Aurantiochytrium limacinum 4W-1b (AL4W-1b) is a newly discovered microalgal strain with unique features. In the present study, we investigated the effects of ethanol extracts of AL4W-1b on lipopolysaccharide- (LPS-) induced inflammatory responses in RAW264 murine macrophage cells. Pretreatment of RAW264 cells with the AL4W-1b extract significantly reduced the production of LPS-induced nitric oxide (NO) and the expression of proinflammatory cytokine genes, including tumor necrosis factor α, interleukin- (IL-) 1β, and IL-6. Treatment with the AL4W-1b extract also decreased the production of IL-1β and IL-6. These results suggest that AL4W-1b might have anti-inflammatory effects in RAW264 cells. The NF-κB inhibitor, BAY 11-7082, synergistically prevented LPS-induced NO production after pretreatment with the AL4W-1b extract. Thus, the AL4W-1b extract may affect not only the NF-κB pathway but also other inflammatory pathways. To the best of our knowledge, this is the first study to report the anti-inflammatory effects of AL4W-1b extract and its mechanism of action in LPS-stimulated murine macrophage cells.
http://bit.ly/2UjP155
Κυριακή 27 Ιανουαρίου 2019
Anti-Inflammatory Effects of Aurantiochytrium limacinum 4W-1b Ethanol Extract on Murine Macrophage RAW264 Cells
Population based study: atopy and autoimmune diseases are associated with functional dyspepsia and irritable bowel syndrome, independent of psychological distress
Summary
Background
The pathogenesis of functional GI disorders (FGIDs) is uncertain. However, underlying immune activation and psychological distress has been documented in irritable bowel syndrome (IBS) and functional dyspepsia (FD). Epidemiological data from the UK suggest that FGIDs are linked to atopy and certain autoimmune diseases but this has not been confirmed.
Aim
To test if allergic or autoimmune diseases are independently associated with FGIDs, irrespective of psychological distress in a large population based study.
Methods
A total of 3542 people (mean age 57.9 years and 52.7% females) randomly selected from the Australian population, returned a mail survey (response rate = 43%). The survey asked about a physician diagnosis of autoimmune disease (scleroderma, psoriasis, rheumatoid arthritis and diabetes mellitus) or allergic conditions (asthma, food, pollen and/or animal allergy). The questionnaire assessed psychological distress and Rome III criteria for FD and IBS.
Results
Asthma, food, pollen and animal allergies, psoriasis and rheumatoid arthritis were univariately significantly associated with IBS and FD. Food allergy (OR = 1.66; 95% CI = 1.15‐2.40, P = 0.007), psoriasis (OR = 1.81; 95% CI = 1.19‐2.74, P = 0.006) and rheumatoid arthritis (OR = 1.68; 95% CI = 1.15‐2.4, P = 0.007) were independent risk factors for IBS, controlling for age, gender and psychological distress. In FD, asthma (OR = 1.32; 95% CI = 1.04‐1.68, P = 0.025) and food allergy (OR = 1.78; 95% CI = 1.28‐2.49, P = 0.001) were independent predictors, controlling for age, sex and psychological distress.
Conclusions
There is evidence that both atopic and autoimmune diseases are risk factors for FGIDs, independent of psychological distress, differing in IBS and FD. This provides evidence that different peripheral pathways may be involved in the pathogenesis of certain FGIDs.
http://bit.ly/2Ti9lUv
Plasma Cell Leukemia: Definition, Presentation, and Treatment
Abstract
Purpose of Review
We discuss current topics on the definition of plasma cell leukemia and the distinction between plasma cell leukemia and multiple myeloma. Moreover, we review the latest literature on how to treat plasma cell leukemia.
Recent Findings
Plasma cell leukemia is clinically and genetically distinct from multiple myeloma. Plasma cell leukemia is defined by the observation in blood of more than 20% clonal plasma cells by differential count of the leucocytes or by counting more than 2 × 109 per liter circulating clonal plasma cells. However, patients with lower levels of circulating plasma cells have the same adverse prognosis, which challenges the disease definition. Survival has improved after implementation of high-dose chemotherapy with stem-cell support, bortezomib, and lenalidomide in the treatment; yet, the prognosis remains poor. The results of allo-transplants have been disappointing.
Summary
The diagnostic criteria of PCL are currently discussed in the international myeloma community. Despite some improvement in survival, the prognosis remains adverse. New, more targeted treatment modalities, including immunotherapies, will hopefully improve the outcome in the near future.
http://bit.ly/2Rl15AZ
Effects of crab shell extract as a coagulant on the textural and sensorial properties of tofu (soybean curd)
The crab shell extract was developed to evaluate the usability as a coagulant for tofu. The texture and sensorial properties of tofu using crab shell extract were equal to those of MgCl2 and GDL. The crab shell extract might be provide a new business item as a natural coagulant for tofu making.
Abstract
To find an economic use of red snow crab (Chionoecetes japonicus) shell waste, we focused on its high mineral content. To evaluate its usability as a coagulant for tofu making, the effects of the crab shell extracts on the textural and sensorial properties of the tofu samples were investigated. The crab shell powder (CSP) and ash (CSA) were used for their extract preparation, and 1%–5% acetic acid treatment led to an abundance of calcium in the resulting extracts. The tofu yields of all the acetic acid extracts were comparable with those of the commercial coagulants MgCl2 and glucono‐δ‐lactone (GDL). Furthermore, the results for the textural attributes and sensorial acceptability demonstrated that either the extract from CSP prepared with 3% acetic acid or the extracts from CSA prepared with 1% or 3% acetic acid could be used as coagulants, because all the values of the extracts were statistically equivalent to those of the MgCl2 and GDL (p < 0.05).
http://bit.ly/2CLGNLT
Reproducibility of the Peritoneal Regression Grading Score (PRGS) for assessment of response to therapy in peritoneal metastasis
Abstract
Introduction
The 4‐tiered Peritoneal Regression Grading Score (PRGS) is assessing response to chemotherapy in peritoneal metastasis (PM). The PRGS is for example used to assess response to Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC). However, the reproducibility of the PRGS is currently unkown. We aimed to evaluate the interobserver and intraobserver variability of the PRGS.
Materials and methods
33 patients who underwent at least 3 PIPAC treatments as part of the PIPAC‐OPC1 or PIPAC‐OPC2 clinical trials at Odense University Hospital, Denmark, were included. Prior to each therapy cycle, peritoneal quadrant biopsies were obtained, and three H&E stained step sections were scanned and uploaded to a pseudonymized web library. For determining the interobserver variability, eight pathologists assessed the PRGS for each quadrant biopsy, and Krippendorff's alpha and Intraclass Correlation Coefficients (ICCs) were calculated. For determining intraobserver variability, three pathologists repeated their own assessments, and Cohen's kappa and ICCs were calculated.
Results
A total of 331 peritoneal biopsies were analyzed. Interobserver variability for PRGS of each biopsy and for the mean and maximum PRGS per biopsy set was moderate to good/substantial. The intraobserver variability for PRGS of each biopsy and for the mean and maximum PRGS per biopsy set was good to excellent/almost perfect.
Discussion
Our data support the Peritoneal Regression Grading Score (PRGS) as a reproducible and useful tool to assess response to intraperitoneal chemotherapy in peritoneal metastasis. Future studies should evaluate the prognostic and predictive role of the PRGS.
This article is protected by copyright. All rights reserved.
http://bit.ly/2sOYpSt
The risk of infective endocarditis among people who inject drugs: a retrospective, population-based time series analysis [Research]
BACKGROUND:
Infective endocarditis is an increasingly common complication among people who inject drugs. We conducted this study to determine whether the removal of traditional controlled-release oxycodone from the Canadian market would be associated with an increase in the use of hydromorphone and an increased risk of infective endocarditis.
METHODS:We conducted a retrospective, population-based time series analysis using the linked health administrative databases of Ontario, Canada. We measured the quarterly risk of admissions for infective endocarditis related to injection drug use and changes in opioid prescription rates from 2006 to 2015. We set the intervention point at the fourth quarter of 2011, when traditional controlled-release oxycodone was removed from the Canadian market.
RESULTS:We observed an increase in the risk of admissions for infective endocarditis related to injection drug use during the study period. Before the intervention point, we observed a mean of 13.4 admissions per quarter, and after the intervention, we observed a mean of 35.1 admissions per quarter. However, no significant change in this risk occurred at the intervention point. Rather, the risk of infectious endocarditis appeared to have increased earlier and in parallel with the rise in hydromorphone prescriptions. Hydromorphone represented 16% of all opioid prescriptions at the start of the observation period and 53% by the end.
INTERPRETATION:The risk of infective endocarditis related to injection drug use is increasing and is temporally associated with increasing prescriptions for hydromorphone. This relation warrants further exploration.
http://bit.ly/2sPlZPd
Emotion Recognition in Low-Spatial Frequencies Is Partly Preserved following Traumatic Brain Injury
After a Traumatic Brain Injury (TBI), emotion recognition is typically impaired. This is commonly attributed to widespread multifocal damage in cortical areas involved in emotion processing as well as to Diffuse Axonal Injury (DAI). However, current models suggest that emotional recognition is subserved by a distributed network cantered on the amygdala, which involves both cortical and subcortical structures. While the cortical system is preferentially tuned to process high spatial frequencies, the subcortical networks are more sensitive to low-spatial frequencies. The aim of this study was to evaluate whether emotion perception from low-spatial frequencies underpinning the subcortical system is relatively preserved in TBI patients. We tested a group of 14 subjects with severe TBI and 20 matched healthy controls. Each participant was asked to recognize the emotion expressed by each stimulus that consisted of happy and fearful faces, filtered for their low and high spatial frequencies components. Results in TBI patients' performances showed that low-spatial frequency expressions were recognized with higher accuracy and faster reaction times when compared to high spatial frequency stimuli. On the contrary, healthy controls did not show any effect in the two conditions, neither for response accuracy nor for reaction times. The outcomes of this study indicate that emotion perception from low-spatial frequencies is relatively preserved in TBI, thereby suggesting spare of functioning in the subcortical system in mediating emotion recognition.
http://bit.ly/2FSKofe
Circular RNA Profiling by Illumina Sequencing via Template-Dependent Multiple Displacement Amplification
Circular RNAs (circRNAs) are newly discovered incipient non-coding RNAs with potential roles in disease progression in living organisms. Significant reports, since their inception, highlight the abundance and putative functional roles of circRNAs in every organism checked for, like O. sativa, Arabidopsis, human, and mouse. CircRNA expression is generally less than their linear mRNA counterparts which fairly explains the competitive edge of canonical splicing over non-canonical splicing. However, existing methods may not be sensitive enough for the discovery of low-level expressed circRNAs. By combining template-dependent multiple displacement amplification (tdMDA), Illumina sequencing, and bioinformatics tools, we have developed an experimental protocol that is able to detect 1,875 novel and known circRNAs from O. sativa. The same method also revealed 9,242 putative circRNAs in less than 40 million reads for the first time from the Nicotiana benthamiana whose genome has not been fully annotated. Supported by the PCR-based validation and Sanger sequencing of selective circRNAs, our method represents a valuable tool in profiling circRNAs from the organisms with or without genome annotation.
http://bit.ly/2G19Qya
Probiotic Studies in Neonatal Mice Using Gavage
http://bit.ly/2FRtQUW
A Controlled Mouse Model for Neonatal Polymicrobial Sepsis
This protocol provides the necessary steps to establish and evaluate neonatal sepsis in 7-day-old mice.
http://bit.ly/2HCMlxY
Sexual Transmission of American Trypanosomes from Males and Females to Naive Mates
http://bit.ly/2S8HFE9
Prevalence of Pulmonary Embolism in Patients Presenting with Syncope
Abstract
Syncope accounts for 1‐3% of emergency department (ED) visits and 1‐6% of hospital admissions. There are numerous etiologies, ranging from relatively benign vasovagal syncope to dangerous dysrhythmias. The ED evaluation and management of syncope is comprised of history, examination, and typically an electrocardiogram, with further investigation dependent upon clinical decision‐making and suspected conditions. Previously, pulmonary embolism (PE) was thought to account for a small minority of patients with syncope. However, a recent study by Prandoni and colleagues reported a high prevalence of PE in admitted patients with syncope (3.8% of ED patients and 17.3% of hospitalized patients).
This article is protected by copyright. All rights reserved.
http://bit.ly/2FVTeZN
Surgical treatment of liver metastases from kidney cancer: a systematic review
Liver metastases are present in 20.3% of metastatic kidney cancers. Surgical resection of liver metastases from kidney cancer represents a valid option for selected patients with metastatic renal cancer.
Background
Liver metastases are present in 20.3% of metastatic kidney cancers. The aim of this literature review was to assess the efficacy of surgical treatment for hepatic metastasis from kidney cancer.
Methods
An extended web search of the literature was independently performed in March 2018 by two authors according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta‐Analyses) statement.
Results
Through electronic searches, we identified 935 potentially relevant citations. Thirteen articles were finally included in the systematic review. Median survival after resection ranged from 15 to 142 months while the 1‐, 3‐ and 5‐year overall survival ranged from 69% to 100%, 26% to 83.3% and 0% to 62%, respectively. Median disease‐free survival ranged from 7.2 to 27 months.
Conclusion
Surgical treatment of hepatic metastases is performed in approximately 1% of patients with liver metastases and in select patients may be potentially curative. Surgical resection of liver metastases from kidney cancer represents a valid option for selected patients with metastatic renal cancer.
http://bit.ly/2WjX6sg
Evaluation of website information provided by paediatric surgery centres in Australia and New Zealand
This is the first study to evaluate the quality of paediatric surgical information provided in hospital websites within Australia and New Zealand. One‐third of centres do not have a hospital webpage. Our findings suggest that an improvement in internet presence of paediatric surgery in Australasia is needed.
Background
Hospital websites are an important source of information for patients, parents and healthcare providers. There are currently no standardized recommendations for the information provided on paediatric surgery websites. We aimed to assess the information available on each hospital website, in Australia and New Zealand, which provides paediatric surgical care.
Methods
Google search was performed of the 16 paediatric surgical centres in Australia and New Zealand to determine whether they had a hospital website and to assess its contents. The presence of patient fact sheets and clinical practice guidelines was recorded. Access to contact information, hospital Facebook page and Twitter handles were noted.
Results
We found that 11 (69%) centres had a specific paediatric surgical section to the hospital website, all provided contact information. Five centres (31%) had paediatric‐specific guidelines available for health professionals. Six websites (37.5%) provided health information sheets on common paediatric surgical conditions. Facebook and Twitter facilities were present on the majority of the websites (75%).
Conclusion
The internet presence of paediatric surgery in Australia and New Zealand is sparse. One‐third of centres do not have hospital web presence. The availability of clinical guidelines and patient information sheets on hospital websites is limited. Our findings would suggest that improvement and increase in the internet presence of paediatric surgery in Australia and New Zealand is needed.
http://bit.ly/2RjLult
Collagenase injections for Dupuytren's contracture: prospective cohort study in a public health setting
Collagenase Clostridium histolyticum injections are a viable alternative treatment for Dupuytren's contracture in the Australian public health setting.
Background
Dupuytren's disease causes a flexion contracture of the hand that limits hand function and reduces quality of life. Traditional management is surgical excision which is associated with potentially serious complications. A viable alternative is collagenase Clostridium histolyticum (CCH) (Xiaflex®; Pfizer Australia) which is an effective, safe, outpatient treatment that to date has no published data in the Australian public health setting.
Methods
A prospective cohort, single centre study, enrolling 54 patients to treat 81 joints with CCH. Patients received a single dose to the cord followed by joint manipulation 48 h later. Primary endpoint was reduction in contracture to 0 to 5° of full extension assessed 4 weeks after injection. Secondary endpoints included range of motion, patient satisfaction and function as measured by the Southampton Dupuytren's Scoring Scheme (SDSS).
Results
Primary endpoint was achieved in 48% of joints (66% metacarpophalangeal and 19% proximal interphalangeal). Mean flexion contracture improved by 40o and 25o for metacarpophalangeal and proximal interphalangeal joints, respectively. Mean active range of motion improved by 39o and 18o, respectively. At 30 days and 12 months, SDSS score demonstrated sustained improvement versus baseline (1.88 versus 8.24 P ≤ 0.0005 and 1.59 versus 8.07 P ≤ 0.0005). Sixty‐eight percent of patients were either very satisfied or satisfied at 12‐month follow‐up. Side effects of treatment were minor; with oedema and bruising the most common (87% and 85%, respectively).
Conclusion
CCH injections are a viable treatment for Dupuytren's contracture in the Australian public health setting.
http://bit.ly/2WmXmqz
Does knee position during wound closure alter patella height following total knee arthroplasty?
The aim of the study was to evaluate the effect of knee position during surgical closure of capsule, and skin on patella tendon length after total knee arthroplasty. Small but statistically significant differences were identified between flexion and extension groups initially postoperatively but this effect was not sustained at 12 months.
Background
Patella infera is a known complication of total knee arthroplasty, and the method of soft tissue closure is a possible contributing factor. The aim of our study was to evaluate the effect of knee position during surgical closure of capsule, subcutaneous tissue and skin on patella tendon length after total knee arthroplasty.
Methods
A three arm retrospective cohort study was conducted in a single institution over a 3‐year period; 75 patients were divided, by surgeon preference, into three groups (Flexed, Extended and Hybrid) of 25 patients. All groups had standardized prosthesis, intraoperative and postoperative protocols, and differed in knee position at closure. Patellar tendon length was assessed radiologically using Insall Salvati ratio (ISR) and modified Insall Salvati ratio, with a 12‐month follow‐up. Intraclass correlation coefficients were used to assess intraobserver variability.
Results
There was a small but significant difference in preoperative to initial postoperative ISR change between Flexed and Extended groups (Extended group mean ISR change = −0.05; t = −2.31, P = 0.025, independent samples t‐test), which was not sustained at 12 months. The incidence of patella infera was similar in Flexed and Extended groups at 12 months with only one case seen in the Hybrid group.
Conclusion
Our study suggests that knee position during soft tissue closure does not have a sustained impact on patella tendon length after knee replacement. A small but statistically significant reduction in patella height was found in the Extended group initially after surgery but this effect was not sustained at 12 months.
http://bit.ly/2RjFlp8
Outcomes from cytoreduction and hyperthermic intraperitoneal chemotherapy for appendiceal epithelial neoplasms
Cytoreductive surgery with HIPEC for PMP and other appendiceal neoplasms is safe and effective. Despite carrying some morbidity, it offers very good 5 year, overall and recurrence‐free survival.
Background
Appendiceal epithelial neoplasms are rare cancers. Management of peritoneal disease from appendiceal neoplasms has historically been with debulking surgery. In recent decades, the advent of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has become the standard of care. Here, we report our single institution 10‐year experience with CRS and HIPEC for appendiceal neoplasms.
Methods
This is a retrospective review from 1 January 2008 to 1 June 2017 of all patients undergoing CRS and HIPEC for appendiceal neoplasms. Institutional ethics approval was granted for this project.
Results
One hundred and seventy‐two patients underwent 208 CRSs during this time. Overall, 83.72% of patients had one CRS and HIPEC procedure. Pseudomyxoma peritonei from a perforated appendiceal mucinous neoplasm accounted for 67.9% of cases. The median peritoneal carcinomatosis index (PCI) was 14, with complete cytoreduction achieved in 74.2% of patients. Fifty‐four percent of patients had at least one complication, with one (0.5%) peri‐operative mortality in our cohort. For the entire cohort, the median overall survival was 104 months and a 5‐year survival of 75%. In those having a complete cytoreduction, 5‐year survival was 90%, with a median disease free interval of 63 months. PCI and completeness of cytoreduction were independent predictors of overall survival.
Conclusion
Our results demonstrate that CRS and HIPEC for appendiceal neoplasms are safe and effective. Despite carrying some morbidity, it offers patients an excellent disease free and overall survival.
http://bit.ly/2WlnaTY
Ureteric implantation into the bowel portion of augmented bladders during kidney transplantation: a review of urological complications and outcomes
Background
In patients with bladder augmentation undergoing kidney transplantation, conventional technique recommends anastomosing the transplanted ureter to the bladder. We report our technique of ureteric implantation into the bowel portion of the enterocystoplasty, and review the urological outcomes of transplantation in these patients.
Methods
Seven patients (mean age: 26 years (range 24–54 years), two females, five deceased donors) with augmented cystoplasty and subsequent kidney transplantation by a single surgeon from 2011 to 2015 were reviewed. Following standard vascular anastomosis and reperfusion of the transplanted kidney, ureteric implantation involved continuous 5/0 polydiaoxanone anastomosis between the spatulated ureter and full thickness bowel portion of the cystoplasty over a 6‐Fr double J stent. A second peri‐anastomosis layer of bowel plication was performed to prevent reflux using interrupted 3/0 vicryl sutures. Short‐term urological and kidney function outcomes were evaluated.
Results
Causes of renal failure included: posterior urethral valve with reflux nephropathy (two patients), bilateral vesicoureteric reflux (two patients), lumbosacral agenesis with neurogenic bladder (one patient), tuberculosis of the urinary tract with post‐infective ureteric stricture (one patient), and lupus nephritis (one patient). Bladder reconstruction was performed at median duration of 103 months (35–171 months) before transplantation. Gastrocystoplasty was performed in two patients while colon and/or ileum were used in the remaining six. After transplantation, all reconstructed bladders except one had a Mitrofanoff for clean intermittent self‐catheterization, 5–8 times per day. There were no post‐operative ureteric/surgical complications. Delayed graft function occurred in three of seven patients. 30‐day asymptomatic bacteriuria rate was three out of seven after stent removal. 1‐year post‐transplantation, patient and graft survival were 100%. Mean serum creatinine was 142.7 (standard deviation: 51.48). Median number of hospital admissions for urinary tract infections was 0.225 (range 0–0.40). Over a median follow‐up period of 4 years (2–7 years), one graft failed from acute T‐cell‐mediated rejection. This patient passed away from cardio‐respiratory collapse after a seizure, 35 months post‐transplantation. As of June 2018, the other six kidney grafts were functioning. No complications including calculi formation and/or malignancy were reported.
Conclusion
In patients with previously augmented bladders now undergoing kidney transplantation, ureteric implantation into the bowel portion of the cystoplasty appears to be safe.
http://bit.ly/2Rik0N4
Euglycemic Ketoacidosis in Spinal Muscular Atrophy
Euglycemic ketoacidosis is defined by the triad of high anion gap acidosis, increased plasma ketones, and the absence of hyperglycemia. Apart from diabetes mellitus, the disorder may occur in prolonged fasting, excessive alcohol consumption, pregnancy, and inborn errors of metabolism. Here, we highlight the diagnosis of euglycemic ketoacidosis in a pediatric nondiabetic patient with spinal muscular atrophy (SMA) type 1 (Werdnig–Hoffmann disease), who, subsequently to her postoperative admission to the intensive care unit following a spinal surgery, developed high anion gap metabolic acidosis. We discuss the pathophysiology of acid-base disorders in SMA, along with the glucose and fatty acids metabolism, the necessary knowledge for medical practitioners.
http://bit.ly/2RSzkVT
Handling Big Data Scalability in Biological Domain Using Parallel and Distributed Processing: A Case of Three Biological Semantic Similarity Measures
In the field of biology, researchers need to compare genes or gene products using semantic similarity measures (SSM). Continuous data growth and diversity in data characteristics comprise what is called big data; current biological SSMs cannot handle big data. Therefore, these measures need the ability to control the size of big data. We used parallel and distributed processing by splitting data into multiple partitions and applied SSM measures to each partition; this approach helped manage big data scalability and computational problems. Our solution involves three steps: split gene ontology (GO), data clustering, and semantic similarity calculation. To test this method, split GO and data clustering algorithms were defined and assessed for performance in the first two steps. Three of the best SSMs in biology [Resnik, Shortest Semantic Differentiation Distance (SSDD), and SORA] are enhanced by introducing threaded parallel processing, which is used in the third step. Our results demonstrate that introducing threads in SSMs reduced the time of calculating semantic similarity between gene pairs and improved performance of the three SSMs. Average time was reduced by 24.51% for Resnik, 22.93%, for SSDD, and 33.68% for SORA. Total time was reduced by 8.88% for Resnik, 23.14% for SSDD, and 39.27% for SORA. Using these threaded measures in the distributed system, combined with using split GO and data clustering algorithms to split input data based on their similarity, reduced the average time more than did the approach of equally dividing input data. Time reduction increased with increasing number of splits. Time reduction percentage was 24.1%, 39.2%, and 66.6% for Threaded SSDD; 33.0%, 78.2%, and 93.1% for Threaded SORA in the case of 2, 3, and 4 slaves, respectively; and 92.04% for Threaded Resnik in the case of four slaves.
http://bit.ly/2RVVeaz
Levels of CEACAM6 in Peripheral Blood Are Elevated in Patients with Plasma Cell Disorders: A Potential New Diagnostic Marker and a New Therapeutic Target?
Introduction. The prognosis of multiple myeloma is still unfavorable due to inherent characteristics of the disease and the often-delayed diagnosis due to widespread and unspecific symptoms such as back pain and fatigue. Therefore, a simple diagnostic blood test would be helpful to speed up the diagnostic procedure in such patients (pts.). Here, we evaluated the diagnostic value of plasma levels of carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) in the peripheral blood and bone marrow of pts. with plasma cell disorders and in healthy controls. Materials and Methods. Immunoreactive CEACAM6 was determined in the peripheral blood and bone marrow () of pts. with monoclonal gammopathy of unknown significance (MGUS: 28/37), newly diagnosed multiple myeloma (NDMM: 42/40), and relapsed/refractory multiple myeloma (RRMM: 25/23) by sandwich ELISA. Results. Median CEACAM6 levels in the peripheral blood of pts. with plasma cell disorders were significantly higher than those of healthy controls (healthy controls: 15.2 pg/ml (12.1-17.1); MGUS: 19.0 pg/ml (16.4-22.5); NDMM: 18.0 pg/ml (13.4-21.2); and RRMM: 18.9 pg/ml (15.2-21.5); ). Plasma levels of CEACAM6 discriminated healthy subjects from MGUS/NDMM pts. (, 95% CI: 0.6-0.8); i.e., a CEACAM6 pg/ml has an 82% (95% CI: 70-90) predictive probability for the identification of MGUS or NDMM. Moreover, CEACAM6 levels in the bone marrow were significantly higher in RRMM pts. than in NDMM pts. (), suggesting a role of this molecule in disease progression. Conclusion. CEACAM6 plasma levels can noninvasively identify pts. with a plasma cell disorder and should be evaluated prospectively as a potential diagnostic marker. Moreover, due to high CEACAM6 levels in the bone marrow in RRMM pts., this adhesion molecule might be a therapeutic target in multiple myeloma pts.
http://bit.ly/2sRFgza
Proinflammatory Role of Angiotensin II in the Aorta of Normotensive Mice
Angiotensin II plays important functions in cardiovascular system mediating actions leading to inflammatory responses such as activation of VSMC in order to produce ROS, inflammatory cytokines, chemokines, and adhesion molecules. Changes in angiotensin II production could stimulate the recruitment and activation of myeloid cells initiating local inflammatory response without effect on BP. We aimed to verify if angiotensin II induces an inflammatory response in the aorta and if it correlates with variations in BP. C57Bl/6 mice treated with saline solution (0.9%, control group) or angiotensin II (30ng/kg, Ang II group) were used. BP and HR levels were measured. Immunohistochemistry for IL1-β, TGF-β, iNOS, CD45, and α-actin was performed in the aorta. BP and HR do not change. A biphasic response was observed both for IL1-β and TGF-β expression and also for the presence of CD45 positive cells, with an acute increase (between 30 and 60 minutes) and a second increase, between 24 and 48 hours. Positive staining for iNOS increased in the earlier period (30 minutes) in perivascular adipose tissue and in a longer period (48 hours) in tunica adventitia. Immunoblotting to α-actin showed no alterations, suggesting that the applied dose of angiotensin II does not alter the aortic VSMCs phenotype. The results suggest that angiotensin II, even at doses that do not alter BP, induces the expression of inflammatory markers and migration of inflammatory cells into the aorta of normotensive mice. Thus, angiotensin II may increase the propensity to develop a cardiovascular injury, even in normotensive individuals.
http://bit.ly/2MyzSKn
“Crack, Reduce, and Implant”: A Safe Phaco Technique in a Case with Hard Brown Cataract
This report describes two maneuvers in different steps of phaco surgery in a case with hard cataract, which provide debulking of the central dense nucleus and prevents posterior capsule rupture (PCR). In the current case, clear corneal incisions were created, and anterior chamber was filled with ophthalmic viscosurgical device (OVD). Anterior capsule was punctured, and capsulorhexis was completed. Nucleus was cracked into two halves following vertical groove formation. Core nucleus was hollowed sideward bilaterally in the capsular bag. Nuclear halves were removed from capsular bag, and each one was pushed to one side on the iris plane. Capsular bag was inflated with OVD, and intraocular lens (IOL) was implanted. Nuclear halves were removed in confidence. The presented maneuvers initially reduce dense nucleus load in the safe zone and allow surgeon to use IOL as a barrier to protect floppy posterior capsule from early steps of the surgery.
http://bit.ly/2sMQJQH
Cancers, Vol. 11, Pages 147: A Simplified Genomic Profiling Approach Predicts Outcome in Metastatic Colorectal Cancer
Cancers, Vol. 11, Pages 147: A Simplified Genomic Profiling Approach Predicts Outcome in Metastatic Colorectal Cancer
Cancers doi: 10.3390/cancers11020147
Authors: Carlo Capalbo Francesca Belardinilli Domenico Raimondo Edoardo Milanetti Umberto Malapelle Pasquale Pisapia Valentina Magri Alessandra Prete Silvia Pecorari Mariarosaria Colella Anna Coppa Caterina Bonfiglio Arianna Nicolussi Virginia Valentini Alessandra Tessitore Beatrice Cardinali Marialaura Petroni Paola Infante Matteo Santoni Marco Filetti Valeria Colicchia Paola Paci Silvia Mezi Flavia Longo Enrico Cortesi Paolo Marchetti Giancarlo Troncone Diana Bellavia Gianluca Canettieri Giuseppe Giannini
The response of metastatic colorectal cancer (mCRC) to the first-line conventional combination therapy is highly variable, reflecting the elevated heterogeneity of the disease. The genetic alterations underlying this heterogeneity have been thoroughly characterized through omic approaches requiring elevated efforts and costs. In order to translate the knowledge of CRC molecular heterogeneity into a practical clinical approach, we utilized a simplified Next Generation Sequencing (NGS) based platform to screen a cohort of 77 patients treated with first-line conventional therapy. Samples were sequenced using a panel of hotspots and targeted regions of 22 genes commonly involved in CRC. This revealed 51 patients carrying actionable gene mutations, 22 of which carried druggable alterations. These mutations were frequently associated with additional genetic alterations. To take into account this molecular complexity and assisted by an unbiased bioinformatic analysis, we defined three subgroups of patients carrying distinct molecular patterns. We demonstrated these three molecular subgroups are associated with a different response to first-line conventional combination therapies. The best outcome was achieved in patients exclusively carrying mutations on TP53 and/or RAS genes. By contrast, in patients carrying mutations in any of the other genes, alone or associated with mutations of TP53/RAS, the expected response is much worse compared to patients with exclusive TP53/RAS mutations. Additionally, our data indicate that the standard approach has limited efficacy in patients without any mutations in the genes included in the panel. In conclusion, we identified a reliable and easy-to-use approach for a simplified molecular-based stratification of mCRC patients that predicts the efficacy of the first-line conventional combination therapy.
http://bit.ly/2TlgBPu
Cancers, Vol. 11, Pages 148: Histone Deacetylase Inhibitors and Phenotypical Transformation of Cancer Cells
Cancers, Vol. 11, Pages 148: Histone Deacetylase Inhibitors and Phenotypical Transformation of Cancer Cells
Cancers doi: 10.3390/cancers11020148
Authors: Anna Wawruszak Joanna Kalafut Estera Okon Jakub Czapinski Marta Halasa Alicja Przybyszewska Paulina Miziak Karolina Okla Adolfo Rivero-Muller Andrzej Stepulak
Histone deacetylase inhibitors (HDIs) are a group of potent epigenetic drugs which have been investigated for their therapeutic potential in various clinical disorders, including hematological malignancies and solid tumors. Currently, several HDIs are already in clinical use and many more are on clinical trials. HDIs have shown efficacy to inhibit initiation and progression of cancer cells. Nevertheless, both pro-invasive and anti-invasive activities of HDIs have been reported, questioning their impact in carcinogenesis. The aim of this review is to compile and discuss the most recent findings on the effect of HDIs on the epithelial-mesenchymal transition (EMT) process in human cancers. We have summarized the impact of HDIs on epithelial (E-cadherin, β-catenin) and mesenchymal (N-cadherin, vimentin) markers, EMT activators (TWIST, SNAIL, SLUG, SMAD, ZEB), as well as morphology, migration and invasion potential of cancer cells. We further discuss the use of HDIs as monotherapy or in combination with existing or novel anti-neoplastic drugs in relation to changes in EMT.
http://bit.ly/2B6RCZ7
Differentiated-Type Intraepithelial Neoplasia-Like Lesion Associated with Squamous Cell Carcinoma of the Anus: A Case Report with Molecular Profile
Differentiated-type Intraepithelial Neoplasia (DIN) is defined as HPV-negative squamous intraepithelial proliferation with abnormal keratinocyte differentiation and basal cell atypia, originally described in the vulva, with following descriptions in the oral cavity. DIN occurring in the anus is quite rare, and to the best of our knowledge, only one publication reported it. In this report, we describe the clinicopathological features of this entity on anal margin, associated with invasive squamous cell carcinoma. In addition, using the next generation sequencing (NGS) technique, we have demonstrated TP53 mutation in the invasive component but not in the associated DIN-like lesion, where p53 immunohistochemical expression was restricted to basal layers.
http://bit.ly/2MxxLXt
Inhibition of LOXL2 Enhances the Radiosensitivity of Castration-Resistant Prostate Cancer Cells Associated with the Reversal of the EMT Process
Introduction. Radiotherapy is the mainstay in the treatment of prostate cancer. However, significant radioresistance of castration-resistant prostate cancer (CRPC) cells constitutes a main obstacle in the treatment of this disease. By using bioinformatic data mining methods, LOXL2 was found to be upregulated in both androgen-independent prostate cancer cell lines and radioresistant tumor samples collected from patients with prostate cancer. We speculate that LOXL2 may play an important role in the radioresistance of CRPC cells. Methods. The effect of LOXL2 knockdown on the radiosensitivity of androgen-independent prostate cancer cells lines was measured by the clonogenic assay and xenograft tumor experiments under in vitro and in vivo conditions, respectively. In studies on the mechanism, we focused on the EMT phenotype changes and cell apoptosis changes induced by LOXL2 knockdown in DU145 cells. The protein levels of three EMT biomarkers, namely, E-cadherin, vimentin, and N-cadherin, were measured by western blotting and immunohistochemical staining. Cell apoptosis after irradiation was measured by flow cytometry and caspase-3 activity assay. Salvage experiment was also conducted to confirm the possible role of EMT in the radiosensitization effect of LOXL2 knockdown in CRPC cells. Results. LOXL2 knockdown in CRPC cells enhanced cellular radiosensitivity under both in vitro and in vivo conditions. A significant reversal of EMT was observed in LOXL2-silenced DU145 cells. Cell apoptosis after irradiation was significantly enhanced by LOXL2 knockdown in DU145 cells. Results from the salvage experiment confirmed the key role of EMT process reversal in the radiosensitization effect of LOXL2 knockdown in DU145 cells. Conclusions. LOXL2 plays an important role in the development of cellular radioresistance in CRPC cells. Targeting LOXL2 may be a rational avenue to overcome radioresistance in CRPC cells. A LOXL2-targeting strategy for CRPC treatment warrants detailed investigation in the future.
http://bit.ly/2UiV6Pe
Vitamin D Regulates the Expressions of AQP-1 and AQP-4 in Mice Kidneys
Aim. Vitamin D plays an important role in water and salt homeostasis. The aim of our study was to investigate the underlying relationship of Vitamin D and Aquaporins (AQP). Methods. The behaviors of 1α (OH)-ase knockout mice and wild type mice were observed before analysis. The ICR mice were treated with vehicle or paricalcitol, a vitamin D analogue, followed by animals receiving a standard diet and free access to drinking water either with aliskiren (renin blocker; 37.5 mg aliskiren in 100 ml water), or telmisartan (a angiotensin II type I receptor blocker; 40 mg telmisartan in 100 ml water) a week before study. The expressions of AQP-1, AQP-4, and renin in mice kidneys were detected by western bolting, immunohistochemistry, and immunofluorescence. Results. Diuresis and polydipsia were observed in 1α (OH)-ase knockout mice, and a decreased water intake and urine output in ICR mice was observed after paricalcitol treatment. Compared with wild type, the AQP-1 expressions were increased in renal papilla and AQP-4 expressions were decreased in renal proximal tubule of 1α(OH) ase knockout mice. In addition, AQP-1 was decreased in renal papilla and AQP-4 expressions were increased in proximal tubule by suppressing renin activity or supplement of Vitamin D analogue. After injecting renin into the lateral ventricle of the 1α(OH)ase knockout mice, the renin expression level was decreased in the kidney, followed by the decrease of AQP-1 in renal papilla and increase of AQP-4 in proximal tubule. Conclusions. Overall, Vitamin D and renin inhibitors have synergistic effects in regulating water channels in mice kidneys.
http://bit.ly/2DCUlLp
Bioinformatics Analysis Reveals the Altered Gene Expression of Patients with Postmenopausal Osteoporosis Using Liuweidihuang Pills Treatment
Postmenopausal osteoporosis (PMOP), as well as its associated increased risk for fragility fracture, is one of the most disabling consequences of aging in women. This present study aimed to identify candidate genes that involve pathogenesis of PMOP and the therapeutic mechanism of Liuweidihuang (LWDH) pills on PMOP. We integrated microarray datasets of PMOP derived from the Gene Expression Omnibus (GEO) to screen differentially expressed genes (DEGs) between PMOP and normal controls as well as patients with PMOP and patients after treatment of LWDH pills. GO and KEGG enrichment analysis for DEGs were performed. The shared DEGs, associated with both the pathogenesis of PMOP and the therapeutic mechanism of LWDH, were further analyzed by protein-protein interaction (PPI) network. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to verify the DEGs obtained by our integrated analysis. Compared with normal controls, 1732 DEGs in PMOP were obtained with p
http://bit.ly/2B4JWX4
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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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