Ultrastructural Characteristics of the Testicular Interstitial Endocrinocytes of Adult Rats Subjected to Total Sialoadenectomy

The major salivary glands of rats release into the saliva and blood a wide spectrum of bioactive substances, essential for many organs, including the testes. Sialoadenectomy leads to the development of degenerative changes in the cells of the twisted testicular tubules. However, the effects of bioactive factors released by the major salivary glands on the morphology and function of Leydig cells remain little studied. Sialoadenectomy in adult rats led (in 1-4 weeks) to a decrease in the nuclear and cytoplasmatic areas of Leydig cells, violation of the plasmalemma integrity, dilatation of perinuclear space and agranular endoplasmatic reticulum vesicles, and to destruction of the mitochondria. Ultrastructural changes caused by sialoadenectomy completely resolved by week 6 of the experiment at the expense of compensatory activation of the synthesis of the major salivary gland factors by other sources in the organism of rats.

https://ift.tt/2lqobZE

Dynamics of dystrophin’s actin-binding domain

We have used pulsed EPR, calorimetry, and molecular dynamics simulations to examine the structural mechanism of binding for dystrophin's N-terminal actin-binding domain (ABD1) and compare it to utrophin's ABD1. Like other members of the spectrin superfamily, dystrophin's ABD1 consists of two calponin-homology domains, CH1 and CH2. Several mutations within dystrophin's ABD1 are associated with development of severe degenerative muscle disorders Duchenne and Becker muscular dystrophies, highlighting the importance of understanding its structural biology.

https://ift.tt/2tmk4Be

Molecular Mechanism of Lipid Nanodisc Formation by Styrene Maleic Acid Copolymers

Experimental characterization of membrane proteins often requires their solubilization. A recent approach is to use styrene maleic acid (SMA) copolymers to isolate membrane proteins in nanometer-sized membrane discs, so called SMA lipid particles (SMALPs). The approach has the advantage of allowing direct extraction of proteins, keeping their native lipid environment. Despite the growing popularity of using SMALPs, the molecular mechanism behind the process remains poorly understood. Here we unravel the molecular details of the nanodisc formation by using coarse-grained molecular dynamics simulations.

https://ift.tt/2lp2kSs

Lipid droplet phase transition in freezing cat embryos and oocytes probed by Raman spectroscopy

Embryo and oocyte cryopreservation is a widely used technology for cryopreservation of genetic resources. One limitation of cryopreservation is the low tolerance to freezing observed for oocytes and embryos rich in lipid droplets. We apply Raman spectroscopy to investigate freezing of lipid droplets inside cumulus-oocyte complexes, mature oocytes and early embryos of a domestic cat. Raman spectroscopy allows one to characterize the degree of lipid unsaturation, lipid phase transition from the liquid-like disordered to solid-like ordered state, and triglyceride polymorphic state.

https://ift.tt/2lqkR0C

Superior vena cava syndrome presenting as position-dependent periorbital oedema

Description 

A 54-year-old woman presented to our dermatology clinic with a 2 months history of periorbital oedema, more prominent after lying down in horizontal position. Her face and throat felt swollen. She experienced dyspnoea on exertion, fatigue and had lost 6 kg of weight. Treatment with antihistamines and oral prednisone were ineffective. She smoked one pack of tobacco per week. Medical history and family history were unremarkable. She did not use any medications. Physical examination revealed prominent periorbital oedema and facial swelling (figure 1). Chest radiograph revealed a pathologically enlarged right hilum, broadened mediastinum and modest pleural effusion (figure 2). Diagnosis of superior vena cava syndrome (SVCS) was made and the patient was referred to the pulmonologist.

Figure 1

Prominent periorbital oedema and facial swelling after lying down the night before as a presenting symptom of superior vena cava syndrome.

...

https://ift.tt/2loGui0

Acute locked superior shoulder dislocation in a patient with cuff tear arthropathy

In the field of traumatic shoulder dislocations, this report of a 61-year-old female patient discusses the case of an acute locked superior shoulder dislocation in conjunction with a chronic rotator cuff arthropathy resulting from a low-energy fall on the outstretched and abducted arm. Radiological assessment revealed a complex combination of associated bony injuries including a fracture of the upper part of the glenoid and an impaction fracture of the inferior articular surface of the humeral head. Closed reduction and immobilisation were not successful in obtaining joint stability. This unique report highlights the clinical importance of accurate management of bony injuries in traumatic shoulder dislocation.

https://ift.tt/2yu8IRJ

Renal pelvicalyceal rupture secondary to extraperitoneal pelvic packing (EPP) in the unstable trauma patient

Presented here is the case of an 86-year-old man who was found to have right-sided pelvicalyceal rupture and anuric renal failure, secondary to obstructive uropathy caused by life-saving extraperitoneal pelvic packing (EPP) in the settling of severe trauma. In efforts to control haemorrhage in this haemodynamically unstable patient, EPP placement deviated from the recognised method of three extraperitoneal packs bilaterally with seven surgical packs placed. Progress postoperative imaging revealed right-sided hydroureteronephrosis with obstruction evident at the level of the extraperitoneal pelvic packs, identified by delayed contrast excretion from the preceding CT angiography imaging. Urology performed bilateral retrograde pyelograms at his relook laparotomy, timed after removal of his extraperitoneal packs and haemostasis, which showed impression of the surgical pack on the distal ureter but no persisting obstruction or short-term complications. Anuric renal failure improved, and renal function returned to near premorbid levels on day 4 postoperatively.

https://ift.tt/2lrkx1P

Massive faecal impaction leading to abdominal compartment syndrome and acute lower limb ischaemia

Abdominal compartment syndrome (ACS) is associated with significant morbidity and mortality requiring prompt treatment. We report a rare case of a 57-year-old man who developed acute lower limb ischaemia, severe metabolic acidosis and renal impairment from massive faecal impaction of unknown aetiology resulting in ACS causing occlusion of the right common iliac artery. This was treated with faecal disimpaction, which eventually resulted in slow but full recovery.

https://ift.tt/2tq1oR7

Laparoscopic revisional surgery for an unusual complication of Roux-en-Y gastric bypass

With the worldwide epidemic of obesity, there has been an increase in the numbers of primary and revisional procedures of bariatric surgery such as the Roux-en-Y gastric bypass (RYGBP). Nevertheless, this type of surgery is not exempt from complications. An excessive length of non-functional Roux limb proximal to the jejunojejunostomy can cause abnormal upper gastrointestinal symptoms after laparoscopic RYGBP. We present the case of a female patient who presented these unspecific abdominal symptoms after laparoscopic RYGBP who underwent laparoscopic resection in order to reduce the length of the dilated blind loop responsible for the symptoms.

https://ift.tt/2lnjuzR

Gorlin-Goltz syndrome: first reported case of bullae in the lungs complicated with tension pneumothorax

A 13-year-old girl was referred by her general practitioner with acute worsening exertional dyspnoea and sudden onset of left-sided chest pain. There was no associated trauma, palpitations or syncope. Clinical examination revealed that the left lung was hyper-resonant on percussion with reduced air entry on auscultation. Chest X-ray showed a left tension pneumothorax. She was treated conservatively with chest drain. Follow-up X-ray revealed multiple bullae within her left lung. Unfortunately, she redeveloped a pneumothorax and was sent to a tertiary centre. She was under the care of the paediatric cardiothoracic surgeons who organised a CT thorax and performed a lobectomy to remove the bullae. She was discharged from the tertiary centre and currently being followed up under the care of the paediatrician in the district general hospital. She have not developed any further pneumothoraxes.

https://ift.tt/2yE3dA7

Posterior root medial meniscus reconstruction: an option in chronic posterior root meniscal injury management

Posterior root medial meniscus (PRMM) tears have shown to be biomechanically equivalent to complete meniscectomy. Drawbacks from PRMM tears repair are unsatisfactory healing rates. In this case report, we outlined a PRMM reconstruction with gracilis graft healing outcome in chronic PRMM tear case, based on clinical and MRI evaluation. A 60-year-old man reported a chief complaint of increasing pain on the right knee joint in the last 1 year after a deep-flexion injury. On MRI investigation, we confirmed the chronic PRMM tear as Osteoarthritis Kellgren-Lawrence grade II. Then, we planned to perform a PRMM reconstruction with gracilis graft per arthroscopy. At the 6-month MRI evaluation, we found healing of the attached PRMM on its footprints, with intact graft transition from the meniscus to the tibial bone tunnel.

https://ift.tt/2ll2KZX

Symptomatic dyspnoea addressed by excision of ossified anterior longitudinal ligament

Ossification of the anterior longitudinal ligament (OALL) in cervical spine is known to cause dysphagia. However, dyspnoea and obstructive sleep apnoea (OSA) due to OALL is a rare entity. A 50-year-old man presented to our clinic 2 years after anterior cervical discectomy and fusion (ACDF) with complaints of dysphagia, dyspnoea and difficulty in sleeping supine. The clinico-neurological examination of patient was normal without any long tract signs. The diagnosis of OALL was made on plain lateral radiographs. Ultrasonic bone cutter was used to convert sessile osteophyte mass into a pedunculated mass. It was then disconnected from the anterior aspect of vertebral bodies with a chisel. The patient showed immediate relief from dysphagia and OSA. Dyspnoea improved over a week and the postoperative change in voice responded well to speech therapy. To the best of our knowledge, this is the first report of dyspnoea due to OALL after ACDF.

https://ift.tt/2ytbeHF

Long-term control of laryngeal plasma cell mucositis with systemic immunosuppression

Plasma cell mucositis (PCM) is a rare non-neoplastic plasma cell proliferative disorder of the mucous membranes, which typically presents as soft tissue lesions involving oral, upper airway or genital mucosa. Laryngeal involvement resulting in stridor has been reported in four other cases previously, with three requiring tracheostomy. We present a case of supraglottic stenosis in a 53-year-old woman presenting with dysphonia and stridor, requiring surgical resection on three occasions accompanied by tracheostomy on two occasions; biopsy was consistent with PCM. Due to relapsing disease activity, high-dose prednisolone and mycophenolate mofetil were commenced with prednisolone eventually being ceased. After 2 years of mycophenolate mofetil therapy, the patient's disease has been controlled without need for further surgical intervention. This is the first reported case of prolonged symptomatic improvement with the use of systemic immunosuppressive therapy with mycophenolate mofetil in PCM.

https://ift.tt/2lnjrEb

The effect of desferrioxamine chelation versus no therapy in patients with non transfusion-dependent thalassaemia: a multicenter prospective comparison from the MIOT network

Abstract

We prospectively assessed by magnetic resonance imaging (MRI) the advantages of desferrioxamine (DFO) with respect to the absence of chelation therapy in non transfusion-dependent thalassaemia (NTDT) patients. We considered 18 patients non-chelated and 33 patients who received DFO alone between the two MRI scans. Iron overload was assessed by the T2* technique. Biventricular function parameters were quantified by cine sequences. No patient treated with DFO had cardiac iron. At baseline, only one non-chelated patient showed a pathological heart T2* value (< 20 ms) and he recovered at the follow-up. The percentage of patients who maintained a normal heart T2* value was 100% in both groups. A significant increase in the right ventricular ejection fraction was detected in DFO patients (3.48 ± 7.22%; P = 0.024). The changes in cardiac T2* values and in the biventricular function were comparable between the two groups. In patients with hepatic iron at baseline (MRI liver iron concentration (LIC) ≥ 3 mg/g/dw), the reduction in MRI LIC values was significant only in the DFO group (− 2.20 ± 4.84 mg/g/dw; P = 0.050). The decrease in MRI LIC was comparable between the groups. In conclusion, in NTDT patients, DFO therapy showed no advantage in terms of cardiac iron but its administration allowed an improvement in right ventricular function. Moreover, DFO reduced hepatic iron in patients with significant iron burden at baseline.

https://ift.tt/2tdiJ0s

Efficacy and safety of resveratrol, an oral hemoglobin F-augmenting agent, in patients with beta-thalassemia intermedia

Abstract

Recently, resveratrol showed induction of γ-globin mRNA synthesis in human erythroid precursors and reducing oxidative stress in red cells of thalassemia patients in many in vitro studies. We aimed to investigate the efficacy and safety of resveratrol, for the first time, in non-transfusion-dependent beta-thalassemia intermedia (B-TI) in Southern Iran. In this double-blind randomized clinical trial, 54 patients with B-TI were investigated during 6 months between October 2016 and March 2017. Patients were randomly allocated into three groups by simple randomization method. Group 1 (hydroxyurea (HU) and placebo, 18 patients), group 2 (resveratrol/piperine and placebo, 16 patients), and group 3(HU and resveratrol/piperine, 20 patients). Primary end point was considered as change in hemoglobin (Hb) levels and need for blood transfusion. Drug safety was considered as a secondary end point. Mean age of the patients was 28.2 ± 5.6 (18–42) years. Response rate was not significantly different among the three groups (P > 0.05). Higher percentages of adverse events were detected in groups 2 (31.3%) and 3 (25%) compared to group 1 (5.6%). However, the difference was not statistically significant (P > 0.05). All reported adverse events were gastrointestinal symptoms. Resveratrol showed a similar efficacy with HU in the small population of non-transfusion B-TI patients during a 6-month follow-up. Complications, mostly gastrointestinal, were observed more frequently in resveratrol groups compared to the HU group. Although it was not statistically significant, more attention should be given to safety and efficacy of resveratrol as an oral HbF-augmenting agent.

https://ift.tt/2M9Hh1u

Clinical Significance of Incidental Pituitary TC-99m MIBI Uptake on Parathyroid Spect and Factors Affecting Uptake Intensity

Cancer Biotherapy and Radiopharmaceuticals, Ahead of Print.


https://ift.tt/2K4ofMJ

Spatial and spectral regularization to discriminate tissues using multispectral photoacoustic imaging

Photoacoustics is a hybrid modality used to image biological tissues. As optical absorption of tissues depends on the wavelength of the transmitted light, multispectral photoacoustic datasets can be obtained b...

https://ift.tt/2JULiu0

Insulin signalling promotes dendrite and synapse regeneration and restores circuit function after axonal injury

Abstract

Dendrite pathology and synapse disassembly are critical features of chronic neurodegenerative diseases. In spite of this, the capacity of injured neurons to regenerate dendrites has been largely ignored. Here, we show that, upon axonal injury, retinal ganglion cells undergo rapid dendritic retraction and massive synapse loss that preceded neuronal death. Human recombinant insulin, administered as eye drops or systemically after dendritic arbour shrinkage and prior to cell loss, promoted robust regeneration of dendrites and successful reconnection with presynaptic targets. Insulin-mediated regeneration of excitatory postsynaptic sites on retinal ganglion cell dendritic processes increased neuronal survival and rescued light-triggered retinal responses. Further, we show that axotomy-induced dendrite retraction triggered substantial loss of the mammalian target of rapamycin (mTOR) activity exclusively in retinal ganglion cells, and that insulin fully reversed this response. Targeted loss-of-function experiments revealed that insulin-dependent activation of mTOR complex 1 (mTORC1) is required for new dendritic branching to restore arbour complexity, while complex 2 (mTORC2) drives dendritic process extension thus re-establishing field area. Our findings demonstrate that neurons in the mammalian central nervous system have the intrinsic capacity to regenerate dendrites and synapses after injury, and provide a strong rationale for the use of insulin and/or its analogues as pro-regenerative therapeutics for intractable neurodegenerative diseases including glaucoma.

https://ift.tt/2lq5sgO

Somatic copy number gains of α-synuclein (SNCA) in Parkinson’s disease and multiple system atrophy brains

Abstract

The α-synuclein protein, encoded by SNCA, has a key role in the pathogenesis of Parkinson's disease and other synucleinopathies. Although usually sporadic, Parkinson's disease can result from inherited copy number variants in SNCA and other genes. We have hypothesized a role of somatic SNCA mutations, leading to mosaicism, in sporadic synucleinopathies. The evidence for mosaicism in healthy and diseased brain is increasing rapidly, with somatic copy number gains of APP reported in Alzheimer's brain. Here we demonstrate somatic SNCA copy number gains in synucleinopathies (Parkinson's disease and multiple system atrophy), focusing on substantia nigra. We selected sporadic cases with relatively young onset or short disease duration, and first excluded high level copy number variant mosaicism by DNA analysis using digital PCR for SNCA, and/or customized array comparative genomic hybridization. To detect low level SNCA copy number variant mosaicism, we used fluorescent in situ hybridization with oligonucleotide custom-designed probes for SNCA, validated on brain and fibroblasts with known copy number variants. We determined SNCA copy number in nigral dopaminergic neurons and other cells in frozen nigra sections from 40 cases with Parkinson's disease and five with multiple system atrophy, and 25 controls, in a blinded fashion. Parkinson's disease cases were significantly more likely than controls to have any SNCA gains in dopaminergic neurons (P = 0.0036), and overall (P = 0.0052). The average proportion of dopaminergic neurons with gains in each nigra was significantly higher in Parkinson's disease than controls (0.78% versus 0.45%; P = 0.017). There was a negative correlation between the proportion of dopaminergic neurons with gains and onset age in Parkinson's disease (P = 0.013), but not with disease duration, or age of death in cases or controls. Cases with tremor at onset were less likely to have gains (P = 0.035). All multiple system atrophy cases had gains, and the highest levels in dopaminergic neurons were in two of these cases (2.76%, 2.48%). We performed selective validation with different probes after dye swapping. All three control probes used showed minimal or no gains (≤0.1% in dopaminergic neurons). We also found occasional SNCA gains in frontal neurons of cases with Parkinson's disease, and the putamen of one multiple system atrophy case. We present evidence of somatic SNCA gains in brain, more commonly in nigral dopaminergic neurons of Parkinson's disease than controls, negatively correlated with onset age, and possibly commonest in some multiple system atrophy cases. Somatic SNCA gains may be a risk factor for sporadic synucleinopathies, or a result of the disease process.

https://ift.tt/2yqDXwM

Corrigendum

Jie Zhang, Wei Cheng, Zhaowen Liu, Kai Zhang, Xu Lei, Ye Yao, Benjamin Becker, Yicen Liu, Keith M. Kendrick, Guangming Lu and Jianfeng Feng. Neural, electrophysiological and anatomical basis of brain-network variability and its characteristic changes in mental disorders. Brain 2016; 139: 2307–21; doi:10.1093/brain/aww143.

https://ift.tt/2lkqs8K

Corrigendum

Cary S. Kogan, Isabelle Boutet, Kim Cornish, Shahin Zangenehpour, Kathy T. Mullen, Jeanette J. A. Holden, Vazken M. Der Kaloustian, Eva Andermann and Avi Chaudhuri. Differential impact of the FMR1 gene on visual processing in fragile X syndrome. Brain 2004; 127: 591–601; doi:10.1093/brain/awh069.

https://ift.tt/2ywdvC8

Characteristics of sauna deaths in Korea in relation to different blood alcohol concentrations

Abstract

Although the benefits of sauna bathing have been demonstrated in epidemiological studies, sauna deaths have been reported. The aim of this study was to determine the demographic and forensic characteristics associated with different blood alcohol concentrations (BACs) in sauna deaths in Korea. In this retrospective analysis, data were collected from a nationwide pool in Korea between January 2008 and December 2015 to determine the role of alcohol intoxication in sauna deaths based on the subjects' BAC and to evaluate the demographic and forensic characteristics associated with different BACs. One hundred and three deaths were classified into 2 groups: the non-intoxication (NI) group (BAC,<0.08%; n = 27) and the intoxication (I) group (BAC,≥0.08%; n = 76). Demographic and forensic characteristics were compared between the groups using a multinomial logistic regression analysis. The proportions of decedents who were male (odds ratio: 17.4, 95.0% confidence interval: 3.8–79.8) and in a prone position at the scene of death (odds ratio: 11.3, 95.0% confidence interval: 2.1–60.1) were significantly higher (P < 0.001 and P < 0.05, retrospectively) in the I group than in the NI group. However, no significant differences were observed with respect to obesity, coronary artery narrowing, and liver pathology. Sauna deaths exhibited different characteristics according to BACs detected at autopsy. The differences in sauna deaths between the I and NI groups may have implications for the targeted prevention of sauna deaths associated with alcohol consumption.

https://ift.tt/2JW2rUf

Molecular Therapies for Muscular Dystrophies

Abstract

Purpose of review

To construct a framework to understand the different molecular interventions for muscular dystrophy.

Recent findings

The recent approval of antisense oligonucleotides treatment for Duchenne muscular dystrophy and spinal muscular atrophy and current clinical trials using recombinant adeno-associated virus for the treatment of those diseases suggests that we are at a tipping point where we are able to treat and potentially cure muscular dystrophies.

Summary

Understanding the basic molecular pathogenesis of muscular dystrophies and the molecular biology of the treatment allows for critical evaluation of the proposed therapies.

https://ift.tt/2llY2el

Response:

We would like to thank Dr Yarze1 for his interest in our study "Predictors of post-colonoscopy emergency department use"2 and his response. In our study, we aimed to determine the frequency, reasons, and relatedness of post-colonoscopy emergency department (ED) visits and to assess for predictors of these visits. We found increased patient complexity, higher endoscopist adenoma detection rates, and EMR to be predictors of unplanned hospital use after colonoscopy. Although post-procedure calls were not assessed in our study, we agree with Dr Yarze that ED use can certainly be influenced by the handling of post-procedure calls.

https://ift.tt/2K14TVn

New technology for the old polyp: Does the benefit justify the cost?

We are deeply and persistently attracted by new technology, irrespective of whether it is the latest smart phone, laptop, or car. This is mainly related to our selfish expectation for an easier, faster, and more attractive experience that is ultimately our own quality of life.

https://ift.tt/2JSRouN

Response:

My colleagues and I thank Matsushita et al1 for their response to our article entitled "Peritoneal carcinomatosis from signet-ring cell adenocarcinoma of the appendix."2 We agree that with signet-ring cell carcinoma, the primary tumor site is most commonly the stomach and that accurate diagnosis of a primary gastric cancer is difficult to make in patients without gastric symptoms. We also agree that positron emission tomography plays a less-useful diagnostic role in the detection of primary gastric cancer, especially in patients with signet-ring cell carcinoma.

https://ift.tt/2M9qETL

Response:

We thank the authors for their thoughtful letter1 discussing our editorial2 about their recently published multicenter, prospective randomized trial on the wide-area transepithelial sampling (WATS) with 3-dimensional cytology brush technique.3 However, our concerns regarding the WATS technique remain.

https://ift.tt/2MDBvq1

Response:

We would like to thank Drs Lee and Chak1 for their thoughtful editorial. We are pleased that they enjoyed our article.2

https://ift.tt/2MaoWkS

Response to “NIDDK diseases workshop on endoscopic ultrasound and related technologies: History of EUS”

We appreciate the historical details from Drs DiMagno and DiMagno,1,2 who were intimately involved with the development of EUS technology. We regret overlooking some of the important contributions of those authors and others. The purpose of the workshop3,4 was not to review the details surrounding the early history of EUS but to provide a review of current applications of EUS in the diagnosis and treatment of pancreatic disease and to identify research priorities for the future.

https://ift.tt/2JUyQug

Predictors of postcolonoscopy emergency department use

I read the recent article by Dr Grossberg et al1 with interest. In their retrospective cohort study, the authors identified multiple patient-related and endoscopist-related factors associated with an unplanned emergency department (ED) visit within 7 days of the index colonoscopic examination. Although not studied, a potentially important factor in determining an individual patient's propensity to seek ED evaluation might be the physician's threshold for recommending the same.

https://ift.tt/2M8OdM9

Is more always better in Barrett’s esophagus?

Patients diagnosed with Barrett' esophagus (BE) often face a challenging conundrum. They are informed that they have a premalignant condition with a risk of neoplastic progression that is proportional to the grade of dysplasia present on esophageal biopsies and that their condition will either be monitored through a surveillance program or treated, depending on this risk. Endoscopic surveillance follows the Seattle protocol, which consists of a detailed examination of the BE segment under high-definition white light endoscopy with targeted biopsies or resection of areas of mucosal irregularities followed by systematic 4-quadrant biopsies at set intervals along the entire length of the BE segment.

https://ift.tt/2JUyML2

Clinical outcome of endoscopic mucosal resection of sporadic, nonampullary duodenal adenoma

I read with interest the study by Tomizawa and Ginsberg1 in Gastrointestinal Endoscopy in 2018. They identified that increasing adenoma size may be associated with increased risk of recurrence and post-EMR bleeding.1 The results were very interesting; however, I am concerned about the statistical methods that estimated the effect of increasing adenoma size on the studied outcomes.

https://ift.tt/2M5HnXV

First-line EUS-guided biliary drainage or ERCP in patients with biliary obstruction and in situ duodenal stent?

ERCP is the most commonly used technique for the palliation of malignant biliary obstruction.1,2 Success rates are high, ranging from 75% to 95%.3,4 Nevertheless, a pre-existing gastroduodenal stent (GDS) poses significant technical challenges for the endoscopist. The stent can be narrow and occluded as a result of tissue or tumor ingrowth, the stent interstices can make it difficult to pass a sphincterotome, and the stent can completely obscure the papilla, thereby preventing biliary access. In such cases, percutaneous transhepatic biliary drainage (PTBD) has traditionally been the mainstay of therapy.

https://ift.tt/2JVe6Cv

WATS for Barrett's surveillance

We appreciate the editorial by Drs. Canto and Montgomery1 related to our article2 focused on wide-area transepithelial sampling (WATS) that showed a 4-times increase in the detection of high-grade dysplasia (HGD) and cancer in patients with Barrett's esophagus (BE) as part of our multicenter trial. The authors of this editorial make many reasonable statements regarding the limitations related to sampling of BE mucosa, including some of the limitations related to WATS. In particular, the authors note a disagreement with regard to the diagnosis of dysplasia in some of the figures in our article.

https://ift.tt/2K6epXs

Primary EUS-guided drainage for malignant distal biliary obstruction: not yet prime time!

Endoscopic drainage has virtually replaced surgery for biliary obstruction, irrespective of a benign or a malignant cause. Compared with surgery, ERCP for palliative drainage of malignant biliary obstruction is less expensive, is associated with reduced morbidity, and provides a better quality of life.1-3 When compared with percutaneous transhepatic biliary drainage (PTBD), ERCP is associated with lower rates of adverse events and a better quality of life.4 Therefore, ERCP has been traditionally preferred over surgery and PTBD in cases with malignant biliary obstruction.

https://ift.tt/2MHJH8s

Response:

We thank Drs Garman and McCall1 for their valuable comments and interest in our recent article in the January issue of Gastrointestinal Endoscopy.2 They bring up 2 separate issues: (1) the role of submucosal glands/ducts in the pathogenesis of Barrett's esophagus (BE) and BE-associated neoplasia and (2) the resemblance, in their opinion, of subsquamous glands in Figure 2A of our article to foci of acinar "ductal metaplasia" that they have previously reported in esophageal submucosal glands (ESMGs) in esophagectomies performed for BE-associated high-grade dysplasia (HGD) or adenocarcinoma.

https://ift.tt/2M6jejU

Continuing Medical Education Exam: July 2018

https://ift.tt/2MIxFfh

Treatment of thrombocytopenic patients with GI bleeding

The treatment of patients with thrombocytopenia who require endoscopy is variable and uncertain, with limited evidence to inform decisions. In addition, the treatment might vary depending on the category of thrombocytopenia. Thrombocytopenia may be due to sequestration (eg, portal-hypertension–induced splenomegaly), reduced production (eg, hematologic disorders, chemotherapy), or increased destruction (eg, immune thrombocytopenia).

https://ift.tt/2K80EHt

Contents

https://ift.tt/2MH3gOx

Instructions for authors

GASTROINTESTINAL ENDOSCOPY publishes original papers reporting investigations and observations relating to endoscopic procedures used in the study and treatment of digestive diseases. All submissions undergo peer review. Submissions may be accompanied by supplemental materials posted to the electronic version of the journal; such materials also will be subject to peer review. Careful adherence to submission guidelines will avoid unnecessary delays, as incomplete submissions will be returned to the authors before initiation of the peer review process.

https://ift.tt/2MavHTU

Editors

https://ift.tt/2JUyaVK

Deep learning–based endoscopic image recognition for detection of early gastric cancer: a Chinese perspective

We read with great interest the recent article in which Kanesaka et al1 reported a computer-aided system for identifying early gastric cancers (EGC). The diagnostic performance (accuracy of 96.3%) suggests the great potential of computer-aided diagnosis for EGC. This is especially true in countries such as China that have a high incidence of gastric cancer but a low EGC detection rate.2 Recent reports3 have estimated that about 679,100 new cases of gastric cancer were confirmed in China each year and that more than 80% of patients received their diagnoses at an advanced stage with poor prognosis.

https://ift.tt/2K5PJ19

Focus on...

https://ift.tt/2JSf2aZ

Circulating biomarkers during treatment in patients with advanced biliary tract cancer receiving cediranib in the UK ABC-03 trial

Circulating biomarkers during treatment in patients with advanced biliary tract cancer receiving cediranib in the UK ABC-03 trial

Circulating biomarkers during treatment in patients with advanced biliary tract cancer receiving cediranib in the UK ABC-03 trial, Published online: 21 June 2018; doi:10.1038/s41416-018-0132-8

Circulating biomarkers during treatment in patients with advanced biliary tract cancer receiving cediranib in the UK ABC-03 trial

https://ift.tt/2ytVTGX

Validation of the IBIS breast cancer risk evaluator for women with lobular carcinoma in-situ

Validation of the IBIS breast cancer risk evaluator for women with lobular carcinoma in-situ

Validation of the IBIS breast cancer risk evaluator for women with lobular carcinoma in-situ, Published online: 21 June 2018; doi:10.1038/s41416-018-0120-z

Validation of the IBIS breast cancer risk evaluator for women with lobular carcinoma in-situ

https://ift.tt/2lm7cYo

Sociogenetic Risks — Ancestry DNA Testing, Third-Party Identity, and Protection of Privacy

The recent capture of the suspected Golden State Killer on "National DNA Day" was a startling public illustration of the reality that DNA information may be pertinent to people far removed from the one who was tested — and the fact that information may derive from testing that an implicated person…

https://ift.tt/2tfhyh7

Florida Teen First Human Case of Another Mosquito-Borne Virus

WEDNESDAY, June 20, 2018 -- The first confirmed human case of Keystone virus -- named after the location in the Tampa Bay area where it was first identified in 1964 -- has been diagnosed in a Florida teen, but it's likely that infection with the...

https://ift.tt/2yr5YEL

AAFP Still Recommends CRC Screening From Age 50 to 75

WEDNESDAY, June 20, 2018 -- In accordance with the U.S. Preventive Services Task Force (USPSTF), the American Academy of Family Physicians (AAFP) does not intend to change its recommendations for colorectal cancer screening based on the recent...

https://ift.tt/2lkRw7A

AMA Seeks to Make Long-Term Care Services More Affordable

WEDNESDAY, June 20, 2018 -- The American Medical Association (AMA) House of Delegates has adopted a policy to make long-term care insurance simpler, more affordable, more innovative, and part of automatic enrollment for current employees and...

https://ift.tt/2toJXjX

70 Sickened So Far in Salmonella-Tainted Melon Outbreak

WEDNESDAY, June 20, 2018 -- A salmonella outbreak linked to melons and fruit salad mixes continues to expand, say officials at the U.S. Centers for Disease Control and Prevention. So far, 70 people have been sickened across seven states after eating...

https://ift.tt/2lkRBYW

NIH Initiative Aims to Address Opioid Misuse Over Long Term

WEDNESDAY, June 20, 2018 -- A novel, innovative initiative is being developed to help end addiction over the long term, according to a viewpoint article published online June 12 in the Journal of the American Medical Association. Francis S. Collins,...

https://ift.tt/2yulm2V

Chilaiditi Syndrome: A Case Report Highlighting the Intermittent Nature of the Disease

Background. Chilaiditi syndrome is a phenomenon where there is an interposition of the colon between the liver and the abdominal wall leading to clinical symptoms. This is distinct from Chilaiditi sign for which there is radiographic evidence of the interposition, but is asymptomatic. Case Presentation. Here, we present the case of a patient who, despite having clinical symptoms for a decade, had a delayed diagnosis presumably due to the interposition being intermittent and episodic. Conclusions. This case highlights the fact that Chilaiditi syndrome may be intermittent and episodic in nature. This raises an interesting question of whether previous case reports, which describe complete resolution of the syndrome after nonsurgical intervention, are perhaps just capturing periods of resolution that may have occurred spontaneously. Because the syndrome may be intermittent with spontaneous resolution and then recurrence, patients should have episodic follow-up after nonsurgical intervention.

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Fission Yeast CENP-C (Cnp3) Plays a Role in Restricting the Site of CENP-A Accumulation

The centromere is a chromosomal locus where a microtubule attachment site, termed kinetochore, is assembled in mitosis. In most eukaryotes, with the exception of holocentric species, each chromosome contains a single distinct centromere. A chromosome with an additional centromere undergoes successive rounds of anaphase bridge formation and breakage, or triggers a cell cycle arrest imposed by DNA damage and replication checkpoints. We report here a study in Schizosaccharomyces pombe to characterize a mutant (cnp3-1) in a gene encoding a homolog of mammalian centromere-specific protein, CENP-C. At the restrictive temperature 36 °C, the Cnp3-1 mutant protein loses its localization at the centromere. In the cnp3-1 mutant, the level of the Cnp1 (a homolog of a centromere-specific histone CENP-A) also decreases at the centromere. Interestingly, the cnp3-1 mutant is prone to promiscuous accumulation of Cnp1 at non-centromeric regions, when Cnp1 is present in excess. Unlike the wild type protein, Cnp3-1 mutant protein is found at the sites of promiscuous accumulation of Cnp1, suggesting that Cnp3-1 may stabilize or promote accumulation of Cnp1 at non-centromeric regions. From these results, we infer the role of Cnp3 in restricting the site of accumulation of Cnp1 and thus to prevent formation of de novo centromeres.

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Cardiac Magnetic Resonance in Stable Coronary Artery Disease: Added Prognostic Value to Conventional Risk Profiling

Aims. Cardiovascular magnetic resonance (CMR) permits a comprehensive evaluation of stable coronary artery disease (CAD). We sought to assess whether, in a large contemporaneous population receiving optimal medical therapy, CMR independently predicts prognosis beyond conventional cardiovascular risk factors (RF). Methods. We performed a single centre, observational prospective study that enrolled 465 CAD patients (80% males; 63±11 years), optimally treated with ACE-inhibitors/ARB, aspirin, and statins (76-85%). Assessments included conventional evaluation (clinical history, atherosclerosis RF, electrocardiography, and echocardiography) and a comprehensive CMR with LV dimensions/function, late gadolinium enhancement (LGE), and stress perfusion CMR (SPCMR). Results. During a median follow-up of 62 months (IQR 23-74) there were 50 deaths and 92 major adverse cardiovascular events (MACE). CMR variables improved multivariate model prediction power of mortality and MACE over traditional RF alone (F-test p

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Nonlinear Biomechanical Characteristics of the Schneiderian Membrane: Experimental Study and Numerical Modeling

Objective. The aim of this study is to quantify the nonlinear mechanical behavior of the Schneiderian membrane. Methods. Thirty cadaveric maxillary sinus membrane specimens were divided into the elongation testing group and the perforation testing group. Mechanical experimental measurements were taken via ex vivo experiments. Theoretical curves were compared with experimental findings to assess the effectiveness of the nonlinear mechanical properties. The FE model with nonlinear mechanical properties was used to simulate the detachment of the Schneiderian membrane under loading. Results. The mean thickness of the membrane samples was 1.005 mm. The mean tensile strength obtained by testing was 6.81 N/mm2. In membrane perforation testing, the mean tensile strength and the linear elastic modulus were significantly higher than those in membrane elongation testing (P

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Primary CNS Lymphomas: Challenges in Diagnosis and Monitoring

Primary Central Nervous System Lymphoma (PCNSL) is a rare neoplasm that can involve brain, eye, leptomeninges, and rarely spinal cord. PCNSL lesions most typically enhance homogeneously on T1-weighted magnetic resonance imaging (MRI) and appear T2-hypointense, but high variability in MRI features is commonly encountered. Neurological symptoms and MRI findings may mimic high grade gliomas (HGGs), tumefactive demyelinating lesions (TDLs), or infectious and granulomatous diseases. Advanced MRI techniques (MR diffusion, spectroscopy, and perfusion) and metabolic imaging, such as Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) or amino acid PET (usually employing methionine), may be useful in distinguishing these different entities and monitoring the disease course. Moreover, emerging data suggest a role for cerebrospinal fluid (CSF) markers in predicting prognosis and response to treatments. In this review, we will address the challenges in PCNSL diagnosis, assessment of response to treatments, and evaluation of potential neurotoxicity related to chemotherapy and radiotherapy.

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An Unusual Neonatal Presentation of Scimitar Syndrome

AJP Rep 2018; 08: e138-e141
DOI: 10.1055/s-0038-1656533

Scimitar syndrome is characterized by partial or total anomalous pulmonary venous return from the right lung along with pulmonary hypoplasia. We present a case of a 37 weeks' gestation male infant with antenatal ultrasound findings of suspected partial anomalous pulmonary venous return (PAPVR) and coarctation of the aorta. The newborn presented with respiratory distress, a chest X-ray and chest computed tomography (CT) angiogram confirmed the diagnosis of scimitar syndrome. The combination of scimitar syndrome with aortic coarctation is extremely rare with only a few cases previously reported.
[...]

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Article in Thieme eJournals:
Table of contents  |  Abstract  |  open access Full text

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Interventions to Reduce Intraoperative Costs: A Systematic Review

Objective: The aim of this study was to systematically review the risks and benefits of interventions designed to reduce intraoperative costs. Summary Background Data: Episode-based payments shift financial risk from insurers onto hospitals and providers. The operating room (OR) is a resource dense environment and there is growing interest in identifying ways to reduce intraoperative costs while maintaining patient safety. Methods: We searched PubMed, Cochrane, and CINAHL for articles published between 2001 and March 2017 that assessed interventions designed to reduce intraoperative costs. We grouped interventions into 6 categories: standardization of instruments, switching to reusable instruments or removing instruments from trays, wound closure comparisons, cost feedback to surgeons, head-to-head instrument trials, and timely arrival of surgeon to the OR. Results: Of 43 included studies, 12 were randomized trials and 31 were observational studies. Gross cost estimates ranged from −$413 (losses) to $3154 (savings) per operation, with only 2 studies reporting losses; however, studies had significant methodologic limitations related to cost data. Studies evaluating standardization and cost feedback were the most robust with estimated cost savings between $38 and $732/case, with no change in OR time, length of stay, or adverse events. Conclusions: Almost all studies assessing interventions to reduce intraoperative costs have demonstrated cost savings with no apparent increase in adverse effects. Methodologic limitations, especially related to cost data, weaken the reliability of these estimates for most intervention categories. However, hospitals seeking to reduce costs may be able to do so safely by standardizing operative instruments or providing cost feedback to surgeons.

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The Association Between Out-of-Pocket Costs and Adherence to Adjuvant Endocrine Therapy Among Newly Diagnosed Breast Cancer Patients

Objective: To determine how out-of-pocket costs for adjuvant endocrine therapy (AET) medication affects adherence among newly diagnosed breast cancer survivors with private health insurance who initiate therapy. Materials and Methods: We examined medical and pharmacy claims for the 1-year period after initiating AET using the Truven Health Analytics MarketScan database. Adherence was defined as ≥80% proportion of days covered. Mean out-of-pocket costs for AET fill were measured as the sum of copayments, coinsurance, and deductibles and adjusted to 30-day amounts. Using a multivariable logistic regression model we calculated adjusted risk ratios controlling for age, comorbidities, type of surgery, use of chemotherapy and/or radiation therapy, average out-of-pocket costs for other services, and pharmacy use characteristics. Results: Of the 6863 women 64 years and younger who were diagnosed with breast cancer and initiated AET, 73.9% were adherent (proportion of days covered≥80%). A total of 19% of patients had $20 were 6% to 8% less likely to be adherent compared with patients paying

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A Review of the Surgical Management of Extrathoracic Solitary Fibrous Tumors

Objectives: Extrathoracic solitary fibrous tumors (ESFTs) are rare low-to-intermediate grade spindle-cell neoplasms of pluripotent fibroblastic or myofibroblastic origin. This review explores prognostic factors in the management of ESFTs and provides guidance on optimal treatment regimens based on the current literature. Patients and Methods: Electronic searches were performed using MEDLINE, Embase, and the Cochrane library to identify studies on prognostic factors in the management of ESFTs published between January 1970 and June 2016. The literature search and review process identified 100 articles that were included in this review article. This included both surgical and nonsurgical studies on the management of ESFTs. Results: Surgical excision with wide resection margins forms the mainstay of treatment and provides optimal long-term oncological outcomes. Large tumor size (>5 to 10 cm diameter), inadequate resection margins, malignant histologic features, dedifferentiation, and tumor location within the abdomen/pelvis are associated with adverse oncological outcomes. Radiotherapy may be used for preoperative tumor shrinkage and/or as adjuvant therapy in patients with malignant disease or incomplete surgical margins. Chemotherapy with molecular-targeted therapies has produced promising results and the results of further phase 2 trials are awaited. Conclusions: Routine long-term follow-up is essential for benign and malignant disease to enable early detection and treatment of recurrent disease.

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Brain MRI morphometric analysis in Parkinson’s disease patients with sleep disturbances

Sleep disturbances are common in patients with advanced Parkinson disease (PD). The aim of this study was to evaluate a possible association of cortical thickness, cortical and subcortical volume with sleep di...

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Features of branch occlusive disease-type intracranial atherosclerotic stroke in young patients

Young ischemic stroke patients are common while classification and analysis based upon imaging characteristics are rarely reported. We intend to compare the clinical and MRI characteristics of cerebral stroke ...

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Evaluation and prognostic significance of manganese superoxide dismutase in clear cell renal cell carcinoma

The antioxidant enzyme manganese superoxide dismutase (MnSOD) is upregulated in renal cell carcinoma (RCC) and has been implicated in multiple stages of RCC tumorigenesis and progression. However, the prognostic significance of MnSOD in RCC has not been fully elucidated. This study aimed to investigate the expression profile of MnSOD in clear cell RCC (ccRCC) tissues and evaluate the clinical significance of this enzyme in ccRCC patients. MnSOD mRNA was assessed in 42 ccRCC and 33 normal kidney tissues by the Oncomine database, and its protein was detected in 145 ccRCC and 3 normal tissues by immunohistochemistry staining (IHC).

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Matrix metalloproteinase-14 induces epithelial-to-mesenchymal transition in synovial sarcoma

Synovial sarcoma (SS) is a highly aggressive malignant soft tissue sarcoma with typical characteristics of both epithelial and mesenchymal differentiation. Matrix metalloproteinase-14 (MMP-14) is reported to play an important role in some of these tumors. It induces epithelial-to-mesenchymal transition (EMT) in some carcinomas, such as breast and prostate cancers. However, the role of MMP-14 in the pathogenesis of SS remains unclear. Therefore, we investigated the role of MMP-14 and EMT/mesenchymal-to-epithelial transition (MET) in SS.

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Outcome After Surgery for Extremity Soft Tissue Sarcoma in Patients Presenting With Metastasis at Diagnosis

Objectives: About 10% of patients present with metastasis at diagnosis in extremity soft tissue sarcoma (STS). Although the prognoses of these patients is generally poor, prolonged survival has been demonstrated in some patients. Thus, better prognostication is needed to guide decisions regarding adjuvant therapy and surveillance. This study sought to analyze the survival and to identify clinicopathologic factors associated with survival in extremity STS patients presenting with metastasis at diagnosis. Materials and Methods: Review of 43 patients presenting with metastasis at diagnosis who underwent resection of the primary tumor was performed. Patient, tumor, and treatment-related factors were analyzed for possible prognostic effect on survival. Results: The median survival of all patients was 22±4.1 months. The 2- and 5-year survival rates were 45.6% and 18.0%, respectively. In univariate analysis, tumor location in lower extremity (P=0.041) and the performance of metastasectomy (P=0.001) were significantly associated with better survival. In multivariate analysis, only the performance of metastasectomy remained significant (hazard ratio=3.8, P=0.012). The median survival of patients who underwent metastasectomy was significantly longer than that of patients who did not undergo metastasectomy (41±8.4 vs. 11±3.8 mo, P=0.001). Conclusions: Extremity STS patients who present with metastasis at diagnosis have a poor prognosis. Patients who undergo metastasectomy have a better chance for prolonged survival.

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Clinical and Economic Evaluation of Treatment Strategies for T1N0 Anal Canal Cancer

Objective: A comparative assessment of treatment alternatives for T1N0 anal canal cancer has never been conducted. We compared the outcomes associated with the treatment alternatives—chemoradiotherapy (CRT), radiotherapy (RT), and surgery or ablation techniques (surgery/ablation)—for T1N0 anal canal cancer. Materials and Methods: This retrospective cohort study was conducted using the Surveillance, Epidemiology and End Results (SEER) registries linked with Medicare longitudinal data (SEER-Medicare database). Analysis included 190 patients who were treated for T1N0 anal canal cancer using surgery/ablation (n=44), RT (n=50), or CRT (n=96). The outcomes were reported in terms of survival and hazards ratios using Kaplan-Meier and Cox proportional hazards modeling, respectively; lifetime costs; and cost-effectiveness measured in terms of incremental cost-effectiveness ratio, that is, the ratio of the difference in costs between the 2 alternatives to the difference in effectiveness between the same 2 alternatives. Results: There was no significant difference in the survival duration between the treatment groups as predicted by the Kaplan-Meier curves. After adjusting for patient characteristics and propensity score, the hazard ratio of death for the patients who received CRT compared with surgery/ablation was 1.742 (95% confidence interval, 0.793-3.829) and RT was 2.170 (95% confidence interval, 0.923-5.101); however, the relationship did not reach statistical significance. Surgery/ablation resulted in lower lifetime cost than RT or CRT. The incremental cost-effectiveness ratio associated with CRT compared with surgery/ablation was $142,883 per life year gained. Conclusions: There was no statistically significant difference in survival among the treatment alternatives for T1N0 anal canal cancer. Given that surgery/ablation costs less than RT or CRT and might be cost-effective compared with RT and CRT, it is crucial to explore this finding further in this era of limited health care resources.

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Impact of Androgen Deprivation Therapy on Overall Mortality in Prostate Brachytherapy Patients With Low Pretreatment Testosterone Levels

Objectives: To evaluate whether the use of androgen deprivation therapy (ADT) in prostate brachytherapy patients impacts overall mortality (OM) in patients with lower pretreatment serum testosterone levels compared with those with normal or high baseline serum testosterone. Materials and Methods: From October 2001 to May 2014, 1916 patients underwent brachytherapy and had a pretreatment serum testosterone. Baseline serum testosterone values were collected prospectively before initiation of therapy. Median follow-up was 7.2 years. In total, 26% of the patients received ADT, primarily men with higher risk disease. OM and prostate cancer–specific mortality were examined to determine whether men with lower baseline serum testosterone were at increased risk of mortality when ADT was used, compared with men with baseline normal or higher testosterone. Results: Prostate cancer–specific mortality and OM at 10 years was 0.8% and 22.0%. Age, tobacco use, diabetes, cardiovascular disease, and percent positive biopsies were the strongest predictors of OM. ADT use by itself was not associated with an increased risk of OM on multivariate analysis (P=0.695). However, ADT use in men with lower baseline testosterone was associated with a significantly higher risk of OM (P

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Hyperfractionated Accelerated Reirradiation for Patients With Recurrent Anal Cancer Previously Treated With Definitive Chemoradiation

Objectives: Although chemoradiation is the standard of care for anal cancer, limited data exist regarding pelvic reirradiation (re-RT) for recurrent disease. We investigated toxicity and outcomes in patients who received prior pelvic radiation therapy (RT), and subsequently underwent hyperfractionated accelerated re-RT to the pelvis for recurrent anal cancer. Materials and Methods: We reviewed records of 10 patients with recurrent anal squamous cell carcinoma who previously received pelvic RT to at least 30 Gy as a component of their chemoradiation and underwent re-RT in 1.5 Gy twice daily fractions to the pelvis, with either preoperative (N=7) or definitive (N=3) intent. Results: The 3-year disease-free survival and 3-year overall survival rates were 40% and 60%. Four patients recurred within the reirradiated field, with a 3-year freedom from local progression rate of 56%. Of the 7 patients treated with preoperative intent, 5 proceeded to surgery, of whom 3 are alive and disease-free at a median duration of 43 months. Of the 3 patients treated definitively with no surgery, all are alive and disease-free at a median duration of 84 months. Re-RT resulted in one grade 3 acute toxicity and no grade 3 or higher late complications. Conclusions: Hyperfractionated accelerated re-RT was well-tolerated in patients with previously irradiated anal cancer. Patients treated with either definitive re-RT or re-RT followed by surgical resection had excellent rates of overall survival and freedom from local progression.

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Clinical Outcomes After Lung Stereotactic Body Radiation Therapy in Patients With or Without a Prior Lung Resection

Objectives: Tumor control (TC), toxicity and survival, following stereotactic body radiation therapy (SBRT) were compared between patients with and without a prior lung resection (PLR). Materials and Methods: The study is comprised of 130 patients with 141 peripheral tumors treated with SBRT at our institution from 2009 to 2013. Primary TC and lobar control (LC) were defined per RTOG 0236. Toxicity was scored using Common Terminology Criteria for Adverse Events version 4.0. Survival/TC and toxicity were compared between patients with and without PLR using the Kaplan-Meier method and cumulative incidence, respectively. Fine and Gray regression was used for univariable/multivariable analysis for radiation pneumonitis (RP). Results: Of the 130 patients with median age 70 years (range, 42 to 93 y), 50 had undergone PLR (median time between PLR and SBRT: 33 mo; range, 1 to 206), including pneumonectomy (12%), lobectomy (46%), wedge resection (42%). With a median follow-up of 21 months in survivors, the PLR group had better TC (1-y 100% vs. 93%; P

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Programmed Cell Death-Ligand 1 (PD-L1) Expression in Anal Cancer

Objective: To evaluate the expression of programmed cell death-ligand 1 (PD-L1) in anal cancer. Patients and Methods: In a retrospective cohort analysis, subjects with squamous cell carcinoma of the anal canal were tested for PD-L1 expression, then followed for recurrence and survival. Crude recurrence rates (CRRs), crude mortality rates (CMRs), and crude event rates (CERs) were assessed for PD-L1-dependent differences using Poisson regression. All 3 types of crude rate were expressed as the number that occurred per hundred person-years (hPY) of follow-up. Results: Samples from 41 subjects were evaluated for PD-L1 expression; 23 (56%) were positive. Subjects with PD-L1-expressing versus PD-L1-negative tumors respectively had CRRs of 30.8 versus 12.1 recurrences/hPY (P=0.082), CMRs of 16.7 versus 12.0 deaths/hPY (P=0.47), and CERs of 39.2 versus 16.9 events/hPY (P=0.069). Conclusions: PD-L1 positivity was associated with worse CRR and CER, and marginally worse CMR. The effect on progression-free and overall survival needs to be validated in a study with a larger sample size.

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Phase II Study of Adjuvant Chemoradiotherapy Using Docetaxel/Cisplatin/5-Fluorouracil Before and After Intensity-modulated Radiotherapy With Concurrent Docetaxel in Patients With Completely (R0) Resected Gastric Carcinoma

Objectives: The Intergroup 0116 study has demonstrated a significant survival benefit for completely resected (R0) gastric cancer patients treated with a fluorouracil/leucovorin chemoradiotherapy regimen. However, this regimen is also toxic and less effective in terms of distant disease control. Therefore, a more efficacious and safer regimen is urgently needed. Methods: Patients with R0 resected gastric carcinoma received up to two 21-day cycles of postoperative adjuvant preradiation and postradiation DCF chemotherapy (docetaxel 37.5 mg/m2 on days 1 and 8, cisplatin 25 mg/m2 on days 1 to 3, and a continuous infusion of fluorouracil 750 mg/m2 on days 1 to 5), respectively. Chemoradiotherapy between preradiation and postradiation chemotherapy was initiated on day 43 and consisted of intensity-modulated radiotherapy (45 Gy) plus concurrent docetaxel 20 mg/m2 weekly for 5 weeks. Results: A total of 55 patients were evaluated and 76% (42) of patients completed the prescribed therapy. With a median follow-up of 61 months, the 3- and 5-year progression-free survival rates were 67% (95% confidence interval [CI], 54%-80%) and 59% (95% CI, 46%-72%), respectively; and the 3- and 5-year overall survival rates were 72% (95% CI, 60%-84%) and 61% (95% CI, 48%-74%), respectively. The most common grade 3 or greater toxicity, during the chemotherapy phase, was neutropenia (24%). Common grade 3/4 toxicities during concurrent chemoradiotherapy were nausea (32%), vomiting (26%), fatigue (15%), and anorexia (19%). Conclusions: These results demonstrate that this adjuvant regimen is active with an acceptable toxicity profile. A randomized phase 3 trial comparing the Intergroup 0116 chemoradiotherapy regimen with this regimen is underway.

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Impact of Postoperative Adjuvant Chemotherapy Following Long-course Chemoradiotherapy in Stage II Rectal Cancer

Objectives: Use of adjuvant chemotherapy (AC) following neoadjuvant chemoradiation (nCRT) is controversial in rectal cancer (RC). We assessed a multi-institutional database to determine if there was benefit from AC for pathologic stage II RC patients and whether the addition of oxaliplatin to fluoropyrimidine (OXAC) therapy impacted outcomes. Materials and Methods: We included patients who underwent nCRT and had pathologic stage II (ypT3/4 ypN0) tumors. Disease-free survival and overall survival were assessed. Multivariate Cox models adjusting for age, sex, Eastern Cooperative Oncology Group, high-risk features (pT4, poor differentiation,

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Benefit of Radiotherapy in Extraskeletal Myxoid Chondrosarcoma: A Propensity Score Weighted Population-based Analysis of the SEER Database

Objectives: Extraskeletal myxoid chondrosarcoma (EMC) is a rare malignancy for which the role of radiotherapy is not well-defined. We examine the effect of external beam radiotherapy (EBRT) on cancer-specific survival (CSS) for patients with localized EMC, in a propensity score weighted, population-based analysis. Materials and Methods: The Surveillance, Epidemiology, and End Results database (1973 to 2012) was queried for cases of localized EMC arising from soft connective tissues of the trunk and extremities treated with surgery and/or EBRT. Inverse probability treatment weighting was utilized, with survival analysis by weighted Cox regression and Kaplan-Meier analysis with log-rank testing. The primary endpoint was CSS. Results: One hundred seventy-two patients were identified, diagnosed from 2004 to 2012. Ninety-four percent and 32% of 156 assessable patients underwent surgery and EBRT, respectively. By inverse probability treatment weighting, balancing covariates of age group, sex, race, grade, T stage, N stage, receipt of surgery, and anatomic site, we observed CSS of 97% versus 85% and 94% versus 85% in patients receiving EBRT versus no EBRT, at 3 and 5 years, respectively, at median follow-up of 33 months, P=0.01. A trend toward an overall survival benefit associated with EBRT was noted, P=0.06. Further adjusting for type of resection performed, CSS benefit persisted, 97% versus 85% at 3 years and 94% versus 85% at 5 years, P=0.02, with trend toward an overall survival benefit, P=0.08. Conclusions: The receipt of EBRT is associated with a CSS benefit in localized EMC. Aggressive local therapy, including EBRT, should be considered in these patients.

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A Multicenter Phase II Study of Gemcitabine, Capecitabine, and Bevacizumab for Locally Advanced or Metastatic Biliary Tract Cancer

Objectives: Vascular endothelial growth factor overexpression, seen in 42% to 76% of biliary tract cancers (BTCs), correlates with poor survival. We explored the safety/efficacy and potential biomarkers for bevacizumab in combination with gemcitabine-capecitabine in advanced BTCs. Patients and Methods: Inoperable stage III/IV BTC patients in our prospective study were given 1000 mg/m2 of gemcitabine (on days 1, 8), 650 mg/m2 of capecitabine (on days 1 to 14), and 15 mg/kg of bevacizumab (on day 1) in 21-day cycles. Circulating tumor cells and quality of life were assessed at baseline and before cycle 2 and 3. Results: In total, 50 patients with gallbladder cancer (22%), intrahepatic (58%), and extrahepatic (20%) cholangiocarcinoma, received a median of 8 treatment cycles for median treatment duration of 5.8 months. Common grade 3/4 toxicities were neutropenia (36%), thrombocytopenia (16%), fatigue (20%), infections (14%), and hand-foot syndrome (10%). There were 12 partial response (24%), 24 stable disease (48%) with clinical benefit rate of 72%. Median progression-free survival was 8.1 months (95% confidence interval, 5.3-9.9). Median overall survival was 10.2 months (95% confidence interval, 7.5-13.7). Circulating tumor cells were identified at baseline in 21/46 patients (46%), who had lower median overall survival compared with those without (9.4 vs. 13.7 mo; P=0.29). Patients with quality of life scores greater than the group median by the end of first cycle of treatment had improved survival compared with those who did not (13.3 vs. 9.4 mo; P=0.39). Conclusions: Addition of bevacizumab to gemcitabine/capecitabine did not improve outcome in an unselected group of patients with advanced BTC compared with historical controls. The selective benefit of vascular endothelial growth factor inhibition in BTC remains to be explored.

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Tolerability and Long-term Outcomes of Dose-Painted Neoadjuvant Chemoradiation to Regions of Vessel Involvement in Borderline or Locally Advanced Pancreatic Cancer

Purpose: We reviewed our experience involving patients with borderline resectable or locally advanced pancreatic cancer, treated with the dose-painted (DP) boost technique to regions of vessel involvement which preclude upfront surgical resection. We evaluated patient outcomes with respect to tolerability and treatment outcomes. Materials and Methods: We retrospectively reviewed 99 patients with borderline resectable (n=25) or locally advanced pancreatic cancer (n=74) treated with DP-neoadjuvant chemoradiation from 2010 to 2015. Tumor and regional lymph nodes were prescribed 50.4 Gy and the region around the involved blood vessel was boosted to 58.8 Gy in 28 fractions. The primary outcome was acute toxicity and late duodenal toxicity. Secondary outcomes included conversion to surgical resectability, local failure, disease-free survival, and overall survival (OS). Cox proportional hazards models were performed to evaluate for predictors of survival. Results: All but 1 patient completed chemoradiation. The rates of grade 2+ and 3+ nausea were 40% and 12%, respectively. With regards to late toxicity, 5 patients developed potential RT-related grade 3+ duodenal complications including duodenal ulceration/bleeding (n=3) and duodenal stricture (n=2). With a median follow-up of 15 months, the median OS was 18.1 months. Among 99 patients in our study, 37 patients underwent surgical resection. For patients who underwent surgical resection (n=37), the median OS was 30.9 months. On multivariate analysis, only normalization of CA 19-9 post-RT was associated with improved OS. Conclusions: We found that DP-neoadjuvant chemoradiation to regions of vessel involvement is both feasible and well tolerated. In addition, we demonstrated that over one third of patients with initially deemed unresectable disease were able to undergo surgical resection after receiving neoadjuvant therapy including DP-chemoradiation.

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Axillary Ultrasound Fine Needle Aspiration Biopsy: Is There a Role in the Post Z-0011 Era?

Objectives: Axillary ultrasound with fine needle aspiration (AXUSFNA) in early-stage breast cancer has required reappraisal. ACOSOG Z-0011 and after mapping of the axilla: radiotherapy or surgery have shown that women with limited nodal disease at sentinel lymph node biopsy got no survival advantage with completion axillary node dissection. We hypothesize that AXUSFNA may be sufficiently accurate for staging for some patients and sentinel lymph node biopsy need not be performed. We define the false negative rate (FNR) of AXUSFNA in different subsets of patients. Materials and Methods: This retrospective cohort study included node positive patients who also underwent AXUSFNA between 1/2006 and 12/2010 followed by axillary surgery. The FNR was calculated for the entire group and for subgroups determined by tumor, nodal, and ultrasound findings. Results: Out of ∼700 AXUSFNA patients, 128 node positive patients were included in the study. The overall AXUSFNA FNR was 35.9% (95% confidence interval, 28.1%-44.6%). There was a significantly higher FNR with smaller tumors and presence of ductal carcinoma in situ on multivariate analysis. On ultrasound, benign-appearing nodes had a higher FNR than indeterminate nodes (78.9% vs. 60.9%, P=0.2) and significantly higher than suspicious nodes (78.9% vs. 2.9%, P

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Challenges in Management of Squamous Cell Carcinoma of the Anus in New England and Across the United States: A Review of the National Cancer Data Base

Background: Management of squamous cell carcinoma of the anus (SCCA) is becoming more relevant, as its incidence continues to increase. The purpose of this study was to evaluate regional and national data to assess trends in epidemiology, access to cancer center care, and overall management strategies in SCCA. Study Design: A review of available data from the American College of Surgeons Committee on Cancer National Cancer Data Base focused on incidence, sex, age, stage at diagnosis, distance traveled for care, and utilization of therapy as first course of treatment (FCT). The analysis included 40,817 patients treated for SCCA at 1513 cancer centers in the United States, of which 2347 patients were treated at 109 cancer centers in New England, between the years 2003 and 2013. Results: Over the 11-year period, incidence of SCCA increased by 76% in the United States and by 83.8% in New England. Stage was unknown in 11.7% of all US cases, significantly higher than more common cancers, for example, breast (4.3%), prostate (6%), or colon (7.8%) (P25 miles less often (14.3% vs. 28.7%) (P

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Safety and Outcome Measures of First-in-Human Intraperitoneal α Radioimmunotherapy With 212Pb-TCMC-Trastuzumab

Purpose: One-year monitoring of patients receiving intraperitoneal (IP) 212Pb-TCMC-trastuzumab to provide long-term safety and outcome data. A secondary objective was to study 7 tumor markers for correlation with outcome. Methods: Eighteen patients with relapsed intra-abdominal human epidermal growth factor receptor-2 expressing peritoneal metastases were treated with a single IP infusion of 212Pb-TCMC-trastuzumab, delivered

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Circulating biomarkers during treatment in patients with advanced biliary tract cancer receiving cediranib in the UK ABC-03 trial

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Validation of the IBIS breast cancer risk evaluator for women with lobular carcinoma in-situ

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Transglutaminase type 2 in the regulation of proteostasis

Journal Name: Biological Chemistry
Issue: Ahead of print


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Specificity profiling of human trypsin-isoenzymes

Journal Name: Biological Chemistry
Issue: Ahead of print


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New clues into the self-assembly of Vmh2, a basidiomycota class I hydrophobin

Journal Name: Biological Chemistry
Issue: Ahead of print


https://ift.tt/2tdbaqE

Model construction of Niemann-Pick type C disease in zebrafish

Journal Name: Biological Chemistry
Issue: Ahead of print


https://ift.tt/2I59hkt

Angiotensin II and tumor necrosis factor-α stimulate the growth, migration and invasion of BEL-7402 cells via down-regulation of GRK2 expression

To investigate the effects of angiotensin II (Ang II) and tumor necrosis factor-α (TNF-α) on the biological characteristics of hepatocellular carcinoma (HCC) cells and the associated changes in G protein-coupled receptor kinase 2 (GRK2) expression.

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Thrombopoietin receptor agonists and risk of portal vein thrombosis in Patients with Liver disease and Thrombocytopenia: a meta-analysis

Treatment of thrombocytopenia with thrombopoietin receptor agonists (TPORAs) seems to be associated with portal vein thrombosis (PVT) in patients with chronic liver disease (CLD). We performed a meta-analysis of the trials carried out in this clinical setting to assess if such association is detectable.

https://ift.tt/2MKsdbV

Tumor analysis: freeze–thawing cycle of triple-negative breast cancer cells alters tumor CD24/CD44 profiles and the percentage of tumor-infiltrating immune cells

The use of novel methods to characterize living tumor cells relies on well-conceived biobanks. Herein, we raised the question of whether the composition of fresh and freeze/thawed dissociated tumor samples is ...

https://ift.tt/2yt4Ctb

The efficacy of high-dose penicillin G for pneumococcal pneumonia diagnosed based on initial comprehensive assessment at admission: an observational study

High-dose penicillin therapy is effective in approximately 90% of pneumococcal pneumonia cases diagnosed based on urinary pneumococcal antigen tests or Gram staining at admission. The efficacy of high-dose pen...

https://ift.tt/2MFuCEq

Value of peripheral blood count for dengue severity prediction

This retrospective study was conducted in 2017 with the objective of evaluating the value of acute phase peripheral blood parameters in predicting dengue haemorrhagic fever (DHF). Patients, who were admitted t...

https://ift.tt/2yDqmCL

A randomized controlled trial comparing efficacy of early video capsule endoscopy with standard of care in the approach to non-hematemesis gastrointestinal bleeding (with videos)

Patients presenting with non-hematemesis GI bleeding represent a diagnostic challenge for physicians. We performed a randomized controlled trial to assess the benefits of deployment of a video capsule soon after admission in the management of patients presenting with melena, hematochezia, or severe anemia compared with standard of care management.Design: Patients admitted with non-hematemesis GI bleeding were randomized and placed into one of 2 study groups. In the experimental group patients ingested a video capsule soon after admission to the hospital.

https://ift.tt/2MH5BZC

Effects of Electronic Chromoendoscopy on Detection of Adenomas During Colonoscopy

I-scan is an electronic chromoendoscopy technology that improves resolution of epithelial and mucosal surfaces and vessels. We performed a randomized controlled trial to compare detection of adenomas by i-scan vs standard high-definition white-light (HDWL) colonoscopy.

https://ift.tt/2K4fjDG

Assessment of Liver Fibrosis with Elastography Point Quantification vs Other Non-Invasive Methods

Elastography point quantification (ElastPQ) is a non-invasive method for assessing liver fibrosis based on liver stiffness. We evaluated the accuracy of ElastPQ for the staging of liver fibrosis in patients with chronic liver disease (CLD) compared with aspartate transaminase to platelet ratio index, fibrosis-4 index, and transient elastography (TE), using liver biopsy as reference standard.

https://ift.tt/2K5cVjb

Incidence and Prevalence of Pediatric Eosinophilic Esophagitis in Utah Based on a 5-Year Population-Based Study

Eosinophilic esophagitis (EoE) is often detected in children and is considered to be a rare disease, with prevalence values reported to be below 60 cases per 100,000 persons. To determine whether the incidence of EoE in children in Utah exceeds estimates from regional reports, we calculated incidence and prevalence values over a 5-year period.

https://ift.tt/2I9aLKh

Loss of Response to Vedolizumab and Ability of Dose Intensification to Restore Response in Patients With Crohn’s Disease or Ulcerative Colitis: a Systematic Review and Meta-analysis

Vedolizumab is effective and safe for the treatment of Crohn's disease (CD) and ulcerative colitis (UC). Little is known about the incidence rate of loss of response to vedolizumab maintenance therapy or whether dose intensification restores response to this drug.

https://ift.tt/2Kdgcgm

Reduced Hepatocellular Expression of Canalicular Transport Proteins in Infants with Neonatal Cholestasis and Congenital Hypopituitarism

To assess whether prolonged neonatal cholestasis, described in congenital hypopituitarism and septo-optic dysplasia (SOD), is associated with altered expression of selected canalicular ectoenzymes and canalicular transport proteins.

https://ift.tt/2I5GUCx

Ethanol extracts from the branch of Taxillus yadoriki parasitic to Neolitsea sericea induces cyclin D1 proteasomal degradation through cyclin D1 nuclear export

Although the inhibitory effect of mistletoe on cancer cell growth has been reported, the underlying mechanisms to explain its anti-proliferative activity are not fully studied. Thus, we elucidated the potentia...

https://ift.tt/2JZXOnY

Hand-foot-mouth disease and use of steroids, intravenous immunoglobulin, and traditional Chinese herbs in a tertiary hospital in Shantou, China

In contrast to the guidelines of World Health Organization (WHO) and United States-Centers for Disease Control and prevention (US-CDC), the Chinese national guidelines recommend the use of steroids, intravenou...

https://ift.tt/2K8Of9z

Heparan Sulfate Binding Coxsackievirus B3 Strain PD: A Novel Avirulent Oncolytic Agent Against Human Colorectal Carcinoma

Human Gene Therapy, Ahead of Print.


https://ift.tt/2toipLz

LDHA in neuroblastoma is associated with poor outcome and its depletion decreases neuroblastoma growth independent of aerobic glycolysis

Purpose: To investigate whether lactate dehydrogenase A (LDHA), an important component of the LDH tetramer crucial for aerobic glycolysis, is associated with patient outcome and constitutes a therapeutic target in neuroblastoma (NB). Experimental Design: Expression of LDHA mRNA and protein was determined in 709 and 110 NB patient samples, respectively, and correlated to survival and risk factors. LDHA and LDHB were depleted in human NB cell lines by CRISPR/Cas9 and shRNA, respectively, and aerobic glycolysis, clonogenicity and tumorigenicity were determined. Expression of LDHA in relation to MYCN was measured in NB cell lines and in the TH-MYCN NB mouse model. Results: Expression of LDHA, both on the mRNA and the protein level, was significantly and independently associated with decreased patient survival. Predominant cytoplasmic localization of LDHA protein was associated with poor outcome. Amplification and expression of MYCN did not correlate with expression of LDHA in NB cell lines or TH-MYCN mice, respectively. Knockout of LDHA inhibited clonogenicity, tumorigenicity and tumor growth without abolishing LDH activity or significantly decreasing aerobic glycolysis. Concomitant depletion of LDHA and the isoform LDHB ablated clonogenicity while not abrogating LDH activity or decreasing aerobic glycolysis. The isoform LDHC was not expressed. Conclusions: High expression of LDHA is independently associated with poor outcome of NB and NB cells can be inhibited by depletion of LDHA or LDHB. This inhibition appears to be unrelated to LDH activity and aerobic glycolysis. Thus, investigations of inhibitory mechanisms beyond attenuation of aerobic glycolysis are warranted, both in NB and normal cells.

https://ift.tt/2I73jzi

Cytogenetic clonal heterogeneity is not an independent prognosis factor in 15–60-year-old AML patients: results on 1291 patients included in the EORTC/GIMEMA AML-10 and AML-12 trials

Abstract

The presence of cytogenetic clonal heterogeneity has been associated with poor prognosis in patients with acute myeloid leukemia (AML). Here, we reassessed this association. The study cohort consisted of all patients with an abnormal karyotype randomized in the EORTC/GIMEMA AML-10 and AML-12 trials. Abnormal karyotypes were classified as no subclones present (cytogenetic abnormality in a single clone), defined subclones present (presence of one to three subclones), and composite karyotypes (CP) (clonal heterogeneity not allowing enumeration of individual subclones). The main endpoints were overall survival (OS) and disease-free survival (DFS). Among 1291 patients with an abnormal karyotype, 1026 had no subclones, 226 at least 1 subclone, and 39 a CP. Patients with defined subclones had an OS similar to those with no subclones (hazard ratio (HR) 1.05, 95% confidence interval (CI) 0.88–1.26), but CP patients had a shorter OS (HR = 1.58, 95% CI 1.11–2.26). However, in a multivariate Cox model stratified by protocol and adjusted for age, cytogenetic risk group, secondary versus primary AML, and performance status, clonal heterogeneity lost its prognostic importance (HR = 1.10, 95% CI 0.91–1.32 for defined subclones versus no subclones; HR = 0.96, 95% CI 0.67–1.38 for CP versus no subclones). Also, the impact of having a donor on DFS was similar in the three clonal subgroups. In summary, in patients with cytogenetic abnormality, presence of subclones had no impact on OS. The dismal outcome in patients with a CP was explained by the known predictors of poor prognosis. Trial registration: AML-10: ClinicalTrials.gov identifier: NCT00002549, retrospectively registered July 19, 2004; AML12: ClinicalTrials.gov identifier: NCT00004128, registered January 27, 2003.

https://ift.tt/2topcFi

Technical complications following implant‐supported restorative therapy performed in Sweden

Clinical Oral Implants Research, EarlyView.


https://ift.tt/2K3yRrU

Concomitant administration of radiation with eribulin improves the survival of mice harboring intracerebral glioblastoma

Cancer Science, EarlyView.


https://ift.tt/2ysH87o

Learning a Phonological Contrast Modulates the Auditory Grouping of Rhythm

Cognitive Science, EarlyView.


https://ift.tt/2MHZfZW

SERPINB2 is a novel indicator of stem cell toxicity

SERPINB2 is a novel indicator of stem cell toxicity

SERPINB2 is a novel indicator of stem cell toxicity, Published online: 20 June 2018; doi:10.1038/s41419-018-0748-x

SERPINB2 is a novel indicator of stem cell toxicity

https://ift.tt/2ln2YzT

Cardiac-derived CTRP9 protects against myocardial ischemia/reperfusion injury via calreticulin-dependent inhibition of apoptosis

Cardiac-derived CTRP9 protects against myocardial ischemia/reperfusion injury via calreticulin-dependent inhibition of apoptosis

Cardiac-derived CTRP9 protects against myocardial ischemia/reperfusion injury via calreticulin-dependent inhibition of apoptosis, Published online: 20 June 2018; doi:10.1038/s41419-018-0726-3

Cardiac-derived CTRP9 protects against myocardial ischemia/reperfusion injury via calreticulin-dependent inhibition of apoptosis

https://ift.tt/2tqGamc

Major changes in the composition of a Southern Ocean bacterial community in response to diatom-derived dissolved organic matter

The publisherapologizes that the one sentence summary in this paper (DOI: 10.1093/femsec/fiy034) contained errors. The text has now been corrected.

https://ift.tt/2JVvGGH

Transient negative effects of antibiotics on phages do not jeopardise the advantages of combination therapies

ABSTRACT

Phages, the viruses of bacteria, have been proposed as antibacterial agents to complement or replace antibiotics due to the growing problem of resistance. In nature and in the clinic, antibiotics are ubiquitous and may affect phages indirectly via impacts on bacterial hosts. Even if the synergistic association of phages and antibiotics has been shown in several studies, the focus is often on bacteria with little known about the impact on phages. Evolutionary studies have demonstrated that time scale is an important factor in understanding the consequences of antimicrobial strategies, but this perspective is generally overlooked in phage-antibiotic combination studies. Here, we explore the effects of antibiotics on phages targeting the opportunistic pathogen Pseudomonas aeruginosa. We go beyond previous studies by testing the interaction between several types of antibiotics and phages, and evaluate the effects on several important phage parameters during 8 days of experimental co-evolution with bacteria. Our study reveals that antibiotics had a negative effect on phage density and efficacy early on, but not in the later stages of the experiment. The results indicate that antibiotics can affect phage adaptation, but that phages can nevertheless contribute to managing antibiotic resistance levels.

https://ift.tt/2M8DyBj

Methods for field measurement of antibiotic concentrations: limitations and outlook

ABSTRACT

The growing prevalence of antibiotic resistance poses an increasingly serious threat to human health. Although an important driver of antibiotic resistance is the continuous exposure of bacteria to sublethal concentrations of antibiotics in natural environments, antibiotic pollutants are not currently tracked globally or systematically. This limits the international capacity to address the rise of antibiotic resistance at its source. To address this lack of data, the development of methods to measure antibiotic concentrations on-site is essential. These methods, ideally, must be sensitive to sublethal concentrations of antibiotics and require minimal technical expertise. Furthermore, factors such as cost, selectivity, biosafety and the ability to multiplex must be evaluated in the context of field use. Based on these criteria, we provide a critical review of current methods in antibiotic detection and evaluate their adaptability for use on-site. We categorize these methods into microbiological assays, physical and chemical assays, immunoassays, aptasensors and whole-cell biosensors. We recommend continued development of a dipstick or microfluidics approach with a bacterial promoter-based mechanism and colorimetric output. This technique would incorporate the advantageous aspects of existing methods, maximize shelf-life and ease-of-use, and require minimal resources to implement in the field.

https://ift.tt/2MHN2of

From Antimicrobial Peptides to Antimicrobial Poly(α‐amino acid)s

Advanced Healthcare Materials, EarlyView.


https://ift.tt/2lnTJzu

Nanocellulose‐Based Antibacterial Materials

Advanced Healthcare Materials, EarlyView.


https://ift.tt/2yuqunY

mRNA Delivery System for Targeting Antigen‐Presenting Cells In Vivo

Advanced Healthcare Materials, EarlyView.


https://ift.tt/2lnTDYE

Multivalent Ligands: Integrin Clustering Matters: A Review of Biomaterials Functionalized with Multivalent Integrin‐Binding Ligands to Improve Cell Adhesion, Migration, Differentiation, Angiogenesis, and Biomedical Device Integration (Adv. Healthcare Mater. 12/2018)

Advanced Healthcare Materials, Volume 7, Issue 12, June 20, 2018.


https://ift.tt/2tnEie8

High exposure compared with standard exposure to metoclopramide associated with a higher risk of parkinsonism: a nationwide population‐based cohort study

British Journal of Clinical Pharmacology, EarlyView.


https://ift.tt/2tpj2ES

The UK's Life Sciences Strategy: opportunities for clinical pharmacology

British Journal of Clinical Pharmacology, EarlyView.


https://ift.tt/2lqfWfX

Appropriateness of oral anticoagulant therapy prescription and its associated factors in hospitalized older people with atrial fibrillation

British Journal of Clinical Pharmacology, EarlyView.


https://ift.tt/2yv0sks

Moderate correlation between systemic IL‐6 responses and CRP with trough concentrations of voriconazole

British Journal of Clinical Pharmacology, EarlyView.


https://ift.tt/2lkUYiD

Physiologically‐based pharmacokinetic model of vaginally administered dapivirine ring and film formulations

British Journal of Clinical Pharmacology, EarlyView.


https://ift.tt/2yuZJje

Stakeholders' views and experiences of pharmacist prescribing: a systematic review

British Journal of Clinical Pharmacology, EarlyView.


https://ift.tt/2lobGxO

HbA1c Targets Should Be Personalized in Type 2 Diabetes

WEDNESDAY, June 20, 2018 -- For non-pregnant adults with type 2 diabetes, hemoglobin A1c (HbA1c) targets should be personalized, according to a Clinical Guidelines Synopsis published in the June 19 issue of the Journal of the American Medical...

https://ift.tt/2I5i1qB

Adult Obesity Prevalence Varies With Level of Urbanization

WEDNESDAY, June 20, 2018 -- For U.S. adult males and females, the prevalence of obesity is 38.9 percent and varies with level of urbanization, according to a study published in the June 19 issue of the Journal of the American Medical...

https://ift.tt/2KcNUTz

Attitudes Among Obese Are Not Aligned With Healthy Living

WEDNESDAY, June 20, 2018 -- Food-related policies differently impact consumers with obesity and healthy weight, according to a report published by the Hudson Institute. Hank Cardello, from the Food Policy Center at the Hudson Institute in...

https://ift.tt/2I5hZit

FIRS: Guidance Offered for Protecting Youth From E-Cigarettes

WEDNESDAY, June 20, 2018 -- Youth should be protected from electronic cigarettes and other nicotine delivery devices, according to a position statement from the Forum of International Respiratory Societies published online May 31 in the European...

https://ift.tt/2K5TEye

Some Neonatal Risks for Lithium Exposure in Pregnancy

WEDNESDAY, June 20, 2018 -- In utero lithium exposure is associated with an increased risk for neonatal readmission and major malformations, according to a meta-analysis published online June 18 in The Lancet Psychiatry. Trine Munk-Olsen, Ph.D.,...

https://ift.tt/2JZvfXM

Various Factors Affect Progress in Back-Related Leg Pain, Sciatica

WEDNESDAY, June 20, 2018 -- In back-related leg pain and sciatica patients, belief in a long recovery and the number of other symptoms attributed to the pain are independently negatively associated with improvement, according to a study published in...

https://ift.tt/2K7gMMD

Gender Difference in Survival Seen After Radical Cystectomy

WEDNESDAY, June 20, 2018 -- Compared with males, females who undergo radical cystectomy for bladder cancer have worse disease-free, cancer-specific, and overall survival, according to a review published in the July issue of The Journal of...

https://ift.tt/2I5hUvb

Sociodemographic Factors Impact Heart-Healthy Behaviors

WEDNESDAY, June 20, 2018 -- Socioeconomic factors, largely outside an individual's control, account for racial differences in cardiovascular health behaviors, according to a study published in the July issue the American Journal of Preventive...

https://ift.tt/2K7uOxL

Many Drugs Made Available Via FDA Expanded Access Programs

WEDNESDAY, June 20, 2018 -- Over the past two decades, close to 100 U.S. Food and Drug Administration (FDA)-approved drugs and biologics were made available before FDA approval through expanded access programs, according to a study published online...

https://ift.tt/2I5hSU5

Cardiovascular Comorbidity Tied to Hearing Loss in Older Old

WEDNESDAY, June 20, 2018 -- Cardiovascular disease (CVD) and related risk factors are associated with hearing loss among the older old, according to a study published online June 14 in JAMA Otolaryngology-Head & Neck Surgery. Kapil Wattamwar,...

https://ift.tt/2K7gIMT

The intersection of financial toxicity and family building in young adult cancer survivors

Cancer, EarlyView.


https://ift.tt/2MHThIw

Imaging FITC-dextran as a Reporter for Regulated Exocytosis

Here we detail a method for live cell imaging of regulated exocytosis. This method utilizes FITC-dextran, which accumulates in lysosome-related organelles, as a reporter. This simple method also allows distinguishing between different modes of regulated exocytosis in cells that are difficult to manipulate genetically.

https://ift.tt/2to4dSN

Fluorescence Live-cell Imaging of the Complete Vegetative Cell Cycle of the Slow-growing Social Bacterium Myxococcus xanthus

Bacterial cells are spatially highly organized. To follow this organization over time in slow growing Myxococcus xanthus cells, a set-up for fluorescence live-cell imaging with high spatiotemporal resolution over several generations was developed. Using this method, spatiotemporal dynamics of important proteins for chromosome segregation and cell division could be determined.

https://ift.tt/2MK6oZF

Induction and Validation of Cellular Senescence in Primary Human Cells

Here, we discuss a series of protocols for induction and validation of cellular senescence in cultured cells. We focus on different senescence-inducing stimuli and describe the quantification of common senescence-associated markers. We provide technical details using fibroblasts as a model, but the protocols can be adapted to various cellular models.

https://ift.tt/2ys84Ef

Surgery in space

BJS, EarlyView.


https://ift.tt/2K4kNyn

Antioxidant Activity of Essential Oils Extracted from Aloysia triphylla and Minthostachys mollis that Improve the Oxidative Stability of Sunflower Oil under Accelerated Storage Conditions

European Journal of Lipid Science and Technology, EarlyView.


https://ift.tt/2JVvhUI

Rapid Biofilm Eradication on Bone Implants Using Red Phosphorus and Near‐Infrared Light

Advanced Materials, EarlyView.


https://ift.tt/2yvhn6o

Bioinspired Hierarchical Porous Structures for Engineering Advanced Functional Inorganic Materials

Advanced Materials, EarlyView.


https://ift.tt/2lnHfYD

Solution‐Processed 3D RGO–MoS2/Pyramid Si Heterojunction for Ultrahigh Detectivity and Ultra‐Broadband Photodetection

Advanced Materials, EarlyView.


https://ift.tt/2tm4qpH

Ultrathin CsPbX3 Nanowire Arrays with Strong Emission Anisotropy

Advanced Materials, EarlyView.


https://ift.tt/2lknNf2

Robust Expandable Carbon Nanotube Scaffold for Ultrahigh‐Capacity Lithium‐Metal Anodes

Advanced Materials, EarlyView.


https://ift.tt/2ysuyF1

Fundamental Properties in Colloidal Quantum Dots

Advanced Materials, EarlyView.


https://ift.tt/2lo67PW

An Ultrabroadband Mid‐Infrared Pulsed Optical Switch Employing Solution‐Processed Bismuth Oxyselenide

Advanced Materials, EarlyView.


https://ift.tt/2lqd9mZ

Recent Advances in Morphology Optimization for Organic Photovoltaics

Advanced Materials, EarlyView.


https://ift.tt/2toe7UI

Adsorption and Detection of Hazardous Trace Gases by Metal–Organic Frameworks

Advanced Materials, EarlyView.


https://ift.tt/2lknMaY

Emerging Hierarchical Aerogels: Self‐Assembly of Metal and Semiconductor Nanocrystals

Advanced Materials, EarlyView.


https://ift.tt/2ysutkH

Remote Control over Underwater Dynamic Attachment/Detachment and Locomotion

Advanced Materials, EarlyView.


https://ift.tt/2lmt1XV

Self‐Folded Gripper‐Like Architectures from Stimuli‐Responsive Bilayers

Advanced Materials, EarlyView.


https://ift.tt/2yvhe2Q

Case of small intestinal bacterial overgrowth carried out by capsule and double‐balloon endoscopy

Digestive Endoscopy, EarlyView.


https://ift.tt/2yulHD0

Neuropeptide Y affects thalamic reticular nucleus neuronal firing and network synchronization associated with suppression of spike‐wave discharges

Epilepsia, EarlyView.


https://ift.tt/2ysuANk

WT1-Expressing Interneurons Regulate Left-Right Alternation during Mammalian Locomotor Activity

The basic pattern of activity underlying stepping in mammals is generated by a neural network located in the caudal spinal cord. Within this network, the specific circuitry coordinating left–right alternation has been shown to involve several groups of molecularly defined interneurons. Here we characterize a population of spinal neurons that express the Wilms' tumor 1 (WT1) gene and investigate their role during locomotor activity in mice of both sexes. We demonstrate that WT1-expressing cells are located in the ventromedial region of the spinal cord of mice and are also present in the human spinal cord. In the mouse, these cells are inhibitory, project axons to the contralateral spinal cord, terminate in close proximity to other commissural interneuron subtypes, and are essential for appropriate left–right alternation during locomotion. In addition to identifying WT1-expressing interneurons as a key component of the locomotor circuitry, this study provides insight into the manner in which several populations of molecularly defined interneurons are interconnected to generate coordinated motor activity on either side of the body during stepping.

SIGNIFICANCE STATEMENT In this study, we characterize WT1-expressing spinal interneurons in mice and demonstrate that they are commissurally projecting and inhibitory. Silencing of this neuronal population during a locomotor task results in a complete breakdown of left–right alternation, whereas flexor-extensor alternation was not significantly affected. Axons of WT1 neurons are shown to terminate nearby commissural interneurons, which coordinate motoneuron activity during locomotion, and presumably regulate their activity. Finally, the WT1 gene is shown to be present in the spinal cord of humans, raising the possibility of functional homology between these species. This study not only identifies a key component of the locomotor circuitry but also begins to unravel the connectivity among the growing number of molecularly defined interneurons that comprise this neural network.

https://ift.tt/2K6mtuy

Identification and Characterization of a Novel Spontaneously Active Bursty GABAergic Interneuron in the Mouse Striatum

The recent availability of different transgenic mouse lines coupled with other modern molecular techniques has led to the discovery of an unexpectedly large cellular diversity and synaptic specificity in striatal interneuronal circuitry. Prior research has described three spontaneously active interneuron types in mouse striatal slices: the cholinergic interneuron, the neuropeptide Y-low threshold spike interneuron, and the tyrosine hydroxylase interneurons (THINs). Using transgenic Htr3a-Cre mice, we now characterize a fourth population of spontaneously active striatal GABAergic interneurons termed spontaneously active bursty interneurons (SABIs) because of their unique burst-firing pattern in cell-attached recordings. Although they bear some qualitative similarity in intrinsic electrophysiological properties to THINs in whole-cell recordings, detailed analysis revealed significant differences in many intrinsic properties and in their morphology. Furthermore, all previously identified striatal GABAergic interneurons have been shown to innervate striatal spiny projection neurons (SPNs), contributing to the suggestion that the principal function of striatal GABAergic interneurons is to provide feedforward inhibition to SPNs. Here, very surprisingly, paired recordings show that SABIs do not innervate SPNs significantly. Further, optogenetic inhibition of striatal Htr3a-Cre interneurons triggers barrages of IPSCs in SPNs. We hypothesize that these IPSCs result from disinhibition of a population of GABAergic interneurons with activity that is constitutively suppressed by the SABIs. We suggest that the SABIs represent the first example of a striatal interneuron-selective interneuron and, further, that their existence, along with previously defined interneuronal networks, may participate in the formation of SPN ensembles observed by others.

SIGNIFICANCE STATEMENT Before ~2010, the main function of the three known subtypes of striatal GABAergic interneurons was assumed to mediate feedforward inhibition of the spiny neurons (SPNs). During the past decade, we and others have described several novel populations of striatal GABAergic interneurons and their synaptic connections and have shown that striatal interneurons and SPNs interact through extensive and highly cell-type-specific connections that form specialized networks. Here, we describe a novel population of striatal GABAergic interneuron and provide several lines of evidence suggesting that it represents the first interneuron-selective interneuron in striatum. Striatal interneurons and their synaptic connections are suggested to play an important role in the formation of ensembles of striatal SPNs interconnected by inhibitory axon collaterals.

https://ift.tt/2K1R6Bl

Optogenetic Activation of Colon Epithelium of the Mouse Produces High-Frequency Bursting in Extrinsic Colon Afferents and Engages Visceromotor Responses

Epithelial cells of the colon provide a vital interface between the internal environment (lumen of the colon) and colon parenchyma. To examine epithelial–neuronal signaling at this interface, we analyzed mice in which channelrhodopsin (ChR2) was targeted to either TRPV1-positive afferents or to villin-expressing colon epithelial cells. Expression of a ChR2-EYFP fusion protein was directed to either primary sensory neurons or to colon epithelial cells by crossing Ai32 mice with TRPV1-Cre or villin-Cre mice, respectively. An ex vivo preparation of the colon was used for single-fiber analysis of colon sensory afferents of the pelvic nerve. Afferents were characterized using previously described criteria as mucosal, muscular, muscular-mucosal, or serosal and then tested for blue light-induced activation. Light activation of colon epithelial cells produced robust firing of action potentials, similar to that elicited by physiologic stimulation (e.g., circumferential stretch), in 50.5% of colon afferents of mice homozygous for ChR2 expression. Light-induced activity could be reduced or abolished in most fibers using a cocktail of purinergic receptor blockers suggesting ATP release by the epithelium contributed to generation of sensory neuron action potentials. Using electromyographic recording of visceromotor responses we found that light stimulation of the colon epithelium evoked behavioral responses in Vil-ChR2 mice that was similar to that seen with balloon distension of the colon. These ex vivo and in vivo data indicate that light stimulation of colon epithelial cells alone, without added mechanical or chemical stimuli, can directly activate colon afferents and elicit behavioral responses.

SIGNIFICANCE STATEMENT Abdominal pain that accompanies inflammatory diseases of the bowel is particularly vexing because it can occur without obvious changes in the structure or inflammatory condition of the colon. Pain reflects abnormal sensory neuron activity that may be controlled in part by release of substances from lining epithelial cells. In support of this mechanism we determined that blue-light stimulation of channelrhodopsin-expressing colon epithelial cells could evoke action potential firing in sensory neurons and produce changes in measures of behavioral sensitivity. Thus, activity of colon epithelial cells alone, without added mechanical or chemical stimuli, is sufficient to activate pain-sensing neurons.

https://ift.tt/2IaUNQc