Αρχειοθήκη ιστολογίου

Αναζήτηση αυτού του ιστολογίου

Τετάρτη 3 Οκτωβρίου 2018

Progression of ductal carcinoma in situ to invasive breast cancer: comparative genomic sequencing

Abstract

Several models have been described as potential mechanisms for the progression of ductal carcinoma in situ (DCIS) to invasive breast cancer (IBC). The aim of our study was to increase our understanding of DCIS progression by using massive parallel sequencing of synchronous DCIS and IBC. We included patients with synchronous DCIS and IBC (n = 4). Initially, IBC and normal tissue were subjected to whole exome sequencing. Subsequently, targeted sequencing was performed to validate those tumor-specific variants identified by whole exome sequencing. Finally, we analyzed whether those specific variants of the invasive component were also present in the DCIS component. There was a high genomic concordance between synchronous DCIS and IBC (52 out of 92 mutations were present in both components). However, the remaining mutations (40 out of 92) were restricted to the invasive component. The proportion of tumor cells with these mutations was higher in the invasive component compared to the DCIS component in a subset of patients. Our findings support the theory that the progression from DCIS to IBC could be driven by the selection of subclones with specific genetic aberrations. This knowledge improves our understanding of DCIS progression, which may lead to the identification of potential markers of progression and novel therapeutic targets in order to develop a more personalized treatment of patients with DCIS.



https://ift.tt/2QoC4oy

Bilateral parameatal cysts with associated hypospadias presenting in a newborn baby

Description 

A male infant presented to the neonatal team on day 1 of life with concerns over cysts on his penis. He had been born at term in good condition following an emergency caesarean section for face presentation and suboptimal cardiotocograph. There was no relevant antenatal history of note and no significant family history.

He had a normal examination other than his genitalia. He had a coronal hypospadias with two symmetrical cystic lesions measuring 2–3 mm each on the glans penis, just distal and lateral to the opening of the urethral meatus on the ventral surface (figure 1). There was no obvious discharge or surrounding erythema. By day 2, there was some mild superficial ulceration of the cyst surfaces. Both testes were palpable in his scrotum. He was discharged home after confirmation of a good urinary stream.

Figure 1

Male genitalia demonstrating two parameatal urethral...



https://ift.tt/2yg1VYe

Sarcoidosis and HIV infection in a native Saudi man

Sarcoidosis is a rare condition among native Saudis. It typically presents with asymptomatic chest radiographs, exertional breathlessness and cough. The coexistence of sarcoidosis and HIV is also rare, and the overlap of the symptoms makes their differential diagnosis challenging. Nevertheless, the outcome of sarcoidosis is favourable with or without the presence of HIV. We present a case of a 55-year-old native Saudi man with extremely atypical sarcoidosis presentation coexisting with HIV. This case highlights the association between the two pathologies, and the difficulties encountered in establishing a proper diagnosis in the presence of two overlapping diseases.



https://ift.tt/2y69C4n

Heart of the matter: reverse takotsubo syndrome in an anthracycline-exposed oncology patient

A 24-year-old man with acute myelogenous leukaemia and a history of anthracycline treatment is hospitalised for non-anthracycline chemotherapy. He develops new-onset heart failure requiring intesive care unit (ICU) admission during his stay. There is debate as to the aetiology of his heart failure, whether anthracycline cardiotoxicity or takotsubo syndrome. He is diuresed and discharged home with close follow-up. Ultimately, the retrospective use of two-dimensional speckle-tracking echocardiography derived strain helps diagnose reverse takotsubo syndrome.



https://ift.tt/2ycJa8a

Cardiac arrest due to critical stenosis of a bicuspid aortic valve mimicking left main coronary artery occlusion on ECG

A 49-year-old man presented to the emergency room after a cardiac arrest. On arrival, the patient's ECG showed ST-segment elevations in the aVR and anteroseptal leads with diffuse ST depression suggestive of left main coronary artery occlusion. Subsequent coronary catheterisation showed normal coronaries but revealed severe stenosis of his bicuspid aortic valve. A surgical replacement of the aortic valve was performed, and the patient recovered successfully.



https://ift.tt/2xTpfMj

Pericardial effusion as first presentation of disseminated non-Hodgkins lymphoma

A 46-year-old woman with quiescent lupus presented with worsening pleuritic chest pain and dyspnoea. Bedside echocardiogram confirmed large pericardial effusion with cardiac tamponade. Emergency bedside pericardiocentesis was performed. Pericardial fluid cytology confirmed diffuse large B cell lymphoma, stage four on positron emission tomography. Conventional rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone chemotherapy achieved good response in all sites except the pericardium. Progressive cardiac involvement was complicated by atrioventricular conduction block requiring permanent pacemaker. Second-line palliative chemotherapy was performed.



https://ift.tt/2ydGkjr

Hereditary angioedema: a mother diagnosing her child using Google as a diagnostic aid

Hereditary angioedema (HAE), due to C1-inhibitor deficiency, is a rare autosomal dominant and potentially life-threatening disease characterised by recurrent oedema attacks of skin, mucosa and viscera. Due to the rarity and the fact that symptoms of HAE imitate other forms of angioedema and other conditions, HAE may be misdiagnosed, especially in emergency settings. Consequently, patients with HAE may experience significant delays in diagnosis. Without an accurate diagnosis patients with HAE may not receive proper treatment. At times 'Doctor Google' may be an important tool in establishing the diagnosis. The aim of this case report is to emphasise the importance of listening to patients and relatives and being humble to 'Doctor Google'. Furthermore, the aim is to remind all healthcare personal of HAE and the importance of considering the rare differential diagnoses to common symptoms.



https://ift.tt/2xTp8jR

Oral ulcer due to dabigatran capsule

Description 

An 80-year-old man with cerebral infarction and no neurological deficits was hospitalised for right empyema. Although the patient's condition improved with antimicrobial therapy and right thoracic drainage, a swelling in his right cheek was observed during clinical rounds. Oral examination revealed ulceration on the right buccal mucosa (figure 1A) with an embedded blue solid matter (figure 1B), which was removed. After confirming the history of prescribed medications, the removed matter was determined to be a dabigatran capsule (figure 1C), and oral ulcer due to dabigatran was suspected. With conservative measures, re-epithelialisation was achieved within 2 weeks.

Figure 1

(A) Oral ulcer on the right buccal mucosa, (B) the removed solid matter, (C) the dabigatran capsule.

Dabigatran is currently used as an alternative to warfarin for venous thromboembolism and non-valvular atrial fibrillation. Dabigatran is formulated with...



https://ift.tt/2yddG1H

Correction: Severe capillary leak syndrome with cardiac arrest triggered by influenza virus infection

Ebdrup L, Druey KM, Mogensen TH. Severe capillary leak syndrome with cardiac arrest triggered by influenza virus infection. BMJ Case Rep 2018. doi: 10.1136/bcr-2018-226108.

In this published article, an author's name has been misspelt.

The correct name is Kirk M Druey.



https://ift.tt/2xToYZN

Borderline Mucinous Testicular Tumour: Diagnostic and Management difficulties

A 45-year-old man presented with right-sided testicular swelling and pain. An examination found a tender, firm right testis, a clinically normal left testis and no palpable lymphadenopathy. Tumour and inflammatory markers were within normal limits. A scrotal ultrasound scan showed an intratesticular, avascular lesion measuring 4.4x2.6x1.8 cm. A CT scan of his chest/abdomen/pelvis (CT C/A/P) showed no metastatic or primary lesions. An elective right-inguinal orchidectomy was subsequently performed. Histopathology showed a cystic mucinous tumour lined with intestinal-type epithelium. Differentials of metastatic adenocarcinoma, possibly of a gastrointestinal origin, a monodermal teratoma, or a borderline mucinous tumour of the testicle (BMTT) were considered. Following 12 p genetic studies and a colonoscopy, both of which found no abnormalities, a presumptive diagnosis of a BMTT was made. The patient is to have an annual urological review with a CT C/A/P and 5 yearly colonoscopies.



https://ift.tt/2ye2Qss

Draft genome sequence of Staphylococcus sp. EZ-P03 isolated from a mesophilic anaerobic digester

Staphylococcus species of the family Staphylococcaceae are facultatively anaerobic Gram-positive cocci growing in clusters, pairs and occasionally in short chains. Staphylococci can be detected in different envir...

https://ift.tt/2ybjtoH

Functional validation of human-specific PowerPlex® 21 System (Promega, USA) in chimpanzee (Pan troglodytes)

This study was aimed to test the PowerPlex® 21 System (Promega, USA), used for human identification applications for its positive cross-species applicability in Chimpanzees (Pan troglodytes) in order to identify ...

https://ift.tt/2Rn5ncx

Architecture-dependent anisotropic hysteresis in smooth muscle cells

Cells within mechanically dynamic tissues like arteries are exposed to ever-changing forces and deformations. In some pathologies, like aneurysms, complex loads may alter how cells transduce forces, driving maladaptive growth and remodeling. Here, we aimed to determine the dynamic mechanical properties of vascular smooth muscle cells (VSMCs) under biaxial load. Using cellular micro-biaxial stretching (CBS) microscopy, we measured the large-strain anisotropic stress-strain hysteresis of VSMCs and found that hysteresis is strongly dependent on load orientation and actin organization.

https://ift.tt/2Pafyj5

Chemotaxis model for breast cancer cells based on signal-to-noise ratio

Chemotaxis, a biased migration of cells under a chemical gradient, plays a significant role in diverse biological phenomena including cancer metastasis. Stromal cells release signaling proteins to induce chemotaxis, which leads to organ-specific metastasis. Epidermal growth factor (EGF) is an example of the chemical attractants, and its gradient stimulates metastasis of breast cancer cells. Hence, the interactions between EGF and breast cancer cells have long been a subject of interest for oncologists and clinicians.

https://ift.tt/2Rpgwtm

In vitro pro-inflammatory enzyme inhibition and anti-oxidant potential of selected Sri Lankan medicinal plants

The extracts of the ten selected Sri Lankan medicinal plants have been traditionally used in the treatment of inflammatory mediated diseases. The extracts were investigated for anti-inflammatory and anti-oxida...

https://ift.tt/2ybjZ5R

A comprehensive study of the potential phytomedicinal use and toxicity of invasive Tithonia species in South Africa

Tithonia diversifolia and T. rotundifolia belong to the Asteraceae family and are native to Mexico and Central America. These plants have become invasive in parts of tropical Africa and Asia where they have becom...

https://ift.tt/2RmFZU9

A phase II study of NK012, a polymeric micelle formulation of SN-38, in unresectable, metastatic or recurrent colorectal cancer patients

Abstract

Purpose

NK012 is a polymeric micelle formulation of SN-38, the active metabolite of irinotecan. We evaluated the efficacy and safety of NK012 in Japanese patients with unresectable metastatic colorectal cancer.

Methods

We conducted a multicenter open-label phase II trial of NK012 monotherapy in 58 patients who had been treated with an oxaliplatin-based chemotherapy regimen (group A: 53 patients with UGT1A1 genotype /, *6/, or *28/; group B: 5 patients with UGT1A1 genotype *6/*28 or *6/*6). The primary endpoint was the response rate (RR). Initial doses of 28 and 18 mg/m2 for group A and group B, respectively, were administered intravenously over 30 min, and these doses were subsequently administered every 3 weeks. Group A was evaluated as the primary efficacy population, while group B was evaluated for reference.

Results

In group A, the RR was 3.8%, and the median progression-free survival and overall survival were 3.30 months and 15.03 months, respectively. In both groups, the most common grade ≥ 3 adverse drug reaction (ADR) was neutropenia and the incidence of grade ≥ 3 diarrhea was low or zero. In group A, 17 serious ADRs were observed in 10 patients (17%); all improved or recovered. In group B, no serious ADRs were observed. No treatment-related deaths were reported in either group.

Conclusions

NK012 monotherapy yielded an RR similar to the RR of irinotecan monotherapy that was reported in the phase III EPIC trial (4.2%), and the incidence of grade ≥ 3 diarrhea was low. Based on the incidence and severity of febrile neutropenia and grade ≥ 3 neutropenia, the initial dose of NK012 28 mg/m2 may be too high for colorectal cancer patients who have previously been treated with an oxaliplatin-based chemotherapy regimen.



https://ift.tt/2QvaJBi

Ethnic variations in the childhood prevalence of Hirschsprung disease in New Zealand

ANZ Journal of Surgery, EarlyView.


https://ift.tt/2xYyURy

AAV-Mediated TAZ Gene Replacement Restores Mitochondrial and Cardioskeletal Function in Barth Syndrome

Human Gene Therapy, Ahead of Print.


https://ift.tt/2Pe6l9G

Locally Targeting the IL-17/IL-17RA Axis Reduced Tumor Growth in a Murine B16F10 Melanoma Model

Human Gene Therapy, Ahead of Print.


https://ift.tt/2OCuWYs

A Need for Better Understanding Is the Major Determinant for Public Perceptions of Human Gene Editing

Human Gene Therapy, Ahead of Print.


https://ift.tt/2P8VGNn

Gene Therapy for Sickle Cell Disease: A Lentiviral Vector Comparison Study

Human Gene Therapy, Volume 29, Issue 10, Page 1153-1166, October 2018.


https://ift.tt/2OzPOiX

An Interview with Michele De Luca

Human Gene Therapy, Volume 29, Issue 10, Page 1076-1082, October 2018.


https://ift.tt/2P8uGxt

Advances in Gene Therapy for Fanconi Anemia

Human Gene Therapy, Volume 29, Issue 10, Page 1114-1123, October 2018.


https://ift.tt/2OyMg0p

Spring Forward: ESGCT Trains the Next Generation of Gene and Cell Therapists

Human Gene Therapy, Volume 29, Issue 10, Page 1074-1075, October 2018.


https://ift.tt/2P4ftgF

Gene Therapy for Hemoglobinopathies

Human Gene Therapy, Volume 29, Issue 10, Page 1106-1113, October 2018.


https://ift.tt/2OyiKb9

Gene and Cell Therapy for Muscular Dystrophies: Are We Getting There?

Human Gene Therapy, Volume 29, Issue 10, Page 1098-1105, October 2018.


https://ift.tt/2P9xBG0

Preclinical Development of a Hematopoietic Stem and Progenitor Cell Bioengineered Factor VIII Lentiviral Vector Gene Therapy for Hemophilia A

Human Gene Therapy, Volume 29, Issue 10, Page 1183-1201, October 2018.


https://ift.tt/2OCuzNw

Isolation and Characterization of an HLA-DRB1*04-Restricted HPV16-E7 T Cell Receptor for Cancer Immunotherapy

Human Gene Therapy, Volume 29, Issue 10, Page 1202-1212, October 2018.


https://ift.tt/2P9t7zk

Gene and Cell Therapy: Tearing Down Walls

Human Gene Therapy, Volume 29, Issue 10, Page 1071-1073, October 2018.


https://ift.tt/2OE1i52

Gestational Diabetes Prevalence at Moderate and High Altitude

High Altitude Medicine &Biology, Ahead of Print.


https://ift.tt/2DTjvYg

Cerebral granulomatosis as a manifestation of Crohn’s disease

Crohn's disease (CD) is associated with a variety of extra-intestinal manifestations. Most commonly these involve the eye, skin, joints, coagulation system and liver. Cerebral manifestations of CD have been re...

https://ift.tt/2Qv4U70

Neurological signs as early determinants of dementia and predictors of mortality among older adults in Latin America: a 10/66 study using the NEUROEX assessment

Neurodegenerative processes in the elderly damage the brain, leading to progressive, incapacitating cognitive, behavioral, and motor dysfunctions which culminate in dementia. Fully manifest dementia is likely ...

https://ift.tt/2RreQiO

Comparative effectiveness of beta-interferons and glatiramer acetate for relapsing-remitting multiple sclerosis: systematic review and network meta-analysis of trials including recommended dosages

We systematically reviewed the comparative effectiveness of injectable beta-interferons (IFN-β) and glatiramer acetate (GA) on annualised relapse rate (ARR), progression and discontinuation due to adverse even...

https://ift.tt/2Qv4NZ8

Trends in stroke outcomes in the last ten years in a European tertiary hospital

Studying the impact of demographic changes and progress in the management of stroke patients is necessary in order to organize care structures for the coming years. Consequently, we analyzed the prognostic tre...

https://ift.tt/2Rn2nNf

The rationale for combination therapy in patients with aggressive B-cell non-Hodgkin lymphoma: ten questions

Future Oncology, Ahead of Print.


https://ift.tt/2zP6hHR

Antibiotic resistance, virulence factors and genotyping of Uropathogenic Escherichia coli strains

The way of treating different types of infectious diseases is really important. Using genotyping method, we can determine the genetic relatedness between the organisms with different resistance profile from di...

https://ift.tt/2xWDNdR

Array‐based profiling of the lymphoma cell DNA methylome does not unequivocally distinguish primary lymphomas of the central nervous system from non‐CNS diffuse large B‐cell lymphomas

Genes, Chromosomes and Cancer, Volume 0, Issue ja, -Not available-.


https://ift.tt/2Rq698t

Correction to: Tumour origin and R1 rates in pancreatic resections: towards consilience in pathology reporting

The authors regret that one of the author's given name was missing and a typographical error was present in Reference 26 of the above article. These are presented correctly in this article.



https://ift.tt/2y9wbnO

Robust EEG-based cross-site and cross-protocol classification of states of consciousness

Abstract
Determining the state of consciousness in patients with disorders of consciousness is a challenging practical and theoretical problem. Recent findings suggest that multiple markers of brain activity extracted from the EEG may index the state of consciousness in the human brain. Furthermore, machine learning has been found to optimize their capacity to discriminate different states of consciousness in clinical practice. However, it is unknown how dependable these EEG markers are in the face of signal variability because of different EEG configurations, EEG protocols and subpopulations from different centres encountered in practice. In this study we analysed 327 recordings of patients with disorders of consciousness (148 unresponsive wakefulness syndrome and 179 minimally conscious state) and 66 healthy controls obtained in two independent research centres (Paris Pitié-Salpêtrière and Liège). We first show that a non-parametric classifier based on ensembles of decision trees provides robust out-of-sample performance on unseen data with a predictive area under the curve (AUC) of ~0.77 that was only marginally affected when using alternative EEG configurations (different numbers and positions of sensors, numbers of epochs, average AUC = 0.750 ± 0.014). In a second step, we observed that classifiers based on multiple as well as single EEG features generalize to recordings obtained from different patient cohorts, EEG protocols and different centres. However, the multivariate model always performed best with a predictive AUC of 0.73 for generalization from Paris 1 to Paris 2 datasets, and an AUC of 0.78 from Paris to Liège datasets. Using simulations, we subsequently demonstrate that multivariate pattern classification has a decisive performance advantage over univariate classification as the stability of EEG features decreases, as different EEG configurations are used for feature-extraction or as noise is added. Moreover, we show that the generalization performance from Paris to Liège remains stable even if up to 20% of the diagnostic labels are randomly flipped. Finally, consistent with recent literature, analysis of the learned decision rules of our classifier suggested that markers related to dynamic fluctuations in theta and alpha frequency bands carried independent information and were most influential. Our findings demonstrate that EEG markers of consciousness can be reliably, economically and automatically identified with machine learning in various clinical and acquisition contexts.

https://ift.tt/2RpqA5J

Identity and validity of conserved B cell epitopes of filovirus glycoprotein: towards rapid diagnostic testing for Ebola and possibly Marburg virus disease

Ebolavirus and Marburgvirus are genera of the virus family Filoviridae. Filoviruses cause rare but fatal viral hemorrhagic fevers (VHFs) in remote villages of equatorial Africa with potential for regional and int...

https://ift.tt/2O64EhO

A high burden of asymptomatic genital tract infections undermines the syndromic management approach among adolescents and young adults in South Africa: implications for HIV prevention efforts

Youth in southern Africa, particularly adolescent girls and young women, are a key population for HIV prevention interventions. Untreated genital tract infections (GTIs) increase both HIV transmission and acqu...

https://ift.tt/2NlJKpz

Variability in antifungal utilization among neonatal, pediatric, and adult inpatients in academic medical centers throughout the United States of America

Identification of factors associated with antifungal utilization in neonatal, pediatric, and adult patient groups is needed to guide antifungal stewardship initiatives in academic medical centers.

https://ift.tt/2O4cbh1

Prevalence and genotypes of group A rotavirus among outpatient children under five years old with diarrhea in Beijing, China, 2011–2016

Rotavirus is a leading cause of severe diarrheal disease, and one of the common causes of death in children aged under five years old. The dominant epidemic strains may change in different years in the same ar...

https://ift.tt/2No9odo

Development of a sandwich ELISA to detect Leishmania 40S ribosomal protein S12 antigen from blood samples of visceral leishmaniasis patients

Visceral leishmaniasis (VL), caused by Leishmania donovani complex parasites, is a neglected parasitic disease that is generally fatal if untreated. Despite decades of research to develop a sensitive VL diagnosti...

https://ift.tt/2O5mMIw

LAP it up, fuzz ball: a short history of LC3-associated phagocytosis

Jennifer Martinez

https://ift.tt/2DXyY9M

Dianhydrogalactitol induces replication-dependent DNA damage in tumor cells preferentially resolved by homologous recombination

Dianhydrogalactitol induces replication-dependent DNA damage in tumor cells preferentially resolved by homologous recombination

Dianhydrogalactitol induces replication-dependent DNA damage in tumor cells preferentially resolved by homologous recombination, Published online: 03 October 2018; doi:10.1038/s41419-018-1069-9

Dianhydrogalactitol induces replication-dependent DNA damage in tumor cells preferentially resolved by homologous recombination

https://ift.tt/2zPMp7z

Hydroxypropyl-beta and -gamma cyclodextrins rescue cholesterol accumulation in Niemann–Pick C1 mutant cell via lysosome-associated membrane protein 1

Hydroxypropyl-beta and -gamma cyclodextrins rescue cholesterol accumulation in Niemann–Pick C1 mutant cell via lysosome-associated membrane protein 1

Hydroxypropyl-beta and -gamma cyclodextrins rescue cholesterol accumulation in Niemann–Pick C1 mutant cell via lysosome-associated membrane protein 1, Published online: 03 October 2018; doi:10.1038/s41419-018-1056-1

Hydroxypropyl-beta and -gamma cyclodextrins rescue cholesterol accumulation in Niemann–Pick C1 mutant cell via lysosome-associated membrane protein 1

https://ift.tt/2ylPeLV

CCAAT/enhancer-binding protein-β functions as a negative regulator of Wnt/β-catenin signaling through activation of AXIN1 gene expression

CCAAT/enhancer-binding protein-β functions as a negative regulator of Wnt/β-catenin signaling through activation of AXIN1 gene expression

CCAAT/enhancer-binding protein-β functions as a negative regulator of Wnt/β-catenin signaling through activation of <i>AXIN1</i> gene expression, Published online: 03 October 2018; doi:10.1038/s41419-018-1072-1

CCAAT/enhancer-binding protein-β functions as a negative regulator of Wnt/β-catenin signaling through activation of AXIN1 gene expression

https://ift.tt/2zPaFa2

Transient receptor potential channel 6 knockdown prevents apoptosis of renal tubular epithelial cells upon oxidative stress via autophagy activation

Transient receptor potential channel 6 knockdown prevents apoptosis of renal tubular epithelial cells upon oxidative stress via autophagy activation

Transient receptor potential channel 6 knockdown prevents apoptosis of renal tubular epithelial cells upon oxidative stress via autophagy activation, Published online: 03 October 2018; doi:10.1038/s41419-018-1052-5

Transient receptor potential channel 6 knockdown prevents apoptosis of renal tubular epithelial cells upon oxidative stress via autophagy activation

https://ift.tt/2yd9A9Y

Novel engineered, membrane-localized variants of vascular endothelial growth factor (VEGF) protect retinal ganglion cells: a proof-of-concept study

Novel engineered, membrane-localized variants of vascular endothelial growth factor (VEGF) protect retinal ganglion cells: a proof-of-concept study

Novel engineered, membrane-localized variants of vascular endothelial growth factor (VEGF) protect retinal ganglion cells: a proof-of-concept study, Published online: 03 October 2018; doi:10.1038/s41419-018-1049-0

Novel engineered, membrane-localized variants of vascular endothelial growth factor (VEGF) protect retinal ganglion cells: a proof-of-concept study

https://ift.tt/2zQoLYD

Suppression of SUN2 by DNA methylation is associated with HSCs activation and hepatic fibrosis

Suppression of SUN2 by DNA methylation is associated with HSCs activation and hepatic fibrosis

Suppression of SUN2 by DNA methylation is associated with HSCs activation and hepatic fibrosis, Published online: 03 October 2018; doi:10.1038/s41419-018-1032-9

Suppression of SUN2 by DNA methylation is associated with HSCs activation and hepatic fibrosis

https://ift.tt/2y8djFy

BMSCs pre-treatment ameliorates inflammation-related tissue destruction in LPS-induced rat DIC model

BMSCs pre-treatment ameliorates inflammation-related tissue destruction in LPS-induced rat DIC model

BMSCs pre-treatment ameliorates inflammation-related tissue destruction in LPS-induced rat DIC model, Published online: 03 October 2018; doi:10.1038/s41419-018-1060-5

BMSCs pre-treatment ameliorates inflammation-related tissue destruction in LPS-induced rat DIC model

https://ift.tt/2zQoLI7

LncRNA-MEG3 inhibits activation of hepatic stellate cells through SMO protein and miR-212

LncRNA-MEG3 inhibits activation of hepatic stellate cells through SMO protein and miR-212

LncRNA-MEG3 inhibits activation of hepatic stellate cells through SMO protein and miR-212, Published online: 03 October 2018; doi:10.1038/s41419-018-1068-x

LncRNA-MEG3 inhibits activation of hepatic stellate cells through SMO protein and miR-212

https://ift.tt/2ygiJOS

Colon-specific eQTL analysis to inform on functional SNPs

Colon-specific eQTL analysis to inform on functional SNPs

Colon-specific eQTL analysis to inform on functional SNPs, Published online: 04 October 2018; doi:10.1038/s41416-018-0018-9

Colon-specific eQTL analysis to inform on functional SNPs

https://ift.tt/2QpPKzJ

Moving the needle on colorectal cancer genetics: it takes more than two to TANGO

Moving the needle on colorectal cancer genetics: it takes more than two to TANGO

Moving the needle on colorectal cancer genetics: it takes more than two to TANGO, Published online: 04 October 2018; doi:10.1038/s41416-018-0219-2

Moving the needle on colorectal cancer genetics: it takes more than two to TANGO

https://ift.tt/2xZzkr4

Primary constitutional MLH1 epimutations: a focal epigenetic event

Primary constitutional MLH1 epimutations: a focal epigenetic event

Primary constitutional MLH1 epimutations: a focal epigenetic event, Published online: 04 October 2018; doi:10.1038/s41416-018-0019-8

Primary constitutional MLH1 epimutations: a focal epigenetic event

https://ift.tt/2QvJFSv

Treatment Linked to Cognitive Scores in Breast Cancer Survivors

WEDNESDAY, Oct. 3, 2018 -- For breast cancer survivors, treatment and age-related phenotypes and genotypes are associated with a longitudinal decrease in cognitive function, according to a study published online Oct. 3 in the Journal of Clinical...

https://ift.tt/2QnsSAI

Sleep Duration, Stroke Link Varies With Race, Sex

WEDNESDAY, Oct. 3, 2018 -- The association of sleep duration with incident stroke varies by race and sex, according to a study published online Oct. 3 in Neurology. Megan E. Petrov, Ph.D., from the Arizona State University in Phoenix, and colleagues...

https://ift.tt/2zOKaBm

JUUL Laboratories Have Largest Market Share of E-Cigarettes

WEDNESDAY, Oct. 3, 2018 -- From 2016 to 2017, sales of electronic cigarettes (e-cigarettes) by JUUL Laboratories increased 641 percent, with their sales comprising 29 percent of total e-cigarette sales by December 2017, according to a research...

https://ift.tt/2QsPWy3

Red Tide May Be Cause of Florida Beachgoers' Breathing Problems

WEDNESDAY, Oct. 3, 2018 -- Red tide may be the reason why some beachgoers on Florida's Atlantic coast have suffered breathing problems, according to Palm Beach County officials. The officials said preliminary water tests found the algae that causes...

https://ift.tt/2zPWL7v

CDC: Salmonella Outbreak Linked to Gravel Ridge Farms Eggs

WEDNESDAY, Oct. 3, 2018 -- The multistate Salmonella outbreak linked to Gravel Ridge Farms cage-free large eggs has grown, and consumers, restaurants, and retailers should not eat, serve, or sell the eggs, the U.S. Centers for Disease Control and...

https://ift.tt/2QtEEtz

Preferences for Help with a Sleep Problem Before Starting Cancer Treatment

Being diagnosed with cancer can be overwhelming and is often associated with significant disruptions. Before beginning cancer treatment, many patients experience poor sleep. Disrupted sleep has meaningful clinical implications beyond 'just' not feeling rested. Patients who sleep poorly prior may experience worse pain, fatigue, and depression during treatment (1). Further, sleep often gets worse as treatment progresses (2) and chronic sleep problems are associated with major negative health consequences (3, 4).

https://ift.tt/2RrcNf1

Control and context are central for people with advanced illness experiencing breathlessness: A systematic review and thematic-synthesis

Breathlessness is common and distressing in advanced illness. It is a challenge to assess, with few effective treatment options. To evaluate new treatments, appropriate outcome measures which reflect the concerns of people experiencing breathlessness are needed.

https://ift.tt/2IzXdta

Gene Expression Profile Signature of Aggressive Waldenström Macroglobulinemia with Chromosome 6q Deletion

Background. Waldenström macroglobulinemia (WM) is a rare, indolent B-cell lymphoma. Clinically, chromosome 6q deletion (6q del) including loss of the B lymphocyte-induced maturation protein 1 gene (BLIMP-1) is reported to be associated with poor prognosis. However, it remains unclear how the underlying biological mechanism contributes to the aggressiveness of WM with 6q del. Methods. Here, we conducted oligonucleotide microarray analysis to clarify the differences in gene expression between WM with and without 6q del. Gene ontology (GO) analysis was performed to identify the main pathways underlying differences in gene expression. Eight bone marrow formalin-fixed paraffin-embedded samples of WM were processed for interphase fluorescence in situ hybridization analysis, and three were shown to have 6q del. Results. GO analysis revealed significant terms including "lymphocyte activation" (corrected p value=6.68E-11), which included 31 probes. Moreover, IL21R and JAK3 expression upregulation and activation of the B-cell receptor signaling (BCR) pathway including CD79a, SYK, BLNK, PLCγ2, and CARD11 were detected in WM with 6q del compared with WM without 6q del. Conclusion. The present study suggested that the BCR signaling pathway and IL21R expression are activated in WM with 6q del. Moreover, FOXP1 and CBLB appear to act as positive regulators of the BCR signaling pathway. These findings might be attributed to the aggressiveness of the WM with 6q del expression signature.

https://ift.tt/2OBSmNM

Serum and urine amino acid profiles of captive cheetahs ( Acinonyx jubatus )

Abstract

Cheetahs in captivity are frequently afflicted by chronic disease conditions that are rare in their free-ranging counterparts and in other felids. To date, clear pathophysiological mechanisms for some of these diseases have not been established. In order to better understand these conditions in this species, we have adopted a systems biology approach to cheetah metabolism, with the hope of generating new hypotheses for future research. As part of a comprehensive metabolome, we determine the serum (N = 42) and urine (N = 26) amino acid profiles of apparently healthy captive cheetahs, housed at the AfriCat Foundation in Namibia, using GC-MS and LC-MS-MS. A total of 36 serum and 38 urine amino acids were identified and quantified. Glutamine was detected in the serum at the highest mean concentration (1624 μmol/L) followed by alanine (771.9 μmol/L), arginine (669.8 μmol/L), and glycine (478.7 μmol/L). Serum glycine, hydroxyproline, prolylproline, proline, and serine concentrations declined significantly with age. Arginine was excreted at the highest mean concentration (740 μmol/L), followed by glutamine (437.1 μmol/L), alanine (397.1 μmol/L), and serine (331.1 μmol/L). The fractional excretion of cystine was by far the highest at 21.92%, followed by hydroxylysine (6.34%), proline-hydroxyproline (5.49%), and α-aminopimelic acid (4.89%). Both urinary glycine and proline-hydroxyproline concentrations decreased significantly with age. None of the serum or urine amino acid concentrations differed significantly between males and females. This study provides some foundational information on the serum and urine amino acid profiles of healthy captive cheetahs.



https://ift.tt/2QtiE1T

Increased Mortality Among Patients With vs Without Cirrhosis and Autoimmune Hepatitis

There have been few reproducible studies of mortality in patients with autoimmune hepatitis (AIH) and its variants. We calculated mortality in a large national cohort of patients with AIH, with vs without cirrhosis, in the Netherlands.

https://ift.tt/2PahhFg

Validation of Effective Dose as a Better Predictor of Radiation Pneumonitis Risk than Mean Lung Dose: Secondary Analysis of a Randomized Trial

We found that a normal tissue complications model based on effective dose (Deff) (with volume parameter n=0.5, corresponding to root mean squared dose) predicts risk of radiation pneumonitis after either intensity-modulated radiation therapy or passively scattering proton therapy more accurately than a model based on mean lung dose and suggests that delivering higher doses to smaller lung volumes (vs. lower doses to larger volumes) may increase RP risk more than previously recognized.

https://ift.tt/2y80uLA

Disseminated tumor cells predict efficacy of regional nodal irradiation in early stage breast cancer

This long-term analysis (median follow-up 11.7 years) confirms the predictive impact of DTC status on the efficacy of regional radiotherapy on locoregional relapse in early breast cancer. This study also confirms that DTC is an independent prognostic factor for locoregional relapse. These data can be used to conduct a prospective comparative study based on DTC or CTC detection to determine whether it could constitute a predictive marker allowing better selection of patients for regional irradiation.

https://ift.tt/2y5aZQP

Virtual chromoendoscopy using optical enhancement improves the detection of Barrett’s esophagus–associated neoplasia

The Seattle protocol for endoscopic Barrett's esophagus surveillance samples a small proportion of the mucosal surface area – risking a potentially high miss rate of early neoplastic lesions. We assess if the new iScan Optical Enhancement system (OE, Pentax) improves the detection of early BE associated neoplasia compared with high definition white light endoscopy (HD-WLE) in both expert and trainee endoscopists to target sampling of suspicious areas. Such a system may both improve early neoplasia detection and reduce the need for random biopsies.

https://ift.tt/2y09GCo

Colon-specific eQTL analysis to inform on functional SNPs



https://ift.tt/2IDCi8w

Moving the needle on colorectal cancer genetics: it takes more than two to TANGO



https://ift.tt/2Rl1jcK

Primary constitutional MLH1 epimutations: a focal epigenetic event



https://ift.tt/2IzmROK

Early Diverging Insect-Pathogenic Fungi of the Order Entomophthorales Possess Diverse and Unique Subtilisin-Like Serine Proteases

Insect-pathogenic fungi use subtilisin-like serine proteases (SLSPs) to degrade chitin-associated proteins in the insect procuticle. Most insect-pathogenic fungi in the order Hypocreales (Ascomycota) are generalist species with a broad host-range, and most species possess a high number of SLSPs. The other major clade of insect-pathogenic fungi is part of the subphylum Entomophthoromycotina (Zoopagomycota, formerly Zygomycota) which consists of high host-specificity insect-pathogenic fungi that naturally only infect a single or very few host species. The extent to which insect-pathogenic fungi in the order Entomophthorales rely on SLSPs is unknown. Here we take advantage of recently available transcriptomic and genomic datasets from four genera within Entomophthoromycotina: the saprobic or opportunistic pathogens Basidiobolus meristosporus, Conidiobolus coronatus, C. thromboides, C. incongruus, and the host-specific insect pathogens Entomophthora muscae and Pandora formicae, specific pathogens of house flies (Muscae domestica) and wood ants (Formica polyctena), respectively. In total 154 SLSP from six fungi in the subphylum Entomophthoromycotina were identified: E. muscae (n = 22), P. formicae (n = 6), B. meristosporus (n = 60), C. thromboides (n = 18), C. coronatus (n = 36), and C. incongruus (n = 12). A unique group of 11 SLSPs was discovered in the genomes of the obligate biotrophic fungi E. muscae, P. formicae and the saprobic human pathogen C. incongruus that loosely resembles bacillopeptidase F-like SLSPs. Phylogenetics and protein domain analysis show this class represents a unique group of SLSPs so far only observed among Bacteria, Oomycetes and early diverging fungi such as Cryptomycota, Microsporidia, and Entomophthoromycotina. This group of SLSPs is missing in the sister fungal lineages of Kickxellomycotina and the fungal phyla Mucoromyocta, Ascomycota and Basidiomycota fungi suggesting interesting gene loss patterns.



https://ift.tt/2Rl1gxA

Highly Contiguous Genome Assemblies of 15 Drosophila Species Generated Using Nanopore Sequencing

The Drosophila genus is a unique group containing a wide range of species that occupy diverse ecosystems. In addition to the most widely studied species, Drosophila melanogaster, many other members in this genus also possess a well-developed set of genetic tools. Indeed, high-quality genomes exist for several species within the genus, facilitating studies of the function and evolution of cis-regulatory regions and proteins by allowing comparisons across at least 50 million years of evolution. Yet, the available genomes still fail to capture much of the substantial genetic diversity within the Drosophila genus. We have therefore tested protocols to rapidly and inexpensively sequence and assemble the genome from any Drosophila species using single-molecule sequencing technology from Oxford Nanopore. Here, we use this technology to present highly contiguous genome assemblies of 15 Drosophila species: 10 of the 12 originally sequenced Drosophila species (ananassae, erecta, mojavensis, persimilis, pseudoobscura, sechellia, simulans, virilis, willistoni, and yakuba), four additional species that had previously reported assemblies (biarmipes, bipectinata, eugracilis, and mauritiana), and one novel assembly (triauraria). Genomes were generated from an average of 29x depth-of-coverage data that after assembly resulted in an average contig N50 of 4.4 Mb. Subsequent alignment of contigs from the published reference genomes demonstrates that our assemblies could be used to close over 60% of the gaps present in the currently published reference genomes. Importantly, the materials and reagents cost for each genome was approximately $1,000 (USD). This study demonstrates the power and cost-effectiveness of long-read sequencing for genome assembly in Drosophila and provides a framework for the affordable sequencing and assembly of additional Drosophila genomes.



https://ift.tt/2IB7J3D

An Anopheles stephensi Promoter-Trap: Augmenting Genome Annotation and Functional Genomics

The piggyBac transposon was modified to generate gene trap constructs, which were then incorporated into the genome of the Asian malaria vector, Anopheles stephensi and remobilized through genetic crosses using a piggyBac transposase expressing line. A total of 620 remobilization events were documented, and 73 were further characterized at the DNA level to identify patterns in insertion site preferences, remobilization frequencies, and remobilization patterns. Overall, the use of the tetameric AmCyan reporter as the fusion peptide displayed a preference for insertion into the 5'-end of transcripts. Notably 183 – 44882 bp upstream of the An. stephensi v1.0 ab initio gene models, which demonstrated that the promoter regions for the genes of An. stephensi are further upstream of the 5'-proximal regions of the genes in the ab inito models than may be otherwise predicted. RNA-Seq transcript coverage supported the insertion of the splice acceptor gene trap element into 5'-UTR introns for nearly half of all insertions identified. The use of a gene trap element that prefers insertion into the 5'-end of genes supports the use of this technology for the random generation of knock-out mutants, as well as the experimental confirmation of 5'-UTR introns in An. stephensi.



https://ift.tt/2RonhM0

Rapid Low-Cost Assembly of the Drosophila melanogaster Reference Genome Using Low-Coverage, Long-Read Sequencing

Accurate and comprehensive characterization of genetic variation is essential for deciphering the genetic basis of diseases and other phenotypes. A vast amount of genetic variation stems from large-scale sequence changes arising from the duplication, deletion, inversion, and translocation of sequences. In the past 10 years, high-throughput short reads have greatly expanded our ability to assay sequence variation due to single nucleotide polymorphisms. However, a recent de novo assembly of a second Drosophila melanogaster reference genome has revealed that short read genotyping methods miss hundreds of structural variants, including those affecting phenotypes. While genomes assembled using high-coverage long reads can achieve high levels of contiguity and completeness, concerns about cost, errors, and low yield have limited widespread adoption of such sequencing approaches. Here we resequenced the reference strain of D. melanogaster (ISO1) on a single Oxford Nanopore MinION flow cell run for 24 hr. Using only reads longer than 1 kb or with at least 30x coverage, we assembled a highly contiguous de novo genome. The addition of inexpensive paired reads and subsequent scaffolding using an optical map technology achieved an assembly with completeness and contiguity comparable to the D. melanogaster reference assembly. Comparison of our assembly to the reference assembly of ISO1 uncovered a number of structural variants (SVs), including novel LTR transposable element insertions and duplications affecting genes with developmental, behavioral, and metabolic functions. Collectively, these SVs provide a snapshot of the dynamics of genome evolution. Furthermore, our assembly and comparison to the D. melanogaster reference genome demonstrates that high-quality de novo assembly of reference genomes and comprehensive variant discovery using such assemblies are now possible by a single lab for under $1,000 (USD).



https://ift.tt/2IC1dJM

Viable Triploid Honey Bees (Apis mellifera capensis) Are Reliably Produced in the Progeny of CO2 Narcotised Queens

The haplodiploid system of sex determination of Hymenoptera acts as an exaptation for species to evolve novel forms of asexual reproduction including thelytoky (clonal offspring of the mother). During normal reproduction in Hymenoptera, three of the four products of meiosis that are present in newly-laid eggs are lost as polar bodies, while the remaining pronucleus either develops as a haploid male or fuses with a sperm nucleus to produce a diploid zygote. In contrast, in thelytokous reproduction, which is uncommon but taxonomically widespread, two of the four products of meiosis fuse, as if one acted as a sperm. Queenless workers of Apis mellifera capensis, a subspecies of honey bee from South Africa, routinely reproduce thelytokously. Unmated A. m. capensis queens can also be induced to lay thelytokously by narcosis with carbon dioxide, but mated queens are never thelytokous. We artificially inseminated A. m. capensis queens using CO2 narcosis. Up to 1/3 of offspring workers carried two maternal alleles and an allele of one father whereas no three-allele progeny were seen in control queens of the arrhenotokous (unfertilized eggs result in males) subspecies A. m. scutellata. Flow cytometry of three-allele individuals revealed that they were triploid and arose from the fertilization of a thelytokous fusion nucleus. We then reared six queens from a narcotized A. m. capensis queen and determined the ploidy of the offspring queens based on microsatellites. One of the five daughters was triploid. Following artificial insemination, this queen produced unfertilized thelytokous diploid eggs at high frequency, and unfertilized triploid eggs at much lower frequency. If fertilized, thelytokous diploid eggs were non-viable, even though triploidy in itself does not impede normal development. In contrast, when the rarer triploid eggs were fertilized, a proportion developed into viable tetraploids. Our study highlights the extraordinary developmental flexibility of haplo-diploid systems.



https://ift.tt/2RnyxZ5

Coping-Style Behavior Identified by a Survey of Parent-of-Origin Effects in the Rat

In this study we investigate the effects of parent of origin on complex traits in the laboratory rat, with a focus on coping style behavior in stressful situations. We develop theory, based on earlier work, to partition heritability into a component due to a combination of parent of origin, maternal, paternal and shared environment, and another component that estimates classical additive genetic variance. We use this theory to investigate the effects on heritability of the parental origin of alleles in 798 outbred heterogeneous stock rats across 199 complex traits. Parent-of-origin-like heritability was on average 2.7fold larger than classical additive heritability. Among the phenotypes with the most enhanced parent-of-origin heritability were 10 coping style behaviors, with average 3.2 fold heritability enrichment. To confirm these findings on coping behavior, and to eliminate the possibility that the parent of origin effects are due to confounding with shared environment, we performed a reciprocal F1 cross between the behaviorally divergent RHA and RLA rat strains. We observed parent-of-origin effects on F1 rat anxiety/coping-related behavior in the Elevated Zero Maze test. Our study is the first to assess genetic parent-of-origin effects in rats, and confirm earlier findings in mice that such effects influence coping and impulsive behavior, and suggest these effects might be significant in other mammals, including humans.



https://ift.tt/2Rl6qd7

Double Selection Enhances the Efficiency of Target-AID and Cas9-Based Genome Editing in Yeast

CRISPR-Cas9 loss of function (LOF) and base editing screens are powerful tools in genetics and genomics. Yeast is one of the main models in these fields, but has only recently started to adopt this new toolkit for high throughput experiments. We developed a double selection strategy based on co-selection that increases LOF mutation rates using the Target-AID base editor. We constructed the pDYSCKO vector, which is amenable to high throughput double selection experiments, and show that the improvement in Target-AID efficiency generalizes across loci. Using modeling, we show that this improvement in efficiency provides the required increased in detection power to measure the fitness effects of thousands of mutations in typical yeast pooled screens. We show that double selection can also improve Cas9 mediated LOF rates, but that this multiplex genome editing causes programmable chromosomal translocations at high frequency. This suggests that multiplex LOF editing should be performed with caution and that base-editors could be preferable tools for some screens in yeast. Base editing using double selection is simple and straightforward and provides an alternative to homology directed repair based high throughput variant strain construction methods.



https://ift.tt/2IBSS91

A Novel Mutation in Brain Tumor Causes Both Neural Over-Proliferation and Neurodegeneration in Adult Drosophila

A screen for neuroprotective genes in Drosophila melanogaster led to the identification of a mutation that causes extreme, progressive loss of adult brain neuropil in conjunction with massive brain overgrowth. We mapped the mutation to the brain tumor (brat) locus, which encodes a tripartite motif-NCL-1, HT2A, and LIN-41 (TRIM-NHL) RNA-binding protein with established roles limiting stem cell proliferation in developing brain and ovary. However, a neuroprotective role for brat in the adult Drosophila brain has not been described previously. The new allele, bratcheesehead (bratchs), carries a mutation in the coiled-coil domain of the TRIM motif, and is temperature-sensitive. We demonstrate that mRNA and protein levels of neural stem cell genes are increased in heads of adult bratchs mutants and that the over-proliferation phenotype initiates prior to adult eclosion. We also report that disruption of an uncharacterized gene coding for a presumptive prolyl-4-hydroxylase strongly enhances the over-proliferation and neurodegeneration phenotypes. Together, our results reveal an unexpected role for brat that could be relevant to human cancer and neurodegenerative diseases.



https://ift.tt/2RpsyCR

Accounting for Programmed Ribosomal Frameshifting in the Computation of Codon Usage Bias Indices

Experimental evidence shows that synonymous mutations can have important consequences on genetic fitness. Many organisms display codon usage bias (CUB), where synonymous codons that are translated into the same amino acid appear with distinct frequency. Within genomes, CUB is thought to arise from selection for translational efficiency and accuracy, termed the translational efficiency hypothesis (TEH). Indeed, CUB indices correlate with protein expression levels, which is widely interpreted as evidence for translational selection. However, these tests neglect -1 programmed ribosomal frameshifting (-1 PRF), an important translational disruption effect found across all organisms of the tree of life. Genes that contain -1 PRF signals should cost more to express than genes without. Thus, CUB indices that do not consider -1 PRF may overestimate genes' true adaptation to translational efficiency and accuracy constraints. Here, we first investigate whether -1 PRF signals do indeed carry such translational cost. We then propose two corrections for CUB indices for genes containing -1 PRF signals. We retest the TEH in Saccharomyces cerevisiae under these corrections. We find that the correlation between corrected CUB index and protein expression remains intact for most levels of uniform -1 PRF efficiencies, and tends to increase when these efficiencies decline with protein expression. We conclude that the TEH is strengthened and that -1 PRF events constitute a promising and useful tool to examine the relationships between CUB and selection for translation efficiency and accuracy.



https://ift.tt/2IFpDSQ

Deletion of GIT1 Impacts eNOS Activity To Aggravate sFlt-1-Induced Preeclampsia Phenotype in Mice

Preeclampsia, a serious multisystem disorder specific to human pregnancy, remains a considerable burden of disease worldwide. Reduced nitric oxide bioavailability is proved to be crucial in the maternal and fetal pathophysiology of preeclampsia. G-protein-coupled Receptor Kinase Interactor-1 (GIT1) is a novel endothelial nitric oxide synthases (eNOS) interactor mediator. The aim of this paper is to investigate the effect of GIT1 on preeclampsia. Blood pressure (BP) was measured using a carotid catheter-calibrated eight-chamber tail-cuff system (CODA) at the same time daily. Urinary albumin excretion (UAE) was determined using Albuwell-M kits (Exocell Inc) and creatinine clearance (CCr) was determined by measuring urinary creatinine concentration with tandem liquid chromatography–mass spectrometry. The release of nitrite was analyzed to detect nitric oxide (NO) production using a Sievers Chemiluminescence NO Analyzer. NOS activity was examined by measuring the conversion of 3H-labeled l-arginine to 3H-labeled l-citrulline. BP was significantly increased in GIT1–/– mice with or without sFIT-1 treatment. In addition, GIT1–/– mice possessed higher UAE and lower CCr. Depletion of GIT1 impedes the NO production and placenta eNOS activity. Additional GIT1 attenuates sFlt-1-induced preeclampsia phenotypes. Our findings suggest that GIT1 significantly extenuates the sFlt-1-induced preeclampsia phenotypes by inhibiting eNOS activity, indicating a crucial role of GIT1 in the progression of preeclampsia.



https://ift.tt/2Rovr6T

Linkage Disequilibrium and Evaluation of Genome-Wide Association Mapping Models in Tetraploid Potato

Genome-wide association studies (GWAS) have become a powerful tool for analyzing complex traits in crop plants. The current study evaluates the efficacy of various GWAS models and methods for elucidating population structure in potato. The presence of significant population structure can lead to detection of spurious marker-trait associations, as well as mask true ones. While appropriate statistical models are needed to detect true marker-trait associations, in most published potato GWAS, a 'one model fits all traits' approach has been adopted. We have examined various GWAS models on a large association panel comprising diverse tetraploid potato cultivars and breeding lines, genotyped with single nucleotide polymorphism (SNP) markers. Phenotypic data were generated for 20 quantitative traits assessed in different environments. Best Linear Unbiased Estimates (BLUEs) for these traits were obtained for use in assessing GWAS models. Goodness of fit of GWAS models, derived using different combinations of kinship and population structure for all traits, was evaluated using Quantile-Quantile (Q-Q) plots and genomic control inflation factors (GC). Kinship was found to play a major role in correcting population confounding effects and results advocate a 'trait-specific' fit of different GWAS models. A survey of genome-wide linkage disequilibrium (LD), one of the critical factors affecting GWAS, is also presented and our findings are compared to other recent studies in potato. The genetic material used here, and the outputs of this study represent a novel resource for genetic analysis in potato.



https://ift.tt/2IzI0by

Genomic Signatures of Adaptation to a Precipitation Gradient in Nigerian Sorghum

Evolution of plants under climatic gradients may lead to clinal adaptation. Understanding the genomic basis of clinal adaptation in crops species could facilitate breeding for climate resilience. We investigated signatures of clinal adaptation in the cereal crop sorghum (Sorghum bicolor L. [Moench]) to the precipitation gradient in West Africa using a panel (n = 607) of sorghum accessions from diverse agroclimatic zones of Nigeria. Significant correlations were observed between common-garden phenotypes of three putative climate-adaptive traits (flowering time, plant height, and panicle length) and climatic variables. The panel was characterized at >400,000 single nucleotide polymorphisms (SNPs) using genotyping-by-sequencing (GBS). Redundancy analysis indicated that a small proportion of SNP variation can be explained by climate (1%), space (1%), and climate collinear with space (3%). Discriminant analysis of principal components identified three genetic groups that are distributed differently along the precipitation gradient. Genome-wide association studies were conducted with phenotypes and three climatic variables (annual mean precipitation, precipitation in the driest quarter, and annual mean temperature). There was no overall enrichment of associations near a priori candidate genes implicated in flowering time, height, and inflorescence architecture in cereals, but several significant associations were found near a priori candidates including photoperiodic flowering regulators SbCN12 and Ma6. Together, the findings suggest that a small (3%) but significant proportion of nucleotide variation in Nigerian sorghum landraces reflects clinal adaptation along the West African precipitation gradient.



https://ift.tt/2Rns6oP

Estimating Genetic Relatedness in Admixed Populations

Estimating genetic relatedness, and inbreeding coefficients is important to the fields of quantitative genetics, conservation, genome-wide association studies (GWAS), and population genetics. Traditional estimators of genetic relatedness assume an underlying model of population structure. Each individual is assigned to a population, depending on a priori assumptions about geographical location of sampling, proximity, or genetic similarity. But often, this population assignment is unknown and assumptions about assignment can lead to erroneous estimates of genetic relatedness. I develop a generalized method of estimating relatedness in admixed populations, to account for (1) multi-allelic genomic data, (2) including all nine Identity By Descent (IBD) states, and implement a maximum likelihood based estimator of pairwise genetic relatedness in structured populations, part of the software, InRelate. Replicated estimations of genetic relatedness between admixed full sib (FS), half sib (HS), first cousin (FC), parent-offspring (PO) and unrelated (UR) dyads in simulated and empirical data from the HGDP-CEPH panel show considerably low bias and error while using InRelate, compared to several previously developed methods. I also propose a bootstrap scheme, and a series of Wald Tests to assign relatedness categories to pairs of individuals.



https://ift.tt/2IBIjTw

Functional Interactions Between rsks-1/S6K, glp-1/Notch, and Regulators of Caenorhabditis elegans Fertility and Germline Stem Cell Maintenance

The proper accumulation and maintenance of stem cells is critical for organ development and homeostasis. The Notch signaling pathway maintains stem cells in diverse organisms and organ systems. In Caenorhabditis elegans, GLP-1/Notch activity prevents germline stem cell (GSC) differentiation. Other signaling mechanisms also influence the maintenance of GSCs, including the highly-conserved TOR substrate ribosomal protein S6 kinase (S6K). Although C. elegans bearing either a null mutation in rsks-1/S6K or a reduction-of-function (rf) mutation in glp-1/Notch produce half the normal number of adult germline progenitors, virtually all these single mutant animals are fertile. However, glp-1(rf) rsks-1(null) double mutant animals are all sterile, and in about half of their gonads, all GSCs differentiate, a distinctive phenotype associated with a significant reduction or loss of GLP-1 signaling. How rsks-1/S6K promotes GSC fate is unknown. Here, we determine that rsks-1/S6K acts germline-autonomously to maintain GSCs, and that it does not act through Cyclin-E or MAP kinase in this role. We found that interfering with translation also enhances glp-1(rf), but that regulation through rsks-1 cannot fully account for this effect. In a genome-scale RNAi screen for genes that act similarly to rsks-1/S6K, we identified 56 RNAi enhancers of glp-1(rf) sterility, many of which were previously not known to interact functionally with Notch. Further investigation revealed at least six candidates that, by genetic criteria, act linearly with rsks-1/S6K. These include genes encoding translation-related proteins, cacn-1/Cactin, an RNA exosome component, and a Hedgehog-related ligand. We found that additional Hedgehog-related ligands may share functional relationships with glp-1/Notch and rsks-1/S6K in maintaining germline progenitors.



https://ift.tt/2Rn3A78

Null Mutation of the Fascin2 Gene by TALEN Leading to Progressive Hearing Loss and Retinal Degeneration in C57BL/6J Mice

Fascin2 (FSCN2) is an actin cross-linking protein that is mainly localized in retinas and in the stereocilia of hair cells. Earlier studies showed that a deletion mutation in human FASCIN2 (FSCN2) gene could cause autosomal dominant retinitis pigmentosa. Recent studies have indicated that a missense mutation in mouse Fscn2 gene (R109H) can contribute to the early onset of hearing loss in DBA/2J mice. To explore the function of the gene, Fscn2 was knocked out using TALEN (transcription activator-like effector nucleases) on the C57BL/6J background. Four mouse strains with deletions of 1, 4, 5, and 41 nucleotides in the target region of Fscn2 were developed. F1 heterozygous (Fscn2+/–) mice carrying the same deletion of 41 nucleotides were mated to generate the Fscn2–/– mice. As a result, the Fscn2–/– mice showed progressive hearing loss, as measured in the elevation of auditory brainstem-response thresholds. The hearing impairment began at age 3 weeks at high-stimulus frequencies and became most severe at age 24 weeks. Moreover, degeneration of hair cells and loss of stereocilia were remarkable in Fscn2–/– mice, as revealed by F-actin staining and scanning electron microscopy. Furthermore, compared to the controls, the Fscn2–/– mice displayed significantly lower electroretinogram amplitudes and thinner retinas at 8, 16, and 24 weeks. These results demonstrate that, in C57BL/6Jmice, Fscn2 is essential for maintaining ear and eye function and that a null mutation of Fscn2 leads to progressive hearing loss and retinal degeneration.



https://ift.tt/2IAdCOf

Comparative Genomics Approaches Accurately Predict Deleterious Variants in Plants

Recent advances in genome resequencing have led to increased interest in prediction of the functional consequences of genetic variants. Variants at phylogenetically conserved sites are of particular interest, because they are more likely than variants at phylogenetically variable sites to have deleterious effects on fitness and contribute to phenotypic variation. Numerous comparative genomic approaches have been developed to predict deleterious variants, but the approaches are nearly always assessed based on their ability to identify known disease-causing mutations in humans. Determining the accuracy of deleterious variant predictions in nonhuman species is important to understanding evolution, domestication, and potentially to improving crop quality and yield. To examine our ability to predict deleterious variants in plants we generated a curated database of 2,910 Arabidopsis thaliana mutants with known phenotypes. We evaluated seven approaches and found that while all performed well, their relative ranking differed from prior benchmarks in humans. We conclude that deleterious mutations can be reliably predicted in A. thaliana and likely other plant species, but that the relative performance of various approaches does not necessarily translate from one species to another.



https://ift.tt/2RovqzR

Behavioral Deficits at 18-22 Months of Age Are Associated with Early Cerebellar Injury and Cognitive and Language Performance in Children Born Extremely Preterm

To investigate associations in toddlers born extremely preterm (<28 weeks) between neonatal neuroimaging and 18- to 22-month developmental and behavioral outcomes.

https://ift.tt/2Qssgdd

Nebulized Tranexamic Acid Use for Pediatric Secondary Post-Tonsillectomy Hemorrhage

Post-tonsillectomy hemorrhage is a frequent occurrence in the emergency department, and management of potentially life-threatening and ongoing bleeding by the emergency physician is challenging. Limited evidence-based guidelines exist, and practice patterns vary widely. We administered nebulized tranexamic acid to achieve hemostasis in a pediatric patient with associated bleeding cessation prior to definitive operative management.

https://ift.tt/2OyZLx5

Managing the Elderly Emergency Department Patient

Older US adults make more than 20 million emergency department (ED) visits annually, accounting for more than 15% of all visits.1 In contrast to younger ED patients, older ones typically have more medical problems, are taking more medications, are more likely to have baseline impairments in function and cognition, and are less likely to fully recover from illness or injury. Older adults are also more likely to experience social isolation, malnutrition, and abuse or neglect,2,3 which may contribute to their ED presentation and influence outcomes.

https://ift.tt/2Nlg6Rj

238 Dynamics and Implications of Benzodiazepine Administration to Older Adults in the Emergency Departments

Benzodiazepine use in the older adults has been associated with a myriad of adverse effects such as delirium, mechanical fall, fractures, and memory disturbances. Despite their particular risk to this population, there is a concern regarding the frequency of benzodiazepine use in US emergency departments (EDs). In this study we utilize national databases to describe trends in utilization of benzodiazepines in the older adult population.

https://ift.tt/2OyZhqL



https://ift.tt/2IC8SI8

Effect of Substrate Stiffness on Mechanical Coupling and Force Propagation at the Infarct Boundary

Heterogeneous intercellular coupling plays a significant role in mechanical and electrical signal transmission in the heart. Although many studies have investigated the electrical signal conduction between myocytes and non-myocytes within the heart muscle tissue, there are not many that have looked into the mechanical counterpart. This study aims to investigate the effect of substrate stiffness and the presence of cardiac myofibroblasts (CMFs) on mechanical force propagation across cardiomyocytes (CMs) and CMFs in healthy and heart attack mimicking matrix stiffness conditions.

https://ift.tt/2ICh2jw

Modeling the axon as an active partner with the growth cone in axonal elongation

Forces generated by the growth cone are vital for the proper development of the axon and thus brain function. Whilst recent experiments show that forces are generated along the axon, it is unknown whether the axon plays a direct role in controlling growth cone advance. Here, we use analytic and finite element modeling of microtubule dynamics and the activity of the molecular motors myosin and dynein to investigate mechanical force balance along the length of the axon and its effects on axonal outgrowth.

https://ift.tt/2IB63XF

Three-dimensional optical tweezers tracking resolves random sideward steps of the kinesin-8 Kip3

The budding yeast kinesin-8 Kip3 is a highly processive motor protein that walks to the ends of cytoskeletal microtubules and shortens them in a collective manner. However, how exactly Kip3 reaches the microtubule end is unclear. While rotations of microtubules in multimotored Kip3 gliding assays implied directed sideward switching between microtubule protofilaments, two-dimensional (2D), single-molecule, optical-tweezers assays indicated that Kip3 randomly switched protofilaments. Here, we topographically suspended microtubules such that Kip3 motors could freely access the microtubules in 3D.

https://ift.tt/2O3b01D

Single-molecule analysis reveals rhomboid proteins are strict and functional monomers in the membrane

Intramembrane proteases hydrolyze peptide bonds within the membrane as a regulatory paradigm that is conserved across all forms of cellular life. Many of these enzymes are thought to be oligomeric, and that the resulting quaternary interactions form the basis of their regulation. However, technical limitations have precluded directly determining the oligomeric state of intramembrane proteases in any membrane. Using single-molecule photobleaching, we determined the quaternary structure of ten different rhomboid proteins (the largest superfamily of intramembrane proteases) and six unrelated control proteins in parallel detergent micelle, planar supported lipid bilayer, and whole-cell systems.

https://ift.tt/2O1rc3s

Passive permeability of planar lipid bilayers to organic anions

The membrane permeability P of organic ions was reported to be governed by the structure of the permeating molecule. Thus far it is unclear whether the ion structure alters membrane partition or translocation proper across the membrane. Here we obtained P values for 24 anionic compounds (18 concrete values, 6 upper limits) measuring the current that they carry through folded planar lipid bilayers. The P values range over more than 10 log units. Our measured permeability values correlate well (r=0.95; logRMSE 0.74) with the hexadecane/water partition coefficients of the respective chemicals predicted by the COSMO-RS theory.

https://ift.tt/2ICh1fs

NUMERICAL EVALUATION OF NON‐BONDED PIEZO SENSOR FOR BIOMEDICAL DIAGNOSTICS USING ELECTRO‐MECHANICAL IMPEDANCE TECHNIQUE

International Journal for Numerical Methods in Biomedical Engineering, Volume 0, Issue ja, -Not available-.


https://ift.tt/2xT05NK

EMCrit 234 – Pardon Me, I Couldn’t Help but Overhear or How to go from being an Ass-hole to an AYS-hole on Twitter

Are you saying?...

EMCrit Project by Scott Weingart.



https://ift.tt/2QunAno

Using the Visual World Paradigm to Study Sentence Comprehension in Mandarin-Speaking Children with Autism

58452fig1.jpg

We present a protocol to examine the use of morphological cues during real-time sentence comprehension by children with autism.

https://ift.tt/2PfunRi

Anaerobic Protein Purification and Kinetic Analysis via Oxygen Electrode for Studying DesB Dioxygenase Activity and Inhibition

Here we present a protocol for anaerobic protein purification, anaerobic protein concentration, and subsequent kinetic characterization using an oxygen electrode system. The method is illustrated using the enzyme DesB, a dioxygenase enzyme which is more stable and active when purified and stored in an anaerobic environment.

https://ift.tt/2O3GHrA

Use of Hematopoietic Stem Cell Transplantation to Assess the Origin of Myelodysplastic Syndrome

We describe the use of hematopoietic stem cell transplantation (HSCT) to assess the malignant potential of genetically engineered hematopoietic cells. HSCT is useful for evaluating various malignant hematopoietic cells in vivo as well as generating a large cohort of mice with myelodysplastic syndromes (MDS) or leukemia to evaluate novel therapies.

https://ift.tt/2P9gHYb

Crohn's mouth ulcers: What to know

People with Crohn's disease may be more prone to mouth ulcers. Learn about the reasons why in this article. We also cover possible treatments.

https://ift.tt/2ycdpw3

Patient and provider communication about employment following a cancer diagnosis

Abstract

Purpose

Cancer treatment can precipitate functional limitations that restrict survivors' ability to work. Yet, it is unclear whether healthcare providers discuss the potential for employment limitations with their patients. We assessed the frequency of patient-provider communication about employment, from the perspectives of survivors, and examined whether receiving a treatment summary was associated with employment communication.

Methods

Cancer survivors who were working at diagnosis were identified from the Health Information National Trends Survey-4, conducted in 2014 (n = 290). Separate multivariable regression analyses examined the associations between survivor characteristics and employment communication and receipt of a treatment summary and employment communication.

Results

Among cancer survivors who were working at diagnosis, 62.69% (95% CI 54.42–70.95) reported discussing employment with any healthcare provider at any time since diagnosis. Younger cancer survivors and those more recently treated were more likely to ever have employment discussions. Survivors who received a treatment summary were also more likely to ever discuss employment with any healthcare provider than survivors who did not receive a treatment summary (OR = 3.47, 95% CI 1.02–11.84).

Conclusions

Approximately two thirds of cancer survivors who were working at diagnosis ever discussed employment with a healthcare provider. Thus, for a sizable portion of cancer survivors, the potential impact of cancer on employment is never discussed with any healthcare provider.

Implications for Cancer Survivors

Efforts are needed to proactively screen patients for cancer-related work limitations, empower patients to discuss employment concerns with their healthcare providers, and develop interventions that support survivors' goals for working throughout treatment and recovery.



https://ift.tt/2O139kU

Distinct Co-Modulation Rules of Synapses and Voltage-Gated Currents Coordinate Interactions of Multiple Neuromodulators

Multiple neuromodulators act in concert to shape the properties of neural circuits. Different neuromodulators usually activate distinct receptors but can have overlapping targets. Therefore, circuit output depends on neuromodulator interactions at shared targets, a poorly understood process. We explored quantitative rules of co-modulation of two principal targets of neuromodulation: synapses and voltage-gated ionic currents. In the stomatogastric ganglion of the male crab Cancer borealis, the neuropeptides proctolin (Proc) and the crustacean cardioactive peptide (CCAP) modulate synapses of the pyloric circuit and activate a voltage-gated current (IMI) in multiple neurons. We examined the validity of a simple dose-dependent quantitative rule, that co-modulation by Proc and CCAP is predicted by the linear sum of the individual effects of each modulator up to saturation. We found that this rule is valid for co-modulation of synapses, but not for the activation of IMI, in which co-modulation was sublinear. The predictions for the co-modulation of IMI activation were greatly improved if we assumed that the intracellular pathways activated by two peptide receptors inhibit one another. These findings suggest that the pathways activated by two neuromodulators could have distinct interactions, leading to distinct co-modulation rules for different targets even in the same neuron. Given the evolutionary conservation of neuromodulator receptors and signaling pathways, such distinct rules for co-modulation of different targets are likely to be common across neuronal circuits.

SIGNIFICANCE STATEMENT We examine the quantitative rules of co-modulation at multiple shared targets, the first such characterization to our knowledge. Our results show that dose-dependent co-modulation of distinct targets in the same cells by the same two neuromodulators follows different rules: co-modulation of synaptic currents is linearly additive up to saturation, whereas co-modulation of the voltage-gated ionic current targeted in a single neuron is nonlinear, a mechanism that is likely generalizable. Given that all neural systems are multiply modulated and neuromodulators often act on shared targets, these findings and the methodology could guide studies to examine dynamic actions of neuromodulators at the biophysical and systems level in sensory and motor functions, sleep/wake regulation, and cognition.



https://ift.tt/2OvEdSc

Active Sound Localization Sharpens Spatial Tuning in Human Primary Auditory Cortex

Spatial hearing sensitivity in humans is dynamic and task-dependent, but the mechanisms in human auditory cortex that enable dynamic sound location encoding remain unclear. Using functional magnetic resonance imaging (fMRI), we assessed how active behavior affects encoding of sound location (azimuth) in primary auditory cortical areas and planum temporale (PT). According to the hierarchical model of auditory processing and cortical functional specialization, PT is implicated in sound location ("where") processing. Yet, our results show that spatial tuning profiles in primary auditory cortical areas (left primary core and right caudo-medial belt) sharpened during a sound localization ("where") task compared with a sound identification ("what") task. In contrast, spatial tuning in PT was sharp but did not vary with task performance. We further applied a population pattern decoder to the measured fMRI activity patterns, which confirmed the task-dependent effects in the left core: sound location estimates from fMRI patterns measured during active sound localization were most accurate. In PT, decoding accuracy was not modulated by task performance. These results indicate that changes of population activity in human primary auditory areas reflect dynamic and task-dependent processing of sound location. As such, our findings suggest that the hierarchical model of auditory processing may need to be revised to include an interaction between primary and functionally specialized areas depending on behavioral requirements.

SIGNIFICANCE STATEMENT According to a purely hierarchical view, cortical auditory processing consists of a series of analysis stages from sensory (acoustic) processing in primary auditory cortex to specialized processing in higher-order areas. Posterior-dorsal cortical auditory areas, planum temporale (PT) in humans, are considered to be functionally specialized for spatial processing. However, this model is based mostly on passive listening studies. Our results provide compelling evidence that active behavior (sound localization) sharpens spatial selectivity in primary auditory cortex, whereas spatial tuning in functionally specialized areas (PT) is narrow but task-invariant. These findings suggest that the hierarchical view of cortical functional specialization needs to be extended: our data indicate that active behavior involves feedback projections from higher-order regions to primary auditory cortex.



https://ift.tt/2OAGZp2

Rhythm and Synchrony in a Cortical Network Model

We studied mechanisms for cortical gamma-band activity in the cerebral cortex and identified neurobiological factors that affect such activity. This was done by analyzing the behavior of a previously developed, data-driven, large-scale network model that simulated many visual functions of monkey V1 cortex (Chariker et al., 2016). Gamma activity was an emergent property of the model. The model's gamma activity, like that of the real cortex, was (1) episodic, (2) variable in frequency and phase, and (3) graded in power with stimulus variables like orientation. The spike firing of the model's neuronal population was only partially synchronous during multiple firing events (MFEs) that occurred at gamma rates. Detailed analysis of the model's MFEs showed that gamma-band activity was multidimensional in its sources. Most spikes were evoked by excitatory inputs. A large fraction of these inputs came from recurrent excitation within the local circuit, but feedforward and feedback excitation also contributed, either through direct pulsing or by raising the overall baseline. Inhibition was responsible for ending MFEs, but disinhibition led directly to only a small minority of the synchronized spikes. As a potential explanation for the wide range of gamma characteristics observed in different parts of cortex, we found that the relative rise times of AMPA and GABA synaptic conductances have a strong effect on the degree of synchrony in gamma.

SIGNIFICANCE STATEMENT Canonical computations used throughout the cerebral cortex are performed in primary visual cortex (V1). Providing theoretical mechanisms for these computations will advance understanding of computation throughout cortex. We studied one dynamical feature, gamma-band rhythms, in a large-scale, data-driven, computational model of monkey V1. Our most significant conclusion is that the sources of gamma band activity are multidimensional. A second major finding is that the relative rise times of excitatory and inhibitory synaptic potentials have strong effects on spike synchrony and peak gamma band power. Insight gained from studying our V1 model can shed light on the functions of other cortical regions.



https://ift.tt/2P8GwHZ

Risk of Serious Bacterial Infection in Infants Aged ≤60 Days Presenting to Emergency Departments with a History of Fever Only

To compare the risk of serious bacterial infection between infants aged ≤60 days who are febrile in the emergency department (ED) and those who have only a history of fever and are afebrile on arrival to the ED.

https://ift.tt/2RoQsOR

Long-Term Cardiovascular Morbidity in Children Born Following Fertility Treatment

To determine the risk of long-term cardiovascular disease (CVD) among children born following in vitro fertilization (IVF) and compared with spontaneous pregnancies.

https://ift.tt/2RnG0ar

Parent Perspectives on Readiness for Discharge Home after Neonatal Intensive Care Unit Admission

To explore the parent perspective on discharge home from the neonatal intensive care unit (NICU).

https://ift.tt/2RmXhRd

Prognostic Factors and Management of Patients with Choanal Atresia

To analyze prognostic factors in the management of patients with choanal atresia.

https://ift.tt/2DVTEiB

Predicting Successful Neonatal Retro-Transfer to a Lower Level of Care

Up to 20% of newborn infants retro-transferred to a lower level of care require readmission to a higher-level facility. In this study, we developed and validated a prediction rule (The Rule for Elective Transfer between Units for Recovering Neonates [RETURN]) to identify clinical characteristics of infants at risk for failing retro-transfer.

https://ift.tt/2DSFpe3

Antenatal Detection of Treatable Critical Congenital Heart Disease Is Associated with Lower Morbidity and Mortality

To establish the impact that timing of diagnosis and place of birth have on neonatal outcomes in those with readily treatable critical congenital heart disease.

https://ift.tt/2DVTUhz

Nondestructive Monitoring of Degradable Scaffold-Based Tissue-Engineered Blood Vessel Development Using Optical Coherence Tomography

A step by step protocol for nondestructive and long-period monitoring the process of vascular remodeling and scaffold degradation in real-time culture of biodegradable polymeric scaffold-based tissue-engineered blood vessels with pulsatile stimulation using optical coherence tomography is described here.

https://ift.tt/2O3z2JQ

Generation of Genome-wide Chromatin Conformation Capture Libraries from Tightly Staged Early Drosophila Embryos

57001fig1.jpg

This work describes a protocol for the generation of high resolution in situ Hi-C libraries from tightly staged pre-gastrulation Drosophila melanogaster embryos.

https://ift.tt/2yeSPLl

The Role of Completion Lymph Node Dissection for Sentinel Lymph Node-Positive Melanoma

Abstract

Purpose and Methods

Completion lymph node dissection (CLND) for sentinel lymph node (SLN)-positive melanoma patients has been guideline-concordant standard of care since adoption of lymphatic mapping and SLN biopsy for the management of clinically node-negative melanoma patients more than 20 years ago. However, a trend for omission of CLND has been observed over the past decade, and we now have randomized, controlled clinical trial data to help guide treatment recommendations. Publication of these data prompted an American Society of Clinical Oncology—Society of Surgical Oncology 2018 clinical practice guideline update for these patients.

Results and Conclusions

Systematic review of current evidence supports a selective, individualized approach to CLND for SLN-positive melanoma. For low-risk, low-volume micrometastatic disease, SLN biopsy may be both diagnostic and therapeutic, and close clinical follow-up with imaging or CLND are reasonable options for appropriately selected patients. For higher-risk patients, omission of CLND requires careful consideration of risks versus benefits, relevant histopathology, and individualized patient discussion. This should address patient comorbidities and life expectancy, the predicted likelihood of additional positive nodes, availability of imaging surveillance, likelihood of adherence to imaging and clinical follow-up, consequences of regional recurrence, and the prognostic value of complete nodal staging and its impact on adjuvant therapy recommendations or clinical trial participation. Data on long-term outcomes, cost, and patient-reported quality of life measures are not yet available.



https://ift.tt/2DWenTa

GLUT1 Variants for Predicting Prognosis After Surgery in Non-small Cell Lung Cancer



https://ift.tt/2xXgfG2

ASO Author Reflections: Even in Pancreatic Cancer, not all N Diseases are Created Equal



https://ift.tt/2E2G3FU

Survival Impact of Total Resected Lymph Nodes in Esophageal Cancer Patients With and Without Neoadjuvant Chemoradiation

Abstract

Background

Current esophageal treatment guidelines suggest that, when more than 15 lymph nodes are detected, dissection should be done as the minimum requirement for staging in esophageal squamous cell carcinoma (ESCC) patients undergoing esophagectomy without induction chemoradiotherapy (CRT). However, for neoadjuvant CRT, there is limited information. We sought to clarify the role of lymphadenectomy in ESCC patients with and without neoadjuvant CRT.

Patients and Methods

Data on 3156 ESCC patients receiving esophagectomy with (group 1, n = 1399) and without (group 2, n = 1757) neoadjuvant CRT between 2008 and 2014 were collected from a national cancer registry in Taiwan. The impact of the resected lymph nodes on overall survival was assessed according to pathologic stages. A Cox regression model was used to identify prognostic factors for overall survival.

Results

Five-year overall survival rates were 35.6% for the entire group, 30.32% for group 1, and 39.55% for group 2 (p < 0.0001 for group 1 vs group 2). The best cutoff value was 21 lymph nodes in both group 1 and group 2. In group 1, the independent prognostic factors included age ≥ 54 years, clinical N status, y-pathologic T, y-pathologic N, y-pathologic stage, grade, location, margin status, esophagectomy (thoracoscopic vs open), and number of total resected lymph nodes (≤ 21 vs > 21). For group 2, the independent prognostic factors were gender, clinical stage, pathologic T, pathologic N, tumor length, grade, and margin status.

Conclusions

Extent of lymphadenectomy was associated with survival in patients with neoadjuvant CRT followed by esophagectomy. The optimum lymphadenectomy should be modulated by pathologic stage.



https://ift.tt/2xZsbH4

ASO Author Reflections: Moving Forward De-escalation of Axillary Surgery After Neoadjuvant Treatment in Breast Cancer



https://ift.tt/2DSp0q8

Increasing Water Intake Can Cut Cystitis Recurrence

WEDNESDAY, Oct. 3, 2018 -- For women at high risk for cystitis recurrence who drink low volumes of fluid daily, increasing water intake prevents recurrence, according to a study published online Oct. 1 in JAMA Internal Medicine. Thomas M. Hooton,...

https://ift.tt/2Oytwyh

Family History Linked to Early-Onset A-Fib in Minorities

WEDNESDAY, Oct. 3, 2018 -- Probands of African or Hispanic/Latino descent with early-onset atrial fibrillation (EOAF) are more likely than European Americans to have a first-degree relative with AF, according to a study published online Sept. 21 in...

https://ift.tt/2OAPKQ4

Fall Risk Screening Strategy Cuts Fall-Related Hospitalizations

WEDNESDAY, Oct. 3, 2018 -- Implementation of a multifactorial fall risk intervention, which includes screening for fall risk assessment for modifiable risk factors, and prescribing evidence-based interventions to reduce fall risk can reduce the...

https://ift.tt/2QqhrrY

Uninsured Rate at 8.8 Percent in First Quarter of 2018

WEDNESDAY, Oct. 3, 2018 -- In the first quarter of 2018, the uninsured rate was 8.8 percent, not significantly different from a year earlier, according to a report released Aug. 29 by the National Center for Health Statistics (NCHS). Robin A. Cohen,...

https://ift.tt/2OvLW2E

High HbA1c After T1DM Diagnosis Predicts Psychiatric Comorbidity

WEDNESDAY, Oct. 3, 2018 -- High average glycated hemoglobin (HbA1c) levels during the first two years after type 1 diabetes onset predict higher risk for psychiatric diagnoses, according to a study published online Sept. 29 in Diabetes Care. Stine...

https://ift.tt/2Qqhmoa

Breastfeeding Inversely Linked to Infant BMI Z Score

WEDNESDAY, Oct. 3, 2018 -- Breastfeeding is inversely associated with body mass index z scores (BMIzs) measured at 12 months, and the association is attenuated with formula supplementation by six months, according to a study published online Sept....

https://ift.tt/2ODJxTo

Opioid-Related Hospital Use Up in Elderly Adults

WEDNESDAY, Oct. 3, 2018 -- Rates of opioid-related prescriptions and health care utilization are rising among seniors, according to two September statistical briefs released by the Agency for Healthcare Research and Quality (AHRQ). The reports...

https://ift.tt/2Qs1nWL

Better Glycemic Control With Closed-Loop Insulin Delivery

WEDNESDAY, Oct. 3, 2018 -- For patients with suboptimally controlled type 1 diabetes, day-and-night hybrid closed-loop insulin delivery improves glucose control compared with sensor-augmented pump therapy, according to a study published online Oct....

https://ift.tt/2Ox7iNa

Medicare Patient Readmit Rates Higher in Proprietary Hospitals

WEDNESDAY, Oct. 3, 2018 -- Among Medicare patients with six major diseases, readmission rates are higher for those receiving care in proprietary hospitals compared with government or nonprofit hospitals, according to a study published online Sept....

https://ift.tt/2QqxJBm

Elevated Blood Pressure Linked to Aortic Valve Disease

WEDNESDAY, Oct. 3, 2018 -- Long-term exposure to elevated blood pressure (BP) is associated with increased risk for aortic valve stenosis (AS) and aortic regurgitation (AR), according to a study published online Sept. 12 in the European Heart...

https://ift.tt/2Qs1kKz

The improved cure fraction for esophageal cancer in Linzhou city

Abstract

Background

Survival of esophageal cancer in Linzhou was seen to increase over the past few decades and is higher than the average level of China due to the implementation of comprehensive prevention and control measures. In population-based studies, relative survival is a common index to approximate disease-specific survival. However, the cure fraction maybe great interest to patients and physicians. This study aimed to investigate the cure fraction of esophageal cancer in Linzou city during 2003–2012 with a cure model.

Methods

We carried out a population-based study of 8067 esophageal cancer patients in the Linzhou city during 2003–2012. Flexible parametric cure models were used to estimate cure proportions and median survival times of uncured by year of diagnosed and age. In each model, an interaction between calendar year and age were included. All variables in the model were included both as constant and time-varying effects.

Results

The 5-year relative survival rate was increased in every age group from 2003 to 2012. The huge increase in the cure proportion was observed in each age group. At the year of 2011–2012, 79.8%, 58.0%, 123.4% and 162.7% improvements of cure proportion were seen in age group 19–49, 50–59, 60–69 and 70–99 years compared with year of 2003–2004. Meanwhile, survival of 'uncured' patients changed little in all age group.

Conclusions

The improvement of survival in Linzhou city during 2003–2012 was mainly due to an increasing cure proportion. Huge improvement of cure fraction within short period is likely due to the organized screening of esophageal cancer in Linzhou city.



https://ift.tt/2xW6Oqe

Health utility scores of family caregivers for leukemia patients measured by EQ-5D-3L: a cross-sectional survey in China

Abstract

Background

This study assessed the health related quality of life of family caregivers (FCs) of leukemia patients by using the health utility scores derived from the EuroQol five-dimensional (EQ-5D) questionnaire.

Methods

A cross-sectional survey was undertaken on 306 family caregivers of leukemia patients to assess their health utility using the EQ-5D-3L. Participants were recruited from three hospitals in China's Heilongjiang province. The health utility scores of the participants were estimated based on the Chinese EQ-5D-3L value set and compared with those of the local general population. Factors predicting the health utility scores were identified through the Kruskal-Wallis analysis of variance and median regression analyses.

Results

FCs had lower health utility scores than the general population (p < 0.001). The participants with a lower socioeconomic status had lower utility scores and reported more problems than those with a higher socio-economic status. Better family function and higher social support were associated with higher health utility scores. The type of leukemia, household income, and social support are significant predictors of health utility scores of the FCs. Chronic lymphocytic leukemia, low socio-economic status, and low social support are associated with lower health utility scores of the FCs.

Conclusions

FCs for leukemia patients have lower health utility scores than the local general population, as measured by the EQ-5D-3L. There is an immediate need to address the health concerns of FCs, who play an important role in the Chinese health care system.



https://ift.tt/2IziuDq

For Small Cell Lung Cancer, Immunotherapy Drug Finally Brings Improved Survival

In a large clinical trial, the immunotherapy drug atezolizumab (Tecentriq), combined with a standard chemotherapy regimen, modestly increased survival in patients with advanced small cell lung cancer (SCLC). The trial is the first in more than 20 years to show a survival improvement in this cancer.



https://ift.tt/2RkrGzw

Joint window and filter optimization for new waveforms in multicarrier systems

One of the demands of the next-generation wireless communication systems is being supportive to asynchronous traffic types. In order to meet this demand, many waveform candidates for next-generation wireless c...

https://ift.tt/2yb1ZZo

Interactome-Seq: A Protocol for Domainome Library Construction, Validation and Selection by Phage Display and Next Generation Sequencing

The protocols described allow the construction, characterization and selection (against the target of choice) of a "domainome" library made from any DNA source. This is achieved by a research pipeline that combines different technologies: phage display, a folding reporter and next generation sequencing with a web tool for data analysis.

https://ift.tt/2xVf9KK

In Situ Monitoring of the Accelerated Performance Degradation of Solar Cells and Modules: A Case Study for Cu(In,Ga)Se2 Solar Cells

Two 'Combined Stress test with in situ measurement' setups, which allow real-time monitoring of accelerated degradation of solar cells and modules, were designed and constructed. These setups allow the simultaneous use of humidity, temperature, electrical biases, and illumination as independently controlled stress factors. The setups and various experiments executed are presented.

https://ift.tt/2Qs216D

Cholecystokinin Switches the Plasticity of GABA Synapses in the Dorsomedial Hypothalamus via Astrocytic ATP Release

Whether synapses in appetite-regulatory brain regions undergo long-term changes in strength in response to satiety peptides is poorly understood. Here we show that following bursts of afferent activity, the neuromodulator and satiety peptide cholecystokinin (CCK) shifts the plasticity of GABA synapses in the dorsomedial nucleus of the hypothalamus of male Sprague Dawley rats from long-term depression to long-term potentiation (LTP). This LTP requires the activation of both type 2 CCK receptors and group 5 metabotropic glutamate receptors, resulting in a rise in astrocytic intracellular calcium and subsequent ATP release. ATP then acts on presynaptic P2X receptors to trigger a prolonged increase in GABA release. Our observations demonstrate a novel form of CCK-mediated plasticity that requires astrocytic ATP release, and could serve as a mechanism for appetite regulation.

SIGNIFICANCE STATEMENT Satiety peptides, like cholecystokinin, play an important role in the central regulation of appetite, but their effect on synaptic plasticity is not well understood. The current data provide novel evidence that cholecystokinin shifts the plasticity from long-term depression to long-term potentiation at GABA synapses in the rat dorsomedial nucleus of the hypothalamus. We also demonstrate that this plasticity requires the concerted action of cholecystokinin and glutamate on astrocytes, triggering the release of the gliotransmitter ATP, which subsequently increases GABA release from neighboring inhibitory terminals. This research reveals a novel neuropeptide-induced switch in the direction of synaptic plasticity that requires astrocytes, and could represent a new mechanism by which cholecystokinin regulates appetite.



https://ift.tt/2P7INmN

A Critical Role for Sorting Nexin 1 in the Trafficking of Metabotropic Glutamate Receptors

Group I metabotropic glutamate receptors (mGluRs) function as modulators of neuronal physiology and they have also been implicated in various neuropsychiatric disorders. Trafficking of mGluRs plays important roles in controlling the precise localization of these receptors at specific region of the cell, as well as it regulates the activity of these receptors. Despite this obvious significance, we know very little about the cellular machineries that control the trafficking of these receptors in the CNS. Sorting nexin 1 (SNX1) has been shown to regulate the endosomal sorting of few cell surface receptors either to lysosomes where they are downregulated or back to the cell surface. Using "molecular replacement" approach in hippocampal neurons derived from mice of both sexes, we show here that SNX1 plays critical role in the trafficking of mGluR1, a member of the group I mGluR family. Overexpression of dominant-negative SNX1 or knockdown of endogenous SNX1 resulted in the rapid recycling of the receptor. Importantly, recycling via the rapid recycling route, did not allow the resensitization of the receptors. Our data suggest that both, N-terminal and C-terminal region of SNX1 play critical role in the normal trafficking of the receptor. In addition, we also show here that SNX1 regulates the trafficking of mGluR1 through the interaction with Hrs (hepatocyte growth factor-regulated tyrosine kinase substrate), a protein that has been implicated in both signaling and vesicular trafficking. Thus, these studies reveal a mechanistic role of SNX1 in the trafficking of group I mGluRs and its physiological implications.

SIGNIFICANCE STATEMENT Group I mGluRs are activated by the neurotransmitter glutamate in the CNS, and play various important roles in the brain. Similar to many other receptors, trafficking plays crucial roles in controlling the precise localization as well as activity of these receptors. Despite this obvious significance very little is known about the cellular machineries that control the trafficking of these receptors. We demonstrate here, that SNX1 plays a critical role in the trafficking of mGluR1, a member of the group I mGluR family. SNX1-mediated trafficking is critical for the resensitization of the receptor. SNX1 controls the trafficking of the receptor through the interaction with another protein, Hrs. The results suggest a role for SNX1 in the regulation of group I mGluRs.



https://ift.tt/2OxtxCx

APD teams up with RapidDeploy to offer complete hosted solution to critical control operations

Software pioneer APD Communications has announced an alliance with fellow technology market leader RapidDeploy to provide a complete hosted solution for control room operations globally. The collaboration brings together complementary, cloud-based technologies to enhance the efficiency and effectiveness of critical control operations. It offers an unrivalled combination of APD's Cortex...

https://ift.tt/2xVp2s0

Metagenome sequencing to analyze the impacts of thiamine supplementation on ruminal fungi in dairy cows fed high-concentrate diets

Ruminal thiamine deficiencies occur when dairy cows are overfed with high-concentrate diet, and thiamine supplementation has been proved to attenuate high-concentrate diet induced SARA. However, there is limit...

https://ift.tt/2ybY92f

Response of microbial community structure and metabolic profile to shifts of inlet VOCs in a gas-phase biofilter

The effects of inlet VOCs (Volatile Organic Compounds) shifts on microbial community structure in a biofiltration system were investigated. A lab-scale biofilter was set up to treat eight VOCs sequentially. Sh...

https://ift.tt/2RnphE4

Analysis of the regulatory mechanism of deoxynivalenol production using omics

Fusarium species are plant pathogens that produce various mycotoxins. Here, the regulatory mechanism of deoxynivalenol production in Fusarium asiaticum was analyzed using proteomic, metabolomic and transcriptomic...

https://ift.tt/2yf6odM

A self‐portrait of Michelangelo Buonarroti hidden in a drawing from the Ashmolean Museum

Clinical Anatomy, Volume 0, Issue ja, -Not available-.


https://ift.tt/2Njb9IX

Active K‐RAS induces the coherent rotation of epithelial cells: A model for collective cell invasion in vitro

Cancer Science, Volume 0, Issue ja, -Not available-.


https://ift.tt/2RmGAFt

Logistical concerns surrounding an overdose mass casualty incident

Overdose cases can create numerous logistical problems when there are multiple overdose cases around the same time in different locations

https://ift.tt/2NZFRMq

Surviving in the absence of flowers: do nectar yeasts rely on overwintering bumblebee queens to complete their annual life cycle?

Abstract
Floral nectar represents an ephemeral habitat that is restricted in time and space to zoophilous flowering vegetation. To survive in these habitats, nectar-inhabiting microorganisms rely on animal vectors to disperse from one flower to the next. However, it remains unclear how nectar yeasts persist when flowers and nectar cease to be present. Here, we tested the hypothesis that hibernating bumblebee queens function as a reservoir for nectar yeasts in the absence of plants or pollinators during winter. Our results show that the nectar yeast Metschnikowia reukaufii, was present in the gastrointestinal tract of wild bumblebee queens that emerged from hibernation and that it could persist inside the gut of hibernating queens under experimental conditions. However, no evidence for such persistence was found in the case of the second most frequent nectar yeast, M. gruessii. Furthermore, a phylloplane yeast that occasionally inhabits nectar, Rhodotorula mucilaginosa, was able to colonize the gut under experimental conditions. Two bumblebee-associated yeasts, Candida bombi and C. bombiphila, were successfully passed down generations after administration in commercial lab-reared bumblebees. Overall, these results demonstrate that bumblebees could act as a reservoir for nectar yeasts during winter when floral nectar is absent.

https://ift.tt/2zPwZ3q

Chemoprevention agents for melanoma: a path forward into phase 3 clinical trials

Cancer, EarlyView.


https://ift.tt/2E5F7B1

Social Class Determines Whether Buying Experiences or Things Makes You Happier

What is the best way to spend money to increase your happiness? It may depend, in part, on how wealthy you are, according to findings published in Psychological Science, a journal of the Association for Psychological Science.

In a series of studies, researchers Jacob C. Lee of Ulsan National Institute of Science and Technology (UNIST), Deborah Hall of Arizona State University, and Wendy Wood of the University of Southern California found that only individuals who were relatively higher in social class showed the well-known effect of greater happiness from purchasing experiences, such as going to a concert or the movies, compared with purchasing material goods, such as a pair of shoes or accessories.

Lower class individuals, on the other hand, did not show the same pattern – in some cases, they reported the same degree of happiness from experiential and material purchases, whereas in others they actually reported that material purchases made them happier.

The conclusion that buying experiences yields more happiness than buying tangible objects is known as the experiential advantage.

"However, this simple answer to the question of how to best spend your money does not consider the huge economic disparities in our society," Wood notes. "We reasoned that the basic motives that shape consumer decisions would vary between higher-class and lower-class consumers. Thus, we anticipated that the degree of happiness obtained from different types of purchases would also vary by social class."

Individuals of higher social class have an abundance of resources, which means they can afford to focus more on internal growth and self-development. Because experiential purchases are more closely related to the self than material ones, higher-class individuals should derive more happiness from an investment in an experience.

People who have fewer resources, on the other hand, are likely to be more concerned with resource management and making wise purchases.

"For lower-class consumers, spending money on concert tickets or a weekend trip might not result in greater happiness than buying a new pair of shoes or a flatscreen TV," Hall explains. "In fact, in some of our studies, lower class consumers were happiest from purchasing things, which makes sense given that material goods have practical benefit, resale value, and are physically longer lasting."

In an initial meta-analysis, the researchers examined data from over 20 studies investigating the experiential advantage among college students at private and public institutions. Consistent with the idea that social class moderates experiential advantage, students with higher tuition costs and those attending private institutions reported greater experiential advantage than did students with lower tuition costs and those attending public schools.

In their next study, Lee, Hall, and Wood had participants recall both an experiential and a material purchase they had recently made and indicate which purchase made them happier. Participants of higher social class reported that their recent experiential purchases provided greater happiness. Conversely, individuals of lower social class reported greater happiness from recent material purchases.

Another study, in which participants were randomly assigned to recall a recent purchase of either an experience or material good, also showed an experiential advantage for participants who had an annual household income of $80,000 or more and at least a bachelor's degree. In this case, participants who had relatively lower income and education (< $30,000 annual household income and a high school degree or less) reported similar levels of happiness, regardless of whether they thought about a recent experiential or material purchase.

But participants didn't actually have to have lower income to show this pattern of results. The final study revealed that those who simply imagined that their monthly income had just decreased by 50% reported feeling similar levels of happiness from recent material and experiential purchases that they had made. In contrast, participants who imagined that their monthly income had just increased by 50% reported greater happiness from experiential purchases. That is, the experiential advantage was muted or amplified in response to even momentary changes in consumers' mindset regarding their financial resources.

The pattern of results was similar regardless of how the researchers measured social class, whether by income, education, or participants' subjective judgments. Furthermore, the relationship between social class and purchase happiness seemed to hold over time, even months after purchases were made, and regardless of how much the purchases cost.

"The take-home message is that, when it comes to increasing one's happiness through discretionary spending, there is no single 'right' answer of what to buy," Lee says. People's available resources are an important factor when deciding whether to purchase experiences or material goods to be happier.

The authors are currently conducting additional studies to better understand the specific consumer motives that underlie class-based differences in the experiential advantage.

All data and materials have been made publicly available via the Open Science Framework. The complete Open Practices Disclosure for this article is available online. This article has received badges for Open Data, Open Materials, and Preregistration.



https://ift.tt/2Qsrw7Y