.MR-CPET is well tolerated in both healthy children and children with class I/II PAH. This study demonstrates that exercise intolerance in children with PAH is in part due to reduced tissue oxygen extraction and may open possibilities to study new pharmacological or exercise based therapeutic strategies.


This research investigated the contribution of the dorsolateral prefrontal cortex (DLPFC) in the attentional resources in episodic encoding for both verbal and non-verbal material. Paired-pulse transcranial magnetic stimulations (TMS) were used to interfere transiently with either the left or right DLPFC during encoding under full attention (FA) or under divided attention (DA) in a recognition paradigm using words and random shapes. Participants recognized fewer items after TMS over the left DLPFC than over the right DLPFC during FA encoding. However, TMS over the left DLPFC did not impair performance when compared to sham condition. Conversely, participants produced fewer items after TMS over the right DLPFC in DA encoding compared to sham condition, but not compared to TMS over the left DLPFC. These effects were found for both words and random shapes. These results suggest that the right DLPFC play an important role in successful encoding with a concomitant task regardless of the type of material.


Regenerative medicine is challenged by the need to conform to rigorous guidelines for establishing safe and effective development and translation of stem cell-based therapies. Counteracting widespread concerns regarding unproven cell therapies, stringent cell-based assays seek not only to avoid harm but also to enhance quality and efficacy. Potency indicates that the cells are functionally fit for purpose before they are administered to the patient. It is a paramount quantitative critical quality attribute serving as a decisive release criterion. Given a broad range of stem cell types and therapeutic contexts the potency assay often comprises one of the most demanding hurdles for release of a cell therapy medicinal product. With need for improved biomarker assessment and expedited measurement, recent advances in graphene-based biosensors suggest that they are poised to be valuable platforms for accelerating potency assay development. Among several potential advantages, they offer versatility for sensitive measurement of a broad range of potential biomarker types, cell biocompatibility for direct measurement, and small sample sufficiency, plus ease of use and point-of-care applicability. A wide range of novel Advanced Therapy Medical Products (ATMP) have been pursued intensively over the last decade. In addition to gene therapy medical products (GTMP) and tissue-engineered products (TEP), the application of stem cells has driven extensive research into somatic cell therapy medicinal products (CTMPs). Although the number of ATMPs in the centralised European Union (EU) Marketing Authorization (MA) phase has been described as low , 2, a nuWith regard to stem cell-based therapies, our growing understanding of one of the most actively investigated cell types, commonly known as human “mesenchymal stem cell” (hMSC), is fostering debate. Arising from studies of nonhematopoietic human bone marrow stromal cells (hBMSC), an authoritative view is that tissue-specific stem/progenitor cells, a subset of which are skeletal stem cells, are not to be confused with similarly named “hMSC” derived from other tissue sources, especially for regeneration of bone or cartilage tissue . Rather,Complementing progress in understanding the diversity of stem cells are advances in large-scale production of therapeutic cells, including bioreactor systems for mesenchymal stem cells . Cell exAmong key requirements for cell-based therapy for regenerative medicine, current guidelines stipulate identity, safety , purity,The challenges to potency assay development are many: (i) inherent heterogeneity in the starting cell population; (ii) a limited cell product lot size and amount available for testing; (iii) limited viability and stability of cellular products; (iv) the difficulties in establishing the mechanism of action (MOA) considering the numerous intrinsic factors and active components; (v) the potential for both positive or negative interactions among active components; (vi) the difficulty of establishing reference standards; (vii) additional complexity if biomaterials are involved; (viii) the difficulty of accurately predicting the in vivo fate from external measurements made before cell administration to the patient.For the widely used hBMSC, starting material heterogeneity concerns not only identity and parity with minimal defining criteria , but alsNotably, clinical study data is not of practical use for establishing the potency assay. The potency assay predicts ability to cause functional effect rather than clinical effectiveness or outcome and needs to be capable of defining individual product lot release criteria. The emerging apparent contradiction is that potency assays benefit from being highly sophisticated yet technically simple. To date, many potency assays rely on definitive end points that match relatively clear phenotypes such as cell proliferation, differentiation, cell death, and ability to induce angiogenesis. Not all traditional assays measuring these phenotypes are necessarily equivalent however, especially for diverse therapeutic cell types and indications. Whereas proliferation may be a phenotype considered useful for evaluating the potency of autologous hematopoietic stem cells for bone marrow transplantation, interlaboratory reproducibility of commonly performed colony forming unit (CFU) assays is problematical . Sample Understandably, the high costs and investigative time needed for developing a suitable potency assay for cell-based products has hindered entry of biologicals into phase III or IV clinical trials. A potency assay needs to be one of the first considerations for any CTMP, yet there is currently a marked discrepancy between the number of phase I/II clinical safety trials and phase III or IV clinical trials that require a validated potency assay . For exa2 can suffice to cover the entire corneal surface of the patient's affected eye. Corneal epithelium that would otherwise be irrevocably damaged is replaced with epithelium with a reservoir of continually regenerating limbal stem cells that provide long-term normal corneal function. Marketing approval came eighteen years after initial proof-of-principle success in two patients [bright expression in the stem cell nuclei of holoclones could be linked to a good clinical outcome. Providing a potency reference, it was found that among the total number of clonogenic cells, presence of >3% holoclone-forming limbal stem cells correlated with successful transplantation [bright cells could serve as a key potency assay biomarker for this cell-based therapy.The first stem cell-based ATMP therapy granted marketing authorization by EMA, Holoclar, treats severe trauma induced limbal stem cell deficiency (LSCD) in adults . A recompatients  and a 20patients . Productantation . Thus, qSeveral other stem cell CTMP have resorted to quantitative ELISA methods in potency assays. Multistem®; an adult allogeneic bone marrow-derived product has shown beneficial effects in animal models of ischemic injury. For potency assays regarding complex indications, when an authentic bioassay is not feasible, surrogate in vitro assays identify biological activity analytically by correlation to a relevant product-specific causal activity. Angiogenic factors secreted by Multistem multipotent adult progenitor cell (MAPC) populations, measured by enzyme-linked immunosorbent assay (ELISA) correlated with induction of tube formation by endothelial cells in vitro for a proposed quantitative potency assay with predefined accept/reject criteria . A more α (IL2Rα) expression on activated T cells. Quantitative metrics included a concentration of at least 13 pg TNFR1 per million MSCs and the ability of inhibiting at least 30% of IL2Rα expression in cocultured CD3/CD28-activated peripheral blood mononuclear cells (PBMCs) relative to control was considered sufficient in order to induce the desired therapeutic effect [An effective surrogate potency measure for the immunoregulatory activity of the Osiris Bone marrow adult mesenchymal stem cell product Prochymal™ was an ELISA measure of tumor necrosis factor receptor 1 (TNFR1) levels in the cell therapy product, in combination with a qualitative measurement of the inhibition of the interleukin 2 receptor c effect .NCT03280056). Notably, microRNA profiling of MSC-NTF cells could distinguish them from matched origin MSC, characterisation that could be useful for a potency assay if biological response is dependent on a threshold number of MSC-NTF cells [The product NurOwn® consists of autologous ex vivo-propagated bone marrow-derived MSCs induced to secrete neurotrophic factors (MSC-NTF cells), currently undergoing a phase III clinical trial for the treatment of Amyotrophic Lateral Sclerosis (ALS). Biomarkers quantified for this stem cell-based therapy product include cell-secreted neurotrophic factors, inflammatory factors, and cytokines in the cerebrospinal fluid (TF cells .NCT02730299). An effective measurement of biological effect for this product was the time for neutrophil engraftment following transplantation [The NiCord® product consists of a cryopreserved stem cell product consisting of allogeneic ex vivo-expanded umbilical cord-derived hematopoietic CD34+ progenitor cells and the noncultured cell fraction of the same cord blood unit. Current phase 3 clinical trials include treatment of hematological malignancies such as acute lymphoid leukemia or myelodysplastic syndrome , hypertrophic pseudoarthrosis of long bones (NCT02230514) and femoral head osteonecrosis (NCT01605383). The product PneumoStem® consists of allogeneic ex vivo-expanded human umbilical cord blood-derived MSCs currently in phase 1/2 clinical trials for the prevention of bronchopulmonary dysplasia in premature infants (NCT02381366), as well as a phase II clinical trial for the treatment of intraventricular hemorrhage (NCT02890953). The results of these trials will be important to evaluate the safety and effectiveness of this approach [NCT02504619) plus severe aplastic anemia and myelodysplastic syndrome (NCT03173937). The product NeuroStem® consisting of allogeneic human umbilical cord-derived MSCs is undergoing phase 1/2 clinical trials for the treatment of Alzheimer's disease (NCT02054208). The product CartiStem®, allogeneic ex vivo-expanded umbilical cord blood-derived MSCs in combination with sodium hyaluronate, is under evaluation in two parallel clinical trials for the treatment of knee chondral defects (NCT01733186) and osteoarthritis (NCT01041001). Although a particular potency assay was not described and biological activity including inhibition of proinflammatory cytokines is poorly characterised, long-term benefit has been reported [Numerous other stem cell-containing cell-based therapy products are currently pending market approval or are undergoing clinical trial evaluation. Notably, the respective definitive potency assays are either proprietary or still a work in progress. Nonetheless, they serve as good examples for considering the scope of applications where graphene-based biosensors might be helpful in early stages of cell therapy development. The blood and tissue bank of Catalonia product XCEL-MT-OSTEO-ALPHA, representing autologous ex vivo-expanded MSCs fixed in allogeneic bone tissue, is currently being tested in phase 1/2 clinical trials for the treatment of spinal fusion  for cell product manufacture . Existinα [γ [Although ELISA and PCR-based quantification seem to be the methods of choice in the current development of stem cell-based products due to their outstanding detection limits, the challenge of guaranteeing high quality measurements is increasingly being met by progress in biosensor design. Various functionalized forms of graphene and nanocomposites  can be uα  and IFN-α [γ ) or apopα [γ ), and plα [γ ). Grapheα [γ .This versatility can help advance development of novel potency assays for future stem cell-based products . GraphenStem cells are characterised by a capacity for both self-renewal and asymmetric division that produces one identical daughter stem cell and a second distinct daughter cell equipped with the potential to commit to a lineage-specific differentiation program . Found iConsistent with providing improved conditions for monitoring stem cell performance, 3D GO-encapsulated gold nanoparticles could serve as nondestructive biosensors of neural stem cell (NSC) differentiation potential. An intrinsic property of graphene is enhanced adherence to molecules that contain aromatic structures. Highly unsaturated metabolites are predominant in undifferentiated stem cells so that Raman spectroscopy peaks of undifferentiated NSC on GO-encapsulated gold nanoparticles were 3.5 times higher than peaks obtained from control metal structures and clearly distinguishable from peaks obtained using differentiated cells that oxidize the metabolites upon differentiation . Given tNanomaterials may be particularly useful in enabling more specific measurements in vivo and this may help bridge the in vitro/in vivo divide, so that what is measured in vitro during cell expansion is genuinely more relevant for the desired therapeutic approach. Graphene oxide can be incorporated in a number of nanocomposites to serve as a platform that enhances electrical properties for biosensing applications in vivo . The uniAs highlighted by the examples above, among the enhanced healing qualities required from cell-based therapies , the fol−1 [For a definitive assay, cell death is a great endpoint. Governing the process of apoptosis or programmed cell death, a cascade of molecular events usually activates a cysteine-dependent aspartate directed protease (caspases), an enzyme family with multiple roles in regulating stem cell properties . GO coul−1 . Two pro−1 .Demonstrating the versatile manner by which graphene platforms can be used to detect potency assay-relevant molecules, a number of different biosensor types have been developed for the angiogenic growth factor VEGF. A field-effect transistor (FET) electronic platform conjugated with VEGF-specific RNA aptamers could recognize target molecules at an unprecedented 100 fM concentration . Alterna−1, with a low detection limit of 1.6 pg mL−1, and good reproducibility and stability, qualities that are key for good potency assays.Stem cell integration in tissues was not only critical for successful corneal recovery using limbal epithelial stem cells but was also found to be important for mesenchymal stem cells in cementogenesis, a process establishing regeneration of cementum for anchoring teeth to alveolar bone. Sorting periodontal ligament cells according to CD146 expression could homogenize cultures and enrich cells with high colony forming potential, capable of subsequently resurfacing dentin with a newly formed cementum-like layer, allowing improved integration in the dentin surface . ModifyiμL of plasma without sample processing [Immunomodulatory mechanisms achieved by mesenchymal stem cells remain to be investigated  and it iocessing .Bone repair is an intensively explored regenerative application for the most commonly employed hBMSC cell type under investigation in clinical trials. Cellular products in the form of allografts containing mesenchymal stem that are currently evaluated for safety and efficacy in many phase I/II clinical trials will require suitable potency assays for progression to subsequent clinical trial phases. Enhanced osteogenesis serves as a prime example where graphene-based biosensors present favourable qualities for improving potency assay development. New quantifiable gene expression biomarker candidates are emerging , 77 withAn important aspect for any potency assay is that it should fit cell expansion timelines and thus fast analysis is advantageous. The potency assays proposed by Murgia et al.  involvedDepending on the nature of the envisioned detection platform, integrating graphene with sustainable production methods will be important for obtaining highly reproducible molecular interactions with biological molecules . VariousGraphenic species are being tested to achieve market grade novel inks for 3D printing applications  and meanThe burgeoning number of stem cell clinical trials requiring a potency assay provides an excellent opportunity for advanced biosensor design to address valuable clinical applications pragmatically within a preclinical context. The versatility of graphene-based biosensors is well suited for the complex nature of potency assays that will be very specific for each therapeutic application. Different versions of graphene allow prospects for a choice of sensor types, especially given successful fabrication of nanoparticle composites allowing the electrochemical characteristics of graphene to enhance specialized sensing platforms. Graphene oxide presents advantages for water dispersion, biocompatibility, and versatile surface modification and electrochemical transduction of the signal allows miniaturization. This can help establish assays suited to limited cell product lot sizes and facilitate measurement prior to administration with point-of-care tools. Particular advantages for potency assays are likely to be derived from appreciating that stem cells are highly responsive to microenvironments; thus surrogate assays based on closer mimicry of the therapeutic situation are likely to provide better correlative measurement of potency biomarkers . Graphen


Vascular closure devices provide a safe and cost-effective method to achieve rapid hemostasis and early ambulation after angiographic procedures. Rarely, they can result in arterial injury with resultant stenosis or acute arterial closure requiring open surgical intervention. We report an Angio-Seal® vascular closure device-induced acute arterial closure successfully treated percutaneously with the SilverHawk® plaque excision system. This report discusses the possible mechanisms of Angio-Seal® induced arterial occlusion and various percutaneous options for treatment. Vascular closure devices (VCD) are increasingly used in place of manual compression to provide rapid hemostasis and early ambulation after angiographic procedures. They have been shown to reduce hospital stay and have been demonstrated to be cost-effective -2. AlthoA 60-year-old Caucasian female with a history of coronary artery bypass surgery, diabetes mellitus, dyslipidemia, and chronic tobacco use was admitted to the hospital with Rutherford Class III exertional claudication in the bilateral hips and buttocks. Non-invasive workup, including a duplex sonogram, demonstrated distal aortic stenosis involving the aortoiliac bifurcation. She underwent an abdominal aortogram with bilateral lower extremity arterial run-offs. During the procedure, vascular access was obtained with #6 French short sheath, which was advanced into the right common femoral artery without complications. The arteriograms confirmed the presence of a distal aortic 70% calcific stenosis with the plaque involving the ostia of both common iliac arteries. The run-off vessels bilaterally were without significant stenosis. A staged percutaneous procedure was planned. An Angio-Seal® device was deployed successfully after an angiogram confirmed suitability for device placement Figure . Immediately after the Angio-Seal® deployment, the patient developed leg discomfort with the loss of arterial pulses in the right leg. A duplex scan confirmed acute occlusion of the right common femoral artery (CFA). Immediate vascular access was obtained at the contralateral (left) CFA and an angiogram of right CFA confirmed a total occlusion Figure . A #7 FrTM filter device placed at the distal SFA. With multiple passes, the lesion was shaved off resulting in no significant residual stenosis  Anchor-induced dissection resulting from the dragging of the anchor along the arterial inner wall during deployment; 2) thrombosis induced by the intraluminal anchor or a portion of the collagen plug that prolapsed into the lumen; and 3) plaque rupture from device-induced trauma, resulting in worsening stenosis at the deployment site. The traditional management for VCD-induced vessel stenosis/occlusion is open surgery and has been well-described . BalloonIn the case presented, balloon angioplasty provided temporary relief likely because the local thrombogenic stimulus with anchor plug/ prolapsing collagen plug and associated dissection flap was still present intraluminally. The SilverHawk® atherectomy system was chosen with the thought that the atherectomy would remove the inciting stimulus (the plug or the anchor) as well as also any dissection flap, if present, and minimize the need for a stent in this unfavorable location. Furthermore, a failed atherectomy would likely not compromise a future open surgical repair.A distal filter device is strongly recommended to prevent the risk of distal embolization with the use of this atherectomy system -8. In thThe use of an Angio-Seal® VCD may rarely result in an acute closure of the artery. Such a stenosis/occlusion may not be treated successfully with angioplasty alone. Although surgical intervention has been the traditional treatment, SilverHawk® plaque excision system can be used successfully and, thus, avoid open surgical repair. However, the use of a distal protection device is strongly recommended.


Biological Psychiatry, Steven Woltering and colleagues demonstrate that children with externalizing behaviors who respond to cognitive behavioral therapy show electroencephalogram-defined neural markers of improved self-regulation  parent management training interventions to reward prosocial behaviors and to extinguish negative behaviors and (2) improving executive functioning through skills training and coaching, psychoanalytic approaches promote emotion regulation through communicating to the child the self-protective meanings of negative behaviors. This intervention alongside developmental help scaffolds the child’s development of alternative emotion regulation capacities . As bothWoltering and colleagues’ study provides a model for exploring this hypothesis. This study recruited 140 children aged 8–12 from outpatient treatment agencies with scores on the externalizing scale of the Child Behavior Checklist  within All children then engaged in an evidence-based cognitive behavioral therapy program with an integrated parent management training . This pThe Child and Adolescent Functional Assessment Scale  was appSeventy-one of the original 140 participants completed the treatment with usable data. Fifty-five percent (39 completers) were treatment non-responders, and 45% (32 completers) were responders. Non-responders, responders, and 24 age-matched children recruited from the community then repeated the go/no-go task under EEG.Treatment responders, but not non-responders, showed reductions in posttreatment relative to pretreatment EEG in needed cortical resources to regulate impulsive behavior during the go/no-go task. Specific findings included, a reduction in the magnitude of the N2 component of the event-related potential (ERP), a defined waveform associated with inhibition of prepotent responses , 15. ThiThis study suggests that successful as opposed to unsuccessful treatment normalizes aberrant biomarkers of executive functioning in children with externalizing behaviors and are associated with improved executive function performance on a go/no-go task.The study of ERPs is an ideal neurobiological modality to bridge the theoretical executive function and emotion regulation literature. Several studies examine ERPs in children with externalizing behaviors as both a neural correlate of emotion regulation , 17–19 aContemporary child psychoanalytic psychotherapy involves the interpretation of children’s defenses against unwelcome affects , 21–23. An 8-week manualized psychoanalytic approach to children aged 6–12 with externalizing behaviors organized around defense analysis  is underThe author confirms being the sole contributor of this work and approved it for publication.The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


The pattern of glomerular disease in adults varies considerably across the globe and haschanged within same geographical regions and clinical settings. Diagnosis of glomerularlesions on basis of biopsy remains a standard approach.The pattern of glomerular disease in adults varies considerably across the globe and has changed within same geographical regions and clinical settings. Diagnosis of glomerular lesions on basis of biopsy remains standard despite arguments of margins of error related with sampling in random fashion. Focal segmental glomerulosclerosis (FSGS) which emerged as separate clinic-pathological entity in 1970s has been reported commonest pattern in glomerular pathology  ExistencDuring last four decades IMN reported most common cause of nephritic syndrome in adults worldwide . Debate IgA nephropathy once reported most frequent cause of glomerulonephritis among patients who undergo renal biopsy. Prevalence of IgA nephropathy to some extent seems to be influenced by policy of proceeding with renal biopsy in all patients coming with microscopic hematuria . In our Minimal change disease (MCD) is less frequent cause of glomerular disease in adults; we have reported 5.8% adults biopsied for nephritic syndrome, acute nephritic syndrome, non-nephritic proteinuria, rapidly progressive glomerular disease and isolated hematuria . Study pSurprisingly FSGS remains very low on list in present study only 6.5% had FSGS as causative pathology. We have reported primary FSGS as most frequent pathological lesion in our studied population which happened to be a large group of 1793 patients. Recently over last 18-20 months we have observed sudden rise in mesangiocapillary pattern in our biopsy population of adult patients (unpublished data).The present study by Modugumudi et al  also claRN was the single author of the manuscript.The author declared no competing interests.Ethical issues  have been completely observed by the author.None.


Tissues within the dipolar field of superparamagnetic contrast agents experience a frequency shift that enables positive contrast MRI with acquisition schemes using on-resonant saturation Figure . The admA cylindrical tube containing a concentrated suspension of 19 nm SPIONs was placed alongside the upper leg in human volunteers Figure , causingThe off-resonance area was selectively excited and visualized with a 0 s delay time Figure . Spins wFlow imaging with iron induced spin tagging (FLIRT) was achieved using external SPIONs which targeted the positive labeling of moving protons. The feasibility of this method was shown in vivo with preliminary data obtained in human volunteers. It allows for flow visualization in the vicinity of ferrimagnetic objects without contrast injection.


We evaluated the influence of pack stock  use on meadow plant communities in Sequoia and Yosemite National Parks in the Sierra Nevada of California. Meadows were sampled to account for inherent variability across multiple scales by: 1) controlling for among-meadow variability by using remotely sensed hydro-climatic and geospatial data to pair stock use meadows with similar non-stock (reference) sites, 2) accounting for within-meadow variation in the local hydrology using in-situ soil moisture readings, and 3) incorporating variation in stock use intensity by sampling across the entire available gradient of pack stock use. Increased cover of bare ground was detected only within “dry” meadow areas at the two most heavily used pack stock meadows . There was no difference in plant community composition for any level of soil moisture or pack stock use. Increased local-scale spatial variability in plant community composition (species dispersion) was detected in “wet” meadow areas at the two most heavily used meadows. These results suggest that at the meadow scale, plant communities are generally resistant to the contemporary levels of recreational pack stock use. However, finer-scale within-meadow responses such as increased bare ground or spatial variability in the plant community can be a function of local-scale hydrological conditions. Wilderness managers can improve monitoring of disturbance in Sierra Nevada meadows by adopting multiple plant community indices while simultaneously considering local moisture regimes. High elevation meadows are a vital ecological component of mountain systems throughout western North America. They provide critical habitat for wildlife , 2, suppThe biophysical characteristics of meadows in the Sierra Nevada are highly variable, especially related to hydrologic regimes and associated plant community types . In the Here, we assessed meadow plant community responses to pack stock use while simultaneously controlling for multi-scale environmental factors known to influence variability of meadow hydrology and plant community structure. Specifically, we asked whether current levels (2004–2009) of pack stock use influence: total vegetation cover and bare ground, plant community composition, and local-scale spatial variability in plant community composition. We used a multi-step approach to: 1) control for large-scale, among-meadow variability by matching pack stock use meadows with non-pack stock reference meadows from a comprehensive database of remotely sensed estimates of hydro-climatic and geospatial attributes; 2) control for within-meadow variation in local hydrology by measuring in-situ soil moisture in all sampling plots and stratifying analyses by vegetation grouped to specific moisture regimes; and 3) control for variation in intensity of pack stock use by sampling across a large gradient in reported use.Pinus contorta), rocky outcrops, and scrub vegetation types interspersed with highly diverse and productive meadow habitats [The study was conducted in subalpine meadows within the Sequoia National Park section of the jointly managed Sequoia & Kings Canyon National Parks (SEKI) and Yosemite National Park (YOSE) in the Sierra Nevada, California . Researchabitats . The SieCarex scopulorum, Calamagrostis muiriana) and forbs , interspersed with moss in the understory. Subalpine meadows are also used by native herbivores including mule deer , voles (Microtus spp.), and pocket gophers (Thomomys spp.).Subalpine meadows generally occur at perennially wet locations where ground water is at or near the surface , and plaPack stock use in Sierra Nevada meadows offers an opportunity to investigate the role of disturbance on plant communities at a scale relevant to management. Many of the meadows used by pack stock occur within National Parks, where meadows are free from confounding influences of other domestic livestock, such as cattle or sheep grazing. And unlike many cattle grazing practices, pack stock use within meadows occurs intermittently throughout the summer season as groups travel through . Pack stTo understand if meadow plant communities were affected by stock use, we paired pack stock meadows to non-stock meadows using an ensemble of biophysical, geospatial, and hydro-climatic remote sensing data, which allowed us to compare sites that theoretically should have similar ecological conditions. Pack stock meadows were any meadow that received reported pack stock use within the past decade, whereas non-stock meadows had no reported pack stock use from any time period. The pool of potential meadows to select from was identified using park-wide meadow GIS layers . Use recThe twenty candidate stock meadows with highest number of stock nights from each park were matched to non-stock meadows, using the package ‘Matching’  in the RThe three highest ranked matched reference meadows were visited and assessed qualitatively based on similarities in meadow size, landscape position , elevation and proximity with the matched stock meadow. The one deemed the best match was then selected as the non-stock  meadow for sampling. This resulted in every stock meadow having one sampled non-stock control meadow totaling to 22 matched pairs, with 14 pairs (14 stock/14 non-stock) sampled during the 2011 and 2012 growing seasons in YOSE and 8 pairs (8 stock/8 non-stock) sampled during the 2012 growing season in SEKI. The YOSE meadows ranged in size from 1.15–22.14 ha with an average meadow size of 5.90 ha, and SEKI meadows ranged in size from 0.42–10.62 ha with an average meadow size of 2.60 ha. The maximum number of stock nights in a single year varied widely during 2004–2009: 10–577 stock nights in YOSE, with an average of 134 per year; and 82–271 stock nights in SEKI, with an average of 155 per year.2) sampling plots were established at 20 m intervals. Ocular aerial estimates of the total vegetation cover (%), litter cover (%) and exposed mineral soil cover  were recorded within each plot. Plant species composition was sampled at every third sampling plot along each transect with ocular aerial estimates of cover by species in eight 25 x 25 cm sub-plots arranged systematically within each 4 m2 plot. Soil moisture was recorded at every 4 m2 plot as volumetric water content (VWC) using a Field Scout Time Domain Reflectometer 100 soil moisture probe  to a depth of 12 cm. Readings were taken within 10 cm of the inside of each corner as well as the center of each plot. The soil VWC values were averaged within each plot.Each meadow was sampled once during the peak summer growing season (June–August). Sampling occurred along 5-m wide belt transects spaced 40 m apart, running across the meadow width, perpendicular to the main meadow drainage. Along the centerline of each belt transect, 2 x 2 m (4 mClassification and Regression Tree (CART) analyses were used  as a noThree metrics were used as response variables: bare ground, species dissimilarity and species dispersion:r = -0.65; and bare ground and vegetation plus litter cover, Pearson’s r = -0.84). We did not use vegetation or litter cover as response variables due to high Pearson’s r values with bare ground.Bare ground—Total cover of bare ground in each plot was used both as a direct measure of exposed soil and as an indirect measure of total vegetation cover. Bare ground and total vegetation cover (live and dead as litter) were negatively correlated  is more heterogeneous than a plot with lower species dispersion.Species dispersion—There is a possibility that plant communities can maintain overall similar species composition and relative abundances, but differ in the spatial patterning and variability of those species . For exaing plot . Speciesing plot . A higheMean soil moisture (VWC) measurements for each plot were used to stratify the analyses across distinct vegetation community types associated with a different dominant soil moisture regime (see Explanatory Variables below). In order to ensure an adequate sample size, those vegetation community types that had less than three plots for any meadow in a pair of matched meadows were dropped from the analysis. Differences in average bare ground and differences in mean species dispersions were calculated by subtracting the bootstrapped means of the non-stock (control) meadow from the bootstrapped means of the paired stock meadow. Each procedure was run 1000 times to produce an estimated mean difference as well as 95% confidence intervals for each meadow pair. These were then used as the response variables in each CART analysis. Mean estimates and 95% confidence intervals for species dissimilarity between matched pairs were calculated based on bootstrapped estimates of mean values for each species within each vegetation community type. Similar to the bare ground response, the procedure was run 1000 times and a median value from the resulting distribution was taken as a mean estimate to be used in the CART analysis.Explanatory variables used in the CART analyses fell into three broad categories:Pack Stock Use—Six measures of pack stock use based on NPS records from 2004–2009 were assigned to each matched pair: mean and maximum annual stock nights, mean and maximum annual stock density , and the standard deviation and coefficient of variation of annual stock nights across the six year period. We considered this six year period as a representative snapshot of contemporary use levels.Within-pair difference -The differences in physical attributes  within each stock and non-stock meadow pair were used to explain differences in vegetation between the pair. A large difference in each response due to Within-pair differences would suggest a weak pairing between stock and non-stock control meadows.Between-pairs difference—The mean physical attributes of each meadow pair were used to evaluate how much the difference in vegetation between stock and non-stock meadows varies with the overall environmental context of the meadow pair .2 and that did not have ties in the covariates selected for the split. We used a bootstrapping method to quantify uncertainty in the estimates of meadow-scale differences between stock and non-stock meadows of each pair to better describe the specific relationships between stock use intensity and meadow responses (described under Response Variables above).Fourteen geospatial and hydro-climatic covariates derived from remote sensing data were used to measure within-pair and between-pairs differences . We exclNatural variability in soil moisture regimes known to influence coarse scale patterns of dominant vegetation within each meadow were addressed by stratifying all analysis across three vegetation community types reflective of local soil moisture conditions . To do this, patterns in the distribution of the 10 most dominant plant species were explored by plotting the mean plot level cover (computed as a running average) along the soil moisture gradient, taken as the mean plot level soil VWC standardized to individual meadow means. The moving average was calculated as a two-sided mean with a window width of 0.25 standard deviations. Vegetation community types were then delineated based on natural breaks and transitions in the distribution of species representative of dominant soil moisture regimes see ; Fig 2.Carex filifolia, a xeric vegetation type indicator species [Carex vesicaria and Carex scopulorom, both characteristic of wet meadow habitats [The top 10 most abundant species showed clear vegetation community changes along the soil moisture gradient . These d species . Carex vhabitats , were hiIndividual CART models were able to explain 58 to 93% of the variance in the difference between stock and non-stock meadows. However, the relative contributions of different classes of explanatory variables  differed among responses  and by vegetation community type . At the One third of cases showed a significant signal of stock use on vegetation differences among meadows when analyses were stratified by individual community types . These iThe previous analysis contrasts the relative contributions of pack stock use and a suite of coarse physical meadow attributes for explaining differences between stock and non-stock meadow pairs. We now evaluate the three cases where splits in the CART models were contributed to more by a Stock Use metric than any of the mean physical attributes. For each example, the individual bootstrapped differences between meadows were plotted against the most contributing Stock Use metric .Differences in bare ground cover within the Dry vegetation community type varied considerably across the entire range of maximum stock nights . Four meIn general, there was little difference in local-scale spatial variability in plant community composition (species dispersion) between stock and non-stock meadows across all stock use intensities for both the Wet and Dry vegetation communities , Fig 6. Sierra Nevada meadows are complex ecosystems that are routinely subjected to natural disturbances such as seasonal flooding from snowmelt , long-teFor bare ground cover, signs of potential impacts were restricted to the Dry vegetation community type. This suggests that current use levels may be having little impact on bare ground or vegetation cover across the majority of meadow plant communities (Wet and Intermediate). Furthermore, bare ground within the Dry vegetation community exhibited a non-linear relationship with pack stock, where only meadows with the highest use intensities (> 156 maximum stock nights/ha) had greater bare ground than their matched control meadows . Such a A contrasting, yet equally important result, was the lack of any observed difference (stock vs. non-stock) in bare ground within the Intermediate or Wet vegetation communities. Meadow soils within these community types stay consistently moist throughout the growing season making them more susceptible to compaction due to lower soil strengths . Soil coDifferences in the mean community composition (species dissimilarity) between paired stock and non-stock meadows was highly variable and showed no clear or consistent trend with stock use for any of the vegetation community types. Instead, results from the CART analysis suggest that hydro-climatic and geospatial attributes of meadow pairs were often the best predictors of large differences between stock and non-stock meadows. Our results support findings from NPS monitoring in SEKI where, over a 25-year monitoring period, meadows showed greater differences across meadow pairs than between individual paired stock and non-stock meadows . Closer Our results suggest that, under certain conditions, variability in plant community composition (as species dispersion) could be a more sensitive response to ecological stressors than mean metrics of vegetation cover or species composition often used in monitoring grazing practices–46. SimiA closer examination of the vegetation community types shows two very different patterns of variability across our study meadows. Dry vegetation communities exhibited lower species dispersion (increased homogenization) within meadows with the lightest use (< 8 maximum stock nights/ha). Decreased spatial variability in plant communities experiencing grazing disturbance is not a novel concept . Yet theWe expected that increased species dispersion would be extended into the Intermediate vegetation community because those areas tend to host more species, and therefore a greater potential for spatial variability among the species present. The failure to detect changes in species dispersion within the Intermediate vegetation community may be a matter of the spatial resolution sampled. Intermediate communities occupy a larger proportion of total meadow area compared to the Wet and Dry vegetation communities. As a result, this community type contains steep hydrologic gradients  with manThe overall transition of the plant communities along the soil moisture gradient  reflecteCompositionally, we observed no differences along the entire pack stock use gradient sampled. Instead, we noticed differences at the highest pack stock use levels for bare ground within Dry communities, and species dispersion within Wet communities. Such results must be placed within the context of contemporary pack stock use records, which are maintained by the NPS. Our study did not account for past impacts from periods when pack stock use levels were much higher than what is currently allowed. For example, historical accounts of Sierra Club outings from the early 1900s have descriptions of over 100 pack animals being used on single trips to the Sierra Nevada high country . With hiMonitoring dynamic ecosystems is challenging, and any measure of change is dependent upon the variables monitored. We demonstrated that using a single variable indicator such as vegetation cover or bare ground could fail to distinguish other changes occurring within the meadow. However, regardless of the variable measured, no differences between stock and non-stock meadows would have been detected if the meadows we surveyed were not evaluated within the context of local hydrologic conditions.S1 TableGeographical locations of study meadows. X, Y coordinates are meadow centroids projected in NAD 1983 UTM Zone 11N; Site refers to the National Park unit where each meadow is located; SampleYear refers to the year sampling occurred; matchGroup indicates the pairing results from the multivariate matching technique; Stock indicates whether a meadow was a pack stock meadow (1) or a non-stock meadow (0).(CSV)Click here for additional data file.


Robotic assisted radical cystectomy (RARC) is an alternative to open radical cystectomy. As experience is gained with the RARC approach the technique is being applied to more complex surgical cases. We describe here our technique for RARC with intracorporeal ileal conduit urinary diversion for a renal transplant recipient.en bloc with the bladder specimen); identification of the transplanted ureter at the right bladder dome; posterior bladder and prostate dissection along Denonvilliers’ fascia; development of the space of Retzius; ligation and transection of the bladder and prostate vascular bundles; apical prostate dissection and transection of urethra; left pelvic lymphadenectomy; ilium resection for creation of the ileal conduit; stapled enteric anastomosis; ureteroileal anastomosis; maturation of the ileal conduit stoma.The patient is a 60-year old man with high-grade muscle invasive bladder cancer. He has a history of renal failure due to polycystic kidney disease and received a deceased donor renal transplant in 2008. His hospital course at time of transplant was complicated by low-level BK virus viremia. Interestingly his trans-urethral bladder tumor resection specimen at time of bladder cancer diagnosis stained positive for SV40. His native kidneys were anuric so bilateral laparoscopic nephrectomy was performed in a staged fashion 2 weeks prior to RARC. Our surgical technique utilizes 6 trocars, of note a 12-mm assistant trocar is placed 1 cm superior to the pubic symphysis, and this trocar is solely used to pass a laparoscopic stapler to facilitate the excision of the ileal segment and the stapled enteric anastomosis. Surgical steps include: identification of native ureters bilaterally (removed The surgery had no intraoperative complications. Operative time was 443 minutes (7.4 hours). Estimated blood loss was 250 cc. Length of hospital stay was 5 days. The patient did not experience any postoperative complications. The patient maintained good renal graft function with no decline in eGFR to date.As surgeon comfort and experience with robotic assisted surgery grows, robotic surgery can successfully be applied to less frequently performed procedures. Here we successfully performed a robotic assisted radical cystoprostatectomy with intracorporeal ileal conduit urinary diversion for a renal transplant recipient.


Recent meta-analysis revealed that elevated presynaptic striatal dopaminergic function is a robust feature of psychosis like schizophrenia. Considering increased dopaminergic capacity in psychotic disorders, it is not surprising that antipsychotic drugs, which primarily block dopaminergic neurotransmission, are mostly effective in the treatment of psychosis.However, it remains obscure what would happen to presynaptic dopaminergic function with antipsychotic treatment. This is an important issue addressing whether the current antipsychotic drugs are correcting the primary dopaminergic abnormality or not. In addition, the issue can give a clue regarding the mechanism of relapse in psychotic disorders.We measured presynaptic dopamine capacity using [18F]DOPA PET before and after the antipsychotic discontinuation in first episode psychosis. The binding potentials of [11C]raclopride were also measured after the discontinuation. Healthy controls had [18F]DOPA and [11C]raclopride scans at the corresponding date.First episode psychosis patients were carefully monitored in the aspects of symptomatic aggravations.The presynaptic dopamine capacity and the density of dopamine receptors showed significant group effect and the interaction between group and time (p<0.005)Dopaminergic function seems to play a critical role in relapse of first episode psychosis.


The Abstract section is missing. The publisher apologizes for the error. The Abstract can be viewed here:in vivo remyelination were observed. Our data suggest that NG2 modulates oligodendroglial migration but is dispensable for successful remyelination after cuprizone-induced demyelination.The expression of the proteoglycan NG2 is characteristic for oligodendroglial progenitor cells (OPC). The protein has been reported to influence OPC behavior in different pathological models. Here we examined the function of NG2 in remyelination ensuing after cuprizone feeding of mice to induce demyelination. OPC isolated from NG2-deficient mice exhibited an increased chemotaxis compared to WT OPC, but no differences in proliferation, differentiation or