Objective:To identify possible stone-promoting microbes,we compared the profiles of microbes grown from stones of patients with and without metabolic syndrome(MetS).The association between MetS and urinary stone disea...Objective:To identify possible stone-promoting microbes,we compared the profiles of microbes grown from stones of patients with and without metabolic syndrome(MetS).The association between MetS and urinary stone disease is well established,but the exact pathophysiologic relationship remains unknown.Recent evidence suggests urinary tract dysbiosis may lead to increased nephrolithiasis risk.Methods:At the time of percutaneous nephrolithotomy,bladder urine and stone fragments were collected from patients with and without MetS.Both sample types were subjected to expanded quantitative urine culture(EQUC)and 16 S ribosomal RNA gene sequencing.Results:Fifty-seven patients included 12 controls(21.1%)and 45 MetS patients(78.9%).Both cohorts were similar with respect to demographics and non-MetS comorbidities.No controls had uric acid stone composition.By EQUC,bacteria were detected more frequently in MetS stones(42.2%)compared to controls(8.3%)(p=0.041).Bacteria also were more abundant in stones of MetS patients compared to controls.To validate our EQUC results,we performed 16 S ribosomal RNA gene sequencing.In 12/16(75.0%)sequence-positive stones,EQUC reliably isolated at least one species of the sequenced genera.Bacteria were detected in both“infectious”and“non-infectious”stone compositions.Conclusion:Bacteria are more common and more abundant in MetS stones than control stones.Our findings support a role for bacteria in urinary stone disease for patients with MetS regardless of stone composition.展开更多
Introduction Asthma is an inflammatory obstructive respiratory lung disease characterized by limited airflow.It is estimated that more than 300 million people worldwide are affected by asthma,and this number is expect...Introduction Asthma is an inflammatory obstructive respiratory lung disease characterized by limited airflow.It is estimated that more than 300 million people worldwide are affected by asthma,and this number is expected to increase over the next few years[1].Uncontrolled asthma is associated with a severely impaired quality of life and increased mortality rates[2].Other adverse effects of poorly controlled asthma include obesity,pneumonia.展开更多
BACKGROUND Esophageal foreign bodies are common around the world.Newer approaches,such as cap-assisted endoscopy,have been introduced as an alternative to conventional methods.Therefore,we performed a meta-analysis on...BACKGROUND Esophageal foreign bodies are common around the world.Newer approaches,such as cap-assisted endoscopy,have been introduced as an alternative to conventional methods.Therefore,we performed a meta-analysis ono cap-assisted endoscopy versus conventional endoscopy for removal of esophageal foreign bodies.AIM To investigated the effectiveness of cap-assisted endoscopy with conventional endoscopy.METHODS An extensive literature search was performed(December 2021).For esophageal foreign body removal,cap-assisted endoscopy was compared to conventional endoscopy for procedure time,technical success of the procedure,time of foreign body retrieval,en bloc removal,and adverse event rate using odds ratio and mean difference.RESULTS Six studies met the inclusion criteria(n=1305).Higher odds of technical success(P=0.002)and en bloc removal(P<0.01)and lower odds of adverse events(P=0.02)and foreign body removal time(P<0.01)were observed with cap-assisted endoscopy as compared to conventional techniques.CONCLUSION For esophageal foreign bodies,the technique of cap-assisted endoscopy demonstrated increased en bloc removal and technical success with decreased time and adverse events as compared to conventional techniques.展开更多
Peripheral nerve injuries are common consequences of extremity trauma or chronic compression with a prevalence of 43.8 per1 million people(on average)reported in the U nited States annually,accompanied by a yearly inc...Peripheral nerve injuries are common consequences of extremity trauma or chronic compression with a prevalence of 43.8 per1 million people(on average)reported in the U nited States annually,accompanied by a yearly increase in cost of care.展开更多
Mixed lineage kinase 3 (MLK3) is a mitogen-activated protein kinase kinase kinase that is activated by tumor necrosis factor-α (TNF-α) and specifically activates c-Jun N-terminal kinase (JNK) on TNF-a stimulat...Mixed lineage kinase 3 (MLK3) is a mitogen-activated protein kinase kinase kinase that is activated by tumor necrosis factor-α (TNF-α) and specifically activates c-Jun N-terminal kinase (JNK) on TNF-a stimulation. The mecha- nism by which TNF-α activates MLK3 is still not known. TNF receptor-associated factors (TRAFs) are adapter molecules that are recruited to cytoplasmic end of TNF receptor and mediate the downstream signaling, including activation of JNK. Here, we report that MLK3 associates with TRAF2, TRAF5 and TRAF6; however only TRAF2 can significantly induce the kinase activity of MLK3. The interaction domain of TRAF2 maps to the TRAF domain and for MLK3 to its C-terminal half (amino acids 511-847). Endogenous TRAF2 and MLK3 associate with each other in response to TNF-α treatment in a time-dependent manner. The association between MLK3 and TRAF2 mediates MLK3 activation and competition with the TRAF2 deletion mutant that binds to MLK3 attenuates MLK3 kinase activity in a dose-dependent manner, on TNF-α treatment. Furthermore the downstream target of MLK3, JNK was activated by TNF-α in a TRAF2-dependent manner. Hence, our data show that the direct interaction between TRAF2 and MLK3 is required for TNF-α-induced activation of MLK3 and its downstream target, JNK.展开更多
Nearly half of orthopaedic trauma patients are intoxicated at the time of injury, and excess alcohol consumption increases the risk for fracture nonunion. Previous studies show alcohol disrupts fracture associated Wnt...Nearly half of orthopaedic trauma patients are intoxicated at the time of injury, and excess alcohol consumption increases the risk for fracture nonunion. Previous studies show alcohol disrupts fracture associated Wnt signaling required for normal bone fracture repair. Intermittent parathyroid hormone(PTH) promotes bone growth through canonical Wnt signaling, however, no studies have investigated the effect of PTH on alcohol-inhibited bone fracture repair. Male C57 BL/6 mice received two-3 day alcohol binges separated by 4 days before receiving a mid-shaft tibia fracture. Postoperatively, mice received PTH daily until euthanasia. Wnt/β-catenin signaling was analyzed at 9 days post-fracture. As previously observed, acute alcohol exposure resulted in a >2-fold decrease in total and the active form of β-catenin and a 2-fold increase in inactive β-catenin within the fracture callus. Intermittent PTH abrogated the effect of alcohol on β-catenin within the fracture callus. Upstream of β-catenin, alcohol-treated animals had a 2-fold decrease in total LRP6, the Wnt co-receptor, which was restored with PTH treatment. Alcohol nor PTH had any significant effect on GSK-3β. These data show that intermittent PTH following a tibia fracture restores normal expression of Wnt signaling proteins within the fracture callus of alcohol-treated mice.展开更多
Background and Objective: Previous research has speculated on the role of pro- and inflammatory immune mediators in the etiologic process of fatigue, with contrasting findings. The preponderance of the evidence suppor...Background and Objective: Previous research has speculated on the role of pro- and inflammatory immune mediators in the etiologic process of fatigue, with contrasting findings. The preponderance of the evidence supports the role of inflammatory mediators in the disease process of Chronic Fatigue Syndrome (CFS). The purpose of this study was to evaluate the production of interleukin (IL)-8 by peripheral blood mononuclear cells derived from individuals with chronic fatigue. A secondary objective was to determine if there was a significant relationship between IL-8 production and plasma cortisol level. Materials and Methodology: Data was collected from three groups, a sample of individuals with CFS (n = 15), a comparison sample of individuals with fatigue that did not meet criteria for CFS (n = 30) and a group of putatively health normative controls (n = 23). Peripheral blood was drawn and plasma samples derived. Peripheral blood mononuclear cells were stimulated with a mitogenic protocol and levels of IL8 in unstimulated and stimulated bulk supernatant determined. Results: Both fatigue groups displayed significantly higher levels of IL8 than the control group. The CFS group demonstrated higher levels of IL8 in plasma than the fatigue comparison group. Conclusion: The findings demonstrate a clear association between fatigue and IL8. The ability to identify an inflammatory marker in association with fatigue could provide a means of identifying those who may be at risk for the development of this disorder.展开更多
Objective:To determine the work engagement levels of hospital nurses and the predictive roles that nurses’personal and organizational characteristics play.Methods:A cross-sectional design was employed in this study,w...Objective:To determine the work engagement levels of hospital nurses and the predictive roles that nurses’personal and organizational characteristics play.Methods:A cross-sectional design was employed in this study,which included 549 nurses working in the Central Philippines.Nurses were selected through purposive sampling,and a self-repor t questionnaire outlining personal and organizational characteristics was employed.The Utrecht Work Engagement Scale(UWES)was applied to gather data about nurse engagement.Results:The dedication score was the highest among the three dimensions of engagement while the vigor score was the lowest.Overall,Filipino nurses experienced an average level of work engagement.We observed significant relationships between a nurse’s age,years of experience in nursing,years in their present unit,and their position at work and their levels of engagement,vigor,sense of dedication,and absorption.Hospital capacity was a negative predictor of vigor,dedication,absorption,and overall work engagement.Fur ther,the type of nursing contract was a negative predictor of vigor and dedication.The type of hospital and the nurse’s position were positive predictors of vigor,dedication,and absorption.Conclusions:Filipino nurses were satisfactorily engaged at work.A number of nurses’personal and organizational characteristics play a predictive role in their work engagement.Thus,nursing administrators must suppor t,develop,and implement activities and measures that engage nurses at work.展开更多
<b>Background:</b> One common method of pain control for total shoulder arthroplasty is long-duration delivery of local anesthetic via interscalene brachial plexus block (ISB) with a continuous catheter. A...<b>Background:</b> One common method of pain control for total shoulder arthroplasty is long-duration delivery of local anesthetic via interscalene brachial plexus block (ISB) with a continuous catheter. Alternatively, liposomal bupivacaine has also been administered as an ISB as a means to prolong the analgesic effect. This study was completed to measure the non-inferiority of single-injection ISB with liposomal bupivacaine compared with ISB continuous catheter for total shoulder arthroplasty. <b>Methods:</b> We performed a retrospective chart review of patients who underwent total shoulder arthroplasty using either an ISB continuous catheter or a single injection ISB with liposomal bupivacaine for post operative analgesia. The primary goal of this study was to determine if single-injection with liposomal bupivacaine conferred non-inferior pain scores compared to the continuous catheter. Secondary outcomes evaluated oxygen saturation as a measure of hemidiaphragmatic paresis, post operative opioid requirements, and difference in cost. <b>Results:</b> We identified 333 patients for the study: 126 received continuous catheter and 207 received single-injection with liposomal bupivacaine. The median length of stay was 1 day. Pain scores for those treated with single-injection with liposomal bupivacaine were non-inferior to pain scores of those treated with the continuous catheter on post-op days 0, 1 and 2. Pain scores were lower for single-injection with liposomal bupivacaine patients on days 3 and 4, however they did not reach statistical significance. There was no significant difference in oxygen saturation between the two groups. Both groups had similar daily morphine milligram equivalent requirements. Liposomal bupivacaine ISB was also found to be less expensive. <b>Conclusion:</b> Single-injection ISB with liposomal bupivacaine provides non-inferior analgesia at a reduced cost compared with continuous catheter ISB for total shoulder arthroplasty.展开更多
Protein phosphorylation plays an important role in physiological processes, such as muscle contraction. Phospho-specific antibodies have become powerful tools to study these processes. Cardiac myosin binding protein-C...Protein phosphorylation plays an important role in physiological processes, such as muscle contraction. Phospho-specific antibodies have become powerful tools to study these processes. Cardiac myosin binding protein-C (cMyBP-C) is one of the proteins that make up the contractile apparatus of cardiomyocytes. Phosphorylation of cMyBP-C is essential for normal cardiac function, since dephosphorylation of this protein leads to its degradation and has been associated with cardiomyopathy. One of the upstream kinases, which phosphorylate cMyBP-C, is protein kinase D (PKD). While studying the role of PKD in cMyBP-C phosphorylation, we tried to analyze phosphorylation of PKD with a phospho-specific PKD-Ser744/748 antibody. Contrary to the expected 115 kDa, a signal was found for a 150-kDa protein. By MALDI-TOF mass spectrometry, we identified this protein to be cMyBP-C. These data were confirmed by immunostaining using the p-PKD-Ser744/748 antibody, which displayed a striated pattern similar to the one observed for a regular cMyBP-C antibody. To our knowledge there are no antibodies commercially available for phosphorylated cMyBP-C. Thus, the p-PKD-Ser744/748 antibody can accelerate research into the role of cMyBP-C phosphorylation in cardiomyocytes.展开更多
Hypertonicity causes severe clinical manifestations and is associated with mortality and severe short-term and long-term neurological sequelae. The main clinical syndromes of hypertonicity are hypernatremia and hyperg...Hypertonicity causes severe clinical manifestations and is associated with mortality and severe short-term and long-term neurological sequelae. The main clinical syndromes of hypertonicity are hypernatremia and hyperglycemia. Hypernatremia results from relative excess of body sodium over body water. Loss of water in excess of intake, gain of sodium salts in excess of losses or a combination of the two are the main mechanisms of hypernatremia. Hypernatremia can be hypervolemic, euvolemic or hypo-volemic. The management of hypernatremia addresses both a quantitative replacement of water and, if present, sodium defcit, and correction of the underlying pathophysiologic process that led to hypernatremia. Hypertonicity in hyperglycemia has two components, solute gain secondary to glucose accumulation in the extracellular compartment and water loss through hyperglycemic osmotic diuresis in excess of the losses of sodium and potassium. Differentiating between these two components of hypertonicity has major therapeutic implications because the frst component will be reversed simply by normalization of serum glucose concentration while the second component will require hypotonic fuid replacement. An estimate of the magnitude of the relative water deficit secondary to osmotic diuresis is obtainedby the corrected sodium concentration, which representsa calculated value of the serum sodium concentrationthat would result from reduction of the serum glucoseconcentration to a normal level.展开更多
Viral infection and chemical carcinogens trigger somatic changes resulting in activation of oncogenes during tumor initiation in the development of cancer. However, a critical interaction resides in the synergism betw...Viral infection and chemical carcinogens trigger somatic changes resulting in activation of oncogenes during tumor initiation in the development of cancer. However, a critical interaction resides in the synergism between these somatic changes and an inflamed tumor microenvironment where myeloid and hematopoietic cells are subverted to enhance tumor progression. The causative molecular mechanisms leading to the development of hepatocellular cancer remain incompletely understood but appear to result from multiple factors related to direct hepatocyte injury and the ensuing inflammatory changes mediated by the host response to tissue injury, DNA damage, repair of cellular damage, and chronic, repetitive injury. In this review, the molecular and cellular changes that regulate inflammation and tissue repair will be compared to the activated local tumor microenvironment. Cell-cell signaling within this microenvironment that enhances tumor progression and inhibits anti-tumor immunity will be展开更多
Most of the millions of Android users worldwide use applications from the official Android market (Google Play store) and unregulated alternative markets to get more functionality from their devices. Many of these app...Most of the millions of Android users worldwide use applications from the official Android market (Google Play store) and unregulated alternative markets to get more functionality from their devices. Many of these applications transmit sensitive data stored on the device, either maliciously or accidentally, to outside networks. In this paper, we will study the ways that Android applications transmit data to outside servers and propose a user-friendly application, DroidData, to inform and protect the user from these security risks. We will use tools such as TaintDroid, AppIntent, and Securacy to propose an application that reveals what types of data are being transmitted from apps, the location to which the data is being transmitted, whether the data is being transmitted through a secure channel (such as HTTPS) and whether the user is aware that the information is being transmitted. The application will generate a report that allows the user to block the application that leaks sensitive information. In doing so, we will examine the importance, relevance, and prevalence of these Android Data security issues.展开更多
Background: The need for axillary lymph node dissection (ALND) when sentinel lymph nodes (SLN) contain micrometastasis is controversial. The purpose of this study was to determine if the size of tumor in the SLN corre...Background: The need for axillary lymph node dissection (ALND) when sentinel lymph nodes (SLN) contain micrometastasis is controversial. The purpose of this study was to determine if the size of tumor in the SLN corresponds with additional positive non-sentinel lymph nodes (non-SLN) in pT1 breast cancer. Methods: This retrospective review of 483 patients with pT1 breast cancer identified 96 patients with tumor positive SLN biopsies between June 1999 and February 2010. The size of SLN metastasis and the number of tumor positive non-SLN were recorded using AJCC criteria. Receiver operating characteristic analysis was used to discriminate the SLN size with the optimal sensitivity, specificity and likelihood ratios (LR) for additional positive non-SLN. Results: Among 96 patients with a tumor positive SLN, 41% (n = 39) had micrometastasis, and 59% (n = 57) had macrometastasis. A positive non-SLN was identified after ALND among 18% (n = 7 of 39) with micrometastasis compared with 39% (n = 22 of 57) with macrometastasis (p = 0.04). The size of the SLN metastasis and presence of additional tumor positive non-SLNs corresponds to a positive likelihood ratio of 1.1 for micrometastasis and 1.6 for macrometastasis (95%CI: 0.56 - 0.74). Conclusions: Increased size of tumor in SLN is associated with greater likelihood of non-SLN positivity and should be considered for more aggressive follow-up and therapy.展开更多
The meaning of "local" in TV news is not as straightforward as one might imagine. "Local" newscasts in several U.S. markets are outsourced to an independent company located hundreds of miles from the communities s...The meaning of "local" in TV news is not as straightforward as one might imagine. "Local" newscasts in several U.S. markets are outsourced to an independent company located hundreds of miles from the communities served. What are the implications of such a delivery system for coverage of local issues and the Jeffersonian ideal of an informed citizenry? This study employs a content analysis of outsourced and local newscasts, using a data set of more than 1,000 stories from more than 30 hours of newscasts to determine if differences exist on story topics and source types. Does one type of station cover more public affairs stories than the other? Does one type use more official sources, or more perspective from private individuals? Even with the wide array of news sources currently available, local TV news still ranks as the most widely used information source. How well that source delivers information to local audiences is an important question to ask, particularly when the information may be coming from a great distance.展开更多
The goal of this study is to enhance the efficiency of bacterial extracellular electron transfer (EET) in Shewanella oneidensis MR-1 by enhancing adhesion to the electrode surface. Our results clearly show a major dif...The goal of this study is to enhance the efficiency of bacterial extracellular electron transfer (EET) in Shewanella oneidensis MR-1 by enhancing adhesion to the electrode surface. Our results clearly show a major difference in attachment and behavior of S. oneidensis MR-1 for Ca2+, Pb2+, Cd2+, and Mg2+ compared to the control. The final microbial coverage, as measured by confocal microscopy and cathodic peak charge in cyclic voltammetry (Qpc), increases with increasing metal ion concentrations. We found the cells attached to the electrode increased more with the addition of metal ion concentrations in the following order of metals: Ca2+ > Pb2+ > Cd2+ > Mg2+ compared to the control. The effect of metal ions on metabolism of the bacteria was tested by the riboflavin production and glucose consumption. Metabolic activity mirrored the same order of the activity as the electrochemical results.展开更多
According to the 22nd edition of "The American Illustrated Medical Dictionary",dialysis[dia=through,apart,across or between;lysis=to loose]is defined as the process of separating crystalloids and colloid... According to the 22nd edition of "The American Illustrated Medical Dictionary",dialysis[dia=through,apart,across or between;lysis=to loose]is defined as the process of separating crystalloids and colloids in solution by the differences in their rates of diffusion through a semipermeable membrane:crystalloids pass through readily,colloids very slowly or not at all(1).……展开更多
BACKGROUND Antagonists of cannabinoid type 1 receptor(CB1)have been shown to promote body weight loss and improve insulin sensitivity.Cannabinoids decrease adiponectin,and CB1 blocker increase adiponectin.However,the ...BACKGROUND Antagonists of cannabinoid type 1 receptor(CB1)have been shown to promote body weight loss and improve insulin sensitivity.Cannabinoids decrease adiponectin,and CB1 blocker increase adiponectin.However,the mediators of CB1 actions are not well defined.AIM To investigate whether the beneficial effects of CB1 inhibition are,at least in part,mediated by adiponectin.METHODS We compared metabolic and inflammatory phenotypes of wild-type(WT)mice,CB1-null(CB1^(-/-))and CB1/adiponectin double-knockout(DKO)mice.We assessed the insulin sensitivity using insulin tolerance test and glucose tolerance test,and inflammation using flow cytometry analysis of macrophages.RESULTS CB1^(-/-)mice exhibited significantly reduced body weight and fat mass when compared to WT mice.While no significance was found in total daily food intake and locomotor activity,CB1^(-/-)mice showed increased energy expenditure,enhanced thermogenesis in brown adipose tissue(BAT),and improved insulin sensitivity compared to WT mice.DKO showed no difference in body weight,adiposity,nor insulin sensitivity;only showed a modestly elevated thermogenesis in BAT compared to CB1^(-/-)mice.The metabolic phenotype of DKO is largely similar to CB1^(-/-)mice,suggesting that adiponectin is not a key mediator of the metabolic effects of CB1.Interestingly,CB1^(-/-)mice showed reduced pro-inflammatory macrophage polarization in both peritoneal macrophages and adipose tissue macrophages compared to WT mice;in contrast,DKO mice exhibited increased pro-inflammatory macrophage polarization in these macrophages compared to CB1^(-/-)mice,suggesting that adiponectin is an important mediator of the inflammatory effect of CB1.CONCLUSION Our findings reveal that CB1 functions through both adiponectin-dependent and adiponectin-independent mechanisms:CB1 regulates energy metabolism in an adiponectin-independent manner,and inflammation in an adiponectin-dependent manner.The differential effects of adiponectin on CB1-mediated metabolic and inflammatory functions should be taken into consideration in CB1 antagonist utilization.展开更多
文摘Objective:To identify possible stone-promoting microbes,we compared the profiles of microbes grown from stones of patients with and without metabolic syndrome(MetS).The association between MetS and urinary stone disease is well established,but the exact pathophysiologic relationship remains unknown.Recent evidence suggests urinary tract dysbiosis may lead to increased nephrolithiasis risk.Methods:At the time of percutaneous nephrolithotomy,bladder urine and stone fragments were collected from patients with and without MetS.Both sample types were subjected to expanded quantitative urine culture(EQUC)and 16 S ribosomal RNA gene sequencing.Results:Fifty-seven patients included 12 controls(21.1%)and 45 MetS patients(78.9%).Both cohorts were similar with respect to demographics and non-MetS comorbidities.No controls had uric acid stone composition.By EQUC,bacteria were detected more frequently in MetS stones(42.2%)compared to controls(8.3%)(p=0.041).Bacteria also were more abundant in stones of MetS patients compared to controls.To validate our EQUC results,we performed 16 S ribosomal RNA gene sequencing.In 12/16(75.0%)sequence-positive stones,EQUC reliably isolated at least one species of the sequenced genera.Bacteria were detected in both“infectious”and“non-infectious”stone compositions.Conclusion:Bacteria are more common and more abundant in MetS stones than control stones.Our findings support a role for bacteria in urinary stone disease for patients with MetS regardless of stone composition.
文摘Introduction Asthma is an inflammatory obstructive respiratory lung disease characterized by limited airflow.It is estimated that more than 300 million people worldwide are affected by asthma,and this number is expected to increase over the next few years[1].Uncontrolled asthma is associated with a severely impaired quality of life and increased mortality rates[2].Other adverse effects of poorly controlled asthma include obesity,pneumonia.
文摘BACKGROUND Esophageal foreign bodies are common around the world.Newer approaches,such as cap-assisted endoscopy,have been introduced as an alternative to conventional methods.Therefore,we performed a meta-analysis ono cap-assisted endoscopy versus conventional endoscopy for removal of esophageal foreign bodies.AIM To investigated the effectiveness of cap-assisted endoscopy with conventional endoscopy.METHODS An extensive literature search was performed(December 2021).For esophageal foreign body removal,cap-assisted endoscopy was compared to conventional endoscopy for procedure time,technical success of the procedure,time of foreign body retrieval,en bloc removal,and adverse event rate using odds ratio and mean difference.RESULTS Six studies met the inclusion criteria(n=1305).Higher odds of technical success(P=0.002)and en bloc removal(P<0.01)and lower odds of adverse events(P=0.02)and foreign body removal time(P<0.01)were observed with cap-assisted endoscopy as compared to conventional techniques.CONCLUSION For esophageal foreign bodies,the technique of cap-assisted endoscopy demonstrated increased en bloc removal and technical success with decreased time and adverse events as compared to conventional techniques.
基金supported in part by the National Institutes of Health Grant R15DC017866(to WMY)the Loyola University Chicago Research Support Award#994(to VCC)。
文摘Peripheral nerve injuries are common consequences of extremity trauma or chronic compression with a prevalence of 43.8 per1 million people(on average)reported in the U nited States annually,accompanied by a yearly increase in cost of care.
文摘Mixed lineage kinase 3 (MLK3) is a mitogen-activated protein kinase kinase kinase that is activated by tumor necrosis factor-α (TNF-α) and specifically activates c-Jun N-terminal kinase (JNK) on TNF-a stimulation. The mecha- nism by which TNF-α activates MLK3 is still not known. TNF receptor-associated factors (TRAFs) are adapter molecules that are recruited to cytoplasmic end of TNF receptor and mediate the downstream signaling, including activation of JNK. Here, we report that MLK3 associates with TRAF2, TRAF5 and TRAF6; however only TRAF2 can significantly induce the kinase activity of MLK3. The interaction domain of TRAF2 maps to the TRAF domain and for MLK3 to its C-terminal half (amino acids 511-847). Endogenous TRAF2 and MLK3 associate with each other in response to TNF-α treatment in a time-dependent manner. The association between MLK3 and TRAF2 mediates MLK3 activation and competition with the TRAF2 deletion mutant that binds to MLK3 attenuates MLK3 kinase activity in a dose-dependent manner, on TNF-α treatment. Furthermore the downstream target of MLK3, JNK was activated by TNF-α in a TRAF2-dependent manner. Hence, our data show that the direct interaction between TRAF2 and MLK3 is required for TNF-α-induced activation of MLK3 and its downstream target, JNK.
基金AO North AmericaNational Institute on Alcohol Abuse and Alcoholism,Grant/Award Number R21AA025551 and T32AA013527。
文摘Nearly half of orthopaedic trauma patients are intoxicated at the time of injury, and excess alcohol consumption increases the risk for fracture nonunion. Previous studies show alcohol disrupts fracture associated Wnt signaling required for normal bone fracture repair. Intermittent parathyroid hormone(PTH) promotes bone growth through canonical Wnt signaling, however, no studies have investigated the effect of PTH on alcohol-inhibited bone fracture repair. Male C57 BL/6 mice received two-3 day alcohol binges separated by 4 days before receiving a mid-shaft tibia fracture. Postoperatively, mice received PTH daily until euthanasia. Wnt/β-catenin signaling was analyzed at 9 days post-fracture. As previously observed, acute alcohol exposure resulted in a >2-fold decrease in total and the active form of β-catenin and a 2-fold increase in inactive β-catenin within the fracture callus. Intermittent PTH abrogated the effect of alcohol on β-catenin within the fracture callus. Upstream of β-catenin, alcohol-treated animals had a 2-fold decrease in total LRP6, the Wnt co-receptor, which was restored with PTH treatment. Alcohol nor PTH had any significant effect on GSK-3β. These data show that intermittent PTH following a tibia fracture restores normal expression of Wnt signaling proteins within the fracture callus of alcohol-treated mice.
文摘Background and Objective: Previous research has speculated on the role of pro- and inflammatory immune mediators in the etiologic process of fatigue, with contrasting findings. The preponderance of the evidence supports the role of inflammatory mediators in the disease process of Chronic Fatigue Syndrome (CFS). The purpose of this study was to evaluate the production of interleukin (IL)-8 by peripheral blood mononuclear cells derived from individuals with chronic fatigue. A secondary objective was to determine if there was a significant relationship between IL-8 production and plasma cortisol level. Materials and Methodology: Data was collected from three groups, a sample of individuals with CFS (n = 15), a comparison sample of individuals with fatigue that did not meet criteria for CFS (n = 30) and a group of putatively health normative controls (n = 23). Peripheral blood was drawn and plasma samples derived. Peripheral blood mononuclear cells were stimulated with a mitogenic protocol and levels of IL8 in unstimulated and stimulated bulk supernatant determined. Results: Both fatigue groups displayed significantly higher levels of IL8 than the control group. The CFS group demonstrated higher levels of IL8 in plasma than the fatigue comparison group. Conclusion: The findings demonstrate a clear association between fatigue and IL8. The ability to identify an inflammatory marker in association with fatigue could provide a means of identifying those who may be at risk for the development of this disorder.
文摘Objective:To determine the work engagement levels of hospital nurses and the predictive roles that nurses’personal and organizational characteristics play.Methods:A cross-sectional design was employed in this study,which included 549 nurses working in the Central Philippines.Nurses were selected through purposive sampling,and a self-repor t questionnaire outlining personal and organizational characteristics was employed.The Utrecht Work Engagement Scale(UWES)was applied to gather data about nurse engagement.Results:The dedication score was the highest among the three dimensions of engagement while the vigor score was the lowest.Overall,Filipino nurses experienced an average level of work engagement.We observed significant relationships between a nurse’s age,years of experience in nursing,years in their present unit,and their position at work and their levels of engagement,vigor,sense of dedication,and absorption.Hospital capacity was a negative predictor of vigor,dedication,absorption,and overall work engagement.Fur ther,the type of nursing contract was a negative predictor of vigor and dedication.The type of hospital and the nurse’s position were positive predictors of vigor,dedication,and absorption.Conclusions:Filipino nurses were satisfactorily engaged at work.A number of nurses’personal and organizational characteristics play a predictive role in their work engagement.Thus,nursing administrators must suppor t,develop,and implement activities and measures that engage nurses at work.
文摘<b>Background:</b> One common method of pain control for total shoulder arthroplasty is long-duration delivery of local anesthetic via interscalene brachial plexus block (ISB) with a continuous catheter. Alternatively, liposomal bupivacaine has also been administered as an ISB as a means to prolong the analgesic effect. This study was completed to measure the non-inferiority of single-injection ISB with liposomal bupivacaine compared with ISB continuous catheter for total shoulder arthroplasty. <b>Methods:</b> We performed a retrospective chart review of patients who underwent total shoulder arthroplasty using either an ISB continuous catheter or a single injection ISB with liposomal bupivacaine for post operative analgesia. The primary goal of this study was to determine if single-injection with liposomal bupivacaine conferred non-inferior pain scores compared to the continuous catheter. Secondary outcomes evaluated oxygen saturation as a measure of hemidiaphragmatic paresis, post operative opioid requirements, and difference in cost. <b>Results:</b> We identified 333 patients for the study: 126 received continuous catheter and 207 received single-injection with liposomal bupivacaine. The median length of stay was 1 day. Pain scores for those treated with single-injection with liposomal bupivacaine were non-inferior to pain scores of those treated with the continuous catheter on post-op days 0, 1 and 2. Pain scores were lower for single-injection with liposomal bupivacaine patients on days 3 and 4, however they did not reach statistical significance. There was no significant difference in oxygen saturation between the two groups. Both groups had similar daily morphine milligram equivalent requirements. Liposomal bupivacaine ISB was also found to be less expensive. <b>Conclusion:</b> Single-injection ISB with liposomal bupivacaine provides non-inferior analgesia at a reduced cost compared with continuous catheter ISB for total shoulder arthroplasty.
文摘Protein phosphorylation plays an important role in physiological processes, such as muscle contraction. Phospho-specific antibodies have become powerful tools to study these processes. Cardiac myosin binding protein-C (cMyBP-C) is one of the proteins that make up the contractile apparatus of cardiomyocytes. Phosphorylation of cMyBP-C is essential for normal cardiac function, since dephosphorylation of this protein leads to its degradation and has been associated with cardiomyopathy. One of the upstream kinases, which phosphorylate cMyBP-C, is protein kinase D (PKD). While studying the role of PKD in cMyBP-C phosphorylation, we tried to analyze phosphorylation of PKD with a phospho-specific PKD-Ser744/748 antibody. Contrary to the expected 115 kDa, a signal was found for a 150-kDa protein. By MALDI-TOF mass spectrometry, we identified this protein to be cMyBP-C. These data were confirmed by immunostaining using the p-PKD-Ser744/748 antibody, which displayed a striated pattern similar to the one observed for a regular cMyBP-C antibody. To our knowledge there are no antibodies commercially available for phosphorylated cMyBP-C. Thus, the p-PKD-Ser744/748 antibody can accelerate research into the role of cMyBP-C phosphorylation in cardiomyocytes.
文摘Hypertonicity causes severe clinical manifestations and is associated with mortality and severe short-term and long-term neurological sequelae. The main clinical syndromes of hypertonicity are hypernatremia and hyperglycemia. Hypernatremia results from relative excess of body sodium over body water. Loss of water in excess of intake, gain of sodium salts in excess of losses or a combination of the two are the main mechanisms of hypernatremia. Hypernatremia can be hypervolemic, euvolemic or hypo-volemic. The management of hypernatremia addresses both a quantitative replacement of water and, if present, sodium defcit, and correction of the underlying pathophysiologic process that led to hypernatremia. Hypertonicity in hyperglycemia has two components, solute gain secondary to glucose accumulation in the extracellular compartment and water loss through hyperglycemic osmotic diuresis in excess of the losses of sodium and potassium. Differentiating between these two components of hypertonicity has major therapeutic implications because the frst component will be reversed simply by normalization of serum glucose concentration while the second component will require hypotonic fuid replacement. An estimate of the magnitude of the relative water deficit secondary to osmotic diuresis is obtainedby the corrected sodium concentration, which representsa calculated value of the serum sodium concentrationthat would result from reduction of the serum glucoseconcentration to a normal level.
文摘Viral infection and chemical carcinogens trigger somatic changes resulting in activation of oncogenes during tumor initiation in the development of cancer. However, a critical interaction resides in the synergism between these somatic changes and an inflamed tumor microenvironment where myeloid and hematopoietic cells are subverted to enhance tumor progression. The causative molecular mechanisms leading to the development of hepatocellular cancer remain incompletely understood but appear to result from multiple factors related to direct hepatocyte injury and the ensuing inflammatory changes mediated by the host response to tissue injury, DNA damage, repair of cellular damage, and chronic, repetitive injury. In this review, the molecular and cellular changes that regulate inflammation and tissue repair will be compared to the activated local tumor microenvironment. Cell-cell signaling within this microenvironment that enhances tumor progression and inhibits anti-tumor immunity will be
文摘Most of the millions of Android users worldwide use applications from the official Android market (Google Play store) and unregulated alternative markets to get more functionality from their devices. Many of these applications transmit sensitive data stored on the device, either maliciously or accidentally, to outside networks. In this paper, we will study the ways that Android applications transmit data to outside servers and propose a user-friendly application, DroidData, to inform and protect the user from these security risks. We will use tools such as TaintDroid, AppIntent, and Securacy to propose an application that reveals what types of data are being transmitted from apps, the location to which the data is being transmitted, whether the data is being transmitted through a secure channel (such as HTTPS) and whether the user is aware that the information is being transmitted. The application will generate a report that allows the user to block the application that leaks sensitive information. In doing so, we will examine the importance, relevance, and prevalence of these Android Data security issues.
文摘Background: The need for axillary lymph node dissection (ALND) when sentinel lymph nodes (SLN) contain micrometastasis is controversial. The purpose of this study was to determine if the size of tumor in the SLN corresponds with additional positive non-sentinel lymph nodes (non-SLN) in pT1 breast cancer. Methods: This retrospective review of 483 patients with pT1 breast cancer identified 96 patients with tumor positive SLN biopsies between June 1999 and February 2010. The size of SLN metastasis and the number of tumor positive non-SLN were recorded using AJCC criteria. Receiver operating characteristic analysis was used to discriminate the SLN size with the optimal sensitivity, specificity and likelihood ratios (LR) for additional positive non-SLN. Results: Among 96 patients with a tumor positive SLN, 41% (n = 39) had micrometastasis, and 59% (n = 57) had macrometastasis. A positive non-SLN was identified after ALND among 18% (n = 7 of 39) with micrometastasis compared with 39% (n = 22 of 57) with macrometastasis (p = 0.04). The size of the SLN metastasis and presence of additional tumor positive non-SLNs corresponds to a positive likelihood ratio of 1.1 for micrometastasis and 1.6 for macrometastasis (95%CI: 0.56 - 0.74). Conclusions: Increased size of tumor in SLN is associated with greater likelihood of non-SLN positivity and should be considered for more aggressive follow-up and therapy.
文摘The meaning of "local" in TV news is not as straightforward as one might imagine. "Local" newscasts in several U.S. markets are outsourced to an independent company located hundreds of miles from the communities served. What are the implications of such a delivery system for coverage of local issues and the Jeffersonian ideal of an informed citizenry? This study employs a content analysis of outsourced and local newscasts, using a data set of more than 1,000 stories from more than 30 hours of newscasts to determine if differences exist on story topics and source types. Does one type of station cover more public affairs stories than the other? Does one type use more official sources, or more perspective from private individuals? Even with the wide array of news sources currently available, local TV news still ranks as the most widely used information source. How well that source delivers information to local audiences is an important question to ask, particularly when the information may be coming from a great distance.
文摘The goal of this study is to enhance the efficiency of bacterial extracellular electron transfer (EET) in Shewanella oneidensis MR-1 by enhancing adhesion to the electrode surface. Our results clearly show a major difference in attachment and behavior of S. oneidensis MR-1 for Ca2+, Pb2+, Cd2+, and Mg2+ compared to the control. The final microbial coverage, as measured by confocal microscopy and cathodic peak charge in cyclic voltammetry (Qpc), increases with increasing metal ion concentrations. We found the cells attached to the electrode increased more with the addition of metal ion concentrations in the following order of metals: Ca2+ > Pb2+ > Cd2+ > Mg2+ compared to the control. The effect of metal ions on metabolism of the bacteria was tested by the riboflavin production and glucose consumption. Metabolic activity mirrored the same order of the activity as the electrochemical results.
文摘 According to the 22nd edition of "The American Illustrated Medical Dictionary",dialysis[dia=through,apart,across or between;lysis=to loose]is defined as the process of separating crystalloids and colloids in solution by the differences in their rates of diffusion through a semipermeable membrane:crystalloids pass through readily,colloids very slowly or not at all(1).……
基金Supported by the NIH,No.DK118334 and No.AG064869and the BrightFocus,No.A2019630S(to Sun Y).
文摘BACKGROUND Antagonists of cannabinoid type 1 receptor(CB1)have been shown to promote body weight loss and improve insulin sensitivity.Cannabinoids decrease adiponectin,and CB1 blocker increase adiponectin.However,the mediators of CB1 actions are not well defined.AIM To investigate whether the beneficial effects of CB1 inhibition are,at least in part,mediated by adiponectin.METHODS We compared metabolic and inflammatory phenotypes of wild-type(WT)mice,CB1-null(CB1^(-/-))and CB1/adiponectin double-knockout(DKO)mice.We assessed the insulin sensitivity using insulin tolerance test and glucose tolerance test,and inflammation using flow cytometry analysis of macrophages.RESULTS CB1^(-/-)mice exhibited significantly reduced body weight and fat mass when compared to WT mice.While no significance was found in total daily food intake and locomotor activity,CB1^(-/-)mice showed increased energy expenditure,enhanced thermogenesis in brown adipose tissue(BAT),and improved insulin sensitivity compared to WT mice.DKO showed no difference in body weight,adiposity,nor insulin sensitivity;only showed a modestly elevated thermogenesis in BAT compared to CB1^(-/-)mice.The metabolic phenotype of DKO is largely similar to CB1^(-/-)mice,suggesting that adiponectin is not a key mediator of the metabolic effects of CB1.Interestingly,CB1^(-/-)mice showed reduced pro-inflammatory macrophage polarization in both peritoneal macrophages and adipose tissue macrophages compared to WT mice;in contrast,DKO mice exhibited increased pro-inflammatory macrophage polarization in these macrophages compared to CB1^(-/-)mice,suggesting that adiponectin is an important mediator of the inflammatory effect of CB1.CONCLUSION Our findings reveal that CB1 functions through both adiponectin-dependent and adiponectin-independent mechanisms:CB1 regulates energy metabolism in an adiponectin-independent manner,and inflammation in an adiponectin-dependent manner.The differential effects of adiponectin on CB1-mediated metabolic and inflammatory functions should be taken into consideration in CB1 antagonist utilization.