Age-related changes in the structure and replication of mitochondrial DNA (mtDNA) were investigated in different organs from young adult (9–10 months' old) and senescent (28–29 months' old) BALB/c mice and Fischer 344 rats. Total mtDNA from brain, heart, kidney and liver was isolated by centrifugation in ethidium bromide—CsCl gradient and examined for the occurrence of complex forms and replicative intermediates by electron microscopy. The frequency of catenated mtDNA (interlinked molecules containing two or more circular units) varied from about 2.5% to 5% in adult tissues and showed a small increase in the majority of senescent organs. The frequency of double-sized circular molecules, or circular dimers, was very low in adult tissues, with an average of about 0.04% in mice and 0.1% in rats. The frequency of circular dimers increased with aging to 1.9% in mouse brain and 1.5% in rat kidney, with smaller increases (0.4% and 0.7%) in heart mtDNA from both species; there was no significant increase in the other organs. It is suggested that the increase in the frequency of circular dimer mtDNA reflects an overall deterioration of tissue physiology rather than intrinsic senescent changes in the mitochondria. The frequencies and types of the various replicative forms of mtDNA varied significantly according to tissue but not according to species or donor age. The only exception was a significant increase in the frequency of larger replicative forms in senescent mouse liver, to about 20% compared with 12% in adult liver, suggesting an age-related change in the rate of mtDNA replication and/or turnover in this organ. 相似文献
We describe the first documented field transmission of West Nile (WN) virus by a North American mosquito. WN was first detected in northern Florida in 2001. An intensive mosquito trapping and surveillance program was conducted in this region for four nights to assess mosquito transmission of WN. Four mosquito traps, each with a single sentinel chicken, were placed at five different locations on each of four nights. A total of 11,948 mosquitoes was collected, and 14 mosquito pools were found to contain WN, giving a minimum infection rate between 1.08 and 7.54 per 1,000. Only one of the 80 sentinel chickens seroconverted to WN, demonstrating a single mosquito transmission event during the study and a mosquito transmission rate of between 0.8 and 1 per 1,000. Culex nigripalpus Theobald was responsible for WN transmission to the sentinel chicken, although both Cx. nigripalpus and Culex quinquefasciatus Say were found infected with WN. Mosquito transmission rates are reported in this study for the first time for a WN outbreak. This information is essential to determine risk of human and animal infection. 相似文献
PurposeCMS has proposed removing postoperative care from the global periods for surgical procedures and instead requiring surgeons to bill for postoperative visits using evaluation & management (E&M) codes. This policy may alter reimbursement to pediatric surgeons.MethodsTo assess the impact of this policy, NSQIP-pediatric data were used to calculate median LOS for high-volume procedures with 10 or 90 day global periods. We then merged these data with CMS physician work time and RVU files. A CMS LOS variable was created by counting the number of hospital-based E&M codes built into the global period based on the fact that if global periods are removed, surgeons may only bill one E&M code per postoperative day. We then compared the CMS and NSQIP LOS values.ResultsThe dataset included 201 CPT codes with NSQIP LOS estimates derived from a median of 137 operations. Twenty-nine procedures (14.4%) had higher, 24 (16.9%) had the same, and 138 (68.7%) had lower NSQIP median LOS than current CMS values. On average, NSQIP values were 40.0% (95% confidence interval [95CI] ? 50.0, ? 29.9%) lower than CMS values. Based on a daily average work RVU per postoperative E&M code of 1.09 (95% CI 1.05, 1.12), and $35.78 per RVU (2017 rate), surgeons in this sample would experience a cumulative annual reduction in reimbursement of approximately $3.4 M following the policy change.ConclusionsMost pediatric surgical procedures have RVU valuations that include more hospital-based E&M codes than the current median number of postoperative days. Holding all else equal, the removal of global periods would therefore reduce reimbursement for pediatric surgeons. The downstream effects of this policy change, such as the impact on the quality of clinical care, are uncertain and warrant further investigation.Type of studyClinical research paper.Level of evidenceLevel II. 相似文献
Sexual fantasies represent a vast and highly personal dimension of human sexuality that remains understudied empirically. This article used a person-oriented approach to examine the reactions of arousal and discomfort that individuals experienced in response to four proposed fantasy scenarios depicting themes of romance, power dynamics (i.e., submission and domination), pain (i.e., sadism and masochism), and sexual violence. Using an online sample of 566 adult participants (250 men and 291 women) from the general population of Canada and the U.S., four classes were identified based on reactions of arousal and discomfort toward the proposed scenarios: Indifferent (relatively low arousal and discomfort to all scenarios, 37%), Romantic (high arousal solely for the romance scenario, high discomfort toward other scenarios, 22%), Enthusiastic (high arousal and low discomfort in response to all scenarios, 26%), and Dissonant (relatively high arousal and discomfort toward all scenarios, 15%). These classes were then compared to examine differences in terms of the following psychosexual characteristics: gender, experiences of childhood sexual abuse, sexual compulsion, and romantic attachment. Findings illustrated distinct patterns of reactions toward fantasies and confirmed the presence of links between reactions toward sexual fantasies, psychosexual characteristics, and traumatic life experiences. This suggests that the relationship between individuals and their sexual fantasies may be indicative of their overall relationship with sexuality.
Ascites are commonly found in ovarian cancer patients with advanced disease and are rich in cellular components and growth-promoting factors. The purpose of this study was to assess the effect of malignant ascites on TRAIL-induced apoptosis. We demonstrate that malignant ascites obtained from women with advanced ovarian cancer protect tumor cells from TRAIL- and FasL-induced apoptosis but not against cisplatin-induced apoptosis. This antiapoptotic effect was consistently found among different malignant ascites while nonmalignant peritoneal fluids or conditioned medium from TRAIL-resistant cells failed to protect tumor cells against TRAIL killing. Malignant ascites strongly inhibits TRAIL-induced caspase-3 activation and PARP cleavage. Furthermore, ascites activate PI3K and its downstream target Akt and increases c-FLIP(S) protein levels without affecting ERK phosphorylation status. The antiapoptotic effect of malignant ascites is abrogated by the inhibition of PI3K with LY294002, by a specific inhibitor of Akt and by Akt siRNA. We further show that the pro-survival effect of ascites can be suppressed by down-regulation of c-FLIP(S). Our data indicate that malignant effusions protect against TRAIL-induced apoptosis by activating the PI3K/Akt pathway. These findings demonstrate that the tumor microenvironment may contribute to the resistance of ovarian cancer cells to death receptor-induced apoptosis. 相似文献
In 1963, Goffman argued that forming a group based on shared stigma may provide benefits. However, there is no empirical research on whether perception that a separate, unique, coherent group exists (i.e., group entitativity) influences coping, such as educating others or secrecy, for the stigmatized individual or his or her spouse. Further, little is known about how spouses influence each other in terms of promoting the education of others about a stigmatizing condition, especially when it comes to the role of believing that stigma-based groups, to which they may both belong, exist. This study provides a step toward bridging this gap in the research by applying the label management model in efforts to understand coping for couples in which one spouse is diagnosed with genetic mutations leading to alpha-1 antitrypsin deficiency (AATD). This study included 50 married couples in which one spouse is diagnosed with genetic mutations leading to alpha-1 antitrypsin deficiency (AATD). We found that group entitativity related to those with AATD counterbalanced the influence of genetic stigma on spouses’ intentions to keep the diagnosis secret or to educate others about it. Intrapersonal and interpersonal influences appeared among spouses. Attention is needed on the power of creating groups for stigmatized persons and their relatives. Indeed, people live within a dynamic world of group entities, and multiple social identities including spousal and familial. While attention has been paid to the diffusion of stigmas to loved ones, less has been paid to the uplift of group entities for them. 相似文献