Cincinnati.com |
No fooling; go get your head (and neck) examined for free
Cincinnati.com Thursday, get your head examined. UC Health is offering free head and neck cancer screenings at the UC Health Barrett Cancer Center from 8:30 a.m. to 4:30 p.m.. Head and neck cancers include cancers of the mouth, nose, sinuses, salivary glands, throat ... |
Laughter is the best medicine
Half Moon Bay Review Tate visited these dark places most notably during two nearly fatal bouts of disfiguring oral cancer and has re-emerged, committed to illuminating the way for others as they discover their own path to healing, purpose and passion. “I had cancer of the ... |
Amandala |
ASTHMA: A Complex Respiratory Condition
Amandala These conditions include bronchial asthma, bronchitis, hay fever, pneumonia, sinusitis, emphysema, and lung cancer. People who have allergic reactions to pollen are only a subgroup of a larger group of respiratory sufferers who have sensitivities ... |
When bad news about a cancer diagnosis is being delivered, patient-centered communication (PCC) has been considered important for patients' adjustment and well-being. However, few studies have explored how interpersonal skills might help cancer patients cope with anxiety and distress during bad-news encounters.
A prospective, experimental design was used to investigate the impact of the physician communication style during a bad-news encounter. Ninety-eight cancer patients and 92 unaffected subjects of both sexes were randomly assigned to view a video of a clinician delivering a first cancer diagnosis with either an enhanced patient-centered communication (E-PCC) style or a low patient-centered communication (L-PCC) style. Participants rated state anxiety and negative affect before and immediately after the video exposure, whereas trust in the physician was rated after the video exposure only. Main and interaction effects were analyzed with generalized linear models.
Viewing the disclosure of a cancer diagnosis resulted in a substantial increase in state anxiety and negative affect among all participants. This emotional response was moderated by the physician's communication style: Participants viewing an oncologist displaying an E-PCC style were significantly less anxious than those watching an oncologist displaying an L-PCC style. They also reported significantly higher trust in the physician.
Under a threatening, anxiety-provoking disclosure of bad news, a short sequence of empathic PCC influences subjects' psychological state, insofar that they report feeling less anxious and more trustful of the oncologist. Video exposure appears to be a valuable method for investigating the impact of a physician's communication style during critical encounters. Cancer 2017. © 2017 American Cancer Society.
In this prospective study, subjective sleep quality and excessive daytime sleepiness prior to, during and after deployment of German soldiers in Afghanistan were examined. Sleep quality (Pittsburgh Sleep Quality Index; PSQI) and daytime sleepiness (Epworth Sleepiness Scale; ESS) were assessed in 118 soldiers of the German army, who were deployed in Afghanistan for 6 months (deployment group: DG) and in 146 soldiers of a non-deployed control group (CG) at baseline. Results of the longitudinal analysis are reported, based on assessments conducted prior to, during the deployment and afterwards in the DG, and in the CG in parallel. Sleep quality and daytime sleepiness in the DG were already impaired during the predeployment training phase and remained at that level during the deployment phase, which clearly indicates the need for more attention on sleep in young soldiers, already at this early stage. The percentage of impaired sleepers decreased significantly after deployment. Programmes to teach techniques to improve sleep and reduce stress should be implemented prior to deployment to reduce sleep difficulties and excessive daytime sleepiness and subsequent psychiatric disorders.
Sleep inertia is affected by circadian phase, with worse performance upon awakening from sleep during the biological night than biological day. Visual search/selective visual attention performance is known to be sensitive to sleep inertia and circadian phase. Individual differences exist in the circadian timing of habitual wake time, which may contribute to individual differences in sleep inertia. Because later chronotypes awaken at an earlier circadian phase, we hypothesized that later chronotypes would have worse visual search performance during sleep inertia than earlier chronotypes if awakened at habitual wake time. We analysed performance from 18 healthy participants [five females (22.1 ± 3.7 years; mean ± SD)] at ~1, 10, 20, 30, 40 and 60 min following electroencephalogram-verified awakening from an 8 h in-laboratory sleep opportunity. Cognitive throughput and reaction times of correct responses were impaired by sleep inertia and took ~10–30 min to improve after awakening. Regardless whether chronotype was defined by dim light melatonin onset or mid-sleep clock hour on free days, derived from the Munich ChronoType Questionnaire, the duration of sleep inertia for cognitive throughput and reaction times was longer for later chronotypes (n = 7) compared with earlier chronotypes (n = 7). Specifically, performance for earlier chronotypes showed significant improvement within ~10–20 min after awakening, whereas performance for later chronotypes took ~30 min or longer to show significant improvement (P < 0.05). Findings have implications for decision making immediately upon awakening from sleep, and are consistent with circadian theory suggesting that sleep inertia contributes to longer-lasting impairments in morning performance in later chronotypes.
Periodic leg movements during sleep (PLMS) are sequences of ≥4 motor events with intermovement intervals (IMI) of 10–90 s. PLMS are a supportive diagnostic criterion for restless legs syndrome (RLS) and entail cardiac activation, particularly when associated with arousal. RLS patients also over-express short-interval leg movements during sleep (SILMS), which have IMI <10 s and are organized mainly in sequences of two movements (doublets). We tested whether the cardiac activation associated with SILMS doublets differs from that associated with PLMS in a sample of 25 RLS patients. We analysed time–series of R–R intervals synchronized to the onset of SILMS doublets or PLMS that entailed an arousal during non-rapid eye movement (NREM) sleep. We assessed cardiac activation based on the R–R interval decrease with respect to baseline during NREM sleep without leg movements. We found that the duration of the R–R interval decrease with SILMS doublets was significantly longer than that with PLMS, whereas the maximal decrease in R–R interval was similar. Scoring SILMS in RLS patients may therefore be relevant from a cardiac autonomic perspective.
A β-1,4-mannanase, termed AoMan134A, that belongs to the GH 134 family was identified in the filamentous fungus Aspergillus oryzae. Recombinant AoMan134A was expressed in Pichia pastoris, and the purified enzyme produced mannobiose, mannotriose, mannotetraose, and mannopentaose from galactose-free β-mannan, with mannotriose being the predominant reaction product. The catalytic efficiency (k cat/K m ) of AoMan134A was 6.8-fold higher toward galactomannan from locust bean gum, than toward galactomannan from guar gum, but similar toward galactomannan from locust bean gum and glucomannan from konjac flour. After incubation at 70°C for 120 min, the activity of AoMan134A toward glucomannan decreased to 50% of the maximal activity at 30°C. AoMan134A retained 50% of its β-1,4-mannanase activity after heating at 90°C for 30 min, indicating that AoMan134A is thermostable. Furthermore, AoMan134A was stable within a neutral-to-alkaline pH range, as well as exhibiting stability in the presence of a range of organic solvents, detergents, and metal ions. These findings suggest that AoMan134A could be useful in a diverse range of industries where conversion of β-mannans is of prime importance.
We previously engineered Escherichia coli YL104 to efficiently produce succinate from glucose. In this study, we investigated the relationships between the NADH/NAD+ ratio, ATP level, and overall yield of succinate production by using glucose as the carbon source in YL104. First, the use of sole NADH dehydrogenases increased the overall yield of succinate by 7% and substantially decreased the NADH/NAD+ ratio. Second, the soluble fumarate reductase from Saccharomyces cerevisiae was overexpressed to manipulate the anaerobic NADH/NAD+ ratio and ATP level. Third, another strategy for reducing the ATP level was applied by introducing ATP futile cycling for improving succinate production. Finally, a combination of these methods exerted a synergistic effect on improving the overall yield of succinate, which was 39% higher than that of the previously engineered strain YL104. The study results indicated that regulation of the NADH/NAD+ ratio and ATP level is an efficient strategy for succinate production.
New anti-Candida albicans drugs are needed due to the emergence of resistant cases in recent years. Perillaldehyde (PAE) is a natural monoterpenoid compound derived from Perilla frutescens. The minimum inhibitory concentration of PAE against C. albicans was 0.4 μL/mL. We aimed to elucidate the antifungal mode of action of PAE against C. albicans. The antifungal activity of PAE against C. albicans was found to correlate with an elevation in intracellular Ca2+ and accumulation of ROS. Several downstream apoptosis events such as the disruption of mitochondrial membrane potential, phosphatidylserine externalization, cytochrome c release, and metacaspase activation were observed in PAE-treated cells. DNA damage and nuclear fragmentation assays also revealed apoptosis of C. albicans cells. In summary, by means of fluorescent microscopy, flow cytometer analysis, and Western blot, our data uncovered that PAE exerts its antifungal activity through Ca2+ and oxidative stress-mediated apoptosis mechanisms. This study deciphered the mode of action of PAE, which will be useful in the design of improved antifungal therapies.
A 63-year-old Caucasian man presented with a 4-month history of disseminated asymptomatic reddish-brown papulonodular lesions. A skin biopsy showed dermal infiltration with CD68+ histiocytes, predominantly with eosinophilic cytoplasm, some with a ground-glass cytoplasm, and a small number of giant cells. The diagnosis of multiple cutaneous reticulohistiocytosis was made. Bone marrow immunophenotyping due to peripheral blood lymphocytosis revealed the presence of a monoclonal population of CD3+, CD8+ CD57+ large granular lymphocytes. The present case suggests the coexistence of multiple cutaneous reticulohistiocytosis with an underlying disorder.
A 75-year-old alcoholic male patient with severe malnutrition was admitted to the hospital with the diagnosis of pneumonia. The finding of a symptomatic umbilical hernia on patient examination mandated a surgical consultation with the question of an operative hernia repair.
Clinically, the abdomen was distended with spider angiomas. Palpation of the umbilical hernia was painless. The hernia content was not reducible. A suspicious murmur (Cruveilhier-Baumgarten murmur) was identified on auscultation of the umbilicus (figure 1). The abdominal CT scan showed signs of portal hypertension. A large recanalised paraumbilical vein coursing from the left side of the portal vein through the falciform ligament and draining into a large umbilical varicose vein was visible. An enlarged right inferior epigastric vein originating from the umbilical varicose vein drained into the right femoral vein. The hernial sac contained only the umbilical varicose (figure 2A,B,C). On further investigation,...
A genetic diagnosis of autosomal dominant polycystic kidney disease (ADPKD) is challenging due to allelic heterogeneity, high GC-content, and homology of the PKD1 gene with six pseudogenes. Short-read next-generation sequencing (NGS) approaches, such as whole genome (WGS) and whole exome sequencing (WES), often fail at reliably characterizing complex regions such as PKD1. However, long-read single-molecule sequencing has been shown to be an alternative strategy that could overcome PKD1 complexities and discriminate between homologous regions of PKD1 and its pseudogenes. In this study, we present the increased power of resolution for complex regions using long-read sequencing to characterize a cohort of 19 patients with ADPKD. Our approach provided high sensitivity in identifying PKD1 pathogenic variants, diagnosing 94.7% of the patients. We show that reliable screening of ADPKD patients in a single test without interference of PKD1 homologous sequences, commonly introduced by residual amplification of PKD1 pseudogenes, by direct long-read sequencing is now possible. This strategy can be implemented in diagnostics and is highly suitable to sequence and resolve complex genomic regions that are of clinical relevance.
This article is protected by copyright. All rights reserved
| Related Articles |
Seizing market shaping opportunities for vaccine cold chain equipment.
Vaccine. 2017 Apr 19;35(17):2260-2264
Authors: Azimi T, Franzel L, Probst N
Abstract
Gavi, the Vaccine Alliance, supports immunisation programmes in eligible countries to reach children with lifesaving vaccines. Dramatic improvement in the scale and performance of current cold chain systems is required to extend the reach of immunisation services - especially for children living in remote locations - to advance progress towards full vaccine coverage. Achieving these improvements will require a healthier market for cold chain equipment where the products meet user needs, are sustainably priced, and are available in sufficient quantities to meet demand. Yet evidence suggests that the cold chain market has suffered from several failures including limited demand visibility, fragmented procurement, and insufficient information exchange between manufacturers and buyers on needs and equipment performance. One of Gavi's strategic goals is to shape markets for vaccines and other immunisation products, including cold chain equipment and in 2015, Gavi created a new mechanism - the Cold Chain Equipment (CCE) Optimisation Platform - to strengthen country cold chain systems by offering financial support and incentives for higher performing CCE. The main objective of the CCE Platform is to get more equipment that is efficient, sustainable, and better performing deployed to every health facility where it is required at an affordable price. To achieve these objectives, Gavi is putting in place tested market shaping approaches and tools adapted for the CCE market: the development of market strategies or 'roadmaps'; improvement of product performance through the development of target product profiles (TPPs); strategic engagement with CCE manufacturers and countries to enhance information sharing; and tailoring procurement tactics to the CCE market. These approaches and tools will allow for increased demand and supply of higher-performing, cost-effective and quality products. By strengthening immunisation systems with improved cold chain equipment, Gavi countries can begin to address the underlying problems limiting vaccine availability and improve the coverage and equity of vaccines.
PMID: 28364940 [PubMed - in process]
| Related Articles |
Long-acting insulin allergy in a diabetic child.
Int J Immunopathol Pharmacol. 2017 Apr 01;:394632017700431
Authors: Mastrorilli C, Rizzuti L, Cangelosi AM, Iovane B, Chiari G, Caffarelli C
Abstract
Insulin allergy has been uncommon since the introduction of human recombinant insulin preparations; the prevalence is 2.4%. Insulin injection could elicit immediate reactions, which are usually induced by an IgE-mediated mechanism, within the first hour after drug administration. In the present study, we describe the case of a child who experienced immediate urticaria after long-acting insulin injection. A 9-year-old girl affected by type I diabetes mellitus referred a history of three episodes of urticaria 30 min after insulin subcutaneous injection. During the first week of insulin therapy, she developed generalized immediate urticaria twice after long-acting insulin glargine first and then once after insulin degludec administration. Symptoms resolved within a few hours after treatment with oral antihistamine. She tolerated rapid insulin lispro. Her personal allergological history was negative. Skin prick tests with degludec, glargine and detemir were performed, showing negative results. Intradermal 1:100000-diluted tests were immediately positive for both degludec and glargine but not for detemir. In light of these findings, detemir was administered without any reaction. Our results show that detemir is tolerated by patients with clinical hypersensitivity reactions to degludec and glargine. Although reactions could be attributable to additives allergy, such as zinc or metacresol, this was excluded since all three preparations contain the same components. So, insulin itself acted as offending allergen. Detemir differs from degludec and glargine in a few aminoacids. Therefore, it is possible that the conformational rather than the linear epitope may be responsible for the reaction. This result suggests integrating intradermal tests in the diagnostic flowchart for insulin allergy. Insulin allergy should always be suspected in patients with immediate symptoms after drug injection. As allergologic work-up, prick by prick test and intradermal test to insulin preparations should be performed. In case of negative results of cutaneous tests, insulin analogs may be administered.
PMID: 28368217 [PubMed - as supplied by publisher]
Vibrio parahaemolyticus expresses one major virulence determinant T6SS2, which is constituted into three putative operons, i.e., VPA1027-1024, VPA1043-1028, and VPA1044-1046. CalR, a LysR-type transcriptional regulator, was originally identified as a repressor of the swarming motility and T3SS1 gene expression. As shown in this study, CalR binds to the promoter-proximal region of each of the three operons to activate their transcription, and moreover, CalR activates the adhesion of V. parahaemolyticus to HeLa cells. In addition, competitive EMSAs demonstrated that CalR acts as an antagonist of H–NS in V. parahaemolyticus. Collectively, these studies confirmed a new physiological role for CalR in V. parahaemolyticus.
Sufficient sleep duration is crucial for maintaining normal physiological function and has been linked to cancer risk; however, its contribution to lung cancer mortality is unclear. Therefore, we evaluated the relationship between average sleep duration in various age-periods across the adult lifecourse, and risk of lung cancer mortality in Xuanwei, China. An ambidirectional cohort study was conducted in 42,422 farmers from Xuanwei, China. Participants or their surrogates were interviewed in 1992 to assess average sleep hours in the age-periods of 21-30, 31-40, 41-50, 51-60, 61-70, and ≥71 years, which were categorized as ≤7, 8 (reference), 9, and ≥10 hours/day. Vital status was followed until 2011. Sex-specific Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CI) for lung cancer mortality in 1994-2011, adjusted for demographic, anthropometric, medical, and household characteristics. J-shaped relationships were found between average sleep duration and lung cancer mortality. The patterns were consistent across sex, age-periods, and fuel usage. Compared to sleeping 8 hours/day on average, ≤7 hours/day was associated with significantly increased HRs ranging from 1.39 to 1.58 in ages ≥41 years in men, and 1.29 to 2.47 in ages ≥51 years in women. Furthermore, sleeping ≥10 hours/day was associated with significantly increased HRs ranging from 2.44 to 3.27 in ages ≥41 year in men, and 1.31 to 2.45 in ages ≤60 years in women. Greater and less than 8 hours/day of sleep in various age-periods may be associated with elevated risk of lung cancer mortality in Xuanwei, China.
KEYT |
On this day: April 4
KEYT 2013: Movie critic Roger Ebert, the first film critic to win the Pulitzer Prize for Criticism, dies at the age of 70 in Chicago, Illinois, after a recurrence of cancer. Ebert, who had lived with cancer of the thyroid and salivary glands since 2002, was ... and more » |
Chemokine and the chemokine receptor have a key role in the tumor progress. Here, we supposed that CCR7 might induce the invasion, migration, and epithelial–mesenchymal transition (EMT) process of breast cancer. In this research, human breast cancer MCF-7 and MDA-MB-231cells were treated with CCL19 and small-interfering RNA (CCR7 siRNA) for activation and inhibition of CCR7, respectively. Cell invasion and transwell assays were used to detect the effect of CCR7 on invasion and migration. The results demonstrated that CCL19 mediated cell invasion and migration by inducing the EMT, with downregulation of E-cadherin and up-regulation of N-cadherin and vimentin levels. On the other hand, knockdown of CCR7 revealed the changes compared with CCL19 group and the control group. Knockdown of CCR7 inhibits CCL19-induced breast cancer cell proliferation, the cell cycle, migration, invasion and EMT. Moreover, we demonstrated that CCL19-induced AKT phosphorylation; however, CCR7 siRNA suppressed CCL19-induced AKT phosphorylation, a key regulator of tumor metastasis. In conclusion, all findings demonstrated that CCL19/CCR7 axis regulated EMT progress in breast cancer cells and mediated the tumor cell invasion and migration process via activation of AKT signal pathway. Our results suggested that CCR7 may regard as a therapeutic target for the breast cancer treatment.
All findings demonstrated that CCL19/CCR7 axis regulated EMT progress in breast cancer cells and mediated the tumor cell invasion and migration process via activation of AKT signal pathway. Our results suggested that CCR7 may regard as a therapeutic target for the breast cancer treatment.
Human papillomavirus (HPV), the causal factor of cervical cancers, was closely linked to the etiology and prognosis of oropharyngeal squamous cell carcinoma (OPSCC), but its role in oral squamous cell carcinoma (OSCC) was unclear. In addition, few researches based on Chinese population were documented. Hence, we sought to investigate the relationship of HPV marker P16 protein to the clinicopathological parameters and survival of OPSCC and OSCC patients systematically to assess the influence of ethnic, regional difference on HPV susceptibility. Specimens from 93 OPSCC patients and 95 OSCC patients were recut, and P16 immunohistochemistry (IHC) was performed. Moreover, survival analysis was conducted to confirm the independent factors that influenced the prognosis. The P16 results were positive in 25.8% and 9.5% of patients with OPSCC and OSCC, respectively. The overall survival (OS) of HPV-positive OPSCC patients was significantly longer than that of HPV-negative OPSCC patients (P = 0.004). Conversely, statistical significance was not observed regarding the OS of OSCC patients (P = 0.343). Cox regression analysis indicated that T stage and P16 status were independent factors that affected the prognosis of OPSCC patients, and the smoking index influenced the prognosis of OSCC patients. Among OPSCC patients who received radiochemotherapy (RCT), HPV-positive patients had a better survival rate than their HPV-negative counterparts (P = 0.015). Conversely, no significant difference was observed between HPV-positive and HPV-negative OSCC patients who received RCT (P = 0.237). P16 is a credible surrogate by which to define HPV status. HPV expression had a favorable effect on OPSCC patients as opposed to their OSCC counterparts in this single center population-based study.
The research regarding to the relationship between HPV and clinicopathological parameters and paprognosis of oral and oropharyngeal squamous cell carcinomas is emerging as a hotspot in the world. Taking account of the difference between The East and The West, we conduct this systematic retrospective investigation including consultation of medical records, collection of specimen, statistical analysis and postoperative follow-up.
The incidences of thyroid cancer keep rising worldwide over the past few decades. Although most thyroid cancers are indolent and highly curable, the treatment for advanced thyroid cancer remains challengeable in clinical practice. We performed two separate cohorts to evaluate the safety and efficiency of Escin in patients with advanced thyroid cancer . In cohort 1, 120 patients were divided into four groups equally and were administrated with placebo or different dosages of Escin. The pharmacokinetics of Escin and the side effects were evaluated. In cohort 2, 120 patients were treated with Escin. Several biomarkers related to the progression of thyroid cancer were evaluated. Kaplan–Meier (KM) analyses were performed to evaluate progression-free survival (PFS) and overall survival (OS). The serum Escin concentrations were stable during the treatment. Escin (0.6 mg/kg/day for 9 days, intravenous injection) was tolerable for patients with thyroid cancer . Escin significantly reduced the serum levels of TSH, TgAb, Tg, and calcitonin and prolonged the PFS and OS for patients with advanced thyroid cancer. This study showed Escin is efficient and well tolerated in patients with advanced thyroid cancer. Future studies are needed to investigate the mechanism of Escin on thyroid cancer and the proper dosage of Escin clinically.
This study showed Escin is efficient and well tolerated in patients with advanced thyroid cancer. Based on the safety, and pharmacokinetic and efficacy profiles of our study, it was concluded that Escin 0.6 mg/kg/day i.v. for 9 days was tolerable.
Cytology-based cervical cancer screening is restricted because of a lack of cytologists. Thus, HPV-based instead of cytology-based screening may be a more suitable strategy in China. Here, we assessed the effectiveness of HPV testing (Cobas® 4800 Test, Roche) and HPV-based programs to detect high-grade cervical intraepithelial neoplasia (CIN) or cancer compared with cytology (Thinprep, Hologic) and cytology-based programs through a cross-sectional study in 11,064 Chinese women aged 21–65 years who were enrolled from Longyou County in Zhejiang Province, China. The rates of HPV positivity and cytology abnormality were 9.8% and 6.1%, respectively. The HPV positivity rate had two age peaks, 21–24 (15.4%) and 60–65 (14.4%) years. According to adjusted data, HPV testing demonstrated significantly higher sensitivity and negative predictive value (NPV) than cytology for detecting CIN2 or worse (90.0% vs. 66.7%, 99.9% vs. 99.5%), and there was an acceptable specificity (91.3%) and positive predictive value (PPV, 12.5%). Furthermore, primary HPV testing with type 16/18 genotyping showed the highest sensitivity (78.6%) and NPV (99.7%) among four screening strategies, and there was similar specificity (96.8%) and PPV (23.9%) compared with co-testing screening to detect CIN2+, while there were fewer colposcopies (4.2) and tests (106.3) performed than with co-testing and primary cytology screening to detect a case of high-grade CIN. The differences in effectiveness were approximately similar when CIN3+ was the identifying target. Our findings suggest that primary HPV testing with type 16/18 genotyping has a higher sensitivity and NPV, possesses optimal cost/effectiveness in the first round of screening and is a feasible strategy of cervical cancer screening for Chinese women.
Cytology-based cervical cancer screening is restricted in China because of a lack of cytologists. We assessed, for the first time in China, the effectiveness of Cobas® HPV testing and HPV-based programs to detect high-grade cervical intraepithelial neoplasia (CIN) or cancer through a population-based cross-sectional study, and found that primary HPV testing with type 16/18 genotyping demonstrated higher sensitivity and negative predictive value (NPV), possessed optimal cost/effectiveness in the first round of screening and could be a feasible strategy of cervical cancer screening for Chinese women.
Sporadic colorectal cancer (CRC) is classified into several molecular subtypes. We previously established two groups of DNA methylation markers through genome-wide DNA methylation analysis to classify CRC into distinct subgroups: high-, intermediate-, and low-methylation epigenotypes (HME, IME, and LME, respectively). HME CRC, also called CpG island methylator phenotype (CIMP)-high CRC, shows methylation of both Group 1 markers (CIMP markers) and Group 2 markers, while IME/CIMP-low CRC shows methylation of Group 2, but not of Group 1 markers, and LME CRC shows no methylation of either Group 1 or Group 2 markers. While BRAF- and KRAS-mutation(+) CRC strongly correlated with HME and IME, respectively, clinicopathological features of NRAS-mutation(+) CRC, including association with DNA methylation, remain unclear. To characterize NRAS-mutation(+) CRC, the methylation levels of 19 methylation marker genes (6 Group 1 and 13 Group 2) were analyzed in 61 NRAS-mutation(+) and 144 NRAS-mutation(−) CRC cases by pyrosequencing, and their correlation with clinicopathological features was investigated. Different from KRAS-mutation(+) CRC, NRAS-mutation(+) CRC significantly correlated with LME. NRAS-mutation(+) CRC showed significantly better prognosis than KRAS-mutation(+) CRC (P = 3 × 10−4). NRAS-mutation(+) CRC preferentially occurred in elder patients (P = 0.02) and at the distal colon (P = 0.006), showed significantly less lymph vessel invasion (P = 0.002), and correlated with LME (P = 8 × 10−5). DNA methylation significantly accumulated at the proximal colon. NRAS-mutation(+) CRC may constitute a different subgroup from KRAS-mutation(+) CRC, showing significant correlation with LME, older age, distal colon, and relatively better prognosis.
Genetic and epigenetic analyses of colorectal cancer (CRC) were conducted to clarify molecular and clinicopathological features of NRAS-mutation(+) CRC compared to KRAS-mutation(+) and other subgroups of CRC. NRAS-mutation(+) CRC presented a low-methylation epigenotype, occurred in elder patients and at the distal colon, and showed relatively better prognosis
In order to maximize efficiency and reduce the risk of failure in operational dams, an effective and efficient method which employs the inverse analysis of a dynamic coupled hydro-mechanical problem is proposed. The numerical model is based on the extended finite element model. The proposed method is able to identify cracks which may be detrimental to structural performance and reliability. An attempt is made using both deterministic and heuristic based strategies to solve the ill-posed inverse problem and identify the location, dimension and orientation of the crack. More so, the influence of the search space and conditioning of the cost function in identifying crack parameters are investigated. The proposed method shows promising results in the identification of cracks in a fully operational dam.
The initial yield envelopes of aluminum (Al) nanocomposites reinforced with carbon nanotubes (CNTs) subjected to biaxial loading are predicted in the presence of thermal residual stress (TRS) arising from the manufacturing process. Micromechanical model based on the unit cell method is presented to generate the yielding surfaces. The formation of the interphase caused by the interfacial reaction between the CNT and Al matrix is taken into account in the analysis. The effects of several important parameters, i.e. the change of temperature, CNT volume fraction, interphase thickness and Al material properties on the yielding onset of the CNT/Al nanocomposite are explored extensively. The results clearly reveal that the initial yield surfaces of nanocomposite are dependent on the TRS. Also, the interphase has a significant influence on the yielding behavior of Al nanocomposite in the presence of TRS. The results demonstrate that the size of initial yield surfaces become minimum with considering the coupled effects of TRS and interphase. With increasing the temperature variation, interphase thickness, elastic modulus and coefficient of thermal expansion of Al matrix, the size of initial yield surfaces reduces. The present study is consequential for understanding the key role of TRS on the initial damage of CNT/Al nanocomposites.
Nearest neighbor search is a core process in many data mining algorithms. Finding reliable closest matches of a test instance is still a challenging task as the effectiveness of many general-purpose distance measures such as \(\ell _p\) -norm decreases as the number of dimensions increases. Their performances vary significantly in different data distributions. This is mainly because they compute the distance between two instances solely based on their geometric positions in the feature space, and data distribution has no influence on the distance measure. This paper presents a simple data-dependent general-purpose dissimilarity measure called ' \(m_p\) -dissimilarity'. Rather than relying on geometric distance, it measures the dissimilarity between two instances as a probability mass in a region that encloses the two instances in every dimension. It deems two instances in a sparse region to be more similar than two instances of equal inter-point geometric distance in a dense region. Our empirical results in k-NN classification and content-based multimedia information retrieval tasks show that the proposed \(m_p\) -dissimilarity measure produces better task-specific performance than existing widely used general-purpose distance measures such as \(\ell _p\) -norm and cosine distance across a wide range of moderate- to high-dimensional data sets with continuous only, discrete only, and mixed attributes.
Urothelial bladder carcinoma (UBC) is one of the most prevalent cancers in men worldwide. Human epidermal growth factor receptor 2 (HER2) expression has been detected in a wide range of urothelial carcinoma. Despite many reports in the literature, the prognostic significance of this overexpression remains unclear. The aim of this study was to assess the expression of HER2 in urothelial bladder carcinomas and its association with clinical and pathological parameters.
103 cases of UBC were diagnosed in our department between January 2014 and December 2015. The tumor specimens obtained by transurethral resection or cystectomy were evaluated by immunohistochemistry using HER2 antibody.
HER2 protein overexpression was present in 11.7% of cases and associated with tumor grade (p = 0.003) and pathological stage (p = 0.015). In multivariate analysis, HER2 overexpression was associated only with tumor grade (P = 0.04).
HER2 protein overexpression is noted in patients with high grade cancer. This expression may select patients for anti HER2 targeted therapy. Future larger and prospective studies will verify the frequency of HER2 alteration and the role of HER2 in the aggressive behavior.
The Guardian |
Belle Gibson mimicked countless fake healers. They aren't delusional
The Guardian Imagine for a moment being diagnosed with cancer and being one of the 14 million people worldwide each year shattered by a diagnosis that sinks the heart like none other. If you are lucky enough to live in one of the handful of sufficiently resourced ... |
Melanins (eumelanin and pheomelanin) are synthesised in insects for several purposes including cuticle sclerotisation and color patterning, clot formation, organogenesis and innate immunity. Traditional views of insect immunity detail the storage of pro-phenoloxidases inside specialized blood cells (hemocytes) and their release upon recognition of foreign bodies. Activated phenoloxidases convert monophenols into reactive quinones in a two-step enzymatic reaction, and until recently, the mechanism of tyrosine hydroxylation remained a mystery. Herein, we present our interpretations of these enzyme-substrate complexes. The resultant melanins are deposited onto the surface of microbes to immobilise, agglutinate and suffocate them. Phenoloxidase activity and melanin production are not limited to the blood (hemolymph) or cuticle, as recent evidence points to more diverse, sophisticated interactions in the gut and with the resident symbionts. This review offers insight into the somewhat neglected areas of insect melanogenesis research, particularly in innate immunity, its role in beneficial insects such as pollinators, the functional versatility of phenoloxidases and the limitations of common experimental approaches that may impede progress inadvertently.
This article is protected by copyright. All rights reserved.
Prostaglandin D2 (PGD2) is primarily produced by mast cells and is contributing to the nasal symptoms including nasal obstruction and rhinorrhea.
This study aimed to evaluate the efficacy and safety of a novel PGD2 receptor 1 (DP1) antagonist, ONO-4053, in patients with seasonal allergic rhinitis (SAR).
This study was a multicenter, randomized, double-blind, parallel-group study of patients with SAR. Following a one-week period of placebo run-in, patients who met the study criteria were randomized to either the ONO-4053, leukotriene receptor antagonist pranlukast, or placebo group for a two-week treatment period. 200 patients were planned to be randomly assigned to receive ONO-4053, pranlukast, or placebo in a 2:2:1 ratio. Nasal and eye symptoms were evaluated.
Both ONO-4053 and pranlukast had higher efficacy than placebo on all nasal and eye symptoms. ONO-4053 outperformed pranlukast in a total of three nasal symptom scores (T3NSS) as well as in individual scores for sneezing, rhinorrhea, and nasal itching. For T3NSS, the Bayesian posterior probabilities that pranlukast was better than placebo and ONO-4053 was better than pranlukast were 70.0% and 81.6%, respectively, suggesting that ONO-4053 has a higher efficacy compared with pranlukast. There was no safety-related issue in this study.
We demonstrated that the efficacy of ONO-4053 was greater than that of pranlukast with a similar safety profile. This study indicates the potential of ONO-4053 for use as a treatment for SAR (JapicCTI-142706).
This article is protected by copyright. All rights reserved.
The antimicrobial peptide (AMP) RNase 7 is constitutively expressed in the epidermis of healthy human skin and has been found to be upregulated in chronic inflammatory skin diseases such as atopic dermatitis and psoriasis. Activated T-cells in lesional skin of patients with atopic dermatitis (AD) and psoriasis (PSO) might be directly exposed to RNase 7. In addition to their antimicrobial activity immunoregulatory functions have been published for several AMPs. In this study we investigated immunoregulatory effects of the antimicrobial peptide RNase 7 on activated T-cells.
Isolated human CD3+ T-cells were stimulated with RNase 7 and screened for possible effects by mRNA microarray analysis. The results of the mRNA microarray were confirmed in isolated CD4+T-cells and in polarised TH2 cells using skin derived native RNase 7 and a recombinant ribonuclease-inactive RNase 7 mutant. Activation of GATA3 was analysed by electrophoretic mobility shift assay.
Treatment of activated human CD4+ T-cells and TH2 cells with RNase 7 selectively reduced the expression of TH2 cytokines (IL-13, IL-4 and IL-5). Experiments with a ribonuclease-inactive recombinant RNase 7 mutant showed that RNase 7 ribonuclease activity is dispensable for the observed regulatory effect. We further demonstrate that CD4+T-cells from AD patients revealed a significantly less pronounced downregulation of IL-13 in response to RNase 7 compared to healthy control. Finally, we show that GATA3 activation was diminished upon cultivation of T-cells with RNase7.
Our data indicate that RNase 7 has immunomodulatory functions on TH2-cells and decreases the production of TH2 cytokines in the skin
This article is protected by copyright. All rights reserved.
The impact of RAS/RAF mutations in localized colon cancer needs clarification. Based on analysis of tumor-specific DNA, this study aimed at elucidating the prognostic influence of mutational status in tumor and serum using an extended panel of mutations.
The study retrospectively included 294 patients with curatively resected stage I–III adenocarcinoma of the colon. Mutations in tumor and serum were determined at time of surgery. Analyses were performed with droplet digital PCR technology. Hazard ratio (HR) for the association between mutational status and survival was estimated in multivariate analysis taking known prognostic factors into account.
Mutational status in tumor did not on its own have significant prognostic impact (P = 0.22). Patients with a RAS mutation simultaneously in tumor and serum had a significantly worse prognosis, overall survival (OS) (HR = 2.30, 95% CI = 1.27–4.15, P = 0.0057), and disease-free survival (DFS) (HR = 2.18, 95%CI = 1.26–3.77, P = 0.0053). BRAF mutation in the serum and proficient mismatch repair (pMMR) protein in tumor also indicated significantly worse prognosis, OS (HR = 3.45, 95% CI = 1.52–7.85, P = 0.0032) and DFS (HR = 3.61, 95% CI = 1.70–7.67, P = 0.0008). In conclusion, RAS mutations in serum, and BRAF mutation in serum combined with pMMR in tumor were strong independent prognostic factors in patients with RAS/RAF mutated tumors.
This work is the first to demonstrate simultaneous RAS/RAF mutational status in tumor and serum in localized colon cancer patients to be a potent prognostic marker.
Digital breast tomosynthesis (DBT) has shown potential to improve breast cancer screening and diagnosis compared to digital mammography (DM). The FDA approved DBT use in conjunction with conventional DM in 2011, but coverage was approved by CMS recently in 2015. Given changes in coverage policies, it is important to monitor diffusion of DBT by insurance type. This study examined DBT trends and estimated associations with insurance type. From June 2011 to September 2014, DBT use in 22 primary care centers in the Dartmouth -Brigham and Women's Hospital Population-based Research Optimizing Screening through Personalized Regimens research center (PROSPR) was examined among women aged 40–89. A longitudinal repeated measures analysis estimated the proportion of DBT performed for screening or diagnostic indications over time and by insurance type. During the study period, 93,182 mammograms were performed on 48,234 women. Of these exams, 16,506 DBT tests were performed for screening (18.1%) and 2537 were performed for diagnosis (15.7%). Between 2011 and 2014, DBT utilization increased in all insurance groups. However, by the latest observed period, screening DBT was used more frequently under private insurance (43.4%) than Medicaid (36.2%), Medicare (37.8%), other (38.6%), or no insurance (32.9%; P < 0.0001). No sustained differences in use of DBT for diagnostic testing were seen by insurance type. DBT is increasingly used for breast cancer screening and diagnosis. Use of screening DBT may be associated with insurance type. Surveillance is required to ensure that disparities in breast cancer screening are minimized as DBT becomes more widely available.
Digital breast tomosynthesis (DBT) is increasingly used for breast cancer screening and diagnosis. Our study finds screening DBT to be associated with insurance type, with lowest use among those with Medicaid and the uninsured. Surveillance is required to ensure that insurance-related disparities in breast cancer screening are minimized as DBT becomes more widely available.
Childhood cancer survivors (CCS) experience higher hospitalization rates compared to the general population for neoplasms, circulatory diseases, endocrine/nutritional/metabolic diseases and eye disorders. We studied trends in hospitalization rates and associated patient and treatment-specific risk factors for diagnosis subgroups among these four diseases. We performed medical record linkage of a ≥5-year CCS cohort with national registers, and obtained a random reference sample matched on age, gender and calendar year per CCS. For each diagnosis subgroup we compared hospitalization rates and trends over time in CCS and the reference population. Further, we analyzed risk factors for hospitalizations within the four CCS diagnosis groups. We used multivariate Poisson regression for all models. We retrieved hospitalization data from 1382 CCS and 26,583 reference persons. CCS had increased hospitalization rates for almost all diagnosis subgroups examined. Hospitalization rates for endocrine/nutritional/metabolic diseases appeared to increase with longer time since primary cancer diagnosis up to 30 years after primary cancer diagnosis. Survivors initially treated with radiotherapy had increased hospitalization rates for neoplasms (P < 0.001), those initially treated with anthracyclines (2.5 [1.1–5.5]) and radiotherapy to thorax and/or abdomen (9.3 [2.4–36.6]) had increased hospitalization rates for diseases of the circulatory system, and those initially treated with radiotherapy to head and/or neck had increased hospitalization rates for endocrine/nutritional/metabolic diseases (6.7 [3.5–12.7]) and diseases of the eye (3.6 [1.5–8.9]). Our study highlights that long-term health problems resulting in hospitalizations are still clinically relevant later in life of CCS. The identified treatment-related risk factors associated with hospitalizations support targeted follow-up care for these risk groups of CCS.
Childhood cancer survivors experience higher hospitalization rates compared to the general population for almost all diagnosis subgroups within neoplasms, circulatory diseases, endocrine/nutritional/metabolic diseases and eye disorders. This study supports the prioritization of follow-up care for the risk groups we identified, namely those survivors originally treated with anthracyclines and radiotherapy to thorax and/or abdomen and head and/or neck.
Colorectal cancer (CRC) screening prevalence remains low among Asians and Pacific Islanders. This study examined disparities and predictors of CRC screening compliance in adults age 50–75 years in Asians and Pacific Islanders in Hawai'i. Hawai'i Behavioral Risk Factor Surveillance System (BRFSS) data for 2011–2014 were analyzed. CRC screening status was dichotomized. Logistic regression was used to examine ethnic differences in and predictors of CRC screening status. Filipinos (OR 0.56), Chinese (OR 0.70), and Hawaiians (OR 0.75) were significantly less likely than whites to be CRC compliant. Higher education and income, employment, regular health provider, and routine checkups were important predictors of CRC compliance. Findings confirm lower CRC screening compliance in three of the four largest Asian and Pacific Islander groups in Hawai'i and that CRC screening compliance is influenced by several factors. Culturally tailored education and navigation services may be effective in reducing these disparities.
The Color of Determination
Champaign/Urbana News-Gazette (blog) Blog Photo The same year his wife was being treated for breast cancer, Querio's brother was diagnosed with tongue cancer. Both of them were treated successfully and are healthy now. Last year, though, another family member was diagnosed with cancer. |
The Institute of Cancer Research |
Drug makes head-and-neck cancer more sensitive to radiotherapy
The Institute of Cancer Research A drug that has shown promise in breast and lung cancer trials also makes the combination of chemotherapy and radiotherapy more successful at killing head-and-neck cancers, a new study has found. The research could lead to more effective treatments for ... |
