Many radiotherapy research centers have recently installed novel research platforms enabling the investigation of the radiation response of tumors and normal tissues in small animal models, possibly in combination with other treatment modalities. Many more research institutes are expected to follow in the coming years. These novel platforms are capable of mimicking human radiotherapy more closely than older technology. To facilitate the optimal use of these novel integrated precision irradiators and various small animal imaging devices, and to maximize the impact of the associated research, the ESTRO committee on coordinating guidelines ACROP (Advisory Committee in Radiation Oncology Practice) has commissioned a report to review the state of the art of the technology used in this new field of research, and to issue recommendations.
from Imaging via alkiviadis.1961 on Inoreader http://ift.tt/2yTQqnI
To investigate the feasibility and accuracy of robot-assisted brachytherapy for skull base tumours.
from Imaging via alkiviadis.1961 on Inoreader http://ift.tt/2BazkIj
Precision medicine offers better treatment options and improved survival for cancer patients based on individual variability. As the success of precision medicine depends on robust biomarkers, the requirement for improved imaging biomarkers that reflect tumor biology has grown exponentially. Radiomics, the field of study in which high-throughput data are generated and large amounts of advanced quantitative features are extracted from medical images, has shown great potential as a source of quantitative biomarkers in the field of oncology. Radiomics provides quantitative information about the morphology, texture, and intratumoral heterogeneity of the tumor itself as well as features related to pulmonary function. Hence, radiomics data can be used to build descriptive and predictive clinical models that relate imaging characteristics to tumor biology phenotypes. In this review, we describe the workflow of CT radiomics, types of CT radiomics, and its clinical application in thoracic oncology.
Positron Emission tomography Response Criteria In Solid Tumors (PERCIST) version 1.0 was introduced in 2009 for objective assessment of tumor metabolic response using 18F-FDG PET/CT. Practical PERCIST: A Simplified Guide to PET Response Criteria in Solid Tumors 1.0 was published in 2016 to review and clarify some of the issues with the PERCIST. In this article, we reflect on the benefits and challenges of implementing PERCIST, and speculate on topics that could be discussed in PERCIST 1.1 in the future.
The development of immune checkpoint inhibitors [monoclonal antibodies targeting cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), programmed cell death protein 1 (PD-1) or programmed death ligand 1 (PD-L1)] represents a major breakthrough in cancer therapy. Although they present a favorable risk/benefit ratio, immune checkpoint blockade therapies have a very specific safety profile. Due to their unique mechanism of action, they entail a new spectrum of adverse events that are mostly immune related [immune-related adverse events (irAEs)], notably mediated by the triggering of cytotoxic CD4+/CD8+ T cell activation. Cutaneous toxicities appear to be one of the most prevalent irAEs, both with anti-PD-1 and anti-CTLA-4 agents or with the newly developed anti-PD-L1 agents, which corresponds to a class effect. They are observed in more than one-third of the treated patients, mainly in the form of a maculopapular rash (eczema-like spongiotic dermatitis) and pruritus. A wide range of other dermatologic manifestations can also occur, including lichenoid reactions, psoriasis, acneiform rashes, vitiligo-like lesions, autoimmune skin diseases (e.g., bullous pemphigoid, dermatomyositis, alopecia areata), sarcoidosis or nail and oral mucosal changes. In addition, the use of anti-CTLA-4 and anti-PD-1 therapies in combination is associated with the development of more frequent, more severe and earlier cutaneous irAEs compared to single agents. In most cases, these dysimmune dermatologic adverse events remain self-limiting and readily manageable. Early recognition and adequate management, however, are critical to prevent exacerbation of the lesions, to limit treatment interruption and to minimize quality of life impairment. This review describes the variable clinical and histopathologic aspects of dermatologic irAEs induced by immune checkpoint inhibitors. Appropriate treatment and counseling are also proposed, with a step-by-step approach for optimized management by both practicing oncologists and dermatologists.
Cosmetics, Vol. 4, Pages 57: Guidelines for Formulating Anti-Pollution Products
Cosmetics doi: 10.3390/cosmetics4040057
Authors: Niraj Mistry
Anti-pollution skin care and cosmetic products are witnessing a significant growth in the last couple of years due to worsening air quality across the world, and increasing awareness and concern regarding the adverse impact of various environmental pollutants on skin. The various pollutants, like particulate matter, oxides of nitrogen and sulphur, ozone, and polyaromatic hydrocarbons damage skin by different mechanism resulting in skin dryness, loss of firmness, dark spots, uneven skin tone, fine lines and wrinkles, aggravation of acne, and inflammation. The task of developing globally harmonized products is very challenging due differences in skin types according to ethnicity, variation in seasonal weather pattern, differences in benefit expectations, and variances in personal care and cosmetics usage habits of consumers in different regions of the world. However, an increasing understanding about the mechanism by which various pollutants damage the skin manifesting into various extrinsic signs of skin damage and development of various actives that counter the impact of different environmental aggressors has helped formulators to develop different products and to establish efficacy by in vitro and in vivo tests. The article summarizes approaches for formulation development, and a list of few actives classified based in their mechanism action is given. A representative list of products based on their mechanism of action is also given and few potential opportunities for the future are suggested.
IJMS, Vol. 18, Pages 2748: Canadine from Corydalis turtschaninovii Stimulates Myoblast Differentiation and Protects against Myotube Atrophy
International Journal of Molecular Sciences doi: 10.3390/ijms18122748
Authors: Heyjin Lee Sang-Jin Lee Gyu-Un Bae Nam-In Baek Jae-Ha Ryu
Cachexia and sarcopenia are the main causes of muscle atrophy. These result in a reduction in the muscle fiber area, myo-protein content, and muscle strength, with various molecular modulators being involved. Although several reports have proposed potential therapeutic agents, no effective treatments have been found for muscle atrophy. We searched for myogenic modulators from medicinal plants to treat muscle diseases. We isolated six alkaloids from Corydalis turtschaninovii and evaluated their myogenic potential by using the MyoD reporter gene assay in C2C12 cells. Among the tested compounds, canadine showed the strongest transactivation of MyoD and increased MHC expression during myogenesis. The activation of p38 MAP kinase and Akt are major mechanisms that contribute to the myogenesis by canadine. Canadine increased the number of multinucleated and cylinder-shaped myotubes during myogenesis of C2C12 myoblasts. To determine the preventive effect of canadine in cancer-induced muscle wasting, differentiated C2C12 myotubes were treated with conditioned media from CT26 colon carcinoma culture (CT26 CM) in the presence of canadine. Canadine ameliorated the muscle protein degradation caused by CT26-CM by down-regulating the muscle specific-E3 ligases, MAFbx/atrogin-1 and MuRF1. In this study, we found that canadine from C. turtschaninovii stimulates myogenesis and also inhibits muscle protein degradation. Therefore, we suggest canadine as a protective agent against muscle atrophy.
IJMS, Vol. 18, Pages 2747: A Molecular Interpretation on the Different Penetration Enhancement Effect of Borneol and Menthol towards 5-Fluorouracil
International Journal of Molecular Sciences doi: 10.3390/ijms18122747
Authors: Ran Wang Zhimin Wu Shufang Yang Shujuan Guo Xingxing Dai Yanjiang Qiao Xinyuan Shi
Borneol and menthol are terpenes that are widely used as penetration enhancers in transdermal drug delivery. To explore their penetration-enhancement effects on hydrophilic drugs, 5-fluorouracil (5-FU) was selected as a model drug. An approach that combined in vitro permeation studies and coarse-grained molecular dynamics was used to investigate their penetration-enhancement effect on 5-FU. The results showed that although both borneol and menthol imparted penetration-enhancement effects on 5-FU, these differed in terms of their mechanism, which may account for the observed variations in penetration-enhancement effects. The main mechanism of action of menthol involves the disruption of the stratum corneum (SC) bilayer, whereas borneol involves multiple mechanisms, including the disruption of the SC bilayer, increasing the diffusion coefficient of 5-FU, and inducing the formation of transient pores. The findings of the present study improve our understanding of the molecular mechanism that is underlying 5-FU penetration-enhancement by borneol and menthol, which may be utilized in future investigations and applications.
Viruses, Vol. 9, Pages 388: Stress Granule-Inducing Eukaryotic Translation Initiation Factor 4A Inhibitors Block Influenza A Virus Replication
Viruses doi: 10.3390/v9120388
Authors: Patrick Slaine Mariel Kleer Nathan Smith Denys Khaperskyy Craig McCormick
Eukaryotic translation initiation factor 4A (eIF4A) is a helicase that facilitates assembly of the translation preinitiation complex by unwinding structured mRNA 5′ untranslated regions. Pateamine A (PatA) and silvestrol are natural products that disrupt eIF4A function and arrest translation, thereby triggering the formation of cytoplasmic aggregates of stalled preinitiation complexes known as stress granules (SGs). Here we examined the effects of eIF4A inhibition by PatA and silvestrol on influenza A virus (IAV) protein synthesis and replication in cell culture. Treatment of infected cells with either PatA or silvestrol at early times post-infection resulted in SG formation, arrest of viral protein synthesis and failure to replicate the viral genome. PatA, which irreversibly binds to eIF4A, sustained long-term blockade of IAV replication following drug withdrawal, and inhibited IAV replication at concentrations that had minimal cytotoxicity. By contrast, the antiviral effects of silvestrol were fully reversible; drug withdrawal caused rapid SG dissolution and resumption of viral protein synthesis. IAV inhibition by silvestrol was invariably associated with cytotoxicity. PatA blocked replication of genetically divergent IAV strains, suggesting common dependence on host eIF4A activity. This study demonstrates that the core host protein synthesis machinery can be targeted to block viral replication.
Early diagnosis of Turner syndrome (TS) is necessary to facilitate appropriate management, including growth promotion. Not all girls with TS have overt short stature, and comparison with parental height (Ht) is needed for appropriate evaluation. We examined both the prevalence and diagnostic sensitivity of measured parental Ht in a dedicated TS clinic between 1989 and 2013. Lower end of parental target range (LTR) was calculated as mid-parental Ht (correction factor 12.5 cm minus 8.5 cm) and converted to standard deviation scores (SDS) using UK 1990 data, then compared with patient Ht SDS at first accurate measurement aged > 1 year. Information was available in 172 girls of whom 142 (82.6%) were short at first measurement. However, both parents had been measured in only 94 girls (54.6%). In 92 of these girls age at measurement was 6.93 ± 3.9 years, Ht SDS vs LTR SDS − 2.63 ± 0.94 vs − 1.77 ± 0.81 (p < 0.001), Ht SDS < LTR in 78/92 (85%). Eleven of the remaining 14 girls were < 5 years, while karyotype was 45,X/46,XX in 2 and 45,X/47,XXX in 3.
Conclusion: This study confirms the sensitivity of evaluating height status against parental height but shows that the latter is not being consistently measured.
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What is Known:
• Girls with Turner syndrome are short in relation to parental heights, with untreated final height approximately 20 cm below female population mean.
• Measured parental height is more accurate than reported height.
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What is New:
• In a dedicated Turner clinic, there was 85% sensitivity when comparing patient height standard deviation score at first accurate measurement beyond 1 year of age with the lower end of the parental target range standard deviation.
• However, measured height in both parents had been recorded in only 54.6% of the Turner girls attending the clinic. This indicates the need to improve the quality of growth assessment in tertiary care.
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Genes, Vol. 8, Pages 392: Deciphering the Relationship between Obesity and Various Diseases from a Network Perspective
Genes doi: 10.3390/genes8120392
Authors: Lei Chen Yu-Hang Zhang JiaRui Li ShaoPeng Wang YunHua Zhang Tao Huang Yu-Dong Cai
The number of obesity cases is rapidly increasing in developed and developing countries, thereby causing significant health problems worldwide. The pathologic factors of obesity at the molecular level are not fully characterized, although the imbalance between energy intake and consumption is widely recognized as the main reason for fat accumulation. Previous studies reported that obesity can be caused by the dysfunction of genes associated with other diseases, such as myocardial infarction, hence providing new insights into dissecting the pathogenesis of obesity by investigating its associations with other diseases. In this study, we investigated the relationship between obesity and diseases from Online Mendelian Inheritance in Man (OMIM) databases on the protein–protein interaction (PPI) network. The obesity genes and genes of one OMIM disease were mapped onto the network, and the interaction scores between the two gene sets were investigated on the basis of the PPI of individual gene pairs, thereby inferring the relationship between obesity and this disease. Results suggested that diseases related to nutrition and endocrine are the top two diseases that are closely associated with obesity. This finding is consistent with our general knowledge and indicates the reliability of our obtained results. Moreover, we inferred that diseases related to psychiatric factors and bone may also be highly related to obesity because the two diseases followed the diseases related to nutrition and endocrine according to our results. Numerous obesity–disease associations were identified in the literature to confirm the relationships between obesity and the aforementioned four diseases. These new results may help understand the underlying molecular mechanisms of obesity–disease co-occurrence and provide useful insights for disease prevention and intervention.
Diese Pressemitteilung ist nur auf Englisch erhältlich.
The association of the risk of suicide with cancer at different time points after a new cancer diagnosis is unclear. This study explored the suicide hazard at different time points after a first cancer diagnosis during the 1-year period before suicide. This case–crossover study included 2,907 suicide cases from 2002 to 2012 in Taiwan and compared the odds of suicide risk at different time points during one year after any cancer diagnosis with self-matched periods. The 13th month preceding the suicide date was used as the control period, and the hazard period was the duration from the 1st to 12th month in the conditional logistic regression for case–crossover comparisons. Among major groups of cancers, group of lip, oral cavity, and pharynx cancers tended to have higher risk of suicide than other groups of cancers. The first month of cancer diagnosis was associated with the highest risk of suicide compared with the 13th month before suicide. The odds ratio of suicide were significantly in the first six months after cancer diagnosis but declined afterwards. For example, the adjusted odds ratio [OR] was 3.47 (95% confidence interval [CI]=2.60-4.62) in the first month and 1.53 (95% CI=1.11-2.12) in the sixth month following cancer diagnosis. These findings provide clinicians with a vital reference period during which sufficient support and necessary referral to mental health support should be provided to reduce the risk of suicide among patients with newly diagnosed cancer morbidity. This article is protected by copyright. All rights reserved.
Neuroblastoma comprises the most common neoplasm during infancy (first year of life). This study describes incidence of neuroblastoma in Southern-Eastern Europe (SEE), including -for the first time- the Nationwide Registry for Childhood Hematological Malignancies and Solid Tumors (NARECHEM-ST)/Greece, compared to the US population, while controlling for Human Development Index (HDI). Age-adjusted incidence rates (AIR) were calculated for 1859 childhood (0-14 years) neuroblastoma cases, retrieved from 13 collaborating SEE registries (1990-2016), and were compared with those of SEER/US (N=3166; 1990-2012); temporal trends were assessed using Poisson regression and Joinpoint analyses. The overall AIR was significantly lower in SEE (10.1/million) compared to SEER (11.7 per million); the difference was maximum during infancy (43.7 vs. 53.3 per million, respectively), when approximately one third of cases were diagnosed. Incidence rates of neuroblastoma at ages <1 and 1-4 years were positively associated with HDI, whereas lower median age at diagnosis was correlated with higher overall AIR. Distribution of primary site and histology were similar in SEE and SEER. Neuroblastoma was slightly more common among males compared to females (male-to-female ratio: 1.1), mainly among SEE infants. Incidence trends decreased in infants in Slovenia, Cyprus and SEER and increased in Ukraine and Belarus. The lower incidence in SEE compared to SEER, especially in infants living in low HDI countries possibly indicates a lower level of overdiagnosis in SEE. Hence, increases in incidence rates in infancy noted in some subpopulations should be carefully monitored to avoid the unnecessary costs health impacts of tumors that could potentially spontaneously regress. This article is protected by copyright. All rights reserved.
Our recent studies demonstrate that X-linked inhibitor of apoptosis protein (XIAP) is essential for regulating colorectal cancer invasion. Here we discovered that RhoGDIβ was a key XIAP downstream effector mediating bladder cancer (BC) invasion in vitro and in vivo. We found that both XIAP and RhoGDIβ expressions were consistently elevated in BCs of N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN)-treated mice in comparison to bladder tissues from vehicle-treated mice and human BCs in comparison to the paired adjacent normal bladder tissues. Knockdown of XIAP attenuated RhoGDIβ expression and reduced cancer cell invasion, whereas RhoGDIβ expression was attenuated in BBN-treated urothelium of RING-deletion knockin mice. Mechanistically, XIAP stabilized RhoGDIβ mRNA by its positively regulating nucleolin mRNA stability via Erks-dependent manner. Moreover, ectopic expression of GFP-RhoGDIβ in T24T(shXIAP) cells restored its lung metastasis in nude mice. Our results demonstrate that XIAP-regulated Erks/nucleolin/RhoGDIβ axis promoted BC invasion and lung metastasis. This article is protected by copyright. All rights reserved.
For more than a decade, urinary free cortisol corrected for creatinine (OUFCC) has been used to assess the systemic bioactivity of inhaled corticosteroids in children with asthma. Paediatric normative ranges, however, have not been established. The aim of the present study was to define a preliminary range for OUFCC in Tanner stage 1 children.
A post hoc analysis was performed of 26 Tanner stage one children (aged 5–11 years) with mild asthma only requiring prn (pro re nata) treatment with short-acting β2-agonists, who participated in a 3-way cross-over knemometry study. The study comprised a run-in, two washout periods and three treatment periods (2 weeks each). Urine was collected at the end of each period. A normative range was derived using the 95% prediction interval for the geometric mean OUFCC, calculated from run-in and washout periods.
Twenty-six children contributed 41 OUFCC values. The geometric mean OUFCC was 9.0 nmol/mmol (95% PI: 3.6, 22.7 nmol/mmol).
The OUFCC preliminary normative range was 3.6 to 22.7 nmol/mmol in Tanner stage one children. A larger study in healthy children is warranted to confirm these findings and to assess potential differences in OUFCC across developmental stages and age groups, and by gender and race.
2013-004719-32,
NCT02063139
Demonstrate the role of endovascular management in the treatment of internal mammary artery (IMA) injuries using transcatheter embolization reviewing our 7-year experience.
Our retrospective analysis of cases consists of a total of 12 patients (8 M and 4 F; mean age 52 years) who underwent angiographic studies and transcatheter embolization for IMA injuries. Causes of vascular injury were divided in high-energy trauma (n = 6), iatrogenic (n = 3) and penetrating injuries (n = 3). Type of trauma, associated injury, imaging findings, treatments and complications were assessed. Imaging findings included active haemorrhage, pseudoaneurysm and focal dissection.
Embolization was performed with microcoils in all patients; complete thrombosis was obtained in four patients by additional injection of Spongostan pledgets and in two patients with 300–500 μm particles. The technical success rate was 100%. No patient died as a direct result of vascular injury; one died of myocardial contusion and one for severe multiorgan failure related to high-energy trauma. No major and minor complications were registered. No patient required emergency surgery or subsequent surgical treatment.
Transcatheter embolization offers an effective, efficient and safe alternative to conventional surgical management of IMA injuries.
We aimed to determine changes in miR-17-92 cluster expression in serum and granulocytes from patients with antithyroid drug (ATD)-induced agranulocytosis.
In this study, real-time polymerase chain reaction (PCR) was used to detect serum miR-17-92 expression levels in 20 ATD-induced agranulocytosis and 16 control patients. Importantly, dynamic changes in neutrophil counts from granulocytopenia to agranulocytosis were observed in 6 of the 20 patients. miR-17-92 expression levels in granulocytes of those six patients under the granulocytopenia condition were measured and compared with corresponding granulocyte samples after recovery. Additionally, the expression levels of these miRNAs in patients with type I or type II bone marrow characteristics were analyzed, and the correlation between miR-17-92 and serum free thyroxine level was analyzed.
We found that levels of miR-17-92 expression decreased in both serum and pre-agranulocytosis granulocytes from patients with ATD-induced agranulocytosis compared with those in serum and granulocytes from both recovered patients and control patients. However, no difference among patients with either type of bone marrow characteristics was observed, and no correlation between serum miR-17-92 and free thyroxine levels was found.
In ATD-induced agranulocytosis, expression of the miR-17-92 cluster is reduced in both serum and granulocytes, though this alteration does not correlate with bone marrow characteristics or thyroid function.
IJERPH, Vol. 14, Pages 1590: Time-Dependent Toxic and Genotoxic Effects of Zinc Oxide Nanoparticles after Long-Term and Repetitive Exposure to Human Mesenchymal Stem Cells
International Journal of Environmental Research and Public Health doi: 10.3390/ijerph14121590
Authors: Pascal Ickrath Martin Wagner Agmal Scherzad Thomas Gehrke Marc Burghartz Rudolf Hagen Katrin Radeloff Norbert Kleinsasser Stephan Hackenberg
Zinc oxide nanoparticles (ZnO-NP) are widely spread in consumer products. Data about the toxicological characteristics of ZnO-NP is still under controversial discussion. The human skin is the most important organ concerning ZnO-NP exposure. Intact skin was demonstrated to be a sufficient barrier against NPs; however, defect skin may allow NP contact to proliferating cells. Within these cells, stem cells are the most important toxicological target for NPs. The aim of this study was to evaluate the genotoxic and cytotoxic effects of ZnO-NP at low-dose concentrations after long-term and repetitive exposure to human mesenchymal stem cells (hMSC). Cytotoxic effects of ZnO-NP were measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Furthermore, genotoxicity was evaluated by the comet assay. For long-term observation over 6 weeks, transmission electron microscopy (TEM) was applied. The results of the study indicated cytotoxic effects of ZnO-NP beginning at high concentrations of 50 μg/mL and genotoxic effects in hMSC exposed to 1 and 10 μg/mL ZnO-NP. Repetitive exposure enhanced cyto- but not genotoxicity. Intracellular NP accumulation was observed up to 6 weeks. The results suggest cytotoxic and genotoxic potential of ZnO-NP. Even low doses of ZnO-NP may induce toxic effects as a result of repetitive exposure and long-term cellular accumulation. This data should be considered before using ZnO-NP on damaged skin.
Our aim was to evaluate the potential role of standard extrinsically activated thromboelastometry (EXTEM) assay in the early detection of neonatal sepsis. We studied 91 hospitalized neonates categorized in two groups: group A included 35 neonates with confirmed sepsis, while group B included 56 neonates with suspected sepsis; 274 healthy neonates served as controls. Whenever sepsis was suspected, EXTEM assay was performed, Score for Neonatal Acute Physiology Perinatal Extension (SNAPPE) and Tοllner score were calculated, and clinical findings and laboratory results were recorded. Septic neonates had significantly prolonged clotting time (CT) and clot formation time (CFT), and reduced maximum clot firmness (MCF), compared to neonates with suspected sepsis (p values 0.001, 0.001, and 0.009, respectively) or healthy neonates (p values 0.001, 0.001, and 0.021, respectively). EXTEM parameters (CT, CFT, MCF) demonstrated a more intense hypocoagulable profile in septic neonates with hemorrhagic diathesis than those without (p values 0.021, 0.007, and 0.033, respectively). In septic neonates, CFT was correlated with platelet count, SNAPPE, Tollner score, and day of full enteral feeding (p values 0.01, 0.02, 0.05, and 0.03, respectively).
Conclusions: A ROTEM hypocoagulable profile at admission seems promising for the early detection of sepsis in neonates while the degree of hypocoagulation may be associated with sepsis severity.
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What is Known:
• The early phase of septicemia might be difficult to be recognized in neonates. In adult septic patients, the diagnostic and prognostic role of thromboelastometry (ROTEM) have been extensively investigated.
• Limited data are available on the role of ROTEM as an indicator of early neonatal sepsis.
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What is New:
• ROTEM measurements indicate an early appearance of hypocoagulability in neonatal sepsis, while the degree of hypocoagulation might be associated with severity of sepsis.
• ROTEM could be a useful tool in the early detection of sepsis in neonates.
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Frontotemporal dementia (FTD) is characterized by behavioural and language impairment, accompanied by atrophic changes in fronto-temporo-insular cortices. In the presymptomatic phases of genetic FTD, subtle or no volumetric changes have been reported. Transcranial magnetic stimulation (TMS) represents an approach to explore cortical connectivity, and some TMS measures have been demonstrated to be impaired in Granulin (GRN) mutation carriers. We aimed at exploring cross-sectional changes in cortical thickness (CT) and surface area (SA) in the presymptomatic phases of GRN-related FTD, and their relationship with TMS parameters. Nineteen presymptomatic GRN mutation carriers and seventeen age and sex-matched non-carriers underwent 3T MRI scanning and a paired-pulse TMS protocol. The surface-based pipeline of FreeSurfer was applied in order to obtain cortical volumes (CVs), CT and SA measures. Then, between groups differences and correlation with TMS parameters were assessed. GRN carriers showed increased CT and decreased SA of the right parietal lobe, without significant volume changes. TMS parameters of intracortical inhibition and facilitation, which were significantly impaired in presymptomatic GRN mutation carriers, correlated with reduced SA and CV of the right insula. Our results suggest that splitting CV into its two main components could improve the sensitivity when exploring structural brain changes in presymptomatic or early phases of neurodegenerative conditions. TMS parameters might reflect damage within cortical regions reported to be affected early in the conversion to the symptomatic phase of the disease.
The cover image, by Erez Shmuel Davidi et al., is based on the Original Article Cisplatin-conjugated gold nanoparticles as a theranostic agent for head and neck cancer, DOI: 10.1002/hed.24935.
There is significant void in establishing validated non-invasive surrogate biomarkers of liver fibrosis/cirrhosis in chronic liver diseases (CLD). Golgi protein 73 (GP73) has been suggested as a potential serum marker for the diagnosis of hepatocellular carcinoma (HCC). However, significant background of cirrhosis could have accounted for the elevation of serum GP73 in HCC. In this study, we have taken advantage of a well-defined extensive cohort of 3044 patients with either compensated cirrhosis (n = 1247), decompensated cirrhosis (n = 841) or pre-cirrhotic CLD (n = 956) and our ability to quantify serum GP73 to define the potential of serum GP73 as a biomarker of liver cirrhosis/fibrosis in CLD. The diagnostic value of GP73 was compared with aspartate aminotransferase-to-platelet ratio index (APRI), fibrosis index based on four factors (FIB-4) and liver stiffness measurement (LSM). Immunohistochemical analysis was performed to measure hepatic GP73 expression. Receiver operating characteristic curve analysis demonstrated that serum GP73 had a good diagnostic potential for compensated cirrhosis regardless of etiology. The diagnostic performance of GP73 is better than APRI, FIB-4 and similar with LSM, especially in patients with severe inflammation, steatosis and cholestasis. Notably, in patients of autoimmune liver diseases, non-alcoholic fatty liver disease and viral hepatitis, serum GP73 also exhibited diagnostic value for advanced fibrosis as well as cirrhosis. Furthermore, there is also a gradual increase in GP73 expression with disease progression from mild fibrosis to cirrhosis. In conclusion, GP73 is an effective and reliable serological marker for the diagnosis of advanced fibrosis and prediction of appearance of cirrhosis.
The aim of this study was to investigate the healing activity of andiroba (Carapa guianensis Aubl.) against oral mucositis (OM) induced by 5-fluorouracil in golden Syrian hamsters.
A total of 122 animals were randomized and divided into six groups: andiroba oil 100%, andiroba oil 10%, andiroba oil 10% refined, no treatment group, all n = 28; and negative control (NC) and cyclophosphamide (CPA) groups, both n = 5. OM was induced by intraperitoneal administration of 60 mg/kg 5-FU on days 0, 5 and 10 followed by mechanical trauma on the oral mucosa on days 1 and 2. From day 1 to day 15, the animals of the andiroba group were treated three times a day. On days 4, 8, 12 and 15, the mucosa was photographed and removed for clinical and histopathological analysis. The bone marrow of the femur was removed and the micronucleus test was performed to evaluate the cytotoxicity and genotoxicity. The data were subjected to analysis of variance, followed by the Tukey and Bonferroni test.
Treatment with 100% andiroba oil reduced the degree of OM compared to that reported in the other groups (p < 0.05). Andiroba oil at both concentrations was not cytotoxic, but treatment with 100% andiroba oil showed a genotoxic potential (p < 0.001).
Frequent administration of andiroba oil accelerated the healing process in an experimental model of 5-fluorouracil-induced OM. However, the genotoxicity of andiroba in other cell systems and under other conditions are being tested.
The use of andiroba in topical form may be associated with reduced intensity of OM. Seek therapeutic alternatives to minimize the pain and suffering that these side effects cause cancer patients is an important scientific step.
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