Inhibition of DNA damage response at telomeres improves the detrimental phenotypes of Hutchinson–Gilford Progeria Syndrome

Hutchinson–Gilford progeria syndrome (HGPS) is a genetic disorder characterized by premature aging features. Cells from HGPS patients express progerin, a truncated form of Lamin A, which perturbs cellular homeostasis leading to nuclear shape alterations, genome instability, heterochromatin loss, telomere dysfunction and premature entry into cellular senescence. Recently, we reported that telomere dysfunction induces the transcription of telomeric non-coding RNAs (tncRNAs) which control the DNA damage response (DDR) at dysfunctional telomeres. Here we show that progerin-induced telomere dysfunction induces the transcription of tncRNAs. Their functional inhibition by sequence-specific telomeric antisense oligonucleotides (tASOs) prevents full DDR activation and premature cellular senescence in various HGPS cell systems, including HGPS patient fibroblasts. We also show in vivo that tASO treatment significantly enhances skin homeostasis and lifespan in a transgenic HGPS mouse model. In summary, our results demonstrate an important role for telomeric DDR activation in HGPS progeroid detrimental phenotypes in vitro and in vivo

A Different Weight Loss Experience: A Qualitative Study Exploring the Behavioral, Physical, and Psychosocial Changes Associated with Yoga That Promote Weight Loss

Yoga interventions improve obesity-related outcomes including body mass index (BMI), body weight, body fat, and waist circumference, yet it is unclear whether these improvements are due to increased physical activity, increased lean muscle mass, and/or changes in eating behaviors. The purpose of this study is to expand our understanding of the experience of losing weight through yoga. Methods. Semistructured interviews were qualitatively analyzed using a descriptive phenomenological approach. Results. Two distinct groups who had lost weight through yoga responded: those who were overweight and had repeatedly struggled in their attempts to lose weight (55%, n=11) and those who were of normal weight and had lost weight unintentionally (45%, n=9). Five themes emerged that differed slightly by group: shift toward healthy eating, impact of the yoga community/yoga culture, physical changes, psychological changes, and the belief that the yoga weight loss experience was different than past weight loss experiences. Conclusions. These findings imply that yoga could offer diverse behavioral, physical, and psychosocial effects that may make it a useful tool for weight loss. Role modeling and social support provided by the yoga community may contribute to weight loss, particularly for individuals struggling to lose weight

Patients’ quest for recognition and continuity in health care: time for a new research agenda?

User involvement is important in democratization of health care and is assumed to contribute to better and more relevant research. Despite increased requirements for user involvement in research, more studies are still needed. This study aimed at exploring what research agenda people with varied health problems consider as important, based on their own experience. The study had a phenomenological approach with a qualitative design. The sample consisted of 23 informants; nine had been critically ill and 14 were suffering from chronic muscle pain. Data were collected in five focus group interviews and one individual interview. A phenomenological approach was used in analyzing the data. Written consent was obtained from all the participants, and ethical considerations were taken throughout the entire research process. Despite various experiences among the participants, a quest to be taken seriously over time by healthcare professionals emerged as a strong meaning structure in both groups. Based on these experiences, continuity across lifetime changes turned out to be an important research topic for future research. User involvement should be appreciated in all parts of the research process. A crucial prerequisite is that the users get the opportunity to bring their own experiences into the process.acceptedVersio

Conversion of the Mycotoxin Patulin to the Less Toxic Desoxypatulinic Acid by the Biocontrol Yeast Rhodosporidium kratochvilovae Strain LS11

Se describe en este artículo el descubrimiento de la degradación de la micotoxina patulina por una levaduraThe infection of stored apples by the fungus Penicillium expansum causes the contamination of fruits and fruit-derived products with the mycotoxin patulin, which is a major issue in food safety. Fungal attack can be prevented by beneficial microorganisms, so-called biocontrol agents. Previous time-course thin layer chromatography analyses showed that the aerobic incubation of patulin with the biocontrol yeast Rhodosporidium kratochvilovae strain LS11 leads to the disappearance of the mycotoxin spot and the parallel emergence of two new spots, one of which disappears over time. In this work, we analyzed the biodegradation of patulin effected by LS11 through HPLC. The more stable of the two compounds was purified and characterized by nuclear magnetic resonance as desoxypatulinic acid, whose formation was also quantitated in patulin degradation experiments. After R. kratochvilovae LS11 had been incubated in the presence of 13C-labeled patulin, label was traced to desoxypatulinic acid, thus proving that this compound derives from the metabolization of patulin by the yeast. Desoxypatulinic acid was much less toxic than patulin to human lymphocytes and, in contrast to patulin, did not react in vitro with the thiol-bearing tripeptide glutathione. The lower toxicity of desoxypatulinic acid is proposed to be a consequence of the hydrolysis of the lactone ring and the loss of functional groups that react with thiol groups. The formation of desoxypatulinic acid from patulin represents a novel biodegradation pathway that is also a detoxification process

The Eyes Have It: Sex and Sexual Orientation Differences in Pupil Dilation Patterns

Recent research suggests profound sex and sexual orientation differences in sexual response. These results, however, are based on measures of genital arousal, which have potential limitations such as volunteer bias and differential measures for the sexes. The present study introduces a measure less affected by these limitations. We assessed the pupil dilation of 325 men and women of various sexual orientations to male and female erotic stimuli. Results supported hypotheses. In general, self-reported sexual orientation corresponded with pupil dilation to men and women. Among men, substantial dilation to both sexes was most common in bisexual-identified men. In contrast, among women, substantial dilation to both sexes was most common in heterosexual-identified women. Possible reasons for these differences are discussed. Because the measure of pupil dilation is less invasive than previous measures of sexual response, it allows for studying diverse age and cultural populations, usually not included in sexuality research

Effect of heat stress on LPS-induced febrile response in D-galactosamine-sensitized rats

. In the present study we have tested whether inhibition of protein synthesis in the liver can reduce the effect of this heat conditioning on the LPS-induced febrile response in the rat. D-galactosamine (D-gal) was used to selectively inhibit liver protein synthesis. D-gal (500 mg/kg) or PBS as control was administered intraperitoneally 1 h before heat stress. LPS (50 g/kg ip) was injected 24 h post-heat exposure. Treatment with D-gal blunted the febrile response to LPS. Moreover, heat-conditioned rats treated first with D-gal and subsequently with LPS demonstrated a profound fall in core temperature 10-18 h post-LPS. A significant increase of serum TNF-␣ accompanied this effect of D-gal on fever. Heat-conditioned animals receiving D-gal showed an inhibition in inducible HSP-70 in the liver. These data support the role of hepatic function in modulating the febrile response to LPS. heat shock proteins; liver; heart; kidney; tumor necrosis factor-␣, interleukin-6, temperature regulation; fever; lipopolysaccharide HEAT STRESS PROVOKES metabolic adaptations in the whole organism. One such response is the production of heat shock proteins (HSPs) (26). The accumulation of HSPs within cells helps both cells and the whole organism survive subsequent, otherwise lethal, thermal stress. Interestingly, heat conditioning sufficient to cause cellular HSP accumulation has also been shown to be protective in a subsequent, otherwise lethal, endotoxin challenge (30). Several studies have demonstrated that HSPs regulate cytokine production in peripheral blood monocytes. Intracellular HSP accumulation is associated with a decrease in synthesis of tumor necrosis factor-␣ (TNF-␣) and interleukin (IL)-1␤ (6, 32). Impaired HSP production causes enhanced TNF-induced cytotoxicity in cells Whereas heat conditioning is protective, pretreatment with D-galactosamine (D-gal) increases sensitivity to subsequent LPS (2, 10). D-gal inhibits protein synthesis primarily in the live

An Evaluation of 10 Percent and 20 Percent Benzocaine Gels in Patients With Acute Toothaches: Efficacy, Tolerability and Compliance With Label Dose Administration Directions

Background The authors evaluated the efficacy and tolerability of 10 percent and 20 percent benzocaine gels compared with those of a vehicle (placebo) gel for the temporary relief of toothache pain. They also assessed the compliance with the label dose administration directions on the part of participants with toothache pain. Methods Under double-masked conditions, 576 participants self-applied study gel to an open tooth cavity and surrounding oral tissues. Participants evaluated their pain intensity and pain relief for 120 minutes. The authors determined the amount of gel the participants applied. Results The responders’ rates (the primary efficacy parameter), defined as the percentage of participants who had an improvement in pain intensity as exhibited by a pain score reduction of at least one unit on the dental pain scale from baseline for two consecutive assessments any time between the five- and 20-minute points, were 87.3 percent, 80.7 percent and 70.4 percent, respectively, for 20 percent benzocaine gel, 10 percent benzocaine gel and vehicle gel. Both benzocaine gels were significantly (P ≤ .05) better than vehicle gel; the 20 percent benzocaine gel also was significantly (P ≤ .05) better than the 10 percent benzocaine gel. The mean amount of gel applied was 235.6 milligrams, with 88.2 percent of participants applying 400 mg or less. Conclusions Both 10 percent and 20 percent benzocaine gels were more efficacious than the vehicle gel, and the 20 percent benzocaine gel was more efficacious than the 10 percent benzocaine gel. All treatments were well tolerated by participants. Practical Implications Patients can use 10 percent and 20 percent benzocaine gels to temporarily treat toothache pain safely

Building Innovative Online Korean and Japanese Courses: A Pilot on Technology- Enhanced Curriculum Development

Our pilot project created blended/online courses to accommodate the growing needs of precollegiate and collegiate students interested in learning Korean and Japanese. In the initial phase, we conducted a survey of students’ experiences with and perceptions about blended/online Asian language learning. We found a general lack of familiarity with, and moderate resistance toward, online language learning modes. With learner attitudes in mind, we developed online modules for beginning Korean and Japanese courses. In this article, we report the survey results and the process of developing these innovative blended and online modalities of content delivery, focusing on the strengths of the modules and the unforeseen development challenges. The impacts that these technology-enhanced environments may have on student perceptions of transactional distance and tele-/copresence are explored. We suggest that transforming conventional East Asian language courses into blended/online modes is not only feasible but also beneficial for foreign language teaching and learning