Prevalence and distribution of hypertension and related risk factors in Jilin Province, China 2015: a cross-sectional study

Objective

This study aimed to investigate the prevalence and distribution of hypertension and its related factors in Jilin province, China.

Design

A cross-sectional study in four cities and four rural counties in Jilin as part of a national Chinese study.

Participants and setting

A total of 15 206 participants who were ≥15 years old and were selected using a stratified multistage random sampling method.

Main outcome measures

The prevalence of hypertension.

Results

The prevalence of hypertension in Jilin province was 24.7%. Moreover, the prevalence of hypertension increased with age in both sexes, and was higher in men than in women. The modifiable factors that were associated with hypertension were body mass index, smoking and alcohol drinking. The risk factors identified are similar to those in southern China, except smoking, which has no association with hypertension prevalence in the South.

Conclusions

Age, sex, body mass index, smoking and alcohol drinking were risk factors of hypertension. Control of these related risk factors, especially smoking, may be helpful in the treatment and management of hypertension in Jilin province.

https://ift.tt/2GlKt7G

DupuytrEn Treatment EffeCtiveness Trial (DETECT): a protocol for prospective, randomised, controlled, outcome assessor-blinded, three-armed parallel 1:1:1, multicentre trial comparing the effectiveness and cost of collagenase clostridium histolyticum, percutaneous needle fasciotomy and limited fasciectomy as short-term and long-term treatment strategies in Dupuytrens contracture

Introduction

Dupuytren's contracture (DC) is a chronic fibroproliferative disorder of the palmar fascia which leads to flexion contracture in one or more fingers. There is no definitive cure for DC, and treatment aims at relieving symptoms by releasing the contracture using percutaneous or operative techniques.

Methods and analysis

We planned a prospective, randomised, controlled, outcome assessor-blinded, three-armed parallel 1:1:1, multicentre trial comparing the effectiveness and cost of (1) collagenase clostridium histolyticum injection followed by limited fasciectomy in non-responsive cases, (2) percutaneous needle fasciotomy followed by limited fasciectomy in non-responsive cases and (3) primary limited fasciectomy during short-term and long-term follow-up for Tubiana I–III stages DC. We will recruit participants from seven national centres in Finland. Primary outcome is the rate of success in the treatment arm at 5 years after recruitment. Success is a composite outcome comprising (1) at least 50% contracture release from the date of recruitment and (2) participants in a patient-accepted symptom state (PASS). Secondary outcomes are (1) angle of contracture, (2) quick disabilities of the arm, a shoulder and hand outcome measure (QuickDASH), (3) perceived hand function, (4) EQ-5D-3L, (5) rate of major adverse events, (6) patient's trust of the treatment, (7) global rating, (8) rate of PASS, (9) rate of minimal clinically important improvement, (10) expenses, (11) progression of disease, (12) progression-free survival, (13) favoured treatment modality, (14) patients achieving full contracture release and >50% improvement and (15) patient satisfaction with the treatment effect. Predictive factors for achieving the PASS will also be analysed.

Ethics and dissemination

The protocol was approved by the Tampere University Hospital Institutional Review Board and Finnish Medicine Agency. The study will be performed according to the principles of good clinical practice. The results of the trial will be disseminated as published articles in peer-reviewed journals.

Trial registration number

NCT03192020; Pre-results.

https://ift.tt/2GnIqjG

Prevalence of stroke, risk factors, disability and care needs in older adults in Singapore: results from the WiSE study

Objectives

The aims of the present study were to establish the prevalence of stroke, and to explore the association between stroke prevalence and sociodemographic and health factors, disability, cognitive functioning and care needs among older adult residents in Singapore.

Setting

Data were drawn from the Well-being of the Singapore Elderly study—a cross-sectional epidemiological survey conducted from 2012 to 2013 on older adults living in Singapore.

Participants

Participants were Singapore residents (citizens and permanent residents) 60 years and above who were living in Singapore during the survey period . Older adult residents who were institutionalised were also included in this study. Those who were not living in Singapore or who were not contactable were excluded from the study. The response rate was 65.6 % (2565/3913). A total population sample of 2562 participants completed the survey. Participants comprised 43.6% males and 56.4% females. The sample comprised 39.4% Chinese, 29.1% Malay, 30.1% Indian and 1.4% other ethnicities .

Primary and secondary outcome measures

History of stroke, along with other health and mental health conditions, disability and cognitive functioning, were determined by self-report.

Results

Weighted stroke prevalence was 7.6% among older adults aged 60 and above. At a multivariate level, Malay ethnicity (OR 0.41, p=0.012, 95% CI 0.20 to 0.82), hypertension (OR 4.58, p=0.001, 95% CI 1.84 to 11.40), heart trouble (OR 2.45, p=0.006, 95% CI 1.30 to 4.63), diabetes (OR 2.60, p=0.001, 95% CI 1.49 to 4.53) and dementia (OR 3.57, p=0.002, 95% CI 1.57 to 8.12) were associated with stroke prevalence.

Conclusions

Several findings of this study were consistent with previous reports. Given that Singapore's population is ageing rapidly, our findings may indicate the need to review existing support services for stroke survivors and their caregivers. Future research could investigate the association between various sociodemographic and health conditions and stroke prevalence to confirm some of the findings of this study.

https://ift.tt/2pM80sm

Exploring factors impacting early childhood health among Aboriginal and Torres Strait Islander families and communities: protocol for a population-based cohort study using data linkage (the 'Defying the Odds study)

Introduction

Empirical evidence on family and community risk and protective factors influencing the comparatively high rates of potentially preventable hospitalisations and deaths among Aboriginal and Torres Strait Islander infants and children is limited. As is evidence on geographical variation in these risks. The 'Defying the Odds' study aims to explore the impact of perinatal outcomes, maternal social and health outcomes and level of culturally secure service availability on the health outcomes of Western Australian (WA) Aboriginal infants and children aged 0–5 years.

Methods and analysis

The study combines a retrospective cohort study that uses state-wide linked health and administrative data from 12 data sources for multiple generations within Aboriginal families in WA, with specifically collected survey data from health and social services supporting Aboriginal families in regions of WA. Data sources include perinatal/birth registration, hospital, emergency department, mental health services, drug and alcohol service use, mortality, infectious disease notifications, and child protection and family services. Multilevel regression models will be used to examine the intensity of admissions and presentations, mortality, intensity of long stays and morbidity-free survival (no admissions) for Aboriginal children born in WA in 2000–2013. Relationships between maternal (and grand-maternal) health and social factors and child health outcomes will be quantified. Community-level variation in outcomes for Aboriginal children and factors contributing to this variation will be examined, including the availability of culturally secure services. Online surveys were sent to staff members at relevant services to explore the scope, reach and cultural security of services available to support Aboriginal families across selected regions of WA.

Ethics and dissemination

Ethics approvals have been granted for the study. Interpretation and dissemination are guided by the study team's Aboriginal leadership and reference groups. Dissemination will be through direct feedback and reports to health services in the study and via scientific publications and policy recommendations.

https://ift.tt/2IcSJaw

Use of neuropsychological tests for the diagnosis of dementia: a survey of Italian memory clinics

Aim

Providing an overview of the neuropsychological tests used in Italian memory clinics (defined as Centers for Cognitive Disorders and Dementias—CCDD in Italy) for the diagnosis of cognitive disorders and dementias.

Methods

A total of 501 CCDD, out of all 536 active CCDD, were surveyed between February 2014 and August 2015 to verify the characteristics of the centres who performed a comprehensive neuropsychological assessment (NPA), defined as the administration of at least one test for verbal and visual episodic memory, attention, constructional praxis, verbal fluency and executive functions (minimum core tests—MCTs), as part of the diagnostic process.

Results

A total of 45.7% of Italian CCDD performed a comprehensive MCT as part of the diagnostic process. The logistic regression model showed that the probability of including at least one psychologist in the team was higher in the CCDD that reported using a comprehensive NPA (OR 4.55; 95% CI 2.92 to 7.1), that CCDD in Southern Italy had a lower probability of using an MCT (OR 0.56; 95% CI 0.35 to 0.89) and that the use of an MCT was higher in university/Institute for Scientific Research and Healthcare CCDD (OR 10.97; 95% CI 3.85 to 31.25).

Conclusion

Almost half of the CCDD administered a set of MCTs; while the remaining centres only performed few tests or screening procedures. The neuropsychological tests used in Italian CCDD were comparable with those used in other European countries. Performing a comprehensive NPA remains the best way to assess and monitor cognitive deficits over time, thus further debate on the current status of NPAs in clinical practice is needed.

https://ift.tt/2pMTuQN

Atypical chronic lymphocytic leukemia presenting with massive IgM paraprotein

https://ift.tt/2GluPt9

Cecum ulcer is a reliable endoscopic finding in cytomegalovirus colitis concomitant with graft-versus-host disease after allogeneic hematopoietic stem cell transplantation

Abstract

Although graft-versus-host disease (GVHD) is the major complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT), cytomegalovirus (CMV) reactivation also occurs in patients after allo-HSCT and these conditions often clinically overlap. The aim of this study was to determine reliable endoscopic findings of CMV colitis in patients with gastrointestinal graft-versus-host-disease (GI-GVHD). Patients after allo-HSCT who were histologically confirmed to have GI-GVHD with or without CMV colitis and patients with an immunosuppressive condition were retrospectively analyzed. We divided the patients into three groups: GI-GVHD with CMV colitis (group A), GI-GVHD without CMV colitis (group B), and CMV colitis without undergoing allo-HSCT (group C). From medical records, the involved colorectal areas and endoscopic findings according to the groups were compared. A total of 70 patients were divided into three groups (group A: n = 19, group B: n = 28, group C: n = 23). Mucosal injuries in groups A and C frequently occurred in the cecum including ileocecal valves. On the other hand, there were no abnormal lesions on ileocecal valves in group B. Furthermore, ulcer lesions were more frequently observed in groups A and C than in group B (p < 0.001). The sensitivity and specificity of mucosal injuries in the cecum for prediction of CMV colitis were 89.5 and 76.5%, respectively, and mucosal injuries in the cecum were more reliable findings than CMV antigenemia. Ulcer lesions in the cecum are reliable endoscopic findings for CMV colitis in patients with GI-GVHD after allo-HSCT.

https://ift.tt/2pMXkts

Hydroxyurea responses in clinically varied beta, HbE-beta thalassaemia and sickle cell anaemia patients of Eastern India

Abstract

The haematological and clinical response to hydroxyurea was estimated in HbE-beta, beta thalassaemia and sickle cell anaemia patients of Eastern India, with variable clinical severity and transfusion requirement to determine whether hydroxyurea can help these patients to maintain their steady haemoglobin level without blood transfusions. Three hundred patients (189 HbE-beta thalassaemia, 95 beta thalassaemia and 16 other haemoglobinopathies including sickle cell anaemia) were selected for hydroxyurea therapy and were followed up for 48–60 months. Results suggest significant response to hydroxyurea therapy in 19 beta and 99 HbE-beta patients in the transfusion-dependent group (GR-I). All of them became transfusion-independent while on hydroxyurea therapy. The majority of responding patients were IVS1-5(G-C) in one of their alleles in HbE-beta cases (83 out of 119). Though IVS1-5(G-C) was found to be the commonest mutation in our selected patients, the mutational background of the patients does not found to have any significant correlation with the response category towards hydroxyurea as per the results observed in our study. But, the drug works pretty well in most of the transfusion-dependent patients, as these patients were withdrawn from regular blood transfusion. At the same time, partial or no response to the drug hydroxyurea was also recorded in our study.

https://ift.tt/2pNqUyN

Combined PD-1 and JAK1/2 inhibition in refractory primary mediastinal B-cell lymphoma

https://ift.tt/2pPo5wB

Prognostic risk models for transplant decision-making in myelofibrosis

Abstract

Prognostic models are widely used in clinical practice for transplant decision-making in myelofibrosis (MF). We have compared the performance of the International Prognostic Scoring System (IPSS), dynamic IPSS (DIPSS), and DIPSS-plus in a series of 544 patients with primary or secondary MF aged ≤ 70 years at the time of diagnosis. The median projected survival of the overall series was 9.46 years (95% confidence interval 7.44–10.59). Median survival for the highest risk groups was less than 4 years in the three prognostic models. By contrast, the projected survival for patients in the intermediate-2 categories by the IPSS, DIPSS, and DIPSS-plus was 6.6, 5.6, and 6.5 years, respectively. The number of patients in the intermediate-2 and high-risk categories was smaller in the DIPSS than in the IPSS or the DIPSS-plus. The IPSS and DIPSS-plus were the best models to discriminate between the intermediate-1 and intermediate-2 risk categories, which is a critical cut-off point for patient selection to transplant. Among patients assigned at diagnosis to the intermediate-2 or high-risk groups by the IPSS, DIPSS, and DIPSS-plus, only 17, 21, and 20%, respectively, were subsequently transplanted. In conclusion, in our contemporary series of younger MF patients only the highest risk categories of the current prognostication systems have a median survival below the 5-year threshold recommended for considering transplantation. Patient selection for transplantation can significantly differ depending on which prognostication model is used for disease risk stratification.

https://ift.tt/2J2vbXf

Mesenchymal stem cells transplantation in hematological patients with acute graft-versus-host disease: characteristics and risk factors for infectious complications

Abstract

The role of MSCs in infection prevention and treatment is still discussed in transplant and hematological patients. The spectrum and risk factors for infections after MSCs transplantation in patients with acute GVHD have not been studied before. To determine the risk factors and spectrum of infectious complications in patients received mesenchymal stem cell transplantation as a treatment for acute GVHD. A prospective observational study was performed to evaluate the risk factors and characteristics of infectious complications after MSCs transplantation in adult patients having acute GVHD. Thirty-four episodes of MSCs transplantation in patients with acute GVHD after allogeneic HSCT were enrolled in the study. MSCs were given at a median dose of 1.32 (interquartile range 0.87–2.16) mln cells/kg per infusion at 91 days (interquartile range 31–131 days) after HSCT. Data relating to age, gender, date, and type of transplantation, characteristics of MSCs, infectious agents, and antimicrobial therapy and prevention regimens were prospectively collected in all of the enrolled patients. The episode of proven infectious complication was set as a primary outcome. There were totally 68 patients with acute GVHD in the study; among them there were 34 cases of MSCs transplantation performed. Among the registered infectious episodes were viral infections (CMV-associated disease, EBV-associated disease), invasive pulmonary aspergillosis, bacterial bloodstream infections, and pneumonia. MSCs transplantation has shown no statistically significant association with risk of infectious complications in patients with acute GVHD in a performed multivariate analysis. Among the most frequent infections in acute GVHD, we have described CMV, invasive aspergillosis, and bacterial infections (bloodstream infections or pneumonia). Among risk factors for infectious complications in patients with acute GVHD with/without MSCs transplantation are progression of main disease and neutropenia below 500 cells/mm³ (for aspergillosis) and unrelated HSCT in the past history and progression of main disease (for bacterial bloodstream infections and pneumonia).

https://ift.tt/2pPnZVL

Correction to: A phase I–II study of plerixafor in combination with fludarabine, idarubicin, cytarabine, and G-CSF (PLERIFLAG regimen) for the treatment of patients with the first early-relapsed or refractory acute myeloid leukemia

Abstract

The name of Pau Montesinos was inadvertently presented as Pau Montesinos Fernández in the original article.

The original version of this article was revised: The name of Pau Montesinos was inadvertently presented as Pau Montesinos Fernández.

https://ift.tt/2J4hVBi

Serious concerns on the inability of FDG-PET in excluding residual viable lymphoma

https://ift.tt/2pQ18cm

Internal tandem duplication mutations in the tyrosine kinase domain of FLT3 display a higher oncogenic potential than the activation loop D835Y mutation

Abstract

Acute myeloid leukemia (AML) remains the most common form of acute leukemia among adults and accounts for a large number of leukemia-related deaths. Mutations in FMS-like tyrosine kinase 3 (FLT3) is one of the most prevalent findings in this heterogeneous disease. The major types of mutations in FLT3 can be categorized as internal tandem duplications (ITD) and point mutations. Recent studies suggest that ITDs not only occur in the juxtamembrane region as originally described, but also in the kinase domain. Although the juxtamembrane ITDs have been well characterized, the tyrosine kinase domain ITDs have not yet been thoroughly studied due to their recent discovery. For this reason, we compared ITD mutations in the juxtamembrane domain with those in the tyrosine kinase domain, as well as with the most common activating point mutation in the tyrosine kinase domain, D835Y. The purpose of this study was to understand whether it is the nature of the mutation or the location of the mutation that plays the main role in leukemogenesis. The various FLT3 mutants were expressed in the murine pro-B cell line Ba/F3 and examined for their capacity to form colonies in semisolid medium. The size and number of colonies formed by Ba/F3 cells expressing either the internal tandem duplication within juxtamembrane domain of the receptor (JMD-ITD) or the tyrosine kinase domain (TKD)-ITD were indistinguishable, while Ba/F3 cells expressing D835Y/FLT3 failed to form colonies. Cell proliferation and cell survival was also significantly higher in TKD-ITD expressing cells, compared to cells expressing D835Y/FLT3. Furthermore, TKD-ITD is capable of inducing phosphorylation of STAT5, while D835Y/FLT3 fails to induce tyrosine phosphorylation of STAT5. Other signal transduction pathways such as the RAS/ERK and the PI3K/AKT pathways were activated to the same level in TKD-ITD cells as compared to D835Y/FLT3 expressing cells. Taken together, our data suggest that TKD-ITD displays similar oncogenic potential to the JMD-ITD but a higher oncogenic potential than the D835Y point mutation.

https://ift.tt/2J5zcdp

Polyneuropathy and myopathy in beta-thalassemia major patients

Abstract

The thalassemias are the most common single gene disorder in the world. Nowadays, the average life expectancy of patients in developed countries has increased significantly, while, there was an increase of complications. We aimed to investigate peripheral neuropathy and myopathy in this patient group using a neurophysiological study. We performed nerve conduction studies and electromyography of upper and lower extremities on 36 beta-thalassemia major (β-thal) patients. The electrophysiological findings were correlated with demographic data and laboratory parameters of the disease. Patients with β-thal present polyneuropathy or myopathy at (50%). Polyneuropathy was detected in (38.9%) and myopathy in (27.8%), while polyneuropathy and myopathy were present at (16.7%) with an overlap of the diseases in 1/3 of the patients. There was not a statistically significant correlation of polyneuropathy and myopathy with age, sex, splenectomy, nor with respect to laboratory parameters, hemoglobin, and ferritin. However, there was a statistically significant correlation of polyneuropathy and myopathy with iron overload, as recorded by the magnetic resonance imaging (MRI) of the heart and the liver. Our findings suggest that iron overload plays a key role in the pathogenesis of polyneuropathy and myopathy in β-thal patients, and performing heart and liver MRI for the prediction of such lesions in an annual basis is warranted.

https://ift.tt/2pLdpyS

Sequential development of monoclonal B cell lymphocytosis-derived small lymphocytic lymphoma and plasma cell leukemia

https://ift.tt/2IZIS9k

PI3K/Akt inhibitor LY294002 potentiates homoharringtonine antimyeloma activity in myeloma cells adhered to stromal cells and in SCID mouse xenograft

Abstract

Homoharringtonine (HHT) is a known anti-leukemia drug that inhibits multiple myeloma (MM) cells both in vitro and in vivo. Our prior study demonstrated that the potency of HHT in MM cells was compromised significantly when myeloma cells were co-cultured with BM stromal cells. This study aimed to investigate whether PI3K/Akt inhibitor LY294002 could potentiate the antimyeloma activity of HHT against MM cells adhered to BM stromal cells and in vivo xenograft models. A co-culture system composed of MM cells and human stromal cells was employed to mimic MM cells in bone marrow niche. The inhibitory and pro-apoptotic effect of HHT and LY294002 was determined by CCK-8 assay or flow cytometry. Expression of PI3K/Akt signaling molecules and anti-apoptotic protein myeloid cell leukemia-1 (Mcl-1) was assessed by western blot analysis and/or reverse transcription real-time quantitative PCR (RT-qPCR). MM xenografts were used to evaluate antitumor effect of combined therapy with HHT and LY294002. Adhesion to BM stromal cells rendered MM cells resistant to HHT whereas silencing Mcl-1 partly reversed the resistance. LY294002 induced apoptosis in MM cells and potentiated the antimyeloma effects of HHT by inhibiting the PI3K/Akt signal pathway which was abnormally activated during adhesion. LY294002 also enhanced the antimyeloma effect of HHT in in vivo xenograft models. These findings suggest that activation of PI3K/Akt signal pathway was responsible for the resistance to HHT in MM cells adhered to stromal cells. LY294002 can potentiate the antimyeloma activity of HHT both in vitro and in vivo, which may represent a new clinical treatment in MM.

https://ift.tt/2pQ17VQ

Relapse of acute promyelocytic leukemia in the external auditory canal confirmed by PML / RARA dual-fusion and RARA break-apart fluorescence in situ hybridization

https://ift.tt/2pPnH17

CD19 targeted CAR-T therapy versus chemotherapy in re-induction treatment of refractory/relapsed acute lymphoblastic leukemia: results of a case-controlled study

Abstract

Chimeric antigen receptor modified T cells against CD19 (CART19s) have potent anti-leukemia activities in patients with refractory/relapsed acute lymphoblastic leukemia (R/R ALL). This study was designed to investigate the correlation between safety/efficacy and therapeutic modalities including chemotherapy and CART19 therapy. Total 23 and 69 patients were enrolled in the CART19 group and in the chemotherapy group, respectively. The safety and efficacy profiles of 66 and 22 patients in the 2 groups were evaluated. The complete remission (CR) rate was higher in the CART19 group than that in the chemotherapy group (90.9 vs 37.9%, P = 0.000). For patients relapsed after allo-HSCT and chemotherapy, CR rates were 100% (8/8) vs 48.0% (12/25) (P = 0.009) and 85.7% (12/14) vs 31.7% (13/41) (P = 0.000), respectively. Moreover, a higher percentage in the CART19 group had results below the threshold for minimal residual disease (100 vs 7.58%, P = 0.000). In survival analysis, the overall survival rate at 12 months was higher in the CART19 group than that in the chemotherapy group (60.9 vs 10.1%, P = 0.000). For post-transplant patients achieving CR, 25.0% (2/8) and 75.0% (9/12) complicated with GVHD (P = 0.04) in the CART19 group and chemotherapy group, respectively. For all CR patients, the median duration of absolute neutrophil count less than 500/μL and platelet count less than 20,000/μL were longer in the CART19 group than in the chemotherapy group (p = 0.0047 and 0.0003, respectively). Our data demonstrated that patients with CART19s therapy acquired higher rates of remission and longer survival, confirming the encouraging application of CART19 therapy in R/R ALL.

https://ift.tt/2J08AdI

Infections associated with ruxolitinib: study in the French Pharmacovigilance database

https://ift.tt/2pSRqpY

The orally available multikinase inhibitor regorafenib (BAY 73-4506) in multiple myeloma

Abstract

A promising approach to the treatment of multiple myeloma (MM) involves agents that target not only the myeloma cells directly, but also the tumor microenvironment which promotes tumor cell growth, angiogenesis, and MM bone disease. Here we investigate the orally available multikinase inhibitor, regorafenib (BAY 73-4506), for its therapeutic efficacy in MM. Regorafenib is a potent inhibitor of angiogenic (VEGFR 1-3, PDGFR-b) as well as oncogenic (c-KIT, RET, FGFR, Raf) kinases. We show that regorafenib induces apoptosis in all MM cell lines at below clinically achievable concentrations. Regorafenib overcomes the growth advantage conferred by a stroma cell MM and an endothelial cell MM, co-culture systems, and abrogates growth factor-stimulated MEK, ERK, and AKT phosphorylation at nanomolar to micromolar concentrations. Moreover, it inhibits endothelial cell growth and tubule formation, abrogates both VEGF secretion and VEGF-induced MM cell migration, inhibits osteoclastogenesis, and shows synergistic cytotoxicity with dexamethasone, the immunomodulatory drug pomalidomide, and the p110δ inhibitor idelalisib. Most importantly, regorafenib significantly delays tumor growth in a xenograft mouse model of human MM. These results provide the rationale for further clinical evaluation of regorafenib, alone and in combination, in the treatment of MM.

https://ift.tt/2J2uSf3

FCS Analysis of Protein Mobility on Lipid Monolayers

In vitro membrane model systems are used to dissect complex biological phenomena under controlled unadulterated conditions. In this context, lipid monolayers are a powerful tool to particularly study the influence of lipid packing on the behavior of membrane proteins. Here, monolayers deposited in miniaturized fixed area-chambers, which require only minute amounts of protein, were used and shown to faithfully reproduce the characteristics of Langmuir monolayers. This assay is ideally suited to be combined with single-molecule sensitive fluorescence correlation spectroscopy (FCS) to characterize diffusion dynamics.

https://ift.tt/2pP2XXg

Referral Regions for Time-Sensitive Acute Care Conditions in the United States

Regional, coordinated care for time-sensitive and high-risk medical conditions is a priority in the United States. A necessary precursor to coordinated regional care is regions that are actionable from clinical and policy standpoints. The Dartmouth Atlas of Health Care, the major health care referral construct in the United States, uses regions that cross state and county boundaries, limiting fiscal or political ownership by key governmental stakeholders in positions to create incentive and regulate regional care coordination.

https://ift.tt/2pNe9Es

Lay (Mis)Perceptions of Sexual Harassment toward Transgender, Lesbian, and Gay Employees

Abstract

LGBTQ (lesbian, gay, bisexual, transgender, and queer-identified) employees commonly experience sexual harassment at work. The perceptions of lay observers of this harassment, such as their coworkers and managers, likely influence beliefs about appropriate individual and organizational responses to harassment. Thus, we conducted an experiment (n = 279 U.S. college students) to examine (a) whether four motivations (power, prejudice, gender policing, and sexual attraction) were perceived to underlie harassment toward LGT individuals; (b) how these motivations were related to perceived acceptability of the harassment; and (c) and how acceptability was related to recommended responses to the harassment. We found that compared to lesbian, gay, or cisgender heterosexual targets, participants perceived harassment toward transgender targets as less acceptable when they viewed it as more motivated by power and prejudice and less by attraction. Compared to male targets, participants perceived sexual harassment toward female targets as less acceptable when they viewed it as more motivated by prejudice. Finally, perceiving the harassment as less acceptable was associated with recommending that the target report the harassment. These results suggest that harassment targeting men and gay and lesbian employees may be minimized, underlining the need for organizations to protect against employees' mistreatment and challenge beliefs about sexual harassment motivations and acceptability.

https://ift.tt/2GiKQE0

Addressing the Horizontal Gender Division of Labor: A Case Study of Support and Obstacles in a Heavy Industry Plant in Iceland

Abstract

In the present article, we analyze a project in a heavy industry plant in Iceland in which the management aims to hire an equal number of women and men and, thereby, to work against the gender segregation of work. For their efforts, called the 50/50 strategy, the plant has received national and international awards. Observations and semi-structured interviews were conducted during five visits to the plant, including 85 interviews with 72 individuals, 49 women and 23 men. We found extensive support for the policy. The managers saw business opportunities in it, but although the employees supported the policy because it was seen as fair and modern, they doubted that achieving equal gender representation would be possible. The main emphasis so far has been on designing work organization and equipment, advertising the policy, presenting job opportunities to women outside the plant, and encouraging both genders to acquire the "right" education. Why the 50/50 target has not been reached lies partly in gender stereotypes outside the plant. Furthermore, our findings suggest that the next steps should be to challenge an alleged male working-culture within the plant. If they fail to do so, their efforts to eliminate horizontal gender segregation are unlikely to succeed and may even become counterproductive.

https://ift.tt/2uwSh5b

Associations between gene polymorphisms and treatment outcomes of methotrexate in patients with juvenile idiopathic arthritis

Pharmacogenomics, Ahead of Print.


https://ift.tt/2J5qEU2

The remains at Lethbridge’s Pocket – the case against the Kenniff brothers

Abstract

On 30th March 1902 Police Constable George Doyle and Carnarvon Station manager Albert Dahlke were allegedly gunned down at Lethbridge's Pocket in Central Queensland. Approximately 90 kg of ash and burnt human remains with articles belonging to the two men were later found in saddle bags left at the scene on a police horse. Subsequently two local cattle and horse thieves, Patrick and James Kenniff, were convicted in the Queensland Supreme Court of the wilful murder of Constable Doyle. Patrick was executed by hanging on 12th January 1903 and James had his sentence reduced to life imprisonment with hard labor. A number of irregularities were subsequently raised about the trial including the use of a "special" jury and the reliability of evidence from a witness who did not actually see the event. Forensic issues to be explored involve the accuracy of the descriptions of the carbonized material, whether the remains were actually those of Doyle and Dahlke, and whether the victims were dismembered before burning, as was alleged by the prosecution.

https://ift.tt/2J3vEbI

De-escalating treatment in the adjuvant setting in HER2-positive breast cancer

Future Oncology, Ahead of Print.


https://ift.tt/2GTLox4

The merit of tyrosine kinase inhibitors in the adjuvant setting of high-risk renal cell carcinoma: a meta-analysis

Future Oncology, Ahead of Print.


https://ift.tt/2IeAvFL

Vps74 Connects the Golgi Apparatus and Telomeres in Saccharomyces cerevisiae

In mammalian cell culture, the Golgi apparatus fragment upon DNA damage. GOLPH3, a Golgi component, is a phosphorylation target of DNA-PK after DNA damage and contributes to Golgi fragmentation. The function of the yeast (Saccharomyces cerevisiae) ortholog of GOLPH3, Vps74, in the DNA damage response has been little studied, although genome-wide screens suggested a role at telomeres. In this study we investigated the role of Vps74 at telomeres and in the DNA damage response. We show that Vps74 decreases the fitness of telomere defective cdc13-1 cells and contributes to the fitness of yku70 cells. Importantly, loss of Vps74 in yku70 cells exacerbates the temperature dependent growth defects of these cells in a Chk1 and Mec1-dependent manner. Furthermore, Exo1 reduces the fitness of vps74 yku70 cells suggesting that ssDNA contributes to the fitness defects of vps74 yku70 cells. Systematic genetic interaction analysis of vps74, yku70 and yku70 vps74 cells suggests that vps74 causes a milder but similar defect to that seen in yku70 cells. vps74 cells have slightly shorter telomeres and loss of VPS74 in yku70 or mre11 cells further shortens the telomeres of these cells. Interestingly, loss of Vps74 leads to increased levels of Stn1, a partner of Cdc13 in the CST telomere capping complex. Overexpression of Stn1 was previously shown to cause telomere shortening, suppression of cdc13-1 and enhancement of yku70 growth defects, suggesting that increased levels of Stn1 may be the route by which Vps74 affects telomere function. These results establish Vps74 as a novel regulator of telomere biology.

https://ift.tt/2IYVxJz

A Strategy To Isolate Modifiers of Caenorhabditis elegans Lethal Mutations: Investigating the Endoderm Specifying Ability of the Intestinal Differentiation GATA Factor ELT-2

The ELT-2 GATA factor normally functions in differentiation of the C. elegans endoderm, downstream of endoderm specification. We have previously shown that, if ELT-2 is expressed sufficiently early, it is also able to specify the endoderm and to replace all other members of the core GATA-factor transcriptional cascade (END-1, END-3, ELT-7). However, such rescue requires multiple copies (and presumably overexpression) of the end-1p::elt-2 cDNA transgene; a single copy of the transgene does not rescue. We have made this observation the basis of a genetic screen to search for genetic modifiers that allow a single copy of the end-1p::elt-2 cDNA transgene to rescue the lethality of the end-1 end-3 double mutant. We performed this screen on a strain that has a single copy insertion of the transgene in an end-1 end-3 background. These animals are kept alive by virtue of an extrachromosomal array containing multiple copies of the rescuing transgene; the extrachromosomal array also contains a toxin under heat shock control to counterselect for mutagenized survivors that have been able to lose the rescuing array. A screen of ~14,000 mutagenized haploid genomes produced 17 independent surviving strains. Whole genome sequencing was performed to identify genes that incurred independent mutations in more than one surviving strain. The C. elegans gene tasp-1 was mutated in four independent strains. tasp-1 encodes the C. elegans homolog of Taspase, a threonine-aspartic acid protease that has been found, in both mammals and insects, to cleave several proteins involved in transcription, in particular MLL1/trithorax and TFIIA. A second gene, pqn-82, was mutated in two independent strains and encodes a glutamine-asparagine rich protein. tasp-1 and pqn-82 were verified as loss-of-function modifiers of the end-1p::elt-2 transgene by RNAi and by CRISPR/Cas9-induced mutations. In both cases, gene loss leads to modest increases in the level of ELT-2 protein in the early endoderm although ELT-2 levels do not strictly correlate with rescue. We suggest that tasp-1 and pqn-82 represent a class of genes acting in the early embryo to modulate levels of critical transcription factors or to modulate the responsiveness of critical target genes. The screen's design, rescuing lethality with an extrachromosomal transgene followed by counterselection, has a background survival rate of <10^–4 without mutagenesis and should be readily adapted to the general problem of identifying suppressors of C. elegans lethal mutations.

https://ift.tt/2pSRZ35

T-Cell Dysfunction in Glioblastoma: Applying a New Framework

A functional, replete T cell repertoire is an integral component to adequate immune surveillance and to the initiation and maintenance of productive anti-tumor immune responses. Glioblastoma (GBM), however, is particularly adept at sabotaging anti-tumor immunity, eliciting severe T cell dysfunction that is both qualitative and quantitative. Understanding and countering such dysfunction are among the keys to harnessing the otherwise stark potential of anti-cancer immune-based therapies. While T cell dysfunction in GBM is long described, newer immunologic frameworks now exist for re-classifying T cell deficits in a manner that better permits their study and reversal. Herein, we divide and discuss the various T cell deficits elicited by GBM within the context of the five relevant categories - Senescence, Tolerance, Anergy, Exhaustion, and Ignorance. Categorization is appropriately made according to the molecular bases of dysfunction. Likewise, we review the mechanisms by which GBM elicits each mode of T cell dysfunction and discuss the emerging immunotherapeutic strategies designed to overcome them.

https://ift.tt/2Gj5HmA

5-Fluorouracil enhances Protoporphyrin IX accumulation and lesion clearance during photodynamic therapy of actinic keratoses: A mechanism-based clinical trial

PURPOSE: Actinic keratoses (AK) are precancerous lesions that can progress to squamous cell carcinoma. Photodynamic therapy (PDT) and topical 5-fluorouracil (5FU) are commonly used for AK. Empirical reports suggest that combining them can improve the therapeutic response. However, the optimal combined regimen was not clear in terms of proper sequence, timing, and mechanism. This clinical study explored mechanisms of action for neoadjuvantal 5FU and PDT for treatment of AK. EXPERIMENTAL DESIGN: A bilaterally controlled trial (17 patients) was performed. One side of the body (face, scalp, forearms) received 5FU pretreatment for 6 days; the other side served as no-pretreatment control. Methylaminolevulinate cream was applied to both sides for 3 h, and PpIX levels measured by noninvasive fluorimetry and skin biopsy. After red light illumination, lesion clearance was assessed at 3, 6, 9, and 12 months post-PDT. RESULTS: PpIX levels were increased 2- to 3-fold in 5FU-pretreated lesions versus controls. Altered expression of heme-synthetic enzymes (CPO and ferrochelatase) and induction of p53 were observed, probably accounting for increased PpIX and subsequent cancer cell death. Relative clearance rates (CR) after PDT with or without 5FU pretreatment were 75% vs. 45% at 3 months, and 67% vs. 39% at 6 months, respectively; these differences were statistically significant. CONCLUSIONS: Serial 5FU and PDT improves AK clearance by at least two mechanisms, enhanced photosensitizer accumulation and p53 induction. Because 5FU and PDT are FDA-approved modalities, the combined regimen can be readily employed in clinical practice to reduce AK burden and reduce SCC risk. ClinicalTrials.gov NCT01525329.

https://ift.tt/2GFp78C

Association Between Serotonin Syndrome and Second‐Generation Antipsychotics via Pharmacological Target‐Adverse Event Analysis

Clinical and Translational Science, EarlyView.


https://ift.tt/2J3rj8z

Assessment of Relative Bioavailability of Moroctocog Alfa and Moroctocog Alfa (AF‐CC) in Subjects With Severe Hemophilia A

Clinical and Translational Science, EarlyView.


https://ift.tt/2pNu3hi

Issue Information

Clinical and Translational Science, Volume 11, Issue 2, Page 95-97, March 2018.


https://ift.tt/2J5ekmz

Fatty Acid Amide Hydrolase Inhibition by JNJ‐42165279: A Multiple‐Ascending Dose and a Positron Emission Tomography Study in Healthy Volunteers

Clinical and Translational Science, EarlyView.


https://ift.tt/2J3r4KH

Hepatocellular carcinoma after direct-acting antiviral agents: can liver stiffness kinetics help identify patients at lower risk?

https://ift.tt/2GmdiRv

Germline mutations as potential causes of childhood solid tumours: comments on the Norwegian childhood cancer cohort study

Germline mutations as potential causes of childhood solid tumours: comments on the Norwegian childhood cancer cohort study

Germline mutations as potential causes of childhood solid tumours: comments on the Norwegian childhood cancer cohort study, Published online: 29 March 2018; doi:10.1038/s41416-018-0059-0

Germline mutations as potential causes of childhood solid tumours: comments on the Norwegian childhood cancer cohort study

https://ift.tt/2GTbh0c

End-of-life decision-making across cancer types: results from a nationwide retrospective survey among treating physicians

End-of-life decision-making across cancer types: results from a nationwide retrospective survey among treating physicians

End-of-life decision-making across cancer types: results from a nationwide retrospective survey among treating physicians, Published online: 29 March 2018; doi:10.1038/s41416-018-0070-5

End-of-life decision-making across cancer types: results from a nationwide retrospective survey among treating physicians

https://ift.tt/2E319yW

Quantitative proteomic profiling of primary cancer-associated fibroblasts in oesophageal adenocarcinoma

Quantitative proteomic profiling of primary cancer-associated fibroblasts in oesophageal adenocarcinoma

Quantitative proteomic profiling of primary cancer-associated fibroblasts in oesophageal adenocarcinoma, Published online: 29 March 2018; doi:10.1038/s41416-018-0042-9

Quantitative proteomic profiling of primary cancer-associated fibroblasts in oesophageal adenocarcinoma

https://ift.tt/2GSg0PN

The effect of selection and referral biases for the treatment of localised prostate cancer with surgery or radiation

The effect of selection and referral biases for the treatment of localised prostate cancer with surgery or radiation

The effect of selection and referral biases for the treatment of localised prostate cancer with surgery or radiation, Published online: 29 March 2018; doi:10.1038/s41416-018-0071-4

The effect of selection and referral biases for the treatment of localised prostate cancer with surgery or radiation

https://ift.tt/2GREJnh

Molecular Minimal Disease in Remission Predicts AML Relapse

WEDNESDAY, March 28, 2018 -- The detection of molecular minimal residual disease is associated with increased relapse rates in acute myeloid leukemia (AML), according to a study published in the March 29 issue of the New England Journal of...

https://ift.tt/2E08zTz

Low-Dose Abiraterone Acetate Noninferior for Prostate Cancer

WEDNESDAY, March 28, 2018 -- For castration-resistant prostate cancer (CRPC), low-dose abiraterone acetate (AA) with a low-fat breakfast is noninferior to standard dose with fasting in terms of the mean change in prostate-specific antigen (PSA),...

https://ift.tt/2GBTFbA

Liquids in E-Cigarettes Are Heterogeneous, Frequently Toxic

WEDNESDAY, March 28, 2018 -- The e-liquids used in electronic cigarettes (e-cigarettes) are a heterogeneous group, and there is a positive correlation between the number of chemicals contained in the liquid and the likelihood of its toxicity,...

https://ift.tt/2GkTzSa

mHealth Program Increases Peak VO2 After Cardiac Rehab

WEDNESDAY, March 28, 2018 -- After cardiac rehabilitation (CR), a 12-week mHealth program involving physical activity trackers and health coaching can increase absolute peak VO2 and moderate-high physical activity, according to a study published in...

https://ift.tt/2GzgrRc

Informal Caregiver Challenges for Advanced Cancer Patients during End-of-Life Care in Johannesburg, South Africa and Distinctions Based on Place of Death

In sub-Saharan Africa, late diagnosis with cancer is common. Many dying patients rely on family members for care; little is known about the challenges African informal caregivers face.

https://ift.tt/2GFj0RI

Barriers to the recognition of medullary thyroid carcinoma on FNA: Implications relevant to the new American Thyroid Association guidelines

Cancer Cytopathology, EarlyView.


https://ift.tt/2pM7k5U

Northern Italy in the American South: Assessing interobserver reliability within the Milan System for Reporting Salivary Gland Cytopathology

Cancer Cytopathology, EarlyView.


https://ift.tt/2Ibh14H

A tale of two cities: prehospital intubation with or without paralysing agents for traumatic brain injury

ANZ Journal of Surgery, EarlyView.


https://ift.tt/2pMZdWf

Peritoneal carcinomatosis or something else?

ANZ Journal of Surgery, EarlyView.


https://ift.tt/2J5ceTW

Day case hernia repair: weak evidence or practice gap?

ANZ Journal of Surgery, EarlyView.


https://ift.tt/2pQm1En

Metronidazole following excisional haemorrhoidectomy: a systematic review and meta‐analysis

ANZ Journal of Surgery, EarlyView.


https://ift.tt/2J4sMLs

Isolated colonic hernia through the oesophageal hiatus causing gastric outlet obstruction

ANZ Journal of Surgery, EarlyView.


https://ift.tt/2pNUd3C

How to do the ‘peritoneal slit’: extracting the sleeve gastrectomy made simple!

ANZ Journal of Surgery, EarlyView.


https://ift.tt/2J4sJiK

Total Estimated Cost of Diagnosed Diabetes $327 Billion in 2017

WEDNESDAY, March 28, 2018 -- The total estimated cost of diagnosed diabetes in 2017 was $327 billion, including $237 billion in direct medical costs, according to a study published online March 22 in Diabetes Care. Under the direction of the...

https://ift.tt/2GgfnlY

Issue Information

International Journal of Cancer, Volume 142, Issue 10, Page 1961-1967, 15 May 2018.


https://ift.tt/2ut7Drf

Isosorbide dinitrate in nephronophthisis treatment

American Journal of Medical Genetics Part A, Volume 176, Issue 4, Page 1023-1026, April 2018.


https://ift.tt/2pMN5Fl

The psychosocial impact of 22q11 deletion syndrome on patients and families: A systematic review

American Journal of Medical Genetics Part A, EarlyView.


https://ift.tt/2pNPRJz

Associations between laterality of orofacial clefts and medical and academic outcomes

American Journal of Medical Genetics Part A, Volume 176, Issue 4, Page 1037-1037, April 2018.


https://ift.tt/2pMMZxt

Biallelic loss‐of‐function WNT5A mutations in an infant with severe and atypical manifestations of Robinow syndrome

American Journal of Medical Genetics Part A, Volume 176, Issue 4, Page 1030-1036, April 2018.


https://ift.tt/2pPA0u5

Congenital sodium diarrhea and chorioretinal coloboma with optic disc coloboma in a patient with biallelic SPINT2 mutations, including p.(Tyr163Cys)

American Journal of Medical Genetics Part A, Volume 176, Issue 4, Page 997-1000, April 2018.


https://ift.tt/2pMMNyf

A recurrent mutation causing Melnick‐Needles syndrome in females confers a severe, lethal phenotype in males

American Journal of Medical Genetics Part A, Volume 176, Issue 4, Page 980-984, April 2018.


https://ift.tt/2pNrOKS

Patients Express Satisfaction, Understanding of Whole‐Genome Sequencing: In primary care and cardiology, patients were generally satisfied with their physicians' communication of WGS results, but expectations about its clinical benefits were not met

American Journal of Medical Genetics Part A, Volume 176, Issue 4, Page 754-755, April 2018.


https://ift.tt/2pP9tgC

Challenges associated with parenting youth with neurofibromatosis: A qualitative investigation

American Journal of Medical Genetics Part A, Volume 176, Issue 4, Page 959-968, April 2018.


https://ift.tt/2pMMgfJ

Table of Contents, Volume 176A, Number 4, April 2018

American Journal of Medical Genetics Part A, Volume 176, Issue 4, Page 749-752, April 2018.


https://ift.tt/2pOdWQF

In this issue

American Journal of Medical Genetics Part A, Volume 176, Issue 4, Page 757-757, April 2018.


https://ift.tt/2pOVR5G

Cover Image, Volume 176A, Number 4, April 2018

American Journal of Medical Genetics Part A, Volume 176, Issue 4, April 2018.


https://ift.tt/2pO8Svz

Publication schedule for 2018

American Journal of Medical Genetics Part A, Volume 176, Issue 4, Page 753-753, April 2018.


https://ift.tt/2pMM5RB

First‐year growth in children with Noonan syndrome: Associated with feeding problems?

American Journal of Medical Genetics Part A, Volume 176, Issue 4, Page 951-958, April 2018.


https://ift.tt/2pMsxvK

Comparison of different grafting materials for treatment of bone defect distal to the molar in canine

Clinical Implant Dentistry and Related Research, EarlyView.


https://ift.tt/2uz2PRi

Peri‐implant parameters, tumor necrosis factor‐alpha, and interleukin‐1 beta levels in vaping individuals

Clinical Implant Dentistry and Related Research, EarlyView.


https://ift.tt/2GitFCw

Guided maxillary sinus floor elevation using deproteinized bovine bone versus graftless Schneiderian membrane elevation with simultaneous implant placement: Randomized clinical trial

Clinical Implant Dentistry and Related Research, EarlyView.


https://ift.tt/2Ghd8yL

Marinobufagenin inhibits glioma growth through sodium pump α1 subunit and ERK signaling‐mediated mitochondrial apoptotic pathway

Cancer Medicine, EarlyView.


https://ift.tt/2GhhohT

Five‐year results of a phase II trial of preoperative 5‐fluorouracil, epirubicin, cyclophosphamide followed by docetaxel with capecitabine (wTX) (with trastuzumab in HER2‐positive patients) for patients with stage II or III breast cancer

Cancer Medicine, EarlyView.


https://ift.tt/2GhI02f

Prostate‐specific antigen nadir within 12 months as an early surrogate marker of biochemical failure and distant metastasis after low‐dose‐rate brachytherapy or external beam radiotherapy for localized prostate cancer

Cancer Medicine, EarlyView.


https://ift.tt/2E3QAvs

Inhibition of breast cancer cell growth by methyl pyropheophenylchlorin photodynamic therapy is mediated though endoplasmic reticulum stress‐induced autophagy in vitro and vivo

Cancer Medicine, EarlyView.


https://ift.tt/2Gfez0t

Attitudes toward early palliative care in cancer patients and caregivers: a Korean nationwide survey

Cancer Medicine, EarlyView.


https://ift.tt/2GfBqsQ

A novel monoclonal antibody KMP1 has potential antitumor activity of bladder cancer by blocking CD44 in vivo and in vitro

Cancer Medicine, EarlyView.


https://ift.tt/2E3QvrE

A phase 4 study of nilotinib in Korean patients with Philadelphia chromosome‐positive chronic myeloid leukemia in chronic phase: ENESTKorea

Cancer Medicine, EarlyView.


https://ift.tt/2GhUhDX

Cancer risk in patients with alopecia areata: a nationwide population‐based matched cohort study

Cancer Medicine, EarlyView.


https://ift.tt/2Ie4rBP

Determination of a radotinib dosage regimen based on dose–response relationships for the treatment of newly diagnosed patients with chronic myeloid leukemia

Cancer Medicine, EarlyView.


https://ift.tt/2Ggq5J1

Impact of pediatric cancer on family relationships

Cancer Medicine, EarlyView.


https://ift.tt/2Ie4ptH

Performance of the UroVysion® FISH assay for the diagnosis of malignant effusions using two cutoff strategies

Cancer Medicine, EarlyView.


https://ift.tt/2GjqISb

The influence of insurance type on stage at presentation, treatment, and survival between Asian American and non‐Hispanic White lung cancer patients

Cancer Medicine, EarlyView.


https://ift.tt/2E3DePI

Functional transcriptomic annotation and protein–protein interaction analysis identify EZH2 and UBE2C as key upregulated proteins in ovarian cancer

Cancer Medicine, EarlyView.


https://ift.tt/2E00PRv

Prognostic significance of the infiltration of CD163+ macrophages combined with CD66b+ neutrophils in gastric cancer

Cancer Medicine, EarlyView.


https://ift.tt/2Ggq5bZ

Genomic analysis identifies masqueraders of full‐term cerebral palsy

Annals of Clinical and Translational Neurology, EarlyView.


https://ift.tt/2GTmAoW

Seronegative antibody‐mediated neurology after immune checkpoint inhibitors

Annals of Clinical and Translational Neurology, EarlyView.


https://ift.tt/2GT3j7n

Estimation of intrathecal IgG synthesis: simulation of the risk of underestimation

Annals of Clinical and Translational Neurology, EarlyView.


https://ift.tt/2GShuJI

Peptide Receptor Radionuclide Therapy and the Treatment of Gastroentero-pancreatic Neuroendocrine Tumors: Current Findings and Future Perspectives

Abstract

Purpose and Methods

Patients with inoperable and metastasized neuroendocrine tumors (NETs), particularly those with grades 1 and 2, usually receive treatment with somatostatin analogues (SSAs). Peptide receptor radionuclide therapy (PRRT) has gained momentum over the past two decades in patients who progress on SSAs. 177Lu-DOTATATE is currently the most widely used radiopeptide for PRRT. We reviewed the recent evidence on PRRT and the treatment of gastroentero-pancreatic neuroendocrine tumors (GEP-NETs).

Results

¹⁷⁷Lu-DOTATATE can be used as neoadjuvant treatment in patients with inoperable GEP-NETs, who might be candidate for surgery after treatment and as adjuvant therapy after surgical intervention. Combination treatments of PRRT with chemotherapy or targeted agents as well as combinations of radionuclides in patients with NETs have been explored over the last few years. The majority of patients with NETs experience partial response or have disease stabilization, a small percentage has complete response, while some 30% of patients, however, will have disease progression. The safety and efficacy of retreatment with extra cycles of PRRT as salvage therapy have been evaluated in small retrospective series.

Conclusion

Overall, there is evidence that disease control and quality of life improve significantly after 117Lu PRRT therapy. Clinical trials on this therapy are scarce, and there is a need for further studies to establish proper management guidelines.

https://ift.tt/2pSiDJo

Rapid on‐site evaluation using telecytology: A major cancer center experience

Diagnostic Cytopathology, EarlyView.


https://ift.tt/2IdfxHt

Paraganglioma: Cytomorphologic features, radiologic and clinical findings in 12 cases

Diagnostic Cytopathology, EarlyView.


https://ift.tt/2I8IrrS

A New Way to Treat Brain Tumors: Targeting Proteins Coded by Microcephaly Genes?

BioEssays, EarlyView.


https://ift.tt/2GyZyGt

An Emerging Group of Membrane Property Sensors Controls the Physical State of Organellar Membranes to Maintain Their Identity

BioEssays, EarlyView.


https://ift.tt/2GCb5EH

Identifying Human Naïve Pluripotent Stem Cells − Evaluating State‐Specific Reporter Lines and Cell‐Surface Markers

BioEssays, EarlyView.


https://ift.tt/2E3AG46

Immune checkpoint inhibitors are superior to docetaxel as second‐line therapy for patients with non‐small cell lung carcinoma

CA: A Cancer Journal for Clinicians, EarlyView.


https://ift.tt/2GCaYJh

Issue highlights

British Journal of Clinical Pharmacology, Volume 84, Issue 4, Page 609-610, April 2018.


https://ift.tt/2GBU0L2

A Cascade‐Targeting Nanocapsule for Enhanced Photothermal Tumor Therapy with Aid of Autophagy Inhibition

Advanced Healthcare Materials, EarlyView.


https://ift.tt/2utmcel

Regenerative Medicine: Hierarchical Design of Tissue Regenerative Constructs (Adv. Healthcare Mater. 6/2018)

Advanced Healthcare Materials, Volume 7, Issue 6, March 21, 2018.


https://ift.tt/2Gha7yr

Chemical, antimicrobial, and molecular characterization of mortiño (Vaccinium floribundum Kunth) fruits and leaves

Food Science &Nutrition, EarlyView.


https://ift.tt/2GCaDGv

Occurrence of filamentous fungi in maize destined for human consumption in South Africa

Food Science &Nutrition, EarlyView.


https://ift.tt/2E3csqK

Effect of ethanol extract of boiled breadfruit (Treculia Africana) seed on the oral glucose tolerance, lipid profile, and body weight of normoglycemic albino rats

Food Science &Nutrition, EarlyView.


https://ift.tt/2GBTYCU

Patterns of dopamine transporter imaging in subtypes of multiple system atrophy

Acta Neurologica Scandinavica, EarlyView.


https://ift.tt/2pP1jou

Retrospective study of perampanel efficacy and tolerability in myoclonic seizures

Acta Neurologica Scandinavica, EarlyView.


https://ift.tt/2J4YcBI

Hippocampal subfield segmentation in temporal lobe epilepsy: Relation to outcomes

Acta Neurologica Scandinavica, EarlyView.


https://ift.tt/2pO3WHe

Quantitative proteomic profiling of primary cancer-associated fibroblasts in oesophageal adenocarcinoma

https://ift.tt/2GU6tHR

Germline mutations as potential causes of childhood solid tumours: comments on the Norwegian childhood cancer cohort study

https://ift.tt/2Ie6PIV

Long‐term outcome of surgical treatment of peri‐implantitis. A 2‐11‐year retrospective study

Clinical Oral Implants Research, EarlyView.


https://ift.tt/2Ie9xOx

Protein Bricks: 2D and 3D Bio‐Nanostructures with Shape and Function on Demand

Advanced Materials, EarlyView.


https://ift.tt/2pNay8A

Metal–Organic Frameworks for Separation

Advanced Materials, EarlyView.


https://ift.tt/2GAEZJv

Covalent Organic Frameworks as a Decorating Platform for Utilization and Affinity Enhancement of Chelating Sites for Radionuclide Sequestration

Advanced Materials, EarlyView.


https://ift.tt/2GgUIKt

Stretchable All‐Gel‐State Fiber‐Shaped Supercapacitors Enabled by Macromolecularly Interconnected 3D Graphene/Nanostructured Conductive Polymer Hydrogels

Advanced Materials, EarlyView.


https://ift.tt/2GESXdm

Recent Progress in Organic Electrodes for Li and Na Rechargeable Batteries

Advanced Materials, EarlyView.


https://ift.tt/2E1Fwiz

Uniaxial Alignment of Conjugated Polymer Films for High‐Performance Organic Field‐Effect Transistors

Advanced Materials, EarlyView.


https://ift.tt/2Gz2bIa

Neutrophil‐Based Drug Delivery Systems

Advanced Materials, EarlyView.


https://ift.tt/2J3KuyU

Chemical‐to‐Electricity Carbon: Water Device

Advanced Materials, EarlyView.


https://ift.tt/2GC4U3z

Cancer Therapy: Emerging Strategies of Cancer Therapy Based on Ferroptosis (Adv. Mater. 12/2018)

Advanced Materials, Volume 30, Issue 12, March 22, 2018.


https://ift.tt/2GF7h5Q

Masthead: (Adv. Mater. 12/2018)

Advanced Materials, Volume 30, Issue 12, March 22, 2018.


https://ift.tt/2E36hmB

Nonlinear Optics with 2D Layered Materials

Advanced Materials, EarlyView.


https://ift.tt/2GEYv7N

In Situ Activation of 3D Porous Bi/Carbon Architectures: Toward High‐Energy and Stable Nickel–Bismuth Batteries

Advanced Materials, EarlyView.


https://ift.tt/2E2Zl98

Polypyridyl Metallo‐Organic Assemblies for Electrochromic Applications

Advanced Materials, EarlyView.


https://ift.tt/2Gz1FtI

Salvage treatment using carbon ion radiation in patients with locoregionally recurrent nasopharyngeal carcinoma: Initial results

Cancer, EarlyView.


https://ift.tt/2pNWNGJ

The Asian American Network for Cancer Awareness, Research, and Training (AANCART)'s contributions toward reducing Asian American cancer health disparities, 2000‐2017

Cancer, Volume 124, Issue S7, Page 1527-1534, April 1, 2018.


https://ift.tt/2GfvCj2

High frequency of the PNPLA3 rs738409 [G] single‐nucleotide polymorphism in Hmong individuals as a potential basis for a predisposition to chronic liver disease

Cancer, Volume 124, Issue S7, Page 1583-1589, April 1, 2018.


https://ift.tt/2GgtJCT

Increased resource use in men with metastatic prostate cancer does not result in improved survival or quality of care at the end of life

Cancer, EarlyView.


https://ift.tt/2pNIfqI

Colorectal cancer beliefs, knowledge, and screening among Filipino, Hmong, and Korean Americans

Cancer, Volume 124, Issue S7, Page 1552-1559, April 1, 2018.


https://ift.tt/2Gg5rca

Time, trust, and transparency: Lessons learned from collecting blood biospecimens for cancer research from the Asian American community

Cancer, Volume 124, Issue S7, Page 1614-1621, April 1, 2018.


https://ift.tt/2pPom2l

Knowledge of colorectal cancer screening guidelines and intention to obtain screening among nonadherent Filipino, Hmong, and Korean Americans

Cancer, Volume 124, Issue S7, Page 1560-1567, April 1, 2018.


https://ift.tt/2GfIPIM

Issue Information

Cancer, Volume 124, Issue S7, Page 1519-1526, April 1, 2018.


https://ift.tt/2pPocYN

A physician‐initiated intervention to increase colorectal cancer screening in Chinese patients

Cancer, Volume 124, Issue S7, Page 1568-1575, April 1, 2018.


https://ift.tt/2pPo8Ix

Perspectives of Chinese American smoker and nonsmoker household pairs about the creating smokefree living together program

Cancer, Volume 124, Issue S7, Page 1599-1606, April 1, 2018.


https://ift.tt/2GfIxla

Capture of tobacco use among population‐based registries: Findings from 10 National Program of Cancer Registries states

Cancer, EarlyView.


https://ift.tt/2pPo1g5

Association of externalizing religious and spiritual beliefs on stage of colon cancer diagnosis among black and white multicenter urban patient populations

Cancer, EarlyView.


https://ift.tt/2GjQPZ6

Cancer survival among Alaska Native people

Cancer, EarlyView.


https://ift.tt/2pNHSMQ

Initial experience with purely laparoscopic living‐donor right hepatectomy

British Journal of Surgery, EarlyView.


https://ift.tt/2GEadj5

Prophylactic Dextrose Gel Does Not Prevent Neonatal Hypoglycemia: A Quasi-Experimental Pilot Study

To test the hypothesis that prophylactic dextrose gel administered to newborn infants at risk for hypoglycemia will increase the initial blood glucose concentration after the first feeding and decrease neonatal intensive care unit (NICU) admissions for treatment of asymptomatic neonatal hypoglycemia compared with feedings alone.

https://ift.tt/2Gk0ISO

Bronchopulmonary Dysplasia: The Ongoing Search for One Definition to Rule Them All

Bronchopulmonary dysplasia (BPD) is among the most common and severe sequelae of extreme preterm birth.1,2 Since the initial descriptions of the disease more than 50 years ago, the definition of BPD has gradually evolved. Owing to limitations of the current definitions, clinicians and investigators are calling for a new, more suitable definition.3-5

https://ift.tt/2pNbWc9

Prediction of Neonatal Hyperthyroidism

To assess whether it is possible to identify the neonatal predictors of neonatal hyperthyroidism at the presymptomatic stage of the disease.

https://ift.tt/2GlOnxr

Venous Thromboembolism in Children with Sickle Cell Disease: A Retrospective Cohort Study

To describe the cumulative incidence of venous thromboembolism (VTE) in children with sickle cell disease (SCD) followed at a single institution and report on the risk factors associated with VTE development.

https://ift.tt/2pSgXjV

Valganciclovir Is Beneficial in Children with Congenital Cytomegalovirus and Isolated Hearing Loss

To evaluate the efficacy of antiviral treatment for infants with congenital cytomegalovirus (cCMV) with isolated sensorineural hearing loss (SNHL).

https://ift.tt/2pOZad2

Cannabis Use During the Perinatal Period in a State With Legalized Recreational and Medical Marijuana: The Association Between Maternal Characteristics, Breastfeeding Patterns, and Neonatal Outcomes

To evaluate state-level prevalence estimates of prenatal and early postnatal cannabis use in a state with legalized medical and recreational marijuana and the association with adverse neonatal outcomes.

https://ift.tt/2GmV02g

Epidemiologic Impact of the New Guidelines for the Diagnosis of Acute Rheumatic Fever

To estimate the incidence of acute rheumatic fever (ARF) in a metropolitan area of Northern Italy and study how the introduction of the 2015 revised Jones criteria affects the epidemiology in a region with moderate to high incidence of ARF.

https://ift.tt/2pP1GQH

Acetaminophen in the Neonatal Intensive Care Unit: Shotgun Approach or Silver Bullet

The availability of intravenous acetaminophen (acetyl-para-aminophenol [APAP]) has resulted in an increase in the use of this drug in neonatal intensive care units for various indications. In term neonates undergoing major noncardiac surgery, it was shown that the use of intravenous APAP significantly decreased the amount of morphine needed to treat their pain.1 This potentially results in not only fewer opioid-related side effects, but also a much smaller number of neonates developing neonatal abstinence syndrome.

https://ift.tt/2E3xOEi

Case 10-2018: An 84-Year-Old Man with Painless Unilateral Testicular Swelling

New England Journal of Medicine, Volume 378, Issue 13, Page 1233-1240, March 2018.


https://ift.tt/2IdNwPP

Tinnitus

New England Journal of Medicine, Volume 378, Issue 13, Page 1224-1231, March 2018.


https://ift.tt/2Iek4JF

Molecular Minimal Residual Disease in Acute Myeloid Leukemia

New England Journal of Medicine, Volume 378, Issue 13, Page 1189-1199, March 2018.


https://ift.tt/2GRlkmo

Cutaneous Diphtheria

New England Journal of Medicine, Volume 378, Issue 13, March 2018.


https://ift.tt/2IcbTxc

Duration of Adjuvant Chemotherapy for Stage III Colon Cancer

New England Journal of Medicine, Volume 378, Issue 13, Page 1177-1188, March 2018.


https://ift.tt/2IcjkES

Osimertinib in EGFR Mutation–Positive Advanced NSCLC

New England Journal of Medicine, Volume 378, Issue 13, Page 1261-1263, March 2018.


https://ift.tt/2GWqb5W

Rethinking Criminalization of HIV Exposure — Lessons from California’s New Legislation

New England Journal of Medicine, Volume 378, Issue 13, Page 1174-1175, March 2018.


https://ift.tt/2GTPeGO

A New IDEA in Adjuvant Chemotherapy for Colon Cancer

New England Journal of Medicine, Volume 378, Issue 13, Page 1242-1244, March 2018.


https://ift.tt/2I8rdLp

Contemporary Hormonal Contraception and the Risk of Breast Cancer

New England Journal of Medicine, Volume 378, Issue 13, Page 1263-1266, March 2018.


https://ift.tt/2GRxrQf

Polluting Developing Brains — EPA Failure on Chlorpyrifos

New England Journal of Medicine, Volume 378, Issue 13, Page 1171-1174, March 2018.


https://ift.tt/2Iek4cD

Influenza Vaccination during Pregnancy and Protection against Pertussis

New England Journal of Medicine, Volume 378, Issue 13, Page 1257-1258, March 2018.


https://ift.tt/2GRxFH8

Ibrutinib plus Venetoclax for the Treatment of Mantle-Cell Lymphoma

New England Journal of Medicine, Volume 378, Issue 13, Page 1211-1223, March 2018.


https://ift.tt/2Ie01eh

The Verge of Collapse

New England Journal of Medicine, Volume 378, Issue 13, March 2018.


https://ift.tt/2GS2Bag

Are We Prepared for Nuclear Terrorism?

New England Journal of Medicine, Volume 378, Issue 13, Page 1246-1254, March 2018.


https://ift.tt/2GXdurD

A CRISPR Way to Restore Hearing

New England Journal of Medicine, Volume 378, Issue 13, Page 1255-1256, March 2018.


https://ift.tt/2I8DJKX

Hepatitis C in Injection-Drug Users — A Hidden Danger of the Opioid Epidemic

New England Journal of Medicine, Volume 378, Issue 13, Page 1169-1171, March 2018.


https://ift.tt/2E3boDa

New policies needed for civilian air medevac transportation

Lawmakers should evaluate billing issues and insurance company procedure to guide healthcare policy and protect patients

https://ift.tt/2J3teJV

Added value of double reading in diagnostic radiology,a systematic review

Abstract

Objectives

Double reading in diagnostic radiology can find discrepancies in the original report, but a systematic program of double reading is resource consuming. There are conflicting opinions on the value of double reading. The purpose of the current study was to perform a systematic review on the value of double reading.

Methods

A systematic review was performed to find studies calculating the rate of misses and overcalls with the aim of establishing the added value of double reading by human observers.

Results

The literature search resulted in 1610 hits. After abstract and full-text reading, 46 articles were selected for analysis. The rate of discrepancy varied from 0.4 to 22% depending on study setting. Double reading by a sub-specialist, in general, led to high rates of changed reports.

Conclusions

The systematic review found rather low discrepancy rates. The benefit of double reading must be balanced by the considerable number of working hours a systematic double-reading scheme requires. A more profitable scheme might be to use systematic double reading for selected, high-risk examination types. A second conclusion is that there seems to be a value of sub-specialisation for increased report quality. A consequent implementation of this would have far-reaching organisational effects.

Key Points

• In double reading, two or more radiologists read the same images.

• A systematic literature review was performed.

• The discrepancy rates varied from 0.4 to 22% in various studies.

• Double reading by sub-specialists found high discrepancy rates.

https://ift.tt/2J2E0jQ

Endocavitary contrast enhanced ultrasound (CEUS): a novel problem solving technique

Abstract

Contrast-enhanced ultrasound (CEUS) is a technique that has developed as an adjunct to conventional ultrasound. CEUS offers a number of benefits over conventional axial imaging with computerised tomography and magnetic resonance imaging, primarily as a "beside" test, without ionising radiation or the safety concerns associated with iodinated/gadolinium-based contrast agents. Intravascular use of ultrasound contrast agents (UCAs) is widespread with extensive evidence for effective use. Despite this, the potential utility of UCAs in physiological and non-physiological cavities has not been fully explored. The possibilities for endocavitary uses of CEUS are described in this review based on a single-centre experience including CEUS technique and utility in confirming drain placement, as well as within the biliary system, urinary system, gastrointestinal tract and intravascular catheters.

Teaching Points

• CEUS offers an excellent safety profile, spatial resolution and is radiation free.

• Endocavitary CEUS provides real-time imaging similar to fluoroscopy in a portable setting.

• Endocavitary CEUS can define internal architecture of physiological cavities.

• Endocavitary CEUS can confirm drain position in physiological and non-physiological cavities.

https://ift.tt/2I84tv1

Adapting 3' Rapid Amplification of CDNA Ends to Map Transcripts in Cancer

The two different 3' rapid amplification of cDNA ends (3' RACE) protocols described here make use of two different DNA polymerases to map sequences that include a segment of the open reading frame (ORF), the stop codon, and the entire 3' UTR of a transcript using RNA obtained from different cancer cell lines.

https://ift.tt/2IXtEBP

Generating Transgenic Plants with Single-copy Insertions Using BIBAC-GW Binary Vector

Using a pBIBAC-GW binary vector makes generating transgenic plants with intact single-copy insertions, an easy process. Here, a series of protocols is presented that guide the reader through the process of generating transgenic Arabidopsis plants, and testing the plants for intactness and copy number of the inserts.

https://ift.tt/2GkI652

Hepatocyte Growth Factor Gene Therapy for Ischemic Diseases

Human Gene Therapy, Ahead of Print.


https://ift.tt/2J3j63W

Reduced Overall Survival for Alcohol-Related Liver Cancer

WEDNESDAY, March 28, 2018 -- Reduced overall survival (OS) is seen for patients with alcohol-related hepatocellular carcinoma (HCC), according to a study published online March 28 in Cancer. Charlotte E. Costentin, M.D., from the Public Hospital...

https://ift.tt/2Gf4mBe

Heart Disease, Stroke Less Prevalent Among Foreign-Born

WEDNESDAY, March 28, 2018 -- Foreign-born adults living in the United States have a lower prevalence of coronary heart disease (CHD) and stroke than adults born in the United States, according to a study published online March 28 in the Journal of...

https://ift.tt/2pO30Tc

Children With ASD, Younger Siblings Are Undervaccinated

WEDNESDAY, March 28, 2018 -- Compared with the general population, children with autism spectrum disorder (ASD) and their younger siblings are undervaccinated, according to a study published online March 26 in JAMA Pediatrics. Ousseny Zerbo, Ph.D.,...

https://ift.tt/2GhQyGc

Total Estimated Cost of Diagnosed Diabetes $327 Billion in 2017

WEDNESDAY, March 28, 2018 -- The total estimated cost of diagnosed diabetes in 2017 was $327 billion, including $237 billion in direct medical costs, according to a study published online March 22 in Diabetes Care. Under the direction of the...

https://ift.tt/2Gm27rN

'Nontrivial' Number of Seniors Lack a Personal Physician

WEDNESDAY, March 28, 2018 -- Medicare beneficiaries without a personal physician report substantially worse patient experiences and less routine care, according to a study published online Feb. 16 in Medical Care. Grant R. Martsolf, Ph.D., from the...

https://ift.tt/2Gfyo85

2007-2013 Saw Increase in THA Revisions for 45- to 64-Year-Olds

WEDNESDAY, March 28, 2018 -- Patients aged 45 to 64 years had an increase in the total hip arthroplasty (THA) revision rate from 2007 to 2013, although decreases were seen in all other age groups, according to a study published in the March 21 issue...

https://ift.tt/2pRZQxR

Recent Years Have Seen Obesity Prevalence Increasing for Adults

WEDNESDAY, March 28, 2018 -- For adults, but not youth, there was an increase in the prevalence of obesity in decade between 2007-2008 and 2015-2016, according to a research letter published online March 23 in the Journal of the American Medical...

https://ift.tt/2GytnHb

Casting, Surgery Equivalent Over Long Term for Unstable Ankle Fx

WEDNESDAY, March 28, 2018 -- For older patients with acute unstable malleolar fractures, equivalence in function between close contact casting and immediate surgery strategies persists at three years, according to a research letter published in the...

https://ift.tt/2pM1ZLi

Use of E-Cigarettes May Hurt Efforts to Quit Smoking

WEDNESDAY, March 28, 2018 -- Among smokers who plan to quit after being discharged from the hospital, electronic cigarette (e-cigarette) users are less likely to abstain from tobacco at six months, compared to nonusers, according to a study...

https://ift.tt/2GgaIk7

Menopausal Hormone Therapy Linked to Reduced Abdominal Fat

WEDNESDAY, March 28, 2018 -- Women who receive menopausal hormone therapy (MHT) have reduced age-adjusted visceral adipose tissue (VAT), according to a study published online March 27 in the Journal of Clinical Endocrinology &...

https://ift.tt/2Gm1XAH

AT&T announces nationwide launch of FirstNet

"The launch of the network core comes a year into the FirstNet public-private partnership" FirstNet Senior Vice President Chris Sambar said

https://ift.tt/2Ggjv1f

Effect of Administration of Ramelteon, a Melatonin Receptor Agonist, on the Duration of Stay in the ICU: A Single-Center Randomized Placebo-Controlled Trial

Objectives: Occurrence of delirium in the ICU is associated with a longer stay in the ICU. To examine whether the use of ramelteon, a melatonin agonist, can prevent delirium and shorten the duration of ICU stay of critically ill patients. Design: A single-center, triple-blinded, randomized placebo-controlled trial. Setting: ICU of an academic hospital. Patients: Eligible patients were ICU patients who could take medicines orally or through a nasogastric tube during the first 48 hours of admission. Interventions: The intervention group received ramelteon (8 mg/d), and the control group received placebo (1 g/d of lactose powder) at 20:00 hours every day until discharge from the ICU. Measurements and Main Results: A total of 88 subjects were randomized to the ramelteon group (45 subjects) or the placebo group (43 subjects). As the primary endpoint, there was a trend toward decrease in the duration of ICU stay (4.56 d) in the ramelteon group compared with the placebo group (5.86 d) (p = 0.082 and p = 0.028 before and after adjustments). As the secondary endpoints, statistically significant decreases in the occurrence rate (24.4% vs 46.5%; p = 0.044) and duration (0.78 vs 1.40 d; p = 0.048) of delirium were observed in the ramelteon group. The nonintubated patients of the ramelteon group showed statistically significantly fewer awakenings per night and a higher proportion of nights without awakenings. Conclusions: Ramelteon tended to decrease the duration of ICU stay as well as decreased the occurrence rate and duration of delirium statistically significantly. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (https://ift.tt/29S62lw). Supported, in part, by the Clinical Research Program at Nagoya University. The authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: m0528332626@yahoo.co.jp Copyright © by 2018 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

https://ift.tt/2GBB8vJ

One-Year Outcomes in Patients With Acute Respiratory Distress Syndrome Enrolled in a Randomized Clinical Trial of Helmet Versus Facemask Noninvasive Ventilation

Objectives: Many survivors of acute respiratory distress syndrome have poor long-term outcomes possibly due to supportive care practices during "invasive" mechanical ventilation. Helmet noninvasive ventilation in acute respiratory distress syndrome may reduce intubation rates; however, it is unknown if avoiding intubation with helmet noninvasive ventilation alters the consequences of surviving acute respiratory distress syndrome. Design: Long-term follow-up data from a previously published randomized controlled trial. Patients: Adults patients with acute respiratory distress syndrome enrolled in a previously published clinical trial. Setting: Adult ICU. Intervention: None. Measurements and Main Results: The primary outcome was functional independence at 1 year after hospital discharge defined as independence in activities of daily living and ambulation. At 1 year, patients were surveyed to assess for functional independence, survival, and number of institution-free days, defined as days alive spent living at home. The presence of ICU-acquired weakness and functional independence was also assessed by a blinded therapist on hospital discharge. On hospital discharge, there was a greater prevalence of ICU-acquired weakness (79.5% vs 38.6%; p = 0.0002) and less functional independence (15.4% vs 50%; p = 0.001) in the facemask group. One-year follow-up data were collected for 81 of 83 patients (97.6%). One-year mortality was higher in the facemask group (69.2% vs 43.2%; p = 0.017). At 1 year, patients in the helmet group were more likely to be functionally independent (40.9% vs 15.4%; p = 0.015) and had more institution-free days (median, 268.5 [0–354] vs 0 [0–323]; p = 0.017). Conclusions: Poor functional recovery after invasive mechanical ventilation for acute respiratory distress syndrome is common. Helmet noninvasive ventilation may be the first intervention that mitigates the long-term complications that plague survivors of acute respiratory distress syndrome managed with noninvasive ventilation. Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT01680783. Drs. Patel, Pohlman, Hall, and Kress participated in the conception of the trial. Drs. Patel, Esbrook, Pawlik, Hall, and Kress participated in study design. Drs. Patel, Pohlman, and Kress recruited patients and collected data. Drs. Wolfe, MacKenzie, Salem, Esbrook, Pawlik, Stulberg, Kemple, Teele, Zeleny, and Macleod collected data alone. Drs. Patel, Wolfe, MacKenzie, Pawlik, Hall, and Kress analyzed the data. All authors participated in the interpretation of the results. Dr. Patel drafted the article. All authors have seen and approved the final version of the article. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (https://ift.tt/29S62lw). Supported, in part, by the Daniel J. Edelman grant, a gift of the Edelman family; NIH/National Heart, Lung and Blood Institute T32 HL007605 Research training in Respiratory Biology; Parker B. Francis Foundation. Drs. Patel's, Stulberg's, and Kemple's institutions received funding from a Daniel Edelman grant. Dr. Patel's institution received funding from a Parker B. Francis Foundation Career Development Award (salary support). Drs. Patel's and Wolfe's institutions received funding from the National Institutes of Health (NIH) T32 salary support, and they received support for article research from the NIH. Dr. Pohlman received funding from B. Braun (consultant). The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: jkress@medicine.bsd.uchicago.edu Copyright © by 2018 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

https://ift.tt/2IaXSzP

Dynamics of Endotoxin, Inflammatory Variables, and Organ Dysfunction After Treatment With Antibiotics in an Escherichia coli Porcine Intensive Care Sepsis Model

Objectives: To investigate the dynamics of antibiotic-induced endotoxin liberation and inflammatory response in vivo in a clinically relevant large animal intensive care sepsis model and whether the addition of an aminoglycoside to a β-lactam antibiotic affects these responses. Design: Prospective, placebo-controlled interventional experimental study. Setting: University research unit. Subjects: Thirty-six healthy pigs administered Escherichia coli as a 3-hour infusion. Interventions: After 2 hours, during E. coli infusion, the animals were exposed to cefuroxime alone, the combination of cefuroxime and tobramycin, or saline. Measurements and Main Results: Plasma endotoxin, interleukin-6, tumor necrosis factor-α, leucocytes, and organ dysfunction were recorded for 4 hours after antibiotic treatment, and differences to the values before treatment were calculated. In vitro experiments were performed to ascertain whether endotoxin is released during antibiotic-induced bacterial killing of this E. coli strain. Despite differences between the treatment arms in vitro, no differences in plasma endotoxin were observed in vivo. Antibiotic-treated animals demonstrated a higher interleukin-6 response (p

https://ift.tt/2IaXTnn

Synaptotagmin 7 Mediates Both Facilitation and Asynchronous Release at Granule Cell Synapses

When an action potential invades a presynaptic terminal it evokes large, brief Ca²⁺ signals that trigger vesicle fusion within milliseconds that is followed by a small residual Ca²⁺ (Ca_res) signal. At many synapses Ca_res produces synaptic facilitation that lasts up to hundreds of milliseconds and, although less common, Ca_res can also evoke asynchronous release (AR) that persists for tens of milliseconds. The properties of facilitation and AR are very different, which suggests that they are mediated by distinct mechanisms. However, recently it has been shown that the slow calcium sensor synaptotagmin 7 (Syt7) mediates facilitation at many synapses where AR does not occur, and conversely Syt7 can mediate AR without mediating facilitation. Here we study cerebellar granule cell synapses onto stellate cells and Purkinje cells in mice of both sexes to assess the role of Syt7 in these phenomena at the same synapse. This is of particular interest at granule cell synapses where AR is much more calcium dependent and shorter-lived than facilitation. We find that Syt7 can mediate these two processes despite their divergent properties. In Syt7 knock-out animals, facilitation and AR are smaller and shorter lived than in wild-type animals, even though the initial probability of release and Ca_res signals are unchanged. Although there are short-lived Syt7-independent mechanisms that mediate facilitation and AR in Syt7 KO animals, we find that at granule cell synapses AR and facilitation are both mediated primarily by Syt7.

SIGNIFICANCE STATEMENT At synapses made by cerebellar granule cells, presynaptic activity elevates calcium for tens of milliseconds, which in turn evokes both asynchronous release (AR) and synaptic facilitation. AR is more calcium sensitive and shorter-lived than facilitation at these synapses, suggesting that they are mediated by different mechanisms. However, we find that the slow calcium sensor synaptotagmin 7 mediates both of these phenomena. Small, rapidly decaying components of AR and facilitation are present in Syt7 KO animals, indicating that additional mechanisms can contribute to both AR and facilitation at these synapses.

https://ift.tt/2E1Z0nb

Kinematic Analysis Using 3D Motion Capture of Drinking Task in People With and Without Upper-extremity Impairments

This protocol describes an objective method to evaluate the movement performance and sensorimotor function of the upper extremity applied to individuals with stroke and healthy controls. A standardized test procedure, kinematic analysis and outcome variables for three-dimensional motion capture of drinking task are provided.

https://ift.tt/2GkAaAP

Chronic Q Fever Infection Mimicking Hematological Malignancy

Chronic Q fever (QF) infection is considered a synonym for endocarditis and, less frequently, hepatitis. Rarely, it may resemble hematological malignancies. We present an unusual chronic QF infection mimicking lymphoma with secondary hemophagocytosis. A high level of suspicion for QF is essential in cases with an unusual course. Correspondence to: Mogher Khamaisi, MD, PhD, Rambam Health Care Campus, HaAliya HaShniya St 8, Haifa, 3109601, Israel. E-mail: m_khamaisi@rambam.health.gov.il. The authors have no funding or conflicts of interest to disclose. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2E1bBHh

A Review of Ceftolozane/Tazobactam for the Treatment of Infections Caused by Multidrug-Resistant Pathogens

Multidrug-resistant (MDR) gram-negative bacterial infection is a serious and growing public health threat, in part due to limited treatment options. A novel cephalosporin and β-lactamase inhibitor, ceftolozane/tazobactam, has a broad spectrum of activity against MDR pathogens and is approved for the treatment of complicated intra-abdominal infections in combination with metronidazole and complicated urinary tract infections, including pyelonephritis. This article reviews published data on the clinical pharmacology, spectrum of activity, pharmacokinetics/pharmacodynamics, clinical efficacy and safety, and dosing and administration of ceftolozane/tazobactam. Searches of MEDLINE from January 2000 to April 2017 were conducted using the following keywords: ceftolozane, tazobactam, and ceftolozane tazobactam. Additional references were identified from a review of the retrieved articles' citations. Ceftolozane is active against organisms producing AmpC β-lactamases and MDR Pseudomonas aeruginosa. The addition of tazobactam enhances activity against extended-spectrum β-lactamase–producing organisms. Data from phase III trials using ceftolozane/tazobactam for the treatment of complicated intra-abdominal infection and complicated urinary tract infections have yielded positive results. Ceftolozane/tazobactam has demonstrated noninferior or superior efficacy to comparators in clinical trials. It has a favorable safety profile and few drug-drug interactions. This novel combination agent has a role in treating MDR infections, particularly P. aeruginosa, although its use should be reserved for patients without other treatment options to limit the risk of resistance. Although case reports of successful treatment have been reported, further investigation is needed into the utility of ceftolozane/tazobactam for the treatment of bacteremia and pneumonia caused by MDR pathogens. Correspondence to: Jamielynn Sebaaly, PharmD, BCPS, Wingate University School of Pharmacy, 515 N. Main St, Wingate, NC 28174. E-mail: j.sebaaly@wingate.edu. The authors have no funding or conflicts of interest to disclose. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2GA7maJ

Minimum Acceptable Susceptibility of Empirical Antibiotic Regimens for Gram-Negative Bloodstream Infections: A Survey of Clinical Pharmacists

Background There is a paucity of data describing the minimum acceptable susceptibility (MAS) of empirical antimicrobial regimens based on severity of illness, prognosis, and practitioner level of comfort. Objective The purpose of this study was to determine the MAS used by pharmacists involved in antimicrobial decision making for gram-negative bloodstream infections. Methods This cross-sectional survey targeted infectious diseases and/or critical care pharmacists. The 11-item survey was distributed electronically in September and October 2014. Survey respondents were asked to indicate a 2-digit number (between 59% and 99%) representing their MAS targets for each clinical scenario (3 cases of gram-negative bloodstream infection of varying complexity and prognosis and 1 control scenario of uncomplicated cystitis). The median MAS were reported by prognosis as estimated by the Bloodstream Infection Mortality Risk Score (BSIMRS) and respondent characteristics. Results Among 316 participant pharmacists, 209 (66%) and 52 (17%) identified infectious diseases and critical care as specialty practice areas, respectively. The median MAS was 90% for both case 1 (poor prognosis; BSIMRS: 13) and case 2 (guarded prognosis; BSIMRS: 8), 85% for case 3 (good prognosis; BSIMRS: 2), and 80% for case 4 (uncomplicated cystitis; BSIMRS: 0). There was a significant increase in median MAS as BSIMRS increased from 0 to 2 (P

https://ift.tt/2GkAqje

Gait Variability and Energy Cost of Over-Ground Walking in Persons with Multiple Sclerosis: A Cross-sectional study

Objective This study examined the associations between gait variability based on common spatiotemporal parameters and energetic cost of walking (Cw) in persons with multiple sclerosis (pwMS). Design Eighty-six pwMS underwent the 6-minute walk (6MW) while wearing a portable metabolic unit. The Cw was generated by dividing the net steady-state VO2 (mL/kg/min) by walking speed during the 6MW. Participants further completed two trials of walking on the GAITRite mat at a self-selected pace for measuring spatiotemporal parameters. Variability of step length, step time, stride length, swing time, stance time, stride velocity, and single and double support time was indexed by the coefficient of variation. Results Variability in the spatiotemporal variables and Expanded Disability Status Scale (EDSS) scores were significantly correlated with Cw (i.e., (|rho|=.25 - .36). Multivariate analysis revealed that disability (EDSS; β = .186), stance time variability (β = 1.446) and step length variability (β = -1.216) explained significant variance (R2 = .38; p<.001 in cw. conclusion we provide evidence of the positive association between gait variability and cw during over-ground walking pwms. findings highlight need for interventions aiming to reduce thereby reducing energetic demands this population. corresponding author emerson sebasti department kinesiology physical education anderson hall dekalb il usa. tel.: fax: email: esebastiao funding: no funding was received work disclosure: authors declare conflict interest related work. copyright wolters kluwer health inc. all rights reserved.>

https://ift.tt/2GfXFuH

Discharge Patterns for Ischemic and Hemorrhagic Stroke Patients Going from Acute Care Hospitals to Inpatient and Skilled Nursing Rehabilitation

Objective To explore variation in acute care use of inpatient (IRF) and skilled nursing (SNF) rehabilitation following ischemic and hemorrhagic stroke. Design A secondary analysis of Medicare claims data linked to IRF and SNF assessment files (2013-2014). Results The sample included 122,084 stroke patients discharged to IRF or SNF from 3,677 acute hospitals. Of the acute hospitals, 3,649 discharged patients with an ischemic stroke (range 1-402 patients/hospital, median=15) compared to 1,832 acute hospitals that discharged patients with hemorrhagic events (range 1-73 patients/hospital, median=4). The intraclass correlation (ICC) examined variation in discharge settings attributed to acute hospitals (Ischemic ICC=0.318, Hemorrhagic ICC=0.176). Patients >85 years and those with greater numbers of comorbid conditions were more likely to discharge to SNF. Comparison of self-care and mobility across stroke type suggests that patients with ischemic stroke have higher functional abilities at admission. Conclusion This study suggests demographic and clinical differences among stroke patients admitted for post-acute rehabilitation at IRF and SNF settings. Furthermore, examination of variation in ischemic and hemorrhagic stroke discharges suggests acute facility level differences and indicates a need for careful consideration of patient and facility factors when comparing the effectiveness of IRF and SNF rehabilitation. Author Disclosures: Conflict of Interest: None declared. Funding: This study was supported with funding from the Agency for Healthcare Quality and Research (R01-HS024711, R24-HS022134), National Institutes of Health (R01-AG033134; R24-HD065702; R01-HD069443; and K01- HD086290), National Institute on Aging OAIC (5P30-AG024832), Institute for Translational Sciences (UL1TR000071). Financial benefits to the authors: Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article. Correspondence: Timothy A. Reistetter, University of Texas Medical Branch, Department of Occupational Therapy, 301 University Blvd, Galveston, Texas 77555-1142. Email: tareiste@utmb.edu. Phone (409)772-944. Fax (409)747-1615 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2GEhnnC

The efficiency of a Multi-Component Training for Prospective Memory Among Healthy Older Adults: A Single-Blind, Randomized Controlled Within-Participants Crossover Trial

OBJECTIVE The main objective of the present trial was to evaluate the efficiency of a preventative multi-component prospective memory (PM) training among healthy older adults. DESIGN This study was a two-arm within-participants trial with 4 and 12-week follow-ups. Allocation ratio was 1:1 and pre- and post-training measurements were included. A total number of 25 healthy older adults were enrolled (M = 63.32, SD = 4.44). Participants were randomly allocated into two conditions: (i) PM training: participants underwent a multi-component PM training, and (ii) control: participants were not contacted during the training phase. After the training phase was finished, participants crossed over to undergo the condition they did not experience before. The differences between pre- and post-training measures of PM, activities of daily living, negative mood (depression) and anxiety were assessed. All changes in the measurements were analyzed using general linear method (GLM). This trial is registered at isrctn.com (#ISRCTN57600070). RESULTS Multi-component PM training program was significantly effective on both subjective and objective PM performances among healthy older adults. Moreover, the training had significant positive effects on activities of daily living (Independence) among participants. Also, negative mood and anxiety levels were reduced after the training was finished. CONCLUSIONS This multi-component PM training improved PM performance and activities of daily living and reduce negative mood (depression) and anxiety levels among healthy older adults. Rahimah Ibrahim, Research Associate, Malaysian Research Institute on Aging, Universiti Putra Malaysia (UPM), Serdang, Selangor, 43400, Malaysia. Associate Professor, Department of Human Development and Family Studies, Faculty of Human Ecology, Universiti Putra Malaysia (UPM), Serdang, Selangor, 43400 Malaysia. Tel-Fax: +603-8946 7149 Email: imahibrahim@upm.edu.my No funding was received. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2IdAEt7

Reversible Visual Field Defect after Isolated Intraventricular Hemorrhage

No abstract available

https://ift.tt/2GzxbrA

Letter from the new Editor-in-Chief for Insights into Imaging

https://ift.tt/2pOonUd

Partial Bile Duct Ligation in the Mouse: A Controlled Model of Localized Obstructive Cholestasis

Here, we present partial bile duct ligation as a surgical model of liver injury and regeneration in rodents.

https://ift.tt/2I9HbF2

Visualization of Thalamocortical Axon Branching and Synapse Formation in Organotypic Cocultures

This protocol describes a method for simultaneous imaging of thalamocortical axon branching and synapse formation in organotypic cocultures of the thalamus and cerebral cortex. Individual thalamocortical axons and their presynaptic terminals are visualized by a single cell electroporation technique with DsRed and GFP-tagged synaptophysin.

https://ift.tt/2GzZ7vj

The British Society of Gastroenterology/UK-PBC primary biliary cholangitis treatment and management guidelines

Primary biliary cholangitis (formerly known as primary biliary cirrhosis, PBC) is an autoimmune liver disease in which a cycle of immune mediated biliary epithelial cell injury, cholestasis and progressive fibrosis can culminate over time in an end-stage biliary cirrhosis. Both genetic and environmental influences are presumed relevant to disease initiation. PBC is most prevalent in women and those over the age of 50, but a spectrum of disease is recognised in adult patients globally; male sex, younger age at onset (<45) and advanced disease at presentation are baseline predictors of poorer outcome. As the disease is increasingly diagnosed through the combination of cholestatic serum liver tests and the presence of antimitochondrial antibodies, most presenting patients are not cirrhotic and the term cholangitis is more accurate. Disease course is frequently accompanied by symptoms that can be burdensome for patients, and management of patients with PBC must address, in a life-long manner, both disease progression and symptom burden. Licensed therapies include ursodeoxycholic acid (UDCA) and obeticholic acid (OCA), alongside experimental new and re-purposed agents. Disease management focuses on initiation of UDCA for all patients and risk stratification based on baseline and on-treatment factors, including in particular the response to treatment. Those intolerant of treatment with UDCA or those with high-risk disease as evidenced by UDCA treatment failure (frequently reflected in trial and clinical practice as an alkaline phosphatase >1.67 x upper limit of normal and/or elevated bilirubin) should be considered for second-line therapy, of which OCA is the only currently licensed National Institute for Health and Care Excellence recommended agent. Follow-up of patients is life-long and must address treatment of the disease and management of associated symptoms.

https://ift.tt/2Gybybf

Nur77 suppression facilitates androgen deprivation-induced cell invasion of prostate cancer cells mediated by TGF-β signaling

Abstract

Background

Androgen deprivation therapy (ADT) remains a standard treatment for advanced prostate cancers. However, recent studies revealed that while inhibiting the growth of certain types of prostate cancer cells, ADT promotes invasion. In the current study, we explored the effects of Nur77, an orphan nuclear receptor, on prostate cancer cell invasion following ADT.

Methods

Androgen receptor (AR) and Nur77 protein expression in patient tissues and cell lines were quantified via ELISA and western blot. The effects of AR-signaling on Nur77 expression were examined. The effects of Nur77 over-expression and knockdown on ADT-induced prostate cancer cell invasion were characterized.

Results

The results showed that AR and Nur77 are both highly expressed in prostate cancers of patients. Nur77 is positively regulated by AR-signaling at transcriptional level in NCI-H660, a widely used prostate cancer cell line. AR antagonists, Casodex and MDV3100 treatment resulted in significant inhibition of prostate cancer cell growth but enhanced cancer cell invasion. Nur77 over-expression blocked invasion-promoting effect of ADT, which is consistent with the down-regulation of MMP9 and Snail protein expression. Further mechanistic investigations showed that Nur77 inhibited transcription of TGF-β target genes (Snail and MMP9), and thereby inhibits TGF-β-mediated prostate cancer cell invasion following androgen antagonism. In addition, our data suggested the nature of this inhibitory effect of Nur77 on TGF-β-signaling is selective, for Smad3-signaling, the classical effector of TGF-β-signaling, was not interrupted by Nur77 over-expression.

Conclusion

Considering the limited success of management of prostate cancer metastasis following ADT, our data strongly suggest that Nur77 regulation could be a promising direction for search of complementary therapeutic strategy on top of classic ADT therapy.

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Testing the Efficacy of Single-Cell Stimulation in Biasing Presubicular Head Direction Activity

To support navigation, the firing of head direction (HD) neurons must be tightly anchored to the external space. Indeed, inputs from external landmarks can rapidly reset the preferred direction of HD cells. Landmark stimuli have often been simulated as excitatory inputs from "visual cells" (encoding landmark information) to the HD attractor network; when excitatory visual inputs are sufficiently strong, preferred directions switch abruptly to the landmark location. In the present work, we tested whether mimicking such inputs via juxtacellular stimulation would be sufficient for shifting the tuning of individual presubicular HD cells recorded in passively rotated male rats. We recorded 81 HD cells in a cue-rich environment, and evoked spikes trains outside of their preferred direction (distance range, 11–178°). We found that HD tuning was remarkably resistant to activity manipulations. Even strong stimulations, which induced seconds-long spike trains, failed to induce a detectable shift in directional tuning. HD tuning curves before and after stimulation remained highly correlated, indicating that postsynaptic activation alone is insufficient for modifying HD output. Our data are thus consistent with the predicted stability of an HD attractor network when anchored to external landmarks. A small spiking bias at the stimulus direction could only be observed in a visually deprived environment in which both average firing rates and directional tuning were markedly reduced. Based on this evidence, we speculate that, when attractor dynamics become unstable (e.g., under disorientation), the output of HD neurons could be more efficiently controlled by strong biasing stimuli.

SIGNIFICANCE STATEMENT The activity of head direction (HD) cells is thought to provide the mammalian brain with an internal sense of direction. To support navigation, the firing of HD neurons must be anchored to external landmarks, a process thought to be supported by associative plasticity within the HD system. Here, we investigated these plasticity mechanisms by juxtacellular stimulation of single HD neurons in vivo in awake rats. We found that HD coding is strongly resistant to external manipulations of spiking activity. Only in a visually deprived environment was juxtacellular stimulation able to induce a small activity bias in single presubicular neurons. We propose that juxtacellular stimulation can bias HD tuning only when competing anchoring inputs are reduced or not available.

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Neuronal Organization in the Inferior Colliculus Revisited with Cell-Type-Dependent Monosynaptic Tracing

The inferior colliculus (IC) is a critical integration center in the auditory pathway. However, because the inputs to the IC have typically been studied by the use of conventional anterograde and retrograde tracers, the neuronal organization and cell-type-specific connections in the IC are poorly understood. Here, we used monosynaptic rabies tracing and in situ hybridization combined with excitatory and inhibitory Cre transgenic mouse lines of both sexes to characterize the brainwide and cell-type-specific inputs to specific neuron types within the lemniscal IC core and nonlemniscal IC shell. We observed that both excitatory and inhibitory neurons of the IC shell predominantly received ascending inputs rather than descending or core inputs. Correlation and clustering analyses revealed two groups of excitatory neurons in the shell: one received inputs from a combination of ascending nuclei, and the other received inputs from a combination of descending nuclei, neuromodulatory nuclei, and the contralateral IC. In contrast, inhibitory neurons in the core received inputs from the same combination of all nuclei. After normalizing the extrinsic inputs, we found that core inhibitory neurons received a higher proportion of inhibitory inputs from the ventral nucleus of the lateral lemniscus than excitatory neurons. Furthermore, the inhibitory neurons preferentially received inhibitory inputs from the contralateral IC shell. Because IC inhibitory neurons innervate the thalamus and contralateral IC, the inhibitory inputs we uncovered here suggest two long-range disinhibitory circuits. In summary, we found: (1) dominant ascending inputs to the shell, (2) two subpopulations of shell excitatory neurons, and (3) two disinhibitory circuits.

SIGNIFICANCE STATEMENT Sound undergoes extensive processing in the brainstem. The inferior colliculus (IC) core is classically viewed as the integration center for ascending auditory information, whereas the IC shell integrates descending feedback information. Here, we demonstrate that ascending inputs predominated in the IC shell but appeared to be separated from the descending inputs. The presence of inhibitory projection neurons is a unique feature of the auditory ascending pathways, but the connections of these neurons are poorly understood. Interestingly, we also found that inhibitory neurons in the IC core and shell preferentially received inhibitory inputs from ascending nuclei and contralateral IC, respectively. Therefore, our results suggest a bipartite domain in the IC shell and disinhibitory circuits in the IC.

https://ift.tt/2IZNHPU