Publication date: Available online 7 December 2017
Source:Journal of the Egyptian National Cancer Institute
Author(s): Yacoob Omar Carrim, Luvo Gaxa, Francisca van der Schyff, Nndweleni Meshack Bida, Fareed Omar, Zarina Lockhat
Colorectal carcinoma in children and adolescents is extremely rare, with an annual incidence <0.3 cases per million, most frequently reported in the second decade of life. It accounts for severe morbidity and poor prognosis owing to the low index of suspicion, delayed diagnosis, advanced stage at presentation and the aggressive tumor nature. Patients present with abdominal pain, vomiting, constipation, abdominal distension, rectal tenesmus, iron-deficiency anemia, change in bowel habit and weight loss. Rectal bleeding is an uncommon presentation in children. Bowel obstruction presents frequently in children compared to adults. In 90% of pediatric cases, colorectal carcinoma occurs sporadically. In 10%, predisposing conditions and syndromes are identified. We present a case study of a 12-year-old female with advanced colorectal cancer without a predisposing disease or syndrome, who received radio-chemotherapy ten weeks prior to radical abdominopelvic surgery, followed by radio-chemotherapy postoperatively, with a positive outcome.
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Πέμπτη 7 Δεκεμβρίου 2017
Does radiotherapy prior to surgery improve long term prognosis in pediatric colorectal cancer in lower- and upper-middle income countries with limited resources? Our experience and literature review
Downregulation of Caspase 8 in a group of Iranian breast cancer patients – A pilot study
Publication date: Available online 7 December 2017
Source:Journal of the Egyptian National Cancer Institute
Author(s): Masoumeh Aghababazadeh, Najmeh Dorraki, Fahimeh Afzal Javan, Asieh Sadat Fattahi, Masoumeh Gharib, Alireza Pasdar
PurposeIt is now well known that evading apoptosis, as a cancer hallmark, can lead to tumour initiation, progression and metastasis. As a result of genome wide association studies, an initiator protease in this pathway, caspase 8 (CASP8), has been found to be an important gene regarding breast cancer susceptibility. The alterations of the expression of this gene have been reported in breast cancer cell lines. Given that in previous studies expression analysis of this gene had only been done in breast cancer cell lines, in this study we aimed to evaluate the expression of this gene in breast cancer tissues versus adjacent normal tissues, using real-time quantitative method.MethodsCaspase 8 mRNA expression was quantified using comparative RT-qPCR in 27 fresh frozen breast tumours and 27 adjacent normal tissues. Moreover, relationship between the expression changes of CASP8 in tumour tissue and various clinical and pathological features were evaluated in an Iranian population.ResultsThe present study showed that expression of CASP8 was significantly reduced in tumour tissues compared to neighbouring normal tissues (p = .004). CASP8 expression was significantly correlated with the status of hormone receptors (ER and PR).ConclusionTo the best of our knowledge, this study is the first report on reduced expression of CASP8 in breast cancer versus adjacent normal tissues. Our data support previous results obtained from cell lines and therefore highlights the seminal role of the induction of CASP8 expression, as a novel therapeutic approach, in order to sensitize tumour cells to apoptotic stimuli.
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Cytological diagnosis of a rare case of cutaneous metastasis from transitional cell carcinoma, renal pelvis
Publication date: Available online 7 December 2017
Source:Journal of the Egyptian National Cancer Institute
Author(s): Pragya Singh, Sachin Kolte, Gunjesh Kumar Singh
Transitional cell carcinoma (TCC) arising from renal pelvis rarely gives rise to cutaneous metastasis. Due to the insufficient literature, the exact incidence is not known till date. Moreover, the diagnosis is confirmed on histopathological examination with the aid of immunohistochemistry wherever needed. We are presenting a case of a 70-year-old female with metastatic TCC from the renal pelvis to the abdominal skin, which was diagnosed on cytology alone along with the cell block preparation. We also highlight the important cytomorphological and immunohistochemical features noted, which need to be known to avoid any diagnostic delay.
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Comments on “Solid pseudopapillary neoplasm of the pancreas: Management and long-term outcome”
Source:European Journal of Surgical Oncology
Author(s): Xing Wang, Xubao Liu
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Reply letter to: Comments on "Solid pseudopapillary neoplasm of the pancreas: Management and long-term outcome"
Source:European Journal of Surgical Oncology
Author(s): Nir Lubezky
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Tennis leg: A mimic of deep venous thrombosis
Source:Medical Journal Armed Forces India
Author(s): Mukul Bhatia, Vinay Maurya, J. Debnath, Preeti Gupta
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Antibacterial resistance patterns of extended spectrum β-lactamase -producing enteropathogenic Escherichia coli strains isolated from children
Publication date: Available online 7 December 2017
Source:Arab Journal of Gastroenterology
Author(s): Pejman Karami, Hassan Bazmamoun, Iraj Sedighi, Amir Sasan Mozaffari Nejad, Mohammad Mehdi Aslani, Mohammad Yousef Alikhani
Background and study aimThis study aimed to determine the antibacterial resistance patterns of extended spectrum β-lactamase (ESBL)-producing enteropathogenic Escherichia coli (EPEC) isolated from Iranian children and to investigate its genetic patterns.Patients and methods192 non-repeats EPEC isolates were collected from stool samples of the children with and without diarrhoea. The EPEC strains were isolated from 1355 stool specimens obtained from 247 children with diarrhoea (0–10 years old; mean age, 5.5 years) and 1108 children without any gastrointestinal symptoms (0–10 years old; mean age, 6.8 years) during the summer months in three Iranian provinces, Tehran, Ilam and Mazandaran. Strains biochemically identified as E. coli were selected and were identified by the presence of eaeA and bfpA as EPEC virulence genes. Antimicrobial susceptibilities were determined by disc diffusion method. The isolates were confirmed to be ESBL producers by the double disk synergy test (DDST). The β-lactamase genes (blaTEM, blaSHV, blaCTX-M, blaOXA) and insertion sequence ISEcp1 were detected by PCR method.ResultsThe highest antibiotic susceptibility was detected to imipenem (100%), followed by gentamicin (82.3%) and ciprofloxacin (79.2%). The highest resistance was detected to cefpodoxime (97.9%), trimethoprim (60.7%), and tetracycline (58.4%), respectively. Totally, 153 EPEC strains (79.7%) were ESBL-producing by DDST test. The PCR showed that 84 (43.8%) EPEC isolates were positive for ESBLs encoding genes. Among 153 ESBLs-producing EPEC, TEM was present in 9.2% of isolates. Also, CTX-M and SHV genes were detected in 7.2% and 7.8%, respectively. The SHV positive strains were associated with the highest resistance rate to tetracycline (56.5%), although the TEM and OXA were associated with the highest resistance rate to gentamicin (23.1%) and ciprofloxacin (21.4%).ConclusionsThe study revealed that 79.7% of EPEC isolates from Iranian children were ESBL-producing and were comparable with the non ESBL-producing isolates regarding susceptibility to the antibiotics.
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Preface – Part 2: Circadian and endocrine rhythms
Publication date: December 2017
Source:Best Practice & Research Clinical Endocrinology & Metabolism, Volume 31, Issue 6
Author(s): Andries Kalsbeek, Eric Fliers
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Bone Marrow Edema Syndrome Of The Medial Femoral Condyle Treated With Extracorporeal Shock Wave Therapy: A Clinical And MRI Retrospective Comparative Study
Publication date: Available online 7 December 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Matteo Vitali, Nadim Naim Rodriguez, Alberto Pedretti, Andreas Drossinos, Pierluigi Pironti, Gaia Di Carlo, Gianfranco Fraschini
ObjectiveTo determine the validity of Extracorporeal Shock Wave Therapy (ESWT) in the treatment of Bone Marrow Edema (BME) of the medial condyle of the kneeDesignRetrospectiveStudy SettingIRCCS San Raffaele Hospital, Orthopedics Outpatient ClinicParticipantsFifty-six symptomatic patients affected by bone marrow edema of the medial condyle of the knee. Patients were equally divided in a ESWT (Extracorporeal Shock Wave Therapy) treated group and a control group, which was managed conservatively.InterventionsExtracorporeal Shock Wave Therapy delivery to the medial condyle of the affected knee.Main Outcome MeasuresClinical and Functional assessment done with the use of the Knee Society Score (KSS), both clinical and functional scores. Pain was measured with Visual Analog Scale (VAS). Bone marrow edema area was measured with Magnetic Resonance Imaging before treatment and at 4 months follow-up.ResultsClinical evaluation of patients at final follow-up of 4 months post-treatment showed a significant improvement (p< 0.0001) of symptoms and knee functionality, both for range of motion and strength in both groups VAS values saw a significant improvement (p< 0.0001) in both groups; with 3 patients in the ESWT group being pain-free (VAS=0) at 4 months follow-up. At 4 months MRI assessments on both sagittal and coronal views showed a significant reduction in bone marrow edema in the ESWT as compared to the control group.ConclusionOur findings show that this type of therapy has shown to be a valid non-pharmacological and non-invasive therapy in the treatment of spontaneous BME of the medial condyle, producing an improvement of the affected vascular and metabolic state present in this pathology through its metabolic mechanisms of action.
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Comparison of neuroplastic responses to cathodal transcranial direct current stimulation and continuous theta burst stimulation in subacute stroke
Publication date: Available online 7 December 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Pierre Nicolo, Cécile Magnin, Elena Pedrazzini, Gijs Plomp, Anaïs Mottaz, Armin Schnider, Adrian G. Guggisberg
ObjectiveTo investigate the effects of cathodal transcranial direct current stimulation (tDCS) and continuous theta burst stimulation (cTBS) on neural network connectivity and motor recovery in individuals with subacute stroke.DesignDouble-blinded, randomized, placebo-controlled study.SettingStroke subjects recruited through a university hospital rehabilitation program.ParticipantsStroke inpatients (N=41; mean age 65y, range 28-85; mean weeks poststroke 5, range 2-10) with resultant paresis in the upper extremity (mean Fugl-Meyer score 14, range 3-48).InterventionStroke subjects were randomly assigned to neuronavigated cTBS (N=14), cathodal tDCS (N=14), or sham TMS/sham tDCS (N=13) over the contralesional primary motor area (M1). Each subject completed nine stimulation sessions over three weeks, combined with physical therapy.Main outcome measuresBrain function was assessed with resting-state directed and non-directed functional connectivity based on high-density electroencephalography (EEG) before and after stimulation sessions. Primary clinical endpoint was the change in slope of multifaceted motor score composed of the Upper-Extremity Fugl-Meyer Assessment (UE-FMA), Box and Block test (BBT), Nine Hole Peg Test (NHPT), Jamar dynamometer between the baseline period and the treatment time.ResultsNeither stimulation treatment enhanced clinical motor gains. Cathodal tDCS and cTBS induced different neural effects. Only cTBS was able to reduce transcallosal influences from the contralesional to the ipsilesional M1 during rest. Conversely, tDCS enhanced perilesional beta-band oscillation coherence as compared to cTBS and sham groups. Correlation analyses indicated that the modulation of interhemispheric driving and perilesional beta-band connectivity were not independent mediators for functional recovery across all patients. However, exploratory subgroup analyses suggest that the enhancement of perilesional beta-band connectivity through tDCS might have more robust clinical gains if started within the first 4 weeks after stroke.ConclusionsThe inhibition of the contralesional primary motor cortex or the reduction of interhemispheric interactions was not clinically useful in heterogeneous group of subacute stroke subjects. An early modulation of perilesional oscillation coherence seems to be a more promising strategy for brain stimulation interventions.
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Disrupted circuits in mouse models of autism spectrum disorder and intellectual disability
Source:Current Opinion in Neurobiology, Volume 48
Author(s): Carla EM Golden, Joseph D Buxbaum, Silvia De Rubeis
Autism spectrum disorder (ASD) and intellectual disability (ID) are caused by a wide range of genetic mutations, a significant fraction of which reside in genes important for synaptic function. Studies have found that sensory, prefrontal, hippocampal, cerebellar, and striatal regions, as well as the circuits that connect them, are perturbed in mouse models of ASD and ID. Dissecting the disruptions in morphology and activity in these neural circuits might help us to understand the shared risk between the two disorders as well as their clinical heterogeneity. Treatments that target the balance between excitation and inhibition in these regions are able to reverse pathological phenotypes, elucidating this deficit as a commonality across models and opening new avenues for intervention.
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Parental perceptions, attitudes and acceptance of childhood immunization in Saudi Arabia: A cross sectional study
Source:Vaccine, Volume 36, Issue 1
Author(s): Thamir M. Alshammari, Gehad M. Subaiea, Talib Hussain, Afrasim Moin, Kazeem B. Yusuff
ObjectivesThe widespread availability and use of vaccines have tremendously reduced morbidity, mortality and health care costs associated with infectious diseases. However, parental beliefs about vaccination are one of the major factors in achieving high vaccination rates. Thus, this study aims to assess the perceptions and attitudes regarding routine childhood immunization among Saudi parents.MethodsA cross sectional study with a pre-tested 18-item questionnaire was conducted using 467 randomly selected parents from the Hail region of Saudi Arabia in the period between February 1st, 2016, and February 1st, 2017. The validated questionnaire consisted of three sections that collected information on participants' demographics, parents' awareness of vaccine benefits, and parents' practices regarding the immunization of their children.ResultsFemale and male parents comprised 54.5% (255) and 45.5% (212) of the sample, respectively, and the response and completion rates were 97%. The majority of the respondents had received a formal education (94.1%, 439), were gainfully employed (62.9%, 294) and had a regular monthly income (73.3%). The majority of the respondents were aware of childhood vaccinations (78.9%), completed vaccinations mandated for children up to 5 years (86.2%), encouraged other parents to do so (89.9%), and had easy access to vaccines (90.5%). Sixty to ninety percent of the respondents were knowledgeable regarding the health benefits of vaccinations in children, even though 18.4% of their children had experienced vaccination-related minor adverse effects during or after vaccination of which 23.2% required doctor's visits. Health care professionals were the most frequent source of parents' vaccine-related information (65.2%), and vaccination reminder services provided by the Ministry of Health (MOH) via mobile phones were cited by 57.5% of respondents.ConclusionsConfidence in and acceptance of childhood vaccinations, perceptions of vaccine-related health benefits and ease of access to immunizations appeared to be quite good among Saudi parents.
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Editorial Board/Aims and Scope
Source:Vaccine, Volume 36, Issue 1
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Assessing the safety of hepatitis B vaccination during pregnancy in the Vaccine Adverse Event Reporting System (VAERS), 1990–2016
Source:Vaccine, Volume 36, Issue 1
Author(s): Pedro L. Moro, Yenlik Zheteyeva, Faith Barash, Paige Lewis, Maria Cano
BackgroundThe safety of hepatitis B vaccination during pregnancy has not been well studied.ObjectiveWe characterized adverse events (AEs) after hepatitis B vaccination of pregnant women reported to the Vaccine Adverse Event Reporting System (VAERS), a spontaneous reporting surveillance system.MethodsWe searched VAERS for AEs reports involving pregnant women who received hepatitis B vaccine from January 1, 1990–June 30, 2016. All reports and available medical records were reviewed by physicians. Observed AEs were compared to expected AEs and known rates of pregnancy outcomes to assess for any unexpected safety concern.ResultsWe found 192 reports involving pregnant women following hepatitis B vaccination of which 110 (57.3%) described AEs; 12 (6.3%) were classified as serious; one newborn death was identified in a severely premature delivery, and there were no maternal deaths. Eighty-two (42.7%) reports did not describe any AEs. Among pregnancies for which gestational age was reported, most women were vaccinated during the first trimester, 86/115 (74.7%). Among reports describing an AE, the most common pregnancy-specific outcomes included spontaneous abortion in 23 reports, preterm delivery in 7 reports, and elective termination in 5 reports. The most common non-pregnancy specific outcomes were general disorders and administration site conditions, such as injection site and systemic reactions, in 21 reports. Among 22 reports describing an AE among infants born to women vaccinated during pregnancy, 5 described major birth defects each affecting different organ systems.ConclusionOur analysis of VAERS reports involving hepatitis B vaccination during pregnancy did not identify any new or unexpected safety concerns.
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Designing an immunocyte-targeting delivery system by use of beta-glucan
Source:Vaccine, Volume 36, Issue 1
Author(s): Noriko Miyamoto, Shinichi Mochizuki, Kazuo Sakurai
A β-1,3-d-glucan called Schizophyllan (SPG) can form a novel complex with homo oligodeoxynucleotides (ODNs) via the combination of hydrogen bonding and hydrophobic interactions. Dectin-1 is a major receptor involved in the recognition of β-1,3-d-glucans and expressed on antigen presenting cells (APCs) including macrophages, dendritic cells, monocytes, neutrophils, and a subset of T cells. Therefore, the SPG/ODN complex can be used as APCs cell-specific delivery of functional ODNs including unmethylated CpG sequences (CpG-ODNs). In fact, CpG-ODN/SPG complex induced high antibody titers when it was administered to cynomolgus monkeys as adjutant of influenza vaccine. These results indicate that SPG can be an excellent immunocyte-targeting drug delivery system.
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Immunization effects of a communication intervention to promote preteen HPV vaccination in primary care practices
Source:Vaccine, Volume 36, Issue 1
Author(s): Joan R. Cates, Jamie L. Crandell, Sandra J. Diehl, Tamera Coyne-Beasley
ObjectivesHPV vaccination at the recommended ages of 11–12 is highly effective yet has stalled well below the goal of 80% of the population. We evaluated a statewide practice-based communication intervention (tools: brochures, posters, online training for providers and resources for parents, video game for preteens) to persuade parents, preteens and providers to vaccinate against HPV. The 9-month intervention started May 1, 2015.MethodsWe compared vaccine initiation and completion rates over three 9-month periods (baseline, intervention, post-intervention) between practices enrolled in the intervention and a comparable comparison group. All practices reported to the North Carolina Immunization Registry (NCIR) and had at least 100 11- and 12-year-olds who had not completed the HPV vaccine series. Of 175 eligible practices, the 14 intervention practices included 19,398 individuals and the 161 comparison practices included 127,896 individuals. An extended Cox model was used to test the intervention effect.ResultsThe intervention had a significant effect on both initiation and completion during the intervention and post-intervention periods; the estimated hazard ratio (HR) for initiation was 1.17 (p = .004) during the intervention and 1.11 (p = .005) post-intervention. Likewise, completion during the intervention period was 17% higher in intervention practices, after controlling for baseline differences. This effect increased in the post-intervention period to 30% higher (p = .03).ConclusionsIndividuals in the intervention practices were 17% more likely to initiate and complete HPV vaccination than in the comparison practices during the intervention period and the effect was sustained post-intervention. This intervention is promising for increasing rates of HPV vaccination at ages 11–12.
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Association of prior HPV vaccination with reduced preterm birth: A population based study
Source:Vaccine, Volume 36, Issue 1
Author(s): Beverley Lawton, Anna S. Howe, Nikki Turner, Sara Filoche, Tania Slatter, Celia Devenish, Noelyn Anne Hung
BackgroundEmerging evidence suggests that HPV infection is associated with negative pregnancy outcomes such as preterm birth (PTB), and pre-eclampsia. We aimed to determine if prior HPV vaccination reduced adverse pregnancy outcomes.MethodsA New Zealand population-based retrospective study linking first pregnancy outcome data (2008–2014 n = 35,646) with prior quadrivalent HPV vaccination status. Primary outcomes were likelihood (odds ratios, ORs) of PTB, pre-eclampsia, and stillbirth. Exposure groups were based on HPV vaccination. Adjusted ORs were calculated for each outcome, controlling for mother's age at delivery, ethnicity, socioeconomic status, health board region at time of delivery, and body mass index and smoking status at time of registration with maternity care provider.ResultsMother's mean age at delivery was 19 (SD 2.1) years. Of 34,994 the pregnancies included in the final study analyses 62.3% of women were unvaccinated, 11.0% vaccinated with one or two doses and 27.7% vaccinated with three doses prior to pregnancy. PTB (OR: 0.87; CI 0.78, 0.96)) was significantly lower for women who previously received the HPV vaccine. A dose response effect was found with each successive dose received decreasing the likelihood of PTB. No associations between the vaccinated and unvaccinated groups were shown for pre-eclampsia or stillbirth.ConclusionsPrior receipt of the quadrivalent HPV vaccine was associated with a significant reduction in PTB (13%); suggesting that HPV vaccination may be effective in reducing PTB. The potential global public health impact is considerable and there is urgency to undertake further research to replicate and explore these findings.
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The risk of lower respiratory tract infection following influenza virus infection: A systematic and narrative review
Source:Vaccine, Volume 36, Issue 1
Author(s): Ryan E. Malosh, Emily T. Martin, Justin R. Ortiz, Arnold S. Monto
BackgroundLower respiratory tract infections (LRTI) are a major cause of morbidity and mortality worldwide, particularly in young children and older adults. Influenza is known to cause severe disease but the risk of developing LRTI following influenza virus infection in various populations has not been systematically reviewed. Such data are important for estimating the impact specific influenza vaccine programs would have on LRTI outcomes in a community. We sought to review the published literature to determine the risk of developing LRTI following an influenza virus infection in individuals of any age.Methods and findingsWe conducted a systematic review to identify prospective studies that estimated the incidence of LRTI following laboratory-confirmed influenza virus infection. We searched PubMed, Medline, and Embase databases for relevant literature. We supplemented this search with a narrative review of influenza and LRTI. The systematic review identified two prospective studies that both followed children less than 5 years. We also identified one additional pediatric study from our narrative review meeting the study inclusion criteria. Finally, we summarized recent case-control studies on the etiology of pneumonia in both adults and children.ConclusionsThere is a dearth of prospective studies evaluating the risk of developing LRTI following influenza virus infection. Determining the burden of severe LRTI that is attributable to influenza is necessary to estimate the benefits of influenza vaccine on this important public health outcome. Vaccine probe studies are an efficient way to evaluate these questions and should be encouraged going forward.
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Immunogenicity, reactogenicity and safety of 2 doses of an adjuvanted herpes zoster subunit vaccine administered 2, 6 or 12 months apart in older adults: Results of a phase III, randomized, open-label, multicenter study
Source:Vaccine, Volume 36, Issue 1
Author(s): Himal Lal, Airi Poder, Laura Campora, Brecht Geeraerts, Lidia Oostvogels, Carline Vanden Abeele, Thomas C. Heineman
BackgroundIn phase III trials, 2 doses of a herpes zoster (HZ) subunit vaccine (HZ/su; 50 µg varicella-zoster virus glycoprotein E [gE] and AS01B Adjuvant System) administered 2-months apart in older adults (≥50 and ≥70 years) demonstrated >90% efficacy in preventing HZ and had a clinically acceptable safety profile. Here we report immunogenicity, reactogenicity and safety following administration of 2 HZ/su doses at intervals longer than 2 months.MethodsIn this Phase III, open-label trial conducted in the US and Estonia, 354 adults ≥50 years were randomized 1:1:1 to receive 2 HZ/su doses 2, 6, or 12 months apart. gE-specific humoral immune responses were evaluated at pre-vaccination, 1 and 12 months post-dose 2. Co-primary objectives were to compare immune responses to HZ/su 1 month post-dose 2 when given 6-months or 12-months apart to those administered 2-months apart. For each participant, safety information was collected from dose 1 to 12 months post-dose 2.Results346 participants completed the study and 343 were included in the according-to-protocol cohort for immunogenicity. One month post-dose 2, vaccine response rates were 96.5% (97.5% confidence interval [CI]: 90.4; 99.2) and 94.5% (97.5% CI: 87.6; 98.3) for the 0, 6- and 0, 12-month schedules, respectively, both schedules meeting the pre-defined criterion. Non-inferiority of anti-gE geometric mean concentrations was demonstrated for HZ/su administered on 0, 6-month compared to a 0, 2-month schedule; however, HZ/su administered on a 0, 12-month schedule did not meet the non-inferiority criterion. Injection site pain was the most commonly reported solicited adverse event (AE). 26 participants each reported at least 1 serious AE; none were assessed as related to vaccination.ConclusionsImmune responses to HZ/su administered at 0, 6-month were non-inferior to those elicited by a 0, 2-month schedule. HZ/su exhibited a clinically acceptable safety profile for all dosing intervals.Clinical Trials Registration: Clinicaltrials.gov (NCT01751165).
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U.S. pregnant women’s knowledge and attitudes about behavioral strategies and vaccines to prevent Zika acquisition
Source:Vaccine, Volume 36, Issue 1
Author(s): Lauren Dapena Fraiz, Ariel de Roche, Christine Mauro, Marina Catallozzi, Gregory D. Zimet, Gilla K. Shapiro, Susan L. Rosenthal
IntroductionZika virus infection during pregnancy can cause significant infant morbidity. Little is known about pregnant women's attitudes regarding behavioral strategies and hypothetical vaccination to prevent Zika infections and sequelae.MethodsPregnant women across the United States (N = 362) completed an online questionnaire regarding attitudes about Zika, including six behavioral prevention strategies (i.e., abstaining from sex, using condoms, not traveling to an area with Zika, their partner not traveling into an area with Zika, using mosquito repellant, wearing long pants and sleeves) and vaccination.ResultsMost women (91%) were married/living with the baby's father, 65% were non-Hispanic White, and 71% had been pregnant. Seventy-four percent were worried about Zika, while 30% thought they were knowledgeable about Zika. The mean knowledge score was 5.0 out of 8 (SD = 2.09), and the mean behavioral strategies score was 4.9 out of 12 (SD = 3.7) with a range of 0 (none would be hard to do) to 12 (all would be hard to do). In a multivariable model, having had a sexually transmitted infection, living/traveling in an area with Zika, and worrying about Zika were significantly related to reporting behavioral strategies as hard to do. Seventy-two percent would be willing to be vaccinated. In the multivariable model, living/traveling in an area with Zika, believing they knew a lot about Zika, worrying about Zika, and considering Zika vaccine development as important were significantly associated with willingness to get vaccinated.ConclusionsPregnant women were worried about Zika, yet had gaps in their factual knowledge. Most women reported they would get vaccinated if a vaccine was available. Pregnant women who reported themselves as vulnerable (being worried, having lived in or traveled to a Zika area) were more likely to view behavioral strategies as hard to do and to accept vaccination.
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Calcification of Thoracic and Abdominal Aneurysms is Associated with Mortality and Morbidity
Publication date: Available online 7 December 2017
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Mohammed M. Chowdhury, Lukasz P. Zieliński, James J. Sun, Simon Lambracos, Jonathan R. Boyle, Seamus C. Harrison, James H.F. Rudd, Patrick A. Coughlin
IntroductionCardiovascular events are common in people with aortic aneurysms. Arterial calcification is a recognised predictor of cardiovascular outcomes in coronary artery disease. Whether calcification within abdominal and thoracic aneurysm walls is correlated with poor cardiovascular outcomes is not known.Patients and methodsCalcium scores were derived from computed tomography (CT) scans of consecutive patients with either infrarenal (AAA) or descending thoracic aneurysms (TAA) using the modified Agatston score. The primary outcome was subsequent all cause mortality during follow-up. Secondary outcomes were cardiovascular mortality and morbidity.ResultsA total of 319 patients (123 TAA and 196 AAA; median age 77 [71–84] years, 72% male) were included with a median follow-up of 30 months. The primary outcome occurred in 120 (37.6%) patients. In the abdominal aortic aneurysm group, the calcium score was significantly related to both all cause mortality and cardiac mortality (odds ratios (OR) of 2.246 (95% CI 1.591–9.476; p < 0.001) and 1.321 (1.076–2.762; p = 0.003)) respectively. In the thoracic aneurysm group, calcium score was significantly related to all cause mortality (OR 6.444; 95% CI 2.574–6.137; p < 0.001), cardiac mortality (OR 3.456; 95% CI 1.765–4.654; p = 0.042) and cardiac morbidity (OR 2.128; 95% CI 1.973–4.342; p = 0.002).ConclusionsAortic aneurysm calcification, in either the thoracic or the abdominal territory, is significantly associated with both higher overall and cardiovascular mortality. Calcium scoring, rapidly derived from routine CT scans, may help identify high risk patients for treatment to reduce risk.
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Re: “Catheter Foam Sclerotherapy of Great Saphenous Vein, with Peri-saphenous Tumescence Infiltration and Saphenous Irrigation”
Publication date: Available online 7 December 2017
Source:European Journal of Vascular and Endovascular Surgery
Author(s): A. Cavezzi, G. Mosti, F. Campana, L. Tessari, L. Bastiani, S.U. Urso
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A Rare Cause of Critical Limb Ischaemia: An Aneurysmal Persistent Sciatic Artery
Publication date: Available online 7 December 2017
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Gabriele Pagliariccio, Luciano Carbonari
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Late Open Surgical Conversion after Endovascular Abdominal Aortic Aneurysm Repair
Publication date: Available online 7 December 2017
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Vinay Kansal, Sudhir Nagpal, Prasad Jetty
IntroductionLate open surgical conversion following endovascular aneurysm repair (EVAR) may occur more frequently after performing EVAR in anatomy outside the instructions for use (IFU). This study reviews predictors and outcomes of late open surgical conversion for failed EVAR.MethodsThis retrospective cohort study reviewed all EVARs performed at the Ottawa Hospital between January 1999 and May 2015. Open surgical conversions >1 month post EVAR were identified. Variables analysed included indication for conversion, pre-intervention AAA anatomy, endovascular device and configuration, operative technique, re-interventions, complications, and death.ResultsOf 1060 consecutive EVARs performed, 16 required late open surgical conversion. Endografts implanted were Medtronic Talent (8.50.0%), Medtronic Endurant (3.18.8%), Cook Zenith (4.25.0%), and Terumo Anaconda (1.6.2%). Eleven grafts were bifurcated (68.8%), five were aorto-uni-iliac (31.2%). The median time to open surgical conversion was 3.1 (IQR 1.0–5.2) years. There was no significant difference in pre-EVAR rupture status (1.4% elective, 2.1% ruptured, p = .54). Indications for conversion included: Type 1 endoleak with sac expansion (n = 4, 25.0%), Type 2 endoleak with expansion (n = 2, 12.5%), migration (n = 3, 18.8%), sac expansion without endoleak (n = 2, 12.5%), graft infection (n = 3, 18.8%), rupture (n = 2, 12.5%). Nine patients (56.2%) underwent stent graft explantation with in situ surgical graft reconstruction, seven had endograft preserving open surgical intervention. The 30 day mortality was 18.8% (n = 3, all of whom having had endograft preservation). Ten patients (62.5%) suffered major in hospital complications. One patient (6.5%) required post-conversion major surgical re-intervention. IFU adherence during initial EVAR was 43.8%, versus 79.0% (p < .01) among uncomplicated EVARs.ConclusionsOpen surgical conversion following EVAR results in significant morbidity and mortality. IFU adherence of EVARs later requiring open surgical conversion is markedly low. More data are required to elucidate the impact of increasing liberalisation of EVAR outside of IFU.
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Exendin-4 partly ameliorates of hyperglycemia-mediated tissue damage in lungs of streptozotocin-induced diabetic mice
Publication date: Available online 7 December 2017
Source:Peptides
Author(s): Fusun Oztay, Serap Sancar Bas, Selda Gezginci-Oktayoglu, Merve Ercin, Sehnaz Bolkent
Glucagon-like peptide-1 (GLP-1) stimulates insulin secretion, and plays anti-inflammatory role in atherosclerosis, and has surfactant-releasing effects in lungs. GLP-1 analogues are used in diabetes therapy. This is the first study to investigate the effects of exendin-4, a GLP-1 receptor agonist, on lung injury in diabetic mice. BALB/c male mice were divided into four groups. The first group was given only citrate buffer, the second group was given only exendin-4, the third group was given only streptozotocin (STZ), and the fourth group was given both exendin-4 and STZ. Exendin-4 (3μg/kg) was administered daily by subcutaneous injection for 30days after mice were rendered diabetic with a single dose of STZ (200mg/kg). Structural alterations, oxidative stress, apoptosis, insulin signaling and expressions of prosurfactant-C, alpha-smooth muscle actin, collagen-I and fibronectin were evaluated in lung tissue. Diabetic mice lungs were characterized by induced oxidative stress, apoptosis, edema, and cell proliferation. They had honeycomb-like alveoli, thick alveolar walls, and hypertrophic pneumocytes. Although exendin-4 treatment improved pulmonary edema, apoptosis, oxidative stress, and lung injury, it led to the disrupted insulin signaling and interstitial collagen accumulation in the lungs of diabetic mice. Exendin-4 reduced hyperglycemia-mediated lung damage by reducing glucose, and oxidative stress and stimulating cell proliferation. However, exendin-4 led to increased risk by reducing insulin signaling in the lungs and collagen accumulation around pulmonary vasculature in diabetic mice.
Graphical abstract
http://ift.tt/2Bjl13Q
Can breast cancer patients with HER2 dual-equivocal tumours be managed as HER2-negative disease?
Source:European Journal of Cancer, Volume 89
Author(s): Yiwei Tong, Xiaosong Chen, Xiaochun Fei, Lin Lin, Jiayi Wu, Ou Huang, Jianrong He, Li Zhu, Weiguo Chen, Yafen Li, Kunwei Shen
BackgroundIncreasing human epidermal growth factor receptor 2 (HER2) immunohistochemistry (IHC)/fluorescence in situ hybridisation (FISH) dual-equivocal breast tumours are reported after the 2013 American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guideline update. The aim of this study is to investigate the clinico-pathologic characteristics, treatment patterns and disease outcome of these patients with HER2 dual-equivocal tumours.Patients and methodsPatients with HER2 IHC 2+ and available FISH results were retrospectively analysed from the Comprehensive Breast Health Center, Shanghai Ruijin Hospital. The 2013 ASCO/CAP guideline was applied to define HER2-positive, dual-equivocal and -negative groups. Patient characteristics, systemic treatment patterns and survival were compared among these groups. Reverse transcriptase-polymerase chain reaction-based assays were applied to test HER2 mRNA expression level.ResultsAmong 691 patients included, 133 (19.25%) were HER2 positive, 25 (3.62%) were HER2 dual-equivocal and 533 (77.13%) were HER2 negative. Univariate and multivariate analyses stated that HER2 dual-equivocal tumours shared more similarity with HER2-negative tumours, whereas HER2-positive tumours had rather different clinico-pathologic features. HER2 dual-equivocal tumours had similar HER2 mRNA levels compared with HER2-negative tumours (P = 0.26), which were much less compared with HER2-positive breast cancer. Besides, adjuvant systemic treatment patterns were comparable between HER2-negative and dual-equivocal tumours, and none of HER2 dual-equivocal patients received anti-HER2 treatment. There was no survival difference among these three groups (P = 0.43).ConclusionHER2 dual-equivocal tumours share more similarity with HER2-negative disease in terms of clinico-pathologic features, HER2 mRNA levels, adjuvant systemic treatment patterns and disease outcome, which deserves further clinical evaluation.
http://ift.tt/2AF2Diy
Long-term efficacy analysis of the randomised, phase II TRYPHAENA cardiac safety study: Evaluating pertuzumab and trastuzumab plus standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer
Source:European Journal of Cancer, Volume 89
Author(s): Andreas Schneeweiss, Stephen Chia, Tamas Hickish, Vernon Harvey, Alexandru Eniu, Maeve Waldron-Lynch, Jennifer Eng-Wong, Sarah Kirk, Javier Cortés
BackgroundWe report long-term efficacy and cardiac safety outcomes in patients with HER2-positive early breast cancer treated with neoadjuvant pertuzumab plus trastuzumab with anthracycline-containing or anthracycline-free chemotherapy.MethodsDescriptive efficacy analyses were conducted in patients randomised to group A (cycles 1–6: trastuzumab [8 mg/kg loading dose and 6 mg/kg maintenance] plus pertuzumab [840 mg loading dose and 420 mg maintenance], plus 5-fluorouracil, epirubicin and cyclophosphamide [FEC] [cycles 1–3; 500 mg/m2 5-fluorouracil/100 mg/m2 epirubicin/600 mg/m2 cyclophosphamide] then docetaxel [cycles 4–6; 75 mg/m2, escalated to 100 mg/m2 if well tolerated]), B (cycles 1–3: FEC, cycles 4–6: trastuzumab plus pertuzumab plus docetaxel as mentioned previously) or C (cycles 1–6: trastuzumab plus pertuzumab plus docetaxel [75 mg/m2, without dose escalation], and carboplatin [AUC 6]), five years after randomisation of the last patient. This study is registered with ClinicalTrials.gov, number NCT00976989.ResultsThree-year Kaplan–Meier survival estimates for disease-free survival (DFS) were 87% (95% confidence interval: 79–95), 88% (80–96) and 90% (82–97) in groups A–C, respectively. Progression-free survival (PFS) rates were 89% (81–96), 89% (81–96) and 87% (80–95). DFS hazard ratio for total pathological complete response (tpCR) versus no tpCR was 0.27 (0.11–0.64). During post-treatment follow-up, 2/72 (2.8%), 3/75 (4.0%) and 4/76 (5.4%) patients in groups A–C had any-grade left ventricular systolic dysfunction; eight (11.1%), 12 (16.0%) and nine (11.8%) patients experienced left ventricular ejection fraction declines ≥10% from baseline to <50%.ConclusionsLong-term DFS and PFS were similar between groups. Patients who achieved tpCR had improved DFS. No new safety signals were identified.
http://ift.tt/2B19G8c
Phase II trial of veliparib in patients with previously treated BRCA-mutated pancreas ductal adenocarcinoma
Source:European Journal of Cancer, Volume 89
Author(s): Maeve A. Lowery, David P. Kelsen, Marinela Capanu, Sloane C. Smith, Jonathan W. Lee, Zsofia K. Stadler, Malcolm J. Moore, Hedy L. Kindler, Talia Golan, Amiel Segal, Hannah Maynard, Ellen Hollywood, MaryEllen Moynahan, Erin E. Salo-Mullen, Richard Kinh Gian Do, Alice P. Chen, Kenneth H. Yu, Laura H. Tang, Eileen M. O'Reilly
PurposeBRCA-associated cancers have increased sensitivity to poly(ADP-ribose) polymerase inhibitors (PARPis). This single arm, non-randomised, multicentre phase II trial evaluated the response rate of veliparib in patients with previously treated BRCA1/2- or PALB2-mutant pancreatic adenocarcinoma (PDAC).MethodsPatients with stage III/IV PDAC and known germline BRCA1/2 or PALB2 mutation, 1–2 lines of treatment, Eastern Cooperative Oncology Group 0–2, were enrolled. Veliparib was dosed at a volume of 300 mg twice-daily (N = 3), then 400 mg twice-daily (N = 15) days 1–28. The primary end-point was to determine the response rate of veliparib; secondary end-points included progression-free survival (PFS), duration of response, overall survival (OS) and safety.ResultsSixteen patients were enrolled; male N = 8 (50%). Median age was 52 years (range 43–77). Five (31%) had a BRCA1 and 11 (69%) had a BRCA2 mutation. Fourteen (88%) patients had received prior platinum-based therapy. No confirmed partial responses (PRs) were seen: one (6%) unconfirmed PR was observed at 4 months with disease progression (PD) at 6 months; four (25%) had stable disease (SD), whereas 11 (69%) had PD as best response including one with clinical PD. Median PFS was 1.7 months (95% confidence interval [CI] 1.57–1.83) and median OS was 3.1 months (95% CI 1.9–4.1). Six (38%) patients had grade III toxicity, including fatigue (N = 3), haematology (N = 2) and nausea (N = 1).ConclusionsVeliparib was well tolerated, but no confirmed response was observed although four (25%) patients remained on study with SD for ≥ 4 months. Additional strategies in this population are needed, and ongoing trials are evaluating PARPis combined with chemotherapy (NCT01585805) and as a maintenance strategy (NCT02184195).
http://ift.tt/2AECyjQ
Enlisting the willing: A study of healthcare professional–initiated and opt-in biobanking consent reveals improvement opportunities throughout the registration process
Publication date: January 2018
Source:European Journal of Cancer, Volume 89
Author(s): Elizabeth A. Fradgley, Shu Er Chong, Martine E. Cox, Christine L. Paul, Craig Gedye
Biobanking consent processes should accord with patients' preferences and be offered in a consistent and systematic manner. However, these aims can be difficult to achieve under healthcare professionals' (HCPs) time-constrained workflows, resulting in low participation rates.This current perspective provides a brief overview of HCP involvement in consent and reports new data on participant attrition at each step of the biobanking consent process as experienced by 113 patients at an Australian tertiary cancer centre. To determine attrition in this HCP-driven consent process, we reviewed medical records for the following events: inclusion of biobanking consent forms; visible patient and HCP signatures; consent status selected (decline or accept) and specimen registration with local biobank. Accessible medical records revealed the following data: 75 of 85 records included viewable forms; 22 of 85 records included patient and 19 of 85 included HCP signatures; 15 of 85 records included signed and completed forms and 3 of 85 had samples banked with annotated clinical data. We compared these data with self-reported experiences of being approached to participate by HCPs. Of the 15 participants (17.6%) who successfully completed consent, only five could recall being asked and providing consent.The low enrolment rate is a considerable lost opportunity because most patients (59%) who were not asked to participate indicated they would have consented if asked. Furthermore, in comparing self-reported experiences with medical records, we believe cancer patients' preferences for participation are mismatched with actual biobanking enrolment, which has considerable attrition at each step in the consent process.
http://ift.tt/2B1VVG2
Are pathological high-risk features in locally advanced rectal cancer a useful selection tool for adjuvant chemotherapy?
Source:European Journal of Cancer, Volume 89
Author(s): Marloes Swets, Peter J.K. Kuppen, Erik J. Blok, Hans Gelderblom, Cornelis J.H. van de Velde, Iris D. Nagtegaal
BackgroundSeveral histological high-risk factors are used as an indication for adjuvant therapy in stage II colon cancer. Those and other factors, including lymphatic invasion, perineural invasion (PNI), venous invasion and tumour budding are associated with decreased outcome. In this study, we evaluated the prognostic and predictive values of these biomarkers in a cohort of rectal cancer patients.Materials and methodsThe trial-based cohort consisted of 221npTNM stage II–III rectal cancer patients, included in the PROCTOR/SCRIPT trial, a multicentre randomised phase III trial. Patients treated with neoadjuvant radiotherapy and TME surgery were randomised between adjuvant chemotherapy or observation. Lymphatic invasion, PNI, extramural venous invasion, intramural venous invasion and tumour budding were determined in standard tissue slides.ResultsThe presence of PNI (HR 3.36; 95% CI 1.82–6.21), extramural vascular invasion (HR 1.93; 95% CI 1.17–3.19) and tumour budding (HR 1.83, 95% CI 1.11–3.03) was associated with a significant worse overall survival. The presence of ≥2 adverse biomarkers resulted in a stronger prediction of adverse outcome in terms of overall survival (HR 2.82; 95% CI 1.66–4.79), disease-free survival (HR 2.27; 95% CI 1.47–3.48), and distant recurrence (HR 2.51; 95% CI 1.56–4.02). None of these markers alone or combined predicted a beneficial effect of adjuvant chemotherapy.DiscussionWe confirmed that several stage-independent biomarkers were significantly associated with a decreased outcome in rectal cancer patients. More importantly, these markers did not have predictive value and are thus not useful to select for adjuvant therapy in rectal cancer.
http://ift.tt/2AF2xYe
Reviewers 2017
Source:European Journal of Cancer
http://ift.tt/2B1AmWg
Eighth American Joint Committee on Cancer (AJCC) melanoma classification: Let us reconsider stage III
Source:European Journal of Cancer
Author(s): Jean Jacques Grob, Dirk Schadendorf, Paul Lorigan, Paolo Ascierto, James Larkin, Paul Nathan, Caroline Robert, Axel Hauschild, Jeffrey Weber, Adil Daud, Omid Hamid, Reinhard Dummer, Johan Hansson, Christoph Hoeller, Jacob Schachter, Alexander C.J. Van Akkooi, Claus Garbe
http://ift.tt/2AF2taW
CO2: Editorial Board/Subscription info.
Source:Progress in Neurobiology, Volume 159
http://ift.tt/2k8jPFy
HDAC11 is a regulator of diverse immune functions
Publication date: Available online 6 December 2017
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Cansu Yanginlar, Colin Logie
Histone deacetylases deacetylate histone and non-histone protein targets. Aberrant HDAC expression and function have been observed in several diseases, which makes these enzymes attractive treatment targets. Here, we summarize recent literature that addresses the roles of HDAC11 on the regulation of different immune cells including neutrophils, myeloid derived suppressor cells and T-cells. HDAC11 was initially identified as a negative regulator of the well-known anti-inflammatory cytokine IL-10. Hence, antagonizing HDAC11 activity may have anti-tumor potential, whereas activating HDAC11 may be useful to treat chronic inflammation or autoimmunity. However, to anticipate biological side-effects of HDAC11 modulators, more molecular insights will be required.
http://ift.tt/2B2QNBP
Regulation of tRNA biogenesis in plants and its link to plant growth and response to pathogens
Publication date: Available online 6 December 2017
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Adriana Santos Soprano, Juliana Helena Costa Smetana, Celso Eduardo Benedetti
tRNA biology has fascinated scientists over the years. Besides their fundamental role in protein translation, new evidence indicates that tRNA-derived molecules also regulate gene expression and protein synthesis in all domains of life. In this review, we will highlight some of the recent findings linking tRNA transcription and modification with plant cell growth and response to pathogens. In fact, mutations in proteins directly involved in tRNA synthesis and modification most often lead to pleiotropic effects on plant growth and immunity. As plants need to optimize and balance their energy and nutrient resources towards growth and defense, regulatory pathways that play a central role in integrating tRNA transcription and protein translation with cell growth control and organ development, such as the auxin-TOR signaling pathway, also influence the plant immune response against pathogens. As a consequence, distinct pathogens employ an array of effector molecules including tRNA fragments to target such regulatory pathways to exploit the plant's translational capacity, gain access to nutrients and evade defenses. An example includes the RNA polymerase III repressor MAF1, a conserved component of the TOR signaling pathway that controls ribosome biogenesis and tRNA synthesis required for plant growth and which is targeted by a pathogen effector molecule to promote disease. This article is part of a Special Issue entitled: SI: Regulation of tRNA synthesis and modification in physiological conditions and disease edited by Dr. Boguta Magdalena.
http://ift.tt/2AEcNAb
PARP1 facilitates EP300 recruitment to the promoters of the subset of RBL2-dependent genes
Publication date: Available online 5 December 2017
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Agnieszka Robaszkiewicz, Ewelina Wiśnik, Zsolt Regdon, Kinga Chmielewska, László Virág
Differentiation of human monocytes is associated with proliferation arrest resulting from activation of the inter alia retinoblastoma protein family of gene repressors, which target gene promoters in an E2F-dependent manner. To investigate RBL2 contribution to defining monocyte phenotype and function, we used primer libraries. We identified genes encoding two surface receptors (CXCR1 and IL17RE) and two TLR signaling mediators (CD86 and NFKB2) that are repressed by the RBL2-E2F4-HDAC1-BRM complex. Surprisingly, PARP1 co-regulated 24 out of the 28 identified genes controlled by RBL2. Upon RBL2 silencing, PARP1 was recruited to one subset of RBL2-dependent genes, represented by MAP2K6 and MAPK3. RBL2 silencing also restored PARP1 transcription. Gene promoters enriched in PARP1 were characterized by increased histone acetylation and the replacement of HDAC1 with EP300. While PARP1 was dispensable for HDAC1 dissociation, EP300 was found only at gene promoters enriched in PARP1. EP300 activated transcription of PARP1/RBL2 co-regulated genes, but not genes solely controlled by RBL2. DNA was a prerequisite to the formation of an immunoprecipitated PARP1-EP300 complex, suggesting that PARP1 enabled EP300 binding, which in turn activated gene transcription. Notably, PARP1 overexpression failed to overcome the inhibitory effect of RBL2 on MAP2K6 and MAPK3 transcription. The same interdependence was observed in proliferating cancer cells; the low abundance of RBL2 resulted in PARP1-mediated EP300 recruitment to promoters of the MAP2K6 and MAPK3 genes. We conclude that RBL2 may indirectly regulate transcription of some genes by controlling PARP1-mediated EP300 recruitment.
Graphical abstract
http://ift.tt/2B2QM0J
Cooperativity between different tRNA modifications and their modification pathways
Publication date: Available online 5 December 2017
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Mikołaj Sokołowski, Roland Klassen, Alexander Bruch, Raffael Schaffrath, Sebastian Glatt
Ribonucleotide modifications perform a wide variety of roles in synthesis, turnover and functionality of tRNA molecules. The presence of particular chemical moieties can refine the internal interaction network within a tRNA molecule, influence its thermodynamic stability, contribute novel chemical properties and affect its decoding behavior during mRNA translation. As the lack of specific modifications in the anticodon stem and loop causes disrupted proteome homeostasis, diminished response to stress conditions, and the onset of human diseases, the underlying modification cascades have recently gained particular scientific and clinical interest. Nowadays, a complicated but conclusive image of the interconnectivity between different enzymatic modification cascades and their resulting tRNA modifications emerges. Here we summarize the current knowledge in the field, focusing on the known instances of cross talk among the enzymatic tRNA modification pathways and the consequences on the dynamic regulation of the tRNA modificome by various factors. This article is part of a Special Issue entitled: SI: Regulation of tRNA synthesis and modification in physiological conditions and disease edited by Dr. Boguta Magdalena.
http://ift.tt/2AZLXoE
5-Azacytidine engages an IRE1α-EGFR-ERK1/2 signaling pathway that stabilizes the LDL receptor mRNA
Publication date: Available online 5 December 2017
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Nourhen Mnasri, Maya Mamarbachi, Bruce G. Allen, Gaétan Mayer
Hepatic low-density lipoprotein receptor (LDLR) is the primary conduit for the clearance of plasma LDL-cholesterol and increasing its expression represents a central goal for treating cardiovascular disease. However, LDLR mRNA is unstable and undergoes rapid turnover mainly due to the three AU-rich elements (ARE) in its proximal 3′-untranslated region (3′-UTR). Herein, our data revealed that 5-azacytidine (5-AzaC), an antimetabolite used in the treatment of myelodysplastic syndrome, stabilizes the LDLR mRNA through a previously unrecognized signaling pathway resulting in a strong increase of its protein level in human hepatocytes in culture. 5-AzaC caused a sustained activation of the inositol-requiring enzyme 1α (IRE1α) kinase domain and c-Jun N-terminal kinase (JNK) independently of endoplasmic reticulum stress. This resulted in activation of the epidermal growth factor receptor (EGFR) and extracellular signal-regulated kinase1/2 (ERK1/2) that, in turn, stabilized LDLR mRNA. Systematic mutation of the AREs (ARE1-3) in the LDLR 3′UTR and expression of each mutant coupled to a luciferase reporter in Huh7 cells demonstrated that ARE1 is required for rapid LDLR mRNA decay and 5-AzaC-induced mRNA stabilization via the IRE1α-EGFR-ERK1/2 signaling cascade. The characterization of this pathway will help to reveal potential targets to enhance plasma LDL clearance and novel cholesterol-lowering therapeutic strategies.
http://ift.tt/2AGcaWW
Regulation of tRNA gene transcription by the chromatin structure and nucleosome dynamics
Publication date: Available online 5 December 2017
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Ashutosh Shukla, Purnima Bhargava
The short, non-coding genes transcribed by the RNA polymerase (pol) III, necessary for survival of a cell, need to be repressed under the stress conditions in vivo. The pol III-transcribed genes have adopted several novel chromatin-based regulatory mechanisms to their advantage. In the budding yeast, the sub-nucleosomal size tRNA genes are found in the nucleosome-free regions, flanked by positioned nucleosomes at both the ends. With their chromosomes-wide distribution, all tRNA genes have a different chromatin context. A single nucleosome dynamics controls the accessibility of the genes for transcription. This dynamics operates under the influence of several chromatin modifiers in a gene-specific manner, giving the scope for differential regulation of even the isogenes within a tRNA gene family. The chromatin structure around the pol III-transcribed genes provides a context conducive for steady-state transcription as well as gene-specific transcriptional regulation upon signaling from the environmental cues.This article is part of a Special Issue entitled: SI: Regulation of tRNA synthesis and modification in physiological conditions and disease edited by Dr. Boguta Magdalena.
http://ift.tt/2AZLUsY
tRNA dynamics between the nucleus, cytoplasm and mitochondrial surface: Location, location, location
Publication date: Available online 28 November 2017
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Kunal Chatterjee, Regina T. Nostramo, Yao Wan, Anita K. Hopper
Although tRNAs participate in the essential function of protein translation in the cytoplasm, tRNA transcription and numerous processing steps occur in the nucleus. This subcellular separation between tRNA biogenesis and function requires that tRNAs be efficiently delivered to the cytoplasm in a step termed "primary tRNA nuclear export". Surprisingly, tRNA nuclear-cytoplasmic traffic is not unidirectional, but, rather, movement is bidirectional. Cytoplasmic tRNAs are imported back to the nucleus by the "tRNA retrograde nuclear import" step which is conserved from budding yeast to vertebrate cells and has been hijacked by viruses, such as HIV, for nuclear import of the viral reverse transcription complex in human cells. Under appropriate environmental conditions cytoplasmic tRNAs that have been imported into the nucleus return to the cytoplasm via the 3rd nuclear-cytoplasmic shuttling step termed "tRNA nuclear re-export", that again is conserved from budding yeast to vertebrate cells. We describe the 3 steps of tRNA nuclear-cytoplasmic movements and their regulation. There are multiple tRNA nuclear export and import pathways. The different tRNA nuclear exporters appear to possess substrate specificity leading to the tantalizing possibility that the cellular proteome may be regulated at the level of tRNA nuclear export. Moreover, in some organisms, such as budding yeast, the pre-tRNA splicing heterotetrameric endonuclease (SEN), which removes introns from pre-tRNAs, resides on the cytoplasmic surface of the mitochondria. Therefore, we also describe the localization of the SEN complex to mitochondria and splicing of pre-tRNA on mitochondria, which occurs prior to the participation of tRNAs in protein translation. This article is part of a Special Issue entitled: SI: Regulation of tRNA synthesis and modification in physiological conditions and disease edited by Dr. Boguta Magdalena.
http://ift.tt/2AEyK22
Elongator—a tRNA modifying complex that promotes efficient translational decoding
Publication date: Available online 21 November 2017
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Marcus J.O. Johansson, Fu Xu, Anders S. Byström
Naturally occurring modifications of the nucleosides in the anticodon region of tRNAs influence their translational decoding properties. Uridines present at the wobble position in eukaryotic cytoplasmic tRNAs often contain a 5-carbamoylmethyl (ncm5) or 5-methoxycarbonylmethyl (mcm5) side-chain and sometimes also a 2-thio or 2′-O-methyl group. The first step in the formation of the ncm5 and mcm5 side-chains requires the conserved six-subunit Elongator complex. Although Elongator has been implicated in several different cellular processes, accumulating evidence suggests that its primary, and possibly only, cellular function is to promote modification of tRNAs. In this review, we discuss the biosynthesis and function of modified wobble uridines in eukaryotic cytoplasmic tRNAs, focusing on the in vivo role of Elongator-dependent modifications in Saccharomyces cerevisiae. This article is part of a Special Issue entitled: SI: Regulation of tRNA synthesis and modification in physiological conditions and disease edited by Dr. Boguta Magdalena.
http://ift.tt/2AZBJEL
The Fine Wire Technique for Flexor Tenolysis
Background: Flexor tenolysis surgery for flexor digitorum profundus and superficialis adhesions is a common procedure performed by hand surgeons. Releasing these adhered tendons can greatly improve hand function and improve quality of life. Recent evidence, however, has shown that the outcomes of tenolysis surgeries are often suboptimal and can result in relapsing adhesions or even tendon ruptures. Methods: This article describes a new technique with potential for reduced complication rates: The Fine Wire Technique for Flexor Tenolysis (FWT). Results: Following FWT, the patient detailed in this article had an excellent recovery of function and no complications: including tendon rupture, infection, hematomas, or any other complications. She reported a major improvement from her preoperative functionality and continues to have this level of success. The wire's thinness allows for a swift tenolysis. Conclusions: The FWT is a new option available to the hand surgeon associated with good functional results. The wire is readily available to the clinician and is also inexpensive.http://ift.tt/2j0AIoS
Dynamic Model of Applied Facial Anatomy with Emphasis on Teaching of Botulinum Toxin A
Background: The use of botulinum toxin type A is considered one of the most revolutionary and promising face rejuvenation methods. Although rare, most of the complications secondary to the use of botulinum toxin A are technician dependent. Among the major shortcomings identified in the toxin administration education is unfamiliarity with applied anatomy. This article proposes the use of body painting as an innovative method of teaching the application of botulinum toxin A. Methods: Using the body painting technique, facial anatomy was represented on the face of a model showing the major muscle groups of botulinum toxin A targets. Photographic records and films were made for documentation of represented muscles at rest and contraction. Results: Using the body painting technique, each of the muscles involved in facial expression and generation of hyperkinetic wrinkles can be faithfully reproduced on the model's face. The documentation of the exact position of the points of application, the distribution of the feature points in the muscular area, the proper angulation and syringe grip, as well as the correlation of the points of application with the presence of hyperkinetic wrinkles, could be properly registered, providing professional training with information of great practical importance, development of highly effective treatments, and low complication rates. Conclusion: By making it possible to interrelate anatomy of a function, body painting is proposed in the present study as an innovative method, which in a demonstrative and highly didactic manner presents great potential as a teaching tool in the application of botulinum toxin A.http://ift.tt/2j17iXN
Potential vulnerability of oak forests to climate change-induced flooding: effects of mild oxygen deficiency on Quercus robur and Quercus petraea seedling physiology
Abstract
Flooding is characterized by saturation of soil pores with water, leading to hypoxic conditions which affect plant root development and metabolism. We investigated the oxygen deficiency tolerance observed in Quercus robur and Quercus petraea and seek to understand whether it can be explained by enhanced efficiency in oxygen use in the roots, as estimated through radial oxygen loss visualization in relation to growth measurements and root apex respiration. The study showed that root growth, under oxygen deficiency conditions, was significantly reduced only in Q. robur seedlings. Root respiration was maintained in Q. robur, whereas it was decreased in Q. petraea. Both species set up a barrier against radial oxygen loss, though measurement of apex oxygen leakage showed greater oxygen efficiency in Q. robur seedlings. This strategy might allow Q. robur to maintain its respiration and thus to survive longer under oxygen deficiency conditions by facilitating the seedling establishment in transient flooded soils.
http://ift.tt/2AXxB8v
Revisiting the alerting effect of light; a systematic review
Light plays an essential role in maintaining alertness levels. Like other non-image-forming responses, the alerting effect of light is influenced by its spectral wavelength, duration and intensity. Alertness levels are also dependent on circadian rhythm (Process C) and homeostatic sleep pressure (Process S), consistent with the classic two-process model of sleep regulation. Over the last decade, there has been increasing recognition of an additional process (referred to as the third process) in sleep regulation.
http://ift.tt/2AncnkU
Muscle recruitment and coordination during upper-extremity functional tests
Source:Journal of Electromyography and Kinesiology
Author(s): Keshia M. Peters, Valerie E. Kelly, Tasha Chang, Madeline C. Weismann, Sarah Westcott-McCoy, Katherine M. Steele
Performance-based tests, such as the Jebsen Taylor Hand Function Test or Chedoke Arm and Hand Activity Inventory, are commonly used to assess functional performance after neurologic injury. However, the muscle activity required to execute these tasks is not well understood, even for unimpaired individuals. The purpose of this study was to evaluate unimpaired muscle recruitment and coordination of the dominant and non-dominant limbs during common clinical tests. Electromyography (EMG) recordings from eight arm muscles were monitored bilaterally for twenty unimpaired participants while completing these tests. Average signal magnitudes, activation times, and cocontraction levels were calculated from the filtered EMG data, normalized by maximum voluntary isometric contractions (MVICs). Overall, performance of these functional tests required low levels of muscle activity, with average EMG magnitudes less than 6.5% MVIC for all tests and muscles, except the extensor digitorum, which had higher activations across all tasks (11.7±2.7% MVIC, dominant arm). When averaged across participants, cocontraction was between 25-62% for all tests and muscle pairs. Tasks evaluated by speed of completion, rather than functional quality of movement demonstrated higher levels of muscle recruitment. These results provide baseline measurements that can be used to evaluate muscle-specific deficits after neurologic injury and track recovery using common clinical tests.
http://ift.tt/2ky0Fwy
Alteration of autophagy-related proteins in peripheral blood mononuclear cells of patients with Parkinson's disease
Source:Neurobiology of Aging, Volume 63
Author(s): Yasuo Miki, Shuji Shimoyama, Tomoya Kon, Tatsuya Ueno, Ryo Hayakari, Kunikazu Tanji, Tomoh Matsumiya, Eiki Tsushima, Fumiaki Mori, Koichi Wakabayashi, Masahiko Tomiyama
Previous postmortem studies demonstrated dysregulation of autophagy in patients with Parkinson's disease (PD). To clarify whether this alteration reflects a fundamental aspect of PD or represents the final stage of autophagy dysregulation resulting from a long neurodegenerative process, we focused on basal autophagy in peripheral blood mononuclear cells (PBMCs) of PD patients (n = 35) and controls (n = 23). The whole-transcriptome assay revealed downregulation of mRNAs for 6 core regulators of autophagy (UNC-51-like kinase [ULK] 3, autophagy-related [Atg] 2A, Atg4B, Atg5, Atg16L1, and histone deacetylase 6). Reverse transcription–polymerase chain reaction and Western blot analysis confirmed significantly increased protein levels of upstream autophagy (ULK1, Beclin1, and autophagy/beclin1 regulator 1) with negative feedback of mRNA expression for these proteins in PD. These protein levels were correlated with increased levels of α-synuclein in PBMCs. The expression level of the oligomeric form of α-synuclein in PBMCs paralleled the clinical severity of PD and the degeneration of cardiac sympathetic nerves. Basal activity of autophagy can be lower in patients with PD. Alteration of basal autophagy may be a fundamental aspect of PD.
http://ift.tt/2jrv6kR
Striking a chord with healthy aging: memory system cooperation is related to preserved configural response learning in older adults
Source:Neurobiology of Aging, Volume 63
Author(s): Michelle W. Voss, Rachel Clark, Michael Freedberg, Timothy Weng, Eliot Hazeltine
Evidence from tasks that primarily tap either hippocampal- or striatal-based memory systems suggests that although these systems often compete for control of behavior, aging is associated with greater cooperation between them. This may stem from altered prefrontal cortex function. Here, we use a configural response task designed to engage both memory systems to test how age affects their interaction with cortical regions including the prefrontal cortex. We found that although older and younger adults learned just as well, older adults showed greater initial activation in cortical networks associated with visuospatial-action mapping and resolving conflict for competing memory representations. Older adults also showed greater functional coupling of the striatum with the left inferior frontal gyrus, in parallel with similar hippocampal coupling to ventral visual regions as young adults. Overall, our results support the proposal that aging is associated with more cooperative memory systems, but we did not find that greater cooperation is associated with less interaction between the prefrontal cortex and core memory system structures during learning.
http://ift.tt/2ADLUyv
Assessment of debris inputs from land into the river in the Three Gorges Reservoir Area, China
Abstract
Riverine debris in the Three Gorges Reservoir Area (TGRA) poses a threat to electricity generation, ship navigation, and water environment. Quantifying riverine debris inputs from land into the river is a foundation for modeling of the transport and accumulation of floating debris on the water surface in the TGRA. However, this has not been researched to date. In this study, debris inputs from land into the river in the TGRA were assessed according to the response relationship between debris inputs and surface runoff. The land-based debris inputs in the TGRA were estimated using simulated surface runoff which was simulated by the Soil and Water Assessment Tool (SWAT) model. Results showed that 15.32 × 106 kg of land-based debris was inputted into the main channel of the TGRA in 2015 which accounted for 9.74% of total debris inputs (the monitoring data of river-sourced and land-sourced debris inputs was 157.27 × 106 kg). Debris inputs varied seasonally and peaked in the summer season (July to September). Compared with monthly measured data, the average relative errors in 2015 were below 30%. In addition, areas with higher debris pollution inputs were mainly located in the upper section of the TGRA, between the Tang River Basin and the Long River Basin. The proposed method was tested and determined to be reliable; thus, it can be used to quickly estimate debris inputs from land into the river by surface runoff of the outlets in a river basin. Moreover, this method provides new insight into the estimation of land-based debris inputs into rivers.
http://ift.tt/2iAZBUr
Time resolution requirements for civilian radioxenon emission data for the CTBT verification regime
Source:Journal of Environmental Radioactivity, Volume 182
Author(s): Pieter De Meutter, Johan Camps, Andy Delcloo, Benoît Deconninck, Piet Termonia
The capability of the noble gas component of the International Monitoring System as a verification tool for the Comprehensive Nuclear-Test-Ban Treaty is deteriorated by a background of radioxenon emitted by civilian sources. One of the possible approaches to deal with this issue, is to simulate the daily radioxenon concentrations from these civilian sources at noble gas stations by using atmospheric transport models. In order to accurately quantify the contribution from these civilian sources, knowledge on the releases is required. However, such data are often not available and furthermore it is not clear what temporal resolution such data should have. In this paper, we assess which temporal resolution is required to best model the 133Xe contribution from civilian sources at noble gas stations in an operational context. We consider different sampling times of the noble gas stations and discriminate between nearby and distant sources. We find that for atmospheric transport and dispersion problems on a scale of 1000 km or more, emission data with subdaily temporal resolution is generally not necessary. However, when the source-receptor distance decreases, time-resolved emission data become more important. The required temporal resolution of emission data thus depends on the transport scale of the problem. In the context of the Comprehensive Nuclear-Test-Ban Treaty, where forty noble gas stations will monitor the whole globe, daily emission data are generally sufficient, but for certain meteorological conditions, better temporally resolved emission data are required.
http://ift.tt/2BKWpxf
Chemical properties and colors of fermenting materials in salmon fish sauce production
Source:Data in Brief, Volume 16
Author(s): Mitsutoshi Nakano, Yoshimasa Sagane, Ryosuke Koizumi, Yozo Nakazawa, Masao Yamazaki, Toshihiro Watanabe, Katsumi Takano, Hiroaki Sato
This data article reports the chemical properties (moisture, pH, salinity, and soluble solid content) and colors of fermenting materials in salmon fish sauce products. The fish sauce was produced by mixing salt with differing proportions of raw salmon materials and fermenting for three months; the salmon materials comprised flesh, viscera, an inedible portion, and soft roe. Chemical properties and colors of the unrefined fish sauce (moromi), and the refined fish sauce, were analyzed at one, two, and three months following the start of fermentation. Data determined for all products are provided in table format.
http://ift.tt/2nGqr2M
The metagenome of Caracolus marginella gut microbiome using culture independent approaches and shotgun sequencing
Source:Data in Brief, Volume 16
Author(s): Robert J. Rabelo-Fernandez, Kevin Santiago-Morales, Luis Morales-Vale, Carlos Rios-Velazquez
Studies underestimate the microbial diversity and genotypic traits in the snails' microbiome. Caracolus marginella, a land snail native to Caribbean islands, can adapt to different environments. Our research focused on the generation of a metagenomic library from C. marginella gut, to further explore the diversity and functional traits. Thirty specimens of C. marginella were collected from the four regions of Puerto Rico. High molecular weight (40kb) metagenomic libraries were generated using a direct DNA isolation method. DNA was end-repaired and ligated into a pCCFOS1 fosmid vector; then, the cloned DNA was transduced into Escherichia coli EPI300. The master pool library contains approximately 60,200 clones and restriction enzyme digestion showed that 90% of the library contains insert. After removing the fosmid and host genome sequences, 567,015 sequences were analyzed using the MG-RAST online server. The Bacteria domain was the most abundant (82.15%), followed by viruses (16.49%), eukaryotes (0.83%) and archaea (0.31%). The Proteobacteria (51.47%) was predominant in the gut environment, followed by unidentified virus (16.28%), and Actinobacteria (8.52%). Escherichia coli, Streptomyces avermitilis, and Burkholderia sp. were the most abundant species present. Subsystem functional analysis showed that 35.00% of genes belong to transposable elements, 10.00% of genes belong to clustering-based subsystems, 4.00% of genes belong to the production of cofactors and secondary metabolites, and 2.00% resistance to antibiotics and toxic compounds. The data generated in this research is the first metagenomic examination of a snail gut in Puerto Rico, and will serve as a baseline to start understanding of C. marginella gut microbiome.
http://ift.tt/2zZ7Cd0
Magnetic record of Mio-Pliocene red clay and Quaternary loess-paleosol sequence in the Chinese Loess Plateau
Source:Data in Brief, Volume 16
Author(s): Yougui Song
This article presents magnetic data of a 300-m-thick Mio-Pliocene red clay and Quaternary loess-paleosol sequence near Chaona town in the Central Chinese Loess Plateau. Detailed magnetostratigraphy shows that the aeolian red clay began to accumulate at ca. 8.1Ma. Here, we presented a high-resolution rock magnetic data at 20–40cm intervals within 4.5–8ka span per sample of this section, which has been published in Song et al. (2014) [1] and (2017) [2]. The dataset including the following magnetic parameters: mass magnetic susceptibility (χ), frequency-dependent susceptibility (χfd), saturation magnetization (Ms), saturation remanent magnetization (Mrs), coercive force (Bc), remanent coercivity (Bcr), saturation isothermal remanent magnetization (SIRM) and S-ratio. Magnetic susceptibility and hysteresis parameters were measured at Lanzhou University and Kyoto University, respectively. This data provides a high-resolution rock magnetic evidences for understanding East Asia Monsoon change, Asian interior aridification and tectonic effect of the uplift of the Tibetan Plateau since middle Miocene period.
http://ift.tt/2nGLSAG
Draft genomes of Enterococcus faecium strains isolated from human feces before and after eradication therapy against Helicobacter pylori
Source:Data in Brief, Volume 16
Author(s): Nikita A. Prianichnikov, Maja V. Malakhova, Vlad V. Babenko, Andrei K. Larin, Evgenii I. Olekhnovich, Elizaveta V. Starikova, Dmitry I. Chuvelev, Oksana E. Glushchenko, Andrei E. Samoilov, Alexander I. Manolov, Boris A. Kovarsky, Alexander V. Tyakht, Alexander V. Pavlenko, Elena N. Ilina, Elena S. Kostryukova
The abundance of Enterococci in the human intestinal microbiota environment is usually < 0.1% of the total bacterial fraction. The multiple resistance to antibiotics of the opportunistic Enterococcus spp. is alarming for the world medical community because of their high prevalence among clinically significant strains of microorganisms. Enterococci are able to collect different mobile genetic elements and transmit resistance to antibiotics to wide range of Gram-positive and Gram-negative species of microorganisms, including the transmission of vancomycin resistance to methicillin-resistant strains of Staphylococcus aureus. The number of infections caused by antibiotics resistant strains of Enterococcus spp. is increasing. Here we present a draft genomes of Enterococcus faecium strains. These strains were isolated from human feces before and after (1 month) Helicobacter pylori eradication therapy. The samples were subject to whole-genome sequencing using Illumina HiSeq. 2500 platform. The data is available at NCBI http://ift.tt/2nDbgHS.
http://ift.tt/2zYfg7f
Can we refine body mass estimations based on femoral head breadth?
Source:Journal of Human Evolution
Author(s): Markku Niskanen, Juho-Antti Junno, Heli Maijanen, Brigitte Holt, Vladimir Sladék, Margit Berner
Femoral head breadth is widely used in body mass estimation in biological anthropology. Earlier research has demonstrated that reduced major axis (RMA) equations perform better than least squares (LS) equations. Although a simple RMA equation to estimate body size from femoral head breadth is sufficient in most cases, our experiments with male skeletons from European data (including late Pleistocene and Holocene skeletal samples) and the Forensic Anthropology Data Bank data (including the W. M. Bass Donated Skeletal Collection sample) show that including femoral length or anatomically estimated stature in an equation with femoral head breadth improves body mass estimation precision. More specifically, although directional bias related to body mass is not reduced within specific samples, the total estimation error range, directional bias related to stature, and temporal fluctuation in estimation error are markedly reduced. The overall body mass estimation precision of individuals representing different temporal periods and ancestry groups (e.g., African and European ancestry) is thus improved.
http://ift.tt/2AmpTVS
Multi-agent chemotherapy in advanced soft tissue sarcoma (STS) – A systematic review and meta-analysis
Source:Cancer Treatment Reviews
Author(s): Alona Zer, Rebecca M. Prince, Eitan Amir, Albiruni R Abdul Razak
BackgroundDespite a lack of improvement in overall survival (OS) with doxorubicin-based combinations over doxorubicin alone in advanced STS, the role of multi-agent chemotherapy remains poorly defined.MethodsWe conducted a systematic review and meta-analysis to evaluate benefits and harms of multi-agent chemotherapy in advanced STS. Eligible studies were randomized trials of chemotherapy in advanced STS comparing single agent to multi-agent therapy. Data from studies reporting a hazard ratio (HR) and 95% confidence intervals (CI) for OS and progression-free survival (PFS) were pooled in a meta-analysis. Meta-regression was utilized to explore the association between efficacy (OS and PFS) and both toxicity and dose intensity.ResultsWe identified 22 trials published between 1974 and April 2016 and comprising 5044 patients. Overall, multi-agent chemotherapy was associated with improved OS (HR:0.79, p=0.02), and borderline improvement in PFS (HR:0.86, p=0.05). While the effect on OS was similar in trials with non-anthracycline controls compared to those with anthracycline controls (HR for OS 0.73 vs. 0.82, p for difference=0.63) there was a non-significantly greater effect for multi-agent chemotherapy on PFS in non-anthracycline RCT (HR for PFS 0.73 vs. 0.91, p for difference=0.13). Compared to studies with cytotoxic therapy-based multi-agent therapy, a non-significantly greater magnitude of effect among studies with biological/cytostatic experimental groups was seen (HR for OS 0.64 vs. 0.86, p for difference=0.37). There was a borderline significant association between dose reductions (which were more common in combination arms) and worse PFS (beta=0.70, p=0.053).ConclusionMulti-agent chemotherapy is associated with a modest, but statistically significant improvement in outcomes in STS. Combining chemotherapy with non-cytotoxic agents might represent a promising strategy.
http://ift.tt/2jrwkMF
What motivates women to breastfeed in Lebanon: An exploratory qualitative analysis
Source:Appetite, Volume 123
Author(s): Sarah BouDiab, Carolina Werle
This exploratory qualitative study examined the influence of injunctive and descriptive norms on breastfeeding, a health-improving behaviour related to a highly committed personal decision. The research explores the different mechanisms through which social norms impact breastfeeding behaviour pre or post-adoption of breastfeeding practice.A qualitative approach was used by performing in-depth analysis of cross-sectional accounts of women in Lebanon contemplating adoption of breastfeeding practice and women who already breastfed. Interviews were also conducted with medical professionals, lactation specialists, and breastfeeding activists.On one hand, the attitude of the medical professionals and the government efforts are two mechanisms that stimulate the injunctive norms. On the other hand, the descriptive norms are defined by community attitude aggregated with societal beliefs and expectations on women's image and role in society. Both types of social norms are in constant interplay with personal norms and each type becomes more salient at different periods over time.The findings suggest that social norms are major determinants of breastfeeding behaviour. The influence of the type of social norm—descriptive or injunctive—on the decision to breastfeed varies according to the moment of life the mother is living. Theoretical and practical implications are discussed.
http://ift.tt/2jqlsyP
Initial validation of the Nine Item Avoidant/Restrictive Food Intake disorder screen (NIAS): A measure of three restrictive eating patterns
Source:Appetite, Volume 123
Author(s): Hana F. Zickgraf, Jordan M. Ellis
Avoidant/Restrictive Food Intake Disorder (ARFID) is an eating or feeding disorder characterized by inadequate nutritional or caloric intake leading to weight loss, nutritional deficiency, supplement dependence, and/or significant psychosocial impairment. DSM-5 lists three different eating patterns that can lead to symptoms of ARFID: avoidance of foods due to their sensory properties (e.g., picky eating), poor appetite or limited interest in eating, or fear of negative consequences from eating. Research on the prevalence and psychopathology of ARFID is limited by the lack of validated instruments to measure these eating behaviors. The present study describes the development and validation of the nine-item ARFID screen (NIAS), a brief multidimensional instrument to measure ARFID-associated eating behaviors. Participants were 455 adults recruited on Amazon's Mechanical Turk, 505 adults recruited from a nationally-representative subject pool, and 311 undergraduates participating in research for course credit. Exploratory and confirmatory factor analyses provided evidence for three factors. The NIAS subscales demonstrated high internal consistency, test-retest reliability, invariant item loadings between two samples, and convergent/discriminant validity with other measures of picky eating, appetite, fear of negative consequences, and psychopathology. The scales were also correlated with measures of ARFID-like symptoms (e.g., low BMI, low fruit/vegetable variety and intake, and eating-related psychosocial interference/distress), although the picky eating, appetite, and fear scales had distinct independent relationships with these constructs. The NIAS is a brief, reliable instrument that may be used to further investigate ARFID-related eating behaviors.
http://ift.tt/2ACANpd
Blocking IL4- and IL13-mediated phosphorylation of STAT6 (Tyr641) decreases M2 polarization of macrophages and protects against macrophage-mediated radioresistance of inflammatory breast cancer
Publication date: Available online 7 December 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Omar M. Rahal, Adam R. Wolfe, Pijus K. Mandal, Richard Larson, Sanda Tin, Cristina Jimenez, Dadong Zhang, Janet Horton, James M. Reuben, John S. McMurray, Wendy A. Woodward
PurposeThe purpose of this study was to determine the role of macrophage polarization on the response of IBC cells to radiation and whether modulation of macrophage plasticity can alter radiation response.Methods and MaterialsThe human THP-1 monocyte cell line and primary human monocytes isolated from peripheral blood mononuclear cells were differentiated into macrophages and polarized to either an "anti-tumor" (M1) or a "pro-tumor" (M2) phenotype. These polarized macrophages were co-cultured with IBC cells (SUM149, KPL4, MDA-IBC3, or SUM190) without direct contact for 24 h, then subjected to irradiation (0, 2, 4, or 6 Gy). Interleukin (IL)4/IL13-induced activation of STAT6 signaling was measured by Western blotting of phospho-STAT6 (Tyr641), and expression of M2 polarization gene markers (CD206, fibronectin, and CCL22) was measured by qPCR.ResultsExpression of M2 polarization markers was higher in M2-polarized macrophages after IL4/IL13 treatment than in control (M0) or M1-polarized macrophages. Co-culture of IBC cell lines with M1-polarized THP-1 macrophages mediated radiosensitivity of IBC cells, while co-culture with M2-polarized macrophages mediated radioresistance. Phosphopeptide mimetic PM37, targeting the SH2 domain of STAT6, prevented and reversed IL4/IL13-mediated STAT6 phosphorylation (Tyr641) and decreased the expression of M2 polarization markers. Pretreatment of M2-THP1 macrophages with PM37 reduced the radioresistance they induced in IBC cells after co-culture. Targeted proteomics analysis of IBC KPL4 cells using a kinase antibody array revealed induction of PRKCZ in these cells only after co-culture with M2-THP1 macrophages, which was prevented by PM37 pretreatment. KPL4 cells with stable shRNA knockdown of PRKCZ exhibited lower radioresistance after M2-THP1 co-culture.ConclusionsThese data suggest that inhibition of M2 polarization of macrophages by PM37 can prevent radioresistance of IBC by downregulating PRKCZ.
Teaser
Here we show that M2-polarized macrophages upon co-culture with IBC cells, promote radioresistance of IBC cells, and this effect was inhibited by PM37, a phosho-STAT6 inhibitor. M2-macrophages mediated radioresistance of KPL4 IBC cells is associated with increased protein expression of PRKCZ kinase in KPL4 cells, after M2-macrophage co-culture, and this was prevented by PM37-mediated inhibition of M2 polarization of THP1 macrophages prior to coculture with KPL4 cells.http://ift.tt/2B0c6DV
Effects of miR-200a and FH535 combined with taxol on proliferation and invasion of gastric cancer
Publication date: Available online 6 December 2017
Source:Pathology - Research and Practice
Author(s): Xi Liu, Ping Du, Lei Han, Anling Zhang, Kui Jiang, Qingyu Zhang
Gastric cancer is one of the most common cancers in the world; taxol displayed modest efficacy as first-line chemotherapy for gastric cancer, conversely, it has limitations used alone. β-catenin is a multifunctional oncogenic protein and the elevation in expression and activity of β-catenin has been implicated in many cancers. Therefore, we assume that the inhibition of β-catenin can enhanced the efficacy of taxol. The purpose of this study was to investigate the inhibitory effect of miR-200a mimics, FH535 combined with taxol on proliferation and invasion of human gastric cancer cell lines SGC-7901 and BGC-823. In the current study, we identified that the combination of FH535 and miR-200a with taxol had potent growth-inhibitory and pro-apoptotic effects. Further, similar results were also observed in vivo, intratumoral injection of FH535, taxol and miR-200a mimics which also delayed tumor growth in nude mice harboring subcutaneous SGC-7901 xenografts. Collectively, miR-200a and FH535 can enhance the inhibitory effect of taxol on cell proliferation and moderate the invasion of human gastric cancer.
http://ift.tt/2AWgljX
Rare frameshift mutations of putative tumor suppressor genes CSMD1 and SLX4 in colorectal cancers
Publication date: Available online 6 December 2017
Source:Pathology - Research and Practice
Author(s): Ju Hwa Lee, Chang Hyeok An, Min Sung Kim, Nam Jin Yoo, Sug Hyung Lee
http://ift.tt/2AF9Wag
Immunophenotypic profile of tumor buds in breast cancer
Publication date: Available online 5 December 2017
Source:Pathology - Research and Practice
Author(s): C Laedrach, Bodour Salhia, N Cihoric, I Zlobec, C Tapia
BackgroundTumor buds are associated with lympho-vascular invasion and lymph node metastases leading to the assumption that they are involved in the early metastatic process. Hence, it would be important to know if tumor buds can be targeted with the most widely used targeted therapies in breast cancer (BC) and if changes in hormone and Her2 status occur. The aim of this study was to answer these questions by determining whether hormone receptor (HR) and Her2 status are expressed in the tumor buds of a large cohort of BCs.DesignWe constructed a tumor bud next-generation tissue microarray (ngTMA) consisting of n=199 BCs of non-special type. Generally, two 1mm punches were taken from the tumor bud areas in the periphery (PTB) and within the tumor center (ITB). HR and Her2 status was assessed using immunohistochemistry and fluorescence in situ hybridization, respectively. HR status was positive if ≥1% of tumor bud cells were positive. Her2 status was considered positive if bud cells showed strong complete membranous Her2 over-expression or Her2 amplification.ResultsMost tumor buds were positive for estrogen (ER) (PTB: 86%; ITB: 88.3) and progesterone receptor (PgR) (PTB: 72%; ITB: 72.8%) and Her2 was positive in: PTB 11.5% and ITB 11%. A difference between the main tumor mass and tumor buds (PTB and ITB) was seen for PgR in 3.5% of cases (n=7). No differences were seen for ER and Her2 between tumor buds and main tumor mass.ConclusionMost tumor buds (96.5%) share the same HR and Her2 expression profile of the main tumor mass, implying that tumor buds relay on the same pathways as the main tumor mass and might be equally responsive to targeted therapies.
http://ift.tt/2AlZNCo
Use of 2,3,5-triphenyltetrazolium chloride-stained brain tissues for immunofluorescence analyses after focal cerebral ischemia in rats
Publication date: Available online 21 November 2017
Source:Pathology - Research and Practice
Author(s): Li Li, Qiong Yu, Weimin Liang
The middle cerebral artery occlusion (MCAO) model in rodents has been widely used as model for studying brain ischemic stroke. TTC (2,3,5-triphenyltetrazolium chloride) staining in fresh tissues is used to evaluate the size of the infarct in MCAO model, and TTC-stained brain tissues are considered to be possible to bring a damage to the anatomical structure of neuronal cells and unsuitable for immunofluorescence analyses of cytology, and discarded after evaluation of infarct volume. Another group of models with in Vivo fixation was required to the pathological or histological analyses of the infarct brains, which lead to double the numbers of animals in researches. However, some evidences indicate that if we properly optimized staining protocol, TTC-stained brain tissues might be suitable for cytological analyses. In this work, we have optimized the immunofluorescent staining methods of TTC-stained brain slices, and found that TTC-stained brain tissues are suitable for quantitative and qualitative analyses of microglia, astrocytes and neuroblasts, the morphology of theses cell were nearly identical to the in-vivo fixed models. Our optimized-protocol provide two advantages over traditional methods one of them is providing the precise the infarct region, which reduces the differences within groups, the other one is decreasing the total number of animals in research dramatically.
http://ift.tt/2ACovLv
Juvenile myelomonocytic leukemia with t(3;5)(q25;q35), Auer rods and marked myelodysplasia
Publication date: Available online 5 December 2017
Source:Pathology - Research and Practice
Author(s): Weijie Li, Linda D. Cooley, Keith August
Juvenile myelomonocytic leukemia (JMML) is a rare aggressive childhood leukemia characterized by an excess proliferation of cells of granulocytic and monocytic lineages. The WHO classifies JMML with the myelodysplastic/myeloproliferative neoplasms. Myelodysplasia in JMML is usually minimal to mild. Auer rods have never been reported in JMML. We present a 2-year-old boy with splenomegaly, leukocytosis, thrombocytopenia, anemia, and excess myeloblasts with easily seen Auer rods, and marked dysgranulopoiesis and dyserythropoiesis. Conventional cytogenetic analysis showed a sole abnormality of t(3;5)(q25;q35). Microarray analysis showed a terminal 21 Mb region of copy-neutral loss of heterozygosity on 19q. Disease-related somatic NRAS mutation was detected. This case represents an unusual JMML with Auer rods and marked myelodysplasia. These unusual histopathologic features may be related to the t(3;5)(q25;q35). A t(3;5) with variable breakpoints has been reported in a small proportion of acute myeloid leukemias and myelodysplastic syndromes. To our knowledge, this is the first JMML case reported with this translocation.
http://ift.tt/2BbNHff
Bone marrow miR-10a overexpression is associated with genetic events but not affects clinical outcome in acute myeloid leukemia
Publication date: Available online 5 December 2017
Source:Pathology - Research and Practice
Author(s): Ting-juan Zhang, Hong Guo, Jing-dong Zhou, Xi-xi Li, Wei Zhang, Ji-chun Ma, Xiang-mei Wen, Xin-yu Yao, Jiang Lin, Jun Qian
BackgroundAccumulating studies have linked the disruptions of microRNA-10 (miR-10) to acute myeloid leukemia (AML) with NPM1 mutation. However, miR-10 expression and its clinical implication in AML remain poorly defined. Although a recent report showed high serum level of miR-10a was associated with adverse prognosis in AML, herein, we found bone marrow (BM) miR-10 overexpression was not a prognostic biomarker in AML.MethodsBM miR-10 expression was examined by real-time quantitative PCR in BM mononuclear cells in 115 de novo AML patients and 45 controls.ResultsBM miR-10 (miR-10a/b) expression was significantly up-regulated in AML patients, and was positively correlated with each other. Overexpression of miR-10a was associated with lower percentage of BM blasts, whereas miR-10b overexpression tended to correlate with higher percentage of BM blasts. Importantly, miR-10a overexpression was significantly associated with FAB-M3/t(15;17) subtypes and NPM1 mutation, meanwhile, overexpression of miR-10b was correlated with NPM1 and DNMT3A mutations. However, miR-10a/b overexpression was not associated with complete remission rate, and did not have an impact on both leukemia free survival and overall survival time in non-M3 AML patients without NPM1 mutation.ConclusionsBM miR-10 overexpression is associated with genetic events but not affects clinical outcome in AML.
http://ift.tt/2AlUYco
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Summary Insulinomas are rare neuroendocrine tumours that classically present with fasting hypoglycaemia. This case report discusses an un...
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