Ulcerative colitis and Crohn's disease are chronic relapsing-remitting inflammatory processes of the intestinal tract. The etiology of these diseases is currently unknown. However, inflammation is hypothesized to ...Ulcerative colitis and Crohn's disease are chronic relapsing-remitting inflammatory processes of the intestinal tract. The etiology of these diseases is currently unknown. However, inflammation is hypothesized to result from inappropriate activation of mucosal immunity by luminal antigens in genetically susceptible individuals. Toll-like receptors (TLRs) are a family of transmembrane proteins that act as microbial pattern recognition receptors. They are crucial initiators of innate immune responses. The role of TLRs in the pathogenesis of inflammatory bowel disease (IBD) has not been fully elucidated. In this review, we aim to analyze the available data connecting individual TLRs to intestinal inflammation and IBD.展开更多
Apoptosis plays a pivotal role in the etiology or pathogenesis of numerous medical disorders, and thus, target- ing of apoptotic cells may substantially advance patient care. In our quest for novel low-molecular-weigh...Apoptosis plays a pivotal role in the etiology or pathogenesis of numerous medical disorders, and thus, target- ing of apoptotic cells may substantially advance patient care. In our quest for novel low-molecular-weight probes for apoptosis, we focused on the uncommon amino acid T-carboxyglutamic acid （Gla）, which plays a vital role in the binding of clotting factors to negatively charged phospholipid surfaces. Based on the alkyl-malonic acid motif of Gla, we have developed and now present ML-10 （2-（5-fluoro-pentyl）-2-methyl-malonic acid, MW=206 Da）, the pro- totypical member of a novel family of small-molecule detectors of apoptosis. ML-10 was found to perform selective uptake and accumulation in apoptotic cells, while being excluded from either viable or necrotic cells. ML-10 uptake correlates with the apoptotic hallmarks of caspase activation, Annexin-V binding and disruption of mitochondrial membrane potential. The malonate moiety was found to be crucial for ML-10 function in apoptosis detection. ML- 10 responds to a unique complex of features of the cell in early apoptosis, comprising irreversible loss of membrane potential, permanent acidification of cell membrane and cytoplasm, and preservation of membrane integrity. ML-10 is therefore the most compact apoptosis probe known to date. Due to its fluorine atom, ML-10 is amenable to radio- labeling with the lSF isotope, towards its potential future use for clinical positron emission tomography imaging of apoptosis.展开更多
Osteoarthritis （OA） is a degenerative joint disease and a major cause of pain and disability in older adults. We have previously identified epidermal growth factor receptor （EGFR） signaling as an important regulat...Osteoarthritis （OA） is a degenerative joint disease and a major cause of pain and disability in older adults. We have previously identified epidermal growth factor receptor （EGFR） signaling as an important regulator of cartilage matrix degradation during epiphyseal cartilage development. To study its function in OA progression, we performed surgical destabilization of the medial meniscus （DMM） to induce OA in two mouse models with reduced EGFR activity, one with genetic modification （, was/＋ mice） and the other one with pharmacological inhibition （gefitinib treatment）. Histological analyses and scoring at 3 months post-surgery revealed increased cartilage destruction and accelerated OA progression in both mouse models. TUNEL staining demonstrated that EGFR signaling protects chondrocytes from OA-induced apoptosis, which was further confirmed in primary chondrocyte culture. Immunohistochemistry showed increased aggrecan degradation in these mouse models, which coincides with elevated amounts of ADAMTS5 and matrix metalloproteinase 13 （MMP13）, the principle proteinases responsible for aggrecan degradation, in the articular cartilage after DMM surgery. Furthermore, hypoxia-inducible factor 2α （HIF2α）, a critical catabolic transcription factor stimulating MMP13 expression during OA, was also upregulated in mice with reduced EGFR signaling. Taken together, our findings demonstrate a primarily protective role of EGFR during OA progression by regulating chondrocyte survival and cartilage degradation.展开更多
Objective:Patients are increasingly turning to the Internet as a source of healthcare information.Given that neck dissection is a common procedure within the field of Otolaryngology-Head and Neck Surgery,the aim of th...Objective:Patients are increasingly turning to the Internet as a source of healthcare information.Given that neck dissection is a common procedure within the field of Otolaryngology-Head and Neck Surgery,the aim of this study was to evaluate the quality and readability of online patient education materials on neck dissection.Methods:A Google search was performed using the term"neck dissection."The first 10 pages of a Google search using the term"neck dissection"were analyzed.The DISCERN instrument was used to assess quality of information.Readability was calculated using the Flesch-Reading Ease,Flesch-Kincaid Grade Level,Gunning-Fog Index,Coleman-Liau Index,and Simple Measure of Gobbledygook Index.Results:Thirty-one online patient education materials were included.Fifty-five percent(n=17)of results originated from academic institutions or hospitals.The mean Flesch-Reading Ease score was 61.2±11.9.Fifty-two percent(n=16)of patient education materials had Flesch-Reading Ease scores above the recommended score of 65.The average reading grade level was 10.5±2.1.The average total DISCERN score was 43.6±10.1.Only 26%of patient education materials(PEMs)had DISCERN scores corresponding to a"good quality"rating.There was a significant positive correlation between DISCERN scores and both Flesch-Reading Ease scores and average reading grade level.Conclusions:The majority of patient education materials were written above the recommended sixth-grade reading level and the quality of online information pertaining to neck dissections was found to be suboptimal.This research highlights the need for patient education materials regarding neck dissection that are high quality and easily understandable by patients.展开更多
This study is devoted to the numerical simulation of the artificial ground freezing process in a fluid-saturated rock mass of the potassium salt deposit. A coupled model of nonstationary thermal conductivity, filtrati...This study is devoted to the numerical simulation of the artificial ground freezing process in a fluid-saturated rock mass of the potassium salt deposit. A coupled model of nonstationary thermal conductivity, filtration and thermo-poroelasticity,which takes into account dependence of the physical properties on temperature and pressure, is proposed on the basis of the accepted hypotheses. The considered area is a cylinder with a depth of 256 meters and diameter of 26.5 meters and includes 13 layers with different thermophysical and filtration properties. Numerical simulation was carried out by the finite-element method. It has been shown that substantial ice wall formation occurs non-uniformly along the layers. This can be connected with geometry of the freezing wells and with difference in physical properties. The average width of the ice wall in each layer was calculated. It was demonstrated that two toroidal convective cells induced by thermogravitational convection were created from the very beginning of the freezing process. The effect of the constant seepage flow on the ice wall formation was investigated. It was shown that the presence of the slow flow lead to the delay in ice wall closure. In case of the flow with a velocity of more than 30 mm per day, closure of the ice wall was not observed at all in the foreseeable time.展开更多
How delightful!Spring is bringing everything a new beginning.Grass is greening.Birds are singing.Buds are blooming.Bells,areringing.Children in the park areswinging.I'm so happy spring is springing,Spring is comi...How delightful!Spring is bringing everything a new beginning.Grass is greening.Birds are singing.Buds are blooming.Bells,areringing.Children in the park areswinging.I'm so happy spring is springing,Spring is coming.春姑娘悄悄向我们走来,挥一挥衣袖,万物复苏。ning鸟儿在歌唱,虫儿在鸣叫。草儿探着头,花儿羞答答地笑。Spring is springing.Everything is shining.你的世界里,还有哪些正在“进行时”?展开更多
Background: Morel-Lavallee lesions (MLLs) are rare internal degloving injuries typically caused by blunt traumatic injuries and most commonly occur around the hips and in association with pelvic or acetabular fracture...Background: Morel-Lavallee lesions (MLLs) are rare internal degloving injuries typically caused by blunt traumatic injuries and most commonly occur around the hips and in association with pelvic or acetabular fractures. MLL is often overlooked in the setting of poly-trauma;therefore, clinicians must maintain a high degree of suspicion and be familiar with the management of such injuries, especially in obese poly-trauma patients. Case presentation: We present a 30-year-old female pedestrian struck by a motor vehicle who sustained multiple long bone fractures, a mesenteric hematoma, and full-thickness abdominal skin friction burn which masked a significant underlying abdominal MLL. The internal degloving caused significant devascularization of the overlying soft tissue and skin which required surgical drainage of hematoma, abdominal wall reconstruction with tangential excision, allografting, negative pressure wound therapy, and ultimately autografting. Conclusion: MLL is a rare, often overlooked, internal degloving injury. Surgeons must maintain a high index of suspicion when dealing with third degree friction burns as they may mask underlying injuries such as MLL, and a delay in diagnosis can lead to increased morbidity.展开更多
Multitarget stool DNA(mt-sDNA) testing was approved for average risk colorectal cancer(CRC) screening by the United States Food and Drug Administration and thereafter reimbursed for use by the Medicare program(2014).T...Multitarget stool DNA(mt-sDNA) testing was approved for average risk colorectal cancer(CRC) screening by the United States Food and Drug Administration and thereafter reimbursed for use by the Medicare program(2014).The United States Preventive Services Task Force(USPSTF) October 2015 draft recommendation for CRC screening included mt-s DNA as an "alternative" screening test that "may be useful in select clinical circumstances",despite its very high sensitivity for early stage CRC.The evidence supporting mt-s DNA for routine screening use is robust.The clinical efficacy of mt-s DNA as measured by sensitivity,specificity,life-years gained(LYG),and CRC deaths averted is similar to or exceeds that of the other more specifically recommended screening options included in the draft document,especially those requiring annual testing adherence.In a population with primarily irregular screening participation,tests with the highest point sensitivity and reasonable specificity are more likely to favorably impact CRC related morbidity and mortality than those depending on annual adherence.This paper reviews the evidence supporting mt-s DNA for routine screening and demonstrates,using USPSTF's modeling data,that mt-s DNA at three-year intervals provides significant clinical net benefits and fewer complications per LYG than annual fecal immunochemical testing,high sensitivity guaiac based fecal occult blood testing and 10-year colonoscopy screening.展开更多
文摘Ulcerative colitis and Crohn's disease are chronic relapsing-remitting inflammatory processes of the intestinal tract. The etiology of these diseases is currently unknown. However, inflammation is hypothesized to result from inappropriate activation of mucosal immunity by luminal antigens in genetically susceptible individuals. Toll-like receptors (TLRs) are a family of transmembrane proteins that act as microbial pattern recognition receptors. They are crucial initiators of innate immune responses. The role of TLRs in the pathogenesis of inflammatory bowel disease (IBD) has not been fully elucidated. In this review, we aim to analyze the available data connecting individual TLRs to intestinal inflammation and IBD.
文摘Apoptosis plays a pivotal role in the etiology or pathogenesis of numerous medical disorders, and thus, target- ing of apoptotic cells may substantially advance patient care. In our quest for novel low-molecular-weight probes for apoptosis, we focused on the uncommon amino acid T-carboxyglutamic acid （Gla）, which plays a vital role in the binding of clotting factors to negatively charged phospholipid surfaces. Based on the alkyl-malonic acid motif of Gla, we have developed and now present ML-10 （2-（5-fluoro-pentyl）-2-methyl-malonic acid, MW=206 Da）, the pro- totypical member of a novel family of small-molecule detectors of apoptosis. ML-10 was found to perform selective uptake and accumulation in apoptotic cells, while being excluded from either viable or necrotic cells. ML-10 uptake correlates with the apoptotic hallmarks of caspase activation, Annexin-V binding and disruption of mitochondrial membrane potential. The malonate moiety was found to be crucial for ML-10 function in apoptosis detection. ML- 10 responds to a unique complex of features of the cell in early apoptosis, comprising irreversible loss of membrane potential, permanent acidification of cell membrane and cytoplasm, and preservation of membrane integrity. ML-10 is therefore the most compact apoptosis probe known to date. Due to its fluorine atom, ML-10 is amenable to radio- labeling with the lSF isotope, towards its potential future use for clinical positron emission tomography imaging of apoptosis.
基金supported by ASBMR Research Career Enhancement Award (to LQ)NIH grants AR060991 (to LQ)AR062908 (to ME-I)
文摘Osteoarthritis （OA） is a degenerative joint disease and a major cause of pain and disability in older adults. We have previously identified epidermal growth factor receptor （EGFR） signaling as an important regulator of cartilage matrix degradation during epiphyseal cartilage development. To study its function in OA progression, we performed surgical destabilization of the medial meniscus （DMM） to induce OA in two mouse models with reduced EGFR activity, one with genetic modification （, was/＋ mice） and the other one with pharmacological inhibition （gefitinib treatment）. Histological analyses and scoring at 3 months post-surgery revealed increased cartilage destruction and accelerated OA progression in both mouse models. TUNEL staining demonstrated that EGFR signaling protects chondrocytes from OA-induced apoptosis, which was further confirmed in primary chondrocyte culture. Immunohistochemistry showed increased aggrecan degradation in these mouse models, which coincides with elevated amounts of ADAMTS5 and matrix metalloproteinase 13 （MMP13）, the principle proteinases responsible for aggrecan degradation, in the articular cartilage after DMM surgery. Furthermore, hypoxia-inducible factor 2α （HIF2α）, a critical catabolic transcription factor stimulating MMP13 expression during OA, was also upregulated in mice with reduced EGFR signaling. Taken together, our findings demonstrate a primarily protective role of EGFR during OA progression by regulating chondrocyte survival and cartilage degradation.
文摘Objective:Patients are increasingly turning to the Internet as a source of healthcare information.Given that neck dissection is a common procedure within the field of Otolaryngology-Head and Neck Surgery,the aim of this study was to evaluate the quality and readability of online patient education materials on neck dissection.Methods:A Google search was performed using the term"neck dissection."The first 10 pages of a Google search using the term"neck dissection"were analyzed.The DISCERN instrument was used to assess quality of information.Readability was calculated using the Flesch-Reading Ease,Flesch-Kincaid Grade Level,Gunning-Fog Index,Coleman-Liau Index,and Simple Measure of Gobbledygook Index.Results:Thirty-one online patient education materials were included.Fifty-five percent(n=17)of results originated from academic institutions or hospitals.The mean Flesch-Reading Ease score was 61.2±11.9.Fifty-two percent(n=16)of patient education materials had Flesch-Reading Ease scores above the recommended score of 65.The average reading grade level was 10.5±2.1.The average total DISCERN score was 43.6±10.1.Only 26%of patient education materials(PEMs)had DISCERN scores corresponding to a"good quality"rating.There was a significant positive correlation between DISCERN scores and both Flesch-Reading Ease scores and average reading grade level.Conclusions:The majority of patient education materials were written above the recommended sixth-grade reading level and the quality of online information pertaining to neck dissections was found to be suboptimal.This research highlights the need for patient education materials regarding neck dissection that are high quality and easily understandable by patients.
基金supported by the Russian Science Foundation (Grant No. 17-11-01204)
文摘This study is devoted to the numerical simulation of the artificial ground freezing process in a fluid-saturated rock mass of the potassium salt deposit. A coupled model of nonstationary thermal conductivity, filtration and thermo-poroelasticity,which takes into account dependence of the physical properties on temperature and pressure, is proposed on the basis of the accepted hypotheses. The considered area is a cylinder with a depth of 256 meters and diameter of 26.5 meters and includes 13 layers with different thermophysical and filtration properties. Numerical simulation was carried out by the finite-element method. It has been shown that substantial ice wall formation occurs non-uniformly along the layers. This can be connected with geometry of the freezing wells and with difference in physical properties. The average width of the ice wall in each layer was calculated. It was demonstrated that two toroidal convective cells induced by thermogravitational convection were created from the very beginning of the freezing process. The effect of the constant seepage flow on the ice wall formation was investigated. It was shown that the presence of the slow flow lead to the delay in ice wall closure. In case of the flow with a velocity of more than 30 mm per day, closure of the ice wall was not observed at all in the foreseeable time.
文摘How delightful!Spring is bringing everything a new beginning.Grass is greening.Birds are singing.Buds are blooming.Bells,areringing.Children in the park areswinging.I'm so happy spring is springing,Spring is coming.春姑娘悄悄向我们走来,挥一挥衣袖,万物复苏。ning鸟儿在歌唱,虫儿在鸣叫。草儿探着头,花儿羞答答地笑。Spring is springing.Everything is shining.你的世界里,还有哪些正在“进行时”?
文摘Background: Morel-Lavallee lesions (MLLs) are rare internal degloving injuries typically caused by blunt traumatic injuries and most commonly occur around the hips and in association with pelvic or acetabular fractures. MLL is often overlooked in the setting of poly-trauma;therefore, clinicians must maintain a high degree of suspicion and be familiar with the management of such injuries, especially in obese poly-trauma patients. Case presentation: We present a 30-year-old female pedestrian struck by a motor vehicle who sustained multiple long bone fractures, a mesenteric hematoma, and full-thickness abdominal skin friction burn which masked a significant underlying abdominal MLL. The internal degloving caused significant devascularization of the overlying soft tissue and skin which required surgical drainage of hematoma, abdominal wall reconstruction with tangential excision, allografting, negative pressure wound therapy, and ultimately autografting. Conclusion: MLL is a rare, often overlooked, internal degloving injury. Surgeons must maintain a high index of suspicion when dealing with third degree friction burns as they may mask underlying injuries such as MLL, and a delay in diagnosis can lead to increased morbidity.
文摘Multitarget stool DNA(mt-sDNA) testing was approved for average risk colorectal cancer(CRC) screening by the United States Food and Drug Administration and thereafter reimbursed for use by the Medicare program(2014).The United States Preventive Services Task Force(USPSTF) October 2015 draft recommendation for CRC screening included mt-s DNA as an "alternative" screening test that "may be useful in select clinical circumstances",despite its very high sensitivity for early stage CRC.The evidence supporting mt-s DNA for routine screening use is robust.The clinical efficacy of mt-s DNA as measured by sensitivity,specificity,life-years gained(LYG),and CRC deaths averted is similar to or exceeds that of the other more specifically recommended screening options included in the draft document,especially those requiring annual testing adherence.In a population with primarily irregular screening participation,tests with the highest point sensitivity and reasonable specificity are more likely to favorably impact CRC related morbidity and mortality than those depending on annual adherence.This paper reviews the evidence supporting mt-s DNA for routine screening and demonstrates,using USPSTF's modeling data,that mt-s DNA at three-year intervals provides significant clinical net benefits and fewer complications per LYG than annual fecal immunochemical testing,high sensitivity guaiac based fecal occult blood testing and 10-year colonoscopy screening.
