Dissociation of the dimer of the intrinsically disordered domain of RNase Y upon antibody binding

Although RNase Y acts as the key enzyme initiating mRNA decay in Bacillus subtilis and likely in many other Gram positive bacteria, its three-dimensional structure remains unknown. An antibody, belonging to the rare IgG2b, λx isotype, was raised against a 12-residue conserved peptide from the N-terminal non-catalytic domain of Bacillus subtilis RNase Y (BsRNaseY) that is predicted to be intrinsically disordered. Here we show that this domain can be produced as a stand-alone protein called Nter-BsRNaseY that undergoes conformational changes between monomeric and dimeric forms.

https://ift.tt/2D5k9k5

Orostachys japonicus induce p53‐dependent cell cycle arrest through the MAPK signaling pathway in OVCAR‐3 human ovarian cancer cells

Food Science &Nutrition, EarlyView.


https://ift.tt/2CGey2H

A qualitative exploration of information-seeking by electronic nicotine delivery systems (ENDS) users in New Zealand

Objectives

Given recent increases in awareness and uptake of electronic nicotine delivery systems (ENDS), we aimed to explore ENDS users' information needs and search behaviours and whether information gaps exist.

Design

Qualitative study using semistructured interviews that probed participants' smoking behaviours and ENDS use; data in this study examine ENDS information-seeking behaviours. We used qualitative description to analyse interview transcripts.

Participants and setting

We recruited 39 current ENDS users (20 dual users and 19 exclusive ENDS users who reported having previously smoked cigarettes regularly) aged 18 and over, from three urban centres in New Zealand.

Results

Several participants used Google to search for information on ENDS' health effects, but described the material they retrieved as vague or contradictory. Some interpreted the absence of information on long-term health effects as evidence ENDS did not pose potential health risks, and several perceived e-liquids as benign. Many relied on information sourced from other ENDS users, gleaned from online forums, YouTube or from discussions with friends and acquaintances; these sources typically presented ENDS positively. Several participants found specialist ENDS retailers provided valuable advice; non-specialist store staff generally lacked detailed product knowledge and sometimes offered inaccurate information.

Conclusion

People seeking information on ENDS' health effects are more likely to retrieve recommendations, product reviews and endorsements from online sources or through exchanges with other users, than they are to find scientific data. Health authorities could help meet potential users' information needs by, first, creating and frequently updating objective lay summaries of the latest scientific evidence; second, by mandating licensing for retailers with guidelines to disclose uncertainty over ENDS' efficacy for cessation and longer-term health effects, and the need for complete substitution of ENDS for combustible cigarettes among those who use these products.

https://ift.tt/2qc7UtR

Spatial distribution of mammography adherence in a Swiss urban population and its association with socioeconomic status

Cancer Medicine, EarlyView.


https://ift.tt/2qcr7vu

Evidence of human‐like Ca2+ Channels and Effects of Ca2+ Channel blockers in Acanthamoeba castellanii

Chemical Biology &Drug Design, Volume 0, Issue ja, -Not available-.


https://ift.tt/2RdzWjZ

Design, Synthesis, Molecular Modelling and In Vitro Evaluation of Tricyclic Coumarins Against Trypanosoma Cruzi

Chemical Biology &Drug Design, Volume 0, Issue ja, -Not available-.


https://ift.tt/2OOjD0r

Clinician perceptions of a prototype wearable exercise biofeedback system for orthopaedic rehabilitation: a qualitative exploration

Objectives

This study explores the opinions of orthopaedic healthcare professionals regarding the opportunities and challenges of using wearable technology in rehabilitation. It continues to assess the perceived impact of an exemplar exercise biofeedback system that incorporates wearable sensing, involving the clinician in the user-centred design process, a valuable step in ensuring ease of implementation, sustained engagement and clinical relevance.

Design

This is a qualitative study consisting of one-to-one semi-structured interviews, including a demonstration of a prototype wearable exercise biofeedback system. Interviews were audio-recorded and transcribed, with thematic analysis conducted of all transcripts.

Setting

The study was conducted in the orthopaedic department of an acute private hospital.

Participants

Ten clinicians from a multidisciplinary team of healthcare professionals involved in the orthopaedic rehabilitation pathway participated in the study.

Results

Participants reported that there is currently a challenge in gathering timely and objective data for the monitoring of patients in orthopaedic rehabilitation. While there are challenges in ensuring reliability and engagement of biofeedback systems, clinicians perceive significant value in the use of wearable biofeedback systems such as the exemplar demonstrated for use following total knee replacement.

Conclusions

Clinicians see an opportunity for wearable technology to continuously track data in real-time, and feel that feedback provided to users regarding exercise technique and adherence can further support the patient at home, although there are clear design and implementation challenges relating to ensuring technical accuracy and tailoring rehabilitation to the individual. There was perceived value in the prototype system demonstrated to participants which supports the ongoing development of such exercise biofeedback platforms.

https://ift.tt/2qdDyak

Systematic review of interventions targeting sickness absence among pregnant women in healthcare settings and workplaces

Objectives

The high rate of sickness absence from work during pregnancy is recognised as a problem, and may be higher than necessary from a health perspective. The aim was to evaluate the effectiveness of interventions in healthcare settings and workplaces targeting sickness absence among pregnant women.

Methods

Studies were eligible if they included pregnant women participating in any intervention in healthcare settings or workplaces. The outcome was length of sickness absence in days or number of episodes. Study design had to be either randomised controlled trials (RCTs) or quasi-experimental studies.

The search for studies was conducted in PubMed, Scopus, CINAHL, PsycINFO, ClinicalTrials.gov and WHO trial registry. Risk of bias was assessed by the Joanna Briggs Institute standardised quality assessment instrument.

Results

A total of nine studies were quality assessed and of these, four were excluded due to insufficient methodological quality. Five RCTs conducted in healthcare settings in Sweden and Norway were included. Due to heterogeneity, meta-analysis was not performed.

Two RCTs examined complementary and alternative medicine and three RCTs the effect of physical exercise. In general, the frequency of women on sickness absence was lower in the intervention groups than the control groups, however, only among pregnant women who participated in a 12-week exercise programme, the frequency was significantly lower (22% vs 30%, p=0.04).

Conclusion

The evidence of interventions targeting sickness absence among pregnant women in healthcare settings is sparse, and no studies were conducted at workplaces.

Future interventions including physical activity provided in collaboration with healthcare settings and workplaces are requested. Studies should measure sickness absence based on valid methods, measure compliance to the intervention and provide transparency of statistical methods.

PROSPERO registration number

CRD42018084802.

https://ift.tt/2CHI2xq

Evolution of transcatheter aortic valve implantation over 7 years: results of a prospective single-centre registry of 2000 patients in a large municipal hospital (TAVIK Registry)

Objectives

Use of transcatheter aortic valve implantation (TAVI) to treat severe aortic stenosis (AS) has gained popularity, accompanied by an evolution of patient and clinical factors. We aimed to characterise changes and evaluate their impact on outcomes.

Setting

In this single-centre, German TAVIK registry patients undergoing TAVI between 2008 and 2015 were documented prospectively.

Participants/interventions

2000 consecutive patients with AS undergoing TAVI were divided in four cohorts. 500 patients underwent TAVI in each of the following time bins: April 2008 to July 2010 (cohort I), July 2010 to April 2013 (cohort II), April 2012 to October 2013 (cohort III) and October 2013 to March 2015 (cohort IV).

Results

The mean age was 81.8 years, without significant variation across cohorts. Compared with cohort I, prior MI (5.4%vs11.0%; p<0.001) and New York Heart Association class IV (10.0%vs3.6%; p<0.001) were less common in cohort IV. Across cohorts, there was a fall in EuroSCORE (24.3%–18.7%), frailty (48.4%–17.0%) and use of transapical access (43.6%–29.0%), while transfemoral access increased (56.4%–71.0%; p<0.001 for each). Periprocedurally, there was a fall in moderate/severe aortic regurgitation (3.2%–0.0%) and rate of unplanned cardiopulmonary bypass (4.0%–1.0%; both p<0.001). A similar trend applied to 30-day rate of major vascular complications (5.2%–1.8%; p=0.006), life-threatening bleeding (7.0%–3.0%; p<0.001) and cardiovascular mortality (4.4%–1.8%; p=0.020). One-year post-TAVI, mortality and stroke rates did not differ.

Conclusions

Evolution of TAVI between 2008 and 2015 saw a trend towards its usage in lower risk patients and rapid progression towards improved safety. Evaluation and refinement should now continue to further lessen stroke and pacemaker rates.

https://ift.tt/2qdfMv0

Harmful effects of early hyperoxaemia in patients admitted to general wards: an observational cohort study in South Korea

Objectives

We evaluated the association between hyperoxaemia induced by a non-invasive oxygen supply for 3 days after emergency department (ED) arrival and the clinical outcomes at day 5 after ED arrival.

Design

Observational cohort study.

Setting and patients

Consecutive ED patients ≥16 years of age with available arterial blood gas analysis results who were admitted to our hospital were enrolled from January 2010 to December 2016.

Interventions

The highest (PaO_2MAX), average (PaO_2AVG) and median (PaO_2MED) PaO₂ (arterial oxygen pressure) values within 72 hours and the area under the curve divided by the time elapsed between ED admittance and the last PaO₂ result (AUC₇₂) were used to assess hyperoxaemia. The AUC₇₂ values were calculated using the trapezoid rule.

Outcomes

The primary outcome was the 90-day in-hospital mortality rate. The secondary outcomes were intensive care unit (ICU) transfer and respiratory failure at day 5 after ED arrival, as well as new-onset cardiovascular, coagulation, hepatic and renal dysfunction at day 5 after ED arrival.

Results

Among the 10 141 patients, the mortality rate was 5.8%. The adjusted ORs of in-hospital mortality for PaO_2MAX, PaO_2AVG, PaO_2MED and AUC₇₂ were 0.79 (95% CI 0.61 to 1.02; p=0.0715), 0.92 (95% CI 0.69 to 1.24; p=0.5863), 0.82 (95% CI 0.61 to 1.11; p=0.2005) and 1.53 (95% CI 1.25 to 1.88; p<0.0001). All of the hyperoxaemia variables showed significant positive correlations with ICU transfer at day 5 after ED arrival (p<0.05). AUC₇₂ was positively correlated with respiratory failure, as well as cardiovascular, hepatic and renal dysfunction (p<0.05). PaO_2MAX was positively correlated with cardiovascular dysfunction. PaO_2MAX and AUC₇₂ were negatively correlated with coagulation dysfunction (p<0.05).

Conclusions

Hyperoxaemia during the first 3 days in patients outside the ICU is associated with in-hospital mortality and ICU transfer at day 5 after arrival at the ED.

https://ift.tt/2CG9z1Z

Comparison of coronary heart disease risk assessments among individuals with metabolic syndrome using three diagnostic definitions: a cross-sectional study from China

Objective

Metabolic syndrome (MetS) is a notable risk factor of coronary heart disease (CHD). However, there are differences in the methods used to define MetS. The purpose of this study was to determine which MetS definition most fully reflects the 10-year probability of CHD based on the Framingham risk algorithm.

Design

Cross-sectional study.

Setting

Data were obtained from the China Health and Nutrition Survey and the Influencing Factors of Chronic Diseases Survey conducted among residents of Nanshan District in Shenzhen, China.

Participants

In total, 1721 participants aged 20–80 years were included in this study.

Methods

MetS was diagnosed according to the criteria of the National Cholesterol Education Program's Adult Treatment Panel (revised NCEP-ATP III), the International Diabetes Federation (IDF) and the Chinese Diabetes Society (CDS). The NCEP-ATP III algorithm was used to calculate the Framingham risk score, and the Framingham risk score was used to define the probability of developing CHD within 10 years either as low (<6%), moderate (6%–10%), moderately high (10%–20%) or high (>20%). Chi-square tests with or without the Bonferroni correction were used to compare the differences in the distribution of the 10-year estimated risk of developing CHD among the three definitions.

Results

Compared with the other definitions, the revised NCEP-ATP III criteria identified more participants (30.96%, 95% CI 28.8% to 33.2%) as having MetS, while the CDS criteria showed the highest 10-year probability of developing CHD. The 10-year probability of developing CHD in the participants with MetS was significantly higher than that in the participants without MetS (CDS: ²=157.65, revised ATP III: ²=45.17, IDF: ²=306.15, all p<0.001), and all definitions more fully reflect the CHD risk in men than in women (revised NCEP-ATP III: ²=72.83; IDF: ²=63.60; CDS: ²=23.84; all p<0.001).

Conclusions

This study demonstrates the differences in the prevalence and distribution of the 10-year estimated risk of developing CHD based on the definition of MetS. A significant finding of this study is that the MetS definitions have better performance for men than for women. Further studies in China, especially longitudinal studies, are needed to determine which definition of MetS is best suited for predicting CHD risk.

https://ift.tt/2qd8cjV

Funding and policy incentives to encourage implementation of point-of-care C-reactive protein testing for lower respiratory tract infection in NHS primary care: a mixed-methods evaluation

Objectives

Utilisation of point-of-care C-reactive protein testing for lower respiratory tract infection has been limited in UK primary care, with costs and funding suggested as important barriers. We aimed to use existing National Health Service funding and policy mechanisms to alleviate these barriers and engage with clinicians and healthcare commissioners to encourage implementation.

Design

A mixed-methods study design was adopted, including a qualitative survey to identify clinicians' and commissioners' perceived benefits, barriers and enablers post-implementation, and quantitative analysis of results from a real-world implementation study.

Interventions

We developed a funding specification to underpin local reimbursement of general practices for test delivery based on an item of service payment. We also created training and administrative materials to facilitate implementation by reducing organisational burden. The implementation study provided intervention sites with a testing device and supplies, training and practical assistance.

Results

Despite engagement with several groups, implementation and uptake of our funding specification were limited. Survey respondents confirmed costs and funding as important barriers in addition to physical and operational constraints and cited training and the value of a local champion as enablers.

Conclusions

Although survey respondents highlighted the clinical benefits, funding remains a barrier to implementation in UK primary care and appears not to be alleviated by the existing financial incentives available to commissioners. The potential to meet incentive targets using lower cost methods, a lack of policy consistency or competing financial pressures and commissioning programmes may be important determinants of local priorities. An implementation champion could help to catalyse support and overcome operational barriers at the local level, but widespread implementation is likely to require national policy change. Successful implementation may reproduce antibiotic prescribing reductions observed in research studies.

https://ift.tt/2CG9Vpl

Why has adolescent smoking declined dramatically? Trend analysis using repeat cross-sectional data from New Zealand 2002-2015

Objectives

Adolescent smoking has declined in New Zealand and in many other countries since the late 1990s, yet the reasons for the decline are not well understood. We investigated the extent to which established risk factors for adolescent smoking (parental, sibling and peer smoking, and exposure to smoking in the home) explained the downward trend.

Design

Trend analysis of repeat cross-sectional data from an annual nationally representative survey.

Setting

New Zealand.

Participants

Secondary school students aged 14–15 (n=398 221).

Outcome measure

Regular (at least monthly) smoking.

Methods

For each risk factor (parental smoking, best friend smoking, older sibling smoking and past week exposure to smoking in the home) we plotted prevalence of exposure, 2002–2015. Next, using multivariable logistic regression, we modelled the trend in regular smoking (expressed as an OR for year) adjusting for age, sex, ethnicity and socioeconomic position. The risk factors were added to the model—individually and collectively—to test whether they attenuated the OR for year.

Results

Exposure to all risk factors except 'past week exposure to smoking in the home' decreased between 2002 and 2015. We observed a strong downward trend in regular smoking among adolescents (OR=0.88 per year, 95% CI 0.88 to 0.88, p<0.001). 'Best friend smoking' was the only risk factor that significantly attenuated the trend. However, due to circularity, this factor provides an unsatisfactory explanation for population level smoking decline.

Conclusions

The established risk factors that we explored do not appear to have contributed to the remarkable decline in adolescent smoking in New Zealand between 2003 and 2015. Further research is needed to assess the possible contribution of factors outside our model, such as changes in the policy context, the social meaning of smoking and broader social and economic conditions.

https://ift.tt/2CG9P0X

Acceptability and feasibility of dual HIV and syphilis point-of-care testing for early detection of infection among pregnant women in China: a prospective study

Objective

To assess the feasibility and acceptability of using WHO prequalified combined dual HIV/syphilis rapid diagnostic tests (RDT) for same-day results in antenatal care (ANC) clinics.

Methods

This is a pragmatic implementation study using quantitative approach to evaluate outcomes. Antenatal clinic attendees from 21 rural and urban township hospitals in two provinces of China were offered with free dual RDTs testing that included HIV and syphilis, in addition to the routine blood tests. Study outcomes included testing uptake before and during dual RDT use, test feasibility and acceptability among pregnant women. Regression model was used to assess acceptance of RDT testing.

Results

In total, 1787 out of 1828 pregnant women attending ANC received the RDT testing. Testing uptake among pregnant women in their first and second trimester increased from 76.0% (2438/3269) using standard blood testing to 90.1% (1626/1787) with concurrent RDT use (²=197.1, p<0.001). Among 1787 pregnant women who received RDT tests, 98.3% (1757/1787) participants were given test result the same day. Positive proportions of HIV and syphilis screened with RDT were 0.06% (1/1787) and 1.0% (18/1787), respectively. Regression analysis indicated that women who did not receive syphilis or HIV testing before were less likely to accept dual RDT (OR 0.28, 95% CI 0.10 to 0.75). Acceptance for dual RDT testing at second or third antenatal visit was lower compared with the first visit (OR 0.37, 95% CI 0.15 to 0.94).

Conclusion

Combined dual HIV/syphilis RDT with same-day results increased uptake of HIV and syphilis testing among pregnant women at primary healthcare facilities. Given the diversity of testing capacities among health services especially in rural areas in China, the dual RDT kit is feasible tool to improve testing uptake among pregnant women.

https://ift.tt/2qd86sz

Molecular features unique to glioblastoma radiation resistant residual cells may affect patient outcome - a short report

Abstract

Purpose

Previously we have shown, using a primary glioblastoma (GBM) cell model, that a subpopulation of innately radiation resistant (RR) GBM cells survive radiotherapy and form multinucleated and giant cells (MNGCs) by homotypic fusions. We also showed that MNGCs may cause relapse. Here, we set out to explore whether molecular characteristics of RR cells captured from patient-derived primary GBM cultures bear clinical relevance.

Methods

Primary cultures were derived from 19 naive GBM tumor samples. RR cells generated from these cultures were characterized using various cell biological assays. We also collected clinicopathological data of the 19 patients and assessed associations with RR variables using Spearman's correlation test and with patient survival using Kaplan-Meier analysis. Significance was determined using a log-rank test.

Results

We found that SF2 (surviving fraction 2) values (p = 0.029), days of RR cell formation (p = 0.019) and percentage of giant cells (p = 0.034) in the RR population independently correlated with a poor patient survival. We also found that low ATM (Ataxia-telangiectasia mutated) expression levels in RR cells showed a significant (p = 0.002) negative correlation with SF2 values. A low ATM expression level in RR cells along with a high tumor volume was also found to negatively correlate with patient survival (p = 0.011). Finally, we found that the ATM expression levels in RR cells independently correlated with a poor patient survival (p = 0.014).

Conclusions

Our data indicate that molecular features of innately radiation resistant GBM cells independently correlate with clinical outcome. Our study also highlights the relevance of using patient-derived primary GBM cultures for the characterization of RR cells that are otherwise inaccessible for analysis.

https://ift.tt/2yAcpTn

Adult bilateral idiopathic occlusion of foramina of Monro: is foraminoplasty really safe and effective?

Idiopathic bilateral occlusion of foramina of Monro is an extremely rare condition in adults and only few cases are reported. Currently, foraminoplasty is indicated as first-line treatment. We reported the case of a 52-year-old woman who presented with headache, instability and urinary incontinence. The imaging demonstrated bilateral occlusion of foramina of Monro and consequent biventricular hydrocephalus. A ventriculo-peritoneal shunt allowed to treat the hydrocephalus, but it was necessary to remove it for the appearance of peritonitis from salpingitis. Since the initial symptomatology reappeared, according to the literature, we performed an endoscopic foraminoplasty with septostomy. The patient immediately developed short-term memory impairment and subsequently we observed the hydrocephalus recurrence. The positioning of a ventriculo-atrial shunt allowed to improve the symptoms, but the memory remained impaired. In case of bilateral true stenosis of foramina of Monro, foraminoplasty may lead to severe memory impairment. Therefore, cerebrospinal fluid shunting should be considered as an effective and safer treatment.

https://ift.tt/2O7UaKa

Prenatal diagnosis and management of fetal discordant alpha-thalassaemia in dichorionic diamniotic (DCDA) twins

A 29-year-old nulliparous woman with a dichorionic diamniotic (DCDA) twin pregnancy was referred to our hospital at 16 weeks' gestation for prenatal diagnosis. She was diagnosed of Haemoglobin H Constant Spring (Hb H CS; --^SEA/α^CSα) and her husband of alpha thalassemia-1 trait (--^SEA/αα). Detailed ultrasound showed that left twin had fetal anaemia and early signs of hydrops while the right one was normal. Both twins were female. Amniocentesis in each sac was performed for prenatal diagnosis of thalassemia after a proper counselling with the couple. DNA analysis confirmed that the left fetus was affected with haemoglobin Bart's hydrops fetalis (--^SEA/--^SEA) while the right one was alpha thalassemia-1 trait (--^SEA/αα). Selective feticide with intracardiac injection of KCl was successfully performed on the hydropic fetus. Identification of the affected fetus is crucial for selective termination. Family counselling about the procedure and complications is also necessary.

https://ift.tt/2yAJ3nP

Histologically confirmed case of complete atrioventricular block due to hepatocellular carcinoma

A 72-year-old man, who had been diagnosed as having hepatocellular carcinoma (HCC) with multiple extrahepatic metastasis, complained a general fatigue which appeared 2 weeks before admission. Because bradycardia was detected on physical examination, ECG was performed which revealed the complete atrioventricular (AV) block. We stopped Ca-blocker and β-blocker, but the bradycardia persisted. He was admitted to our hospital for an emergent pacemaker implantation. On admission, he complained dyspnoea. After the surgery, he died due to deterioration of heart failure. The autopsy revealed cardiac metastasis of HCC on AV node, so it was suspected that cardiac metastasis caused the AV block. We thought that the cause of his death was the exacerbation of heart failure associated with bradycardia. It was likely that complete AV block as a very rare complication caused by cardiac metastasis of HCC influenced the prognosis of this patient.

https://ift.tt/2O7U994

Umbilical cord anomalies: antenatal ultrasound findings and postnatal correlation

Umbilical cord anomalies are rare. The differential diagnosis for a cystic structure around the umbilical cord and its insertion include pseudocyst, omphalomesenteric duct cyst, haemangioma, omphalocele or anterior abdominal wall defects. Although cord anomalies can be detected through antenatal ultrasound scans (US), very often a definitive diagnosis cannot be made. This may affect the management of the infant at birth. In cases where antenatal US was not diagnostic, current evidence supports the use of MRI to help in making an accurate diagnosis. We report two cases of umbilical cord anomalies. The first case was diagnosed in antenatal US as an omphalocele, but was found to be an allantoic cyst with hamartoma on postnatal diagnosis. The second case was not detected on antenatal US, and was diagnosed postnatally as a small omphalocele with vitellointestinal duct remnants.

https://ift.tt/2yA32mD

Coronary artery vasospasm in a patient withChurg-Strauss syndrome

Patients with Churg-Strauss syndrome often suffer from unusual cardiac manifestations and sudden cardiac death. This differs from patients with other autoimmune disorders, who typically present with premature ischaemic heart disease. We report the case of a 56-year-old man with recurrent coronary vasospasm, including an inferoposterior ST-elevation myocardial infarction, complicated by bradycardic arrest. There was only minor coronary artery disease on coronary angiography. An elevated eosinophil count was noted. His medical history included allergic rhinitis with polyposis, adult-onset asthma and biopsy-proven eosinophilic oesophagitis. Review of his sinus biopsies demonstrated blood vessels with marked accumulation of eosinophils in extravascular areas. The patient, therefore, met the American College of Rheumatology criteria for Churg-Strauss syndrome. The patient was commenced on immunosuppression, with the return of the eosinophil count to within normal limits, and remains free of cardiovascular events over 24 months.

https://ift.tt/2O7U7xY

Not just another diplopia: neurocysticercosis in a postpartum woman

Description 

A 23-year-old woman with a history of child birth 2 weeks back presented to the outpatient department with binocular diplopia and slight blurring of vision in both eyes (BE) for last 1 week. She also had four bouts of vomiting with associated nausea and hemicranial dull headache for last 3 days. The antenatal and immediate perinatal period was uneventful. Previous history as well as systemic history was not significant. The patient was afebrile. On systemic examination, neck stiffness could be elucidated. The blood pressure was recorded to be 124/74 mm Hg. Ocular examination revealed the visual acuity to be 20/40 in BE. There was restricted abduction of the right eye (figure 1) and diplopia charting revealed isolated sixth cranial nerve palsy. Pupillary reaction was brisk in BE with no evidence of relative afferent pupillary defect. Slit lamp evaluation of the anterior segment showed no abnormality. On fundus evaluation, bilateral disc oedema with ill-defined...

https://ift.tt/2yCktD9

Giant vesicle calculi leading to spontaneous bladder rupture and acute renal failure: an unusual presentation

Spontaneous rupture of the urinary bladder is extremely rare. We report a case of a 70-year-old man with spontaneous bladder rupture secondary to neglected giant vesicle calculi who presented as acute renal failure. The patient was stabilised with per-urethral catheterisation and extravesical drain placement. About 700 mL pus mixed with urine was drained through the per-urethral catheter and approximately 2000 mL of pus was drained through the extravesical drain. Cystolithotomy showed two large calculi which were removed.

https://ift.tt/2O7U5WS

Acute aortic dissection: a missed diagnosis

A 60-year-old man with a history of indigestion and untreated hypertension presented with sudden-onset central chest pain which radiated to his back. Acute coronary syndrome was initially suspected but excluded in the emergency department before the patient was discharged. The pain subsequently abated to mild intermittent episodes and was misdiagnosed as indigestion. A week later the patient developed new shortness of breath and 'flu-like' symptoms with a positive d-dimer test. CT angiography revealed a Stanford type B aortic dissection which was causing hypoperfusion of the right kidney, resulting in an acute kidney injury. Due to uncontrolled hypertension despite rigorous antihypertensive medication and his failing renal function, the patient underwent endovascular repair and made a good recovery postoperatively.

https://ift.tt/2yA30ev

Proximal humerus deformity, in a four-limb amputee following meningococcal septicaemia

We present a challenging case of proximal humerus varus deformity in a four-limb amputee, caused by growth arrest from meningococcal septicaemia. The deformity resulted in a loss of function for our patient with inhibition of activities of daily living, requiring corrective osteotomy to help improve the range of motion of the shoulder. We describe in detail the management of our patient, highlight the importance of the orthopaedic manifestations of meningococcal septicaemia, and demonstrate the importance of monitoring potential deformities from growth arrest in these patients.

https://ift.tt/2O7U4lM

Tuberous sclerosis complex: a clinical case with multiple ophthalmological manifestations

The tuberous sclerosis complex is a rare disease, with autosomal dominant transmission, with multisystemic involvement including ophthalmologic. Retinal hamartomas and retinal achromic patch are the most frequent ocular findings. Other ophthalmic signs and symptoms are relatively rare in this disease.

We describe the case of a young woman with tuberous sclerosis who presented with horizontal binocular diplopia and decreased visual acuity without complaints of nausea, vomiting or headache. She had right abducens nerve palsy, pale oedema of both optic discs and retinal hamartomas. An obstructive hydrocephalus caused by an intraventricular expansive lesion was identified in brain CT.

Observation by the ophthalmologist is indicated in all confirmed or suspected cases of tuberous sclerosis to aid in clinical diagnosis, monitoring of retinal hamartomas or identification of poorly symptomatic papilloedema.

https://ift.tt/2yzfrqS

Chest pain following permanent pacemaker insertion... a case of pneumopericardium due to atrial lead perforation

Permanent pacemaker (PPM) implantation is an increasingly common procedure with complication rate estimated between 3% and 6%. Cardiac perforation by pacemaker lead(s) is rare, but a previous study has shown that it is probably an underdiagnosed complication. We are presenting a case of a patient who presented 5 days after PPM insertion with new-onset pleuritic chest pain. She had a normal chest X-ray (CXR), and acceptable pacing checks. However, a CT scan of the chest showed pneumopericardium and pneumothorax secondary to atrial lead perforation. The pain only settled by replacing the atrial lead. A repeat chest CT scan a few months later showed complete resolution of the pneumopericardium and pneumothorax. We believe that cardiac perforation can be easily missed if associated with normal CXR and acceptable pacing parameters. Unexplained chest pain following PPM insertion might be the only clue for such complication, although it might not always be present.

https://ift.tt/2O7l6JO

Solitary fibrous tumour of caecum wall: an unlikely cause of low gastrointestinal haemorrhage

Solitary fibrous tumour (SFT), previously denominated as haemangiopericytoma, is a rare, spindle cell neoplasm that was first described in the thoracic pleura. It is now known that this tumour may develop from almost any anatomic location. We report a case of SFT, in a 65-year-old man, which was located in the muscularis propria layer of the caecum with involvement of the serosa and the ileocecal appendix, location never described in the literature, and with an uncommon clinical presentation of hematochezia. A radical right hemicolectomy was performed, and the patient was asymptomatic without evidence of metastasis or relapse after 6 months of follow-up.

https://ift.tt/2yA2Xzl

Neck carbuncle associated with methicillin-susceptible Staphylococcus aureus bacteraemia

Description 

A 66-year-old man presented with a 14-day history of painful posterior neck swelling and fever for a week prior to presentation. A restricted neck movements was noted over the last 3 days. Generally, he had a fever of 37.5°C and tachycardia at 121 bpm, whereas the other vital signs were normal. Local physical examination showed large posterior neck swelling with erythema and multiple sinuses discharging pus.

A neck carbuncle was diagnosed (figure 1).1 2 Skin eruptions were noted also on the lower extremities and gluteal region.

Figure 1

Physical examination. (a) A pustule in posterior neck which is surrounded by an extensive erythematous swelling (white dotted circle). (b) The pustules that have the same features were seen at lower extremity and gluteal region.

Laboratory evaluation showed a haemoglobin level of 14.3 g/dL, leucocyte count of 38 800x109/L, sodium of 132 mmol/L, creatinine of...

https://ift.tt/2O7U19A

Effect of Oral Vitamin C Supplementation on High-Altitude Hyperuricemia in Young Men Initially Migrating to High Altitude: A Pilot Study

High Altitude Medicine &Biology, Ahead of Print.


https://ift.tt/2Rj39Kt

Bleeding small bowel: methylene blue guided resection

ANZ Journal of Surgery, EarlyView.


https://ift.tt/2PlUHMV

Keeping your cool – a simple reusable neck cooler in orthopaedic surgery: a pilot randomized controlled trial

ANZ Journal of Surgery, EarlyView.


https://ift.tt/2JlraOg

Double trouble: two sites of internal hernia following total gastrectomy

ANZ Journal of Surgery, EarlyView.


https://ift.tt/2PlUDwF

Prospective randomized comparative study of pigtail catheter drainage versus percutaneous needle aspiration in treatment of liver abscess

ANZ Journal of Surgery, EarlyView.


https://ift.tt/2JfHK21

Tooth loss can indicate malnutrition, study finds

Older adults are at risk for both impaired oral health and malnutrition, according to a new study.

https://ift.tt/2D976OK

Correction to: The Future of Precision Medicine: Potential Impacts for Health Technology Assessment

The article The Future of Precision Medicine: Potential Impacts for Health Technology Assessment written by James Love‑Koh, Alison Peel Juan, Carlos Rejon‑Parrilla, KateAnastasia Chalkidou, Hannah Wood, Matthew Taylor was originally published electronically on the publisher's internet portal (currently Springer Link) on [13th July, 2018] with incorrect spelling of the co-author "Juan Carlos Rejon-Parilla". The correct spelling is "Juan Carlos Rejon-Parrilla".

https://ift.tt/2As2Ib4

Comorbidities, concomitant medications and potential drug‐drug interactions with interferon‐free direct‐acting antiviral agents in hepatitis C patients in Taiwan

Alimentary Pharmacology &Therapeutics, EarlyView.


https://ift.tt/2AsgeeH

Dead or alive: how the immune system detects microbial viability

Matteo Ugolini | Leif E Sander

https://ift.tt/2PVsLgd

Temozolomide induces senescence and repression of DNA repair pathways in glioblastoma cells via activation of ATR-CHK1, p21, and NF-kB

The DNA methylating drug temozolomide (TMZ), which induces cell death through apoptosis, is used for the treatment of malignant glioma. Here we investigate the mechanisms underlying the ability of TMZ to induce senescence in glioblastoma cells. TMZ-induced senescence was triggered by the specific DNA lesion O6MeG and characterized by arrest of cells in the G2/M phase. Inhibitor experiments revealed that TMZ-induced senescence was initiated by damage recognition through the MRN complex, activation of the ATR/CHK1 axis of the DNA damage response pathway, and mediated by degradation of CDC25c. TMZ-induced senescence required functional p53 and was dependent on sustained p21 induction. p53-deficient cells failed to induce senescence but were still able to induce a G2/M arrest. p14 and p16, targets of p53, were silenced in our cell system, and did not seem to play a role in TMZ-induced senescence. In addition to p21, the NF-κB pathway was required for senescence, which was accompanied by induction of the senescence-associated secretory phenotype (SASP). Upon TMZ exposure, we found a strong repression of the mismatch repair proteins MSH2, MSH6, and EXO1 as well as the homologous recombination protein RAD51, which were downregulated by disruption of the E2F1/DP1 complex. Repression of these repair factors was not observed in G2/M arrested p53-deficient cells and therefore represents a specific trait of TMZ-induced senescence.

https://ift.tt/2PSSRjW

Homophilic CD44 interactions mediate tumor cell aggregation and polyclonal metastasis in patient-derived breast cancer models [Research Articles]

Circulating tumor cells (CTCs) seed cancer metastases; however, the underlying cellular and molecular mechanisms remain unclear. CTC clusters were less frequently detected but more metastatic than single CTCs of triple negative breast cancer patients and representative patient-derived-xenograft (PDX) models. Using intravital multiphoton microscopic imaging, we found that clustered tumor cells in migration and circulation resulted from aggregation of individual tumor cells rather than collective migration and cohesive shedding. Aggregated tumor cells exhibited enriched expression of the breast cancer stem cell marker CD44 and promoted tumorigenesis and polyclonal metastasis. Depletion of CD44 effectively prevented tumor cell aggregation and decreased PAK2 levels. The intercellular CD44-CD44 homophilic interactions directed multicellular aggregation, requiring its N-terminal domain, and initiated CD44-PAK2 interactions for further activation of FAK signaling. Our studies highlight that CD44+ CTC clusters, whose presence is correlated with a poor prognosis of breast cancer patients, can serve as novel therapeutic targets of polyclonal metastasis.

https://ift.tt/2RfQ04D

Although Approved, Dacomitinib Might Not Be Used [News in Brief]

The EGFR inhibitor—the fifth for initial NSCLC treatment—isn't likely to be prescribed.

https://ift.tt/2OPSo5t

Comparative Genomics of Aspergillus flavus S and L Morphotypes Yield Insights into Niche Adaptation

Aspergillus flavus, the primary causal agent for aflatoxin contamination on crops, consists of isolates with two distinct morphologies: isolates of the S morphotype produce numerous small sclerotia and lower numbers of conidia while isolates of the L morphotype produce fewer large sclerotia and abundant conidia. The morphotypes also differ in aflatoxin production with S isolates consistently producing high concentrations of aflatoxin, whereas L isolates range from atoxigenic to highly toxigenic. The production of abundant sclerotia by the S morphotype suggests adaptation for long-term survival in the soil, whereas the production of abundant conidia by the L morphotype suggests adaptation for aerial dispersal to the phyllosphere. To identify genomic changes that support differential niche adaption, the sequences of three S and three L morphotype isolates were compared. Differences in genome structure and gene content were identified between the morphotypes. A >530 kb inversion between the morphotypes affect a secondary metabolite gene cluster and a cutinase gene. The morphotypes also differed in proteins predicted to be involved in carbon/nitrogen metabolism, iron acquisition, antimicrobial defense, and evasion of host immunity. The S morphotype genomes contained more intact secondary metabolite clusters indicating there is higher selection pressure to maintain secondary metabolism in the soil and that is not limited to aflatoxin production. The L morphotype genomes were enriched in amino acid transporters, suggesting efficient nitrogen transport may be critical in the nutrient limited phyllosphere. These findings indicate the genomes of the two morphotypes differ beyond developmental genes and have diverged as they adapted to their respective niches.

https://ift.tt/2qbZ1jZ

Safety and pharmacokinetics of MM-302, a HER2-targeted antibody–liposomal doxorubicin conjugate, in patients with advanced HER2-positive breast cancer: a phase 1 dose-escalation study

Safety and pharmacokinetics of MM-302, a HER2-targeted antibody–liposomal doxorubicin conjugate, in patients with advanced HER2-positive breast cancer: a phase 1 dose-escalation study

Safety and pharmacokinetics of MM-302, a HER2-targeted antibody–liposomal doxorubicin conjugate, in patients with advanced HER2-positive breast cancer: a phase 1 dose-escalation study, Published online: 26 October 2018; doi:10.1038/s41416-018-0235-2

Safety and pharmacokinetics of MM-302, a HER2-targeted antibody–liposomal doxorubicin conjugate, in patients with advanced HER2-positive breast cancer: a phase 1 dose-escalation study

https://ift.tt/2O7GTBk

Pneumococcal Vaccine Recs Cause Confusion Among Docs

THURSDAY, Oct. 25, 2018 -- While primary care physicians overwhelmingly recommend pneumococcal vaccines, there is a gap in their knowledge of how to implement related vaccine recommendations, according to a study published in the Journal of the...

https://ift.tt/2ShCuPj

Bill to Fight U.S. Opioid Crisis Signed Into Law

THURSDAY, Oct. 25, 2018 -- A bipartisan bill meant to combat the United States' opioid abuse epidemic was signed into law Oct. 24 by President Donald Trump. The legislation, which also covers other types of substance abuse, expands treatment options...

https://ift.tt/2z2KBGJ

Oxygen Saturation Should Not Top 96 Percent in Acutely Ill

THURSDAY, Oct. 25, 2018 -- For acutely ill patients, an oxygen saturation of no more than 96 percent should be maintained, according to a clinical practice guideline published online Oct. 24 in the BMJ. Reed A.C. Siemieniuk, M.D., Ph.D., from...

https://ift.tt/2SgBDyq

Neither Haloperidol, Ziprasidone Shortens Delirium in ICU

THURSDAY, Oct. 25, 2018 -- For patients with acute respiratory failure or shock and hypoactive or hyperactive delirium in the intensive care unit, neither haloperidol nor ziprasidone alters the duration of delirium compared with placebo, according...

https://ift.tt/2z44VaL

Sinomenine derivative YL064: a novel STAT3 inhibitor with promising anti-myeloma activity

Sinomenine derivative YL064: a novel STAT3 inhibitor with promising anti-myeloma activity

Sinomenine derivative YL064: a novel STAT3 inhibitor with promising anti-myeloma activity, Published online: 25 October 2018; doi:10.1038/s41419-018-1147-z

Sinomenine derivative YL064: a novel STAT3 inhibitor with promising anti-myeloma activity

https://ift.tt/2Atprng

Sublethal UV irradiation induces squamous differentiation via a p53-independent, DNA damage-mitosis checkpoint

Sublethal UV irradiation induces squamous differentiation via a p53-independent, DNA damage-mitosis checkpoint

Sublethal UV irradiation induces squamous differentiation via a p53-independent, DNA damage-mitosis checkpoint, Published online: 25 October 2018; doi:10.1038/s41419-018-1130-8

Sublethal UV irradiation induces squamous differentiation via a p53-independent, DNA damage-mitosis checkpoint

https://ift.tt/2Q3IREg

Establishment of stably expandable induced myogenic stem cells by four transcription factors

Establishment of stably expandable induced myogenic stem cells by four transcription factors

Establishment of stably expandable induced myogenic stem cells by four transcription factors, Published online: 25 October 2018; doi:10.1038/s41419-018-1114-8

Establishment of stably expandable induced myogenic stem cells by four transcription factors

https://ift.tt/2Ar9HAT

circRNA_104075 stimulates YAP-dependent tumorigenesis through the regulation of HNF4a and may serve as a diagnostic marker in hepatocellular carcinoma

circRNA_104075 stimulates YAP-dependent tumorigenesis through the regulation of HNF4a and may serve as a diagnostic marker in hepatocellular carcinoma

circRNA_104075 stimulates YAP-dependent tumorigenesis through the regulation of HNF4a and may serve as a diagnostic marker in hepatocellular carcinoma, Published online: 25 October 2018; doi:10.1038/s41419-018-1132-6

circRNA_104075 stimulates YAP-dependent tumorigenesis through the regulation of HNF4a and may serve as a diagnostic marker in hepatocellular carcinoma

https://ift.tt/2PUWVA7

Do Different Stemness Markers Identify Different Pools of Cancer Stem Cells in Malignancies: A Study on ER+ and ER-Breast Cancer Cell Lines

Abstract

In view of popularity of cancer stem cell (CSC) model all events in evolution of cancer are being explained in that context. Breast cancer is first solid tumor in which CSCs were identified. We aimed to compare stemness profile of two major subtypes [Estrogen receptor positive (ER⁺) and negative (ER⁻)] breast cancer using different sets of markers. Expression of CD44/CD24, CK/Vimentin, E-Cadherin/Fibronectin and percentage of side population (SP) was studied in ER⁺ (T47D) and ER⁻ (MDA-MB-231) cell lines by flow cytometry. Breast CSCs (BCSCs) were sorted using CD44⁺/CD24^−/low expression and SP analysis and cultured. BCSCs were then compared with Non-CSCs (NCSCs) for response to drugs (Paclitaxel and Cisplatin), Ki67 and ER expression. Results showed higher expression of stemness markers (CD44⁺/CD24^−/low, CK⁺/Vimentin⁺ and E-Cadherin⁻/Fibrinectin^F+) in MDA-MB-231 cells. Percentage SP representing BCSCs was found to be significantly more in later (3.20 ± 0.002 cf. T47D 1.25% ± 0.0007). BCSCs were found to be more resistant to drugs as compared to NCSCs in both cell lines. ER expression was weak in BCSCs sorted from T47D as compared to NCSCs. Ki67 was expressed in both BCSCs and NCSCs. Differences in expression of stemness markers help to explain aggressive behavior, higher recurrence rate and metastatic potential of MDA-MB-231 cells. However, no correlation amongst different markers used suggests that they may be identifying varied populations of cells in tumor hierarchy. A weak ER expression in BCSCs may be strategy used by BCSCs to escape effect of hormone therapy in ER⁺ breast cancers.

https://ift.tt/2D68l15

Five New Cases of Primary Renal Carcinoid Tumor: Case Reports and Literature Review

Abstract

Carcinoid tumors, a slow-growing NET, most commonly arise in the gastrointestinal tract (73.7%), followed by the bronchopulmonary system (25.1%), and least commonly in the genitourinary system (<1%). Primary carcinoid tumors of the kidney—with approximately 100 cases reported in the literature since the first described case in 1966—are thought to be so rare because neuroendocrine cells are not typically found in the renal parenchyma. Here we present a series of five cases at our institution with primary carcinoid tumors of the kidney followed by a literature review. In the literature we describe the diagnostic stains used to determine renal carcinoid tumors. We also describe why partial nephrectomies are the gold standard treatment in these cases, while radical nephrectomy can be used in certain circumstances. Limited research on treatment of metastasis of these tumors exists, but we summarize the results of existing treatments. Major prognostic factors and survival of patients with these tumors is described as well as the increased prevalence of this tumors in patients with horseshoe kidneys. This study presents five new cases of primary renal carcinoid tumors and a comprehensive review of the previously published cases. We are able to make limited prognostic predictions from currently published literature, but we will continue to learn from our patients' long-term courses to draw conclusions about biological behavior, treatment outcomes, and recurrence of rare disease.

https://ift.tt/2D50GQv

Predictive Factors of Lateral Lymph Node Metastasis in Papillary Thyroid Microcarcinoma

Abstract

This study was designed to determine the incidence and predictive factors for lateral lymph node metastasis (LNM) in patients with papillary thyroid microcarcinoma (PTMC). From January 2014 to July 2015, a retrospective review was conducted of 215 patients with PTMC who underwent total thyroidectomy and central lymph node dissection (LND) with lateral LND. Correlations of lateral LNM with clinicopathological features were examined using univariate analyses. Risk factors for lateral LNM were identified by multivariate analysis. Lateral LNM was observed in 163(75.8%) cases of 215 patients and often involved in level III (82.2%) and level IV (65.6%), with most found in two-levels (41.1%) and single-level (33.7%) models. Multivariate analyses showed that central LNM (odds ratio [OR]: 8.28, 95% confidence interval [CI]: 3.43–19.98, p < 0.001) and upper portion location (OR: 2.87 [CI: 1.34–6.09]; p = 0.007) were independent predictive factors for lateral LNM. The incidence of skip metastasis-Lateral LNM with central Lymph nodes negative-was 8.6% (14/163). Age ≥ 45 years old (OR: 4.37 [CI: 1.14–16.66]; p = 0.031) and upper portion location (OR: 4.34 [CI: 1.27–14.78]; p = 0.019) were independent risk factors for skip metastasis by multivariate analyses. Taken together, patients with PTMC with central LNM and tumor in the upper pole were more likely to present with lateral LNM. Even if there was no central LNM, patients with an age ≥ 45 years old and tumors in the upper portion of the thyroid should be evaluated carefully for possible lateral LNM.

https://ift.tt/2EFOEPg

CML with Megakaryocytic Blast Crisis: Report of 3 Cases

Abstract

Chronic myelogenous leukemia (CML) is a chronic myeloproliferative neoplasm consistently associated with the BCR-ABL1 fusion gene located in the Philadelphia chromosome. The Blast Phase is diagnosed when blasts are ≥20% of the peripheral blood white cell count or of bone marrow nucleated cells or when there is an extramedullary blast proliferation. Megakaryocytic blast crisis as the presenting manifestation of CML is extremely rare and only 7 reported cases were found in the literature. Out of 34 cases of CML-Blast Phase between April 2015 and June 2016, 3 cases showed megakaryocytic differentiation. 2 of these presented in Blast phase as the first manifestation of CML and the third case was a known case of CML-Chronic phase. Flow cytometric immunophenotyping was performed on peripheral blood/bone marrow using 6- color flow cytometer Navios. On CD45 vs SSC two distinct populations of blasts were seen in two cases and single population in the third case. All the 3 cases were positive for CD61, cCD41, cCD61 confirming the megakaryocytic lineage. The clinical features, morphologic and cytogenetic findings help in the identification and distinction of megakaryocytic blast phase of CML from Acute Megakayoblastic Leukemia. The diagnosis of such rare presentation of CML is essential for determining the choice of treatment. Therefore including a megakaryocytic marker in the primary flow cytometry panel is important so that these cases are not under-diagnosed as Acute myeloid leukemia because of expression of CD13 and CD33 only.

https://ift.tt/2D50Xmv

The Role of Testin in Human Cancers

Abstract

Testin is a protein expressed in almost all normal human tissues. It locates in the cytoplasm along stress fibers being recruited to focal adhesions. Together with zyxin and vasodilator stimulated protein it forms complexes with various cytoskeleton proteins such as actin, talin and paxilin. They jointly play significant role in cell motility and adhesion. In addition, their involvement in the cell cycle has been demonstrated. Expression of testin protein level correlates positively with percentage of cells in G1 phase, while overexpression can induce apoptosis and decreased colony forming ability. Decreased testin expression associate with loss by cells epithelial morphology and gain migratory and invasive properties of mesenchymal cells. Latest reports indicate that TES is a tumor suppressor gene which can contribute to cancerogenesis but the mechanism of loss TES gene expression is still unknown. Some authors point out hypermethylation of the CpG island as a main factor, however loss of heterozygosity may also play an important role [4, 5]. The altered expression of testin was found in malignant neoplasm, i.a. ovarian, lung, head and neck squamous cell cancer, breast, endometrial, colorectal, prostate and gastric cancers [1–9]. Testin participate in the processes of tumor growth, angiogenesis, and metastasis [10]. Many researchers stated involvement of testin in tumor progression, what suggest its potential usage in immunotherapy [7, 11]. Understanding the molecular functions of testin may be crucial in development personalized treatment. In the present manuscript up-to-date review of literature can be found.

https://ift.tt/2ENSwxL

Non-target Genes Regulate miRNAs-Mediated Migration Steering of Colorectal Carcinoma

Abstract

MicroRNAs (miRNAs) trigger a two-layer regulatory network directly or through transcription factors and their co-regulators. Unlike miR-375, the role of miR-145 and miR-224 in inhibiting or driving cancer cell migration is controversial. This study is a step towards addressing the potential of miR-375, miR-145 and miR-224 expression modulation to inhibit colorectal carcinoma (CRC) cells migration in vitro through regulation of non-target genes VEGFA, TGFβ1, IGF1, CD105 and CD44. Transwell migration assay results revealed a significant subdue of migration ability of cells transfected with miR-375 and miR-145 mimics and miR-224 inhibitor. Real time PCR data showed that expression of VEGFA, TGFβ1, IGF1, CD105 and CD44 was downregulated as a consequence of exogenous re-expression of miR-375 and inhibition of miR-224. On the other hand, ectopic expression of miR-145 did not affect VEGFA, TGFβ1 and CD44 expression, while it elevated CD105 and suppressed IGF1 expression. MAP4K4, a predicted target of miR-145, was validated as a target that could play a role in miR-145-mediated regulation of migration. At mRNA level, no change was observed in expression of MAP4K4 in cells with restored expression of miR-145, while western blotting analysis revealed a 25% reduction of protein level. By applying luciferase reporter assay, a significant decrease in luciferase activity was observed, supporting that miR-145 directly target 3' UTR of MAP4K4. The study highlighted the involvement of non-target genes VEGFA, TGFβ1, IGF1, CD105 and CD44 in mediating anti- and pro-migratory effect of miR-375 and miR-224, respectively, and validated MAP4K4 as a direct target of anti-migratory miR-145.

https://ift.tt/2D50T6f

BCL3 Expression Is a Potential Prognostic and Predictive Biomarker in Acute Myeloid Leukemia of FAB Subtype M2

Abstract

Although the implication of BCL3 has been disclosed in human chronic lymphocytic leukemia as well as other solid tumors, the diagnostic and prognostic of BCL3 expression in acute myeloid leukemia (AML) remains largely unclear. In this study, we isolated total RNA from bone marrow mononuclear cells collected from 101 de novo AML patients and 27 healthy donors. After reverse transcription, quantitative real-time PCR was performed to detect BCL3 expression level. BCL3 mRNA level was significantly down-regulated in BMMCs of AML patients compared with healthy controls (P = 0.0015). BCL3 was showed a higher level in AML patients with poor-risk karyotypes than that of in patients with favorable/intermediate-risk karyotypes (P = 0.014). ROC analysis demonstrated that BCL3 could effectively differentiate AML patients from normal controls. Among the French-American-British (FAB) subtypes, the frequency of low BCL3 expression in M2 subtypes is significantly higher than that of in the other subtypes M1/M4/M5/M6/M7 (P = 0.006), and mildly lower in myelomonocytic/monocytic subtypes M4/M5 (P = 0.064) than those in M1/M2/M6/M7 subtypes. Chromosome analysis revealed that BCL3^low patients had a remarkably higher frequency of t (8;21) abnormality (P = 0.0047) and lower frequency of normal karyotype (P = 0.0059) than BCL3^high patients. BCL3^high patients showed a significantly higher frequency of FLT3-ITD mutation (P = 0.028) and lower frequency of C-Kit mutation (P = 0.0232) than BCL3^low patients. Although there were no significant differences in complete remission and overall survival between BCL3^low and BCL3^high groups, patients with high BCL3 expression markedly shorter overall survival (OS, P = 0.049), relapse-free survival (RFS, P = 0.027) and disease-free survival (DFS, P = 0.042) in M2 AML than low BCL3 expression patients. Additionally, in AMLs of M2 subtype, high BCL3 expression patients had markedly lower complete remission (CR) rate (P = 0.0317) after the second induction treatment than patients with BCL3 low expression. Thus, these findings indicated that BCL3 appeared as a promising molecular biomarker of pediatric acute myeloid leukemia with unfavorable prognosis.

https://ift.tt/2ENSsOx

Primary Osteosarcoma of the Liver: Case Report and Literature Review

Abstract

Extraskeletal osteosarcoma is a rare, highly malignant, osteoid formation mesenchymal neoplasm in the absence of bone involvement, associated with exceptionally poor prognosis. It frequently arises in the soft tissues of the extremities or in the retroperitoneum, but rarely in visceral organ. We describe a primary osteosarcoma of the liver in a 70-year-old man who presented with an episode of fever, accompanied by abdominal discomfort, after an accident abdominal strike. Ultrasonography and computed tomography revealed a large heterogeneous mass with areas of dense calcification involving most of the right lobe of liver. Radiography did not show evidence of primary tumor or primary bone lesion at any other site. Histologically, the tumor showed an essentially similar appearance as osteosarcoma originating in the skeleton, comprised of polygonal or spindle shaped cells, along with abundant eosinophilic lace-like osteoids, or irregularly arranged bone trabeculae. Immunohistochemistry showed that the tumor cells were positive for vimentin, CD10, and focally for SMA and CD56, but negative for other lineage-specific markers. Thus, the findings favored a primary hepatic osteosarcoma. This patient received palliative chemotherapy to ease the signs of his sickness due to the large size of the tumor and he died 4 moths later.

https://ift.tt/2D68odh

Standard Dose of Ibrutinib is Effective in the Treatment of Bing-Neel Syndrome

https://ift.tt/2ENSoyh

Sonic Hedgehog Expression is Associated with Lymph Node Invasion in Urothelial Bladder Cancer

Abstract

Bladder cancer (BC) is a deadly disease characterized by high recurrence rates and frequent progression to an aggressive phenotype. Dysregulation of various signaling pathways have been implicated in BC tumorigenesis, however, the clinical relevance of sonic hedgehog pathway (Shh) remains under investigated. The aim of the current study was to analyze the prognostic value of Shh expression in patients with bladder carcinoma. Immunohistochemical expression of Shh was performed using tissue microarray with 128 specimens from bladder cancer patients. Kaplan-meier survival was analysed and correlation between Shh protein expression and patients' clinicopathological parameters wasexamined using Fisher's exact test. The immuno-staining results revealed that Shh protein exhibits cytoplasmic localization and is expressed in 49% of the analyzed bladder cancer cohort. Our data indicated that high Shh expression significantly correlated with increased lymph node metastasis (p = 0.02), however no association was reported between Shh expression and other clinicopatholigical parameters. High expression of sonic hedgehog was associated with lymph node invasion which may indicate that Shh might play an important role in progression and metastasis of bladder cancer.

https://ift.tt/2D50PU3

Low Prevalence of TERT Promoter, BRAF and RAS Mutations in Papillary Thyroid Cancer in the Greek Population

Abstract

Thyroid cancer is a common endocrine malignancy and displays a variety of histological patterns ranging from adenoma to malignant tumors. Molecular diagnostics have given significant insights into the genetic basis of thyroid tumorigenesis, known to be linked with signaling pathways affected by oxidative stress. We report for the first time a genotype study of TERT promoter combined with BRAF and RAS mutations in Papillary Thyroid Cancer (PTC) cases in the Greek population. Polymerase Chain Reaction and sequencing were used to identify TERT promoter (C228T, C250T, CC243-243TT) mutations, the BRAF (T1799A) mutation and mutations in codons 12, 13, 61 of the HRAS, KRAS and NRAS genes. The most common C228T TERT promoter mutation was identified in 2 PTC cases co-existing with the BRAF mutation. The BRAF T1799A mutation was detected in 10 PTC cases, while two different NRAS mutations in codon 61 (C181A and A182G) were found in 2 PTC cases. These mutations occur in a mutually exclusive manner. Our results indicate that despite the low frequencies, the study of the specific mutations should be encouraged because they are indicative of aggressive forms of thyroid cancer of the papillary histotype in this patient cohort, thus providing insights towards their therapeutic management.

https://ift.tt/2ELeVfh

C-MYC , HIF-1α , ERG , TKT , and GSTP1 : an Axis in Prostate Cancer?

Abstract

To analyze putative biomarkers for prostate cancer (PCA) characterization, the second leading cause of cancer-associated mortality in men. Quantification of the expression level of c-myc and HIF-1α was performed in 72 prostate cancer specimens. A cohort of 497 prostate cancer patients from The Cancer Genome Atlas (TCGA) database was further analyzed, in order to test our hypothesis. We found that high c-myc level was significantly associated with HIF-1α elevated expression (p = 0.008) in our 72 samples. Statistical analysis of 497 TCGA prostate cancer specimens confirmed the strong association (p = 0.0005) of c-myc and HIF-1α expression levels, as we found in our series. Moreover, we found high c-myc levels significantly associated with low Glutatione S-transferase P1 (GSTP1) expression (p = 0.01), with high Transketolase (TKT) expression (p < 0.0001). High TKT levels were found in TCGA samples with low GSTP1 mRNA (p < 0.0001), as shown for c-myc, and with ERG increased expression (p = 0.02). Finally, samples with low GSTP1 expression displayed higher ERG mRNA levels than samples with high GSTP1 score (p < 0.0001), as above shown for c-myc. Our study emphasizes the notion of a potential value of HIF-1α and c-myc as putative biomarkers in prostate cancer; moreover TCGA data analysis showed a putative crosstalk between c-myc, HIF-1α, ERG, TKT, and GSTP1, suggesting a potential use of this axis in prostate cancer.

https://ift.tt/2EFOAiu

Correlation Between Tumor Vasculogenic Mimicry and Poor Prognosis of Human Digestive Cancer Patients: A Systematic Review and Meta-Analysis

Abstract

Vasculogenic mimicry (VM) is a new pattern of blood supplement independent of endothelial vessels, which is related with tumor invasion, metastasis and prognosis. However, the role of VM in the prognosis of cancer patients is controversial. This study aimed to perform a meta-analysis of the published data to attempt to clarify the prognostic value of VM in the digestive cancer. Relevant studies were retrieved from the PubMed, Web of Science, Cochrane Library, Chinese National Knowledge Infrastructure and VIP databases published before March 29, 2018. Studies were included if they detected VM in the digestive cancer and analyzed the overall survival (OS) or disease-free survival (DFS) according to VM status. Two independent reviewers screened the studies, extracted data, and evaluated the quality of included studies with the Newcastle-Ottawa scale. Meta-analysis was performed using STATA 12.0 software. A total of 22 studies with 2411 patients were included in this meta-analysis. Meta-analysis showed that VM was related with the poor OS (HR = 2.30, 95% CI: 2.06–2.56, P < 0.001) and DFS (HR = 2.60, 95% CI: 2.07–3.27, P < 0.001) of patients with digestive cancer. Subgroup analysis showed VM was related with tumor differentiation, lymph node metastasis and TNM stage. Moreover, the present meta-analysis was reliable, and there was no obvious publication bias. This meta-analysis suggested that VM was a poor prognosis of digestive cancer patients. Further large and well-designed studies are required.

https://ift.tt/2D68iCr

Comparison of Native Aspirates and Cytological Smears Obtained by EUS-Guided Biopsies for Effective DNA/RNA Marker Testing in Pancreatic Cancer

Abstract

We compare two types of pancreatic carcinoma samples obtained by EUS-guided fine needle biopsy (EUS-FNB) in terms of the success rates and clinical validity of analysis of two most commonly investigated DNA/RNA pancreatic cancer markers, KRAS mutations and miR-21 expression. 118 patients with pancreatic ductal adenocarcinoma underwent EUS-FNB. The collected sample was divided, one part was stored in a stabilizing solution as native aspirate (EUS-FNA) and second part was processed into the cytological smear (EUS-FNC). DNA/RNA extraction was followed by analysis of KRAS mutations and miR-21 expression. For both sample types, the yields of DNA/RNA extraction and success rates of KRAS mutation and miRNA expression were evaluated. Finally, the resulting KRAS mutation frequency and miR-21 prognostic role were compared to literature data from tissue resections. The overall amount of isolated DNA/RNA from EUS-FNC was lower compared to the EUS-FNA, average yield 10 ng vs 147 ng for DNA and average yield 164 vs. 642 ng for RNA, but the success rates for KRAS and miR-21 analysis was 100% for both sample types. The KRAS-mutant detection frequency in EUS-FNC was 12% higher than in EUS-FNA (90 vs 78%). The prognostic role of miR-21 was confirmed in EUS-FNC (p = 0.02), but did not reach statistical significance in EUS-FNA (p = 0.06). Although both types of EUS-FNB samples are suitable for DNA/RNA extraction and subsequent DNA mutation and miRNA expression analysis, reliable results with clinical validity were only obtained for EUS-FNC.

https://ift.tt/2ELyKmC

Tumor Associated Tissue Eosinophilia in Ameloblastoma

https://ift.tt/2D50Jf9

Blood Vessel Invasion in Endometrial Cancer Is One of the Mechanisms of Spread to the Cervix

Abstract

To evaluate the association between type of invaded vessels (blood or lymphatic) and cervical involvement in endometrial cancer (EC). Pathological slides of 93 patients with EC who had vascular space invasion in hematoxylin-eosin staining underwent immunohistochemical assay with CD31 and podoplanin. CD31 and podoplanin were used to identify blood and lymphatic invaded vessels, respectively. Cervical stromal invasion (CSI) was determined in 21 (30%) patients. The rate of CD31-positivity was significantly higher in patients with CSI than without (76.2 and 34.7%, p = 0.001; respectively). Podoplanin-positivity was determined in 47.6 and 81.6% of patients with and without CSI, respectively (p = 0.005). Age, myometrial invasion and the combination of CD31-positivity with podoplanin-negativity were found as independent predictors for CSI. Blood vessel invasion is an important factor for CSI in EC. Blood vessel invasion rather than lymphatic vessel invasion is one of the predominant ways by which EC spreads to the cervix.

https://ift.tt/2EIQj6N

Effectiveness of the Combination of Rituximab and Standard Chemotherapeutic Regimens in Previously Untreated Patients with Chronic Lymphocytic Leukaemia in Real-Life: Results from a Noninterventional Study (CILI Study)

Abstract

Chronic lymphocytic leukemia (CLL) is one of the most common haematological malignancies exhibiting remarkable heterogeneity in clinical course. Rituximab added to standard chemotherapy has been proven to increase response rate and eventually survival among previously untreated CLL patients. CILI was an open-label, non-randomized, single arm, multicentric, observational study aimed to collect real-life effectiveness data for rituximab used according to the current label in combination with standard chemotherapy in previously untreated CLL patients. Overall response rates (ORR) in the entire study population as well as in various subgroups were estimated. Adverse events were recorded during the entire course of the study. A total number of 150 patients were enrolled by 15 Hungarian study sites. Out of these, 82 patients received 6 cycles of rituximab containing treatment. Overall response rates of 88.24% (CI_95%: 81.6–93.12%) and 94.59% (CI_95%: 86.73–98.51%) were recorded in the intent-to-treat (ITT) and per-protocol (PP) populations, respectively. In both study populations, somewhat higher ORR was observed in patients aged ≥65 years. Subgroups defined according to either chromosomal aberrations (presence of 11q and 17p deletions) showed apparently high ORRs, though these rates were most probably biased by low patient numbers. 144 adverse events were reported during the study, of which 15 AEs were considered to be related to the administration of rituximab. Analyses of the efficacy variables have revealed comparable results to those previously reported by controlled clinical trials.

https://ift.tt/2EJj2Zd

Expression of Programmed Death-Ligand 1 in Laryngeal Carcinoma and its Effects on Immune Cell Subgroup Infiltration

Abstract

To study the expression of programmed death-ligand 1 (PD-L1), and its effects on CD8⁺ tumor infiltrating lymphocytes (TILs) and tumor associated macrophages (TAMs) in human laryngeal squamous cell carcinoma. Sixty-nine patients with laryngeal carcinoma and 10 with vocal cord leukoplakia received tumor resection at Neck Surgery Department in the Second Affiliation Hospital of Jilin University (Changchun, Jilin) from Jan. 2010 to Dec. 2015. The expressions of PD-L1, CD8, CD16 and CD206 in laryngeal carcinoma, paracancerous and vocal cord leukoplakia tissues were detected with immunohistochemistry. The associations between PD-L1 expression and clinicopathologic features, expression of TAMs and CD8⁺ T cell infiltration were analyzed. Expression of PD-L1 is significantly higher in laryngeal carcinoma than in paracancerous or leukoplakia tissue. The expression of PD-L1 is closely associated with stage of laryngeal cancer, histological differentiation and neck lymphatic metastasis. PD-L1 expression is negatively correlated with the number of CD8⁺ TILs and CD16⁺ cells (M1 type TAMs), while is positively associated with CD206⁺ (M2 type TAMs). PD-L1 is highly expressed in the laryngeal cancer with the tumor microenvironment immunosuppression.

https://ift.tt/2D50FMr

The Infiltration of ICOS + Cells in Nasopharyngeal Carcinoma is Beneficial for Improved Prognosis

Abstract

Nasopharyngeal carcinoma (NPC) is a highly malignant tumor, associated with poor patient prognoses, and high rates of morbidity and mortality. Currently, immune checkpoint therapy has brought new treatment strategy for NPC. The inducible T cell co-stimulator (ICOS) belongs to the B7-CD28 immunoglobulin superfamily, which is currently the subject of intense study due to great successes gained in treatment of different malignancies by disrupting their family members. However, the role of ICOS played in NPC remains poorly understood. Immunohistochemistry (IHC) was stained with the ICOS specific antibody and ICOS expression is decreased in patients with either lymphatic or distant metastasis and inversely associated with TNM stage of NPC patients. Importantly, high ICOS expression is significantly correlated with overall survival (OS) of NPC patients (N = 185, p < 0.001), and ICOS expression is also proved to be an independent prognostic factor by multivariate analysis. Surgical excised fresh NPC specimens (N = 185) were homogenized to analyze the specific cytokine expression by ELISA assay. ICOS expression level is associated with increased cytotoxic T lymphocyte number and high interferon IFNγ expression, the characteristics of Th1 cells. In addition, the correlation between the percentage of ICOS⁺ T cells in tumor tissue and survival was detected. Conclusively, expression of ICOS is associated with improved survival in NPC and percentage of ICOS⁺ cells acting as Th1 cells in primary tumor tissue may be a clinical biomarker for good prognosis of NPC patients.

https://ift.tt/2EUiqjg

Ultrasound Risk Assessment Combined with Molecular Markers of Galectin-3, c-MET, HBME-1 and CK19 for Diagnosis of Malignant and Benign Thyroid Nodules

Abstract

To investigate the effect of ultrasound combined with expression of Galectin-3, c-Met, HBME-1 and CK19 in differentiating malignant from benign thyroid nodules. Forty-six patients with thyroid nodules were studied with ultrasound and immunohistochemical staining of excised thyroid nodules. The data were classified and compared. The immunohistochemical staining revealed 8 benign and 41 malignant thyroid lesions. In ultrasound risk assessment, the malignancy risk was low in four nodules, medium in five and high in 37 with lymphatic metastasis in 26. A significant (P < 0.05) association existed in the expression of Galectin-3 with nodule boundary and lymphatic metastasis, in HBME-1 with nodule micro-calcification and in c-Met with nodule micro-calcification and lymphatic metastasis. CK19 expression was not significantly (P > 0.05) associated with any of ultrasound features of nodule. Galectin-3, c-Met, HBME-1 and CK19 were significantly (P < 0.05) different in malignant and benign thyroid lesions, with a significant (P < 0.01) tendency in all the molecular markers in predicting the malignant from benign lesions. The ultrasound characteristics could significantly (P < 0.001) predict malignant nodules with a significant (P < 0.05) prediction tendency. The scores of Galectin-3, c-Met and CK19 significantly (P < 0.05) increased with increase of ultrasound malignancy risk degree. In malignant and benign lesions differentiated by ultrasound, no significant (P > 0.05) difference existed in HBME-1 expression, however, with ultrasound malignancy risk increase, the score of HBME-1 expression increased significantly (P = 0.03). Galectin-3, c-Met, HBME-1 and CK19 have significantly greater expressions in thyroid malignant than benign lesions and their expression increases with increase of ultrasound malignancy risk. The combination of both ultrasound and molecular markers can be used to differentiate malignant and benign thyroid lesions.

https://ift.tt/2D50DEj

Long non-coding RNAs as monitoring tools and therapeutic targets in breast cancer

Abstract

Background

Current therapeutic strategies that are used to combat breast cancer vary widely and largely depend on its clinicopathological features, including tumor subtype, size, stage, lymph node involvement, the presence of hormone receptors and/or HER2, as well as the degree of proliferative activity. Recent work has focused on improving our knowledge on the molecular mechanisms that underlie this complex disease. Most of the human genome is transcribed into RNAs that do not encode proteins. These noncoding RNAs may act as mediators in the regulation of gene expression. Based on their size and function, noncoding RNAs are classified into small noncoding RNAs (sncRNAs) and long noncoding RNAs (lncRNAs). LncRNAs have been found to play key roles in relevant biological processes, including breast cancer. As such, lncRNAs have been proposed as diagnostic and prognostic biomarkers, as predictive biomarkers and as putative therapeutic targets.

Conclusions

In this review, we discuss the potential application of lncRNAs for the monitoring and treatment of breast cancer. We conclude that lncRNAs play important roles in the pathophysiology of this disease and may serve as putative therapeutic targets. As such, tumor-specific lncRNAs may be instrumental for improving current breast cancer clinical practices.

https://ift.tt/2yzH7fv

Structured Training for Fetal Diagnostic Skills in a Maternal-Fetal Medicine Fellowship

AJP Rep 2018; 08: e251-e260
DOI: 10.1055/s-0038-1675344

Objective The American Institute of Ultrasound in Medicine has described what constitutes a detailed fetal anatomic examination but what comprises an appropriate physician training program has not been described. The purpose of this paper is to describe a highly-structured program developed by our center to train maternal-fetal medicine fellows in a systematic approach to fetal diagnostic imaging. Study Design We describe this approach in three phases. Phase I: Development of Skills as a Perinatal Sonographer, Phase II: Mentored Evolution to a Perinatal Sonologist and Phase III: Supervised Independent Practice as Consultant-in-training. Results This curriculum was implemented in 2006. Of the eight maternal-fetal medicine fellows who completed this program, 100% were capable of following this curriculum and 100% felt comfortable performing and interpreting detailed sonograms including sonograms with significant and uncommon anomalies. Qualitative feedback was also positive. Finally, this structured approach resulted in an increase in the average total number of sonograms interpreted. Conclusion Our curriculum, by following the explicit guidelines and expectations set out by the American Institute of Ultrasound in Medicine and the American Board of Obstetrics and Gynecology for practicing maternal-fetal medicine fellowship graduates, provides an opportunity to explore national standardization for this component of training.
[...]

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

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

https://ift.tt/2ONiztA

Thyroid Peroxidase as an Autoantigen in Hashimoto’s Disease: Structure, Function, and Antigenicity

Horm Metab Res
DOI: 10.1055/a-0717-5514

Human thyroid peroxidase (TPO), is an important enzyme responsible for the biosynthesis of thyroid hormones and is a major autoantigen in autoimmune thyroid diseases (AITDs) such as the destructive Hashimoto's thyroiditis. Although the structure of TPO has yet to be determined, its extracellular domain consists of three regions that exhibit a high degree of sequence similarity to domains of known three-dimensional structure: the myeloperoxidase (MPO)-like domain, complement control protein (CCP)-like domain, and epidermal growth factor (EGF)-like domain. Homology models of TPO can therefore be constructed, providing some structural context to its known function, as well as facilitating the mapping of regions that are responsible for its autoantigenicity. In this review, we highlight recent progress in this area, in particular how a molecular modelling approach has advanced the visualisation and interpretation of epitope mapping studies for TPO, facilitating the dissection of the interplay between TPO protein structure, function, and autoantigenticity.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

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

https://ift.tt/2z4Fm9C

Design and Implementation of Patient Portal-based Advance Care Planning Tools

Electronic health record-based portal tools may help patients engage in advance care planning (ACP). We designed and implemented portal-based ACP tools to enable patients to create a Medical Durable Power of Attorney (MDPOA).

https://ift.tt/2JeW8Y9

Underwater endoscopic mucosal resection for colorectal lesions: a systematic review with meta-analysis (with video)

Underwater endoscopic mucosal resection (UEMR) is an alternative way to have nonpedunculated colorectal (CR) lesions lifted before being resected. The endoscopist takes advantage of the behavior of mucosal lesions floating away from the muscular layer, once immersed in liquid. We performed a systematic review with meta-analysis to evaluate the efficacy and safety of this technique.

https://ift.tt/2CCbCnX

Ultrasound guided dorsal penile neurolysis for malignant priapism pain management

Malignant priapism is a rare, painful condition typically associated with advanced disease and a poor prognosis. (1) Palliative pain treatment includes opioids and adjuvant analgesics, and in selected cases, systemic chemotherapy, radiotherapy, local excision or surgical management. There are few published cases of this condition and best pain management practices are yet to be defined. We present a complex case of melanoma-related malignant priapism in which a minimally invasive technique—ultrasound-guided dorsal penile nerves neurolysis—yielded good results.

https://ift.tt/2PkA2Jk

A Systematic Review and Gap Analysis of Advance Care Planning Intervention Components and Outcomes Among Cancer Patients Using the Transtheoretical Model of Health Behavior Change

Despite the benefits of advance care planning (ACP), cancer patients rarely engage in ACP. ACP is process that parallels health behavior change. This makes the Transtheoretical Model of Health Behavior Change (TTM) an important framework for understanding how to increase ACP among cancer patients.

https://ift.tt/2Jhh6Wd

Prediction of individuals at high absolute risk of esophageal squamous cell carcinoma

This study aimed to develop a prediction model for identifying individuals at high absolute risk of esophageal squamous cell carcinoma (ESCC) for endoscopic screening at a curable stage based on readily identifiable risk factors.

https://ift.tt/2q7OupU

Automatic detection of erosions and ulcerations in wireless capsule endoscopy images based on a deep convolutional neural network

Although erosions and ulcerations are the most commonly found small-bowel abnormalities on wireless capsule endoscopy (WCE), a computer-aided detection method has not been established. We aimed to develop an artificial intelligence system with deep learning to automatically detect erosions and ulcerations in WCE images.

https://ift.tt/2q9n2bc

Safety and pharmacokinetics of MM-302, a HER2-targeted antibody–liposomal doxorubicin conjugate, in patients with advanced HER2-positive breast cancer: a phase 1 dose-escalation study

https://ift.tt/2PXwUA8

Hepatocellular Carcinoma Screening is Associated with Increased Survival of Patients with Cirrhosis

Hepatocellular carcinoma (HCC) screening of patients with cirrhosis is recommended by professional societies to increase detection of early-stage tumors and survival but is underused in clinical practice.

https://ift.tt/2z5aeqB

Hypokalemia Associated With a Claudin 10 Mutation: A Case Report

Hypokalemia of renal origin can arise from genetic abnormalities in a variety of transporters or channel proteins that mediate tubular handling of potassium. Recently, mutations in claudin 10 have been documented in patients with hypokalemia in association with a range of other electrolyte abnormalities and skin and sweat gland manifestations. We report a 12-year-old Hispanic boy who presented with anhydrosis, aptyalism, alacrima, hypokalemia, and hypocalciuria, in whom we detected a homozygous mutation in the claudin 10 gene.

https://ift.tt/2yAuMI5

Identification and Prioritization of Quality Indicators for Conservative Kidney Management

Conservative kidney management is holistic patient-centered care for patients with kidney failure that focuses on delaying the progression of kidney disease and symptom management, without the provision of renal replacement therapy. Currently there is no consensus as to what constitutes high-quality conservative kidney management. We aimed to develop a set of quality indicators for the conservative management of kidney failure.

https://ift.tt/2O5ba3x

Dialysis in Older Adults: Is Later Start the Preferred Approach?

The US population of adults older than 75 years is expected to double by 2030.1 The question of how best to manage older adults who develop progressive chronic kidney disease (CKD) is of critical importance. Patients who start dialysis therapy early, at estimated glomerular filtration rates (eGFRs)>10mL/min/1.73m2, accounted for most of the growth in the US dialysis population between 1996 and 2005.2 This trend to early start is more prominent with increasing age.2 A disturbing feature of the early start trend is a yearly increase in the percent of new starts with eGFRs>15mL/min/1.73m2 between 1996 and 2008.

https://ift.tt/2yBn6Fl

Three Hours, Three Days a Week

When was the last time you spent 3 hours with a patient?

https://ift.tt/2O7oCUK

Does the Severe Sepsis and Septic Shock Early Management Bundle (SEP-1) Improve Survival in Septic Adults?

After screening of 56,563 references, 18 reports representing 20 studies met inclusion criteria and compared survival in septic patients receiving one or more of the SEP-1 interventions versus a control group. Meta-analysis was not performed because of the large heterogeneity between included studies.

https://ift.tt/2PpjtvC

Irish Famine victims' heavy smoking led to dental decay, new research reveals

Irish Famine victims were heavy smokers which caused badly rotten teeth, researchers have discovered.

https://ift.tt/2O7wwNA

Correction to: Statistically inferred time warping: extending the cyclostationarity paradigm from regular to irregular statistical cyclicity in scientific data

Following publication of the original article [1], the author noticed that the equation on page 9, right column, 14th line from the bottom was incorrect. The correct equation is mentioned below.

https://ift.tt/2qaX0UZ

Improvement of caproic acid production in a Clostridium kluyveri H068 and Methanogen 166 co-culture fermentation system

The aim of this study was to develop a bioprocess capable of producing caproic acid using a binary fermentation system consisting of Clostridium kluyveri H068 and Methanogen 166 which could then be applied to the...

https://ift.tt/2z3fM4O

IBCC chapter & cast: Acute pancreatitis

Management of severe pancreatitis has remained in a state of controlled chaos and persistent debate for years (mirroring evolution in our treatment of septic shock).  This confusion shows no signs of abating in the near future.  This chapter explores a reasonable approach to pancreatitis, with the caveat that there is very little evidence available to guide our combat against this challenging foe.  

EMCrit Project by Josh Farkas.

https://ift.tt/2Pjq8aU

Quasi-metagenomic Analysis of Salmonella from Food and Environmental Samples

Here, we present a protocol to prepare DNA samples from food and environmental microbiomes for concerted detection and subtyping of Salmonella through quasimetagenomic sequencing. The combined use of culture enrichment, immunomagnetic separation (IMS), and multiple displacement amplification (MDA) allows effective concentration of Salmonella genomic DNA from food and environmental samples. 

https://ift.tt/2PWfS5p

Functional Surface-immobilization of Genes Using Multistep Strand Displacement Lithography

We describe a simple lithographic procedure for the immobilization of gene-length DNA molecules on a surface, which can be used to perform cell-free gene expression experiments on biochips.

https://ift.tt/2D5jTls

Using Clicker Training and Social Observation to Teach Rats to Voluntarily Change Cages

This protocol introduces a method of cage change for rats via clicker training. Rats learn the desired behavior not only by direct training but also by observational learning. The implementation of this fast and easy protocol might help to improve well-being and hygiene in rodent facilities.

https://ift.tt/2D8ER2G

ATAC-seq on TCGA: Insights Into the Noncoding Region in Primary Cancers

Researchers used ATAC-seq to profile the chromatin accessibility of 410 TCGA samples representing 23 primary cancers. The study uncovered a vast number of novel DNA regulatory elements and their potential roles in cancer development, prognosis, and response to therapy.

https://ift.tt/2AukXwF

Prion protein is essential for diabetic retinopathy-associated neovascularization

Abstract

Diabetic retinopathy (DR), a major complication of diabetes caused by vascular damage and pathological proliferation of retinal vessels, often progresses to vision loss. Vascular endothelial growth factor (VEGF) signaling plays a pivotal role in the development of DR, but the exact underlying molecular mechanisms remain ill-defined. Cellular prion protein (PrP^c) is a surface protein expressed by vascular endothelial cells, and the increased expression of PrP^c is associated with physiological and pathological vascularization. Nevertheless, a role for PrP^c in the development of DR has not been appreciated. Here, we addressed this question. We found that the development of streptozocin (STZ)-induced DR, but not the STZ-induced hyperglycemia/diabetes itself, was significantly attenuated in PrP^c-KO mice, compared to control wildtype (WT) mice, evident by measurement of retinal vascular leakage, retinal neovascularization, a retinopathy score and visual acuity assessment. Moreover, the attenuation of DR severity seemingly resulted from attenuation of retinal neovascularization via VEGF/ras/rac signaling. Together, our study suggests a previously unappreciated role for PrP^c in the development of DR.

https://ift.tt/2SmboH5

Endothelial loss of Fzd5 stimulates PKC/Ets1-mediated transcription of Angpt2 and Flt1

Abstract

Aims

Formation of a functional vascular system is essential and its formation is a highly regulated process initiated during embryogenesis, which continues to play important roles throughout life in both health and disease. In previous studies, Fzd5 was shown to be critically involved in this process and here we investigated the molecular mechanism by which endothelial loss of this receptor attenuates angiogenesis.

Methods and results

Using short interference RNA-mediated loss-of-function assays, the function and mechanism of signaling via Fzd5 was studied in human endothelial cells (ECs). Our findings indicate that Fzd5 signaling promotes neovessel formation in vitro in a collagen matrix-based 3D co-culture of primary vascular cells. Silencing of Fzd5 reduced EC proliferation, as a result of G₀/G₁ cell cycle arrest, and decreased cell migration. Furthermore, Fzd5 knockdown resulted in enhanced expression of the factors Angpt2 and Flt1, which are mainly known for their destabilizing effects on the vasculature. In Fzd5-silenced ECs, Angpt2 and Flt1 upregulation was induced by enhanced PKC signaling, without the involvement of canonical Wnt signaling, non-canonical Wnt/Ca²⁺-mediated activation of NFAT, and non-canonical Wnt/PCP-mediated activation of JNK. We demonstrated that PKC-induced transcription of Angpt2 and Flt1 involved the transcription factor Ets1.

Conclusions

The current study demonstrates a pro-angiogenic role of Fzd5, which was shown to be involved in endothelial tubule formation, cell cycle progression and migration, and partly does so by repression of PKC/Ets1-mediated transcription of Flt1 and Angpt2.

https://ift.tt/2z3aCpk

Analysis of Cancer Cell Invasion and Anti-metastatic Drug Screening Using Hydrogel Micro-chamber Array (HMCA)-based Plates

A HMCA-based imaging plate is presented for invasion assay performance. This plate facilitates the formation of three-dimensional (3D) tumor spheroids and the measurement of cancer cell invasion into the extracellular matrix (ECM). The invasion assay quantification is achieved by semi-automatic analysis.

https://ift.tt/2EK2Dnb

Apparatus for Harvesting Tissue Microcolumns

Here we describe a protocol for producing harvesting needles that can be used to collect full-thickness skin tissue without causing donor site scarring. The needles can be combined with a simple collection system to achieve high-volume harvesting.

https://ift.tt/2PomoEZ

Studying “Total Diet” and Its Impact on Health, Including Cancer Risk

Researchers are shifting how they assess diet and cancer risk, looking beyond the impact of individual foods or nutrients on health, and taking a more holistic approach, considering dietary patterns across the lifespan.

https://ift.tt/2PoMM1s

Should future paramedics be required to obtain associate degrees?

Our co-hosts tackle the topic of paramedic education and how it would affect the EMS industry

https://ift.tt/2Ra1U02

Pace of Change Has Accelerated in Alternative Payment Models

THURSDAY, Oct. 25, 2018 -- The impact of alternative payment models (APMs) on physician practices has been described in a study published by the RAND Corp. and the American Medical Association. In a follow-up to a 2014 study that examined the...

https://ift.tt/2Jf9UKo

Open Surgery for Early Lung CA Tied to Long-Term Opioid Use

THURSDAY, Oct. 25, 2018 -- Surgical invasiveness might play a role in the odds of becoming a long-term opioid user after early-stage lung cancer surgery, according to a research letter published online Sept. 24 in JAMA Oncology. Stephanie Tuminello,...

https://ift.tt/2Pk13wu

Allopurinol Linked to Reduced Risk for CKD Stage ≥3 in Gout

THURSDAY, Oct. 25, 2018 -- For patients with gout, allopurinol is associated with a reduced risk for developing chronic kidney disease stage ≥3, according to a study published online Oct. 8 in JAMA Internal Medicine. Ana Beatriz Vargas-Santos,...

https://ift.tt/2JfJok9

Half of Women to Develop Stroke, Dementia, or Parkinsonism

THURSDAY, Oct. 25, 2018 -- One in two women and one in three men will develop dementia, stroke, or parkinsonism during their lifetime, according to a study published online Oct. 1 in the Journal of Neurology, Neurosurgery & Psychiatry. Silvan...

https://ift.tt/2Pk12bU

Tobacco Use Remains Leading Modifiable Cause of Cancer

THURSDAY, Oct. 25, 2018 -- Tobacco use remains the leading modifiable cause of cancer and should be a priority for cancer control, according to a report published online Oct. 10 in CA: A Cancer Journal for Clinicians. Susan M. Gapstur, Ph.D.,...

https://ift.tt/2PkXqpT

HEART Pathway Can Safely Identify Low-Risk ER Patients

THURSDAY, Oct. 25, 2018 -- Implementation of the HEART Pathway is associated with decreased hospitalizations, increased identification of myocardial infarction (MI) at the index visit, and a very low death and MI rate among low-risk emergency...

https://ift.tt/2JhPFvN

Loss to Follow-Up Common With IBD, But Many Have Flare-Ups

THURSDAY, Oct. 25, 2018 -- Loss to follow-up is common with inflammatory bowel disease (IBD), and both low C-reactive protein levels and long travel time to the hospital are predictors of follow-up loss, according to a study published in the Journal...

https://ift.tt/2JeqmKR

Infant HIV Infection Ups Risk for Congenital CMV Infection

THURSDAY, Oct. 25, 2018 -- HIV-exposed infants have high rates of congenital cytomegalovirus (cCMV) infection, and in utero HIV infection seems to be a major risk factor for cCMV, according to a study published in the October issue of The Pediatric...

https://ift.tt/2Pk0YZI

Nearly Half of Children Seen in ED for Bronchiolitis Get Radiography

THURSDAY, Oct. 25, 2018 -- Despite guideline recommendations to the contrary, nearly half of children seen in the emergency department for bronchiolitis receive radiography, according to a research letter published online Oct. 16 in the Journal of...

https://ift.tt/2JkxXYw

Outcomes Studied for Surgical Tx of Stress Urinary Incontinence

THURSDAY, Oct. 25, 2018 -- Among women undergoing midurethral mesh sling insertion, the rate of mesh sling removal at nine years is estimated to be 3.3 percent, according to a study published online Oct. 23 in the Journal of the American Medical...

https://ift.tt/2Pk0Wky

A novel allele for inducible Cre expression in germinal center B cells

European Journal of Immunology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2PUFZcV

The deubiquitinating enzyme UCHL1 is a favorable prognostic marker in neuroblastoma as it promotes neuronal differentiation

Abstract

Background

Neuroblastoma (NB) is the most common pediatric solid tumor that originates from neural crest-derived sympathoadrenal precursor cells that are committed to development of sympathetic nervous system. The well differentiated histological phenotype of NB tumor cells has been reportedly associated with favorable patient outcome. Retinoic acid (RA) can effectively induce NB cell differentiation, thereby being used in the clinic as a treatment agent for inducing the differentiation of high-risk NB. However, the underlying molecular mechanisms of regulating differentiation remain elusive.

Methods

The correlation between clinical characteristics, survival and the deubiquitinating enzyme ubiquitin C-terminal hydrolase 1 (UCHL1) expression were assessed using a neuroblastic tumor tissue microarray, and then validated in three independent patient datasets. The different expression of UCHL1 in ganglioneuroblastoma, ganglioneuroma and NB was detected by immunohistochemistry, mass spectra and immunoblotting analysis, and the correlation between UCHL1 expression and the differentiated histology was analyzed, which was also validated in three independent patient datasets. Furthermore, the roles of UCHL1 in NB cell differentiation and proliferation and the underlying mechanisms were studied by using short hairpin RNA and its inhibitor LDN57444 in vitro.

Results

Based on our neuroblastic tumor tissue microarrays and three independent validation datasets (Oberthuer, Versteeg and Seeger), we identified that UCHL1 served as a prognostic marker for better clinical outcome in NB. We further demonstrated that high UCHL1 expression was associated with NB differentiation, indicated by higher UCHL1 expression in ganglioneuroblastomas/ganglioneuromas and well-differentiated NB than poorly differentiated NB, and the positive correlation between UCHL1 and differentiation markers. As expected, inhibiting UCHL1 by knockdown or LDN57444 could significantly inhibit RA-induced neural differentiation of NB tumor cells, characterized by decreased neurite outgrowth and neural differentiation markers. This effect of UCHL1 was associated with positively regulating RA-induced AKT and ERK1/2 signaling activation. What's more, knockdown of UCHL1 conferred resistance to RA-induced growth arrest.

Conclusion

Our findings identify a pivotal role of UCHL1 in NB cell differentiation and as a prognostic marker for survival in patients with NB, potentially providing a novel therapeutic target for NB.

https://ift.tt/2Pr0YqG

Metabolic and cardiovascular consequences of shift work: the role of circadian disruption and sleep disturbances

European Journal of Neuroscience, Volume 0, Issue ja, -Not available-.


https://ift.tt/2CDApba

Antigenic Liposomes for Generation of Disease-specific Antibodies

Described is the preparation of antigenic liposomal nanoparticles and their use in stimulating B-cell activation in vitro and in vivo. Consistent and robust antibody responses led to the development of a new peanut allergy model. The protocol for generating antigenic liposomes can be extended to different antigens and immunization models.

https://ift.tt/2qciotc

A Combinatorial Single-cell Approach to Characterize the Molecular and Immunophenotypic Heterogeneity of Human Stem and Progenitor Populations

Bulk gene expression measurements cloud individual cell differences in heterogeneous cell populations. Here, we describe a protocol for how single-cell gene expression analysis and index sorting by Florescence Activated Cell Sorting (FACS) can be combined to delineate heterogeneity and immunophenotypically characterize molecularly distinct cell populations.

https://ift.tt/2CCGDIl

Cost‐effectiveness of revascularization in patients with intermittent claudication

BJS, EarlyView.


https://ift.tt/2q9Cion

Systematic review of shared decision‐making in surgery

BJS, EarlyView.


https://ift.tt/2RipGXR

d(GC)10 sequence within promoter region enhances the promoter activity in Saccharomyces cerevisiae

https://ift.tt/2yxRkci

Birth control and breast cancer: An unclear connection

Cancer Cytopathology, Volume 126, Issue 9, Page 751-752, September 2018.


https://ift.tt/2PpiBY0

Issue Information

Cancer Cytopathology, Volume 126, Issue 9, Page 745-750, September 2018.


https://ift.tt/2JhsXnc

Issue Information

Developmental Psychobiology, Volume 60, Issue 7, Page 749-752, November 2018.


https://ift.tt/2Ppir2Q

People overestimate benefits, and underestimate risks, of medical interventions

From major heart surgery to a course of minor drugs, people overestimate the benefits and underestimate the risks of a variety of medical procedures, according to new research.

https://ift.tt/2Jg2IO4

Effects of FGFR gene polymorphisms on response and toxicity of cyclophosphamide-epirubicin-docetaxel-based chemotherapy in breast cancer patients

Abstract

Background

The chemotherapy resistance and toxicity of chemotherapy are major problems in breast cancer treatment. However, candidate biomarkers for predicting clinical outcomes and better prognosis remain lacking.

Methods

In this study, we analyzed possible impact of 8 genetic variants of fibroblast growth factor receptor1–4 (FGFR1–4) on the treatment response and toxicities in 211 breast cancer patients. DNA was extracted from peripheral blood cells, and the genotypes were examined using the TaqMan Pre-Designed SNP Genotyping Assays.

Results

The FGFR4 rs1966265 and FGFR2 rs2981578 contributed to clinical outcome of breast cancer treated with docetaxel–epirubicin-cyclophosphamide (CET)-based chemotherapy. For rs1966265, AA genotype had significant correlation with the clinical response to neoadjuvant chemotherapy (NCT) when compared with GG and AG/GG genotype (P = 0.019 and P = 0.004, respectively). Moreover, A allele of FGFR2 rs2981578 had significant rates of response (P = 0.025). In addition, rs2420946 CC genotype was associated with higher frequency of toxicities compared with TT and CT/TT genotypes (P = 0.038 and P = 0.019, respectively). Also, rs2981578 AG genotype showed higher frequency of toxicities compared with GG genotype (P < 0.0001).

Conclusions

The results suggest these polymorphisms, especially rs1966265 and rs2981578, might be candidate pharmacogenomics factors to the response and prognosis prediction for individualized CET-based chemotherapy in breast cancer patients.

https://ift.tt/2Q2QElK