Improving Cardiac Arrest Outcomes with Hands-Only CPR

Bystander CPR is one of the most effective and necessary components of cardiac arrest management, increasing survival rates by two to three times. However, rates of bystander CPR are inadequately low. Hands-only CPR has been found to be an effective intervention in the management of cardiac arrest and addresses many of the barriers to bystander CPR.https://scholarworks.uvm.edu/fmclerk/1496/thumbnail.jp

Radon, From the Ground into Our Schools: Parent/Guardian Awareness of Radon Levels in Vermont Schools

Introduction. Radon is the leading cause of lung cancer among non-smokers. Ex- posure to radon in schools may be harmful to schoolchildren, faculty, and staff, but there is currently no legislation mandating testing or mitigation of radon levels in Vermont schools. Objectives. The goal of our study was to assess Vermont parents’ awareness of radon’s harmful effects, as well as awareness of and support for testing and mitigation of radon levels in their children’s schools. Methods. We distributed paper and online surveys to Vermont parents of children grades K-12. 126 surveys were received and quantitatively analyzed. We held a focus group of two Vermont parents to gather qualitative data. Results. Most surveyed parents demonstrated general knowledge of radon, but only 51% believed that radon affects the lungs. 8% were confident that their children’s schools had informed them about radon levels. 91.2% believe their children’s schools should take action to address elevated radon levels and 87% would support mandated mitigation. There is some concern and lack of knowledge about the financial implications of radon mitigation. Conclusions. Most Vermont parents of children grades K-12 are unaware that radon is a lung carcinogen and do not know their children’s school’s radon levels or mitigation status. However, most are in favor of legislation that would require testing and dis- closure of schools’ high radon levels. Educating parents about school radon levels and their association with lung cancer could be a foundation for community support of legislation that mandates testing and mitigation of radon in Vermont schools.https://scholarworks.uvm.edu/comphp_gallery/1252/thumbnail.jp

A Low-Cost Microprocessor-Controlled Stance-Control Knee Orthosis for Pediatric Mobility Impairments

Knee-ankle-foot orthoses (KAFOs) are commonly prescribed for individuals with knee instability or quadriceps weakness resulting from a variety of conditions such as spinal cord injury, stroke, spina bifida, and cerebral palsy. A locking KAFO fixes the leg fully straight and is the most prescribed orthotic intervention for these conditions. However, the functional benefits of lower extremity orthoses are maximally realized in stance-controlled knee-ankle-foot orthoses (SC-KAFOs) which allow free knee motion during swing but lock during stance. Existing SC-KAFO options are generally unreliable or expensive, and thus an unmet need exists for a reliable, versatile orthosis which can be manufactured at relatively low cost. The SC-KO team is working to meet this need by developing an intelligent stance-controlled knee orthotic with an any-angle locking mechanism controlled by a microprocessor based on information received from onboard inertial gait-phase sensing. The resulting device will allow for reliable knee locking for support during the stance phase, easy unlocking even under load for the free swing phase, and predictable, safe behavior on stairs and uneven terrain. The system is being developed as a knee-only orthosis but can be adapted for a full knee-ankle-foot orthosis, with ankle support being prescribed as needed. The first system developed will be configured for pediatric use to address mobility impairments arising from cerebral palsy and spina bifida with CURE Ethiopia serving as the clinical partner for the development and testing. Funding for this work provided by The Collaboratory for Strategic Partnerships and Applied Research.https://mosaic.messiah.edu/engr2022/1017/thumbnail.jp

Geminin regulates the transcriptional and epigenetic status of neuronal fate-promoting genes during mammalian neurogenesis

Regulating the transition from lineage-restricted progenitors to terminally differentiated cells is a central aspect of nervous system development. Here, we investigated the role of the nucleoprotein geminin in regulating neurogenesis at a mechanistic level during both Xenopus primary neurogenesis and mammalian neuronal differentiation in vitro. The latter work utilized neural cells derived from embryonic stem and embryonal carcinoma cells in vitro and neural stem cells from mouse forebrain. In all of these contexts, geminin antagonized the ability of neural basic helix-loop-helix (bHLH) transcription factors to activate transcriptional programs promoting neurogenesis. Furthermore, geminin promoted a bivalent chromatin state, characterized by the presence of both activating and repressive histone modifications, at genes encoding transcription factors that promote neurogenesis. This epigenetic state restrains the expression of genes that regulate commitment of undifferentiated stem and neuronal precursor cells to neuronal lineages. However, maintaining geminin at high levels was not sufficient to prevent terminal neuronal differentiation. Therefore, these data support a model whereby geminin promotes the neuronal precursor cell state by modulating both the epigenetic status and expression of genes encoding neurogenesis-promoting factors. Additional developmental signals acting in these cells can then control their transition toward terminal neuronal or glial differentiation during mammalian neurogenesis

MuRF1 activity is present in cardiac mitochondria and regulates reactive oxygen species production in vivo

Erratum: https://link.springer.com/article/10.1007/s10863-014-9597-1MuRF1 is a previously reported ubiquitin-ligase found in striated muscle that targets troponin I and myosin heavy chain for degradation. While MuRF1 has been reported to interact with mitochondrial substrates in yeast two-hybrid studies, no studies have identified MuRF1’s role in regulating mitochondrial function to date. In the present study, we measured cardiac mitochondrial function from isolated permeabilized muscle fibers in previously phenotyped MuRF1 transgenic and MuRF1−/− mouse models to determine the role of MuRF1 in intermediate energy metabolism and ROS production. We identified a significant decrease in reactive oxygen species production in cardiac muscle fibers from MuRF1 transgenic mice with increased α-MHC driven MuRF1 expression. Increased MuRF1 expression in ex vivo and in vitro experiments revealed no alterations in the respiratory chain complex I and II function. Working perfusion experiments on MuRF1 transgenic hearts demonstrated significant changes in glucose oxidation. This is an factual error as written; however, total oxygen consumption was decreased. This data provides evidence for MuRF1 as a novel regulator of cardiac ROS, offering another mechanism by which increased MuRF1 expression may be cardioprotective in ischemia reperfusion injury, in addition to its inhibition of apoptosis via proteasome-mediate degradation of c-Jun. The lack of mitochondrial function phenotype identified in MuRF1−/− hearts may be due to the overlapping interactions of MuRF1 and MuRF2 with energy regulating proteins found by yeast two-hybrid studies reported here, implying a duplicity in MuRF1 and MuRF2’s regulation of mitochondrial function.Funding support from Medical Research Council, United Kingdom; National Institutes of Health, United States; British Heart Foundation, United Kingdo

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Co-administering Melatonin With an Estradiol-Progesterone Menopausal Hormone Therapy Represses Mammary Cancer Development in a Mouse Model of HER2-Positive Breast Cancer.

Melatonin has numerous anti-cancer properties reported to influence cancer initiation, promotion, and metastasis. With the need for effective hormone therapies (HT) to treat menopausal symptoms without increasing breast cancer risk, co-administration of nocturnal melatonin with a natural, low-dose HT was evaluated in mice that develop primary and metastatic mammary cancer. Individually, melatonin (MEL) and estradiol-progesterone therapy (EPT) did not significantly affect mammary cancer development through age 14 months, but, when combined, the melatonin-estradiol-progesterone therapy (MEPT) significantly repressed tumor formation. This repression was due to effects on tumor incidence, but not latency. These results demonstrate that melatonin and the HT cooperate to decrease the mammary cancer risk. Melatonin and EPT also cooperate to alter the balance of the progesterone receptor (PR) isoforms by significantly increasing PRA protein expression only in MEPT mammary glands. Melatonin significantly suppressed amphiregulin transcripts in MEL and MEPT mammary glands, suggesting that amphiregulin together with the higher PRA:PRB balance and other factors may contribute to reducing cancer development in MEPT mice. Melatonin supplementation influenced mammary morphology by increasing tertiary branching in the mouse mammary glands and differentiation in human mammary epithelial cell cultures. Uterine weight in the luteal phase was elevated after long-term exposure to EPT, but not to MEPT, indicating that melatonin supplementation may reduce estrogen-induced uterine stimulation. Melatonin supplementation significantly decreased the incidence of grossly-detected lung metastases in MEL mice, suggesting that melatonin delays the formation of metastatic lesions and/or decreases aggressiveness in this model of HER

Co-administering melatonin with an estradiol-progesterone menopausal hormone therapy represses mammary cancer development in a mouse model of her2-positive breast cancer

Melatonin has numerous anti-cancer properties reported to influence cancer initiation, promotion, and metastasis. With the need for effective hormone therapies (HT) to treat menopausal symptoms without increasing breast cancer risk, co-administration of nocturnal melatonin with a natural, low-dose HT was evaluated in mice that develop primary and metastatic mammary cancer. Individually, melatonin (MEL) and estradiol-progesterone therapy (EPT) did not significantly affect mammary cancer development through age 14 months, but, when combined, the melatonin-estradiol-progesterone therapy (MEPT) significantly repressed tumor formation. This repression was due to effects on tumor incidence, but not latency. These results demonstrate that melatonin and the HT cooperate to decrease the mammary cancer risk. Melatonin and EPT also cooperate to alter the balance of the progesterone receptor (PR) isoforms by significantly increasing PRA protein expression only in MEPT mammary glands. Melatonin significantly suppressed amphiregulin transcripts in MEL and MEPT mammary glands, suggesting that amphiregulin together with the higher PRA:PRB balance and other factors may contribute to reducing cancer development in MEPT mice. Melatonin supplementation influenced mammary morphology by increasing tertiary branching in the mouse mammary glands and differentiation in human mammary epithelial cell cultures. Uterine weight in the luteal phase was elevated after long-term exposure to EPT, but not toMEPT, indicating thatmelatonin supplementationmay reduce estrogen-induced uterine stimulation. Melatonin supplementation significantly decreased the incidence of grossly-detected lung metastases in MEL mice, suggesting that melatonin delays the formation of metastatic lesions and/or decreases aggressiveness in this model of HER2+ breast cancer. Mammary tumor development was similar in EPT and MEPT mice until age 8.6 months, but after 8.6 months, only MEPT continued to suppress cancer development. These data suggest that melatonin supplementation has a negligible effect in young MEPT mice, but is required in older mice to inhibit tumor formation. Sincemelatonin binding was significantly decreased in oldermammary glands, irrespective of treatment, melatonin supplementation may overcome reduced melatonin responsiveness in the agedMEPTmice. Sincemelatonin levels are known to decline near menopause, nocturnal melatonin supplementation may also be needed in aging women to cooperate with HT to decrease breast cancer risk

The Finland–United States Investigation of Non–Insulin-Dependent Diabetes Mellitus Genetics (FUSION) Study. I. An Autosomal Genome Scan for Genes That Predispose to Type 2 Diabetes

We performed a genome scan at an average resolution of 8 cM in 719 Finnish sib pairs with type 2 diabetes. Our strongest results are for chromosome 20, where we observe a weighted maximum LOD score (MLS) of 2.15 at map position 69.5 cM from pter and secondary weighted LOD-score peaks of 2.04 at 56.5 cM and 1.99 at 17.5 cM. Our next largest MLS is for chromosome 11 (MLS = 1.75 at 84.0 cM), followed by chromosomes 2 (MLS = 0.87 at 5.5 cM), 10 (MLS = 0.77 at 75.0 cM), and 6 (MLS = 0.61 at 112.5 cM), all under an additive model. When we condition on chromosome 2 at 8.5 cM, the MLS for chromosome 20 increases to 5.50 at 69.0 cM (P=.0014). An ordered-subsets analysis based on families with high or low diabetes-related quantitative traits yielded results that support the possible existence of disease-predisposing genes on chromosomes 6 and 10. Genomewide linkage-disequilibrium analysis using microsatellite marker data revealed strong evidence of association for D22S423 (P=.00007). Further analyses are being carried out to confirm and to refine the location of these putative diabetes-predisposing genes