KLF6 activates Sp1-mediated prolidase transcription during TGF-ß1 signaling.

Prolidase (PEPD) is the only hydrolase that cleaves the dipeptides containing C-terminal proline or hydroxyproline-the rate-limiting step in collagen biosynthesis. However, the molecular regulation of prolidase expression remains largely unknown. In this study, we have identified overlapping binding sites for the transcription factors Krüppel-like factor 6 (KLF6) and Specificity protein 1 (Sp1) in the PEPD promoter and demonstrate that KLF6/Sp1 transcriptionally regulate prolidase expression. By cloning the PEPD promoter into a luciferase reporter and through site-directed deletion, we pinpointed the minimal sequences required for KLF6 and Sp1-mediated PEPD promoter-driven transcription. Interestingly, Sp1 inhibition abrogated KLF6-mediated PEPD promoter activity, suggesting that Sp1 is required for the basal expression of prolidase. We further studied the regulation of PEPD by KLF6 and Sp1 during transforming growth factor ß1 (TGF-ß1) signaling, since both KLF6 and Sp1 are key players in TGF-ß1 mediated collagen biosynthesis. Mouse and human fibroblasts exposed to TGF-ß1 resulted in the induction of PEPD transcription and prolidase expression. Inhibition of TGF-ß1 signaling abrogated PEPD promoter-driven transcriptional activity of KLF6 and Sp1. Knock-down of KLF6 as well as Sp1 inhibition also reduced prolidase expression. Chromatin immunoprecipitation assay supported direct binding of KLF6 and Sp1 to the PEPD promoter and this binding was enriched by TGF-ß1 treatment. Finally, immunofluorescence studies showed that KLF6 co-operates with Sp1 in the nucleus to activate prolidase expression and enhance collagen biosynthesis. Collectively, our results identify functional elements of the PEPD promoter for KLF6 and Sp1-mediated transcriptional activation and describe the molecular mechanism of prolidase expression.

Spontaneous Ogilvie's Syndrome in a Nonagenarian Male: A Study of a Rare Case With Literature Review.

Ogilvie's syndrome, or acute colonic pseudo-obstruction (ACPO), is an occasional disorder that occurs in hospitalized patients who have undergone major surgery. It presents with the clinical features of intestinal obstruction without any definitive intrinsic or extrinsic anatomical cause. Without prompt treatment, it can lead to life-threatening complications. The risk factors of this syndrome must be sought to prevent its occurrence. We report a rare case of idiopathic, spontaneous, and non-traumatic Ogilvie's syndrome, with old age as the only present risk factor in our case. To our best knowledge, this is the first-ever case reported in English scientific literature from Pakistan.

Speech Performance among Healthy Malay Female Speakers during Dual Tasks and Sentence Complexity.

OBJECTIVES: This study aimed to identify how different dual tasks influence speech performance among young Malay speakers by manipulating the complexity of sentences. Fifteen female speakers (20-30 years old) were audio recorded while executing a series of simple and complex sentence repetition tasks. METHODS: Hierarchical linear modeling was conducted to examine the effects of task (speech task only, speech + cognitive tasks, speech + linguistic tasks, and speech + manual tasks) and sentence complexity (simple vs. complex), as well as their interaction on 3 outcome measures (word accuracy rate [WAR], response reaction time [RRT], and duration of sentence [DoS]). RESULTS: Significantly higher WAR were found when participants read the sentences only compared to when they completed another task simultaneously. The pairwise comparison further revealed that the conditions of speech + manual tasks produced the lowest WAR. For RRT, participants responded significantly faster when they only read the sentences (mean = 1.36, SE = 0.17) than when they read the sentences and conducted another task at the same time (mean = 1.66, SE = 0.14; p < 0.0001). A pairwise comparison showed that the conditions of speech + manual tasks produced the longest DoS. Neither the effect of sentence complexity nor the interaction between task and sentence complexity was statistically significant across WAR, RRT, and DoS. CONCLUSIONS: The results augment what is known about interference between speech and other concurrent tasks and provides evidence that divided attention affects manual task performance more than other tasks. In addition, sentence complexity did not affect speech performance in healthy adults. This paradigm could be used in future studies to serve as a clinical marker that can potentially distinguish mild cognitive impairment from normal aging.

A comparative assessment of information recall and comprehension between conventional leaflets and an animated video in adolescent patients undergoing fixed orthodontic treatment: A single-center, randomized controlled trial.

INTRODUCTION: The objective of this 2-arm parallel trial was to investigate the recall and comprehension of the information of orthodontic patients undergoing fixed orthodontic treatment using either the verbal explanation supported with the British Orthodontic Society (BOS) leaflet or 3-dimensional (3D) animated content. METHODS: Patients aged 12-18 years, with no relevant medical history or learning and reading difficulties, who were to undergo orthodontic treatment, were randomized to receive information about fixed orthodontic treatment, using either verbal explanation supported with the BOS leaflet or 3D animated content on the basis of the BOS leaflet. Randomization was performed by block randomization; block size of 4 was used, from which 6 blocks with 6 different sequences (AABB, ABBA, ABAB, BBAA, BAAB, BABA). The blinded author asked patients a series of open-ended questions. The primary outcome measure was the total score of the questions. An independent 2 sample t test was conducted to determine if there was a statistical difference in total questions score between the conventional method (verbal and leaflet) and the 3D animation at the time of consent taking (T0) and again 1 year later (T1). The secondary outcome measure was the time spent by the clinician delivering the information to the patient. RESULTS: Thirty-two patients were randomized into each group. After 1 year, 1 patient was lost in each group. At the time of consent, the conventional group scored 79.1 ± 18.4 compared with 76.4 ± 12.8 for the 3D animation group with no statistically significant difference (95% confidence interval, -11.0 to 5.3), (P = 0.492). One year later, again, there was no statistically significant difference (P = 0.639) between the conventional group (75.6 ± 12.3) and the 3D animation group (74.4 ± 9.0) (95% confidence interval, -7.0 to 4.4). The average exposure time to the educational intervention in the conventional group was 8.5 minutes more than the 3D animation group. CONCLUSIONS: The use of 3D animation or verbal and leaflet information is relatively equivalent in transferring knowledge to the orthodontic patient. The use of a 3D animated video reduces the clinician time needed in the clinic to deliver information to the patients and also allows multiple views and better suits the younger generation. Patients undergoing short- or long-term orthodontic treatment do not recall root damage as a risk of orthodontic treatment, which requires special attention from the orthodontist to reinforce this information. REGISTRATION: This trial was not registered. PROTOCOL: The protocol was not published before trial commencement.

Evaluation of triclosan exposures on secretion of pro-inflammatory cytokines from human immune cells.

Triclosan (TCS) is widely used in personal hygiene products, such as mouthwash and toothpaste, and is found in human tissues. Interleukin (IL)-1 beta (IL-1ß), IL-6, tumor necrosis factor alpha (TNFα), and interferon gamma (IFNγ) are pro-inflammatory cytokines and inappropriately elevated levels of each have been associated with pathologies including rheumatoid arthritis and certain cancers. Here we examine effects of TCS on the secretion of the pro-inflammatory cytokines from human immune cell preparations. TCS at concentrations between 0.05-5 µM consistently increased the secretion of IL-1ß, IL-6, and TNFα within 24 h of exposure and the increases often maintained out to 6 days of exposure. TCS also induced increases in IFNγ secretion, however the increases were most consistent after 48 h of exposure rather than within 24 h. Additionally, a role for both p44/42 and p38 MAPK in TCS-stimulated increases in IL-1ß was seen in cells from some donors.

Tributyltin stimulates synthesis of interferon gamma and tumor necrosis factor alpha in human lymphocytes.

Tributyltin (TBT) is found in human blood and other tissues and thus is of considerable concern as to its effects on human health. Previous studies have demonstrated that TBT has detrimental effects on immune function. Recently, we found that exposures to TBT caused increased secretion of two important proinflammatory cytokines, tumor necrosis factor alpha (TNFα) and interferon gamma (IFNγ). Elevation of either of these cytokines has the potential to cause chronic inflammation, which is an important factor in a number of diseases including cancer. The current study examined the mechanism of TBT-induced elevations of TNFα and IFNγ secretion and found that the p38 mitogen-activated protein kinase pathway was essential to the ability of TBT to stimulate secretion. Additionally, this study demonstrated that increased secretion of these cytokines was due to TBT-induced increases in their overall synthesis, rather than simply being due to an increase in the release of already formed proteins. The TBT-induced increases in synthesis were evident within 6 hours of exposure. The p38 mitogen-activated protein kinase pathway is also necessary for the TBT-induced increases in both TNFα and IFNγ synthesis. The role of increased transcription of TNFα and IFNγ mRNA in response to TBT exposures as a possible explanation for the increased synthesis of these cytokines was also examined. It was found that increased mRNA levels did not appear to explain fully the increases in either TNFα or IFNγ synthesis. Thus, TBT is able to increase secretion of two important proinflammatory cytokines by increasing their synthesis.

Dating violence and the health of young women: a feminist narrative study.

Dating violence is a significant public health problem in the lives of young women. Their age, in conjunction with perceived pressures to engage in intimate relationships, makes these women particularly vulnerable to dating violence. The pressures to be in relationships can be intense and therefore may add to young women's willingness to overlook, forgive, or excuse the violence that is occurring. The authors' purposes in this feminist study were to examine the experience of dating violence from young women's perspectives; investigate how contextual factors shape their experiences; examine how health is shaped by these experiences; and explore ways that dating violence is perpetuated and normalized in young women's lives. Findings revealed that family environment and gender are critical in shaping young women's experiences. The participants described a range of physical and emotional health problems and perceived few sources of support. Their efforts to obtain support were often met with skeptical and dismissive attitudes on the part of health care providers and other trusted adults. Recommendations for health care practice, education, and research are presented.