Chemical methods to induce beta-cell proliferation

Pancreatic beta-cell regeneration, for example, by inducing proliferation, remains an important goal in developing effective treatments for diabetes. However, beta cells have mainly been considered quiescent. This "static" view has recently been challenged by observations of relevant physiological conditions in which metabolic stress is compensated by an increase in beta-cell mass. Understanding the molecular mechanisms underlining these process could open the possibility of developing novel small molecules to increase beta-cell mass. Several cellular cell-cycle and signaling proteins provide attractive targets for high throughput screening, and recent advances in cell culture have enabled phenotypic screening for small molecule-induced beta-cell proliferation. We present here an overview of the current trends involving small-molecule approaches to induce beta-cell regeneration by proliferation

The Effect of Timing and Type of Exercise on the Quality of Sleep in Trained Individuals

International Journal of Exercise Science 13(7): 837-858, 2020. Sleep is an extremely important component for overall health and for a well-balanced training program. Recent studies have highlighted the interaction between sleep, recovery, and performance in elite and recreational athletes alike. Exercise has been known to affect the quality of sleep, nevertheless the impact is not well understood in the current research, particularly the effects of exercise timing and intensity on sleep quality. The purpose of this study was to understand if exercise timing and intensity significantly impact sleep quality among recreational exercisers. The participants involved were recreational exercisers who were self-grouped into an AM or PM exercise group. They participated in a seven-day quantitative, quasi-experimental, exploratory study wearing an Actigraph watch. The participant’s intensity was also self-grouped into moderate intensity or high intensity based on criteria cut points. Data was analyzed using a factorial ANOVA to examine if there was a significant difference between exercise timing and intensity on sleep quality of the participants. There were no significant differences in sleep quality in either the time group (AM vs PM) or the intensity group (MOD vs VIG) within the four measures of sleep that were looked at throughout this study; total sleep time, sleep onset latency, sleep efficiency % and wake after sleep onset (TST, SOL, SE, and WASO). Results within both, the AM and PM group and the MOD and VIG group, results showed no significant differences. These results conclude that neither exercise intensity or timing had an effect on sleep quality

Retrospective evaluation of antimicrobial prophylaxis in prevention of surgical site infection in the pediatric population

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/108107/1/pan12436.pd

Equatorial Pacific productivity changes near the Eocene-Oligocene boundary

There is general agreement that productivity in high latitudes increased in the late Eocene and remained high in the early Oligocene. Evidence for both increased and decreased productivity across the Eocene-Oligocene transition (EOT) in the tropics has been presented, usually based on only one paleoproductivity proxy and often in sites with incomplete recovery of the EOT itself. A complete record of the Eocene-Oligocene transition was obtained at three drill sites in the eastern equatorial Pacific Ocean (ODP Site 1218 and IODP Sites U1333 and U1334). Four paleoproductivity proxies that have been examined at these sites, together with carbon and oxygen isotope measurements on early Oligocene planktonic foraminifera, give evidence of ecologic and oceanographic change across this climatically important boundary. Export productivity dropped sharply in the basal Oligocene (~33.7�Ma) and only recovered several hundred thousand years later; however, overall paleoproductivity in the early Oligocene never reached the average levels found in the late Eocene and in more modern times. Changes in the isotopic gradients between deep- and shallow-living planktonic foraminifera suggest a gradual shoaling of the thermocline through the early Oligocene that, on average, affected accumulation rates of barite, benthic foraminifera, and opal, as well as diatom abundance near 33.5�Ma. An interval with abundant large diatoms beginning at 33.3�Ma suggests an intermediate thermocline depth, which was followed by further shoaling, a dominance of smaller diatoms, and an increase in average primary productivity as estimated from accumulation rates of benthic foraminifera

Pass This Message Along: Self-edited Email Messages Promoting Colon Cancer Screening among Friends and Family

Encouraging communication within a social network may promote uptake of desired medical services or health behaviors. Little is known about the use of this approach to promote colorectal cancer (CRC) screening. We conducted in-person interviews with 438 insured adults ages 42-73 in Massachusetts, Hawaii, and Georgia. Participants were shown a sample message in which the sender shares that he has completed a colonoscopy and urges the recipient to discuss CRC screening with a doctor. We asked participants to edit the message to create one they would be willing to send to friends and family via email or postcard. Changes to the message were recorded. Edited text was analyzed for content and concordance with original message. The majority of participants (61.6%) modified the message; 14.2% added to or reframed the existing personalizing words (e.g. adding ‘because I love you’), 10.3% added urgency to the message (e.g. “please don’t delay”) and 8% added reassurance (e.g. “It’s really not that bad.”) Almost one in five (18.3%) deleted a negatively framed sentence on colon cancer risks. In 5.7% of cases, the meaning of at least one sentence was changed but only 2.7% created messages with factual inaccuracies. Modifiable messages transmitted within a social network offer a way for screened individuals to promote CRC screening. Further study is needed to identify the optimal combination of user-generated content and pre-written text, allowing for creation of messages that are acceptable to senders, persuasive and factually accurate

Discovery of Small-Molecule Enhancers of Reactive Oxygen Species That are Nontoxic or Cause Genotype-Selective Cell Death

Elevation of reactive oxygen species (ROS) levels has been observed in many cancer cells relative to nontransformed cells, and recent reports have suggested that small-molecule enhancers of ROS may selectively kill cancer cells in various in vitro and in vivo models. We used a high-throughput screening approach to identify several hundred small-molecule enhancers of ROS in a human osteosarcoma cell line. A minority of these compounds diminished the viability of cancer cell lines, indicating that ROS elevation by small molecules is insufficient to induce death of cancer cell lines. Three chemical probes (BRD5459, BRD56491, BRD9092) are highlighted that most strongly elevate markers of oxidative stress without causing cell death and may be of use in a variety of cellular settings. For example, combining nontoxic ROS-enhancing probes with nontoxic doses of l-buthionine sulfoximine, an inhibitor of glutathione synthesis previously studied in cancer patients, led to potent cell death in more than 20 cases, suggesting that even nontoxic ROS-enhancing treatments may warrant exploration in combination strategies. Additionally, a few ROS-enhancing compounds that contain sites of electrophilicity, including piperlongumine, show selective toxicity for transformed cells over nontransformed cells in an engineered cell-line model of tumorigenesis. These studies suggest that cancer cell lines are more resilient to chemically induced increases in ROS levels than previously thought and highlight electrophilicity as a property that may be more closely associated with cancer-selective cell death than ROS elevation.Chemistry and Chemical Biolog

Synthesis of Oxazocenones via Gold(I)-Catalyzed 8-Endo-Dig Hydroalkoxylation of Alkynamides

Several benzoxazocenones have been found to exhibit novel cellular activities. In the present study, we report a gold(I)-catalyzed 8-endo-dig hydroalkoxylation reaction of alkynamides to access analogous oxazocenone scaffolds. This methodology provided an advanced intermediate, which was elaborated to a des-benzo analog of a bioactive benzoxazocenone

Adult Willingness to Use Email and Social Media for Peer-to-Peer Cancer Screening Communication: Quantitative Interview Study

BACKGROUND: Adults over age 40 are increasing their use of email and social media, raising interest in use of peer-to-peer Internet-based messaging to promote cancer screening. OBJECTIVE: The objective of our study was to assess current practices and attitudes toward use of email and other e-communication for peer-to-peer dialogues on cancer screening. METHODS: We conducted in-person interviews with 438 insured adults ages 42-73 in Georgia, Hawaii, and Massachusetts. Participants reported on use of email and other e-communication including social media to discuss with peers routine health topics including breast and colorectal cancer (CRC). We ascertained willingness to share personal CRC screening experiences via conversation, postcard, email, or other e-communication. Health literacy scores were measured. RESULTS: Email had been used by one-third (33.8%, 148/438) to discuss routine health topics, by 14.6% (64/438) to discuss breast cancer screening, and by 12.6% (55/438) to discuss CRC screening. Other e-communication was used to discuss routine health topics (11.6%, 51/438), screening for breast cancer (3.9%, 17/438), and CRC (2.3%, 10/438). In the preceding week, 84.5% (370/438) of participants had used email, 55.9% (245/438) had used e-communication of some type; 44.3% (194/438) text, 32.9% (144/438) Facebook, 12.3% (54/438) instant message, 7.1% (31/438) video chat, and 4.8% (21/438) Twitter. Many participants were willing to share their CRC screening experiences via email (32.4%, 142/438 might be willing; 36.3%, 159/438 very willing) and via other e-communication (15.8%, 69/438 might be willing; 14.4%, 63/438 very willing). Individuals willing to send CRC screening emails scored significantly higher on tests of health literacy compared to those willing to send only postcards (P\u3c.001). CONCLUSIONS: Many adults are willing to use email and e-communication to promote cancer screening to peers. Optimal approaches for encouraging peer-to-peer transmission of accurate and appropriate cancer screening messages must be studied

Health Links: Who Acts as a Source of Health Information in a Social Network?

Background: Members of a social network can influence the preventive health choices and cancer screening behaviors of other network members. Study Design: We conducted in-person interviews with 438 insured adults ages 40-70 in Massachusetts, Hawaii, and Georgia. We gathered information on social network communication regarding routine health topics and cancer screening. Participants reported whether family members and friends ask them for information or advice on health topics. Characteristics of each respondent’s social network were explored, including number of people with whom the participant has discussed colorectal cancer (CRC) screening. Participants were asked whether communication with social network members had ever led them to seek cancer screening. Principal Findings:80% of respondents in our group described themselves as a source of health information or advice for others in their social network (89% of women vs. 68% of men, p Conclusions: People who identified themselves as a source of health information within their social network were more likely to have discussed CRC screening with others and communicated with more people. Further study is necessary to understand the roles played by these individuals. As “health information ambassadors,” they may be effective targets for interventions that promote preventive screening

A Small-Molecule Probe of the Histone Methyltransferase G9a Induces Cellular Senescence in Pancreatic Adenocarcinoma

Post-translational modifications of histones alter chromatin structure and play key roles in gene expression and specification of cell states. Small molecules that target chromatin-modifying enzymes selectively are useful as probes and have promise as therapeutics, although very few are currently available. G9a (also named euchromatin histone methyltransferase 2 (EHMT2)) catalyzes methylation of lysine 9 on histone H3 (H3K9), a modification linked to aberrant silencing of tumor-suppressor genes, among others. Here, we report the discovery of a novel histone methyltransferase inhibitor, BRD4770. This compound reduced cellular levels of di- and trimethylated H3K9 without inducing apoptosis, induced senescence, and inhibited both anchorage-dependent and -independent proliferation in the pancreatic cancer cell line PANC-1. ATM-pathway activation, caused by either genetic or small-molecule inhibition of G9a, may mediate BRD4770-induced cell senescence. BRD4770 may be a useful tool to study G9a and its role in senescence and cancer cell biology.Chemistry and Chemical Biolog