Mycetoma is a chronic mutilating disease of the skin and the underlying tissues caused by fungi or bacteria. Although recently included in the list of neglected tropical diseases by the World Health Organizati...
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Παρασκευή 10 Αυγούστου 2018
Mycetoma: a clinical dilemma in resource limited settings
Maximizing Recovery From Concussions for Youth Participating in Sports and Recreational Activities
Concussions have become a public health issue. This public health concern has drawn the attention of many states in which laws were created to address concussions safety, recognition of signs and symptoms, immediate removal, medical clearance, and return to play protocols. The vast majority of state legislation focused on student athletes participating in organized sports. However the rise in concussion can be directly attributed to children, youth and adolescents participating in non-sports related events. Maximizing recovery from a concussion involves implementing education programs that focus on recognition of symptoms, treatment, and return to learn options. Treatment strategies employed to address concussed youth include physical and cognitive rest and minimizing external stimuli that can increase symptoms. Since learning is a direct outcome for all youth, a return to learn protocol based on a collaborative school-based team approach is suggested. All authors report no conflict of interest All authors report no funding, grants, or equipment for this project All authors report no financial benefits All authors report no previous research, manuscript, or abstract in any form Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
https://ift.tt/2MCwBch
https://ift.tt/2MCwBch
The management of locally advanced cervical cancer
Purpose of review Cervical cancer is still a major cause of morbidity and mortality among women worldwide. Surgery and chemoradiation are widely utilized treatments for cervical cancer. Despite the available standard treatment of choice, outcome is suboptimal among patients with LACC. It is vital to integrate the evidence generated from high-quality research work for effective management of these cases. This review intends to critically evaluate the latest evidence supporting the available treatment modalities and to provide a comprehensive overview of recent advances and ongoing research in the management of LACC. Recent findings Research advances in imaging and radiotherapy technologies, incorporating imaging into brachytherapy planning, use of newer targeted agents, chemotherapy intensification and immunotherapy are some of the new therapeutic options that have been in the forefront of research to improve the outcome of patients with LACC. Summary Advanced imaging modalities are increasingly being utilized to tailor treatments. Neoadjuvant chemotherapy followed by surgery does not improve outcomes in FIGO Stage IB2–IIB. Although cisplatin-based concurrent chemoradiation is the standard of care, more aggressive systemic therapies (neoadjuvant or adjuvant chemotherapy and chemoradiation) and use of newer agents, still remains investigational.https://ift.tt/2P1bhi7
New insights in the pathogenesis of T-cell lymphomas
Purpose of review Peripheral T-cell lymphomas (PTCLs) represent diverse and aggressive malignancies, with few recent therapeutic improvements. Recent high-throughput genomic studies have revealed the complex mutational landscape of these rare diseases. These novel findings provide the grounds to a more comprehensive classification of these diseases, reflected in the 2017 WHO classification. Recent findings Our review is focused on selected PTCL entities. Angioimmunoblastic T-cell lymphoma and other lymphomas derived from T follicular helper cells feature a rather homogeneous mutational landscape. These neoplasms recapitulate a multistep oncogenic process associating epigenetic deregulation, and second hit mutations affecting the T-cell receptor signaling pathway. This model inferred from comprehensive analyses of patients samples, was confirmed in mouse models. Among ALK-negative anaplastic large-cell lymphomas, translocation-associated subsets are found in both systemic and cutaneous types, and the newly described breast implant-associated type is usually indolent. Extranodal lymphomas of the innate immune system also harbor a combination of mutations affecting different classes of epigenetic modifiers, and mutation-induced activation of the Janus Kinase/signal transduction and activator of transcription pathway. Summary Understanding of PTCL pathogenesis has substantially improved, and oncogenic events have been identified. The current challenge is to mount efficient therapeutic strategies targeting these aberrations to improve patients' outcome.https://ift.tt/2MzwFtf
Immunotherapy-based combinations: an update
Purpose of review The advent of immunotherapy significantly improved clinical outcomes in cancer patients, although immune checkpoint blockade (ICB) still lack of efficacy in a consistent proportion of treated patients. The purpose of this article is to review the most innovative and clinically promising ICB-based combinations designed to improve the efficacy of cancer immunotherapy. Recent findings First-line combinatorial treatment with ipilimumab and nivolumab has recently shown to be superior to the standard of care in a subset of metastatic nonsmall cell lung cancer (NSCLC) and renal cell carcinoma (RCC). The combination of programmed cell death protein 1 (PD-1)/PD-L1 blockade with antiangiogenics has demonstrated a consistent clinical efficacy, especially for the combination of bevacizumab and atezolizumab as first-line therapy in metastatic RCC. The sequential combination of definitive chemoradiotherapy followed by durvalumab maintenance in advanced, unresectable NSCLC became the new standard of care, while the addition of pembrolizumab to first-line chemotherapy in metastatic NSCLC significantly improves overall survival. Despite promising results for the combination of ICBs with v-raf murine sarcoma viral oncogene homolog B/MAPK/ERK kinase inhibitors or epidermal growth factor receptor inhibitors, especially in melanoma and NSCLC, safety concerns slowed down the development of such strategies. Summary Immunotherapy-based combinations are becoming the standard of care for cancer treatment, in particularly for advanced melanoma, NSCLC and RCC.https://ift.tt/2Mk8Zwf
New perspectives in the therapeutic approach of peripheral T-cell lymphoma
Purpose of review Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of mature T-cell and natural killer (NK)-cell neoplasms in the WHO 2016 classification. Patient prognosis is poor when treated with CHOP, and there is an unmet need for new drugs. Several agents have been developed for PTCL, and their use is the subject of this review. Recent findings Phase 2 studies demonstrated the activity of new drugs in Relapsed/refractory PTCL. Only four compounds were approved by the food and drug administration: romidepsin and belinostat, which are epigenetic modifiers, the antifolate agent pralatrexate, the immuno-conjugate brentuximab vedotin. New combinations have been tested, but the results were disappointing. Given the latest progress in biology, targeted agents are evaluated in different subtypes of PTCL. Relapsed anaplastic large-cell lymphoma exhibits improved prognosis with the approved anti-CD30 drug conjugate brentuximab vedotin. Localized nasal NK/T is treated with radiotherapy and nonanthracycline chemotherapy with L-asparaginase. Recently, immune checkpoint inhibitors demonstrated activity in NK/T lymphoma and can be used in elderly patients. Summary Treatment remains a challenge for PTCL, and several targeted drugs provide new approaches. Progress will be made incrementally in the different subtypes. One of the critical situations facing new drugs is the ability to run robust clinical trials in rare diseases.https://ift.tt/2MCodtr
Targeting CD47 as a cancer therapeutic strategy: the cutaneous T-cell lymphoma experience
Purpose of review To describe the relevance of CD47 in the tumor microenvironment and summarize data on anti-CD47 therapies, including its role in cutaneous T-cell lymphoma (CTCL). Recent findings CD47 is expressed on all normal cells and targets SIRPα on the surface of myeloid cells. However, CD47 is found to be overexpressed on cancer cells. CD47–SIRPα interaction inhibits macrophage phagocytosis, allowing cancer cells to escape immune surveillance. Current focus in immunotherapy has been targeted toward inhibiting CD47–SIRPα interaction via anti-CD47 antibodies. This activates innate immunity, promoting cancer cell destruction by macrophages. It also activates adaptive immunity resulting in antigen-presentation, mostly by dendritic cells, leading to antitumor cytotoxic reactions. Current CD47 antagonists undergoing clinical trials include Hu5F9 (an anti-CD47 antibody that directly inhibits the CD47–SIRPα interaction) and TTI-621, (a fusion protein composed of CD47 binding domain of human SIRPα and linked to the Fc region of IgG1). These agents have continued to show strong efficacy against solid and hematological tumors. Summary In the CTCL tumor microenvironment, increased immune checkpoint inhibition expression via CD47 bound to SIRPα correlates with a more advanced disease state. Continued success in treating these patients requires further studies on CD47 antagonists, specifically when combined with other antibodies.https://ift.tt/2Mcl9Y7
New insights into breast implant-associated anaplastic large cell lymphoma
Purpose of review Breast implant-associated anaplastic large cell lymphoma (BI-ALCL) is a rare form of lymphoma arising adjacent to a breast implant. We aim to review the pathogenesis and clinico-biological features of BI-ALCL. Recent findings BI-ALCL is a new provisional entity in the 2017 updated WHO classification. Among several hypotheses, BI-ALCL development seems to be determined by the interaction of immune response related to implant products and additional genetic events. Summary BI-ALCL is an uncommon T-cell lymphoma which is increasingly diagnosed since its first description in 1997 with 500 estimated cases worldwide. Two BI-ALCL subtypes correlating with clinical presentation have been described. Although most BI-ALCL patients with tumor cell proliferation restricted to the periprosthetic effusion and capsule have excellent outcomes, other patients presenting with a tumor mass, may have a more aggressive disease. The pathogenesis of BI-ALCL remains elusive. It is postulated that local chronic inflammation elicitated by bacterial infection or implant products may promote the activation and proliferation of T cells. Additional genetic events resulting in the activation JAK/STAT pathway are also incriminated. Further investigations are needed to better characterize the pathogenesis of this disease in order to determine the potential risk to develop BI-ALCL after surgical implants.https://ift.tt/2KKFrms
The role of allogeneic stem cell transplantation in T-cell lymphoma
Purpose of review T – and natural killer (NK) cell neoplasms are a heterogeneous group of rare diseases with often inferior outcome. Only few studies exist, clarifying the role of allogeneic transplantation in different clinical scenarios. Larger prospective randomized studies are largely missing even for the more frequent entities. Mostly retrospective analysis and anecdotal reports of patients with advanced disease are available, hampering direct conclusions on the significance of allogeneic stem cell transplantation (alloSCT). Recent findings Looking at recent data for T and NK cell neoplasm, it becomes evident that advances in donor search and availability of alternative stem cell sources as haploidentical or mismatched donors in addition to substantial improvements in graft-versus-host-disease prophylaxis reduce treatment-related mortality in alloSCT. The time point of transplantation has been described in a number of studies to be critically impacting outcome results as patients with advanced, chemorefractory disease often profit much less from alloSCT. Summary Allogeneic transplantation offers a treatment option that can induce long-term remissions even in the relapsed setting. Many patients do not reach transplantation though because of chemorefractory disease and efforts should be made to bring more patients to transplantation earlier in the course of disease.https://ift.tt/2MzwC0x
Tackling the challenges of brain metastases in solid tumors
No abstract availablehttps://ift.tt/2Mk8RwL
Hodgkin lymphoma in elderly patients
Purpose of review We aim to summarize the current knowledge on the treatment of elderly Hodgkin lymphoma patients with a focus on evidence from clinical trials and novel drugs. Recent findings For elderly Hodgkin lymphoma patients above 60 years without precluding comorbidities a curative treatment approach is warranted. Early favorable stage patients should receive two cycles of multiagent chemotherapy followed by 20 Gy localized radiotherapy. Early unfavorable stage patients should receive four cycles of multiagent chemotherapy followed by 30 Gy localized radiotherapy. For advanced stage patients six cycles of multiagent chemotherapy can be recommended and should be followed by localized radiotherapy on residual disease manifestations. Relapsed or refractory patients should be treated in an individually tailored approach that considers both the patient's objectives and comorbidities. The antibody–drug conjugate brentuximab vedotin is a very effective option for elderly patients with a high response rate albeit limited durability. Anti-programed cell death protein 1 antibodies might also be effective in elderly Hodgkin lymphoma patients with a mechanism of action distinct from chemotherapy. Summary In conclusion, the goal of treatment in newly diagnosed elderly Hodgkin lymphoma patients is curative whenever possible and prospective and retrospective evidence has shown that this is feasible for all disease stages with a variety of multiagent chemotherapy regimen. Relapsed and refractory elderly Hodgkin lymphoma patients can mostly only be treated with the goal of palliation. However, it remains to be seen if novel substances and new combination regimen are able to change that.https://ift.tt/2MCbp6f
Targeting cancer metabolism through synthetic lethality-based combinatorial treatment strategies
Purpose of review Targeting cancer metabolism for therapy has received much attention over the last decade with various small molecule inhibitors entering clinical trials. The present review highlights the latest strategies to target glucose and glutamine metabolism for cancer therapy with a particular emphasis on novel combinatorial treatment approaches. Recent findings Inhibitors of glucose, lactate, and glutamine transport and the ensuing metabolism are in preclinical to clinical trial stages of investigation. Recent advances in our understanding of cell-intrinsic and cell-extrinsic factors that dictate dependence on these targets have informed the development of rational, synthetic lethality-based strategies to exploit these metabolic vulnerabilities. Summary Cancer cells exhibit a number of metabolic alterations with functional consequences beyond that of sustaining cellular energetics and biosynthesis. Elucidating context-specific metabolic dependencies and their connections to oncogenic signaling and epigenetic programs in tumor cells represents a promising approach to identify new metabolic drug targets for cancer therapy.https://ift.tt/2MiT9BR
Inherited gynaecological cancers
Purpose of review There is an increasing interest in the role of routine testing for germline mutations in the management and outcome of gynaecological cancers as the therapeutic options for these patients develop, and knowledge about specific gene risks increase. This review focuses on recent literature assessing these areas of interest. Recent findings Systemic treatment options continue to increase, with two recent studies (SOLO2 and ARIEL-3) of the use of PARP inhibitors in the maintenance setting; and approval of pembrolizomab for mismatch repair deficient/microsatellite unstable tumours. Several studies have addressed the resultant increased demand for testing for Lynch syndrome and BRCA1/2 mutations in endometrial and ovarian cancers, respectively. Finally, several studies have assessed gene and age-specific risks for ovarian cancer, and the role of specific site mutations within BRCA2 in determining duration of PARP response, and clinical outcome. Summary The use of genomic information to guide treatment choices, and inform outcome is an exciting and rapidly expanding field. These recent studies provide additional support to suggest that testing for inherited mutations should be a routine part of care for these gynaecological patients care.https://ift.tt/2MCocFT
Reappraisal of eligibility criteria in cancer clinical trials
Purpose of review We aimed to summarize the recent reflections and collaborative initiatives pertaining to the definition of more appropriate eligibility criteria in cancer clinical trials. Recent findings There is an intrinsic tension between two opposite purposes when it comes to defining eligibility criteria: on the one hand, participants must be protected, and on the other, the study population must be defined as accurately as possible. However, stringent eligibility criteria jeopardize the feasibility of trials, and, consequently, the generalizability of trial results. Therefore, interdisciplinary working groups under the auspices of the American Society of Clinical Oncology and Friends of Cancer Research propose to adapt/relax some of the classical eligibility criteria. Summary In-depth reflection of the existing eligibility criteria, and implementation of recent recommendations are needed.https://ift.tt/2Mk8LoT
Images of Thin and Plus-Size Models Produce Opposite Effects on Women’s Body Image, Body Dissatisfaction, and Anxiety
Abstract
Mainstream media's promotion of dangerously thin female images likely lowers self-image satisfaction and contributes to pathological body concerns and disordered eating among women. We tested upward and downward social-comparison effects on self-evaluations by exposing 145 Spanish women to images of thin (upward) or overweight (downward) models. We also tested whether explicitly asking or not asking participants to compare themselves with the models would moderate social comparison effects. Exposure to thin models deteriorated body image while increasing body dissatisfaction and anxiety. Conversely, exposure to overweight models improved body image and decreased body dissatisfaction but it did not affect anxiety. Whether participants were asked to compare themselves to the models explicitly or implicitly had no effect on the participants' responses. Furthermore, pre-existing body image concerns were not associated with the pre-to-post exposure effects. We propose that increasing the representation of normal weight and overweight women in media advertisements could help to neutralize or at least reduce the negative impact of media's practice to idealize thin and overly thin women as symbols of female beauty.
https://ift.tt/2nuxJ6I
Nuclear loss and cytoplasmic expression of androgen receptor in penile carcinomas: role as a driver event and as a prognosis factor
Abstract
Androgen receptor (AR) is a member of the steroid and nuclear family receptor that acts as transcription factor. AR signaling plays pivotal role in the development and progression of prostate cancer. However, the role of AR in penile cancer (PeCa) is poorly explored. Our previous molecular studies unveiled frequent AR mRNA loss in PeCa, which was further predicted as a major driver alteration in this neoplasm. Herein, we assessed the AR protein expression in 59 usual PeCa tissues and 42 surrounding normal tissues (SNT) by immunohistochemistry using a tissue microarray. In a paired analysis, we found a total absence of nuclear AR expression in PeCa while 95.2% of SNT samples presented strong nuclear AR expression (P < 0.001). Interestingly, 17 of 42 PeCa presented weak or moderate cytoplasmic AR staining, contrasting with 5 of 42 SNT (P = 0.008). Increased levels of AR cytoplasmic expression were related with poor prognosis features including advanced clinical staging (P = 0.044), compromised surgical margins (P = 0.005), and pathological inguinal node status (P = 0.047). Furthermore, AR cytoplasmic expression was also related with shorter overall survival (P = 0.032). In conclusion, the frequent loss of nuclear AR protein levels suggests a potential function in PeCa development. Based on this result, the androgen deprivation therapy is not indicated for PeCa patients. In addition, the AR cytoplasmic expression found in a significant number of cases (40.5%) showed prognostic value and pathways activated by the non-genomic AR signaling may represent a promising therapeutic strategy.
https://ift.tt/2B2OEHq
Diffusible signal factor signaling regulates multiple functions in the opportunistic pathogen Stenotrophomonas maltophilia
Stenotrophomonas maltophilia is a Gram-negative bacterium commonly isolated from nosocomial infections. Analysis of the genome of the clinical S. maltophilia isolate K279a indicates that it encodes a diffusible s...
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Young children with psychotic symptoms and risk for suicidal thoughts and behaviors: a research note
Suicidal thoughts and behaviors (STBs) are prevalent among youth with psychotic disorders (PD) relative to the general population. Recent research now suggests that STBs may present during the prodromal phase ...
https://ift.tt/2vzWkM9
Investigating the causal relationship between employment and informal caregiving of the elderly
Examining the causal relationship between employment and informal caring to date has been impeded in countries like Ireland where there is a lack of suitable panel data and/or variables for instrument construc...
https://ift.tt/2B2WBwi
Flawed mothering or infant signaling? The effects of deficient acoustic cues on ovine maternal response
Developmental Psychobiology, EarlyView.
https://ift.tt/2Mjv1is
A trajectory analysis of childhood motor development following stress in pregnancy: The QF2011 flood study
Developmental Psychobiology, EarlyView.
https://ift.tt/2MCsmNW
Economic analysis of inadequate symptom control in carcinoid syndrome in the United States
Future Oncology, Ahead of Print.
https://ift.tt/2M61kCt
Severely injured patients benefit from in-house attending trauma surgeons
Publication date: Available online 10 August 2018
Source: Injury
Author(s): Quirine M.J. van der Vliet, Oscar E.C. van Maarseveen, Diederik P.J. Smeeing, Roderick M. Houwert, Karlijn J.P. van Wessem, Rogier K.J. Simmermacher, Geertje A.M. Govaert, Mirjam B. de Jong, Ivar G.J. de Bruin, Luke P.H. Leenen, Falco Hietbrink
Abstract
Introduction
There is continuous drive to optimize healthcare for the most severely injured patients. Although still under debate, a possible measure is to provide 24/7 in-house (IH) coverage by trauma surgeons. The aim of this study was to compare process-related outcomes for severely injured patients before and after transition of attendance policy from an out-of-hospital (OH) on-call attending trauma surgeon to an in-house attending trauma surgeon.
Methods
Retrospective before-and-after study using prospectively gathered data in a Level 1 Trauma Center in the Netherlands. All trauma patients with an Injury Severity Score (ISS) >24 presenting to the emergency department for trauma before (2011 – 2012) and after (2014 – 2016) introduction of IH attendings were included. Primary outcome measures were the process-related outcomes Emergency Department length of stay (ED-LOS) and time to first intervention.
Results
After implementation of IH trauma surgeons, ED-LOS decreased (p = 0.009). Time from the ED to the intensive care unit (ICU) for patients directly transferred to the ICU was significantly shorter with more than doubling of the percentage of patients that reached the ICU within an hour. The percentage of patients undergoing emergency surgery within 30 minutes nearly doubled as well, with a larger amount of patients undergoing CT imaging before emergency surgery.
Conclusions
Introduction of a 24/7 in-house attending trauma surgeon led to improved process-related outcomes for the most severely injured patients. There is clear benefit of continuous presence of physicians with sufficient experience in trauma care in hospitals treating large numbers of severely injured patients.
https://ift.tt/2nqQmZr
Phytochemical analysis and evaluation of the cytotoxic, antimicrobial and antioxidant activities of essential oils from three Plectranthus species grown in Saudi Arabia
Cancers and microbial infections are still a major health problem, therefore research on new anticancer and antimicrobial agents ought to be continued. Natural products including essential oils from medicinal ...
https://ift.tt/2OoMCD8
Double Selection Enhances the Efficiency of Target-AID and Cas9-Based Genome Editing in Yeast
CRISPR-Cas9 loss of function (LOF) and base editing screens are powerful tools in genetics and genomics. Yeast is one of the main models in these fields, but has only recently started to adopt this new toolkit for high throughput experiments. We developed a double selection strategy based on co-selection that increases LOF mutation rates using the Target-AID base editor. We constructed the pDYSCKO vector, which is amenable to high throughput double selection experiments, and show that the improvement in Target-AID efficiency generalizes across loci. Using modeling, we show that this improvement in efficiency provides the required increased in detection power to measure the fitness effects of thousands of mutations in typical yeast pooled screens. We show that double selection can also improve Cas9 mediated LOF rates, but that this multiplex genome editing causes programmable chromosomal translocations at high frequency. This suggests that multiplex LOF editing should be performed with caution and that base-editors could be preferable tools for some screens in yeast. Base editing using double selection is simple and straightforward and provides an alternative to homology directed repair-based high throughput variant strain construction methods.
https://ift.tt/2vSvwpu
Whole Genome Sequencing, de Novo Assembly and Phenotypic Profiling for the New Budding Yeast Species Saccharomyces jurei
Saccharomyces sensu stricto complex consist of yeast species, which are not only important in the fermentation industry but are also model systems for genomic and ecological analysis. Here, we present the complete genome assemblies of Saccharomyces jurei, a newly discovered Saccharomyces sensu stricto species from high altitude oaks. Phylogenetic and phenotypic analysis revealed that S. jurei is more closely related to S. mikatae, than S. cerevisiae, and S. paradoxus. The karyotype of S. jurei presents two reciprocal chromosomal translocations between chromosome VI/VII and I/XIII when compared to the S. cerevisiae genome. Interestingly, while the rearrangement I/XIII is unique to S. jurei, the other is in common with S. mikatae strain IFO1815, suggesting shared evolutionary history of this species after the split between S. cerevisiae and S. mikatae. The number of Ty elements differed in the new species, with a higher number of Ty elements present in S. jurei than in S. cerevisiae. Phenotypically, the S. jurei strain NCYC 3962 has relatively higher fitness than the other strain NCYC 3947T under most of the environmental stress conditions tested and showed remarkably increased fitness in higher concentration of acetic acid compared to the other sensu stricto species. Both strains were found to be better adapted to lower temperatures compared to S. cerevisiae.
https://ift.tt/2nuNeMc
Genomic Signatures of Adaptation to a Precipitation Gradient in Nigerian Sorghum
Evolution of plants under climatic gradients may lead to clinal adaptation. Understanding the genomic basis of clinal adaptation in crops species could facilitate breeding for climate resilience. We investigated signatures of clinal adaptation in the cereal crop sorghum (Sorghum bicolor L. [Moench]) to the precipitation gradient in West Africa using a panel (n = 607) of sorghum accessions from diverse agroclimatic zones of Nigeria. Significant correlations were observed between common-garden phenotypes of three putative climate-adaptive traits (flowering time, plant height, and panicle length) and climatic variables. The panel was characterized at >400,000 single nucleotide polymorphisms (SNPs) using genotyping-by-sequencing (GBS). Redundancy analysis indicated that a small proportion of SNP variation can be explained by climate (1%), space (1%), and climate collinear with space (3%). Discriminant analysis of principal components identified three genetic groups that are distributed differently along the precipitation gradient. Genome-wide association studies were conducted with phenotypes and three climatic variables (annual mean precipitation, precipitation in the driest quarter, and annual mean temperature). There was no overall enrichment of associations near a priori candidate genes implicated in flowering time, height, and inflorescence architecture in cereals, but several significant associations were found near a priori candidates including photoperiodic flowering regulators SbCN12 and Ma6. Together, the findings suggest that a small (3%) but significant proportion of nucleotide variation in Nigerian sorghum landraces reflects clinal adaptation along the West African precipitation gradient.
https://ift.tt/2vXuSau
A PHASE I/IIa TRIAL USING CD19-TARGETED THIRD GENERATION CAR T CELLS FOR LYMPHOMA AND LEUKEMIA
Purpose: CAR T cell therapy has been effective for patients with CD19+ B cell malignancies. Most studies have investigated second generation CARs with either CD28 or 4-1BB co-stimulatory domains in the CAR receptor. Here we describe the first clinical phase I/IIa trial using third generation CAR T cells targeting CD19 to evaluate safety and efficacy. Experimental Design: Fifteen patients with B cell lymphoma or leukemia were treated with CAR T cells. The lymphoma patients received chemotherapy during CAR manufacture and eleven of fifteen were given low dose cyclophosphamide and fludarabine conditioning prior to CAR infusion. Peripheral blood was sampled before and at multiple time points post CAR infusion to evaluate the persistence of CAR T cells and for immune profiling, using quantitative PCR, flow cytometry and a proteomic array. Results: Treatment with third generation CAR T cells was generally safe with four patients requiring hospitalization due to adverse reactions. Six of the fifteen patients had initial complete responses (4/11 lymphoma and 2/4 ALL), and three of the lymphoma patients were in remission at 3 months. Two patients are still alive. Best predictor of response was a good immune status prior to CAR infusion with high IL12, DC-Lamp, Fas ligand and TRAIL. Responding patients had low monocytic MDSCs (CD14+CD33+HLA-DR-) and low levels of IL6, IL8, NAP3, sPDL1 and sPDL2. Conclusions: Third generation CARs may be efficient in patients with advanced B-cell lymphoproliferative malignancy with only modest toxicity. Immune profiling pre and post treatment can be used to find response biomarkers.
https://ift.tt/2Md7elq
A phase I trial of a guadecitabine (SGI-110) and irinotecan in metastatic colorectal cancer patients previously exposed to irinotecan
Purpose: Chemotherapeutic resistance eventually develops in all patients with metastatic colorectal cancer (mCRC). Gene silencing through promoter demethylation is one potential reversible mechanism of resistance with administration of hypomethylating agents. We evaluated the safety and tolerability of guadecitabine and irinotecan in mCRC patients previously treated with irinotecan. Experimental Design: In this 3+3 dose-escalation study, mCRC patients previously exposed to irinotecan received guadecitabine days 1-5 of a 28 day cycle and irinotecan 125mg/m2 days 8 and 15 [dose level (DL) 1, guadecitabine 45mg/m2; DL -1: guadecitabine 30mg/m2; DL -1G: guadecitabine 30mg/m2 with growth factor support (GFS); DL 1G: guadecitabine 45mg/m2 with GFS. Results: Twenty-two patients were treated across four DLs. Dose-limiting toxicities were neutropenic fever (DL 1 and -1G), biliary drain infection (DL -1), colonic obstruction (DL -1), and severe dehydration (DL 1G). Most common toxicities were neutropenia (82% any grade, 77% Grade 3/4), neutropenic fever (23%), leukopenia (73% any grade, 50% Grade 3/4), and injection site reactions (64% total, 0% Grade 3/4). Patients received a median of 4.5 cycles of treatment; 12/17 evaluable patients had stable disease as best response, with one having initial disease progression but subsequently durable partial response. Circulating tumor DNA showed decrease in global demethylation by LINE-1 after treatment. Conclusions:We report the first study of chemo-priming with epigenetic therapy in GI cancers. Guadecitabine 45 mg/m2 and irinotecan 125mg/m2 with GFS was safe and tolerable in mCRC patients, with early indication of benefit. These data have provided the basis for an ongoing phase II randomized, multicenter trial.
https://ift.tt/2KJbuTK
Loss of nuclear localized Parathyroid Hormone-related Protein in primary breast cancer predicts poor clinical outcome and correlates with suppressed Stat5 signaling
Purpose: Parathyroid Hormone-related Protein (PTHrP) is required for normal mammary gland development and biology. A PTHLH gene polymorphism is associated with breast cancer risk, and PTHrP promotes growth of osteolytic breast cancer bone metastases. Accordingly, current dogma holds that PTHrP is up-regulated in malignant primary breast tumors, but solid evidence for this assumption is missing. Experimental Design: We used quantitative immunohistochemistry to measure PTHrP in normal and malignant breast epithelia, and correlated PTHrP levels in primary breast cancer with clinical outcome. Results: PTHrP levels were markedly down-regulated in malignant compared to normal breast epithelia. Moreover, low levels of nuclear localized PTHrP in cancer cells correlated with unfavorable clinical outcome in a test and a validation cohort of breast cancer treated at different institutions totaling nearly 800 cases. PTHrP mRNA levels in tumors of a third cohort of 737 patients corroborated this association, also after multivariable adjustment for standard clinicopathological parameters. Breast cancer PTHrP levels correlated strongly with transcription factors Stat5a/b, which are established markers of favorable prognosis and key mediators of prolactin signaling. Prolactin stimulated PTHrP transcript and protein in breast cancer cell lines in vitro and in vivo, effects mediated by Stat5 through the P2 gene promoter, producing transcript AT6 encoding the PTHrP 1-173 isoform. Low levels of AT6, but not two alternative transcripts, correlated with poor clinical outcome. Conclusions: This study overturns the prevailing view that PTHrP is upregulated in primary breast cancers and identifies a direct prolactin-Stat5-PTHrP axis that is progressively lost in more aggressive tumors.
https://ift.tt/2M9MFWP
ERG Retargets BAF Complexes to Promote Prostate Oncogenesis [Research Watch]
In TMPRSS2–ERG-positive prostate cancer, ERG retargets BAF chromatin remodeling complexes to ETS motifs.
https://ift.tt/2nuLylS
A KAT6A/B Inhibitor Induces Senescence to Suppress Tumorigenesis [Research Watch]
The reversible competitive KAT6A/B inhibitor WM-1119 enhanced oncogene-induced senescence.
https://ift.tt/2w1gsGc
AKT1 Can Be Activated via Distinct Phosphorylation-Based Mechanisms [Research Watch]
Phosphorylation of Ser473 and dual phosphorylation of Ser477/Thr479 activate AKT via distinct mechanisms.
https://ift.tt/2nrVEDR
Glioblastoma Arises from Cells in the Subventricular Zone [Research Watch]
Low-level driver mutations in subventricular zone (SVZ) cells are sufficient to induce glioblastoma.
https://ift.tt/2vXtjJE
Bundling Doesn't Cut Medicare Payments for Medical Conditions
FRIDAY, Aug. 10, 2018 -- Bundling of payments for five common medical conditions is not associated with changes in Medicare payments per episode or health outcomes, according to a study published in the July 19 issue of the New England Journal of...
https://ift.tt/2vvs05h
CDC: Rates of Opioid Use Disorder Seen at Time of Delivery Up
FRIDAY, Aug. 10, 2018 -- Opioid use disorder rates at delivery more than quadrupled nationally from 1999 to 2014, according to research published in the Aug. 10 issue of the U.S. Centers for Disease Control and Prevention's Morbidity and Mortality...
https://ift.tt/2B1Pog1
Will Lunar and Planet Dust Be Health Concerns of the Future?
FRIDAY, Aug. 10, 2018 -- Dust could pose a health hazard if astronauts start spending extended periods of time on the Moon, Mars, or other airless planets, according to a study published recently in GeoHealth. Rachel Caston, Ph.D., of the Stony...
https://ift.tt/2P1rljU
Dermatologist Intervention Tied to Better Sun Protection
FRIDAY, Aug. 10, 2018 -- A brief intervention delivered by dermatologists is associated with improvements in patients' sun protection behavior as well as their satisfaction with dermatologists' communication, according to a study published online...
https://ift.tt/2B0Ud99
Court Rules That U.S. Must Halt Sales of Pesticide Chlorpyrifos
FRIDAY, Aug. 10, 2018 -- The Environmental Protection Agency must remove the pesticide chlorpyrifos from sale in the United States within 60 days, a federal appeals court ordered yesterday. The 9th U.S. Circuit Court of Appeals in San Francisco said...
https://ift.tt/2P0Ntef
Mechanistic Pathways of Selenium in the Treatment of Graves’ Disease and Graves’ Orbitopathy
Horm Metab Res
DOI: 10.1055/a-0658-7889
Based on the role of oxidative stress in the pathogenesis of Graves' hyperthyroidism and Graves' orbitopathy, the use of the antioxidant agent selenium has been proposed and several studies on the subject have been conducted, both in vitro and in vivo. Whereas a true benefit related to the use of selenium in patients with Graves' hyperthyroidism has been questioned, its use in patients with mild Graves' orbitopathy is generally believed to be beneficial because of which selenium has entered in the clinical practice for this eye condition.
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© Georg Thieme Verlag KG Stuttgart · New York
Article in Thieme eJournals:
Table of contents | Abstract | Full text
https://ift.tt/2B0HjIg
Recurrence of Hepatocellular Carcinoma after Direct Acting Antiviral Treatment for Hepatitis C Virus Infection: Literature Review and Risk Analysis
Although studies suggest decreased incident hepatocellular carcinoma (HCC) after treatment with direct-acting antivirals (DAAs) for hepatitis C virus (HCV) infection, data are conflicting regarding risk and aggressiveness of recurrence in patients who have a history of treated HCC. This review analyses data available in literature in order to elucidate the impact of DAAs on the risk of HCC recurrence after successful treatment of the tumor. Overall 24 papers were identified. The available data cannot be considered definitive, but the initial alarmist data indicating an increased risk of recurrence have not been confirmed by most subsequent studies.
https://ift.tt/2KJWuoF
Effectiveness and safety of vedolizumab for maintenance treatment in inflammatory bowel disease- the Israeli real world experience
Several real-world experience (RWE) studies with vedolizumab (VDZ) for induction of remission in inflammatory bowel diseases (IBD) have been published; However, long-term RWE data is scarce.
https://ift.tt/2MgNQ6c
T. marneffei infection complications in an HIV-negative patient with pre-existing pulmonary sarcoidosis: a rare case report
Talaromyces marneffei (T. marneffei) is a thermal dimorphic pathogenic fungus that often causes fatal opportunistic infections in human immunodeficiency virus (HIV)-infected patients. Although T. marneffei-infect...
https://ift.tt/2B6SsqS
Vaccination demonstration zone successfully controls rabies in Guangxi Province, China
Guangxi is the province most seriously affected by rabies virus (RABV) in China. Those most affected by RABV each year are people in rural areas, where dogs are the main cause of human infection with the virus.
https://ift.tt/2OWRG2V
Combination of PCT, sNFI and dCHC for the diagnosis of ascites infection in cirrhotic patients
It is difficult to diagnose ascites infection early in cirrhotic patients. The present study was to create and evaluate a new bioscore combined with PCT, sNFI and dCHC in the diagnosis of ascites infection in ...
https://ift.tt/2B6Smj0
Persistent detection of Zika virus RNA from an infant with severe microcephaly – a case report
Zika virus (ZIKV) is a recently emerged arbovirus, which infection during pregnancy is associated with a series of congenital malformations, collectively denominated Congenital Zika Syndrome (CZS). Following i...
https://ift.tt/2OZ1fhC
Infection characteristics and treatment of Staphylococcus aureus bacteraemia at a tertiary children’s hospital
Staphylococcus aureus bacteraemia (SAB) causes considerable morbidity and mortality in children. Despite this, its epidemiology and risk factors are poorly understood, with minimal paediatric clinical trial data ...
https://ift.tt/2B6Sj6O
17α-Ethinyl-androst-5-ene-3β, 17β-diol, a novel potent oral radioprotective agent, confers radioprotection of hematopoietic stem and progenitor cells in a granulocyte colony stimulating factor-independent manner
To develop a novel oral radioprotector, the radioprotective effects of 17α-Ethinyl-androst-5-ene-3β,17β-diol (EAD) were evaluated in mice subjected to total-body irradiated mice. Oral administration of EAD before irradiation significantly improved survival after lethal irradiation and promoted multilineage reconstitution by stimulating hematopoietic stem and progenitor cells in a G-CSF independent manner. Given its oral efficacy and low toxicity, EAD has potential as an optimal radioprotector for use by first responders as well as at-risk civilian populations.
https://ift.tt/2OZJVcd
Wilms tumor, pleuropulmonary blastoma, and DICER1: case report and literature review
Abstract
Background
Pleuroblastoma (PPB) is a rare pediatric tumor which, in 30% of cases, is associated with cystic nephroma. It has been recently linked to the DICER1 mutation as part of a predisposition syndrome for various tumors. However, if DICER 1 anomalies have been reported in patients with Wilms tumor (WT), to date, no cases of PPB, WT, and DICER1 mutations have been reported in the same patient.
Case presentation
We report the case of a 3-year-old patient, initially managed for metastatic WT. During his clinical course, the diagnosis of a PPB was made after detecting the DICER1 mutation and subsequent management was therefore modified.
Conclusion
This case highlights that in case of simultaneous discovery of a renal tumor and a pulmonary lesion in a child, the DICER 1 mutations should be looked for as these could help adapt management and schedule the surgical procedures.
https://ift.tt/2B2Kqzu
The combined effect of non-alcoholic fatty liver disease and metabolic syndrome on colorectal carcinoma mortality: a retrospective in Chinese females
Abstract
Background
This research aimed to investigate whether metabolic syndrome (MetS) and non-alcoholic fatty liver disease (NAFLD) had both individual and synergistic effects on the prognosis for female colorectal carcinoma (CRC) patients.
Methods
The relationship between CRC prognosis and NAFLD as well as MetS was evaluated in 764 female participants. Based on the NAFLD level, patients were divided into significant NAFLD (SNAFLD), "moderate" and "severe" level, and non-SNAFLD, "non" and "mild" level. All the patients were categorized into four subgroups according to the status of SNAFLD and MetS and then a comparison of CRC prognosis among those four groups was performed.
Results
NAFLD, SNAFLD, and MetS were independent factors for CRC-specific mortality with the adjustment of age and other confounders. The hazard ratio (HR) of CRC-specific mortality in MetS (+) SNAFLD (+) group was significantly higher than that in other three groups. Relative excess risk of interaction (RERI) was 2.203 with 95% CI ranged from 0.197 to 4.210, attributable proportion (AP) was 0.444 with range from 0.222 to 0.667, and synergy index (SI) of 2.256 with 95% CI from 1.252 to 4.065, indicating SNAFLD and MetS had a significant synergic effect on CRC-specific mortality.
Conclusions
SNAFLD and MetS are independent risk factors for CRC-specific mortality in females. Moreover, those two diseases have a synergistic effect on promoting CRC-specific mortality.
https://ift.tt/2vzoMgU
Genome-wide investigation of an ID cohort reveals de novo 3′UTR variants affecting gene expression
Abstract
Intellectual disability (ID) is a severe neurodevelopmental disorder with genetically heterogeneous causes. Large-scale sequencing has led to the identification of many gene-disrupting mutations; however, a substantial proportion of cases lack a molecular diagnosis. As such, there remains much to uncover for a complete understanding of the genetic underpinnings of ID. Genetic variants present in non-coding regions of the genome have been highlighted as potential contributors to neurodevelopmental disorders given their role in regulating gene expression. Nevertheless the functional characterization of non-coding variants remains challenging. We describe the identification and characterization of de novo non-coding variation in 3′UTR regulatory regions within an ID cohort of 50 patients. This cohort was previously screened for structural and coding pathogenic variants via CNV, whole exome and whole genome analysis. We identified 44 high-confidence single nucleotide non-coding variants within the 3′UTR regions of these 50 genomes. Four of these variants were located within predicted miRNA binding sites and were thus hypothesised to have regulatory consequences. Functional testing showed that two of the variants interfered with miRNA-mediated regulation of their target genes, AMD1 and FAIM. Both these variants were found in the same individual and their functional consequences may point to a potential role for such variants in intellectual disability.
https://ift.tt/2B11o19
Alpha-1 Antitrypsin Deficiency as a Candidate for Gene Editing
Human Gene Therapy, Volume 29, Issue 8, Page 843-844, August 2018.
https://ift.tt/2vGwW7B
EMCrit – A Debate on the Use of Cognitive Decision Aids for Resuscitation and why Twitter is absolute, utter Crap
After the initial publication of the Resus Crisis Manual, a thread started on twitter The Tweets that Inspired the Debate Sorry, but if you need a "how to do it" bullet list to handle resus pts your no1 priority should be to call someone who does not need that list! #HQCC no excuses, no exceptions! […]
EMCrit Project by Scott Weingart.
https://ift.tt/2MbwWq6
Measuring Active and Passive Tameness Separately in Mice
https://ift.tt/2nqTKn9
In Vivo Photolabeling of Cells in the Colon to Assess Migratory Potential of Hematopoietic Cells in Neonatal Mice
https://ift.tt/2vUxgyJ
Limiting exposure to asbestos during and after disaster management
Environmental disasters can expose first responders to asbestos, putting them at risk for mesothelioma
https://ift.tt/2nqPYKv
How to keep PTSD out of your EMS department
Recognize the risk factors and symptoms of PTSD, and how to manage self-talk and meditate to reduce its physical and emotional effects
https://ift.tt/2vAlMkJ
Magnetic-Activated Cell Sorting Strategies to Isolate and Purify Synovial Fluid-Derived Mesenchymal Stem Cells from a Rabbit Model
https://ift.tt/2M99LwL
Light-sheet Fluorescence Microscopy to Capture 4-Dimensional Images of the Effects of Modulating Shear Stress on the Developing Zebrafish Heart
https://ift.tt/2OuK7zn
Generation of Large Numbers of Myeloid Progenitors and Dendritic Cell Precursors from Murine Bone Marrow Using a Novel Cell Sorting Strategy
https://ift.tt/2MjlA2H
A 3D-printed Chamber for Organic Optoelectronic Device Degradation Testing
https://ift.tt/2MwBgfQ
ACS Briefing Discusses Use of Lessons From Combat Care
FRIDAY, Aug. 10, 2018 -- The American College of Surgeons (ACS) hosted a briefing on Capitol Hill to discuss the successes and challenges of combat casualty care in Iraq and Afghanistan by the U.S. military, and how an integrated military-civilian...
https://ift.tt/2AZKY9e
Sexual Minorities Have Lower Health-Related Quality of Life
FRIDAY, Aug. 10, 2018 -- Sexual minority women and men are more likely to be unemployed and uninsured and have worse health-related quality of life (HRQL) than heterosexual individuals, according to a study published recently in BMJ Open. Brittany...
https://ift.tt/2OZDCFJ
Childbearing Surgical Residents Often Feel Career Dissatisfaction
FRIDAY, Aug. 10, 2018 -- More than half of women who have a baby during surgical residency express some type of career dissatisfaction, according to a study published online Aug. 1 in JAMA Surgery. Erika L. Rangel, M.D., from Brigham and Women's...
https://ift.tt/2AWClwk
AMA Adopts Policy on Augmented Intelligence
FRIDAY, Aug. 10, 2018 -- The American Medical Association (AMA) House of Delegates has adopted a policy on augmented intelligence, according to a report published in the association's AMA Wire. Though computational methods, techniques, and systems...
https://ift.tt/2OWa9N3
Cardiac Profiles Up With Exercise, Less Sitting in Early Old Age
FRIDAY, Aug. 10, 2018 -- For adults aged 60 to 64 years, greater light physical activity (PA) and moderate-to-vigorous intensity PA and less sedentary time are associated with more favorable cardiovascular profiles, according to a study published...
https://ift.tt/2OWa8IZ
Parental Depression Ups Odds of Child Use of Health Services
FRIDAY, Aug. 10, 2018 -- Parental depression is linked to increased use of health services by their offspring, according to a study published in the July issue of BMJ Paediatrics Open. Kathryn Dreyer, from The Health Foundation in London, and...
https://ift.tt/2AVMMQy
Teen Sudden Cardiac Death Causes Often Not ID'd on Screens
FRIDAY, Aug. 10, 2018 -- Among adolescent soccer players in the United Kingdom, the incidence of sudden cardiac death is 6.8 per 100,000 athletes, and most of the deaths were due to cardiomyopathies not identified on cardiac screening, according to...
https://ift.tt/2vwF3mK
Review Addresses Nutritional Hype for Popular Foods
FRIDAY, Aug. 10, 2018 -- While many dietary patterns, foods, and nutrients receive substantial media attention and are hyped as having cardiovascular benefits, some have evidence for these benefits and others do not, according to a review published...
https://ift.tt/2AVMHwe
Military-Civilian Trauma System Partnership Developed
FRIDAY, Aug. 10, 2018 -- A growing partnership between the Military Health System and permanent civilian trauma institutions is being fostered, according to an article published in the August issue of the Journal of the American College of...
https://ift.tt/2vwF0HA
Sufficient Preconception Vitamin D Tied to Lower Miscarriage Risk
FRIDAY, Aug. 10, 2018 -- Preconception vitamin D levels may play a role in maintaining pregnancy, according to a study published recently in The Lancet Diabetes & Endocrinology. Sunni Mumford, Ph.D., from the National Institutes of Health in...
https://ift.tt/2AZ5dnl
Systemic Delivery of MicroRNA Using Recombinant Adeno-associated Virus Serotype 9 to Treat Neuromuscular Diseases in Rodents
Here we describe the delivery of microRNA using a recombinant adeno-associated virus serotype 9 in a mouse model of a neuromuscular disease. A single peripheral administration in mice resulted in sustained miRNA overexpression in muscle and motor neurons, providing an opportunity to study miRNA function and therapeutic potential in vivo.
https://ift.tt/2B0IlUR
Md. hits record-high drug deaths, fueled by fentanyl
Maryland, a state that already had one of the country's most punishing overdose mortality rates, notched a record-high number of drug deaths last year
https://ift.tt/2B0tXMl
Anesthesia and postoperative pain control following spine surgery
Publication date: Available online 10 August 2018
Source: Seminars in Spine Surgery
Author(s): Michael T. Nolte, Islam M. Elboghdady, Sravisht Iyer
Abstract
The focus of this manuscript will be to discuss the evidence supporting the various modalities, routes of administration, and timing of analgesic medication in the setting of spine surgery. We outline the evidence supporting multi-modal analgesia and describe strategies to optimize pain control while limiting opioid use. We discuss the importance of pre-emptive analgesia, optimal intraoperative pain regimens and non-opioid alternatives that may be used to help treat post-operative pain. The role of regional anesthesia as an adjunct to oral medications is also discussed.
https://ift.tt/2vVblY9
CMTM4 regulates angiogenesis by promoting cell surface recycling of VE-cadherin to endothelial adherens junctions
Abstract
Vascular endothelial (VE) cadherin is a key component of endothelial adherens junctions (AJs) and plays an important role in maintaining vascular integrity. Endocytosis of VE-cadherin regulates junctional strength and a decrease of surface VE-cadherin reduces vascular stability. However, disruption of AJs is also a requirement for vascular sprouting. Identifying novel regulators of endothelial endocytosis could enhance our understanding of angiogenesis. Here, we evaluated the angiogenic potential of (CKLF-like MARVEL transmembrane domain 4) CMTM4 and assessed in which molecular pathway CMTM4 is involved during angiogenesis. Using a 3D vascular assay composed of GFP-labeled HUVECs and dsRED-labeled pericytes, we demonstrated in vitro that siRNA-mediated CMTM4 silencing impairs vascular sprouting. In vivo, CMTM4 silencing by morpholino injection in zebrafish larvae inhibits intersomitic vessel growth. Intracellular staining revealed that CMTM4 colocalizes with Rab4+ and Rab7+ vesicles, both markers of the endocytic trafficking pathway. CMTM4 colocalizes with both membrane-bound and internalized VE-cadherin. Adenovirus-mediated CMTM4 overexpression enhances the endothelial endocytic pathway, in particular the rapid recycling pathway, shown by an increase in early endosomal antigen-1 positive (EEA1+), Rab4+, Rab11+ , and Rab7+ vesicles. CMTM4 overexpression enhances membrane-bound VE-cadherin internalization, whereas CMTM4 knockdown decreases internalization of VE-cadherin. CMTM4 overexpression promotes endothelial barrier function, shown by an increase in recovery of transendothelial electrical resistance (TEER) after thrombin stimulation. We have identified in this study a novel regulatory function for CMTM4 in angiogenesis. CMTM4 plays an important role in the turnover of membrane-bound VE-cadherin at AJs, mediating endothelial barrier function and controlling vascular sprouting.
https://ift.tt/2vVTjVD
Prospective comparison of various radiological response criteria and pathological response to preoperative chemotherapy and survival in operable high-grade soft tissue sarcomas in the Japan Clinical Oncology Group study JCOG0304
Abstract
Background
Soft tissue sarcomas (STS) are rare malignant tumors. The efficacy of preoperative chemotherapy for STS is evaluated using various tumor size-based radiological response criteria. However, it is still unclear which set of criteria would show the best association with pathological response and survival of the patients with STS.
Methods
We compared radiological responses to preoperative chemotherapy for operable STS by the Response Evaluation Criteria in Solid Tumors (RECIST), modified RECIST, World Health Organization criteria, Japanese Orthopaedic Association criteria, and modified Choi criteria and analyzed the association with pathological response and survival using the data from the Japan Clinical Oncology Group (JCOG) study JCOG0304, a phase II clinical trial evaluating the efficacy of perioperative chemotherapy for STS in the extremities.
Results
Seventy eligible patients in JCOG0304 were analyzed. The results demonstrated that none of the size-based radiological response criteria showed significant association with pathological response to preoperative chemotherapy for STS. The difference between overall survival of the patients assessed as partial response and stable disease/progressive disease by RECIST was not significant (hazard ratio 1.37, p = 0.63), and calculated C-index was 0.50. All other response criteria also could not exhibit significant association between radiological responses and survival.
Conclusion
In the present study, none of the radiological response criteria analyzed demonstrated association of response to preoperative chemotherapy with pathological response or survival of the patients with operable STS. Further prospective investigation is required to develop criteria to evaluate not only tumor shrinkage but biological effects of preoperative chemotherapy for the patients with localized STS.
Trial registration
UMIN Clinical Trials Registry C000000096. Registered 30 August, 2005 (retrospectively registered).
https://ift.tt/2Mf0AKu
Searching for the Culprit: Metastases from a Cancer of Unknown Primary
We report a case of metastases from a cancer of unknown primary whose primary site could not be identified during the appropriate pretreatment evaluation. The patient was a 58-year-old woman with a history of passive smoking and with no history of cancer in the family. Her current condition started with asthenia, adynamia, and pallor, followed by palpitations. An abdominopelvic computed tomography (CT) scan was performed, showing multiple osteolytic lesions distributed in all bone structures and axillary adenopathy on the left side. As part of the approach and given the high suspicion of multiple myeloma, tests were performed. The results were negative for multiple myeloma. A PET-CT scan was performed and showed left axillary adenopathy. The breasts and other organs were not affected. Left axillary lymph node resection revealed breast primary metastatic pleomorphic lobular carcinoma. Due to the metastatic disease (caused by the primary breast cancer), it was decided to start chemotherapy.
Case Rep Oncol 2018;11:541–548
https://ift.tt/2B1OBLW
A Case of Vanishing Metastatic Mass: Right Atrial Mass in the Setting of Primary Epithelioid Hemangioendothelioma of the Spine
Epithelioid hemangioendothelioma (EHE) is a rare low-grade vascular neoplasm that is characterized as intermediate between benign hemangioma and high-grade angiosarcoma affecting 1 in 1,000,000 people worldwide. It has been described throughout the body with lung, liver, skin, and bone being the most frequent sites. Primary EHE of the spine has been reported in 56 cases so far with no correlation of age and sex. Our case highlights a rare clinical presentation, etiopathogenesis, diagnosis, and treatment of EHE of the spine with metastasis to the right atrium. This is the first documented case of EHE of the spine with metastatic spread to the heart treated with bevacizumab leading to resolution of the heart metastatic mass. Further studies are warranted to develop a treatment formula for this rare tumor, to consider combination chemotherapy and new adjuvant targeted immunotherapies to prevent progression of disease.
Case Rep Oncol 2018;11:534–540
https://ift.tt/2vA3PTk
Cancers, Vol. 10, Pages 269: 4-Acetyl-Antroquinonol B Suppresses SOD2-Enhanced Cancer Stem Cell-Like Phenotypes and Chemoresistance of Colorectal Cancer Cells by inducing hsa-miR-324 re-Expression
Cancers, Vol. 10, Pages 269: 4-Acetyl-Antroquinonol B Suppresses SOD2-Enhanced Cancer Stem Cell-Like Phenotypes and Chemoresistance of Colorectal Cancer Cells by inducing hsa-miR-324 re-Expression
Cancers doi: 10.3390/cancers10080269
Authors: Oluwaseun Adebayo Bamodu Ching-Kuo Yang Wei-Hong Cheng David T.W. Tzeng Kuang-Tai Kuo Chun-Chih Huang Li Deng Michael Hsiao Wei-Hwa Lee Chi-Tai Yeh
Background: Colorectal cancer (CRC) remains a leading cause of cancer-related morbidity and mortality in both sexes globally. This is not unconnected with the heterogeneity and plasticity of CRC stem cells (CRC-SCs) which stealthily exploit the niche-related and (epi)genetic factors to facilitate metastasis, chemoresistance, tumor recurrence, and disease progression. Despite the accumulating evidence of the role of dysregulated microRNAs in malignancies, the therapeutic efficacy of pharmacological-targeting of CRC-SC-associated microRNAs is relatively under-explored. Experimental approach: In this present study, we employed relatively new bioinformatics approaches, analyses of microarray data, Western blot, real-time polymerase chain reaction (RT-PCR), and functional assays to show that hsa-miR-324-5p expression is significantly suppressed in CRC cells, and inversely correlates with the aberrant expression of SOD2. Results: This converse hsa-miR-324-5p/SOD2 relationship is associated with enhanced oncogenicity, which is effectively inhibited by 4-acetylantroquinonol B (4-AAQB), as evidenced by inhibited cell viability and proliferation, as well as attenuated migration, invasion, and clonogenicity in 4-AAQB-treated DLD1 and HCT116 cells. Interestingly, 4-AAQB did not affect the viability and proliferation of normal colon cells. We also showed that 4-AAQB-induced re-expression of hsa-miR-324-5p, akin to short-interfering RNA, reduced SOD2 expression, correlates with the concurrent down-regulation of SOD2, N-cadherin, vimentin, c-Myc, and BcL-xL2, with concomitant up-regulation of E-cadherin and BAX2 proteins. Enhanced expression of hsa-miR-324-5p in the CRC cells suppressed their tumorigenicity in vitro and in vivo. Additionally, 4-AAQB synergistically potentiates the FOLFOX (folinate (leucovorin), fluorouracil (5FU), and oxaliplatin) anticancer effect by eliciting the re-expression of SOD2-suppressed hsa-miR-324, and inhibiting SOD2-mediated tumorigenicity. Conclusion: Our findings highlight the pre-clinical anti-CSC efficacy of 4-AAQB, with or without FOLFOX in CRC, and suggest a potential novel therapeutic strategy for CRC patients.
https://ift.tt/2nstPeR
Initiation and duration of breastfeeding of Aboriginal infants in South Australia
Publication date: Available online 10 August 2018
Source: Women and Birth
Author(s): Stephanie Brown, Deanna Stuart-Butler, Cathy Leane, Karen Glover, Amanda Mitchell, Janiene Deverix, Theresa Francis, Jackie Ah Kit, Donna Weetra, Deirdre Gartland, Jane Yelland
Abstract
Background
Benefits of breastfeeding are well-established. Few studies have examined initiation and duration of breastfeeding of Aboriginal infants.
Methods
Population-based study of women giving birth to an Aboriginal infant in South Australia, July 2011–June 2013.
Findings
344 women took part. Participants were representative in relation to maternal age, infant birthweight and gestation. Eighty-six percent initiated breastfeeding, declining to 54% at 12 weeks postpartum. Women living in remote areas were more likely to be breastfeeding at 12 weeks than women living in Adelaide (Odds Ratio = 2.6, 95% Confidence Interval 1.5–4.7). Two-thirds of women (67%) attending standard public antenatal care in regional areas and 61% attending regional Aboriginal Family Birthing Program Services were breastfeeding at 12 weeks, compared to one third of women (36%) attending standard metropolitan public antenatal care and 49% of women attending metropolitan Aboriginal Family Birthing Program Services. Less than half of women (45%) described their postnatal care as 'very good', and 40% were not always able to access support with infant feeding when needed. The most common reasons for switching to formula before 6 weeks were: low milk supply/baby not gaining weight, mastitis/sore breasts or other feeding problems. Mothers also identified their own health as a factor.
Conclusion
While the findings must be treated with caution due to small numbers, they suggest benefits for women attending Aboriginal Family Birthing Program services in the urban environment where rates of initiation and continued breastfeeding are lowest. Provision of culturally appropriate support to Aboriginal women during and after pregnancy is key to improving outcomes.
https://ift.tt/2MdWFh2
Women’s views and experiences of publicly-funded homebirth programs in Victoria, Australia: A cross-sectional survey
Publication date: Available online 10 August 2018
Source: Women and Birth
Author(s): Della A. Forster, Heather McKay, Mary-Ann Davey, Rhonda Small, Fiona Cullinane, Michelle Newton, Rhonda Powell, Helen L. McLachlan
Abstract
Background
It is critical women's voices are heard if there is to be more widespread implementation of midwifery-led continuity models. Publicly-funded homebirth is one such model, yet there has been limited systematic evaluation from the women's perspective.
Aim
Examine women's experiences of and views about the two publicly-funded homebirth programs in Victoria, Australia.
Methods
A cross-sectional design was used. All eligible women enrolled in the two pilot homebirth programs in metropolitan Melbourne whose infants were eight weeks of age or more during the evaluation period were invited to participate in a postal survey. A structured questionnaire was used, with some open-ended questions to enable extra comments. We explored women's reasons for choosing homebirth; views of care; experience of labour and birth; views on transfer; and overall experience of the homebirth program. Data were analysed using descriptive statistics. Simple thematic analysis was used for open-ended questions.
Findings
The survey response rate was 71% (96/136). A high percentage of women rated their care as 'Very good': pregnancy 81%; labour and birth 90%; and the early postpartum period 83%. Women reported low levels of anxiety during labour and birth, were able to express their feelings, felt in control, and coped physically and emotionally better than they had expected. They felt well supported by midwives and overall reported very positive experiences of the homebirth programs.
Conclusions
These two publicly-funded homebirth pilot programs demonstrated very positive care ratings by women. These findings, along with the clinical outcomes (reported separately), support the continuation and expansion of the program.
https://ift.tt/2Mz9dMM
Correction to: To See or NOsee: The Debate on the Nocebo Effect and Optimizing the Use of Biosimilars
The article "To See or NOsee: The Debate on the Nocebo Effect and Optimizing the Use of Biosimilars", written by Mourad F. Rezk and Burkhard Pieper was originally published electronically on the publisher's internet portal (currently SpringerLink) on June 5, 2018 without open access.
https://ift.tt/2vTTEbv
Prostate Cancer in Primary Care
Abstract
Prostate cancer is a common malignancy seen worldwide. The incidence has risen in recent decades, mainly fuelled by more widespread use of prostate-specific antigen (PSA) testing, although prostate cancer mortality rates have remained relatively static over that time period. A man's risk of prostate cancer is affected by his age and family history of the disease. Men with prostate cancer generally present symptomatically in primary care settings, although some diagnoses are made in asymptomatic men undergoing opportunistic PSA screening. Symptoms traditionally thought to correlate with prostate cancer include lower urinary tract symptoms (LUTS), such as nocturia and poor urinary stream, erectile dysfunction and visible haematuria. However, there is significant crossover in symptoms between prostate cancer and benign conditions affecting the prostate such as benign prostatic hypertrophy (BPH) and prostatitis, making it very challenging to distinguish between them on the basis of symptoms. The evidence for the performance of PSA in asymptomatic and symptomatic men for the diagnosis of prostate cancer is equivocal. PSA is subject to false positive and false negative results, affecting its clinical utility as a standalone test. Clinicians need to counsel men about the risks and benefits of PSA testing to inform their decision-making. Digital rectal examination (DRE) by primary care clinicians has some evidence to show discrimination between benign and malignant conditions affecting the prostate. Patients referred to secondary care for diagnostic testing for prostate cancer will typically undergo a transrectal or transperineal biopsy, where a number of samples are taken and sent for histological examination. These biopsies are invasive procedures with side effects and a risk of infection and sepsis, and alternative tests such as multiparametric magnetic resonance imaging (mpMRI) are currently being trialled for their accuracy and safety in diagnosing clinically significant prostate cancer.
https://ift.tt/2Mhsp4H
Shadow over abdomen
Description
Male neonate was born by normal vaginal delivery at 38 weeks. He was antenatally diagnosed to have dextrocardia, congenitally corrected transposition of great arteries, moderate ventricular septal defect and pulmonary atresia. He was born in good condition and cried at birth. However, he was noted to have saturation of 65%–70% in air and started on continuous positive airway pressure and transferred to neonatal intensive care unit for further monitoring. Postnatal echocardiography confirmed the diagnosis, and he was started on prostaglandin E1 (PGE1) at 5 nanogram/kg/min.
On day 3 of life, he underwent a cardiac gated CT angiography (CTA) for further understanding of anatomy and confirmation of diagnosis. In view of need for PGE1 until transfer to tertiary cardiac surgical centre, a peripherally inserted central venous catheter was inserted in the following 12 hours. He underwent an abdominal X-ray to check long line position (figure 1).
...
https://ift.tt/2vB3LT3
Unexpected cause for eyelid swelling and ptosis: rigid gas permeable contact lens migration following a 28-year-old trauma
A patient presented with left upper eyelid swelling and ptosis. The MRI reported a cyst with proteinaceous content. On surgical excision of the cyst, a rigid gas permeable (RGP) contact lens was found. The RGP lens was encapsulated within the upper eyelid soft tissue. It was later revealed that the patient experienced childhood trauma while wearing RGP contact lenses 28 years previously. The patient assumed that the RGP lens fell out and was lost; however, it can be inferred that the lens migrated into the eyelid and resided there asymptomatically for 28 years.
https://ift.tt/2AZ0ylp
Kikuchi-Fujimoto disease: a rare cause of cervical lymphadenopathy and fever
A 28-year-old Pakistani man with previously treated latent tuberculosis (TB) presented with a 3-month history of productive cough, fever, drenching night sweats, anorexia, sore throat and tender left cervical lymphadenopathy. Extensive biochemical and microbiological tests, and imaging studies were all inconclusive. Lymph node biopsy revealed the diagnosis of Kikuchi-Fujimoto disease (KFD). He had persistent fever and anorexia during admission despite supportive measures which resolved quickly on starting prednisolone. He remained well after being weaned off steroids on 18 weeks' follow-up. KFD is a rare, self-limiting disease which can mimic several serious conditions such as TB and lymphoma. Prompt diagnosis with lymph node biopsy is paramount in addressing diagnostic uncertainty and avoids starting potentially toxic treatment on these patients.
https://ift.tt/2vz73pR
Bitter experience with liquorice sweetening agent resulting in apparent mineralocorticoid excess with periodic paralysis
Chronic liquorice ingestion is a rare cause of secondary hypertension and hypokalaemia with periodic paralysis. We report the case of a middle-aged Indian man who presented with hypertension and hypokalaemic alkalosis with recurrent bouts of periodic paralysis. Biochemical investigations revealed suppressed plasma renin and aldosterone concentrations with normal cortisol concentration. A detailed history revealed that he was addicted for the last 5 years to a form of chewing tobacco mixed with herbal preparations as a sweetening agent which on analysis revealed active principles of glycyrrhizin using the thin liquid chromatography method. The hypokalaemia resolved and hypertension control improved significantly after discontinuing liquorice consumption, and the patient was asymptomatic at 1-year follow-up. Long-term liquorice ingestion should be kept in mind as a reversible cause of hypokalaemic periodic paralysis, with a meticulous history and biochemical evaluation helping in identifying this recognisable and curable medical disorder.
https://ift.tt/2AWPPYE
Johanson-Blizzard syndrome with associated urogenital anomalies
We present a case of a child with pancreatic insufficiency and facial defects typical of Johanson-Blizzard syndrome (JBS), along with the more facultative anomalies of the JBS, such as those of the urogenital system including persistent urogenital sinus, urethral duplication and dysplastic kidneys. Fetal ultrasound in a 21-year-old G1P1 woman revealed ambiguous genitalia. Examination at birth revealed a phallic structure with urethral meatus, non-palpable gonads, two orifices in close proximity in the perineum, with the anterior being a common urogenital channel and the posterior, the rectum. A voiding cystourethrogram/genitogram showed bilateral high-grade vesicoureteral reflux and a common urogenital sinus extending 1.5 cm before dividing into three channels: the native urethra, an accessory urethra directed anteriorly towards the clitoris and a septate vagina with uterus didelphys. JBS was suspected by clinical presentation and confirmed by UBR1 molecular testing (46,XX). At 16 months of age, she underwent feminising genitoplasty and posterior sagittal anorectoplasty.
https://ift.tt/2vwlOtw
Post-traumatic bony impingement into vagina: a rare cause of urethrovaginal fistula
A 22-year-old woman met with road traffic accident 6 months back following which she underwent exploratory laparotomy with intraperitoneal bladder rupture repair. She presented with urethrovaginal fistula due to a fragment of fractured pubic bone impinging into the anterior vaginal wall. The findings were confirmed on CT scan and cystoscopy. The patient was managed with removal of the bony spicule and transvaginal repair of urethrovaginal fistula with Martius fat pad interposition.
https://ift.tt/2AZ0qlV
Mediastinal lipoblastoma: a rare entity discovered on physical exam
Description
A 3-year-old male with no significant medical or surgical history presents to his paediatrician for annual examination. On auscultation, he was noted to have diminished left-sided breath sounds and heart sounds displaced to the right. The patient had no complaints of pain, difficulty swallowing, shortness of breath or dyspnoea on exertion. An initial chest X-ray was performed which demonstrated complete opacification of the left hemithorax with mediastinal shift towards the right. This was followed by a radiation dose reduced CT of the chest with intravenous contrast, which demonstrated a 7.8x7.4x13.3 cm fat density mass filling the majority of the left lung and extending to the pleura and mediastinum (figure 1A). The patient was optimised for the operating room and underwent a left lateral thoracotomy. Intraoperatively, the mass was identified and noted to have fusion to the pericardium and pleura in its superior margin with all other...
https://ift.tt/2vz5okb
Cross-leg free flap for limb salvage in the setting of radiation
Limb salvage in an irradiated patient with limited recipient vessels leaves few options for reconstruction. Cross-leg free flaps have been used to reconstruct defects that would otherwise lead to amputation in patients with no ipsilateral recipient vessels. We present the first documented case of a cross-leg free flap for limb salvage in a radiated bed after infection and tumour resection.
https://ift.tt/2AZ0m5F
Irinotecan-platinum combination therapy for previously untreated extensive-stage small cell lung cancer patients: a meta-analysis
Abstract
Background
There is still a debate regarding whether regimens combining irinotecan with platinum could replace regimens combining etoposide with platinum, as first-line chemotherapy for extensive-stage small cell lung cancer (ES-SCLC). We performed a meta-analysis to compare these regimens as first-line chemotherapy for ES-SCLC.
Methods
A literature search for randomized controlled trials was performed using the Cochrane Library, PubMed, and Embase. The inverse variance method was used to estimate summary hazard ratios and their 95% confidence intervals for overall survival and progression free survival. Relative risk was used to estimate the overall response rate, disease control rate, 1-year survival, 2-year survival, and adverse event data.
Result
Nine randomized controlled trials (2451 patients) were included. Regimens combining irinotecan and platinum improved overall survival, progression-free survival and overall response rate compared to combination etoposide and platinum regimens. Meanwhile, superior progression-free survival and overall response rate outcomes were observed in the Asian subgroup of patients. These patients receiving a combination irinotecan and platinum regimen experienced grade 3–4 diarrhea more frequently and experienced less hematologic toxic events than the non-Asian groups.
Conclusions
Our data suggest that a combination irinotecan and platinum regimen can prolong overall survival, progression-free survival and overall response rate for patients with ES-SCLC as compared to a combination etoposide and platinum regimen. And the Asian patients could benefit from irinotecan combined with platinum easier.
https://ift.tt/2Mh1sON
Natural product derivative Gossypolone inhibits Musashi family of RNA-binding proteins
Abstract
Background
The Musashi (MSI) family of RNA-binding proteins is best known for the role in post-transcriptional regulation of target mRNAs. Elevated MSI1 levels in a variety of human cancer are associated with up-regulation of Notch/Wnt signaling. MSI1 binds to and negatively regulates translation of Numb and APC (adenomatous polyposis coli), negative regulators of Notch and Wnt signaling respectively.
Methods
Previously, we have shown that the natural product (−)-gossypol as the first known small molecule inhibitor of MSI1 that down-regulates Notch/Wnt signaling and inhibits tumor xenograft growth in vivo. Using a fluorescence polarization (FP) competition assay, we identified gossypolone (Gn) with a > 20-fold increase in Ki value compared to (−)-gossypol. We validated Gn binding to MSI1 using surface plasmon resonance, nuclear magnetic resonance, and cellular thermal shift assay, and tested the effects of Gn on colon cancer cells and colon cancer DLD-1 xenografts in nude mice.
Results
In colon cancer cells, Gn reduced Notch/Wnt signaling and induced apoptosis. Compared to (−)-gossypol, the same concentration of Gn is less active in all the cell assays tested. To increase Gn bioavailability, we used PEGylated liposomes in our in vivo studies. Gn-lip via tail vein injection inhibited the growth of human colon cancer DLD-1 xenografts in nude mice, as compared to the untreated control (P < 0.01, n = 10).
Conclusion
Our data suggest that PEGylation improved the bioavailability of Gn as well as achieved tumor-targeted delivery and controlled release of Gn, which enhanced its overall biocompatibility and drug efficacy in vivo. This provides proof of concept for the development of Gn-lip as a molecular therapy for colon cancer with MSI1/MSI2 overexpression.
https://ift.tt/2OqHka6
Inhibition of JAK2/STAT3 signaling suppresses bone marrow stromal cells proliferation and osteogenic differentiation, and impairs bone defect healing
Journal Name: Biological Chemistry
Issue: Ahead of print
https://ift.tt/2nqwNAr
Comparison of esophageal submucosal glands in experimental models for esophagus tissue engineering applications
Abstract
Objective
Esophagus tissue engineering holds promises to overcome the limitations of the presently employed esophageal replacement procedures. This study investigated 5 animal models for esophageal submucosal glands (ESMG) to identify models appropriate for regenerative medicine applications. Furthermore, this study aimed to measure geometric parameters of ESMG that could be utilized for fabrication of ESMG-specific scaffolds for esophagus tissue engineering applications.
Methods
Ovine, avian, bovine, murine, and porcine esophagus were investigated using Hematoxylin–Eosin (HE), Periodic Acid Schiff (PAS), and Alcian Blue (AB), with AB applied in 3 pH levels (0.2, 1.0, and 2.5) to detect sulphated mucous. Celleye® (version F) was employed to gain parametric data on ESMGs (size, perimeter, distance to lumen, and acini concentration) necessary for scaffold fabrication.
Results
Murine, bovine, and ovine esophagus were devoid of ESMG. Avian esophagus demonstrated sulphated acid mucous producing ESMGs with a holocrine secretion pattern, whereas sulphated acid and neutral mucous producing ESMGs with a merocrine secretion pattern were observed in porcine esophagus. Distance of ESMGs to lumen ranged from 127–340 μm (avian) to 916–983 μm (porcine). ESMGs comprised 35% (avian) to 45% (porcine) area of the submucosa. ESMG had an area of 125000 μm2 (avian) to 580000 μm2 (porcine).
Conclusion
Avian and porcine esophagus possesses ESMGs. However, porcine esophagus correlates with data available on human ESMGs. Geometric and parametric data obtained from ESMG are valuable for the fabrication of ESMG-specific scaffolds for esophagus tissue engineering using the hybrid construct approach.
https://ift.tt/2M960av
Impact of deformable image registration on dose accumulation applied electrocardiograph-gated 4DCT in the heart and left ventricular myocardium during esophageal cancer radiotherapy
Abstract
Background
The deformable image registration (DIR) technique has the potential to realize the dose accumulation during radiotherapy. This study will analyze the feasibility of evaluating dose-volume parameters for the heart and left ventricular myocardium (LVM) by applying DIR.
Methods
The electrocardiograph-gated four-dimensional CT (ECG-gated 4DCT) data of 21 patients were analyzed retrospectively. The heart and LVM were contoured on 20 phases of 4DCT (0%, 5%,…,95%). The heart and LVM in the minimum volume/dice similarity coefficient (DSC) phase (Volume min/DSC min) were deformed to the maximum volume/DSC phase (Volume max/ DSC max), which used the intensity-based free-form DIR algorithm of MIM software. The dose was deformed according to the deformation vector. The variations in volume, mean dose (Dmean), V20, V30 and V40 for the heart and LVM before and after DIR were compared, and the reference phase was the Volume max/DSC max phase.
Results
For the heart, the difference between the pre- and post-registration Volume min and Volume max were reduced from 13.87 to 1.72%; the DSC was increased from 0.899 to 0.950 between the pre- and post-registration DSC min phase relative to the DSC max phase. The post-registration Dmean, V20, V30 and V40 of the heart were statistically significant compared to those in the Volume max/DSC max phase (p < 0.05). For the LVM, the difference between the pre- and post-registration Volume min and Volume max were only reduced from 18.77 to 17.38%; the DSC reached only 0.733 in the post-registration DSC min phase relative to the DSC max phase. The pre- and post-registration volume, Dmean, V20, V30 and V40 of the LVM were all statistically significant compared to those in the Volume max/DSC max phase (p < 0.05).
Conclusions
There was no significant relationship between the variation in dose-volume parameters and the variation in the volume and morphology for the heart; however, the inconsistency of the variation in the volume and morphology for the LVM was a major factor that led to uncertainty in the dose-volume evaluation. In addition, the individualized local deformation registration technology should be applied in dose accumulation for the heart and LVM.
https://ift.tt/2KGYFtq
New Research From Psychological Science
Read about the latest research published in Psychological Science:
The Common Time Course of Memory Processes Revealed
John R. Anderson, Jelmer P. Borst, Jon M. Fincham, Avniel Singh Ghuman, Caitlin Tenison, and Qiong Zhang
What happens in the short period of time during which someone retrieves a well-known fact? Anderson and colleagues used magnetoencephalography (MEG), a neuroimaging technique that allows the mapping of brain activity on a millisecond-by-millisecond basis, to identify the stages of generating answers from memory, their duration, and their brain location. In two experiments, while participants were in a MEG device, they were asked either to recognize previously learned word-pairs or to answer arithmetic problems by recalling previously solved problems. By using hidden semi-Markov chain models and multivariate pattern analysis, the authors identified similar "bumps" of activity in both tasks. These bumps took place in similar brain regions and had similar duration during the course of the memory processes in both experiments, despite the fact that one involved the processing of words and the other involved the processing of numbers. Moreover, the bumps showed a separation between the retrieval stage that identified relevant information in memory and the decision stage that determined the response. These results support a two-stage model of memory recognition and recall.
In Defense of the Commons: Young Children Negatively Evaluate and Sanction Free Riders
Fan Yang, You-Jung Choi, Antonia Misch, Xin Yang, and Yarrow Dunham
Contributing to the common good at some personal cost is at the heart of human society, but free riders can benefit from others' contributions without paying costs themselves. In several studies, Yang and colleagues explored the development of the tendencies to track and sanction free riders by testing 4- to 5-year-olds and 6- to 10-year-olds. In several studies, the authors presented children with scenarios in which a group could get large rewards if all members contributed or small rewards if only some members contributed. They then indicated each member's contribution and asked children to judge each group member. Across six studies, results indicated that children as young as 4 years old negatively evaluated the free riders. When given a chance to punish the free riders, children would do it, and they would also not choose to collaborate or reward free riders. The intentionality of free riding only mattered for older children who did not evaluate an unintentional free rider as harshly as an intentional one. These results indicate a strong and early-emerging tendency to negatively evaluate and punish free riders.
Reexamining the Link Between Economic Downturns and Racial Antipathy: Evidence That Prejudice Against Blacks Rises During Recessions
Emily C. Bianchi, Erika V. Hall, and Sarah Lee
It has been suggested that economic downturns might heighten animosity and violence toward people dissimilar to oneself, intensifying racial discord. To test this suggestion, Bianchi and colleagues analyzed the answers of White respondents participating in the American National Survey, from 1964 to 2012, regarding perceptions towards Blacks. The authors compared the respondents' perceptions of Black people across the years in relation to the economic conditions of each year, as measured by the unemployment rate of the entire population. In years of higher unemployment, White respondents reported feeling less warmly toward Black people, regardless of the employment status or education level of the respondents. This pattern of results was also obtained in another study that used implicit measures of racism. Furthermore, Bianchi and colleagues also found that in bad economic years, Black musicians were less likely to have a recording enter the Billboard top 10 American hits, and Black politicians were less likely to be elected to the U.S. House of Representatives. These results suggest an association between bad economic conditions and negative attitudes and greater discrimination toward Black individuals.
https://ift.tt/2MzjXuI
Communications principles for inviting inquiry and exploration through science and data visualization
Abstract
Science, in the popular imagination, is about finding answers to questions. Scientists make discoveries, develop theories, and deliver those discoveries and theories to audiences with an interest in the truth as backed up by science. Well-designed data visualization (dataviz), by contrast, can generate and address not only new questions but new kinds of questions. It has the particular quality of allowing its viewers, users and makers the ability to generate new inquiries, and to put them in a better place to answer them. Dataviz offers aesthetic and interactive platforms for discussion and inquiry that can help scientists to both do their work and better communicate their work to broader audiences.Here I will illustrate and examine case studies from multiple points along the rich and varied possibility space that opens up when science and dataviz work together. I will also introduce three communication principles that I have learned from my involvement with hundreds of dataviz projects over the years. Well-designed dataviz can help scientists and those involved with science find ways to navigate the multiple competing interests and priorities inherent in both communication to non-scientists and exploratory data-rich interfaces.http://sicb.org/meetings/2018/abstracts/correctsymposia.phphttps://ift.tt/2vwbwKi
Sexually dimorphic eye-loss driven by ecological selection in an ostracod crustacean: support for the reproductive role hypothesis
Abstract
Euphilomedes carcharodonta ostracods exhibit sex-specific eye-loss, with females lacking image-forming compound eyes compared to males and related species. The standard assumption is that sexual dimorphism is driven by sexual selection. However, previous work in E. carcharodonta suggests that male eyes are used to evade predators in the male-specific ecological niche, and that male-eyes lack the resolution to search for females. In this study, we examine whether sexual selection or ecological selection drives the retention of male eyes. Ecological niche differentiation was hypothesized by Darwin (1871) to be an alternative selective force for sexual dimorphism either through food competition or through dimorphic sex-role behavior, the reproductive role hypothesis. As of yet, there is little experimental evidence supporting this hypothesis. Here, we experimentally blindfold male E. carcharodonta to mimic the female phenotype and examine the effects on sex-specific niches and behavior. Blindfolding does not appear to grossly change male behavior, nor do females behave differently when exposed to blindfolded males. This leads us to conclude that the development of complex eyes in male E. arises from ecological selection rather than sexual selection.https://ift.tt/2OrqQPn
The Genetics of Dementia with Lewy Bodies: Current Understanding and Future Directions
Abstract
Purpose of Review
Dementia with Lewy bodies (DLB) is a neurodegenerative disease that can be clinically and pathologically similar to Parkinson's disease (PD) and Alzheimer's disease (AD). Current understanding of DLB genetics is insufficient and has been limited by sample size and difficulty in diagnosis. The first genome-wide association study (GWAS) in DLB was performed in 2017; a time at which the post-GWAS era has been reached in many diseases.
Recent Findings
DLB shares risk loci with AD, in the APOE E4 allele, and with PD, in variation at GBA and SNCA. Interestingly, the GWAS suggested that DLB may also have genetic risk factors that are distinct from those in AD and PD.
Summary
Although off to a slow start, recent studies have reinvigorated the field of DLB genetics and these results enable us to start to have a more complete understanding of the genetic architecture of this disease.
https://ift.tt/2AXtR7U
Flexor carpi radialis brevis: a rare accessory muscle presenting as an intersection syndrome of the wrist
Abstract
The flexor carpi radialis brevis (FCRB) is a rare accessory muscle of the forearm and wrist. It is typically asymptomatic, but has been discovered either incidentally during cadaveric studies or at the time of surgery in patients with distal forearm injury. Rarely, the FCRB muscle is associated with pain. We report a patient with wrist pain related to intersection between the tendon of the FCRB muscle and the tendon of the flexor carpi radialis (FCR) muscle, with an associated longitudinal split tear of the FCR tendon, documented by magnetic resonance imaging (MRI). To our knowledge, this is only the second report in the English literature of this intersection syndrome.
https://ift.tt/2M4IvQ1
The understanding of healthcare workers on the content of palliative care policy in Shesilweni Swaziland: a qualitative study
Teluleko Nhlonipho Maseko, Collin Pfaff and Aziza Mwisongo
https://ift.tt/2vVkXSQ
Cancers, Vol. 10, Pages 268: The Methylation Status of the Epigenome: Its Emerging Role in the Regulation of Tumor Angiogenesis and Tumor Growth, and Potential for Drug Targeting
Cancers, Vol. 10, Pages 268: The Methylation Status of the Epigenome: Its Emerging Role in the Regulation of Tumor Angiogenesis and Tumor Growth, and Potential for Drug Targeting
Cancers doi: 10.3390/cancers10080268
Authors: Luciano Pirola Oskar Ciesielski Aneta Balcerczyk
Approximately 50 years ago, Judah Folkman raised the concept of inhibiting tumor angiogenesis for treating solid tumors. The development of anti-angiogenic drugs would decrease or even arrest tumor growth by restricting the delivery of oxygen and nutrient supplies, while at the same time display minimal toxic side effects to healthy tissues. Bevacizumab (Avastin)—a humanized monoclonal anti VEGF-A antibody—is now used as anti-angiogenic drug in several forms of cancers, yet with variable results. Recent years brought significant progresses in our understanding of the role of chromatin remodeling and epigenetic mechanisms in the regulation of angiogenesis and tumorigenesis. Many inhibitors of DNA methylation as well as of histone methylation, have been successfully tested in preclinical studies and some are currently undergoing evaluation in phase I, II or III clinical trials, either as cytostatic molecules—reducing the proliferation of cancerous cells—or as tumor angiogenesis inhibitors. In this review, we will focus on the methylation status of the vascular epigenome, based on the genomic DNA methylation patterns with DNA methylation being mainly transcriptionally repressive, and lysine/arginine histone post-translational modifications which either promote or repress the chromatin transcriptional state. Finally, we discuss the potential use of “epidrugs” in efficient control of tumor growth and tumor angiogenesis.
https://ift.tt/2vxEHfQ
Cancers, Vol. 10, Pages 267: The Current Role of Salvage Surgery in Recurrent Head and Neck Squamous Cell Carcinoma
Cancers, Vol. 10, Pages 267: The Current Role of Salvage Surgery in Recurrent Head and Neck Squamous Cell Carcinoma
Cancers doi: 10.3390/cancers10080267
Authors: Marc Hamoir Sandra Schmitz Carlos Suarez Primoz Strojan Kate A Hutcheson Juan P Rodrigo William M Mendenhall Ricard Simo Nabil F Saba Anil K D'Cruz Missak Haigentz Carol R Bradford Eric M Genden Alessandra Rinaldo Alfio Ferlito
Chemoradiotherapy has emerged as a gold standard in advanced squamous cell carcinoma of the head and neck (SCCHN). Because 50% of advanced stage patients relapse after nonsurgical primary treatment, the role of salvage surgery (SS) is critical because surgery is generally regarded as the best treatment option in patients with recurrent resectable SCCHN. Surgeons are increasingly confronted with considering operation among patients with significant effects of failed non-surgical primary treatment. Wide local excision to achieve clear margins must be balanced with the morbidity of the procedure, the functional consequences of organ mutilation, and the likelihood of success. Accurate selection of patients suitable for surgery is a major issue. It is essential to establish objective criteria based on functional and oncologic outcomes to select the best candidates for SS. The authors propose first to understand preoperative prognostic factors influencing survival. Predictive modeling based on preoperative information is now available to better select patients having a good chance to be successfully treated with surgery. Patients with a high comorbidity index, advanced oropharyngeal or hypopharyngeal primary tumors, and both local and regional recurrence have a very limited likelihood of success with salvage surgery and should be strongly considered for other treatments. Following SS, identifying patients with postoperative prognostic factors predicting high risk of recurrence is essential because those patients could benefit of adjuvant treatment or be included in clinical trials. Finally, defining HPV tumor status is needed in future studies including recurrent oropharyngeal SCC patients.
https://ift.tt/2MA2qlW
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Αλέξανδρος Γ. Σφακιανάκης Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,0030693260717...
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heory of COVID-19 pathogenesis Publication date: November 2020Source: Medical Hypotheses, Volume 144Author(s): Yuichiro J. Suzuki ScienceD...
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Alimentary Pharmacology &Therapeutics, EarlyView. https://ift.tt/2qECBIJ
