Sample records for aipl1 effective rescue

  1. Gene therapy using self-complementary Y733F capsid mutant AAV2/8 restores vision in a model of early onset Leber congenital amaurosis.

    PubMed

    Ku, Cristy A; Chiodo, Vince A; Boye, Sanford L; Goldberg, Andrew F X; Li, Tiansen; Hauswirth, William W; Ramamurthy, Visvanathan

    2011-12-01

    Defects in the photoreceptor-specific gene aryl hydrocarbon receptor interacting protein-like 1 (Aipl1) are associated with Leber congenital amaurosis (LCA), a childhood blinding disease with early-onset retinal degeneration and vision loss. Furthermore, Aipl1 defects are characterized at the most severe end of the LCA spectrum. The rapid photoreceptor degeneration and vision loss observed in the LCA patient population are mimicked in a mouse model lacking AIPL1. Using this model, we evaluated if gene replacement therapy using recent advancements in adeno-associated viral vectors (AAV) provides advantages in preventing rapid retinal degeneration. Specifically, we demonstrated that the novel self-complementary Y733F capsid mutant AAV2/8 (sc-Y733F-AAV) provided greater preservation of photoreceptors and functional vision in Aipl1 null mice compared with single-stranded AAV2/8. The benefits of sc-Y733F-AAV were evident following viral administration during the active phase of retinal degeneration, where only sc-Y733F-AAV treatment achieved functional vision rescue. This result was likely due to higher and earlier onset of Aipl1 expression. Based on our studies, we conclude that the sc-Y733F-AAV2/8 viral vector, to date, achieves the best rescue for rapid retinal degeneration in Aipl1 null mice. Our results provide important considerations for viral vectors to be used in future gene therapy clinical trials targeting a wider severity spectrum of inherited retinal dystrophies.

  2. Unique structural features of the AIPL1–FKBP domain that support prenyl lipid binding and underlie protein malfunction in blindness

    PubMed Central

    Yadav, Ravi P.; Gakhar, Lokesh; Yu, Liping

    2017-01-01

    FKBP-domain proteins (FKBPs) are pivotal modulators of cellular signaling, protein folding, and gene transcription. Aryl hydrocarbon receptor-interacting protein-like 1 (AIPL1) is a distinctive member of the FKBP superfamily in terms of its biochemical properties, and it plays an important biological role as a chaperone of phosphodiesterase 6 (PDE6), an effector enzyme of the visual transduction cascade. Malfunction of mutant AIPL1 proteins triggers a severe form of Leber congenital amaurosis and leads to blindness. The mechanism underlying the chaperone activity of AIPL1 is largely unknown, but involves the binding of isoprenyl groups on PDE6 to the FKBP domain of AIPL1. We solved the crystal structures of the AIPL1–FKBP domain and its pathogenic mutant V71F, both in the apo form and in complex with isoprenyl moieties. These structures reveal a module for lipid binding that is unparalleled within the FKBP superfamily. The prenyl binding is enabled by a unique “loop-out” conformation of the β4-α1 loop and a conformational “flip-out” switch of the key W72 residue. A second major conformation of apo AIPL1–FKBP was identified by NMR studies. This conformation, wherein W72 flips into the ligand-binding pocket and renders the protein incapable of prenyl binding, is supported by molecular dynamics simulations and appears to underlie the pathogenicity of the V71F mutant. Our findings offer critical insights into the mechanisms that underlie AIPL1 function in health and disease, and highlight the structural and functional diversity of the FKBPs. PMID:28739921

  3. Pharmacoethnicity in Paclitaxel-Induced Sensory Peripheral Neuropathy

    PubMed Central

    Komatsu, Masaaki; Wheeler, Heather E.; Chung, Suyoun; Low, Siew-Kee; Wing, Claudia; Delaney, Shannon M.; Gorsic, Lidija K.; Takahashi, Atsushi; Kubo, Michiaki; Kroetz, Deanna L.; Zhang, Wei; Nakamura, Yusuke; Dolan, M. Eileen

    2015-01-01

    Purpose Paclitaxel is used worldwide in the treatment of breast, lung, ovarian and other cancers. Sensory peripheral neuropathy is an associated adverse effect that cannot be predicted, prevented or mitigated. To better understand the contribution of germline genetic variation to paclitaxel-induced peripheral neuropathy, we undertook an integrative approach that combines genome-wide association study (GWAS) data generated from HapMap lymphoblastoid cell lines (LCLs) and Asian patients. Methods GWAS was performed with paclitaxel-induced cytotoxicity generated in 363 LCLs and with paclitaxel-induced neuropathy from 145 Asian patients. A gene-based approach was used to identify overlapping genes and compare to a European clinical cohort of paclitaxel-induced neuropathy. Neurons derived from human induced pluripotent stem cells were used for functional validation of candidate genes. Results SNPs near AIPL1 were significantly associated with paclitaxel-induced cytotoxicity in Asian LCLs (P < 10−6). Decreased expression of AIPL1 resulted in decreased sensitivity of neurons to paclitaxel by inducing neurite morphological changes as measured by increased relative total outgrowth, number of processes and mean process length. Using a gene-based analysis, there were 32 genes that overlapped between Asian LCL cytotoxicity and Asian patient neuropathy (P < 0.05) including BCR. Upon BCR knockdown, there was an increase in neuronal sensitivity to paclitaxel as measured by neurite morphological characteristics. Conclusion We identified genetic variants associated with Asian paclitaxel-induced cytotoxicity and functionally validated the AIPL1 and BCR in a neuronal cell model. Furthermore, the integrative pharmacogenomics approach of LCL/patient GWAS may help prioritize target genes associated with chemotherapeutic-induced peripheral neuropathy. PMID:26015512

  4. Identification of mutations in the AIPL1, CRB1, GUCY2D, RPE65, and RPGRIP1 genes in patients with juvenile retinitis pigmentosa.

    PubMed

    Booij, J C; Florijn, R J; ten Brink, J B; Loves, W; Meire, F; van Schooneveld, M J; de Jong, P T V M; Bergen, A A B

    2005-11-01

    To identify mutations in the AIPL1, CRB1, GUCY2D, RPE65, and RPGRIP1 genes in patients with juvenile retinitis pigmentosa. Mutation analysis was carried out in a group of 35 unrelated patients with juvenile autosomal recessive retinitis pigmentosa (ARRP), Leber's congenital amaurosis (LCA), or juvenile isolated retinitis pigmentosa (IRP), by denaturing high performance liquid chromatography followed by direct sequencing. All three groups of patients showed typical combinations of eye signs associated with retinitis pigmentosa: pale optic discs, narrow arterioles, pigmentary changes, and nystagmus. Mutations were found in 34% of in CRB1 (11%), GUCY2D (11%), RPE65 (6%), and RPGRIP1 (6%). Nine mutations are reported, including a new combination of two mutations in CRB1, and new mutations in GUCY2D and RPGRIP1. The new GUCY2D mutation (c.3283delC, p.Pro1069ArgfsX37) is the first pathological sequence change reported in the intracellular C-terminal domain of GUCY2D, and did not lead to the commonly associated LCA, but to a juvenile retinitis pigmentosa phenotype. The polymorphic nature of three previously described (pathological) sequence changes in AIPL1, CRB1, and RPGRIP1 was established. Seven new polymorphic changes, useful for further association studies, were found. New and previously described sequence changes were detected in retinitis pigmentosa in CRB1, GUCY2D, and RPGRIP1; and in LCA patients in CRB1, GUCY2D, and RPE65. These data, combined with previous reports, suggest that LCA and juvenile ARRP are closely related and belong to a continuous spectrum of juvenile retinitis pigmentosa.

  5. Clinical and genetic characteristics of Leber congenital amaurosis with novel mutations in known genes based on a Chinese eastern coast Han population.

    PubMed

    Wang, Shiyuan; Zhang, Qi; Zhang, Xiang; Wang, Zhaoyang; Zhao, Peiquan

    2016-11-01

    To study the genotype-phenotype characteristics of Leber congenital amaurosis (LCA) in the Chinese eastern coast Han population. Children with strictly defined LCA with novel mutations of known LCA genes identified by targeted next-generation sequencing (NGS) and a prediction of pathogenicity (in silico) were included in this study (2013-2015). Mutations were confirmed using Sanger sequencing and segregation analysis. The clinical findings were recorded, including visual function, refractive error, fundus changes, and electroretinograms (ERGs). Spectral-domain optical coherence tomography (SD-OCT) examination, fundus fluorescein angiography (FFA), and ultra-wide field scanning laser ophthalmoscopy (UWF SLO) were performed on children when available. A total of 65 patients underwent NGS for mutation screening and 45 patients were identified as carrying known LCA genes. Of these, 36(80 %) children harbored novel mutations, and they were all from the eastern coast of China. A total of 50 novel variants were identified, which covered 15 known LCA genes. GUCY2D (17 %), CEP290 (14 %), NMNAT1 (14 %), AIPL1 (11 %) and RPGRIP1 (11 %) were the five most frequently mutated genes with novel mutations. A total of four (11 %) patients with AIPL1 mutations harbored the same novel mutated allele (c.C241T p.Q81X), which was homozygous in patients 1 and 2. Unusual manifestations were detected in patient 16 who had novel mutations in CRB1 with a dense proliferative membrane adhering to the posterior retina of the right eye with numerous fine glistening crystals spreading over the retina of both eyes. Ten (40 %) of the 25 available patients who underwent SD-OCT showed a normal macular appearance using fundus photography but an abnormal macular structure using OCT imaging, most of whom presented with a thickened fovea with maldevelopment of the inner and outer retinal laminae. There may be a high frequency of AIPL1 novel mutations and a founder mutation of p.Q81X in the Chinese eastern coast Han population. Our findings of specific features in this population broaden the spectrum of novel mutations and the phenotype of LCA with ethnic and regional variations. Fundus multimodality imaging may help guide comprehensive assessments for patients with LCA.

  6. Brain mechanisms associated with internally directed attention and self-generated thought.

    PubMed

    Benedek, Mathias; Jauk, Emanuel; Beaty, Roger E; Fink, Andreas; Koschutnig, Karl; Neubauer, Aljoscha C

    2016-03-10

    Internal cognition like imagination and prospection require sustained internally directed attention and involve self-generated thought. This fMRI study aimed to disentangle the brain mechanisms associated with attention-specific and task-specific processes during internally directed cognition. The direction of attention was manipulated by either keeping a relevant stimulus visible throughout the task, or by masking it, so that the task had to be performed "in the mind's eye". The level of self-directed thought was additionally varied between a convergent and a divergent thinking task. Internally directed attention was associated with increased activation in the right anterior inferior parietal lobe (aIPL), bilateral lingual gyrus and the cuneus, as well as with extended deactivations of superior parietal and occipital regions representing parts of the dorsal attention network. The right aIPL further showed increased connectivity with occipital regions suggesting an active top-down mechanism for shielding ongoing internal processes from potentially distracting sensory stimulation in terms of perceptual decoupling. Activation of the default network was not related to internally directed attention per se, but rather to a higher level of self-generated thought. The findings hence shed further light on the roles of inferior and superior parietal cortex for internally directed cognition.

  7. Homozygosity Mapping in Leber Congenital Amaurosis and Autosomal Recessive Retinitis Pigmentosa in South Indian Families

    PubMed Central

    Srilekha, Sundaramurthy; Arokiasamy, Tharigopala; Srikrupa, Natarajan N.; Umashankar, Vetrivel; Meenakshi, Swaminathan; Sen, Parveen; Kapur, Suman; Soumittra, Nagasamy

    2015-01-01

    Leber congenital amaurosis (LCA) and retinitis pigmentosa (RP) are retinal degenerative diseases which cause severe retinal dystrophy affecting the photoreceptors. LCA is predominantly inherited as an autosomal recessive trait and contributes to 5% of all retinal dystrophies; whereas RP is inherited by all the Mendelian pattern of inheritance and both are leading causes of visual impairment in children and young adults. Homozygosity mapping is an efficient strategy for mapping both known and novel disease loci in recessive conditions, especially in a consanguineous mating, exploiting the fact that the regions adjacent to the disease locus will also be homozygous by descent in such inbred children. Here we have studied eleven consanguineous LCA and one autosomal recessive RP (arRP) south Indian families to know the prevalence of mutations in known genes and also to know the involvement of novel loci, if any. Complete ophthalmic examination was done for all the affected individuals including electroretinogram, fundus photograph, fundus autofluorescence, and optical coherence tomography. Homozygosity mapping using Affymetrix 250K HMA GeneChip on eleven LCA families followed by screening of candidate gene(s) in the homozygous block identified mutations in ten families; AIPL1 – 3 families, RPE65- 2 families, GUCY2D, CRB1, RDH12, IQCB1 and SPATA7 in one family each, respectively. Six of the ten (60%) mutations identified are novel. Homozygosity mapping using Affymetrix 10K HMA GeneChip on the arRP family identified a novel nonsense mutation in MERTK. The mutations segregated within the family and was absent in 200 control chromosomes screened. In one of the eleven LCA families, the causative gene/mutation was not identified but many homozygous blocks were noted indicating that a possible novel locus/gene might be involved. The genotype and phenotype features, especially the fundus changes for AIPL1, RPE65, CRB1, RDH12 genes were as reported earlier. PMID:26147992

  8. Homozygosity Mapping in Leber Congenital Amaurosis and Autosomal Recessive Retinitis Pigmentosa in South Indian Families.

    PubMed

    Srilekha, Sundaramurthy; Arokiasamy, Tharigopala; Srikrupa, Natarajan N; Umashankar, Vetrivel; Meenakshi, Swaminathan; Sen, Parveen; Kapur, Suman; Soumittra, Nagasamy

    2015-01-01

    Leber congenital amaurosis (LCA) and retinitis pigmentosa (RP) are retinal degenerative diseases which cause severe retinal dystrophy affecting the photoreceptors. LCA is predominantly inherited as an autosomal recessive trait and contributes to 5% of all retinal dystrophies; whereas RP is inherited by all the Mendelian pattern of inheritance and both are leading causes of visual impairment in children and young adults. Homozygosity mapping is an efficient strategy for mapping both known and novel disease loci in recessive conditions, especially in a consanguineous mating, exploiting the fact that the regions adjacent to the disease locus will also be homozygous by descent in such inbred children. Here we have studied eleven consanguineous LCA and one autosomal recessive RP (arRP) south Indian families to know the prevalence of mutations in known genes and also to know the involvement of novel loci, if any. Complete ophthalmic examination was done for all the affected individuals including electroretinogram, fundus photograph, fundus autofluorescence, and optical coherence tomography. Homozygosity mapping using Affymetrix 250K HMA GeneChip on eleven LCA families followed by screening of candidate gene(s) in the homozygous block identified mutations in ten families; AIPL1 - 3 families, RPE65- 2 families, GUCY2D, CRB1, RDH12, IQCB1 and SPATA7 in one family each, respectively. Six of the ten (60%) mutations identified are novel. Homozygosity mapping using Affymetrix 10K HMA GeneChip on the arRP family identified a novel nonsense mutation in MERTK. The mutations segregated within the family and was absent in 200 control chromosomes screened. In one of the eleven LCA families, the causative gene/mutation was not identified but many homozygous blocks were noted indicating that a possible novel locus/gene might be involved. The genotype and phenotype features, especially the fundus changes for AIPL1, RPE65, CRB1, RDH12 genes were as reported earlier.

  9. Autosomal-dominant Leber Congenital Amaurosis Caused by a Heterozygous CRX Mutation in a Father and Son.

    PubMed

    Arcot Sadagopan, Karthikeyan; Battista, Robert; Keep, Rosanne B; Capasso, Jenina E; Levin, Alex V

    2015-06-01

    Leber congenital amaurosis (LCA) is most often an autosomal recessive disorder. We report a father and son with autosomal dominant LCA due to a mutation in the CRX gene. DNA screening using an allele specific assay of 90 of the most common LCA-causing variations in the coding sequences of AIPL1, CEP290, CRB1, CRX, GUCY2D, RDH12 and RPE65 was performed on the father. Automated DNA sequencing of his son examining exon 3 of the CRX gene was subsequently performed. Both father and son have a heterozygous single base pair deletion of an adenine at codon 153 in the coding sequence of the CRX gene resulting in a frameshift mutation. Mutations involving the CRX gene may demonstrate an autosomal dominant inheritance pattern for LCA.

  10. Effect of rescue breathing by lay rescuers for out-of-hospital cardiac arrest caused by respiratory disease: a nationwide, population-based, propensity score-matched study.

    PubMed

    Fukuda, Tatsuma; Ohashi-Fukuda, Naoko; Kondo, Yutaka; Sera, Toshiki; Yahagi, Naoki

    2017-06-01

    The importance of respiratory care in cardiopulmonary resuscitation may vary depending on the cause of cardiac arrest. No previous study has investigated the effects of rescue breathing performed by a lay rescuer on the outcomes of patients with out-of-hospital cardiac arrest (OHCA) caused by intrinsic respiratory diseases. The aim of this study was to investigate whether rescue breathing performed by a lay rescuer is associated with outcomes after respiratory disease-related OHCA. In a nationwide, population-based, propensity score-matched study in Japan, among adult patients with OHCA caused by respiratory disease who received bystander cardiopulmonary resuscitation from January 1, 2005 to December 31, 2010, we compared patients with rescue breathing to those without rescue breathing. The primary outcome was neurologically favorable survival 1 month after OHCA. Of the eligible 14,781 patients, 4970 received rescue breathing from a lay rescuer and 9811 did not receive rescue breathing. In a propensity score-matched cohort (4897 vs. 4897 patients), the neurologically favorable survival rate was similar between patients with and without rescue breathing from a lay rescuer [0.9 vs. 0.7 %; OR 1.23 (95 % CI 0.79-1.93)]. Additionally, in subgroup analyses, rescue breathing was not associated with neurological outcome regardless of the type of rescuer [family member: adjusted OR 0.83 (95 % CI 0.39-1.70); or non-family member: adjusted OR 1.91 (95 % CI 0.79-5.35)]. Even among patients with OHCA caused by respiratory disease, rescue breathing performed by a lay rescuer was not associated with neurological outcomes, regardless of the type of lay rescuer.

  11. Objects tell us what action we can expect: dissociating brain areas for retrieval and exploitation of action knowledge during action observation in fMRI

    PubMed Central

    Schubotz, Ricarda I.; Wurm, Moritz F.; Wittmann, Marco K.; von Cramon, D. Yves

    2014-01-01

    Objects are reminiscent of actions often performed with them: knife and apple remind us on peeling the apple or cutting it. Mnemonic representations of object-related actions (action codes) evoked by the sight of an object may constrain and hence facilitate recognition of unrolling actions. The present fMRI study investigated if and how action codes influence brain activation during action observation. The average number of action codes (NAC) of 51 sets of objects was rated by a group of n = 24 participants. In an fMRI study, different volunteers were asked to recognize actions performed with the same objects presented in short videos. To disentangle areas reflecting the storage of action codes from those exploiting them, we showed object-compatible and object-incompatible (pantomime) actions. Areas storing action codes were considered to positively co-vary with NAC in both object-compatible and object-incompatible action; due to its role in tool-related tasks, we here hypothesized left anterior inferior parietal cortex (aIPL). In contrast, areas exploiting action codes were expected to show this correlation only in object-compatible but not incompatible action, as only object-compatible actions match one of the active action codes. For this interaction, we hypothesized ventrolateral premotor cortex (PMv) to join aIPL due to its role in biasing competition in IPL. We found left anterior intraparietal sulcus (IPS) and left posterior middle temporal gyrus (pMTG) to co-vary with NAC. In addition to these areas, action codes increased activity in object-compatible action in bilateral PMv, right IPS, and lateral occipital cortex (LO). Findings suggest that during action observation, the brain derives possible actions from perceived objects, and uses this information to shape action recognition. In particular, the number of expectable actions quantifies the activity level at PMv, IPL, and pMTG, but only PMv reflects their biased competition while observed action unfolds. PMID:25009519

  12. Model for Bi-objective emergency rescue vehicle routing optimization

    NASA Astrophysics Data System (ADS)

    Yang, Yuhang

    2017-03-01

    Vehicle routing problem is an important research topic in management science. In this paper, one vehicle can rescue multiple disaster points and two optimization objectives are rescue time and rescue effect. Rescue effect is expressed as the ratio of unloaded material to arrival time when rescue vehicles participate in rescue every time. In this paper, the corresponding emergency rescue model is established and the effectiveness of the model is verified by simulated annealing algorithm. It can provide the basis for practical decision-making.

  13. An oncolytic adenovirus enhances antiangiogenic and antitumoral effects of a replication-deficient adenovirus encoding endostatin by rescuing its selective replication in nasopharyngeal carcinoma cells

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Liu, Ran-yi, E-mail: liuranyi@mail.sysu.edu.cn; Zhou, Ling; Zhang, Yan-ling

    2013-12-13

    Highlights: •H101 promotes endostatin expression by Ad-Endo via rescuing Ad-Endo replication. •H101 rescued Ad-Endo replication by supplying E1A and E1B19k proteins. •Ad-Endo enhanced the cytotoxicity of H101 in NPC cells. •Ad-Endo and oncolytic Ad H101 have synergistic antitumor effects on NPC. -- Abstract: A replication-deficient adenovirus (Ad) encoding secreted human endostatin (Ad-Endo) has been demonstrated to have promising antiangiogenic and antitumoral effects. The E1B55k-deleted Ad H101 can selectively lyse cancer cells. In this study, we explored the antitumor effects and cross-interactions of Ad-Endo and H101 on nasopharyngeal carcinoma (NPC). The results showed that H101 dramatically promoted endostatin expression by Ad-Endomore » via rescuing Ad-Endo replication in NPC cells, and the expressed endostatin proteins significantly inhibited the proliferation of human umbilical vein endothelial cells. E1A and E1B19k products are required for the rescuing of H101 to Ad-Endo replication in CNE-1 and CNE-2 cells, but not in C666-1 cells. On the other hand, Ad-Endo enhanced the cytotoxicity of H101 by enhancing Ad replication in NPC cells. The combination of H101 and Ad-Endo significantly inhibited CNE-2 xenografts growth through the increased endostatin expression and Ad replication. These findings indicate that the combination of Ad-Endo gene therapy and oncolytic Ad therapeutics could be promising in comprehensive treatment of NPC.« less

  14. [Medical rescue of China National Earthquake Disaster Emergency Search and Rescue Team in Lushan earthquake].

    PubMed

    Liu, Ya-hua; Yang, Hui-ning; Liu, Hui-liang; Wang, Fan; Hu, Li-bin; Zheng, Jing-chen

    2013-05-01

    To summarize and analyze the medical mission of China National Earthquake Disaster Emergency Search and Rescue Team (CNESAR) in Lushan earthquake, to promote the medical rescue effectiveness incorporated with search and rescue. Retrospective analysis of medical work data by CNESAR from April 21th, 2013 to April 27th during Lushan earthquake rescue, including the medical staff dispatch and the wounded case been treated. The reasonable medical corps was composed by 22 members, including 2 administrators, 11 doctors [covering emergency medicine, orthopedics (joints and limbs, spinal), obstetrics and gynecology, gastroenterology, cardiology, ophthalmology, anesthesiology, medical rescue, health epidemic prevention, clinical laboratory of 11 specialties], 1 ultrasound technician, 5 nurses, 1 pharmacist, 1 medical instrument engineer and 1 office worker for propaganda. There were two members having psychological consultants qualifications. The medical work were carried out in seven aspects, including medical care assurance for the CNESAR members, first aid cooperation with search and rescue on site, clinical work in refugees' camp, medical round service for scattered village people, evacuation for the wounded, mental intervention, and the sanitary and anti-epidemic work. The medical work covered 24 small towns, and medical staff established 3 medical clinics at Taiping Town, Shuangshi Town of Lushan County and Baoxing County. Medical rescue, mental intervention for the old and kids, and sanitary and anti-epidemic were performed at the above sites. The medical corps had successful evacuated 2 severe wounded patients and treated the wounded over thousands. Most of the wounded were soft tissue injuries, external injury, respiratory tract infections, diarrhea, and heat stroke. Compared with the rescue action in 2008 Wenchuan earthquake, the aggregation and departure of rescue team in Lushan earthquake, the traffic control order in disaster area, the self-aid and buddy aid are better, which give rise to the casualties to the lowest. The medical mission incorporated with search and rescue work showed that the medical performance manner altered with stages, the medical staff match changed with the mission, and the focus related with rescue time.

  15. Rescue of the mouse DDK syndrome by parent-of-origin-dependent modifiers.

    PubMed

    Ideraabdullah, Folami Y; Kim, Kuikwon; Pomp, Daniel; Moran, Jennifer L; Beier, David; de Villena, Fernando Pardo-Manuel

    2007-02-01

    When females of the DDK inbred mouse strain are mated to males of other strains, 90-100% of the resulting embryos die during early embryonic development. This DDK syndrome lethality results from incompatibility between an ooplasmic DDK factor and a non-DDK paternal gene, which map to closely linked loci on chromosome 11. It has been proposed that the expression of the gene that encodes the ooplasmic factor is subject to allelic exclusion in oocytes. Previous studies have demonstrated the existence of recessive modifiers that increase lethality in the C57BL/6 and BALB/c strains. These modifiers are thought to skew the choice of allele undergoing allelic exclusion in the oocytes of heterozygous females. In the present study, we demonstrate the presence of modifiers in three Mus musculus domesticus wild-derived strains, PERA, PERC, and RBA. These modifiers completely rescued DDK syndrome lethality. We mapped the major locus that is responsible for rescue in PERA and PERC crosses to proximal chromosome 13 and named this locus Rmod1 (Rescue Modifier of the DDK Syndrome 1). Our experiments demonstrate that PERA or PERC alleles at Rmod1 rescue lethality independently of allelic exclusion. In addition, rescue of the lethal phenotype depends on the parental origin of the Rmod1 alleles; transmission through the dam leads to rescue, while transmission through the sire has no effect.

  16. A multicenter dose-escalation study of the analgesic and adverse effects of an oral cannabis extract (Cannador) for postoperative pain management.

    PubMed

    Holdcroft, Anita; Maze, Mervyn; Doré, Caroline; Tebbs, Susan; Thompson, Simon

    2006-05-01

    Cannabinoids have dose-related antinociceptive effects in animals. This clinical study aimed to investigate whether a single oral dose of cannabis plant extract (Cannador; Institute for Clinical Research, IKF, Berlin, Germany) could provide pain relief with minimal side effects for postoperative pain. Patients (aged 18-75 yr) were recruited and consented before surgery if patient-controlled analgesia was planned for provision of postoperative pain relief. Each patient received a single dose of 5, 10, or 15 mg Cannador if he or she had at least moderate pain after stopping patient-controlled analgesia. Starting with 5 mg, dose escalation was based on the number of patients requesting rescue analgesia and adverse effects. Pain relief, pain intensity, and side effects were recorded over 6 h and analyzed using tests for trend with dose. Rescue analgesia was requested by all 11 patients (100%) receiving 5 mg, 15 of 30 patient (50%) receiving 10 mg, and 6 of 24 patients (25%) receiving 15 mg Cannador (log rank test for trend in time to rescue analgesia with dose P < 0.001). There were also significant trends across the escalating dose groups for decreasing pain intensity at rest (P = 0.01), increasing sedation (P = 0.03), and more adverse events (P = 0.002). The number needed to treat to prevent one rescue analgesia request for the 10-mg and 15-mg doses, relative to 5 mg, were 2.0 (95% confidence interval, 1.5-3.1) and 1.3 (95% confidence interval, 1.1-1.7), respectively. The study was terminated because of a serious vasovagal adverse event in a patient receiving 15 mg. These significant dose-related improvements in rescue analgesia requirements in the 10 mg and 15 mg groups provide a number needed to treat that is equivalent to many routinely used analgesics without frequent adverse effects.

  17. Parecoxib sodium reduces the need for opioids after tonsillectomy in children: a double-blind placebo-controlled randomized clinical trial.

    PubMed

    Li, Xiuze; Zhou, Mengjun; Xia, Qing; Li, Juan

    2016-03-01

    Postoperative pain is a common phenomenon after pediatric tonsillectomy. This prospective randomized double-blind placebo-controlled clinical trial was performed to evaluate the analgesic efficacy of intravenous parecoxib sodium in children undergoing tonsillectomy. Sixty children (American Society of Anesthesiologists physical status I-III, aged three to seven years, and scheduled to undergo elective tonsillectomy under general anesthesia) were randomly allocated into one of two groups to receive intravenous parecoxib sodium 1 mg·kg(-1) (Group P, n = 30) or the same volume of saline (Group S, n = 30) just after induction of general anesthesia. Between-group comparisons were made for the number of patients requiring rescue morphine, total number of doses of postoperative rescue morphine, time to first rescue analgesic, postoperative pain and sedation scores, and adverse effects. Rescue morphine was given to more children in Group S (25/30, 83%) than in Group P (17/30, 57%) [relative risk (RR), 1.5; 95% confidence interval (CI), 1.0 to 2.1; P = 0.024]. The mean (SD) time to first rescue analgesic was shorter in Group S than in Group P [132 (54) min vs 193 (78) min, respectively; mean difference, 61; 95% CI, 26.6 to 96.1; P = 0.001]. The median (interquartile range [IQR]) Children's Hospital of Eastern Ontario Pain Scale scores in the postanesthesia care unit were lower in Group P than in Group S (7 [5-8] vs 9 [8-11], respectively; P = 0.001). The incidence of postoperative nausea and vomiting (PONV) was higher in Group S than in Group P [11/30 (37%) vs 4/30 (13%), respectively; RR, 2.8; 95% CI, 1.0 to 7.7; P = 0.037]. A single intravenous injection of parecoxib sodium 1 mg·kg(-1) after anesthesia induction is an effective method for the control of postoperative pain. It provides a morphine-sparing effect, prolongs the time to first rescue analgesic, and reduces PONV in children undergoing tonsillectomy.

  18. Developing a new perspective to study the health of survivors of Sichuan earthquakes in China: a study on the effect of post-earthquake rescue policies on survivors’ health-related quality of life

    PubMed Central

    2013-01-01

    Background Sichuan is a province in China with an extensive history of earthquakes. Recent earthquakes, including the Lushan earthquake in 2013, have resulted in thousands of people losing their homes and their families. However, there is a research gap on the efficiency of government support policies. Therefore, this study develops a new perspective to study the health of earthquake survivors, based on the effect of post-earthquake rescue policies on health-related quality of life (HRQOL) of survivors of the Sichuan earthquake. Methods This study uses data from a survey conducted in five hard-hit counties (Wenchuan, Qingchuan, Mianzhu, Lushan, and Dujiangyan) in Sichuan in 2013. A total of 2,000 questionnaires were distributed, and 1,672 were returned; the response rate was 83.6%. Results Results of the rescue policies scale and Medical Outcomes Study Short Form 36 (SF-36) scale passed the reliability test. The confirmatory factor analysis model showed that the physical component summary (PCS) directly affected the mental component summary (MCS). The results of structural equation model regarding the effects of rescue policies on HRQOL showed that the path coefficients of six policies (education, orphans, employment, poverty, legal, and social rescue policies) to the PCS of survivors were all positive and passed the test of significance. Finally, although only the path coefficient of the educational rescue policy to the MCS of survivors was positive and passed the test of significance, the other five policies affected the MCS indirectly through the PCS. Conclusions The general HRQOL of survivors is not ideal; the survivors showed a low satisfaction with the post-earthquake rescue policies. Further, the six post-earthquake rescue policies significantly improved the HRQOL of survivors and directly affected the promotion of the PCS of survivors. Aside from the educational rescue policy, all other policies affected the MCS indirectly through the PCS. This finding indicates relatively large differences in the effects of different post-earthquake rescue policies on the HRQOL of survivors. PMID:24168028

  19. Developing a new perspective to study the health of survivors of Sichuan earthquakes in China: a study on the effect of post-earthquake rescue policies on survivors' health-related quality of life.

    PubMed

    Liang, Ying; Wang, Xiukun

    2013-10-29

    Sichuan is a province in China with an extensive history of earthquakes. Recent earthquakes, including the Lushan earthquake in 2013, have resulted in thousands of people losing their homes and their families. However, there is a research gap on the efficiency of government support policies. Therefore, this study develops a new perspective to study the health of earthquake survivors, based on the effect of post-earthquake rescue policies on health-related quality of life (HRQOL) of survivors of the Sichuan earthquake. This study uses data from a survey conducted in five hard-hit counties (Wenchuan, Qingchuan, Mianzhu, Lushan, and Dujiangyan) in Sichuan in 2013. A total of 2,000 questionnaires were distributed, and 1,672 were returned; the response rate was 83.6%. Results of the rescue policies scale and Medical Outcomes Study Short Form 36 (SF-36) scale passed the reliability test. The confirmatory factor analysis model showed that the physical component summary (PCS) directly affected the mental component summary (MCS). The results of structural equation model regarding the effects of rescue policies on HRQOL showed that the path coefficients of six policies (education, orphans, employment, poverty, legal, and social rescue policies) to the PCS of survivors were all positive and passed the test of significance. Finally, although only the path coefficient of the educational rescue policy to the MCS of survivors was positive and passed the test of significance, the other five policies affected the MCS indirectly through the PCS. The general HRQOL of survivors is not ideal; the survivors showed a low satisfaction with the post-earthquake rescue policies. Further, the six post-earthquake rescue policies significantly improved the HRQOL of survivors and directly affected the promotion of the PCS of survivors. Aside from the educational rescue policy, all other policies affected the MCS indirectly through the PCS. This finding indicates relatively large differences in the effects of different post-earthquake rescue policies on the HRQOL of survivors.

  20. Who is going to rescue the rescuers? Post-traumatic stress disorder among rescue workers operating in Greece during the European refugee crisis.

    PubMed

    Sifaki-Pistolla, Dimitra; Chatzea, Vasiliki-Eirini; Vlachaki, Sofia-Aikaterini; Melidoniotis, Evangelos; Pistolla, Georgia

    2017-01-01

    During the European refugee crisis, numerous Greek and international rescue workers are operating in Lesvos, offering search, rescue, and first aid services. Exposure to stressful life events while engaging in this rescue work can result in developing Post-Traumatic Stress Disorder (PTSD). The study aimed to assess the prevalence of PTSD and explore potential differences between different categories of rescuers. A cross-sectional study was conducted among 217 rescue workers. Participants were grouped according to affiliation: "Greek Professionals Rescuers/GPR", "International Professionals Rescuers/IPR" and "Volunteer Rescuers/VR". The PTSD Checklist-Civilian Version (PCL-C) was utilized. All tests were two-tailed (a = 0.05). Mann-Whitney, Kruskal-Wallis, and multivariate logistic regression were performed. Overall probable PTSD prevalence found was 17.1%. Rates varied significantly per rescuer's category; 23.1% in GPR, 11.8% in IPR, and 14.6% in VR (p = 0.02). GPR demonstrated the highest risk compared to IPR and VR (p < 0.001). Females had approximately two times higher risk. Other significant risk factors included marital status, age, and number of children. Lack of previous experience, longer operation period, longer shift hours, and handling dead refugees and dead children were also considered major risk factors. Rescue workers providing substantial aid to the refugees and migrants at Lesvos experience significant psychological distress. The present findings indicate the urgent need for targeted interventions. Further studies are needed to address long-term effects of the refugee crisis on rescuers, and explore effective measures to prevent PTSD.

  1. Propranolol Effects on Decompression Sickness in a Simulated DISSUB Rescue in Swine.

    PubMed

    Forbes, Angela S; Regis, David P; Hall, Aaron A; Mahon, Richard T; Cronin, William A

    2017-04-01

    Disabled submarine (DISSUB) survivors may face elevated CO2 levels and inert gas saturation, putting them at risk for CO2 toxicity and decompression sickness (DCS). Propranolol was shown to reduce CO2 production in an experimental DISSUB model in humans but its effects on DCS in a DISSUB rescue scenario are unknown. A 100% oxygen prebreathe (OPB) reduces DCS incidence and severity and is incorporated into some DISSUB rescue protocols. We used a swine model of DISSUB rescue to study the effect of propranolol on DCS incidence and mortality with and without an OPB. In Experiment 1, male Yorkshire Swine (70 kg) were pressurized to 2.8 ATA for 22 h. Propranolol 1.0 mg · kg-1 (IV) was administered at 21.25 h. At 22 h, the animal was rapidly decompressed and observed for DCS type, onset time, and mortality. Experimental animals (N = 21; 69 ± 4.1 kg), PROP1.0, were compared to PROP1.0-OPB45 (N = 8; 69 ± 2.8 kg) with the same dive profile, except for a 45 min OPB prior to decompression. In Experiment 2, the same methodology was used with the following changes: swine pressurized to 2.8 ATA for 28 h; experimental group (N = 25; 67 ± 3.3 kg), PROP0.5 bis, propranolol 0.5 mg · kg-1 bis (twice) (IV) was administered at 22 h and 26 h. Control animals (N = 25; 67 ± 3.9 kg) received normal saline. OPB reduced mortality in PROP1.0-OBP45 compared to PROP1.0 (0% vs. 71%). PROP0.5 bis had increased mortality compared to CONTROL (60-% vs. 4%). Administration of beta blockers prior to saturation decompression appears to increase DCS and worsen mortality in a swine model; however, their effects in bounce diving remain unknown.Forbes AS, Regis DP, HallAA, Mahon RT, Cronin WA. Propranolol effects on decompression sickness in a simulated DISSUB rescue in swine. Aerosp Med Hum Perform. 2017; 88(4):385-391.

  2. FEMA Urban Search and Rescue Teams: Considering an Improved Strategy for an Evolving Homeland Security Enterprise

    DTIC Science & Technology

    2012-09-01

    and Rescue (US&R) teams be used more effectively and efficiently in the Homeland Security Enterprise ( HSE )? 1. Are there other strategies that would...allow the FEMA US&R resources to be more adaptable in the HSE ? 2. What other disciplines could be integrated with the FEMA US&R task forces to...consideration of the questions: 1. Can the FEMA US&R teams be used more effectively in the Homeland Security Enterprise ( HSE )? 2. Are there other

  3. Assessing the efficacy of rescue equipment in lifeguard resuscitation efforts for drowning.

    PubMed

    Barcala-Furelos, Roberto; Szpilman, David; Palacios-Aguilar, Jose; Costas-Veiga, Javier; Abelairas-Gomez, Cristian; Bores-Cerezal, Antonio; López-García, Sergio; Rodríguez-Nuñez, Antonio

    2016-03-01

    The whole drowning process usually occurs within seconds to a few minutes. An early rescue may stop and/or prevent most medical complications. Fins, rescue tube, and rescue board (RB) are the equipment most frequently used by lifeguards. Our objective was to compare, in a water rescue quasiexperimental trial, these different pieces of rescue equipment to define the safest and with the lower rescue time as well as to assess their effects on the lifeguards' physiological state and cardiopulmonary resuscitation (CPR) performance. A controlled trial was conducted to study the time effect of 4 different rescue techniques and assess CPR quality, along with the physiological effects of each rescue technique (blood lactate and subjective Borg's scale effort perception) on 35 lifeguards. Among the final sample subjects (n = 23), a total of 92 rescues were completed. Total water rescue time was longer without equipment (NE). The total rescue time was significantly lower using RB (P < .001). Similar good quality of CPR before and after water rescue was observed in all trials (P > .05), although correct ventilations represented less than 50% of total in all trials. Blood lactate increased after all rescues. The subjective effort Borg's scale showed significantly less effort using RB vs without equipment, fins, and fins and rescue tube. The use of propelling and/or floating equipment saves precious time with repercussions in the reduction of drowning mortality and morbidity. The RB offers a significant advantage. Lifeguards need more CPR training, especially considering the importance of efficient ventilations for drowning victims. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Chewing rescues stress-suppressed hippocampal long-term potentiation via activation of histamine H1 receptor.

    PubMed

    Ono, Yumie; Kataoka, Tsuyoshi; Miyake, Shinjiro; Sasaguri, Kenichi; Sato, Sadao; Onozuka, Minoru

    2009-08-01

    We have previously found in rats that chewing, an active behavioral strategy to cope with a stressful situation, rescues long-term potentiation (LTP) in the hippocampus through activating stress-suppressed N-methyl-D-aspartate (NMDA) receptor function. To further examine the mechanisms underlying this ameliorative effect of chewing, we studied the involvement of the histaminergic system, which has been shown to be activated by mastication, in the LTP of hippocampal slices of rats that were allowed to chew a wooden stick during exposure to immobilization stress. Chewing failed to rescue stress-suppressed LTP in the rats treated with histamine H1 receptor (H1R) antagonist pyrilamine (5 mg/kg, i.p.) before exposure to stress, although administration of pyrilamine did not affect LTP in naive rats and in stressed rats that did not chew. However, when pyrilamine was administrated immediately after exposure to stress, chewing rescued LTP whose magnitude was statistically comparable to that in the rats that chewed without drug treatment. These results suggest that chewing-induced histamine release in the hippocampus and the subsequent H1 receptor activation may be essential to rescue stress-suppressed synaptic plasticity.

  5. Group Task Force on Satellite Rescue and Repair

    NASA Astrophysics Data System (ADS)

    1992-09-01

    The Group Task Force was chartered by the Administrator of NASA to recommend 'a policy outlining the criteria, the design standards, and the pricing model to guide NASA in assessing the responsibilities for government and nongovernment Satellite Rescue and Repair Missions.' Criteria for accepting such missions, risks, and benefits to all sectors of our economy involved in satellite services, adequacy of planning and training, and the impact on NASA's primary mission were reviewed. The Group began by asking a more fundamental question; is satellite rescue and repair a logical element of NASA's mission? Factors considered were: (1) the probability of rescue or repair opportunities arising; (2) the economic justification for such attempts; (3) the benefits to NASA, both from such ad hoc learning experiences in space operations and the impact on the public perception of NASA; (4) the effect of such unanticipated missions on NASA's scheduled activities; (5) any potential effect on NASA's technical capability to work in space; and (6) any potential effect on U.S. economic competitiveness.

  6. Group Task Force on Satellite Rescue and Repair

    NASA Technical Reports Server (NTRS)

    1992-01-01

    The Group Task Force was chartered by the Administrator of NASA to recommend 'a policy outlining the criteria, the design standards, and the pricing model to guide NASA in assessing the responsibilities for government and nongovernment Satellite Rescue and Repair Missions.' Criteria for accepting such missions, risks, and benefits to all sectors of our economy involved in satellite services, adequacy of planning and training, and the impact on NASA's primary mission were reviewed. The Group began by asking a more fundamental question; is satellite rescue and repair a logical element of NASA's mission? Factors considered were: (1) the probability of rescue or repair opportunities arising; (2) the economic justification for such attempts; (3) the benefits to NASA, both from such ad hoc learning experiences in space operations and the impact on the public perception of NASA; (4) the effect of such unanticipated missions on NASA's scheduled activities; (5) any potential effect on NASA's technical capability to work in space; and (6) any potential effect on U.S. economic competitiveness.

  7. Corrector VX-809 stabilizes the first transmembrane domain of CFTR.

    PubMed

    Loo, Tip W; Bartlett, M Claire; Clarke, David M

    2013-09-01

    Processing mutations that inhibit folding and trafficking of CFTR are the main cause of cystic fibrosis (CF). A potential CF therapy would be to repair CFTR processing mutants. It has been demonstrated that processing mutants of P-glycoprotein (P-gp), CFTR's sister protein, can be efficiently repaired by a drug-rescue mechanism. Many arginine suppressors that mimic drug-rescue have been identified in the P-gp transmembrane (TM) domains (TMDs) that rescue by forming hydrogen bonds with residues in adjacent helices to promote packing of the TM segments. To test if CFTR mutants could be repaired by a drug-rescue mechanism, we used truncation mutants to test if corrector VX-809 interacted with the TMDs. VX-809 was selected for study because it is specific for CFTR, it is the most effective corrector identified to date, but it has limited clinical benefit. Identification of the VX-809 target domain will help to develop correctors with improved clinical benefits. It was found that VX-809 rescued truncation mutants lacking the NBD2 and R domains. When the remaining domains (TMD1, NBD1, TMD2) were expressed as separate polypeptides, VX-809 only increased the stability of TMD1. We then performed arginine mutagenesis on TM6 in TMD1. Although the results showed that TM6 had distinct lipid and aqueous faces, CFTR was different from P-gp as no arginine promoted maturation of CFTR processing mutants. The results suggest that TMD1 contains a VX-809 binding site, but its mechanism differed from P-gp drug-rescue. We also report that V510D acts as a universal suppressor to rescue CFTR processing mutants. Copyright © 2013 Elsevier Inc. All rights reserved.

  8. Actin-interacting Protein 1 Promotes Disassembly of Actin-depolymerizing Factor/Cofilin-bound Actin Filaments in a pH-dependent Manner.

    PubMed

    Nomura, Kazumi; Hayakawa, Kimihide; Tatsumi, Hitoshi; Ono, Shoichiro

    2016-03-04

    Actin-interacting protein 1 (AIP1) is a conserved WD repeat protein that promotes disassembly of actin filaments when actin-depolymerizing factor (ADF)/cofilin is present. Although AIP1 is known to be essential for a number of cellular events involving dynamic rearrangement of the actin cytoskeleton, the regulatory mechanism of the function of AIP1 is unknown. In this study, we report that two AIP1 isoforms from the nematode Caenorhabditis elegans, known as UNC-78 and AIPL-1, are pH-sensitive in enhancement of actin filament disassembly. Both AIP1 isoforms only weakly enhance disassembly of ADF/cofilin-bound actin filaments at an acidic pH but show stronger disassembly activity at neutral and basic pH values. However, a severing-defective mutant of UNC-78 shows pH-insensitive binding to ADF/cofilin-decorated actin filaments, suggesting that the process of filament severing or disassembly, but not filament binding, is pH-dependent. His-60 of AIP1 is located near the predicted binding surface for the ADF/cofilin-actin complex, and an H60K mutation of AIP1 partially impairs its pH sensitivity, suggesting that His-60 is involved in the pH sensor for AIP1. These biochemical results suggest that pH-dependent changes in AIP1 activity might be a novel regulatory mechanism of actin filament dynamics. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  9. Tactile massage reduces rescue doses for pain and anxiety: an observational study.

    PubMed

    Pedersen, Karina; Björkhem-Bergman, Linda

    2018-03-01

    The aim of this study was to evaluate the effect of tactile massage (TM) on palliative care patients. An observational study at a hospice ward in Sweden was carried out. Forty-one palliative patients were offered TM, at an average of three treatments per patient. Before and after every treatment, self-assessed pain, well-being and anxiety according to the Edmonton Symptom Assessment Scale (0-10) were recorded. In addition, the number of rescue doses for pain and anxiety was monitored 24 hours before and after the treatment and in two consecutive days before the patients were offered TM (control data). TM resulted in improvement of self-assessed pain by 1.7 points (SD 1.6), anxiety by 2.3 points (SD 2.0) and well-being by 2.6 points (SD 1.4). The number of rescue doses for pain was reduced from 1.6 to 0.84 doses/patient (P<0.001) and for anxiety from 0.52 to 0.24 doses/patient (P<0.01). The number of rescue doses was not changed in the same patients in two consecutive days before the patients were offered TM. The effect was evident already after the first treatment and did not increase further with repeated treatments. No patients reported any harmful effects of the treatment. TM reduced the need for administration of rescue doses for pain and anxiety and improved well-being in palliative care patients. Larger randomised studies with parallel control groups are needed to confirm the findings from this observational pilot study. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  10. Comparison of Efficacy of Epidural Ropivacaine versus Bupivacaine for Postoperative Pain Relief in Total Knee Replacement Surgeries.

    PubMed

    Bhasin, Sidharth; Dhar, Mridul; Sreevastava, Deepak Kumar; Nair, Rajiv; Chandrakar, Saurabh

    2018-01-01

    Epidural analgesia has become the standard of care for knee replacement surgeries worldwide. Bupivacaine has been used successfully for many years. Epidural ropivacaine is now being used increasingly and seems to have benefits other than just pain relief, in terms of a better safety profile. To compare the efficacy of bupivacaine 0.125% (Group B) versus two concentrations of ropivacaine 0.1% (Group R1) and 0.2% (Group R2), in terms of pain scores, requirement of rescue analgesia, related adverse effects, and duration of postoperative (PO) hospital stay. A retrospective study was conducted from the acute pain service data of patients who underwent joint replacement surgeries in one or both limbs, over a span of 6 months. Patients were allocated to and analyzed under one of the three groups based on the drug concentration used postoperatively by epidural infusion. Data retrieved were demographic data, daily average visual analog scale (VAS) pain scores, rescue analgesia given, adverse effects, and PO hospital stay days for all three groups. Demographic data were comparable between the three groups. Daily average VAS pain scores on days 1 and 2 were significantly higher in Group R1. Groups B and R2 were comparable. There was significantly more requirement of rescue analgesia in Group R1 on day 1. Day 2 showed no significant difference in rescue analgesic requirement in all three groups. Days of PO hospital stay were significantly higher in Group R1. Adverse effects such as hypotension and delayed motor block were higher in Group B. Ropivacaine 0.2% and bupivacaine 0.125% were equally efficacious in terms of VAS pain scores, rescue analgesic requirement, and duration of PO hospital stay, but ropivacaine had a better safety profile in terms of less hypotension and lesser motor block.

  11. Comparison of Efficacy of Epidural Ropivacaine versus Bupivacaine for Postoperative Pain Relief in Total Knee Replacement Surgeries

    PubMed Central

    Bhasin, Sidharth; Dhar, Mridul; Sreevastava, Deepak Kumar; Nair, Rajiv; Chandrakar, Saurabh

    2018-01-01

    Background: Epidural analgesia has become the standard of care for knee replacement surgeries worldwide. Bupivacaine has been used successfully for many years. Epidural ropivacaine is now being used increasingly and seems to have benefits other than just pain relief, in terms of a better safety profile. Aim: To compare the efficacy of bupivacaine 0.125% (Group B) versus two concentrations of ropivacaine 0.1% (Group R1) and 0.2% (Group R2), in terms of pain scores, requirement of rescue analgesia, related adverse effects, and duration of postoperative (PO) hospital stay. Materials and Methods: A retrospective study was conducted from the acute pain service data of patients who underwent joint replacement surgeries in one or both limbs, over a span of 6 months. Patients were allocated to and analyzed under one of the three groups based on the drug concentration used postoperatively by epidural infusion. Data retrieved were demographic data, daily average visual analog scale (VAS) pain scores, rescue analgesia given, adverse effects, and PO hospital stay days for all three groups. Results: Demographic data were comparable between the three groups. Daily average VAS pain scores on days 1 and 2 were significantly higher in Group R1. Groups B and R2 were comparable. There was significantly more requirement of rescue analgesia in Group R1 on day 1. Day 2 showed no significant difference in rescue analgesic requirement in all three groups. Days of PO hospital stay were significantly higher in Group R1. Adverse effects such as hypotension and delayed motor block were higher in Group B. Conclusion: Ropivacaine 0.2% and bupivacaine 0.125% were equally efficacious in terms of VAS pain scores, rescue analgesic requirement, and duration of PO hospital stay, but ropivacaine had a better safety profile in terms of less hypotension and lesser motor block. PMID:29628549

  12. Rescue of cardiac leptin receptors in db/db mice prevents myocardial triglyceride accumulation.

    PubMed

    Hall, Michael E; Maready, Matthew W; Hall, John E; Stec, David E

    2014-08-01

    Increased leptin levels have been suggested to contribute to cardiac hypertrophy and attenuate cardiac lipid accumulation in obesity, although it has been difficult to separate leptin's direct effects from those caused by changes in body weight and adiposity. To determine whether leptin attenuates cardiac lipid accumulation in obesity or directly causes left ventricular hypertrophy (LVH), we generated a novel mouse model in which the long form of the leptin receptor (LepR) was "rescued" only in cardiomyocytes of obese db/db mice. Reexpression of cardiomyocyte leptin receptors in db/db mice did not cause LVH but reduced cardiac triglycerides and improved cardiac function. Compared with lean wild-type (WT) or db/db-cardiac LepR rescue mice, db/db mice exhibited significantly lower E/A ratio, a measurement of early to late diastolic filling, which averaged 1.5 ± 0.07 in db/db vs. 1.9 ± 0.08 and 1.8 ± 0.11 in WT and db/db-cardiac LepR rescue mice, respectively. No differences in systolic function were observed. Although db/db and db/db-cardiac LepR rescue mice exhibited similar increases in plasma triglycerides, insulin, glucose, and body weight, cardiac triglycerides were significantly higher in db/db compared with WT and db/db cardiac LepR rescue mice, averaging 13.4 ± 4.2 vs. 3.8 ± 1.6 vs. 3.8 ± 0.7 mg/g, respectively. These results demonstrate that despite significant obesity and increases in plasma glucose and triglycerides, db/db cardiac LepR rescue mice are protected against myocardial lipid accumulation. However, we found no evidence that leptin directly causes LVH. Copyright © 2014 the American Physiological Society.

  13. Attenuation of cadmium-induced necrotic cell death by necrostatin-1: Potential necrostatin-1 acting sites

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hsu, T.-S.; Yang, P.-M.; Tsai, J.-S.

    2009-03-01

    Cadmium (Cd) induces necrotic death in Chinese hamster ovary (CHO) K1 cells and we have established the responsible signaling pathway. Reportedly, necrostatin-1 (Nec-1) rescues cells from necrotic death by mediating through the death domain receptor (DR) signaling pathway. We show here that Nec-1 also effectively attenuates necrotic death triggered by Cd. Two other treatments that cause necrotic cell death, one can (z-VAD-fmk/TNF-{alpha} on U937 cells) and the other cannot (etherynic acid (EA) on DLD-1 cells) be rescued by Nec-1, were also studied in parallel for comparison. Results show that Nec-1 is ineffectual in modulating intracellular calcium contents, calpain activity (amore » downstream protease), or reactive oxygen species production. It can counteract the reduction in mitochondrial membrane potential (MMP) caused by treating CHO K1 or U937 cells with necrosis-inducing agent. However, this effect was not found in EA-treated DLD-1 cells. Notably, Nec-1 elevates NF-{kappa}B activity in the presence or absence of necrosis-inducing agents. Our study shows that, in addition to DR-mediated necrosis, Nec-1 is effective in attenuating Cd-induced necrosis. It rescues cells with reduced MMP implying that mitochondrion is its major acting site.« less

  14. An unconventional origin of metal-ion rescue and inhibition in the Tetrahymena group I ribozyme reaction.

    PubMed Central

    Shan, S O; Herschlag, D

    2000-01-01

    The presence of catalytic metal ions in RNA active sites has often been inferred from metal-ion rescue of modified substrates and sometimes from inhibitory effects of alternative metal ions. Herein we report that, in the Tetrahymena group I ribozyme reaction, the deleterious effect of a thio substitution at the pro-Sp position of the reactive phosphoryl group is rescued by Mn2+. However, analysis of the reaction of this thio substrate and of substrates with other modifications strongly suggest that this rescue does not stem from a direct Mn2+ interaction with the Sp sulfur. Instead, the apparent rescue arises from a Mn2+ ion interacting with the residue immediately 3' of the cleavage site, A(+1), that stabilizes the tertiary interactions between the oligonucleotide substrate (S) and the active site. This metal site is referred to as site D herein. We also present evidence that a previously observed Ca2+ ion that inhibits the chemical step binds to metal site D. These and other observations suggest that, whereas the interactions of Mn2+ at site D are favorable for the chemical reaction, the Ca2+ at site D exerts its inhibitory effect by disrupting the alignment of the substrates within the active site. These results emphasize the vigilance necessary in the design and interpretation of metal-ion rescue and inhibition experiments. Conversely, in-depth mechanistic analysis of the effects of site-specific substrate modifications can allow the effects of specific metal ion-RNA interactions to be revealed and the properties of individual metal-ion sites to be probed, even within the sea of metal ions bound to RNA. PMID:10864040

  15. Rescue Manual. Module 8.

    ERIC Educational Resources Information Center

    Ohio State Univ., Columbus. Instructional Materials Lab.

    This learner manual for rescuers covers the current techniques or practices required in the rescue service. The eighth of 10 modules contains 6 chapters: (1) trench rescue; (2) shoring and tunneling techniques; (3) farm accident rescue; (4) wilderness search and rescue; (5) aircraft rescue; and (6) helicopter information. Key points, an…

  16. Clinical and economic analysis of rescue intracytoplasmic sperm injection cycles.

    PubMed

    Shalom-paz, Einat; Alshalati, Jana; Shehata, Fady; Jimenez, Luis; Son, Weon-Young; Holzer, Hananel; Tan, Seang Lin; Almog, Benny

    2011-12-01

    To identify clinical and embryological factors that may predict success in rescue intracytoplasmic sperm injection (ICSI) cycles (after total fertilization failure has occurred) and to evaluate the cost effectiveness of rescue ICSI strategy. Additionally, follow-up of 20 rescue ICSI pregnancies is reported. Retrospective analysis of total fertilization failure cycles. University-based tertiary medical center. In total, 92 patients who had undergone conventional in-vitro fertilization (IVF) cycles with total fertilization failure were included. The patients were divided into two subgroups: those who conceived through rescue ICSI and those who did not. The pregnant members of the rescue ICSI subgroup were found to be significantly younger (32.9 ± 4.2 vs. 36.3 ± 4.5, respectively, p = 0.0035,) and to have better-quality embryos than those who did not conceive (cumulative embryo score: 38.3 ± 20.4 vs. 29.3 ± 14.7, p = 0.025). Cost effectiveness analysis showed 25% reduction in the cost per live birth when rescue ICSI is compared to cycle cancellation approach. The pregnancies follow-up did not show adverse perinatal outcome. Rescue ICSI is an option for salvaging IVF cycles complicated by total fertilization failure. Success in rescue ICSI was found to be associated with younger age and higher quality of embryos. Furthermore, the cost effectiveness of rescue ICSI in terms of total fertilization failure was found to be worthwhile.

  17. BACE1 inhibition by microdose lithium formulation NP03 rescues memory loss and early stage amyloid neuropathology.

    PubMed

    Wilson, E N; Do Carmo, S; Iulita, M F; Hall, H; Ducatenzeiler, A; Marks, A R; Allard, S; Jia, D T; Windheim, J; Cuello, A C

    2017-08-01

    Lithium is first-line therapy for bipolar affective disorder and has recently been shown to have protective effects in populations at risk for Alzheimer's disease (AD). However, the mechanism underlying this protection is poorly understood and consequently limits its possible therapeutic application in AD. Moreover, conventional lithium formulations have a narrow therapeutic window and are associated with a severe side effect profile. Here we evaluated a novel microdose formulation of lithium, coded NP03, in a well-characterized rat model of progressive AD-like amyloid pathology. This formulation allows microdose lithium delivery to the brain in the absence of negative side effects. We found that NP03 rescued key initiating components of AD pathology, including inactivating GSK-3β, reducing BACE1 expression and activity, and reducing amyloid levels. Notably, NP03 rescued memory loss, impaired CRTC1 promoter binding of synaptic plasticity genes and hippocampal neurogenesis. These results raise the possibility that NP03 be of therapeutic value in the early or preclinical stages of AD.

  18. BACE1 inhibition by microdose lithium formulation NP03 rescues memory loss and early stage amyloid neuropathology

    PubMed Central

    Wilson, E N; Do Carmo, S; Iulita, M F; Hall, H; Ducatenzeiler, A; Marks, A R; Allard, S; Jia, D T; Windheim, J; Cuello, A C

    2017-01-01

    Lithium is first-line therapy for bipolar affective disorder and has recently been shown to have protective effects in populations at risk for Alzheimer’s disease (AD). However, the mechanism underlying this protection is poorly understood and consequently limits its possible therapeutic application in AD. Moreover, conventional lithium formulations have a narrow therapeutic window and are associated with a severe side effect profile. Here we evaluated a novel microdose formulation of lithium, coded NP03, in a well-characterized rat model of progressive AD-like amyloid pathology. This formulation allows microdose lithium delivery to the brain in the absence of negative side effects. We found that NP03 rescued key initiating components of AD pathology, including inactivating GSK-3β, reducing BACE1 expression and activity, and reducing amyloid levels. Notably, NP03 rescued memory loss, impaired CRTC1 promoter binding of synaptic plasticity genes and hippocampal neurogenesis. These results raise the possibility that NP03 be of therapeutic value in the early or preclinical stages of AD. PMID:28763060

  19. 30 CFR 49.7 - Physical requirements for mine rescue team.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Physical requirements for mine rescue team. 49... EDUCATION AND TRAINING MINE RESCUE TEAMS Mine Rescue Teams for Underground Metal and Nonmetal Mines § 49.7 Physical requirements for mine rescue team. (a) Each member of a mine rescue team shall be examined...

  20. 30 CFR 49.7 - Physical requirements for mine rescue team.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Physical requirements for mine rescue team. 49... EDUCATION AND TRAINING MINE RESCUE TEAMS Mine Rescue Teams for Underground Metal and Nonmetal Mines § 49.7 Physical requirements for mine rescue team. (a) Each member of a mine rescue team shall be examined...

  1. 30 CFR 49.7 - Physical requirements for mine rescue team.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Physical requirements for mine rescue team. 49... EDUCATION AND TRAINING MINE RESCUE TEAMS Mine Rescue Teams for Underground Metal and Nonmetal Mines § 49.7 Physical requirements for mine rescue team. (a) Each member of a mine rescue team shall be examined...

  2. LRSAM1 Depletion Affects Neuroblastoma SH-SY5Y Cell Growth and Morphology: The LRSAM1 c.2047-1G>A Loss-of-Function Variant Fails to Rescue The Phenotype.

    PubMed

    Minaidou, Anna; Nicolaou, Paschalis; Christodoulou, Kyproula

    2018-10-01

    Deleterious variants in LRSAM1, a RING finger ubiquitin ligase which is also known as TSG101-associated ligase (TAL), have recently been associated with Charcot-Marie-Tooth disease type 2P (CMT2P). The mechanism by which mutant LRSAM1 contributes to the development of neuropathy is currently unclear. The aim of this study was to induce LRSAM1 deficiency in a neuronal cell model, observe its effect on cell growth and morphology and attempt to rescue the phenotype with ancestral and mutant LRSAM1 transfections. In this experimental study, we investigated the effect of LRSAM1 downregulation on neuroblastoma SH-SY5Y cells by siRNA technology where cells were transfected with siRNA against LRSAM1. The effects on the expression levels of TSG101, the only currently known LRSAM1 interacting molecule, were also examined. An equal dosage of ancestral or mutant LRSAM1 construct was transfected in LRSAM1-downregulated cells to investigate its effect on the phenotype of the cells and whether cell proliferation and morphology could be rescued. A significant reduction in TSG101 levels was observed with the downregulation of LRSAM1. In addition, LRSAM1 knockdown significantly decreased the growth rate of SH-SY5Y cells which is caused by a decrease in cell proliferation. An effect on cell morphology was also observed. Furthermore, we overexpressed the ancestral and the c.2047-1G>A mutant LRSAM1 in knocked down cells. Ancestral LRSAM1 recovered cell proliferation and partly the morphology, however, the c.2047-1G>A mutant did not recover cell proliferation and further aggravated the observed changes in cell morphology. Our findings suggest that depletion of LRSAM1 affects neuroblastoma cells growth and morphology and that overexpression of the c.2047-1G>A mutant form, unlike the ancestral LRSAM1, fails to rescue the phenotype. Copyright© by Royan Institute. All rights reserved.

  3. Lunar mission safety and rescue: Escape/rescue analysis and plan

    NASA Technical Reports Server (NTRS)

    1971-01-01

    The results are presented of the technical analysis of escape/rescue/survival situations, crew survival techniques, alternate escape/rescue approaches and vehicles, and the advantages and disadvantages of each for advanced lunar exploration. Candidate escape/rescue guidelines are proposed and elements of a rescue plan developed. The areas of discussions include the following: lunar arrival/departure operations, lunar orbiter operations, lunar surface operations, lunar surface base escape/rescue analysis, lander tug location operations, portable airlock, emergency pressure suit, and the effects of no orbiting lunar station, no lunar surface base, and no foreign lunar orbit/surface operations on the escape/rescue plan.

  4. Evaluation of a topical treatment for the relief of sensitive skin

    PubMed Central

    Heinicke, Ingrid R; Adams, Damian H; Barnes, Tanya M; Greive, Kerryn A

    2015-01-01

    Background Approximately, 50% of the population claim to have sensitive skin, which has created an important challenge for dermatologists and the cosmetic industry. This study evaluates the properties of QV Face Rescue Gel (Rescue Gel) that contains a combination of moisturizing and anti-irritant ingredients, and which is used to relieve the symptoms of sensitive facial skin. Methods The ability of Rescue Gel to induce collagen types I and III in cultured neonatal human foreskin fibroblasts compared to transforming growth factor beta 1, a known potent inducer of collagen types I and III, was measured using immunofluorescence staining. Furthermore, healthy volunteers were recruited to measure the potential for Rescue Gel to reduce erythema induced by solar-simulated ultraviolet radiation on the skin compared to 0.5% hydrocortisone cream (positive control) as well as it’s ability to decrease transepidermal water loss compared to baseline levels. In addition, the formulation was tested for its potential to be 1) nonstinging using a facial sting/discomfort assay performed on volunteers who reacted positively to lactic acid, 2) nonirritating as determined by repeat insult patch tests, and 3) noncomedogenic. Results Rescue Gel significantly induced collagen types I and III in cultured human foreskin fibroblasts similarly to transforming growth factor beta 1. In volunteers, Rescue Gel was shown to significantly reduce erythema induced by solar-simulated ultraviolet radiation similarly to 0.5% hydrocortisone, and to significantly reduce transepidermal water loss compared to baseline levels. Further, the formulation was found to be nonstinging, nonirritating, and noncomedogenic. No adverse events were observed. Conclusion In this study, Rescue Gel has been shown to exhibit properties that make it effective for use on sensitive or irritated facial skin, without exacerbation of the symptoms associated with sensitive skin. PMID:26251625

  5. Mortality among survivors of the Sept 11, 2001, World Trade Center disaster: results from the World Trade Center Health Registry cohort.

    PubMed

    Jordan, Hannah T; Brackbill, Robert M; Cone, James E; Debchoudhury, Indira; Farfel, Mark R; Greene, Carolyn M; Hadler, James L; Kennedy, Joseph; Li, Jiehui; Liff, Jonathan; Stayner, Leslie; Stellman, Steven D

    2011-09-03

    The Sept 11, 2001 (9/11) World Trade Center (WTC) disaster has been associated with several subacute and chronic health effects, but whether excess mortality after 9/11 has occurred is unknown. We tested whether excess mortality has occurred in people exposed to the WTC disaster. In this observational cohort study, deaths occurring in 2003-09 in WTC Health Registry participants residing in New York City were identified through linkage to New York City vital records and the National Death Index. Eligible participants were rescue and recovery workers and volunteers; lower Manhattan area residents, workers, school staff and students; and commuters and passers-by on 9/11. Study participants were categorised as rescue and recovery workers (including volunteers), or non-rescue and non-recovery participants. Standardised mortality ratios (SMR) were calculated with New York City rates from 2000-09 as the reference. Within the cohort, proportional hazards were used to examine the relation between a three-tiered WTC-related exposure level (high, intermediate, or low) and total mortality. We identified 156 deaths in 13,337 rescue and recovery workers and 634 deaths in 28,593 non-rescue and non-recovery participants. All-cause SMRs were significantly lower than that expected for rescue and recovery participants (SMR 0·45, 95% CI 0·38-0·53) and non-rescue and non-recovery participants (0·61, 0·56-0·66). No significantly increased SMRs for diseases of the respiratory system or heart, or for haematological malignancies were found. In non-rescue and non-recovery participants, both intermediate and high levels of WTC-related exposure were significantly associated with mortality when compared with low exposure (adjusted hazard ratio 1·22, 95% CI 1·01-1·48, for intermediate exposure and 1·56, 1·15-2·12, for high exposure). High levels of exposure in non-rescue and non-recovery individuals, when compared with low exposed non-rescue and non-recovery individuals, were associated with heart-disease-related mortality (adjusted hazard ratio 2·06, 1·10-3·86). In rescue and recovery participants, level of WTC-related exposure was not significantly associated with all-cause mortality (adjusted hazard ratio 1·25, 95% CI 0·56-2·78, for high exposure and 1·03, 0·52-2·06, for intermediate exposure when compared with low exposure). This exploratory study of mortality in a well defined cohort of 9/11 survivors provides a baseline for continued surveillance. Additional follow-up is needed to establish whether these associations persist and whether a similar association over time will occur in rescue and recovery participants. US Centers for Disease Control and Prevention (National Institute for Occupational Safety and Health, Agency for Toxic Substances and Disease Registry, and National Center for Environmental Health); New York City Department of Health and Mental Hygiene. Copyright © 2011 Elsevier Ltd. All rights reserved.

  6. Evaluation of interobserver agreement for postoperative pain and sedation assessment in cats.

    PubMed

    Benito, Javier; Monteiro, Beatriz P; Beauchamp, Guy; Lascelles, B Duncan X; Steagall, Paulo V

    2017-09-01

    OBJECTIVE To evaluate agreement between observers with different training and experience for assessment of postoperative pain and sedation in cats by use of a dynamic and interactive visual analog scale (DIVAS) and for assessment of postoperative pain in the same cats with a multidimensional composite pain scale (MCPS). DESIGN Randomized, controlled, blinded study. ANIMALS 45 adult cats undergoing ovariohysterectomy. PROCEDURES Cats received 1 of 3 preoperative treatments: bupivacaine, IP; meloxicam, SC with saline (0.9% NaCl) solution, IP, (positive control); or saline solution only, IP (negative control). All cats received premedication with buprenorphine prior to general anesthesia. An experienced observer (observer 1; male; native language, Spanish) used scales in English, and an inexperienced observer (observer 2; female; native language, French) used scales in French to assess signs of sedation and pain. Rescue analgesia was administered according to MCPS scoring by observer 1. Mean pain and sedation scores per treatment and time point, proportions of cats in each group with MCPS scores necessitating rescue analgesia, and mean MCPS scores assigned at the time of rescue analgesia were compared between observers. Agreement was assessed by intraclass correlation coefficient determination. Percentage disagreement between observers on the need for rescue analgesia was calculated. RESULTS Interobserver agreements for pain scores were good, and that for sedation scores was fair. On the basis of observer 1's MCPS scores, a greater proportion of cats in the negative control group received rescue analgesia than in the bupivacaine or positive control groups. Scores from observer 2 indicated a greater proportion of cats in the negative control group than in the positive control group required rescue analgesia but identified no significant difference between the negative control and bupivacaine groups for this variable. Overall, disagreement regarding need for rescue analgesia was identified for 22 of 360 (6.1%) paired observations. CONCLUSIONS AND CLINICAL RELEVANCE Interobserver differences in assessing pain can lead to different conclusions regarding treatment effectiveness.

  7. 46 CFR 108.575 - Survival craft and rescue boat equipment.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Fishing kit 1 1 12 Flashlight 1 1 1 1 1 1 13 Hatchet 2 2 14 Heaving line 2 1 2 2 1 2 15 Instruction card 1... rigid/inflated rescue boats. 4 A hatchet counts toward this requirement in rigid rescue boats. 5 Oars...

  8. 46 CFR 133.140 - Stowage of rescue boats.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 4 2012-10-01 2012-10-01 false Stowage of rescue boats. 133.140 Section 133.140... SYSTEMS Requirements for All OSVs § 133.140 Stowage of rescue boats. (a) Rescue boats must be stowed as follows: (1) Each rescue boat must be ready for launching in not more than 5 minutes. (2) Each rescue boat...

  9. 46 CFR 133.140 - Stowage of rescue boats.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 4 2014-10-01 2014-10-01 false Stowage of rescue boats. 133.140 Section 133.140... SYSTEMS Requirements for All OSVs § 133.140 Stowage of rescue boats. (a) Rescue boats must be stowed as follows: (1) Each rescue boat must be ready for launching in not more than 5 minutes. (2) Each rescue boat...

  10. 46 CFR 133.140 - Stowage of rescue boats.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 4 2013-10-01 2013-10-01 false Stowage of rescue boats. 133.140 Section 133.140... SYSTEMS Requirements for All OSVs § 133.140 Stowage of rescue boats. (a) Rescue boats must be stowed as follows: (1) Each rescue boat must be ready for launching in not more than 5 minutes. (2) Each rescue boat...

  11. 30 CFR 49.17 - Physical requirements for mine rescue team.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Physical requirements for mine rescue team. 49... EDUCATION AND TRAINING MINE RESCUE TEAMS Mine Rescue Teams for Underground Coal Mines § 49.17 Physical requirements for mine rescue team. (a) Each member of a mine rescue team shall be examined annually by a...

  12. 30 CFR 49.17 - Physical requirements for mine rescue team.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Physical requirements for mine rescue team. 49... EDUCATION AND TRAINING MINE RESCUE TEAMS Mine Rescue Teams for Underground Coal Mines § 49.17 Physical requirements for mine rescue team. (a) Each member of a mine rescue team shall be examined annually by a...

  13. 30 CFR 49.18 - Training for mine rescue teams.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Training for mine rescue teams. 49.18 Section... TRAINING MINE RESCUE TEAMS Mine Rescue Teams for Underground Coal Mines § 49.18 Training for mine rescue teams. (a) Prior to serving on a mine rescue team each member shall complete, at a minimum, an initial...

  14. 30 CFR 49.8 - Training for mine rescue teams.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Training for mine rescue teams. 49.8 Section 49... TRAINING MINE RESCUE TEAMS Mine Rescue Teams for Underground Metal and Nonmetal Mines § 49.8 Training for mine rescue teams. (a) Prior to serving on a mine rescue team each member shall complete, at a minimum...

  15. 30 CFR 49.17 - Physical requirements for mine rescue team.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Physical requirements for mine rescue team. 49... EDUCATION AND TRAINING MINE RESCUE TEAMS Mine Rescue Teams for Underground Coal Mines § 49.17 Physical requirements for mine rescue team. (a) Each member of a mine rescue team shall be examined annually by a...

  16. 30 CFR 49.8 - Training for mine rescue teams.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Training for mine rescue teams. 49.8 Section 49... TRAINING MINE RESCUE TEAMS Mine Rescue Teams for Underground Metal and Nonmetal Mines § 49.8 Training for mine rescue teams. (a) Prior to serving on a mine rescue team each member shall complete, at a minimum...

  17. 30 CFR 49.18 - Training for mine rescue teams.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Training for mine rescue teams. 49.18 Section... TRAINING MINE RESCUE TEAMS Mine Rescue Teams for Underground Coal Mines § 49.18 Training for mine rescue teams. (a) Prior to serving on a mine rescue team each member shall complete, at a minimum, an initial...

  18. 30 CFR 49.17 - Physical requirements for mine rescue team.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Physical requirements for mine rescue team. 49... EDUCATION AND TRAINING MINE RESCUE TEAMS Mine Rescue Teams for Underground Coal Mines § 49.17 Physical requirements for mine rescue team. (a) Each member of a mine rescue team shall be examined annually by a...

  19. 30 CFR 49.17 - Physical requirements for mine rescue team.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Physical requirements for mine rescue team. 49... EDUCATION AND TRAINING MINE RESCUE TEAMS Mine Rescue Teams for Underground Coal Mines § 49.17 Physical requirements for mine rescue team. (a) Each member of a mine rescue team shall be examined annually by a...

  20. 30 CFR 49.18 - Training for mine rescue teams.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Training for mine rescue teams. 49.18 Section... TRAINING MINE RESCUE TEAMS Mine Rescue Teams for Underground Coal Mines § 49.18 Training for mine rescue teams. (a) Prior to serving on a mine rescue team each member shall complete, at a minimum, an initial...

  1. 30 CFR 49.18 - Training for mine rescue teams.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Training for mine rescue teams. 49.18 Section... TRAINING MINE RESCUE TEAMS Mine Rescue Teams for Underground Coal Mines § 49.18 Training for mine rescue teams. (a) Prior to serving on a mine rescue team each member shall complete, at a minimum, an initial...

  2. 30 CFR 49.8 - Training for mine rescue teams.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Training for mine rescue teams. 49.8 Section 49... TRAINING MINE RESCUE TEAMS Mine Rescue Teams for Underground Metal and Nonmetal Mines § 49.8 Training for mine rescue teams. (a) Prior to serving on a mine rescue team each member shall complete, at a minimum...

  3. 30 CFR 49.18 - Training for mine rescue teams.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Training for mine rescue teams. 49.18 Section... TRAINING MINE RESCUE TEAMS Mine Rescue Teams for Underground Coal Mines § 49.18 Training for mine rescue teams. (a) Prior to serving on a mine rescue team each member shall complete, at a minimum, an initial...

  4. Turmeric Extract Rescues Ethanol-Induced Developmental Defect in the Zebrafish Model for Fetal Alcohol Spectrum Disorder (FASD).

    PubMed

    Muralidharan, Pooja; Connors, Craig T; Mohammed, Arooj S; Sarmah, Swapnalee; Marrs, Kathleen; Marrs, James A; Chism, Grady W

    2017-09-01

    Prenatal ethanol exposure causes the most frequent preventable birth disorder, fetal alcohol spectrum disorder (FASD). The effect of turmeric extracts in rescuing an ethanol-induced developmental defect using zebrafish as a model was determined. Ethanol-induced oxidative stress is one of the major mechanisms underlying FASD. We hypothesize that antioxidant inducing properties of turmeric may alleviate ethanol-induced defects. Curcuminoid content of the turmeric powder extract (5 mg/mL turmeric in ethanol) was determined by UPLC and found to contain Curcumin (124.1 ± 0.2 μg/mL), Desmethoxycurcumin (43.4 ± 0.1 μg/mL), and Bisdemethoxycurcumin (36.6 ± 0.1 μg/mL). Zebrafish embryos were treated with 100 mM (0.6% v/v) ethanol during gastrulation through organogenesis (2 to 48 h postfertilization (hpf)) and supplemented with turmeric extract to obtain total curcuminoid concentrations of 0, 1.16, 1.72, or 2.32 μM. Turmeric supplementation showed significant rescue of the body length at 72 hpf compared to ethanol-treated embryos. The mechanism underlying the rescue remains to be determined. © 2017 Institute of Food Technologists®.

  5. CD40 agonist converting CTL exhaustion via the activation of the mTORC1 pathway enhances PD-1 antagonist action in rescuing exhausted CTLs in chronic infection

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Xu, Aizhang; Wang, Rong; Department of Oncology, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan

    Expansion of PD-1-expressing CD8{sup +} cytotoxic T lymphocytes (CTLs) and associated CTL exhaustion are chief issues for ineffective virus-elimination in chronic infectious diseases. PD-1 blockade using antagonistic anti-PD-L1 antibodies results in a moderate conversion of CTL exhaustion. We previously demonstrated that CD40L signaling of ovalbumin (OVA)-specific vaccine, OVA-Texo, converts CTL exhaustion via the activation of the mTORC1 pathway in OVA-expressing adenovirus (AdVova)-infected B6 mice showing CTL inflation and exhaustion. Here, we developed AdVova-infected B6 and transgenic CD11c-DTR (termed AdVova-B6 and AdVova-CD11c-DTR) mice with chronic infection, and assessed a potential effect of CD40 agonist on the conversion of CTL exhaustion andmore » on a potential enhancement of PD-1 antagonist action in rescuing exhausted CTLs in our chronic infection models. We demonstrate that a single dose of anti-CD40 alone can effectively convert CTL exhaustion by activating the mTORC1 pathway, leading to CTL proliferation, up-regulation of an effector-cytokine IFN-γ and the cytolytic effect in AdVova-B6 mice. Using anti-CD4 antibody and diphtheria toxin (DT) to deplete CD4{sup +} T-cells and dendritic cells (DCs), we discovered that the CD40 agonist-induced conversion in AdVova-B6 and AdVova-CD11c-DTR mice is dependent upon host CD4{sup +} T-cell and DC involvements. Moreover, CD40 agonist significantly enhances PD-1 antagonist effectiveness in rescuing exhausted CTLs in chronic infection. Taken together, our data demonstrate the importance of CD40 signaling in the conversion of CTL exhaustion and its ability to enhance PD-1 antagonist action in rescuing exhausted CTLs in chronic infection. Therefore, our findings may positively impact the design of new therapeutic strategies for chronic infectious diseases. - Highlights: • Anti-CD40 agonistic Ab can convert CTL exhaustion in chronically infected mice. • The conversion relies on the activation of the mTORC1 pathway in exhausted CTLs. • The conversion depends on the involvement of host DCs and CD4{sup +} T cells. • Anti-CD40 Ab enhances the effect of PD-1 blockade in rescuing CTL exhaustion.« less

  6. Rescuing mutant CFTR: a multi-task approach to a better outcome in treating cystic fibrosis.

    PubMed

    Amaral, Margarida D; Farinha, Carlos M

    2013-01-01

    Correcting multiple defects of mutant CFTR with small molecule compounds has been the goal of an increasing number of recent Cystic Fibrosis (CF) drug discovery programmes. However, the mechanism of action (MoA) by which these molecules restore mutant CFTR is still poorly understood, in particular of CFTR correctors, i.e., compounds rescuing to the cells surface the most prevalent mutant in CF patients--F508del-CFTR. However, there is increasing evidence that to fully restore the multiple defects associated with F508del-CFTR, different small molecules with distinct corrective properties may be required. Towards this goal, a better insight into MoA of correctors is needed and several constraints should be addressed. The methodological approaches to achieve this include: 1) testing the combined effect of compounds with that of other (non-pharmacological) rescuing strategies (e.g., revertants or low temperature); 2) assessing effects in multiple cellular models (non-epithelial vs epithelial, non-human vs human, immortalized vs primary cultures, polarized vs non polarized, cells vs tissues); 3) assessing compound effects on isolated CFTR domains (e.g., compound binding by surface plasmon resonance, assessing effects on domain folding and aggregation); and finally 4) assessing compounds specificity in rescuing different CFTR mutants and other mutant proteins. These topics are reviewed and discussed here so as to provide a state-of-the art review on how to combine multiple ways of rescuing mutant CFTR to the ultimate benefit of CF patients.

  7. Rescue Manual. Module 6.

    ERIC Educational Resources Information Center

    Ohio State Univ., Columbus. Instructional Materials Lab.

    This learner manual for rescuers covers the current techniques or practices required in the rescue service. The sixth of 10 modules contains 4 chapters: (1) industrial rescue; (2) rescue from a confined space; (3) extrication from heavy equipment; and (4) rescue operations involving elevators. Key points, an introduction, and conclusion accompany…

  8. Lack of tau proteins rescues neuronal cell death and decreases amyloidogenic processing of APP in APP/PS1 mice.

    PubMed

    Leroy, Karelle; Ando, Kunie; Laporte, Vincent; Dedecker, Robert; Suain, Valérie; Authelet, Michèle; Héraud, Céline; Pierrot, Nathalie; Yilmaz, Zehra; Octave, Jean-Noël; Brion, Jean-Pierre

    2012-12-01

    Lack of tau expression has been reported to protect against excitotoxicity and to prevent memory deficits in mice expressing mutant amyloid precursor protein (APP) identified in familial Alzheimer disease. In APP mice, mutant presenilin 1 (PS1) enhances generation of Aβ42 and inhibits cell survival pathways. It is unknown whether the deficient phenotype induced by concomitant expression of mutant PS1 is rescued by absence of tau. In this study, we have analyzed the effect of tau deletion in mice expressing mutant APP and PS1. Although APP/PS1/tau(+/+) mice had a reduced survival, developed spatial memory deficits at 6 months and motor impairments at 12 months, these deficits were rescued in APP/PS1/tau(-/-) mice. Neuronal loss and synaptic loss in APP/PS1/tau(+/+) mice were rescued in the APP/PS1/tau(-/-) mice. The amyloid plaque burden was decreased by roughly 50% in the cortex and the spinal cord of the APP/PS1/tau(-/-) mice. The levels of soluble and insoluble Aβ40 and Aβ42, and the Aβ42/Aβ40 ratio were reduced in APP/PS1/tau(-/-) mice. Levels of phosphorylated APP, of β-C-terminal fragments (CTFs), and of β-secretase 1 (BACE1) were also reduced, suggesting that β-secretase cleavage of APP was reduced in APP/PS1/tau(-/-) mice. Our results indicate that tau deletion had a protective effect against amyloid induced toxicity even in the presence of mutant PS1 and reduced the production of Aβ. Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  9. Fourth-line rescue therapy with rifabutin in patients with three Helicobacter pylori eradication failures.

    PubMed

    Gisbert, J P; Castro-Fernandez, M; Perez-Aisa, A; Cosme, A; Molina-Infante, J; Rodrigo, L; Modolell, I; Cabriada, J L; Gisbert, J L; Lamas, E; Marcos, E; Calvet, X

    2012-04-01

    In some cases, Helicobacter pylori infection persists even after three eradication treatments. To evaluate the efficacy of an empirical fourth-line rescue regimen with rifabutin in patients with three eradication failures. Multicentre, prospective study. In whom the following three treatments had consecutively failed: first (PPI + clarithromycin + amoxicillin); second (PPI + bismuth + tetracycline + metronidazole); third (PPI + amoxicillin + levofloxacin). A fourth regimen with rifabutin (150 mg b.d.), amoxicillin (1 g b.d.) and a PPI (standard dose b.d.) was prescribed for 10 days. Eradication was confirmed by (13) C-urea breath test 4-8 weeks after therapy. Compliance and tolerance: Compliance was determined through questioning and recovery of empty medication envelopes. Adverse effects were evaluated using a questionnaire. One-hundred patients (mean age 50 years, 39% men, 31% peptic ulcer/69% functional dyspepsia) were included. Eight patients did not take the medication correctly (in six cases due to adverse effects). Per-protocol and intention-to-treat eradication rates were 52% (95% CI = 41-63%) and 50% (40-60%). Adverse effects were reported in 30 (30%) patients: nausea/vomiting (13 patients), asthenia/anorexia (8), abdominal pain (7), diarrhoea (5), fever (4), metallic taste (4), myalgia (4), hypertransaminasemia (2), leucopenia (<1,500 neutrophils) (2), thrombopenia (<150,000 platelets) (2), headache (1) and aphthous stomatitis (1). Myelotoxicity resolved spontaneously in all cases. Even after three previous H. pylori eradication failures, an empirical fourth-line rescue treatment with rifabutin may be effective in approximately 50% of the cases. Therefore, rifabutin-based rescue therapy constitutes a valid strategy after multiple previous eradication failures with key antibiotics, such as clarithromycin, metronidazole, tetracycline and levofloxacin. © 2012 Blackwell Publishing Ltd.

  10. 30 CFR 49.5 - Mine rescue station.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Mine rescue station. 49.5 Section 49.5 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR EDUCATION AND TRAINING MINE RESCUE TEAMS Mine Rescue Teams for Underground Metal and Nonmetal Mines § 49.5 Mine rescue station. (a) Except...

  11. 30 CFR 49.15 - Mine rescue station.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Mine rescue station. 49.15 Section 49.15 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR EDUCATION AND TRAINING MINE RESCUE TEAMS Mine Rescue Teams for Underground Coal Mines § 49.15 Mine rescue station. (a) Every operator...

  12. 30 CFR 49.15 - Mine rescue station.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Mine rescue station. 49.15 Section 49.15 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR EDUCATION AND TRAINING MINE RESCUE TEAMS Mine Rescue Teams for Underground Coal Mines § 49.15 Mine rescue station. (a) Every operator...

  13. 30 CFR 49.5 - Mine rescue station.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Mine rescue station. 49.5 Section 49.5 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR EDUCATION AND TRAINING MINE RESCUE TEAMS Mine Rescue Teams for Underground Metal and Nonmetal Mines § 49.5 Mine rescue station. (a) Except...

  14. 30 CFR 49.15 - Mine rescue station.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Mine rescue station. 49.15 Section 49.15 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR EDUCATION AND TRAINING MINE RESCUE TEAMS Mine Rescue Teams for Underground Coal Mines § 49.15 Mine rescue station. (a) Every operator...

  15. 30 CFR 49.5 - Mine rescue station.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Mine rescue station. 49.5 Section 49.5 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR EDUCATION AND TRAINING MINE RESCUE TEAMS Mine Rescue Teams for Underground Metal and Nonmetal Mines § 49.5 Mine rescue station. (a) Except...

  16. 30 CFR 49.15 - Mine rescue station.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Mine rescue station. 49.15 Section 49.15 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR EDUCATION AND TRAINING MINE RESCUE TEAMS Mine Rescue Teams for Underground Coal Mines § 49.15 Mine rescue station. (a) Every operator...

  17. 30 CFR 49.15 - Mine rescue station.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Mine rescue station. 49.15 Section 49.15 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR EDUCATION AND TRAINING MINE RESCUE TEAMS Mine Rescue Teams for Underground Coal Mines § 49.15 Mine rescue station. (a) Every operator...

  18. Decoy Oligonucleotide Rescues IGF1R Expression from MicroRNA-223 Suppression

    PubMed Central

    Wang, Rong; He, Bao Mei; Qi, Bing; Xu, Chang Jun; Wu, Xing Zhong

    2013-01-01

    A mature miRNA generally suppresses hundreds of mRNA targets. To evaluate the selective effect of synthetic oligonucleotide decoys on hsa-miR-223 activity, reporters containing 3’ untranslated regions (UTR) of IGF1R, FOXO1, POLR3G, FOXO3, CDC27, FBXW7 and PAXIP1 mRNAs were constructed for the luciferase assay. The oligonucleotide decoys were designed and synthesized according to mature miR-223 sequence and its target mRNA sequence. Quantitative RT-PCR & western analysis were used to measure miR-223-targeted mRNA expression, Interestingly, apart from the antisense oligonucleotide, decoy nucleotides which were complementary to the 5’, central or 3’ region of mature miR-223 suppressed miR-223 targeting the 3’UTR of IGF1R, FOXO1, FOXO3, CDC27, POLR3G, and FBXW7 mRNAs and rescued the expression of these genes to varying degrees from miR-223 suppression at both mRNA and protein levels. All decoys had no effect on PAXIP1 which was not targeted by miR-223. The decoy 1 that was based on the sequence of IGF1R 3’UTR rescued the expression of IGF1R more significantly than other decoy nucleotides except the antisense decoy 4. Decoy 1 also rescued the expression of FOXO3 and POLR3G of which their 3’UTRs have similar binding sites for miR-223 with IGF1R 3’UTR. However decoy 1 failed to recover Sp1, CDC27 and FBXW7 expression. These data support that the sequence-specific decoy oligonucleotides might represent exogenous competing RNA which selectively inhibits microRNA targeting. PMID:24324762

  19. Decoy oligonucleotide rescues IGF1R expression from MicroRNA-223 suppression.

    PubMed

    Wu, Li Hui; Cai, Qian Qian; Dong, Yi Wei; Wang, Rong; He, Bao Mei; Qi, Bing; Xu, Chang Jun; Wu, Xing Zhong

    2013-01-01

    A mature miRNA generally suppresses hundreds of mRNA targets. To evaluate the selective effect of synthetic oligonucleotide decoys on hsa-miR-223 activity, reporters containing 3' untranslated regions (UTR) of IGF1R, FOXO1, POLR3G, FOXO3, CDC27, FBXW7 and PAXIP1 mRNAs were constructed for the luciferase assay. The oligonucleotide decoys were designed and synthesized according to mature miR-223 sequence and its target mRNA sequence. Quantitative RT-PCR & western analysis were used to measure miR-223-targeted mRNA expression, Interestingly, apart from the antisense oligonucleotide, decoy nucleotides which were complementary to the 5', central or 3' region of mature miR-223 suppressed miR-223 targeting the 3'UTR of IGF1R, FOXO1, FOXO3, CDC27, POLR3G, and FBXW7 mRNAs and rescued the expression of these genes to varying degrees from miR-223 suppression at both mRNA and protein levels. All decoys had no effect on PAXIP1 which was not targeted by miR-223. The decoy 1 that was based on the sequence of IGF1R 3'UTR rescued the expression of IGF1R more significantly than other decoy nucleotides except the antisense decoy 4. Decoy 1 also rescued the expression of FOXO3 and POLR3G of which their 3'UTRs have similar binding sites for miR-223 with IGF1R 3'UTR. However decoy 1 failed to recover Sp1, CDC27 and FBXW7 expression. These data support that the sequence-specific decoy oligonucleotides might represent exogenous competing RNA which selectively inhibits microRNA targeting.

  20. 46 CFR 12.613 - Requirements to qualify for an STCW endorsement in proficiency in survival craft and rescue boats...

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... proficiency in survival craft and rescue boats other than fast rescue boats (PSC). 12.613 Section 12.613... STCW endorsement in proficiency in survival craft and rescue boats other than fast rescue boats (PSC... fast rescue boats (PSC), the applicant must— (1) Be at least 18 years of age; (2) Meet the requirements...

  1. Structures of oncogenic, suppressor and rescued p53 core-domain variants: mechanisms of mutant p53 rescue

    PubMed Central

    Wallentine, Brad D.; Wang, Ying; Tretyachenko-Ladokhina, Vira; Tan, Martha; Senear, Donald F.; Luecke, Hartmut

    2013-01-01

    To gain insights into the mechanisms by which certain second-site suppressor mutations rescue the function of a significant number of cancer mutations of the tumor suppressor protein p53, X-ray crystallographic structures of four p53 core-domain variants were determined. These include an oncogenic mutant, V157F, two single-site suppressor mutants, N235K and N239Y, and the rescued cancer mutant V157F/N235K/N239Y. The V157F mutation substitutes a smaller hydrophobic valine with a larger hydrophobic phenylalanine within strand S4 of the hydrophobic core. The structure of this cancer mutant shows no gross structural changes in the overall fold of the p53 core domain, only minor rearrangements of side chains within the hydrophobic core of the protein. Based on biochemical analysis, these small local perturbations induce instability in the protein, increasing the free energy by 3.6 kcal mol−1 (15.1 kJ mol−1). Further biochemical evidence shows that each suppressor mutation, N235K or N239Y, acts individually to restore thermodynamic stability to V157F and that both together are more effective than either alone. All rescued mutants were found to have wild-type DNA-binding activity when assessed at a permissive temperature, thus pointing to thermodynamic stability as the critical underlying variable. Interestingly, thermodynamic analysis shows that while N239Y demonstrates stabilization of the wild-type p53 core domain, N235K does not. These observations suggest distinct structural mechanisms of rescue. A new salt bridge between Lys235 and Glu198, found in both the N235K and rescued cancer mutant structures, suggests a rescue mechanism that relies on stabilizing the β-sandwich scaffold. On the other hand, the substitution N239Y creates an advantageous hydrophobic contact between the aromatic ring of this tyrosine and the adjacent Leu137. Surprisingly, the rescued cancer mutant shows much larger structural deviations than the cancer mutant alone when compared with wild-type p53. These suppressor mutations appear to rescue p53 function by creating novel intradomain interactions that stabilize the core domain, allowing compensation for the destabilizing V157F mutation. PMID:24100332

  2. SURGICAL OUTCOME OF SIMULTANEOUS INTRAOCULAR LENS RESCUE AND SUTURELESS INTRASCLERAL TUNNEL FIXATION OF DISLOCATED INTRAOCULAR LENSES.

    PubMed

    Kim, Min; Lee, Dong H; Koh, Hyoung J; Lee, Sung C; Kim, Sung S

    2015-07-01

    To report short-term surgical outcomes of single-stage simultaneous rescue and sutureless intrascleral fixation of dislocated intraocular lens (IOLs). Sixteen eyes of 16 patients who underwent simultaneous rescue and intrascleral fixation of dislocated 3-piece IOLs were retrospectively evaluated. Partial thickness limbal-based scleral flaps (2.0 × 2.0 mm) were created, and a 22-gauge round needle was used to create a sclerotomy at 1.5 mm from the limbus under the previously created scleral flap, and a 23-gauge trans pars plana vitrectomy was performed. Bimanual maneuvers using two 23-gauge end-grasping forceps under chandelier illumination and a wide-angle viewing system enabled 1 step rescue of IOLs from the posterior vitreous cavity with 1 hand and simultaneous haptic externalization through sclerotomy with the other hand. An externalized haptic was placed into the 3-mm intrascleral tunnel created using a bent 26-gauge needle. Fibrin glue was used to fixate haptics and close the scleral flaps. Intraocular lenses were successfully rescued and sclera-fixated through intrascleral tunnels in all 16 eyes (mean age, 56.56 ± 19.89 years). The mean preoperative logarithm of the minimum angle of resolution best-corrected visual acuity was 0.92 ± 0.68, and this significantly improved at 6 months to 0.289 ± 0.36 (P = 0.003). During the follow-up period (10.1 ± 3.21 months), no significant change of endothelial cell count or central foveal thickness was noted postoperatively (P = 0.203 and P = 0.979, respectively). There were no significant postoperative complications such as IOL dislocation, IOL decentration, retinal detachment, endophthalmitis, or postoperative hypotony. Simultaneous rescue and sutureless intrascleral haptic fixation of dislocated 3-piece IOLs using bimanual maneuvers is an effective, safe, and minimally invasive surgical method to rescue and fixate the dislocated IOL without further explant.

  3. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Braly, Ian L.; Hillhouse, Hugh W.

    The development of stable high-bandgap hybrid perovskites (HPs) with high optoelectronic quality may enable tandem solar cells with power conversion efficiencies approaching 30%. The halide composition of HPs has been observed to effect bandgap, carrier lifetime, and material stability. Here we report optoelectronic quality and stability under illumination of thousands of compositions ranging from the pure iodide (CH3NH3PbI3) to the diiodomonobromide (CH3NH3PbI2Br). Hyperspectral maps of steady-state absolute intensity photoluminescence (AIPL) are used to determine the quasi-Fermi level splitting (QFLS) at each point after synthesis. The QFLS upon first illumination increases with bandgap and reaches a maximum of 1.27 eV undermore » 1 sun illumination intensity for a bandgap of 1.75 eV. However, the optoelectronic quality (χ), defined as the ratio of the QFLS to the maximum theoretical QFLS for bandgap, decreases with bandgap from around 88% for 1.60 eV bandgap down to 82% for 1.84 eV bandgap. Further, we show that a reversible light induced defect forms that reduces the optoelectronic quality, particularly for high-bandgap materials. Composition analysis shows that the halide to lead ratio, (I + Br)/Pb, decreases from 3 for the pure iodide to 2.5 for the diiodomonobromide, suggesting a role of halide vacancies or halide substitution defects in the light-induced instability for this synthesis route. Even with the light-induced defect, a stable QFLS of about 1.17 eV is possible. Comparing our QFLS to Voc values from HP devices reported in the literature indicates that higher open circuit voltages are possible but may require optimization of band alignment. Further, the spectral shape of the PL emission is found to be more commensurate with Franz–Keldysh broadening from local electric fields or from a screened Thomas–Fermi density of states (as opposed to a joint density of states due to Urbach disorder).« less

  4. Efficient and Robust Paramyxoviridae Reverse Genetics Systems

    PubMed Central

    Beaty, Shannon M.; Won, Sohui T.; Hong, Patrick; Lyons, Michael; Vigant, Frederic; Freiberg, Alexander N.; tenOever, Benjamin R.; Duprex, W. Paul

    2017-01-01

    ABSTRACT The notoriously low efficiency of Paramyxoviridae reverse genetics systems has posed a limiting barrier to the study of viruses in this family. Previous approaches to reverse genetics have utilized a wide variety of techniques to overcome the technical hurdles. Although robustness (i.e., the number of attempts that result in successful rescue) has been improved in some systems with the use of stable cell lines, the efficiency of rescue (i.e., the proportion of transfected cells that yield at least one successful rescue event) has remained low. We have substantially increased rescue efficiency for representative viruses from all five major Paramyxoviridae genera (from ~1 in 106-107 to ~1 in 102-103 transfected cells) by the addition of a self-cleaving hammerhead ribozyme (Hh-Rbz) sequence immediately preceding the start of the recombinant viral antigenome and the use of a codon-optimized T7 polymerase (T7opt) gene to drive paramyxovirus rescue. Here, we report a strategy for robust, reliable, and high-efficiency rescue of paramyxovirus reverse genetics systems, featuring several major improvements: (i) a vaccinia virus-free method, (ii) freedom to use any transfectable cell type for viral rescue, (iii) a single-step transfection protocol, and (iv) use of the optimal T7 promoter sequence for high transcription levels from the antigenomic plasmid without incorporation of nontemplated G residues. The robustness of our T7opt-HhRbz system also allows for greater latitude in the ratios of transfected accessory plasmids used that result in successful rescue. Thus, our system may facilitate the rescue and interrogation of the increasing number of emerging paramyxoviruses. IMPORTANCE The ability to manipulate the genome of paramyxoviruses and evaluate the effects of these changes at the phenotypic level is a powerful tool for the investigation of specific aspects of the viral life cycle and viral pathogenesis. However, reverse genetics systems for paramyxoviruses are notoriously inefficient, when successful. The ability to efficiently and robustly rescue paramyxovirus reverse genetics systems can be used to answer basic questions about the biology of paramyxoviruses, as well as to facilitate the considerable translational efforts being devoted to developing live attenuated paramyxovirus vaccine vectors. PMID:28405630

  5. Development of a Search and Rescue Simulation to Study the Effects of Prolonged Isolation on Team Decision Making

    NASA Technical Reports Server (NTRS)

    Entin, Elliot E.; Kerrigan, Caroline; Serfaty, Daniel; Young, Philip

    1998-01-01

    The goals of this project were to identify and investigate aspects of team and individual decision-making and risk-taking behaviors hypothesized to be most affected by prolonged isolation. A key premise driving our research approach is that effects of stressors that impact individual and team cognitive processes in an isolated, confined, and hazardous environment will be projected onto the performance of a simulation task. To elicit and investigate these team behaviors we developed a search and rescue task concept as a scenario domain that would be relevant for isolated crews. We modified the Distributed Dynamic Decision-making (DDD) simulator, a platform that has been extensively used for empirical research in team processes and taskwork performance, to portray the features of a search and rescue scenario and present the task components incorporated into that scenario. The resulting software is called DD-Search and Rescue (Version 1.0). To support the use of the DDD-Search and Rescue simulator in isolated experiment settings, we wrote a player's manual for teaching team members to operate the simulator and play the scenario. We then developed a research design and experiment plan that would allow quantitative measures of individual and team decision making skills using the DDD-Search and Rescue simulator as the experiment platform. A description of these activities and the associated materials that were produced under this contract are contained in this report.

  6. Live Birth after Rescue In vitro Maturation-intracytoplasmic Sperm Injection in Type 1 Diabetes, Polycystic Ovary Syndrome Patient Using Clomiphene-antagonist Protocol.

    PubMed

    Sankari, Samundi; Elanchezhian, M; Selvamani, Divya; Nagarajan, M; Gopikrishnan, D

    2018-01-01

    Infertility in patients with polycystic ovary syndrome (PCOS) associated with diabetes leads to challenging situations seeking alternative treatments. In vitro maturation (IVM) followed by intracytoplasmic sperm injection (ICSI) could overcome the challenges with promising pregnancies in such patients. In the treatment of a 32-year-old diabetic woman who also had PCOS, single immature oocyte was retrieved. Rescue IVM followed by ICSI yielded a grade 1 day 3 embryo which on transferring resulted in pregnancy and a healthy infant was delivered. Rescue IVM-ICSI could help in achieving pregnancy and live birth. Stimulation involving clomiphene and gonadotropin-releasing hormone antagonist is an effective and patient-friendly protocol for women with PCOS and diabetes and also for poor responders.

  7. 46 CFR 108.565 - Stowage of rescue boats.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 4 2010-10-01 2010-10-01 false Stowage of rescue boats. 108.565 Section 108.565... AND EQUIPMENT Lifesaving Equipment § 108.565 Stowage of rescue boats. (a) Rescue boats must be stowed as follows: (1) Each rescue boat must be ready for launching in not more than 5 minutes. (2) Each...

  8. 46 CFR 108.565 - Stowage of rescue boats.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 4 2013-10-01 2013-10-01 false Stowage of rescue boats. 108.565 Section 108.565... AND EQUIPMENT Lifesaving Equipment § 108.565 Stowage of rescue boats. (a) Rescue boats must be stowed as follows: (1) Each rescue boat must be ready for launching in not more than 5 minutes. (2) Each...

  9. 30 CFR 49.12 - Availability of mine rescue teams.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Availability of mine rescue teams. 49.12... TRAINING MINE RESCUE TEAMS Mine Rescue Teams for Underground Coal Mines § 49.12 Availability of mine rescue teams. (a) Except where alternative compliance is permitted for small and remote mines (§ 49.13), every...

  10. 30 CFR 49.2 - Availability of mine rescue teams.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Availability of mine rescue teams. 49.2 Section... TRAINING MINE RESCUE TEAMS Mine Rescue Teams for Underground Metal and Nonmetal Mines § 49.2 Availability of mine rescue teams. (a) Except where alternative compliance is permitted for small and remote mines...

  11. 30 CFR 49.12 - Availability of mine rescue teams.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Availability of mine rescue teams. 49.12... TRAINING MINE RESCUE TEAMS Mine Rescue Teams for Underground Coal Mines § 49.12 Availability of mine rescue teams. (a) Except where alternative compliance is permitted for small and remote mines (§ 49.13), every...

  12. 30 CFR 49.12 - Availability of mine rescue teams.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Availability of mine rescue teams. 49.12... TRAINING MINE RESCUE TEAMS Mine Rescue Teams for Underground Coal Mines § 49.12 Availability of mine rescue teams. (a) Except where alternative compliance is permitted for small and remote mines (§ 49.13), every...

  13. 30 CFR 49.12 - Availability of mine rescue teams.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Availability of mine rescue teams. 49.12... TRAINING MINE RESCUE TEAMS Mine Rescue Teams for Underground Coal Mines § 49.12 Availability of mine rescue teams. (a) Except where alternative compliance is permitted for small and remote mines (§ 49.13), every...

  14. 30 CFR 49.12 - Availability of mine rescue teams.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Availability of mine rescue teams. 49.12... TRAINING MINE RESCUE TEAMS Mine Rescue Teams for Underground Coal Mines § 49.12 Availability of mine rescue teams. (a) Except where alternative compliance is permitted for small and remote mines (§ 49.13), every...

  15. 30 CFR 49.2 - Availability of mine rescue teams.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Availability of mine rescue teams. 49.2 Section... TRAINING MINE RESCUE TEAMS Mine Rescue Teams for Underground Metal and Nonmetal Mines § 49.2 Availability of mine rescue teams. (a) Except where alternative compliance is permitted for small and remote mines...

  16. 30 CFR 49.2 - Availability of mine rescue teams.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Availability of mine rescue teams. 49.2 Section... TRAINING MINE RESCUE TEAMS Mine Rescue Teams for Underground Metal and Nonmetal Mines § 49.2 Availability of mine rescue teams. (a) Except where alternative compliance is permitted for small and remote mines...

  17. Structures of oncogenic, suppressor and rescued p53 core-domain variants: mechanisms of mutant p53 rescue

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wallentine, Brad D.; Wang, Ying; Tretyachenko-Ladokhina, Vira

    2013-10-01

    X-ray crystallographic structures of four p53 core-domain variants were determined in order to gain insights into the mechanisms by which certain second-site suppressor mutations rescue the function of a significant number of cancer mutations of the tumor suppressor protein p53. To gain insights into the mechanisms by which certain second-site suppressor mutations rescue the function of a significant number of cancer mutations of the tumor suppressor protein p53, X-ray crystallographic structures of four p53 core-domain variants were determined. These include an oncogenic mutant, V157F, two single-site suppressor mutants, N235K and N239Y, and the rescued cancer mutant V157F/N235K/N239Y. The V157F mutationmore » substitutes a smaller hydrophobic valine with a larger hydrophobic phenylalanine within strand S4 of the hydrophobic core. The structure of this cancer mutant shows no gross structural changes in the overall fold of the p53 core domain, only minor rearrangements of side chains within the hydrophobic core of the protein. Based on biochemical analysis, these small local perturbations induce instability in the protein, increasing the free energy by 3.6 kcal mol{sup −1} (15.1 kJ mol{sup −1}). Further biochemical evidence shows that each suppressor mutation, N235K or N239Y, acts individually to restore thermodynamic stability to V157F and that both together are more effective than either alone. All rescued mutants were found to have wild-type DNA-binding activity when assessed at a permissive temperature, thus pointing to thermodynamic stability as the critical underlying variable. Interestingly, thermodynamic analysis shows that while N239Y demonstrates stabilization of the wild-type p53 core domain, N235K does not. These observations suggest distinct structural mechanisms of rescue. A new salt bridge between Lys235 and Glu198, found in both the N235K and rescued cancer mutant structures, suggests a rescue mechanism that relies on stabilizing the β-sandwich scaffold. On the other hand, the substitution N239Y creates an advantageous hydrophobic contact between the aromatic ring of this tyrosine and the adjacent Leu137. Surprisingly, the rescued cancer mutant shows much larger structural deviations than the cancer mutant alone when compared with wild-type p53. These suppressor mutations appear to rescue p53 function by creating novel intradomain interactions that stabilize the core domain, allowing compensation for the destabilizing V157F mutation.« less

  18. 46 CFR 160.156-1 - Scope.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... APPROVAL LIFESAVING EQUIPMENT Rescue Boats and Fast Rescue Boats (SOLAS) § 160.156-1 Scope. This subpart... fast rescue boat, complying with SOLAS and the IMO LSA Code, for use on waters other than protected...

  19. 46 CFR 160.156-1 - Scope.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... APPROVAL LIFESAVING EQUIPMENT Rescue Boats and Fast Rescue Boats (SOLAS) § 160.156-1 Scope. This subpart... fast rescue boat, complying with SOLAS and the IMO LSA Code, for use on waters other than protected...

  20. 46 CFR 160.156-1 - Scope.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... APPROVAL LIFESAVING EQUIPMENT Rescue Boats and Fast Rescue Boats (SOLAS) § 160.156-1 Scope. This subpart... fast rescue boat, complying with SOLAS and the IMO LSA Code, for use on waters other than protected...

  1. Quorum Sensing Down-Regulation Counteracts the Negative Impact of Pseudomonas aeruginosa on CFTR Channel Expression, Function and Rescue in Human Airway Epithelial Cells

    PubMed Central

    Maillé, Émilie; Ruffin, Manon; Adam, Damien; Messaoud, Hatem; Lafayette, Shantelle L.; McKay, Geoffrey; Nguyen, Dao; Brochiero, Emmanuelle

    2017-01-01

    The function of cystic fibrosis transmembrane conductance regulator (CFTR) channels is crucial in human airways. However unfortunately, chronic Pseudomonas aeruginosa infection has been shown to impair CFTR proteins in non-CF airway epithelial cells (AEC) and to alter the efficiency of new treatments with CFTR modulators designed to correct the basic CFTR default in AEC from cystic fibrosis (CF) patients carrying the F508del mutation. Our aim was first to compare the effect of laboratory strains, clinical isolates, engineered and natural mutants to determine the role of the LasR quorum sensing system in CFTR impairment, and second, to test the efficiency of a quorum sensing inhibitor to counteract the deleterious impact of P. aeruginosa both on wt-CFTR and on the rescue of F508del-CFTR by correctors. We first report that exoproducts from either the laboratory PAO1 strain or a clinical ≪Early≫ isolate (from an early stage of infection) altered CFTR expression, localization and function in AEC expressing wt-CFTR. Genetic inactivation of the quorum-sensing LasR in PAO1 (PAO1ΔlasR) or in a natural clinical mutant (≪Late≫ CF-adapted clinical isolate) abolished wt-CFTR impairment. PAO1 exoproducts also dampened F508del-CFTR rescue by VRT-325 or Vx-809 correctors in CF cells, whereas PAO1ΔlasR had no impact. Importantly, treatment of P. aeruginosa cultures with a quorum sensing inhibitor (HDMF) prevented the negative effect of P. aeruginosa exoproducts on wt-CFTR and preserved CFTR rescue by correctors in CF AEC. These findings indicate that LasR-interfering strategies could be of benefits to counteract the deleterious effect of P. aeruginosa in infected patients. PMID:29177135

  2. Failure-to-rescue after injury is associated with preventability: The results of mortality panel review of failure-to-rescue cases in trauma.

    PubMed

    Kuo, Lindsay E; Kaufman, Elinore; Hoffman, Rebecca L; Pascual, Jose L; Martin, Niels D; Kelz, Rachel R; Holena, Daniel N

    2017-03-01

    Failure-to-rescue is defined as the conditional probability of death after a complication, and the failure-to-rescue rate reflects a center's ability to successfully "rescue" patients after complications. The validity of the failure-to-rescue rate as a quality measure is dependent on the preventability of death and the appropriateness of this measure for use in the trauma population is untested. We sought to evaluate the relationship between preventability and failure-to-rescue in trauma. All adjudications from a mortality review panel at an academic level I trauma center from 2005-2015 were merged with registry data for the same time period. The preventability of each death was determined by panel consensus as part of peer review. Failure-to-rescue deaths were defined as those occurring after any registry-defined complication. Univariate and multivariate logistic regression models between failure-to-rescue status and preventability were constructed and time to death was examined using survival time analyses. Of 26,557 patients, 2,735 (10.5%) had a complication, of whom 359 died for a failure-to-rescue rate of 13.2%. Of failure-to-rescue deaths, 272 (75.6%) were judged to be non-preventable, 65 (18.1%) were judged potentially preventable, and 22 (6.1%) were judged to be preventable by peer review. After adjusting for other patient factors, there remained a strong association between failure-to-rescue status and potentially preventable (odds ratio 2.32, 95% confidence interval, 1.47-3.66) and preventable (odds ratio 14.84, 95% confidence interval, 3.30-66.71) judgment. Despite a strong association between failure-to-rescue status and preventability adjudication, only a minority of deaths meeting the definition of failure to rescue were judged to be preventable or potentially preventable. Revision of the failure-to-rescue metric before use in trauma care benchmarking is warranted. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. 30 CFR 49.7 - Physical requirements for mine rescue team.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Physical requirements for mine rescue team. 49... EDUCATION AND TRAINING MINE RESCUE TEAMS § 49.7 Physical requirements for mine rescue team. (a) Each member of a mine rescue team shall be examined annually by a physician who shall certify that each person is...

  4. 30 CFR 49.8 - Training for mine rescue teams.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Training for mine rescue teams. 49.8 Section 49... TRAINING MINE RESCUE TEAMS § 49.8 Training for mine rescue teams. (a) Prior to serving on a mine rescue team each member shall complete, at a minimum, an initial 20-hour course of instruction as prescribed...

  5. 30 CFR 49.7 - Physical requirements for mine rescue team.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Physical requirements for mine rescue team. 49... EDUCATION AND TRAINING MINE RESCUE TEAMS § 49.7 Physical requirements for mine rescue team. (a) Each member of a mine rescue team shall be examined annually by a physician who shall certify that each person is...

  6. 30 CFR 49.8 - Training for mine rescue teams.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Training for mine rescue teams. 49.8 Section 49... TRAINING MINE RESCUE TEAMS § 49.8 Training for mine rescue teams. (a) Prior to serving on a mine rescue team each member shall complete, at a minimum, an initial 20-hour course of instruction as prescribed...

  7. Genetic rescue in an inbred Arctic fox (Vulpes lagopus) population.

    PubMed

    Hasselgren, Malin; Angerbjörn, Anders; Eide, Nina E; Erlandsson, Rasmus; Flagstad, Øystein; Landa, Arild; Wallén, Johan; Norén, Karin

    2018-03-28

    Isolation of small populations can reduce fitness through inbreeding depression and impede population growth. Outcrossing with only a few unrelated individuals can increase demographic and genetic viability substantially, but few studies have documented such genetic rescue in natural mammal populations. We investigate the effects of immigration in a subpopulation of the endangered Scandinavian arctic fox ( Vulpes lagopus ), founded by six individuals and isolated for 9 years at an extremely small population size. Based on a long-term pedigree (105 litters, 543 individuals) combined with individual fitness traits, we found evidence for genetic rescue. Natural immigration and gene flow of three outbred males in 2010 resulted in a reduction in population average inbreeding coefficient ( f ), from 0.14 to 0.08 within 5 years. Genetic rescue was further supported by 1.9 times higher juvenile survival and 1.3 times higher breeding success in immigrant first-generation offspring compared with inbred offspring. Five years after immigration, the population had more than doubled in size and allelic richness increased by 41%. This is one of few studies that has documented genetic rescue in a natural mammal population suffering from inbreeding depression and contributes to a growing body of data demonstrating the vital connection between genetics and individual fitness. © 2018 The Author(s).

  8. Examination of the mGluR mTOR Pathway for the Identification of Potential Therapeutic Targets to Treat Fragile X

    DTIC Science & Technology

    2015-10-01

    as 5 years of age both to control weight gain and to treat type II diabetes. If metformin is effective in the fly and mouse model, clinical trials...study the efficacy of metformin in more detail, we have tested the effect of treating dfmr1 mutants during development, during adulthood or both and...tested for short-term memory as well as for rescue of circadian behavior. We have found that even with adult treatment alone we can rescue the memory

  9. Failure-to-rescue after injury is associated with preventability: The results of mortality panel review of failure-to-rescue cases in trauma

    PubMed Central

    Kuo, Lindsay E.; Kaufman, Elinore; Hoffman, Rebecca L.; Pascual, Jose L.; Martin, Niels D.; Kelz, Rachel R.; Holena, Daniel N.

    2018-01-01

    Background Failure-to-rescue is defined as the conditional probability of death after a complication, and the failure-to-rescue rate reflects a center’s ability to successfully “rescue” patients after complications. The validity of the failure-to-rescue rate as a quality measure is dependent on the preventability of death and the appropriateness of this measure for use in the trauma population is untested. We sought to evaluate the relationship between preventability and failure-to-rescue in trauma. Methods All adjudications from a mortality review panel at an academic level I trauma center from 2005–2015 were merged with registry data for the same time period. The preventability of each death was determined by panel consensus as part of peer review. Failure-to-rescue deaths were defined as those occurring after any registry-defined complication. Univariate and multivariate logistic regression models between failure-to-rescue status and preventability were constructed and time to death was examined using survival time analyses. Results Of 26,557 patients, 2,735 (10.5%) had a complication, of whom 359 died for a failure-to-rescue rate of 13.2%. Of failure-to-rescue deaths, 272 (75.6%) were judged to be non-preventable, 65 (18.1%) were judged potentially preventable, and 22 (6.1%) were judged to be preventable by peer review. After adjusting for other patient factors, there remained a strong association between failure-to-rescue status and potentially preventable (odds ratio 2.32, 95% confidence interval, 1.47–3.66) and preventable (odds ratio 14.84, 95% confidence interval, 3.30–66.71) judgment. Conclusion Despite a strong association between failure-to-rescue status and preventability adjudication, only a minority of deaths meeting the definition of failure to rescue were judged to be preventable or potentially preventable. Revision of the failure-to-rescue metric before use in trauma care benchmarking is warranted. PMID:27788924

  10. The Effect of Perioperative Rescue Transesophageal Echocardiography on the Management of Trauma Patients

    PubMed Central

    Griffee, Matthew J.; Singleton, Andrew; Zimmerman, Joshua M.; Morgan, David E.; Nirula, Raminder

    2018-01-01

    To evaluate the effect of rescue transesophageal echocardiography (TEE) on the management of trauma patients, we reviewed imaging and charts of unstable trauma patients at a level I trauma center. Critical rescue TEE findings included acute right ventricular failure, stress cardiomyopathy, type B aortic dissection, mediastinal air, and dynamic left ventricular outflow tract obstruction. Left ventricular filling was classified as low (underfilled) in 57% of all cases. Rescue TEE revealed a variety of new diagnoses and led to a change in resuscitation strategy about half of the time. PMID:27301053

  11. Rescue of bilirubin-induced neonatal lethality in a mouse model of Crigler-Najjar syndrome type I by AAV9-mediated gene transfer

    PubMed Central

    Bortolussi, Giulia; Zentilin, Lorena; Baj, Gabriele; Giraudi, Pablo; Bellarosa, Cristina; Giacca, Mauro; Tiribelli, Claudio; Muro, Andrés F.

    2012-01-01

    Crigler-Najjar type I (CNI) syndrome is a recessively inherited disorder characterized by severe unconjugated hyperbilirubinemia caused by uridine diphosphoglucuronosyltransferase 1A1 (UGT1A1) deficiency. The disease is lethal due to bilirubin-induced neurological damage unless phototherapy is applied from birth. However, treatment becomes less effective during growth, and liver transplantation is required. To investigate the pathophysiology of the disease and therapeutic approaches in mice, we generated a mouse model by introducing a premature stop codon in the UGT1a1 gene, which results in an inactive enzyme. Homozygous mutant mice developed severe jaundice soon after birth and died within 11 d, showing significant cerebellar alterations. To rescue neonatal lethality, newborns were injected with a single dose of adeno-associated viral vector 9 (AAV9) expressing the human UGT1A1. Gene therapy treatment completely rescued all AAV-treated mutant mice, accompanied by lower plasma bilirubin levels and normal brain histology and motor coordination. Our mouse model of CNI reproduces genetic and phenotypic features of the human disease. We have shown, for the first time, the full recovery of the lethal effects of neonatal hyperbilirubinemia. We believe that, besides gene-addition-based therapies, our mice could represent a very useful model to develop and test novel technologies based on gene correction by homologous recombination.—Bortolussi, G., Zentilin, L., Baj, G., Giraudi, P., Bellarosa, C., Giacca, M., Tiribelli, C., Muro, A. F. Rescue of bilirubin-induced neonatal lethality in a mouse model of Crigler-Najjar syndrome type I by AAV9-mediated gene transfer. PMID:22094718

  12. 30 CFR Appendix to Subpart B of... - Optional Form for Certifying Mine Rescue Teams

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Optional Form for Certifying Mine Rescue Teams... LABOR EDUCATION AND TRAINING MINE RESCUE TEAMS Mine Rescue Teams for Underground Coal Mines Pt. 49, Subpt. B, App. Appendix to Subpart B of Part 49—Optional Form for Certifying Mine Rescue Teams ER08FE08...

  13. 30 CFR Appendix to Subpart B of... - Optional Form for Certifying Mine Rescue Teams

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Optional Form for Certifying Mine Rescue Teams... LABOR EDUCATION AND TRAINING MINE RESCUE TEAMS Mine Rescue Teams for Underground Coal Mines Pt. 49, Subpt. B, App. Appendix to Subpart B of Part 49—Optional Form for Certifying Mine Rescue Teams ER08FE08...

  14. 30 CFR Appendix to Subpart B - Optional Form for Certifying Mine Rescue Teams

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Optional Form for Certifying Mine Rescue Teams... EDUCATION AND TRAINING MINE RESCUE TEAMS Mine Rescue Teams for Underground Coal Mines Pt. 49, Subpt. B, App. Appendix to Subpart B—Optional Form for Certifying Mine Rescue Teams ER08FE08.000 ER08FE08.001 ...

  15. 30 CFR Appendix to Subpart B - Optional Form for Certifying Mine Rescue Teams

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Optional Form for Certifying Mine Rescue Teams... EDUCATION AND TRAINING MINE RESCUE TEAMS Mine Rescue Teams for Underground Coal Mines Pt. 49, Subpt. B, App. Appendix to Subpart B—Optional Form for Certifying Mine Rescue Teams ER08FE08.000 ER08FE08.001 ...

  16. 30 CFR Appendix to Subpart B - Optional Form for Certifying Mine Rescue Teams

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Optional Form for Certifying Mine Rescue Teams... EDUCATION AND TRAINING MINE RESCUE TEAMS Mine Rescue Teams for Underground Coal Mines Pt. 49, Subpt. B, App. Appendix to Subpart B—Optional Form for Certifying Mine Rescue Teams ER08FE08.000 ER08FE08.001 ...

  17. FGFR4 signaling couples to Bim and not Bmf to discriminate subsets of alveolar rhabdomyosarcoma cells.

    PubMed

    Wachtel, Marco; Rakic, Jelena; Okoniewski, Michal; Bode, Peter; Niggli, Felix; Schäfer, Beat W

    2014-10-01

    Biological heterogeneity represents a major obstacle for cancer treatment. Therefore, characterization of treatment-relevant tumor heterogeneity is necessary to develop more effective therapies in the future. Here, we uncovered population heterogeneity among PAX/FOXO1-positive alveolar rhabdomyosarcoma by characterizing prosurvival networks initiated by FGFR4 signaling. We found that FGFR4 signaling rescues only subgroups of alveolar rhabdomyosarcoma cells from apoptosis induced by compounds targeting the IGF1R-PI3K-mTOR pathway. Differences in both proapoptotic machinery and FGFR4-activated signaling are involved in the different behavior of the phenotypes. Proapoptotic stress induced by the kinase inhibitors is sensed by Bim/Bad in rescue cells and by Bmf in nonrescue cells. Anti-apoptotic ERK1/2 signaling downstream of FGFR4 is long-lasting in rescue and short-termed in most non-rescue cells. Gene expression analysis detected signatures specific for these two groups also in biopsy samples. The different cell phenotypes are present in different ratios in alveolar rhabdomyosarcoma tumors and can be identified by AP2β expression levels. Hence, inhibiting FGFR signaling might represent an important strategy to enhance efficacy of current RMS treatments. © 2014 UICC.

  18. Understanding the Outcome in the Chinese Changjiang Disaster in 2015: A Retrospective Study.

    PubMed

    Yang, Ce; Gao, Jie; Du, Juan; Wang, Haiyan; Jiang, Jianxin; Wang, Zhengguo

    2017-02-01

    Rescue after a maritime disaster remains a great challenge in emergency medicine. We performed an overview of rescue efforts among the victims in the sunken cruise ship Eastern Star in the 2015 Changjiang River marine disaster, as well as possible preventive measures in maritime transport situations. The rescue records of 454 victims of the sunken ship were analyzed retrospectively. Their demographic data, rescue effects, accident inducement, and injury disposition were reviewed. A thorough analysis from the point of view of maritime traffic safety was also performed. Of the 454 victims, 442 (97.36%) were killed and only 12 (2.64%) survived. The survivors were classified based on their gender, rescue type, and rescue spot as follows: male (91.67%), female (8.33%); tourists (50.00%), and ship staff (50.00%), after the breakdown of the rescue spot in Jianli, Hubei province, China. The survivors were saved only during the initial 17 h after the disaster. The survivors suffering from somato- and psychotrauma were urgently treated for limb injuries, infections of the upper respiratory tract and lungs, fluid and electrolyte imbalance, and acute traumatic stress. This incident was the most severe maritime disaster since the establishment of the People's Republic of China on October 1, 1949, due to the large number of elderly victims, fast overturning speed, and severe weather. Emergency rescue requires more automated and intelligent systems for maritime safety. An increased focus must be placed on public welfare and ethics, with the goal of influencing more prosocial behavior rather than the pursuit of profit. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Rescue and serotypic characterization of noncultivable human rotavirus by gene reassortment.

    PubMed Central

    Greenberg, H B; Wyatt, R G; Kapikian, A Z; Kalica, A R; Flores, J; Jones, R

    1982-01-01

    Thirty-three of 50 noncultivable human rotavirus strains from a variety of locations were successfully rescued by gene reassortment. The serotype of each of the 33 strains was investigated by a qualitative cytopathic effect neutralization assay. Nineteen strains resembled the previously characterized human rotavirus serotype Wa, whereas three strains were serologically related to the DS-1 strain. Eleven strains appeared to be serotypically distinct from the Wa and DS-1 strains and thus apparently represent one or more new human rotavirus serotypes. Images PMID:6286486

  20. WASP-1, a canonical Wnt signaling potentiator, rescues hippocampal synaptic impairments induced by Aβ oligomers.

    PubMed

    Vargas, Jessica Y; Ahumada, Juan; Arrázola, Macarena S; Fuenzalida, Marco; Inestrosa, Nibaldo C

    2015-02-01

    Amyloid-β (Aβ) oligomers are a key factor in Alzheimer's disease (AD)-associated synaptic dysfunction. Aβ oligomers block the induction of hippocampal long-term potentiation (LTP) in rodents. The activation of Wnt signaling prevents Aβ oligomer-induced neurotoxic effects. The compound WASP-1 (Wnt-activating small molecule potentiator-1), has been described as a synergist of the ligand Wnt-3a, enhancing the activation of Wnt/β-catenin signaling. Herein, we report that WASP-1 administration successfully rescued Aβ-induced synaptic impairments both in vitro and in vivo. The activation of canonical Wnt/β-catenin signaling by WASP-1 increased synaptic transmission and rescued hippocampal LTP impairments induced by Aβ oligomers. Additionally, intra-hippocampal administration of WASP-1 to the double transgenic APPswe/PS1dE9 mouse model of AD prevented synaptic protein loss and reduced tau phosphorylation levels. Moreover, we found that WASP-1 blocked Aβ aggregation in vitro and reduced pathological tau phosphorylation in vivo. These results indicate that targeting canonical Wnt signaling with WASP-1 could have value for treating AD. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Live birth and normal 1-year follow-up of a baby born after transfer of cryopreserved embryos from rescue intracytoplasmic sperm injection of 1-day-old oocytes.

    PubMed

    Lombardi, Eduardo; Tiverón, Marisa; Inza, Roberto; Valcárcel, Alberto; Young, Edgardo; Bisioli, Claudio

    2003-09-01

    To report the birth and normal pediatric follow-up of the first baby born after transfer of embryos derived from cryopreserved rescue intracytoplasmic sperm injection (ICSI). Case report. Academic fertility unit. A 36-year-old woman with unexplained infertility. Reinsemination by ICSI ("rescue" ICSI) followed by cryopreservation at the pronuclear stage was performed after partial fertilization failure. Pregnancy, birth, and 1-year follow-up of the baby born after the transfer of the cryopreserved rescue ICSI embryos. Zygotes obtained after rescue ICSI were able to tolerate the process of cryopreservation and resulted in a viable pregnancy and delivery.

  2. Peroral endoscopic myotomy is a viable option for failed surgical esophagocardiomyotomy instead of redo surgical Heller myotomy: a single center prospective study.

    PubMed

    Onimaru, Manabu; Inoue, Haruhiro; Ikeda, Haruo; Yoshida, Akira; Santi, Esperanza Grace; Sato, Hiroki; Ito, Hiroaki; Maselli, Roberta; Kudo, Shin-ei

    2013-10-01

    Surgical Heller myotomy has high rates of successful long-term results, but failed cases still remain. Moreover, the treatment strategy in patients with surgical myotomy failure is controversial. Recently, peroral endscopic myotomy (POEM) was reported to be efficient and safe in primary treatment of achalasia. In this study, we aimed to evaluate the efficacy and safety of POEM for surgical myotomy failure as a rescue second-line treatment, and we discuss the treatment options adapted in achalasia recurrence. A total of 315 consecutive achalasia patients received POEM from September 2008 to December 2012 in our hospital. Eleven (3.5%) patients who had persistent or recurrent achalasia and had received surgical myotomy as a first-line treatment from other hospitals were included in this study. Patient background, barium swallow studies, esophagogastroduodenoscopy (EGD), manometry, and symptom scores were prospectively evaluated. In principle, all patients in whom surgical myotomy failed received pneumatic balloon dilatation (PBD) as the first line "rescue" treatment, and only if PBD failed were patients considered for rescue POEM. The PBD alone was effective in 1 patient, and in the remaining 10 patients, rescue POEM was performed successfully without complications. Three months after rescue POEM, significant reduction in lower esophageal sphincter (LES) resting pressures (22.1 ± 6.6 mmHg vs 10.9 ± 4.5 mmHg, p < 0.01) and Eckardt symptom scores (6.5 ± 1.3 vs 1.1 ± 1.3, p < 0.001) were observed. Short-term results of POEM for failed surgical myotomy were excellent. Long-term results are awaited. Copyright © 2013 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

  3. Enhanced Rescue Lift Capability

    NASA Technical Reports Server (NTRS)

    Young, Larry A.

    2007-01-01

    The evolving and ever-increasing demands of emergency response and disaster relief support provided by rotorcraft dictate, among other things, the development of enhanced rescue lift capability for these platforms. This preliminary analysis is first-order in nature but provides considerable insight into some of the challenges inherent in trying to effect rescue using a unique form of robotic rescue device deployed and operated from rotary-wing aerial platforms.

  4. Multivariate Prediction Equations for HbA1c Lowering, Weight Change, and Hypoglycemic Events Associated with Insulin Rescue Medication in Type 2 Diabetes Mellitus: Informing Economic Modeling.

    PubMed

    Willis, Michael; Asseburg, Christian; Nilsson, Andreas; Johnsson, Kristina; Kartman, Bernt

    2017-03-01

    Type 2 diabetes mellitus (T2DM) is chronic and progressive and the cost-effectiveness of new treatment interventions must be established over long time horizons. Given the limited durability of drugs, assumptions regarding downstream rescue medication can drive results. Especially for insulin, for which treatment effects and adverse events are known to depend on patient characteristics, this can be problematic for health economic evaluation involving modeling. To estimate parsimonious multivariate equations of treatment effects and hypoglycemic event risks for use in parameterizing insulin rescue therapy in model-based cost-effectiveness analysis. Clinical evidence for insulin use in T2DM was identified in PubMed and from published reviews and meta-analyses. Study and patient characteristics and treatment effects and adverse event rates were extracted and the data used to estimate parsimonious treatment effect and hypoglycemic event risk equations using multivariate regression analysis. Data from 91 studies featuring 171 usable study arms were identified, mostly for premix and basal insulin types. Multivariate prediction equations for glycated hemoglobin A 1c lowering and weight change were estimated separately for insulin-naive and insulin-experienced patients. Goodness of fit (R 2 ) for both outcomes were generally good, ranging from 0.44 to 0.84. Multivariate prediction equations for symptomatic, nocturnal, and severe hypoglycemic events were also estimated, though considerable heterogeneity in definitions limits their usefulness. Parsimonious and robust multivariate prediction equations were estimated for glycated hemoglobin A 1c and weight change, separately for insulin-naive and insulin-experienced patients. Using these in economic simulation modeling in T2DM can improve realism and flexibility in modeling insulin rescue medication. Copyright © 2017 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

  5. Transcorneal electrical stimulation rescues axotomized retinal ganglion cells by activating endogenous retinal IGF-1 system.

    PubMed

    Morimoto, Takeshi; Miyoshi, Tomomitsu; Matsuda, Satoshi; Tano, Yasuo; Fujikado, Takashi; Fukuda, Yutaka

    2005-06-01

    To investigate the effect of transcorneal electrical stimulation (TES) on the survival of axotomized RGCs and the mechanism underlying the TES-induced neuroprotection in vivo. Adult male Wistar rats received TES after optic nerve (ON) transection. Seven days after the ON transection, the density of the surviving RGCs was determined, to evaluate the neuroprotective effect of TES. The levels of the mRNA and protein of insulin-like growth factor (IGF)-1 in the retina after TES were determined by RT-PCR and Northern and Western blot analyses. The localization of IGF-1 protein in the retina was examined by immunohistochemistry. TES after ON transection increased the survival of axotomized RGCs in vivo, and the degree of rescue depended on the strength of the electric charge. RT-PCR and Northern and Western blot analyses revealed a gradual upregulation of intrinsic IGF-1 in the retina after TES. Immunohistochemical analysis showed that IGF-1 immunoreactivity was localized initially in the endfeet of Muller cells and then diffused into the inner retina. TES can rescue the axotomized RGCs by increasing the level of IGF-1 production by Muller cells. These findings provide a new therapeutic approach to prevent or delay the degeneration of retinal neurons without the administration of exogenous neurotrophic factors.

  6. Tramadol wound infiltration is not different from intravenous tramadol in children: a randomized controlled trial.

    PubMed

    Giraldes, Ana Laura Albertoni; Sousa, Angela Maria; Slullitel, Alexandre; Guimarães, Gabriel Magalhães Nunes; Santos, Melina Geneviève Mary Egan; Pinto, Renata Evangelista; Ashmawi, Hazem Adel; Sakata, Rioko Kimiko

    2016-02-01

    The purpose of this trial was to assess if tramadol wound infiltration is superior to intravenous (IV) tramadol after minor surgical procedures in children because tramadol seems to have local anesthetic-like effect. Randomized double-blind controlled trial. Postanesthesia care unit. Forty children, American Society of Anesthesiologists physical status I or II, scheduled to elective inguinal hernia repair. Children were randomly distributed in 1 of 2 groups: IV tramadol (group 1) or subcutaneous infiltration with tramadol (group 2). At the end of the surgery, group 1 received 2 mg/kg tramadol (3 mL) by IV route and 3-mL saline into the surgical wound; group 2 received 2 mg/kg tramadol (3 mL) into the surgical wound and 3-mL saline by IV route. In the postanesthesia care unit, patients were evaluated for pain intensity, nausea and vomiting, time to first rescue medication, and total rescue morphine and dipyrone consumption. Pain scores measured during the postanesthesia recovery time were similar between groups. Time to first rescue medication was shorter, but not statistically significant in the IV group. The total dose of rescue morphine and dipyrone was also similar between groups. We concluded that tramadol was effective in reducing postoperative pain in children, and there was no difference in pain intensity, nausea and vomiting, or somnolence regarding IV route or wound infiltration. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. DKK1 rescues osteogenic differentiation of mesenchymal stem cells isolated from periodontal ligaments of patients with diabetes mellitus induced periodontitis

    PubMed Central

    Liu, Qi; Hu, Cheng-Hu; Zhou, Cui-Hong; Cui, Xiao-Xia; Yang, Kun; Deng, Chao; Xia, Jia-Jia; Wu, Yan; Liu, Lu-Chuan; Jin, Yan

    2015-01-01

    Multiple studies have shown that diabetes mellitus is an established risk factor for periodontitis. Recently mesenchymal stem cells derived from periodontal ligament (PDLSCs) have been utilized to reconstruct tissues destroyed by chronic inflammation. However, impact of periodontitis with diabetes mellitus on PDLSCs and mechanisms mediating effects of complex microenvironments remain poorly understood. In this study, we found multiple differentiation potential of PDLSCs from chronic periodontitis with diabetes mellitus donors (D-PDLSCs) was damaged significantly. Inhibition of NF-κB signaling could rescue osteogenic potential of PDLSCs from simple chronic periodontitis patients (P-PDLSCs), whereas did not promote D-PDLSCs osteogenesis. In addition, we found expression of DKK1 in D-PDLSCs did not respond to osteogenic signal and decreased osteogenic potential of D-PDLSCs treated with DKK1 could be reversed. To further elucidate different character between P-PDLSCs and D-PDLSCs, we treated PDLSCs with TNF-α and advanced glycation end products (AGEs), and find out AGEs which enhance effect of TNF-α in PDLSCs might mediate special personality of D-PDLSCs. The adverse effect of AGEs in PDLSCs could be reversed when PDLSCs were treated with DKK1. These results suggested DKK1 mediating WNT signaling might be a therapy target to rescue potential of PDLSCs in periodontitis with diabetes mellitus. PMID:26278788

  8. Metal Binding by the D,DX35E Motif of Human Immunodeficiency Virus Type 1 Integrase: Selective Rescue of Cys Substitutions by Mn2+ In Vitro

    PubMed Central

    Gao, Kui; Wong, Steven; Bushman, Frederic

    2004-01-01

    The D,DX35E motif characteristic of retroviral integrase enzymes (INs) is expected to bind the required metal cofactors (Mg2+ or Mn2+), but direct evidence for a catalytic role has been lacking. Here we used a metal rescue strategy to investigate metal binding. We established conditions for analysis of an activity of IN, disintegration, in both Mg2+ and Mn2+, and tested IN mutants with cysteine substitutions in each acidic residue of the D,DX35E motif. Mn2+ but not Mg2+ can bind tightly to Cys, so if metal binding at the acidic residues is mechanistically important, it is expected that the Cys-substituted enzymes would be active in the presence of Mn2+ only. Of the three acidic residues, a strong metal rescue effect was obtained for D116C, a weaker rescue was seen for D64C, and no rescue was seen with E152C. Modest rescue could also be detected for D116C in normal integration in vitro. Comparison to Ser and Ala substitutions at D116 established that the rescue was selective for Cys. Further studies of the response to pH suggest that the metal cofactor may stabilize the deprotonated nucleophile active in catalysis, and studies of the response to NaCl titrations disclose an additional role for the metal cofactor in stabilizing the IN-DNA complex. PMID:15194746

  9. Rescue Manual. Module 4.

    ERIC Educational Resources Information Center

    Ohio State Univ., Columbus. Instructional Materials Lab.

    This learner manual for rescuers covers the current techniques or practices required in the rescue service. The fourth of 10 modules contains 8 chapters: (1) construction and characteristics of rescue rope; (2) knots, bends, and hitches; (3) critical angles; (4) raising systems; (5) rigging; (6) using the brake-bar rack for rope rescue; (7) rope…

  10. 46 CFR 117.210 - Rescue boats.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 4 2014-10-01 2014-10-01 false Rescue boats. 117.210 Section 117.210 Shipping COAST... Number and Type of Survival Craft § 117.210 Rescue boats. (a) Each vessel must carry at least one rescue boat unless the cognizant OCMI determines that: (1) The vessel is sufficiently maneuverable, arranged...

  11. 46 CFR 117.210 - Rescue boats.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 4 2012-10-01 2012-10-01 false Rescue boats. 117.210 Section 117.210 Shipping COAST... Number and Type of Survival Craft § 117.210 Rescue boats. (a) Each vessel must carry at least one rescue boat unless the cognizant OCMI determines that: (1) The vessel is sufficiently maneuverable, arranged...

  12. 46 CFR 117.210 - Rescue boats.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 4 2011-10-01 2011-10-01 false Rescue boats. 117.210 Section 117.210 Shipping COAST... Number and Type of Survival Craft § 117.210 Rescue boats. (a) Each vessel must carry at least one rescue boat unless the cognizant OCMI determines that: (1) The vessel is sufficiently maneuverable, arranged...

  13. 46 CFR 117.210 - Rescue boats.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 4 2013-10-01 2013-10-01 false Rescue boats. 117.210 Section 117.210 Shipping COAST... Number and Type of Survival Craft § 117.210 Rescue boats. (a) Each vessel must carry at least one rescue boat unless the cognizant OCMI determines that: (1) The vessel is sufficiently maneuverable, arranged...

  14. 30 CFR 49.4 - Alternative mine rescue capability for special mining conditions.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Alternative mine rescue capability for special mining conditions. 49.4 Section 49.4 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR EDUCATION AND TRAINING MINE RESCUE TEAMS Mine Rescue Teams for Underground Metal and...

  15. 30 CFR 49.4 - Alternative mine rescue capability for special mining conditions.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Alternative mine rescue capability for special mining conditions. 49.4 Section 49.4 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR EDUCATION AND TRAINING MINE RESCUE TEAMS Mine Rescue Teams for Underground Metal and...

  16. 30 CFR 49.4 - Alternative mine rescue capability for special mining conditions.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Alternative mine rescue capability for special mining conditions. 49.4 Section 49.4 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR EDUCATION AND TRAINING MINE RESCUE TEAMS Mine Rescue Teams for Underground Metal and...

  17. 30 CFR 49.5 - Mine rescue station.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Mine rescue station. 49.5 Section 49.5 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR EDUCATION AND TRAINING MINE RESCUE TEAMS § 49.5 Mine rescue station. (a) Except where alternative compliance is permitted, every operator...

  18. 30 CFR 49.5 - Mine rescue station.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Mine rescue station. 49.5 Section 49.5 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR EDUCATION AND TRAINING MINE RESCUE TEAMS § 49.5 Mine rescue station. (a) Except where alternative compliance is permitted, every operator...

  19. Comparison of rescue techniques for failed chloral hydrate sedation for magnetic resonance imaging scans--additional chloral hydrate vs intranasal dexmedetomidine.

    PubMed

    Zhang, Wenhua; Wang, Zixin; Song, Xingrong; Fan, Yanting; Tian, Hang; Li, Bilian

    2016-03-01

    Chloral hydrate, a commonly used sedative in children during noninvasive diagnostic procedures, is associated with side effects like prolonged sedation, paradoxical excitement, delirium, and unpleasant taste. Dexmedetomidine, a highly selective α-2 agonist, has better pharmacokinetic properties than chloral hydrate. We conducted this prospective, double-blind, randomized controlled trial to evaluate efficacy of intranasal dexmedetomidine with that of a second oral dose of chloral hydrate for rescue sedation during magnetic resonance imaging (MRI) studies in infants. One hundred and fifty infants (age group: 1-6 months), who were not adequately sedated after initial oral dose of 50 mg · kg(-1) chloral hydrate, were randomly divided into three groups with the following protocol for each group. Group C: second oral dose chloral hydrate 25 mg · kg(-1); Group L and Group H: intranasal dexmedetomidine in a dosage of 1 and 2 mcg · kg(-1), respectively. Status of sedation, induction time, time to wake up, vital signs, oxygen saturation, and recovery characteristics were recorded. Successful rescue sedation in Groups C, L, and H were achieved in 40 (80%), 47 (94%), and 49 (98%) of infants, respectively, on an intention to treat analysis, and the proportion of infants successfully sedated in Group H was more than that of Group L (P ˂ 0.01). There were no significant differences in sedation induction time; however, the time to wake up was significantly shorter in Group L as compared to that in Group C or H (P < 0.01). No significant adverse hemodynamic or hypoxemic effects were observed in the study. Intranasal dexmedetomidine induced satisfactory rescue sedation in 1- to 6-month-old infants during MRI study, and appears to cause sedation in a dose-dependent manner. © 2015 John Wiley & Sons Ltd.

  20. MicroRNA-Mediated Rescue of Fear Extinction Memory by miR-144-3p in Extinction-Impaired Mice.

    PubMed

    Murphy, Conor P; Li, Xiang; Maurer, Verena; Oberhauser, Michael; Gstir, Ronald; Wearick-Silva, Luis Eduardo; Viola, Thiago Wendt; Schafferer, Simon; Grassi-Oliveira, Rodrigo; Whittle, Nigel; Hüttenhofer, Alexander; Bredy, Timothy W; Singewald, Nicolas

    2017-06-15

    MicroRNA (miRNA)-mediated control of gene expression suggests that miRNAs are interesting targets and/or biomarkers in the treatment of anxiety- and trauma-related disorders, where often memory-associated gene expression is adversely affected. The role of miRNAs in the rescue of impaired fear extinction was assessed using the 129S1/SvlmJ (S1) mouse model of impaired fear extinction. miRNA microarray analysis, reverse transcription polymerase chain reaction, fluorescent in situ hybridization, lentiviral overexpression, and Luciferase reporter assays were used to gain insight into the mechanisms underlying miRNA-mediated normalization of deficient fear extinction. Rescuing impaired fear extinction via dietary zinc restriction was associated with differential expression of miRNAs in the amygdala. One candidate, miR-144-3p, robustly expressed in the basolateral amygdala, showed specific extinction-induced, but not fear-induced, increased expression in both extinction-rescued S1 mice and extinction-intact C57BL/6 (BL6) mice. miR-144-3p upregulation and effects on subsequent behavioral adaption was assessed in S1 and BL6 mice. miR-144-3p overexpression in the basolateral amygdala rescued impaired fear extinction in S1 mice, led to enhanced fear extinction acquisition in BL6 mice, and furthermore protected against fear renewal in BL6 mice. miR-144-3p targets a number of genes implicated in the control of plasticity-associated signaling cascades, including Pten, Spred1, and Notch1. In functional interaction studies, we revealed that the miR-144-3p target, PTEN, colocalized with miR-144-3p in the basolateral amygdala and showed functional downregulation following successful fear extinction in S1 mice. These findings identify a fundamental role of miR-144-3p in the rescue of impaired fear extinction and suggest this miRNA as a viable target in developing novel treatments for posttraumatic stress disorder and related disorders. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  1. Isobutanol production as an alternative metabolic sink to rescue the growth deficiency of the glycogen mutant of Synechococcus elongatus PCC 7942

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Li, XQ; Shen, CR; Liao, JC

    2014-03-04

    Glycogen synthesis initiated by glucose-1-phosphate adenylyltransferase (glgC) represents a major carbon storage route in cyanobacteria which could divert a significant portion of assimilated carbon. Significant growth retardation in cyanobacteria with glgC knocked out (Delta glgC) has been reported in high light conditions. Here, we knocked out the glgC gene and analyzed its effects on carbon distribution in an isobutanol-producing strain of Synechococcus elongatus PCC7942 and its parental wild-type strain. We showed that isobutanol production was able to partially rescue the growth of Delta glgC mutant where the growth rescue effect positively correlated with the rate of isobutanol production. Using (NaHCO3)-C-14more » incorporation analysis, we observed a 28 % loss of total carbon fixation rate in the Delta glgC mutant compared to the wild-type. Upon expression of the isobutanol production pathway in Delta glgC mutant, the total carbon fixation rate was restored to the wild-type level. Furthermore, we showed that 52 % of the total carbon fixed was redirected into isobutanol biosynthesis in the Delta glgC mutant expressing enzymes for isobutanol production, which is 2.5 times higher than that of the wild-type expressing the same enzymes. These results suggest that biosynthesis of non-native product such as isobutanol can serve as a metabolic sink for replacing glycogen to rescue growth and restore carbon fixation rate. The rescue effect may further serve as a platform for cyanobacteria energy and carbon metabolism study.« less

  2. 30 CFR 49.50 - Certification of coal mine rescue teams.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Certification of coal mine rescue teams. 49.50... TRAINING MINE RESCUE TEAMS Mine Rescue Teams for Underground Coal Mines § 49.50 Certification of coal mine... coal mine, the mine operator shall send the District Manager an annual statement certifying that each...

  3. 30 CFR 49.50 - Certification of coal mine rescue teams.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Certification of coal mine rescue teams. 49.50... TRAINING MINE RESCUE TEAMS Mine Rescue Teams for Underground Coal Mines § 49.50 Certification of coal mine... coal mine, the mine operator shall send the District Manager an annual statement certifying that each...

  4. 30 CFR 49.50 - Certification of coal mine rescue teams.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Certification of coal mine rescue teams. 49.50... TRAINING MINE RESCUE TEAMS Mine Rescue Teams for Underground Coal Mines § 49.50 Certification of coal mine... coal mine, the mine operator shall send the District Manager an annual statement certifying that each...

  5. 30 CFR 49.50 - Certification of coal mine rescue teams.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Certification of coal mine rescue teams. 49.50... TRAINING MINE RESCUE TEAMS Mine Rescue Teams for Underground Coal Mines § 49.50 Certification of coal mine... coal mine, the mine operator shall send the District Manager an annual statement certifying that each...

  6. 30 CFR 49.50 - Certification of coal mine rescue teams.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Certification of coal mine rescue teams. 49.50... TRAINING MINE RESCUE TEAMS Mine Rescue Teams for Underground Coal Mines § 49.50 Certification of coal mine... coal mine, the mine operator shall send the District Manager an annual statement certifying that each...

  7. 30 CFR 57.15031 - Location of self-rescue devices.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... around mobile equipment, self-rescue devices may be placed in a readily accessible location on such... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Location of self-rescue devices. 57.15031... Protection Underground Only § 57.15031 Location of self-rescue devices. (a) Except as provided in paragraph...

  8. 46 CFR 133.175 - Survival craft and rescue boat equipment.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 4 2011-10-01 2011-10-01 false Survival craft and rescue boat equipment. 133.175... LIFESAVING SYSTEMS Requirements for All OSVs § 133.175 Survival craft and rescue boat equipment. (a) All rescue boat equipment must be as follows: (1) The equipment must be secured within the boat by lashings...

  9. 46 CFR 108.575 - Survival craft and rescue boat equipment.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 4 2013-10-01 2013-10-01 false Survival craft and rescue boat equipment. 108.575... DRILLING UNITS DESIGN AND EQUIPMENT Lifesaving Equipment § 108.575 Survival craft and rescue boat equipment. (a) All lifeboat and rescue boat equipment must be as follows: (1) The equipment must be secured...

  10. 46 CFR 133.175 - Survival craft and rescue boat equipment.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 4 2014-10-01 2014-10-01 false Survival craft and rescue boat equipment. 133.175... LIFESAVING SYSTEMS Requirements for All OSVs § 133.175 Survival craft and rescue boat equipment. (a) All rescue boat equipment must be as follows: (1) The equipment must be secured within the boat by lashings...

  11. 46 CFR 133.175 - Survival craft and rescue boat equipment.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 4 2012-10-01 2012-10-01 false Survival craft and rescue boat equipment. 133.175... LIFESAVING SYSTEMS Requirements for All OSVs § 133.175 Survival craft and rescue boat equipment. (a) All rescue boat equipment must be as follows: (1) The equipment must be secured within the boat by lashings...

  12. 46 CFR 133.175 - Survival craft and rescue boat equipment.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 4 2013-10-01 2013-10-01 false Survival craft and rescue boat equipment. 133.175... LIFESAVING SYSTEMS Requirements for All OSVs § 133.175 Survival craft and rescue boat equipment. (a) All rescue boat equipment must be as follows: (1) The equipment must be secured within the boat by lashings...

  13. 30 CFR 49.4 - Alternative mine rescue capability for special mining conditions.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Alternative mine rescue capability for special mining conditions. 49.4 Section 49.4 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR EDUCATION AND TRAINING MINE RESCUE TEAMS § 49.4 Alternative mine rescue capability for...

  14. 30 CFR 49.2 - Availability of mine rescue teams.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Availability of mine rescue teams. 49.2 Section... TRAINING MINE RESCUE TEAMS § 49.2 Availability of mine rescue teams. (a) Except where alternative... teams which are available at all times when miners are underground; or (2) Enter into an arrangement for...

  15. 30 CFR 49.4 - Alternative mine rescue capability for special mining conditions.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Alternative mine rescue capability for special mining conditions. 49.4 Section 49.4 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR EDUCATION AND TRAINING MINE RESCUE TEAMS § 49.4 Alternative mine rescue capability for...

  16. 30 CFR 49.2 - Availability of mine rescue teams.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Availability of mine rescue teams. 49.2 Section... TRAINING MINE RESCUE TEAMS § 49.2 Availability of mine rescue teams. (a) Except where alternative... teams which are available at all times when miners are underground; or (2) Enter into an arrangement for...

  17. 46 CFR 12.10-9 - Endorsement for proficiency in fast rescue boats.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 1 2011-10-01 2011-10-01 false Endorsement for proficiency in fast rescue boats. 12.10... SEAMEN REQUIREMENTS FOR RATING ENDORSEMENTS Lifeboatman § 12.10-9 Endorsement for proficiency in fast rescue boats. (a) Each person engaged or employed as a lifeboatman proficient in fast rescue boats must...

  18. 46 CFR 12.10-9 - Endorsement for proficiency in fast rescue boats.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 1 2013-10-01 2013-10-01 false Endorsement for proficiency in fast rescue boats. 12.10... SEAMEN REQUIREMENTS FOR RATING ENDORSEMENTS Lifeboatman § 12.10-9 Endorsement for proficiency in fast rescue boats. (a) Each person engaged or employed as a lifeboatman proficient in fast rescue boats must...

  19. 46 CFR 12.10-9 - Endorsement for proficiency in fast rescue boats.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 1 2010-10-01 2010-10-01 false Endorsement for proficiency in fast rescue boats. 12.10... SEAMEN REQUIREMENTS FOR RATING ENDORSEMENTS Lifeboatman § 12.10-9 Endorsement for proficiency in fast rescue boats. (a) Each person engaged or employed as a lifeboatman proficient in fast rescue boats must...

  20. 46 CFR 12.10-9 - Endorsement for proficiency in fast rescue boats.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 1 2012-10-01 2012-10-01 false Endorsement for proficiency in fast rescue boats. 12.10... SEAMEN REQUIREMENTS FOR RATING ENDORSEMENTS Lifeboatman § 12.10-9 Endorsement for proficiency in fast rescue boats. (a) Each person engaged or employed as a lifeboatman proficient in fast rescue boats must...

  1. Field studies of safety security rescue technologies through training and response activities

    NASA Astrophysics Data System (ADS)

    Murphy, Robin R.; Stover, Sam

    2006-05-01

    This paper describes the field-oriented philosophy of the Institute for Safety Security Rescue Technology (iSSRT) and summarizes the activities and lessons learned during calendar year 2005 of its two centers: the Center for Robot-Assisted Search and Rescue and the NSF Safety Security Rescue industry/university cooperative research center. In 2005, iSSRT participated in four responses (La Conchita, CA, Mudslides, Hurricane Dennis, Hurricane Katrina, Hurricane Wilma) and conducted three field experiments (NJTF-1, Camp Hurricane, Richmond, MO). The lessons learned covered mobility, operator control units, wireless communications, and general reliability. The work has collectively identified six emerging issues for future work. Based on these studies, a 10-hour, 1 continuing education unit credit course on rescue robotics has been created and is available. Rescue robots and sensors are available for loan upon request.

  2. 46 CFR 199.140 - Stowage of rescue boats.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 7 2014-10-01 2014-10-01 false Stowage of rescue boats. 199.140 Section 199.140... boats. (a) General. Rescue boats must be stowed— (1) To be ready for launching in not more than 5 minutes. (2) In a position suitable for launching and recovery; (3) In a way that neither the rescue boat...

  3. 46 CFR 199.140 - Stowage of rescue boats.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 7 2012-10-01 2012-10-01 false Stowage of rescue boats. 199.140 Section 199.140... boats. (a) General. Rescue boats must be stowed— (1) To be ready for launching in not more than 5 minutes. (2) In a position suitable for launching and recovery; (3) In a way that neither the rescue boat...

  4. 46 CFR 199.140 - Stowage of rescue boats.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Stowage of rescue boats. 199.140 Section 199.140... boats. (a) General. Rescue boats must be stowed— (1) To be ready for launching in not more than 5 minutes. (2) In a position suitable for launching and recovery; (3) In a way that neither the rescue boat...

  5. 46 CFR 199.140 - Stowage of rescue boats.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 7 2011-10-01 2011-10-01 false Stowage of rescue boats. 199.140 Section 199.140... boats. (a) General. Rescue boats must be stowed— (1) To be ready for launching in not more than 5 minutes. (2) In a position suitable for launching and recovery; (3) In a way that neither the rescue boat...

  6. 46 CFR 199.140 - Stowage of rescue boats.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 7 2013-10-01 2013-10-01 false Stowage of rescue boats. 199.140 Section 199.140... boats. (a) General. Rescue boats must be stowed— (1) To be ready for launching in not more than 5 minutes. (2) In a position suitable for launching and recovery; (3) In a way that neither the rescue boat...

  7. Nonintravenous rescue medications for pediatric status epilepticus: A cost-effectiveness analysis.

    PubMed

    Sánchez Fernández, Iván; Gaínza-Lein, Marina; Loddenkemper, Tobias

    2017-08-01

    To quantify the cost-effectiveness of rescue medications for pediatric status epilepticus: rectal diazepam, nasal midazolam, buccal midazolam, intramuscular midazolam, and nasal lorazepam. Decision analysis model populated with effectiveness data from the literature and cost data from publicly available market prices. The primary outcome was cost per seizure stopped ($/SS). One-way sensitivity analyses and second-order Monte Carlo simulations evaluated the robustness of the results across wide variations of the input parameters. The most cost-effective rescue medication was buccal midazolam (incremental cost-effectiveness ratio ([ICER]: $13.16/SS) followed by nasal midazolam (ICER: $38.19/SS). Nasal lorazepam (ICER: -$3.8/SS), intramuscular midazolam (ICER: -$64/SS), and rectal diazepam (ICER: -$2,246.21/SS) are never more cost-effective than the other options at any willingness to pay. One-way sensitivity analysis showed the following: (1) at its current effectiveness, rectal diazepam would become the most cost-effective option only if its cost was $6 or less, and (2) at its current cost, rectal diazepam would become the most cost-effective option only if effectiveness was higher than 0.89 (and only with very high willingness to pay of $2,859/SS to $31,447/SS). Second-order Monte Carlo simulations showed the following: (1) nasal midazolam and intramuscular midazolam were the more effective options; (2) the more cost-effective option was buccal midazolam for a willingness to pay from $14/SS to $41/SS and nasal midazolam for a willingness to pay above $41/SS; (3) cost-effectiveness overlapped for buccal midazolam, nasal lorazepam, intramuscular midazolam, and nasal midazolam; and (4) rectal diazepam was not cost-effective at any willingness to pay, and this conclusion remained extremely robust to wide variations of the input parameters. For pediatric status epilepticus, buccal midazolam and nasal midazolam are the most cost-effective nonintravenous rescue medications in the United States. Rectal diazepam is not a cost-effective alternative, and this conclusion remains extremely robust to wide variations of the input parameters. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

  8. Differential sensitivities of cellular XPA and PARP-1 to arsenite inhibition and zinc rescue.

    PubMed

    Ding, Xiaofeng; Zhou, Xixi; Cooper, Karen L; Huestis, Juliana; Hudson, Laurie G; Liu, Ke Jian

    2017-09-15

    Arsenite directly binds to the zinc finger domains of the DNA repair protein poly (ADP ribose) polymerase (PARP)-1, and inhibits PARP-1 activity in the base excision repair (BER) pathway. PARP inhibition by arsenite enhances ultraviolet radiation (UVR)-induced DNA damage in keratinocytes, and the increase in DNA damage is reduced by zinc supplementation. However, little is known about the effects of arsenite and zinc on the zinc finger nucleotide excision repair (NER) protein xeroderma pigmentosum group A (XPA). In this study, we investigated the difference in response to arsenite exposure between XPA and PARP-1, and the differential effectiveness of zinc supplementation in restoring protein DNA binding and DNA damage repair. Arsenite targeted both XPA and PARP-1 in human keratinocytes, resulting in zinc loss from each protein and a pronounced decrease in XPA and PARP-1 binding to chromatin as demonstrated by Chip-on-Western assays. Zinc effectively restored DNA binding of PARP-1 and XPA to chromatin when zinc concentrations were equal to those of arsenite. In contrast, zinc was more effective in rescuing arsenite-augmented direct UVR-induced DNA damage than oxidative DNA damage. Taken together, our findings indicate that arsenite interferes with PARP-1 and XPA binding to chromatin, and that zinc supplementation fully restores DNA binding activity to both proteins in the cellular context. Interestingly, rescue of arsenite-inhibited DNA damage repair by supplemental zinc was more sensitive for DNA damage repaired by the XPA-associated NER pathway than for the PARP-1-dependent BER pathway. This study expands our understanding of arsenite's role in DNA repair inhibition and co-carcinogenesis. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Rescuing Israeli travellers: effects of substance abuse, mental health, geographic region of rescue, gender and age of rescuees.

    PubMed

    Bonny-Noach, Hagit; Sagiv-Alayoff, Moran

    2017-09-01

    Research conducted on young Israeli travellers has pointed to high substance usage rates. For some drug-using backpackers, actual extraction and rescue from their trip abroad is necessary. This study represents a first attempt to explore the influence of geographic region in which rescue occurs, cause for rescue and gender and age differences among Israeli rescuees. Sub-analysis of all logs of individual rescuees during a 5-year period from 2011 to 2016 ( N  = 86) included 66 men and 20 women, with an average age of 27.83 (SD = 7.86). The findings demonstrate that Israelis are most frequently rescued from South and Southeast Asia (57%) followed by Europe (22%), South America (17%), North America (2.3%) and Africa (1.2%). India was the country with the highest rate of rescue incidents ( N  = 36) followed by Thailand ( N  = 8) and the Netherlands ( N  = 5). The most common cause for rescue was substance abuse (87%). However, significant regional differences were found based on the variable of age ( F  = 3.21, df = 3,50, P  < 0.05). The youngest rescuees were evacuated from South America ( M  = 24.20 years, SD  =   3.8), while the oldest were from Europe ( M  = 32.86 years, SD  =   10.9). The most frequent mental diagnosis for rescuees was acute psychosis due to substance use disorder (81%) and bipolar disorder, manic subtype due to substance abuse (7%). Significant gender differences were found among rescuees diagnosed with bipolar disorder, manic type: 25% were female, while men only accounted for 1.5% ( χ 2 = 61.70, df = 24, P  < 0.0001). Region, age and gender of young travellers should be taken into consideration when thinking about induced acute psychosis caused by substance use. Policymakers need to consider prevention and harm reduction interventions relevant to this risk group. © International Society of Travel Medicine, 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

  10. Success of Intubation Rescue Techniques after Failed Direct Laryngoscopy in Adults: A Retrospective Comparative Analysis from the Multicenter Perioperative Outcomes Group.

    PubMed

    Aziz, Michael F; Brambrink, Ansgar M; Healy, David W; Willett, Amy Wen; Shanks, Amy; Tremper, Tyler; Jameson, Leslie; Ragheb, Jacqueline; Biggs, Daniel A; Paganelli, William C; Rao, Janavi; Epps, Jerry L; Colquhoun, Douglas A; Bakke, Patrick; Kheterpal, Sachin

    2016-10-01

    Multiple attempts at tracheal intubation are associated with mortality, and successful rescue requires a structured plan. However, there remains a paucity of data to guide the choice of intubation rescue technique after failed initial direct laryngoscopy. The authors studied a large perioperative database to determine success rates for commonly used intubation rescue techniques. Using a retrospective, observational, comparative design, the authors analyzed records from seven academic centers within the Multicenter Perioperative Outcomes Group between 2004 and 2013. The primary outcome was the comparative success rate for five commonly used techniques to achieve successful tracheal intubation after failed direct laryngoscopy: (1) video laryngoscopy, (2) flexible fiberoptic intubation, (3) supraglottic airway as part of an exchange technique, (4) optical stylet, and (5) lighted stylet. A total of 346,861 cases were identified that involved attempted tracheal intubation. A total of 1,009 anesthesia providers managed 1,427 cases of failed direct laryngoscopy followed by subsequent intubation attempts (n = 1,619) that employed one of the five studied intubation rescue techniques. The use of video laryngoscopy resulted in a significantly higher success rate (92%; 95% CI, 90 to 93) than other techniques: supraglottic airway conduit (78%; 95% CI, 68 to 86), flexible bronchoscopic intubation (78%; 95% CI, 71 to 83), lighted stylet (77%; 95% CI, 69 to 83), and optical stylet (67%; 95% CI, 35 to 88). Providers most frequently choose video laryngoscopy (predominantly GlideScope [Verathon, USA]) to rescue failed direct laryngoscopy (1,122/1,619; 69%), and its use has increased during the study period. Video laryngoscopy is associated with a high rescue intubation success rate and is more commonly used than other rescue techniques.

  11. Emergency Preparedness and Role Clarity among Rescue Workers during the Terror Attacks in Norway July 22, 2011.

    PubMed

    Pedersen, May Janne Botha; Gjerland, Astrid; Rund, Bjørn Rishovd; Ekeberg, Øivind; Skogstad, Laila

    2016-01-01

    Few studies address preparedness and role clarity in rescue workers after a disaster. On July 22, 2011, Norway was struck by two terror attacks; 77 people were killed and many injured. Healthcare providers, police officers and firefighters worked under demanding conditions. The aims of this study were to examine the level of preparedness, exposure and role clarity. In addition, the relationship between demographic variables, preparedness and exposure and a) role clarity during the rescue operations and; b) achieved mastering for future disaster operations. In this cross-sectional study, healthcare providers (n = 859), police officers (n = 252) and firefighters (n = 102) returned a questionnaire approximately 10 months after the terror attacks. The rescue personnel were trained and experienced, and the majority knew their professional role (healthcare providers M = 4.1 vs. police officers: M = 3.9 vs. firefighters: M = 4.2, p < .001, [scale 1-5]). The police officers reported significantly more lack of control (p < .001). In the multivariable analysis, being female (OR 1.4, p < .05), having more years of work experience (OR 2.3, p = < .001), previous training (OR 1.6, p < .05) and the experience of an event with > 5 fatalities (OR 1.6, p < .05) were all associated with role clarity, together with a feeling of control, not being obstructed in work and perceiving the rescue work as a success. Moreover, independent predictors of being more prepared for future operations were arousal during the operation (OR 2.0, p < .001) and perceiving the rescue work as a success (OR 1.5, p < .001). Most of the rescue workers were experienced and knew their professional role. Training and everyday-work-experience must be a focal point when preparing rescue workers for disaster.

  12. Emergency Preparedness and Role Clarity among Rescue Workers during the Terror Attacks in Norway July 22, 2011

    PubMed Central

    Pedersen, May Janne Botha; Gjerland, Astrid; Rund, Bjørn Rishovd; Ekeberg, Øivind; Skogstad, Laila

    2016-01-01

    Background Few studies address preparedness and role clarity in rescue workers after a disaster. On July 22, 2011, Norway was struck by two terror attacks; 77 people were killed and many injured. Healthcare providers, police officers and firefighters worked under demanding conditions. The aims of this study were to examine the level of preparedness, exposure and role clarity. In addition, the relationship between demographic variables, preparedness and exposure and a) role clarity during the rescue operations and; b) achieved mastering for future disaster operations. Methods In this cross-sectional study, healthcare providers (n = 859), police officers (n = 252) and firefighters (n = 102) returned a questionnaire approximately 10 months after the terror attacks. Results The rescue personnel were trained and experienced, and the majority knew their professional role (healthcare providers M = 4.1 vs. police officers: M = 3.9 vs. firefighters: M = 4.2, p < .001, [scale 1–5]). The police officers reported significantly more lack of control (p < .001). In the multivariable analysis, being female (OR 1.4, p < .05), having more years of work experience (OR 2.3, p = < .001), previous training (OR 1.6, p < .05) and the experience of an event with > 5 fatalities (OR 1.6, p < .05) were all associated with role clarity, together with a feeling of control, not being obstructed in work and perceiving the rescue work as a success. Moreover, independent predictors of being more prepared for future operations were arousal during the operation (OR 2.0, p < .001) and perceiving the rescue work as a success (OR 1.5, p < .001). Conclusion Most of the rescue workers were experienced and knew their professional role. Training and everyday-work-experience must be a focal point when preparing rescue workers for disaster. PMID:27280520

  13. 46 CFR 12.617 - Requirements to qualify for an STCW endorsement in proficiency in fast rescue boats.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... proficiency in fast rescue boats. 12.617 Section 12.617 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY... Endorsements § 12.617 Requirements to qualify for an STCW endorsement in proficiency in fast rescue boats. (a) To qualify for an STCW endorsement in proficiency in fast rescue boats, an applicant must— (1) Be not...

  14. Ethylene Receptor 1 (ETR1) Is Sufficient and Has the Predominant Role in Mediating Inhibition of Ethylene Responses by Silver in Arabidopsis thaliana*

    PubMed Central

    McDaniel, Brittany K.; Binder, Brad M.

    2012-01-01

    Ethylene influences many processes in Arabidopsis thaliana through the action of five receptor isoforms. All five isoforms use copper as a cofactor for binding ethylene. Previous research showed that silver can substitute for copper as a cofactor for ethylene binding activity in the ETR1 ethylene receptor yet also inhibit ethylene responses in plants. End-point and rapid kinetic analyses of dark-grown seedling growth revealed that the effects of silver are mostly dependent upon ETR1, and ETR1 alone is sufficient for the effects of silver. Ethylene responses in etr1-6 etr2-3 ein4-4 triple mutants were not blocked by silver. Transformation of these triple mutants with cDNA for each receptor isoform under the promoter control of ETR1 revealed that the cETR1 transgene completely rescued responses to silver while the cETR2 transgene failed to rescue these responses. The other three isoforms partially rescued responses to silver. Ethylene binding assays on the binding domains of the five receptor isoforms expressed in yeast showed that silver supports ethylene binding to ETR1 and ERS1 but not the other isoforms. Thus, silver may have an effect on ethylene signaling outside of the ethylene binding pocket of the receptors. Ethylene binding to ETR1 with silver was ∼30% of binding with copper. However, alterations in the Kd for ethylene binding to ETR1 and the half-time of ethylene dissociation from ETR1 do not underlie this lower binding. Thus, it is likely that the lower ethylene binding activity of ETR1 with silver is due to fewer ethylene binding sites generated with silver versus copper. PMID:22692214

  15. Comparison of clinical effects of epidural levobupivacaine morphine versus bupivacaine morphine in dogs undergoing elective pelvic limb surgery.

    PubMed

    Cerasoli, Ilaria; Tutunaru, Alexandru; Cenani, Alessia; Ramirez, Juan; Detilleux, Johann; Balligand, Marc; Sandersen, Charlotte

    2017-03-01

    To evaluate the efficacy, in terms of the amount of rescue analgesia required, and the clinical usefulness of epidural injection of morphine with bupivacaine or levobupivacaine for elective pelvic limb surgery in dogs during a 24-hour perioperative period. Prospective, blinded, randomized clinical study. A group of 26 dogs weighing 31.7 ± 14.2 (mean ± standard deviation) kg and aged 54 ± 36 months. All dogs were premedicated with methadone intravenously (0.2 mg kg -1 ) and anaesthesia induced with diazepam (0.2 mg kg -1 ) and propofol intravenously to effect. After induction of anaesthesia, dogs randomly received a lumbosacral epidural injection of morphine 0.1 mg kg -1 with either levobupivacaine 0.5% (1 mg kg -1 ; group LevoBM) or bupivacaine 0.5% (1 mg kg -1 ; group BM). Cardiovascular, respiratory and temperature values were recorded during the intra- and postoperative period. A visual analogue scale, subjective pain scale, sedation scale and the short form of the Glasgow pain scale were assessed every 6 hours after epidural injection during 24 hours. The ability to stand and walk, neurological deficits and other side effects were assessed at the same time points. The amount of rescue analgesia (sufentanil intraoperatively and methadone postoperatively) was recorded. No statistically significant differences were found between groups for any of the recorded data, with the exception of the incidence of spontaneous urination and postoperative rescue analgesia requirement. In group LevoBM four dogs spontaneously urinated at recovery while none of the dogs in group BM did (p = 0.03) and seven dogs of group LevoBM required postoperative rescue analgesia versus none of the dogs in the BM group (p = 0.005). and clinical relevance Epidural LevoBM is a suitable alternative to BM in healthy dogs during elective pelvic limb surgery. Epidural BM produced more urinary retention but better pain control compared to the same concentration and dose of LevoBM in dogs. Copyright © 2017 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.

  16. A chemical corrector modifies the channel function of F508del-CFTR.

    PubMed

    Kim Chiaw, Patrick; Wellhauser, Leigh; Huan, Ling Jun; Ramjeesingh, Mohabir; Bear, Christine E

    2010-09-01

    The deletion of Phe-508 (F508del) constitutes the most prevalent cystic fibrosis-causing mutation. This mutation leads to cystic fibrosis transmembrane conductance regulator (CFTR) misfolding and retention in the endoplasmic reticulum and altered channel activity in mammalian cells. This folding defect can however be partially overcome by growing cells expressing this mutant protein at low (27 degrees C) temperature. Chemical "correctors" have been identified that are also effective in rescuing the biosynthetic defect in F508del-CFTR, thereby permitting its functional expression at the cell surface. The mechanism of action of chemical correctors remains unclear, but it has been suggested that certain correctors [including 4-cyclohexyloxy-2-(1-[4-(4-methoxy-benzenesulfonyl)-piperazin-1-yl]-ethyl)-quinazoline (VRT-325)] may act to promote trafficking by interacting directly with the mutant protein. To test this hypothesis, we assessed the effect of VRT-325 addition on the channel activity of F508del-CFTR after its surface expression had been "rescued" by low temperature. It is noteworthy that short-term pretreatment with VRT-325 [but not with an inactive analog, 4-hydroxy-2-(1-[4-(4-methoxy-benzenesulfonyl)-piperazin-1-yl]-ethyl)-quinazoline (VRT-186)], caused a modest but significant inhibition of cAMP-mediated halide flux. Furthermore, VRT-325 decreased the apparent ATP affinity of purified and reconstituted F508del-CFTR in our ATPase activity assay, an effect that may account for the decrease in channel activity by temperature-rescued F508del-CFTR. These findings suggest that biosynthetic rescue mediated by VRT-325 may be conferred (at least in part) by direct modification of the structure of the mutant protein, leading to a decrease in its ATP-dependent conformational dynamics. Therefore, the challenge for therapy discovery will be the design of small molecules that bind to promote biosynthetic maturation of the major mutant without compromising its activity in vivo.

  17. Risk of large-scale evacuation based on the effectiveness of rescue strategies under different crowd densities.

    PubMed

    Wang, Jinghong; Lo, Siuming; Wang, Qingsong; Sun, Jinhua; Mu, Honglin

    2013-08-01

    Crowd density is a key factor that influences the moving characteristics of a large group of people during a large-scale evacuation. In this article, the macro features of crowd flow and subsequent rescue strategies were considered, and a series of characteristic crowd densities that affect large-scale people movement, as well as the maximum bearing density when the crowd is extremely congested, were analyzed. On the basis of characteristic crowd densities, the queuing theory was applied to simulate crowd movement. Accordingly, the moving characteristics of the crowd and the effects of typical crowd density-which is viewed as the representation of the crowd's arrival intensity in front of the evacuation passageways-on rescue strategies was studied. Furthermore, a "risk axle of crowd density" is proposed to determine the efficiency of rescue strategies in a large-scale evacuation, i.e., whether the rescue strategies are able to effectively maintain or improve evacuation efficiency. Finally, through some rational hypotheses for the value of evacuation risk, a three-dimensional distribution of the evacuation risk is established to illustrate the risk axle of crowd density. This work aims to make some macro, but original, analysis on the risk of large-scale crowd evacuation from the perspective of the efficiency of rescue strategies. © 2012 Society for Risk Analysis.

  18. 33 CFR 149.304 - What type and how many survival craft and rescue boats must a manned deepwater port have?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... craft and rescue boats must a manned deepwater port have? 149.304 Section 149.304 Navigation and... What type and how many survival craft and rescue boats must a manned deepwater port have? (a) Except as... of survival craft and the number of rescue boats indicated for the deepwater port in paragraphs (a)(1...

  19. 33 CFR 149.304 - What type and how many survival craft and rescue boats must a manned deepwater port have?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... craft and rescue boats must a manned deepwater port have? 149.304 Section 149.304 Navigation and... What type and how many survival craft and rescue boats must a manned deepwater port have? (a) Except as... survival craft and the number of rescue boats indicated for the deepwater port in paragraphs (a)(1) through...

  20. 33 CFR 149.304 - What type and how many survival craft and rescue boats must a manned deepwater port have?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... craft and rescue boats must a manned deepwater port have? 149.304 Section 149.304 Navigation and... What type and how many survival craft and rescue boats must a manned deepwater port have? (a) Except as... survival craft and the number of rescue boats indicated for the deepwater port in paragraphs (a)(1) through...

  1. 33 CFR 149.304 - What type and how many survival craft and rescue boats must a manned deepwater port have?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... craft and rescue boats must a manned deepwater port have? 149.304 Section 149.304 Navigation and... What type and how many survival craft and rescue boats must a manned deepwater port have? (a) Except as... of survival craft and the number of rescue boats indicated for the deepwater port in paragraphs (a)(1...

  2. The Impact of Prophylactic Dexamethasone on Nausea and Vomiting after Thyroidectomy: A Systematic Review and Meta-Analysis

    PubMed Central

    Zou, Zhenhong; Jiang, Yuming; Xiao, Mingjia; Zhou, Ruiyao

    2014-01-01

    Background We carried out a systematic review and meta-analysis to evaluate the impact of prophylactic dexamethasone on post-operative nausea and vomiting (PONV), post-operative pain, and complications in patients undergoing thyroidectomy. Methods We searched Pubmed, Embase, and Cochrane Library databases for randomized controlled trials (RCTs) that evaluated the prophylactic effect of dexamethasone versus placebo with or without other antiemetics for PONV in patients undergoing thyroidectomy. Meta-analyses were performed using RevMan 5.0 software. Results Thirteen RCTs that considered high quality evidence including 2,180 patients were analyzed. The meta-analysis demonstrated a significant decrease in the incidence of PONV (RR 0.52, 95% CI 0.43 to 0.63, P<0.00001), the need for rescue anti-emetics (RR 0.42, 95% CI 0.30 to 0.57, P<0.00001), post-operative pain scores (WMD –1.17, 95% CI –1.91 to –0.44, P = 0.002), and the need for rescue analgesics (RR 0.65, 95% CI 0.50–0.83, P = 0.0008) in patients receiving dexamethasone compared to placebo, with or without concomitant antiemetics. Dexamethasone 8–10mg had a significantly greater effect for reducing the incidence of PONV than dexamethasone 1.25–5mg. Dexamethasone was as effective as other anti-emetics for reducing PONV (RR 1.25, 95% CI 0.86–1.81, P = 0.24). A significantly higher level of blood glucose during the immediate post-operative period in patients receiving dexamethasone compared to controls was the only adverse event. Conclusions Prophylactic dexamethasone 8–10mg administered intravenously before induction of anesthesia should be recommended as a safe and effective strategy for reducing the incidence of PONV, the need for rescue anti-emetics, post-operative pain, and the need for rescue analgesia in thyroidectomy patients, except those that are pregnant, have diabetes mellitus, hyperglycemia, or contraindications for dexamethasone. More high quality trials are warranted to define the benefits and risks of prophylactic dexamethasone in potential patients with a high risk for PONV. PMID:25330115

  3. Transmission of feline immunodeficiency virus (FIV) among cohabiting cats in two cat rescue shelters.

    PubMed

    Litster, Annette L

    2014-08-01

    Conflicting accounts have been published in the veterinary literature regarding transmission of feline immunodeficiency virus (FIV) between cohabiting cats in mixed households, and the mechanics of possible casual transmission, if it occurs, are poorly understood. Similarly, there are conflicting reports of vertical transmission of FIV. The aim of the present study was to document the FIV serological status of cats taken into two rescue shelters. At rescue shelter 1 (Rescue 1), cats cohabited in a multi-cat household of FIV-negative and naturally-infected, FIV-positive cats. A study was performed that combined a retrospective review of records of FIV serological status at intake (Test 1) and prospective FIV serological testing (Tests 2 and 3). Retrospective records were analyzed at rescue shelter 2 (Rescue 2), where FIV-positive queens with litters of nursing kittens were taken into the shelter, before being rehomed. FIV serology was performed on all kittens after weaning. Initial test results (Test 1) for 138 cohabiting cats from Rescue 1 showed that there were 130 FIV-negative cats and eight FIV-positive cats (six male neutered and two female spayed). A second test (Test 2), performed in 45 of the FIV-negative and five of the FIV-positive cats at median 28 months after Test 1 (range, 1 month to 8.8 years) showed that results were unchanged. Similarly, a third test (Test 3), performed in four of the original FeLV-negative cats and one remaining FIV-positive cat at median 38 months after Test 1 (range, 4 months to 4 years), also showed that results were unchanged. These results show a lack of evidence of FIV transmission, despite years of exposure to naturally-infected, FIV-positive cats in a mixed household. At Rescue 2, records were available from five FIV-positive queens with 19 kittens. All 19 kittens tested FIV-negative, suggesting that vertical transmission had not occurred. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. [Effectiveness of resuscitation delivered by Polish paramedics].

    PubMed

    Guła, Przemysław; Koszowska, Małgorzata; Larysz, Dawid; Koszowski, Marcin; Nabzdyk, Andrzej; Maślanka, Marek

    2008-01-01

    The aim of the study was to evaluate the effectiveness and skills in BLS and use of automatic external defibrillators (AED) by paramedics from units of the National Fire and Rescue System. One hundred and fifty-eight rescuers participated in the study. They included both volunteers and professionals, and were recruited from 40 different rescue organizations. The results were evaluated by experienced physicians, nurses and paramedics, all holders of ALS and BLS-AED instructor diplomas. The following skills were evaluated: initial assessment, ventilation, chest compression, and use of the AED. The quality of the BLS-AED was rated against the professional experience of the rescuers, and the frequency of repetition training. Although theoretical background was rated good, 45% of participants omitted assessment of consciousness. Airway patency and respiration were properly assessed by 82.5% and 72.5% of paramedics respectively, but only 20% could provide adequate rescue breaths to the phantom victims. Circulation was correctly assessed by 65% of participants, but once again, only 34.4% of paramedics could provide adequate chest compression. The results correlated positively with professional experience, based on the number of rescue missions (0-250, mean 4.3, median 1). The results proved that despite adequate theoretical knowledge, practical skills of paramedics were poor, due to the inadequate time devoted to practical training and the lack of certificate courses.

  5. Single-step generation of gene knockout-rescue system in pluripotent stem cells by promoter insertion with CRISPR/Cas9.

    PubMed

    Matsunaga, Taichi; Yamashita, Jun K

    2014-02-07

    Specific gene knockout and rescue experiments are powerful tools in developmental and stem cell biology. Nevertheless, the experiments require multiple steps of molecular manipulation for gene knockout and subsequent rescue procedures. Here we report an efficient and single step strategy to generate gene knockout-rescue system in pluripotent stem cells by promoter insertion with CRISPR/Cas9 genome editing technology. We inserted a tetracycline-regulated inducible gene promoter (tet-OFF/TRE-CMV) upstream of the endogenous promoter region of vascular endothelial growth factor receptor 2 (VEGFR2/Flk1) gene, an essential gene for endothelial cell (EC) differentiation, in mouse embryonic stem cells (ESCs) with homologous recombination. Both homo- and hetero-inserted clones were efficiently obtained through a simple selection with a drug-resistant gene. The insertion of TRE-CMV promoter disrupted endogenous Flk1 expression, resulting in null mutation in homo-inserted clones. When the inserted TRE-CMV promoter was activated with doxycycline (Dox) depletion, Flk1 expression was sufficiently recovered from the downstream genomic Flk1 gene. Whereas EC differentiation was almost completely perturbed in homo-inserted clones, Flk1 rescue with TRE-CMV promoter activation restored EC appearance, indicating that phenotypic changes in EC differentiation can be successfully reproduced with this knockout-rescue system. Thus, this promoter insertion strategy with CRISPR/Cas9 would be a novel attractive method for knockout-rescue experiments. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Evacuation and rescue in automated guideway transit. Volume 1 : data collection, scenarios, and evaluation

    DOT National Transportation Integrated Search

    1979-12-01

    Evacuation and rescue are significant problems in all transportation systems. Serious injuries and loss of life can result from situations in which inadequate means of evacuating and rescuing passengers exist. In conventional transportation systems, ...

  7. Emergency medical rescue efforts after a major earthquake: lessons from the 2008 Wenchuan earthquake.

    PubMed

    Zhang, Lulu; Liu, Xu; Li, Youping; Liu, Yuan; Liu, Zhipeng; Lin, Juncong; Shen, Ji; Tang, Xuefeng; Zhang, Yi; Liang, Wannian

    2012-03-03

    Major earthquakes often result in incalculable environmental damage, loss of life, and threats to health. Tremendous progress has been made in response to many medical challenges resulting from earthquakes. However, emergency medical rescue is complicated, and great emphasis should be placed on its organisation to achieve the best results. The 2008 Wenchuan earthquake was one of the most devastating disasters in the past 10 years and caused more than 370,000 casualties. The lessons learnt from the medical disaster relief effort and the subsequent knowledge gained about the regulation and capabilities of medical and military back-up teams should be widely disseminated. In this Review we summarise and analyse the emergency medical rescue efforts after the Wenchuan earthquake. Establishment of a national disaster medical response system, an active and effective commanding system, successful coordination between rescue forces and government agencies, effective treatment, a moderate, timely and correct public health response, and long-term psychological support are all crucial to reduce mortality and morbidity and promote overall effectiveness of rescue efforts after a major earthquake. Copyright © 2012 Elsevier Ltd. All rights reserved.

  8. 49 CFR Figure 1a to Subpart B of... - Example of Location of Rescue Access Windows-§ 238.114

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Example of Location of Rescue Access Windows-§ 238.114 1A Figure 1A to Subpart B of Part 238 Transportation Other Regulations Relating to... B of Part 238—Example of Location of Rescue Access Windows—§ 238.114 ER01FE08.002 [73 FR 6403, Feb...

  9. Glutathione peroxidase mimic ebselen improves glucose-stimulated insulin secretion in murine islets.

    PubMed

    Wang, Xinhui; Yun, Jun-Won; Lei, Xin Gen

    2014-01-10

    Glutathione peroxidase (GPX) mimic ebselen and superoxide dismutase (SOD) mimic copper diisopropylsalicylate (CuDIPs) were used to rescue impaired glucose-stimulated insulin secretion (GSIS) in islets of GPX1 and(or) SOD1-knockout mice. Ebselen improved GSIS in islets of all four tested genotypes. The rescue in the GPX1 knockout resulted from a coordinated transcriptional regulation of four key GSIS regulators and was mediated by the peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α)-mediated signaling pathways. In contrast, CuDIPs improved GSIS only in the SOD1 knockout and suppressed gene expression of the PGC-1α pathway. Islets from the GPX1 and(or) SOD1 knockout mice provided metabolically controlled intracellular hydrogen peroxide (H2O2) and superoxide conditions for the present study to avoid confounding effects. Bioinformatics analyses of gene promoters and expression profiles guided the search for upstream signaling pathways to link the ebselen-initiated H2O2 scavenging to downstream key events of GSIS. The RNA interference was applied to prove PGC-1α as the main mediator for that link. Our study revealed a novel metabolic use and clinical potential of ebselen in rescuing GSIS in the GPX1-deficient islets and mice, along with distinct differences between the GPX and SOD mimics in this regard. These findings highlight the necessities and opportunities of discretional applications of various antioxidant enzyme mimics in treating insulin secretion disorders. REBOUND TRACK: This work was rejected during standard peer review and rescued by Rebound Peer Review (Antioxid Redox Signal 16: 293-296, 2012) with the following serving as open reviewers: Regina Brigelius-Flohe, Vadim Gladyshev, Dexing Hou, and Holger Steinbrenner.

  10. Determining the need for rescue intracytoplasmic sperm injection in partial fertilisation failure during a conventional IVF cycle.

    PubMed

    Cao, S; Wu, X; Zhao, C; Zhou, L; Zhang, J; Ling, X

    2016-12-01

    To explore the need for rescue intracytoplasmic sperm injection (ICSI) in cases of partial fertilisation failure during a conventional in vitro fertilisation cycle, rescue ICSI was performed for cycles with a fertilisation rate of <50%. The data were divided into three groups based on the fertilisation rate: group 1 (0%), group 2 (<25%) and group 3 (>25%). The impact of rescue ICSI on each group was then analysed in terms of ovum fertilisation, embryo development, embryo utilisation and selection of embryos for transfer. Rescue ICSI was performed on 1831 unfertilised oocytes from 313 cycles. The fertilisation rates for group 1, group 2 and group 3 were 74.66, 68.35 and 65.46%, and the rate of polyploidy in the three groups was 8.55, 11.33, and 14.47%. The percentage of embryos that can be transferred from rescue ICSI for group 2 was 38.33%, and this value was higher than those of the other two groups. It is concluded that rescue ICSI is not recommended for patients with an IVF rate of >25% as the procedure is associated with a greater risk and low returns. However, it is feasible to perform rescue ICSI for patients with IVF rates of <25%. © 2016 Blackwell Verlag GmbH.

  11. Minocycline protects, rescues and prevents knockdown transgenic parkin Drosophila against paraquat/iron toxicity: Implications for autosomic recessive juvenile parkinsonism.

    PubMed

    Ortega-Arellano, Hector Flavio; Jimenez-Del-Rio, Marlene; Velez-Pardo, Carlos

    2017-05-01

    Autosomal recessive Juvenile Parkinsonism (AR-JP) is a chronic, progressive neurodegenerative disorder caused by mutation in the PARKIN gene, and invariably associated with dopaminergic (DAergic) neuronal loss and brain iron accumulation. Since current medical therapy is symptomatic and lacks significant disease-modifying effects, other treatment approaches are urgently needed it. In the present work, we investigate the role of minocycline (MC) in paraquat (PQ)/iron-induced neurotoxicity in the Drosophila TH>parkin-RNAi/+ (w[*]; UAS-parkin-RNAi; TH-GAL4) fly and have shown the following: (i) MC increased life span and restored the locomotor activity of knockdown (KD) transgenic parkin flies in comparison with the control (vehicle) group; (ii) MC at low (0.1 and 0.3mM) and middle (0.5mM) concentrations protected, rescued and prevented KD parkin Drosophila against PQ toxicity. However, MC at high (1mM) concentration aggravated the toxic effect of PQ; (iii) MC protected and rescued DAergic neurons against the PQ toxic effect according to tyrosine hydroxylase (TH)>green-fluorescent protein (GFP) reporter protein microscopy and anti-TH Western blotting analysis; (iv) MC protected DAergic neurons against PQ/iron toxicity; (v) MC significantly abridged lipid peroxidation (LPO) in the protection, rescue and prevention treatment in TH>parkin-RNAi/+ flies against PQ or iron alone or combined (PQ/iron)-induced neuronal oxidative stress (OS). Our results suggest that MC exerts neuroprotection against PQ/iron-induced OS in DAergic neurons most probably by the scavenging activity of reactive oxygen species (ROS), and by chelating iron. Therefore, MC might be a potential therapeutic drug to delay, revert, or prevent AR-JP. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. N-Acetylcysteine improves mitochondrial function and ameliorates behavioral deficits in the R6/1 mouse model of Huntington's disease

    PubMed Central

    Wright, D J; Renoir, T; Smith, Z M; Frazier, A E; Francis, P S; Thorburn, D R; McGee, S L; Hannan, A J; Gray, L J

    2015-01-01

    Huntington's disease (HD) is a neurodegenerative disorder, involving psychiatric, cognitive and motor symptoms, caused by a CAG-repeat expansion encoding an extended polyglutamine tract in the huntingtin protein. Oxidative stress and excitotoxicity have previously been implicated in the pathogenesis of HD. We hypothesized that N-acetylcysteine (NAC) may reduce both excitotoxicity and oxidative stress through its actions on glutamate reuptake and antioxidant capacity. The R6/1 transgenic mouse model of HD was used to investigate the effects of NAC on HD pathology. It was found that chronic NAC administration delayed the onset and progression of motor deficits in R6/1 mice, while having an antidepressant-like effect on both R6/1 and wild-type mice. A deficit in the astrocytic glutamate transporter protein, GLT-1, was found in R6/1 mice. However, this deficit was not ameliorated by NAC, implying that the therapeutic effect of NAC is not due to rescue of the GLT-1 deficit and associated glutamate-induced excitotoxicity. Assessment of mitochondrial function in the striatum and cortex revealed that R6/1 mice show reduced mitochondrial respiratory capacity specific to the striatum. This deficit was rescued by chronic treatment with NAC. There was a selective increase in markers of oxidative damage in mitochondria, which was rescued by NAC. In conclusion, NAC is able to delay the onset of motor deficits in the R6/1 model of Huntington's disease and it may do so by ameliorating mitochondrial dysfunction. Thus, NAC shows promise as a potential therapeutic agent in HD. Furthermore, our data suggest that NAC may also have broader antidepressant efficacy. PMID:25562842

  13. 46 CFR 133.175 - Survival craft and rescue boat equipment.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... line 1 2 1 2 15 Instruction card 1 1 17 Knife 1,3 1 1 1 1 18 Ladder 1 1 19 Mirror, signalling 1 1 20... Not required for inflated or rigid-inflated rescue boats. 3 A hatchet counts towards this requirement...

  14. The E3 ubiquitin ligases β-TrCP and FBXW7 cooperatively mediates GSK3-dependent Mcl-1 degradation induced by the Akt inhibitor API-1, resulting in apoptosis.

    PubMed

    Ren, Hui; Koo, Junghui; Guan, Baoxiang; Yue, Ping; Deng, Xingming; Chen, Mingwei; Khuri, Fadlo R; Sun, Shi-Yong

    2013-11-22

    The novel Akt inhibitor, API-1, induces apoptosis through undefined mechanisms. The current study focuses on revealing the mechanisms by which API-1 induces apoptosis. API-1 rapidly and potently reduced the levels of Mcl-1 primarily in API-1-senstive lung cancer cell lines. Ectopic expression of Mcl-1 protected cells from induction of apoptosis by API-1. API-1 treatment decreased the half-life of Mcl-1, whereas inhibition of the proteasome with MG132 rescued Mcl-1 reduction induced by API-1. API-1 decreased Mcl-1 levels accompanied with a rapid increase in Mcl-1 phosphorylation (S159/T163). Moreover, inhibition of GSK3 inhibited Mcl-1 phosphorylation and reduction induced by API-1 and antagonized the effect of API-1 on induction of apoptosis. Knockdown of either FBXW7 or β-TrCP alone, both of which are E3 ubiquitin ligases involved in Mcl-1 degradation, only partially rescued Mcl-1 reduction induced by API-1. However, double knockdown of both E3 ubiquitin ligases enhanced the rescue of API-1-induced Mcl-1 reduction. API-1 induces GSK3-dependent, β-TrCP- and FBXW7-mediated Mcl-1 degradation, resulting in induction of apoptosis.

  15. The E3 ubiquitin ligases β-TrCP and FBXW7 cooperatively mediates GSK3-dependent Mcl-1 degradation induced by the Akt inhibitor API-1, resulting in apoptosis

    PubMed Central

    2013-01-01

    Background The novel Akt inhibitor, API-1, induces apoptosis through undefined mechanisms. The current study focuses on revealing the mechanisms by which API-1 induces apoptosis. Results API-1 rapidly and potently reduced the levels of Mcl-1 primarily in API-1-senstive lung cancer cell lines. Ectopic expression of Mcl-1 protected cells from induction of apoptosis by API-1. API-1 treatment decreased the half-life of Mcl-1, whereas inhibition of the proteasome with MG132 rescued Mcl-1 reduction induced by API-1. API-1 decreased Mcl-1 levels accompanied with a rapid increase in Mcl-1 phosphorylation (S159/T163). Moreover, inhibition of GSK3 inhibited Mcl-1 phosphorylation and reduction induced by API-1 and antagonized the effect of API-1 on induction of apoptosis. Knockdown of either FBXW7 or β-TrCP alone, both of which are E3 ubiquitin ligases involved in Mcl-1 degradation, only partially rescued Mcl-1 reduction induced by API-1. However, double knockdown of both E3 ubiquitin ligases enhanced the rescue of API-1-induced Mcl-1 reduction. Conclusions API-1 induces GSK3-dependent, β-TrCP- and FBXW7-mediated Mcl-1 degradation, resulting in induction of apoptosis. PMID:24261825

  16. Optoelectronic Quality and Stability of Hybrid Perovskites from MAPbI 3 to MAPbI 2 Br Using Composition Spread Libraries

    DOE PAGES

    Braly, Ian L.; Hillhouse, Hugh W.

    2015-12-22

    The development of stable high-bandgap hybrid perovskites (HPs) with high optoelectronic quality may enable tandem solar cells with power conversion efficiencies approaching 30%. The halide composition of HPs has been observed to effect bandgap, carrier lifetime, and material stability. Here we report optoelectronic quality and stability under illumination of thousands of compositions ranging from the pure iodide (CH3NH3PbI3) to the diiodomonobromide (CH3NH3PbI2Br). Hyperspectral maps of steady-state absolute intensity photoluminescence (AIPL) are used to determine the quasi-Fermi level splitting (QFLS) at each point after synthesis. The QFLS upon first illumination increases with bandgap and reaches a maximum of 1.27 eV undermore » 1 sun illumination intensity for a bandgap of 1.75 eV. However, the optoelectronic quality (χ), defined as the ratio of the QFLS to the maximum theoretical QFLS for bandgap, decreases with bandgap from around 88% for 1.60 eV bandgap down to 82% for 1.84 eV bandgap. Further, we show that a reversible light induced defect forms that reduces the optoelectronic quality, particularly for high-bandgap materials. Composition analysis shows that the halide to lead ratio, (I + Br)/Pb, decreases from 3 for the pure iodide to 2.5 for the diiodomonobromide, suggesting a role of halide vacancies or halide substitution defects in the light-induced instability for this synthesis route. Even with the light-induced defect, a stable QFLS of about 1.17 eV is possible. Comparing our QFLS to Voc values from HP devices reported in the literature indicates that higher open circuit voltages are possible but may require optimization of band alignment. Further, the spectral shape of the PL emission is found to be more commensurate with Franz–Keldysh broadening from local electric fields or from a screened Thomas–Fermi density of states (as opposed to a joint density of states due to Urbach disorder).« less

  17. Inhibition of chlorine-induced lung injury by the type 4 phosphodiesterase inhibitor rolipram

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Chang, Weiyuan; Chen, Jing; Schlueter, Connie F.

    2012-09-01

    Chlorine is a highly toxic respiratory irritant that when inhaled causes epithelial cell injury, alveolar-capillary barrier disruption, airway hyperreactivity, inflammation, and pulmonary edema. Chlorine is considered a chemical threat agent, and its release through accidental or intentional means has the potential to result in mass casualties from acute lung injury. The type 4 phosphodiesterase inhibitor rolipram was investigated as a rescue treatment for chlorine-induced lung injury. Rolipram inhibits degradation of the intracellular signaling molecule cyclic AMP. Potential beneficial effects of increased cyclic AMP levels include inhibition of pulmonary edema, inflammation, and airway hyperreactivity. Mice were exposed to chlorine (whole bodymore » exposure, 228–270 ppm for 1 h) and were treated with rolipram by intraperitoneal, intranasal, or intramuscular (either aqueous or nanoemulsion formulation) delivery starting 1 h after exposure. Rolipram administered intraperitoneally or intranasally inhibited chlorine-induced pulmonary edema. Minor or no effects were observed on lavage fluid IgM (indicative of plasma protein leakage), KC (Cxcl1, neutrophil chemoattractant), and neutrophils. All routes of administration inhibited chlorine-induced airway hyperreactivity assessed 1 day after exposure. The results of the study suggest that rolipram may be an effective rescue treatment for chlorine-induced lung injury and that both systemic and targeted administration to the respiratory tract were effective routes of delivery. -- Highlights: ► Chlorine causes lung injury when inhaled and is considered a chemical threat agent. ► Rolipram inhibited chlorine-induced pulmonary edema and airway hyperreactivity. ► Post-exposure rolipram treatments by both systemic and local delivery were effective. ► Rolipram shows promise as a rescue treatment for chlorine-induced lung injury.« less

  18. The genetic rescue of two bottlenecked South Island robin populations using translocations of inbred donors.

    PubMed

    Heber, S; Varsani, A; Kuhn, S; Girg, A; Kempenaers, B; Briskie, J

    2013-02-07

    Populations forced through bottlenecks typically lose genetic variation and exhibit inbreeding depression. 'Genetic rescue' techniques that introduce individuals from outbred populations can be highly effective in reversing the deleterious effects of inbreeding, but have limited application for the majority of endangered species, which survive only in a few bottlenecked populations. We tested the effectiveness of using highly inbred populations as donors to rescue two isolated and bottlenecked populations of the South Island robin (Petroica australis). Reciprocal translocations significantly increased heterozygosity and allelic diversity. Increased genetic diversity was accompanied by increased juvenile survival and recruitment, sperm quality, and immunocompetence of hybrid individuals (crosses between the two populations) compared with inbred control individuals (crosses within each population). Our results confirm that the implementation of 'genetic rescue' using bottlenecked populations as donors provides a way of preserving endangered species and restoring their viability when outbred donor populations no longer exist.

  19. A 14-day regimen of esomeprazole 20 mg/day for frequent heartburn: durability of effects, symptomatic rebound, and treatment satisfaction.

    PubMed

    Peura, David; Le Moigne, Anne; Pollack, Charles; Nagy, Peter; Lind, Tore

    2016-08-01

    Esomeprazole 20 mg once daily has been shown to be effective for treating frequent heartburn over 14 days in subjects who are likely to self-treat with over-the-counter medications. These analyses were conducted to assess durability of effects and symptomatic rebound after cessation of treatment, treatment satisfaction, and rescue antacid use with esomeprazole 20 mg once daily for 14 days. Adults with frequent heartburn (≥ two days/week in the past four weeks) were randomly assigned to 14 days of double-blind treatment with esomeprazole 20 mg or placebo in two identical multicenter studies. All subjects entered a 1-week single-blind placebo follow-up period after treatment. The results of the primary efficacy endpoints were reported previously. The percentage of heartburn-free days during the 1-week follow-up, use of rescue antacids, and treatment satisfaction, measured with the Global Assessment Questions instrument, are described. The percentage of heartburn-free days was maintained during the 1-week follow-up period; the proportion was 43% among esomeprazole subjects in these studies, suggesting no evidence of symptomatic rebound. Rescue antacid use generally decreased compared with the run-in period in the 14-day treatment and 1-week follow-up periods. Significantly more subjects taking esomeprazole were "very satisfied" or "satisfied" with treatment versus placebo (Study 1: 78% vs. 63%, respectively, P = 0.0038; Study 2: 81% vs. 60%, respectively, P = 0.0002). Subjects who are likely to self-treat their frequent heartburn with over-the-counter medications reported satisfaction with esomeprazole 20 mg. Esomeprazole's treatment effect was maintained for ≥ one week after treatment ended, with no sign of symptomatic rebound. These trials were registered at ClinicalTrials.gov: NCT01370525; NCT01370538.

  20. Rescue Manual. Module 2.

    ERIC Educational Resources Information Center

    Ohio State Univ., Columbus. Instructional Materials Lab.

    This learner manual for rescuers covers the current techniques or practices required in the rescue service. The second of 10 modules contains 5 chapters: (1) patient care and handling techniques; (2) rescue carries and drags; (3) emergency vehicle operations; (4) self-contained breathing apparatus; and (5) protective clothing. Key points, an…

  1. Mice heterozygous for the oxytocin receptor gene (Oxtr(+/-)) show impaired social behaviour but not increased aggression or cognitive inflexibility: evidence of a selective haploinsufficiency gene effect.

    PubMed

    Sala, M; Braida, D; Donzelli, A; Martucci, R; Busnelli, M; Bulgheroni, E; Rubino, T; Parolaro, D; Nishimori, K; Chini, B

    2013-02-01

    We characterised the behavioural phenotype of mice heterozygous (Oxtr(+/-)) for the oxytocin receptor gene (Oxtr) and compared it with that of Oxtr null mice (Oxtr(-/-)), which display autistic-like behaviours, including impaired sociability and preference for social novelty, impaired cognitive flexibility, and increased aggression. Similar to Oxtr(-/-) mice, the Oxtr(+/-) showed impaired sociability and preference for social novelty but, unlike the null genotype, their cognitive flexibility and aggression were normal. By autoradiography, Oxtr(+/-) mice were found to have approximately 50% fewer oxytocin receptors (OXTRs) in all of the examined brain regions. Thus, because a partial reduction in Oxtr gene expression is sufficient to compromise social behaviour, the Oxtr acts as a haploinsufficient gene. Furthermore, the inactivation of the Oxtr gene affects specific behaviours in a dose-dependent manner: social behaviour is sensitive to even a partial reduction in Oxtr gene expression, whereas defects in aggression and cognitive flexibility require the complete inactivation of the Oxtr gene to emerge. We then investigated the rescue of the Oxtr(+/-) social deficits by oxytocin (OT) and Thr(4)Gly(7)OT (TGOT) administered i.c.v. at different doses. TGOT was more potent than OT in rescuing sociability and social novelty in both genotypes. Furthermore, the TGOT doses that reverted impaired sociability and preference for social novelty in Oxtr(+/-) were lower than those required in Oxtr(-/-), thus suggesting that the rescue effect is mediated by OXTR in Oxtr(+/-) and by other receptors (presumably vasopressin V1a receptors) in Oxtr(-/-). In line with this, a low dose of the selective oxytocin antagonist desGlyDTyrOVT blocks the rescue effect of TGOT only in the Oxtr(+/-) genotype, whereas the less selective antagonist SR49059 blocks rescue in both genotypes. In conclusion, the Oxtr(+/-) mouse is a unique animal model for investigating how partial loss of the Oxtr gene impair social interactions, and for designing pharmacological rescue strategies. © 2012 British Society for Neuroendocrinology.

  2. 49 CFR Figure 1b to Subpart B of... - Example of Location and Staggering of Emergency Window Exits and Location of Rescue Access...

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Example of Location and Staggering of Emergency Window Exits and Location of Rescue Access Windows-§§ 238.113 and 238.114 1B Figure 1B to Subpart B of... of Emergency Window Exits and Location of Rescue Access Windows—§§ 238.113 and 238.114 ER01FE08.003...

  3. A new approach to road accident rescue.

    PubMed

    Morales, Alejandro; González-Aguilera, Diego; López, Alfonso I; Gutiérrez, Miguel A

    2016-01-01

    This article develops and validates a new methodology and tool for rescue assistance in traffic accidents, with the aim of improving its efficiency and safety in the evacuation of people, reducing the number of victims in road accidents. Different tests supported by professionals and experts have been designed under different circumstances and with different categories of damaged vehicles coming from real accidents and simulated trapped victims in order to calibrate and refine the proposed methodology and tool. To validate this new approach, a tool called App_Rescue has been developed. This tool is based on the use of a computer system that allows an efficient access to the technical information of the vehicle and sanitary information of the common passengers. The time spent during rescue using the standard protocol and the proposed method was compared. This rescue assistance system allows us to make vital information accessible in posttrauma care services, improving the effectiveness of interventions by the emergency services, reducing the rescue time and therefore minimizing the consequences involved and the number of victims. This could often mean saving lives. In the different simulated rescue operations, the rescue time has been reduced an average of 14%.

  4. 46 CFR 199.176 - Markings on lifesaving appliances.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... ARRANGEMENTS LIFESAVING SYSTEMS FOR CERTAIN INSPECTED VESSELS Requirements for All Vessels § 199.176 Markings on lifesaving appliances. (a) Lifeboats and rescue boats. Each lifeboat and rescue boat must be plainly marked as follows: (1) Each side of each lifeboat and rescue boat bow must be marked in block...

  5. 30 CFR 49.16 - Equipment and maintenance requirements.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... TRAINING MINE RESCUE TEAMS Mine Rescue Teams for Underground Coal Mines § 49.16 Equipment and maintenance... team members. (1) Twelve self-contained breathing apparatus, each with a minimum of 4 hours capacity... apparatus and sufficient to sustain each team for 8 hours while using the breathing apparatus during rescue...

  6. 30 CFR 49.16 - Equipment and maintenance requirements.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... TRAINING MINE RESCUE TEAMS Mine Rescue Teams for Underground Coal Mines § 49.16 Equipment and maintenance... team members. (1) Twelve self-contained breathing apparatus, each with a minimum of 4 hours capacity... apparatus and sufficient to sustain each team for 8 hours while using the breathing apparatus during rescue...

  7. 30 CFR 49.16 - Equipment and maintenance requirements.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... TRAINING MINE RESCUE TEAMS Mine Rescue Teams for Underground Coal Mines § 49.16 Equipment and maintenance... team members. (1) Twelve self-contained breathing apparatus, each with a minimum of 4 hours capacity... apparatus and sufficient to sustain each team for 8 hours while using the breathing apparatus during rescue...

  8. 30 CFR 49.16 - Equipment and maintenance requirements.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... TRAINING MINE RESCUE TEAMS Mine Rescue Teams for Underground Coal Mines § 49.16 Equipment and maintenance... team members. (1) Twelve self-contained breathing apparatus, each with a minimum of 4 hours capacity... apparatus and sufficient to sustain each team for 8 hours while using the breathing apparatus during rescue...

  9. 30 CFR 49.16 - Equipment and maintenance requirements.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... TRAINING MINE RESCUE TEAMS Mine Rescue Teams for Underground Coal Mines § 49.16 Equipment and maintenance... team members. (1) Twelve self-contained breathing apparatus, each with a minimum of 4 hours capacity... apparatus and sufficient to sustain each team for 8 hours while using the breathing apparatus during rescue...

  10. The Future Mission Tasking and Resourcing of the U.S. Coast Guard Auxiliary

    DTIC Science & Technology

    2012-09-01

    Time Between Overhaul TC Transport Canada USPS U.S. Power Squadrons VE Vessel Examination VISAR Virgin Islands Search and Rescue VSC...70% of the nation’s search and rescue with 1,800 volunteers who serve at 66 stations and operate 160 lifeboats.52 (7) The (British) Virgin Islands...Search and Rescue (VISAR). It was modeled after RNLI and operates two rescue boats, one based on Tortola, and the other Virgin Gorda. The

  11. [Anti-emetic effect of granisetron in patients undergoing cranial and craniospinal radiotherapy].

    PubMed

    Yamasaki, Fumiyuki; Watanabe, Yosuke; Nosaka, Ryo; Kenjo, Masahiro; Nakamura, Kazuhiro; Takayasu, Takeshi; Saito, Taiichi; Tominaga, Atsushi; Sugiyama, Kazuhiko; Kurisu, Kaoru

    2014-01-01

    Approximately 30-59% of patients undergoing cranial or craniospinal radiotherapy experience nausea and/or vomiting. Here, we evaluated the effectiveness of granisetron for controlling emesis in patients treated with cranial or craniospinal radiotherapy. Between December 2011 and January 2013, 34 patients(19 males, 15 females;age range, 3-80 years)received cranial or craniospinal radiotherapy at our department. All but one male patient, who developed meningitis during the irradiation period were enrolled in this retrospective study. Patients who experienced irradiation-induced vomiting(grade 1)or nausea(grade 2)were treated with granisetron as a rescue anti-emetic. Episodes were graded as(1)no vomiting, no nausea, no anti-emetic;(2)no vomiting, nausea, no anti-emetic;(3)no vomiting, nausea with anti-emetic;and(4)vomiting. Of the 9 patients who underwent whole-brain or whole neural-axis irradiation, 5(55.6%)experienced grade 2 nausea or vomiting. Two of 6 patients(33.3%)treated with whole ventricle irradiation experienced grade 2 nausea or vomiting. Three of 18 patients(16.7%)who underwent local-field irradiation experienced grade 2 nausea or vomiting. Patients who underwent wide-field irradiation experienced nausea, vomiting, and anorexia(p<0.05). Complete response(no vomiting, no additional rescue anti-emetic, and no nausea)was observed in 5 of 9 patients treated with granisetron. Four of 9 patients(44.4%)treated with granisetron experienced constipation(grade 1 or 2);its administration had no major adverse effects in our study population. Rescue therapy with granisetron is safe and effective to treat nausea and vomiting in patients subjected to cranial or craniospinal irradiation.

  12. Soft tissue and intra-articular injection of bupivacaine, epinephrine, and morphine has a beneficial effect after total knee arthroplasty.

    PubMed

    Lombardi, Adolph V; Berend, Keith R; Mallory, Thomas H; Dodds, Kathleen L; Adams, Joanne B

    2004-11-01

    The purpose of this study was to determine if an intraoperative intraarticular and soft-tissue injection of local anaesthetic, epinephrine, and morphine has a beneficial effect for total knee arthroplasty. A control group of 138 patients (181 knees) received no intraoperative injection. The study group of 171 patients (197 knees) received intraoperative injection of 0.25% bupivacaine with epinephrine and morphine with 2/3 injected into the soft tissues and 1/3 injected into the joint. Patients having bilateral simultaneous procedures received a divided dose. The pain treatment protocol otherwise was identical. Pain, sedation, rescue narcotic usage, narcotic reversal and blood loss were examined. Pain levels during the immediate postoperative period, blood loss, and bleeding indices were reduced with injection. Considerably more control patients required rescue doses of narcotics. Preemptive analgesia with soft tissue and intra-articular injection of long-acting local anesthetic with epinephrine and morphine provides better pain control in the immediate postoperative period, decreases blood loss, and decreases the need for rescue narcotics and reversal agents. This simple, inexpensive method provides an effective adjunct to a multimodal approach in improving the postoperative course of primary total knee arthroplasty.

  13. Structure of human POFUT1, its requirement in ligand-independent oncogenic Notch signaling, and functional effects of Dowling-Degos mutations

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    McMillan, Brian J.; Zimmerman, Brandon; Egan, Emily D.

    Protein O-fucosyltransferase-1 (POFUT1), which transfers fucose residues to acceptor sites on serine and threonine residues of epidermal growth factor-like repeats of recipient proteins, is essential for Notch signal transduction in mammals. Here, we examine the consequences of POFUT1 loss on the oncogenic signaling associated with certain leukemia-associated mutations of human Notch1, report the structures of human POFUT1 in free and GDP-fucose bound states, and assess the effects of Dowling-Degos mutations on human POFUT1 function. CRISPR-mediated knockout of POFUT1 in U2OS cells suppresses both normal Notch1 signaling, and the ligand-independent signaling associated with leukemogenic mutations of Notch1. Normal and oncogenic signalingmore » are rescued by wild-type POFUT1 but rescue is impaired by an active-site R240A mutation. The overall structure of the human enzyme closely resembles that of the Caenorhabditis elegans protein, with an overall backbone RMSD of 0.93 Å, despite primary sequence identity of only 39% in the mature protein. GDP-fucose binding to the human enzyme induces limited backbone conformational movement, though the side chains of R43 and D244 reorient to make direct contact with the fucose moiety in the complex. The reported Dowling-Degos mutations of POFUT1, except for M262T, fail to rescue Notch1 signaling efficiently in the CRISPR-engineered POFUT1 -/- background. Together, these studies identify POFUT1 as a potential target for cancers driven by Notch1 mutations and provide a structural roadmap for its inhibition.« less

  14. Improved transcription and translation with L-leucine stimulation of mTORC1 in Roberts syndrome.

    PubMed

    Xu, Baoshan; Gogol, Madelaine; Gaudenz, Karin; Gerton, Jennifer L

    2016-01-05

    Roberts syndrome (RBS) is a human developmental disorder caused by mutations in the cohesin acetyltransferase ESCO2. We previously reported that mTORC1 signaling was depressed and overall translation was reduced in RBS cells and zebrafish models for RBS. Treatment of RBS cells and zebrafish RBS models with L-leucine partially rescued mTOR function and protein synthesis, correlating with increased cell division and improved development. In this study, we use RBS cells to model mTORC1 repression and analyze transcription and translation with ribosome profiling to determine gene-level effects of L-leucine. L-leucine treatment partially rescued translational efficiency of ribosomal subunits, translation initiation factors, snoRNA production, and mitochondrial function in RBS cells, consistent with these processes being mTORC1 controlled. In contrast, other genes are differentially expressed independent of L-leucine treatment, including imprinted genes such as H19 and GTL2, miRNAs regulated by GTL2, HOX genes, and genes in nucleolar associated domains. Our study distinguishes between gene expression changes in RBS cells that are TOR dependent and those that are independent. Some of the TOR independent gene expression changes likely reflect the architectural role of cohesin in chromatin looping and gene expression. This study reveals the dramatic rescue effects of L-leucine stimulation of mTORC1 in RBS cells and supports that normal gene expression and translation requires ESCO2 function.

  15. Cinnarizine for Sea Sickness During a Remote Pacific Ocean Rescue Mission.

    PubMed

    Lyon, Regan F; Rush, Stephen C; Roland, J Thomas; Jethanamest, Daniel; Schwan, Christopher P; Kharon, Chetan U

    2015-01-01

    Motion sickness can be a limiting factor for sea and air missions. We report the experience of a Pararescue (PJ) team on a Pacific Ocean rescue mission in which motion sickness was prevalent. Cinnarizine, an antagonist of H1-histamine receptors, was used to treat affected PJs. We also report findings of a survey of PJs regarding motion sickness. A family of four on a disabled sailboat 900 miles off the coast of Mexico sent out a distress call because their 1-year-old daughter became severely ill with fever and diarrhea. Four PJs were deployed on a C-130, performed a free-fall parachute insertion into the ocean, and boarded the sailboat. All four PJs experienced onset of motion sickness at some point during the early part of the mission and symptoms persisted through the first 24 hours. Three PJs experienced ongoing nausea, vomiting, dizziness, and sensory imbalances. The captain of the sailboat offered the three sick PJs approximately 18mg of cinnarizine two or three times a day with relief of symptoms and improvement on operational effectiveness. A new, anonymous, voluntary survey of Air National Guard PJs and combat rescue officers revealed that 78.4% of Operators have experienced motion sickness at sea. We discuss the current theories on motion sickness, the effect of motion sickness on operational effectiveness, and research on treatment of motion sickness, including the medication cinnarizine. 2015.

  16. Factors influencing mine rescue team behaviors.

    PubMed

    Jansky, Jacqueline H; Kowalski-Trakofler, K M; Brnich, M J; Vaught, C

    2016-01-01

    A focus group study of the first moments in an underground mine emergency response was conducted by the National Institute for Occupational Safety and Health (NIOSH), Office for Mine Safety and Health Research. Participants in the study included mine rescue team members, team trainers, mine officials, state mining personnel, and individual mine managers. A subset of the data consists of responses from participants with mine rescue backgrounds. These responses were noticeably different from those given by on-site emergency personnel who were at the mine and involved with decisions made during the first moments of an event. As a result, mine rescue team behavior data were separated in the analysis and are reported in this article. By considering the responses from mine rescue team members and trainers, it was possible to sort the data and identify seven key areas of importance to them. On the basis of the responses from the focus group participants with a mine rescue background, the authors concluded that accurate and complete information and a unity of purpose among all command center personnel are two of the key conditions needed for an effective mine rescue operation.

  17. Functional antigen binding by the defective B cells of CBA/N mice.

    PubMed

    Snippe, H; Merchant, B; Lizzio, E F; Inman, J K

    1982-01-01

    CBA/N mice have an X-linked B cell defect which prevents them from responding to nonmitogenic thymic independent (TI-2) antigens such as dinitrophenylated DNP-Ficoll (1,2). The F1 male progeny of CBA/N female mice express the same defect. Spleen cell suspensions from such defective mice (CBA/N X C3H/HeN F1 males) could not respond to DNP-Ficoll following in vitro immunization and subsequent transfer into irradiated, syngeneic, F1 male recipients as expected. In contrast, normal CBA/N X C3H/HeN F1 female spleen cells could respond and effect a "rescue"; they mounted strong plaque-forming cell responses 7 days after in vitro exposure to DNP-Ficoll and subsequent transfer into irradiated F1 male recipients. Defective F1 male spleen cells, however, could bind significant quantities of 125I-DNP-Ficoll after in vitro exposure. Extensive washing of these spleen cells could not reverse this binding. Such DNP-Ficoll-exposed and washed F1 male spleen cells could, after transfer, aid normal untreated F1 female cells in their rescue function. The defective F1 male spleen cells could convey immunogenic quantities of DNP-Ficoll to the "rescuing" F1 female cells. Mitomycin treatment of F1 male cells did not interfere with their conveyor function. Goat anti-mouse mu serum impeded the passive antigen conveyor function of defective F1 male cells as did prior exposure to high concentrations of free DNP hapten. Our data support the view that the B cell defect of CBA/N X C3H/HeN F1 male mice does not relate to antigen binding, but rather to an inability to be effectively triggered by certain cell-bound polymeric antigens.

  18. 30 CFR 49.20 - Requirements for all coal mines.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Requirements for all coal mines. 49.20 Section... TRAINING MINE RESCUE TEAMS Mine Rescue Teams for Underground Coal Mines § 49.20 Requirements for all coal mines. (a) The operator of each underground coal mine shall make available two certified mine rescue...

  19. 30 CFR 49.20 - Requirements for all coal mines.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Requirements for all coal mines. 49.20 Section... TRAINING MINE RESCUE TEAMS Mine Rescue Teams for Underground Coal Mines § 49.20 Requirements for all coal mines. (a) The operator of each underground coal mine shall make available two certified mine rescue...

  20. 30 CFR 49.20 - Requirements for all coal mines.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Requirements for all coal mines. 49.20 Section... TRAINING MINE RESCUE TEAMS Mine Rescue Teams for Underground Coal Mines § 49.20 Requirements for all coal mines. (a) The operator of each underground coal mine shall make available two certified mine rescue...

  1. 30 CFR 49.20 - Requirements for all coal mines.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Requirements for all coal mines. 49.20 Section... TRAINING MINE RESCUE TEAMS Mine Rescue Teams for Underground Coal Mines § 49.20 Requirements for all coal mines. (a) The operator of each underground coal mine shall make available two certified mine rescue...

  2. 30 CFR 49.20 - Requirements for all coal mines.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Requirements for all coal mines. 49.20 Section... TRAINING MINE RESCUE TEAMS Mine Rescue Teams for Underground Coal Mines § 49.20 Requirements for all coal mines. (a) The operator of each underground coal mine shall make available two certified mine rescue...

  3. Does modern helicopter construction reduce noise exposure in helicopter rescue operations?

    PubMed

    Küpper, Thomas; Jansing, Paul; Schöffl, Volker; van Der Giet, Simone

    2013-01-01

    During helicopter rescue operations the medical personnel are at high risk for hearing damage by noise exposure. There are two important factors to be taken into account: first, the extreme variability, with some days involving no exposure but other days with extreme exposure; second, the extreme noise levels during work outside the helicopter, e.g. during winch operations. The benefit of modern, less noisier constructions and the consequences for noise protection are still unknown. We estimated the noise exposure of the personnel for different helicopter types used during rescue operations in the Alps and in other regions of the world with special regard to the advanced types like Eurocopter EC 135 to compare the benefit of modern constructions for noise protection with earlier ones. The rescue operations over 1 year of four rescue bases in the Alps (Raron and Zermatt in Switzerland; Landeck and Innsbruck in Austria, n = 2731) were analyzed for duration of rescue operations (noise exposure). Noise levels were measured during rescue operations at defined points inside and outside the different aircraft. The setting is according to the European standard (Richtlinie 2003/10/EG Amtsblatt) and to Class 1 DIN/IEC 651. With both data sets the equivalent noise level L(eq8h) was calculated. For comparison it was assumed that all rescue operations were performed with a specific type of helicopter. Then model calculations for noise exposure by different helicopter types, such as Alouette IIIb, Alouette II 'Lama', Ecureuil AS350, Bell UH1D, Eurocopter EC135, and others were performed. Depending on modern technologies the situation for the personnel has been improved significantly. Nevertheless noise prevention, which includes noise intermissions in spare time, is essential. Medical checks of the crews by occupational medicine (e.g. 'G20' in Germany) are still mandatory.

  4. Rescue of Outer Hair Cells with Antisense Oligonucleotides in Usher Mice Is Dependent on Age of Treatment.

    PubMed

    Ponnath, Abhilash; Depreux, Frederic F; Jodelka, Francine M; Rigo, Frank; Farris, Hamilton E; Hastings, Michelle L; Lentz, Jennifer J

    2018-02-01

    The absence of functional outer hair cells is a component of several forms of hereditary hearing impairment, including Usher syndrome, the most common cause of concurrent hearing and vision loss. Antisense oligonucleotide (ASO) treatment of mice with the human Usher mutation, Ush1c c.216G>A, corrects gene expression and significantly improves hearing, as measured by auditory-evoked brainstem responses (ABRs), as well as inner and outer hair cell (IHC and OHC) bundle morphology. However, it is not clear whether the improvement in hearing achieved by ASO treatment involves the functional rescue of outer hair cells. Here, we show that Ush1c c.216AA mice lack OHC function as evidenced by the absence of distortion product otoacoustic emissions (DPOAEs) in response to low-, mid-, and high-frequency tone pairs. This OHC deficit is rescued by treatment with an ASO that corrects expression of Ush1c c.216G>A. Interestingly, although rescue of inner hairs cells, as measured by ABR, is achieved by ASO treatment as late as 7 days after birth, rescue of outer hair cells, measured by DPOAE, requires treatment before post-natal day 5. These results suggest that ASO-mediated rescue of both IHC and OHC function is age dependent and that the treatment window is different for the different cell types. The timing of treatment for congenital hearing disorders is of critical importance for the development of drugs such ASO-29 for hearing rescue.

  5. 30 CFR 49.1 - Purpose and scope.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Purpose and scope. 49.1 Section 49.1 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR EDUCATION AND TRAINING MINE RESCUE TEAMS Mine Rescue Teams for Underground Metal and Nonmetal Mines § 49.1 Purpose and scope. This part...

  6. 30 CFR 49.1 - Purpose and scope.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Purpose and scope. 49.1 Section 49.1 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR EDUCATION AND TRAINING MINE RESCUE TEAMS Mine Rescue Teams for Underground Metal and Nonmetal Mines § 49.1 Purpose and scope. This part...

  7. 30 CFR 49.1 - Purpose and scope.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Purpose and scope. 49.1 Section 49.1 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR EDUCATION AND TRAINING MINE RESCUE TEAMS Mine Rescue Teams for Underground Metal and Nonmetal Mines § 49.1 Purpose and scope. This part...

  8. Osteoblast Specific Overexpression of Human Interleukin-7 Rescues the Bone Mass Phenotype of Interleukin-7 Deficient Female Mice

    PubMed Central

    Aguila, Hector L.; Mun, Se Hwan; Kalinowski, Judith; Adams, Douglas J.; Lorenzo, Joseph A.; Lee, Sun-Kyeong

    2012-01-01

    Interleukin-7 is a critical cytokine for lymphoid development and a direct inhibitor of in vitro osteoclastogenesis in murine bone marrow cultures. To explore the role of IL-7 in bone, we generated transgenic mouse lines bearing the 2.3 Kb rat collagen 1A1 promoter driving the expression of human IL-7 specifically in osteoblasts. In addition we crossed these mice with IL-7 deficient mice to determine if the alterations in lymphopoiesis, bone mass and osteoclast formation observed in the IL-7 KO mice could be rescued by osteoblast-specific overexpression of IL-7. Here we show that mice overexpressing human IL-7 in the osteoblast lineage demonstrated increased trabecular bone volume in vivo by µCT and decreased osteoclast formation in vitro. Furthermore, targeted overexpression of IL-7 in osteoblasts rescued the osteopenic bone phenotype and B cell development of IL-7 KO mice but did not have an effect on T lymphopoiesis, which occurs in the periphery. The bone phenotypes in IL-7 KO mice and targeted IL-7 overexpressing mouse models were observed only in females. These results likely reflect both a direct inhibitory effects of IL-7 on osteoclastogenesis in vivo and gender specific differences in responses to IL-7. PMID:22258693

  9. Role of CTGF in White Matter Development in Tuberous Sclerosis

    DTIC Science & Technology

    2015-02-01

    previously shown to affect CTGF expression. Our preliminary results show that SRF is downregulated in Tsc1 mutant brains and this can be rescued by rapamycin ...expression. Our preliminary results show that SRF is downregulated in Tsc1 mutant brains and this can be rescued by rapamycin treatment suggesting a...on SRF pathway in our previous report, here we show that SRF levels are decreased in vivo in mutant mice, and this can be rescued by rapamycin

  10. The effect of intraoperative dexmedetomidine on postoperative analgesia and sedation in pediatric patients undergoing tonsillectomy and adenoidectomy.

    PubMed

    Olutoye, Olutoyin A; Glover, Chris D; Diefenderfer, John W; McGilberry, Michael; Wyatt, Matthew M; Larrier, Deidre R; Friedman, Ellen M; Watcha, Mehernoor F

    2010-08-01

    The immediate postoperative period after tonsillectomy and adenoidectomy, one of the most common pediatric surgical procedures, is often difficult. These children frequently have severe pain but postoperative airway edema along with increased sensitivity to the respiratory-depressant effects of opioids may result in obstructive symptoms and hypoxemia. Opioid consumption may be reduced by nonsteroidal antiinflammatory drugs, but these drugs may be associated with increased bleeding after this operation. Dexmedetomidine has mild analgesic properties, causes sedation without respiratory depression, and does not have an effect on coagulation. We designed a prospective, double-blind, randomized controlled study to determine the effects of intraoperative dexmedetomidine on postoperative recovery including pain, sedation, and hemodynamics in pediatric patients undergoing tonsillectomy and adenoidectomy. One hundred nine patients were randomized to receive a single intraoperative dose of dexmedetomidine 0.75 microg/kg, dexmedetomidine 1 microg/kg, morphine 50 microg/kg, or morphine 100 microg/kg over 10 minutes after endotracheal intubation. There were no significant differences among the 4 groups in patient demographics, ASA physical status, postoperative opioid requirements, sedation scores, duration of oxygen supplementation in the postanesthetic care unit, and time to discharge readiness. The median time to first postoperative rescue analgesic was similar in patients receiving dexmedetomidine 1 microg/kg and morphine 100 microg/kg, but significantly longer compared with patients receiving dexmedetomidine 0.75 microg/kg or morphine 50 microg/kg (P < 0.01). In addition, the number of patients requiring >1 rescue analgesic dose was significantly higher in the dexmedetomidine 0.75 microg/kg group compared with the dexmedetomidine 1 microg/kg and morphine 100 microg/kg groups, but not the morphine 50 microg/kg group. Patients receiving dexmedetomidine had significantly slower heart rates in the first 30 minutes after surgery compared with those receiving morphine (P < 0.05). There was no significant difference in sedation scores among the groups. The total postoperative rescue opioid requirements were similar in tonsillectomy patients receiving intraoperative dexmedetomidine or morphine. However, the use of dexmedetomidine 1 microg/kg and morphine 100 microg/kg had the advantages of an increased time to first analgesic and a reduced need for additional rescue analgesia doses, without increasing discharge times.

  11. Reducing the Gap of Pain: A Strategy for Optimizing Federal Resource Availability in Response to Major Incidents

    DTIC Science & Technology

    2007-03-01

    TM Transportation Means TX- TF1 Texas Task Force 1; a US&R team UPS United Parcel Service, Inc.; a major commercial cargo carrier US&R Urban...Pennsylvania Urban Search and Rescue (US&R) Task Force One (PA- TF1 ) were pre-deployed to the area in advance of the storm. In a moving report of their...4 it would be a good idea to add swiftwater/flood rescue components to all of the US&R Task Forces.” Lt. Douglas Bair, a PA- TF1 rescue squad

  12. Unexpected nerve gas exposure in the city of Matsumoto: report of rescue activity in the first sarin gas terrorism.

    PubMed

    Okudera, H; Morita, H; Iwashita, T; Shibata, T; Otagiri, T; Kobayashi, S; Yanagisawa, N

    1997-09-01

    This report describes the rescue activities and the exposure of rescue and hospital personnel from the first unexpected nerve gas terrorist attack using sarin (isopropyl methylphophonofluoridate) in the city of Matsumoto at midnight on June 27, 1994. The details of the emergency activities in the disaster were studied based on the records from emergency departments of the affiliated hospitals and records from the firehouse. About 600 people, including residents and rescue staff, were exposed to sarin gas. Fifty-eight residents were admitted to hospitals, and 7 died. Among 95 rescuers and the duty doctor from the doctor car, 8 had mild symptoms of poisoning. All the rescue activity took place without gas masks or decontamination procedures. In this case of unexpected mass exposure to sarin gas, the emergency rescue system for a large disaster in Matsumoto city, which had been established for a conflagration or a local earthquake, was effective.

  13. A new type of gene-disruption cassette with a rescue gene for Pichia pastoris.

    PubMed

    Shibui, Tatsuro; Hara, Hiroyoshi

    2017-09-01

    Pichia pastoris has been used for the production of many recombinant proteins, and many useful mutant strains have been created. However, the efficiency of mutant isolation by gene-targeting is usually low and the procedure is difficult for those inexperienced in yeast genetics. In order to overcome these issues, we developed a new gene-disruption system with a rescue gene using an inducible Cre/mutant-loxP system. With only short homology regions, the gene-disruption cassette of the system replaces its target-gene locus containing a mutation with a compensatory rescue gene. As the cassette contains the AOX1 promoter-driven Cre gene, when targeted strains are grown on media containing methanol, the DNA fragment, i.e., the marker, rescue and Cre genes, between the mutant-loxP sequences in the cassette is excised, leaving only the remaining mutant-loxP sequence in the genome, and consequently a target gene-disrupted mutant can be isolated. The system was initially validated on ADE2 gene disruption, where the disruption can easily be detected by color-change of the colonies. Then, the system was applied for knocking-out URA3 and OCH1 genes, reported to be difficult to accomplish by conventional gene-targeting methods. All three gene-disruption cassettes with their rescue genes replaced their target genes, and the Cre/mutant-loxP system worked well to successfully isolate their knock-out mutants. This study identified a new gene-disruption system that could be used to effectively and strategically knock out genes of interest, especially whose deletion is detrimental to growth, without using special strains, e.g., deficient in nonhomologous end-joining, in P. pastoris. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:1201-1208, 2017. © 2017 American Institute of Chemical Engineers.

  14. Efficacy and safety of fosfomycin plus imipenem as rescue therapy for complicated bacteremia and endocarditis due to methicillin-resistant Staphylococcus aureus: a multicenter clinical trial.

    PubMed

    del Río, Ana; Gasch, Oriol; Moreno, Asunción; Peña, Carmen; Cuquet, Jordi; Soy, Dolors; Mestres, Carlos A; Suárez, Cristina; Pare, Juan C; Tubau, Fe; Garcia de la Mària, Cristina; Marco, Francesc; Carratalà, Jordi; Gatell, José M; Gudiol, Francisco; Miró, José M

    2014-10-15

    There is an urgent need for alternative rescue therapies in invasive infections caused by methicillin-resistant Staphylococcus aureus (MRSA). We assessed the clinical efficacy and safety of the combination of fosfomycin and imipenem as rescue therapy for MRSA infective endocarditis and complicated bacteremia. The trial was conducted between 2001 and 2010 in 3 Spanish hospitals. Adult patients with complicated MRSA bacteremia or endocarditis requiring rescue therapy were eligible for the study. Treatment with fosfomycin (2 g/6 hours IV) plus imipenem (1 g/6 hours IV) was started and monitored. The primary efficacy endpoints were percentage of sterile blood cultures at 72 hours and clinical success rate assessed at the test-of-cure visit (45 days after the end of therapy). The combination was administered in 12 patients with endocarditis, 2 with vascular graft infection, and 2 with complicated bacteremia. Therapy had previously failed with vancomycin in 9 patients, daptomycin in 2, and sequential antibiotics in 5. Blood cultures were negative 72 hours after the first dose of the combination in all cases. The success rate was 69%, and only 1 of 5 deaths was related to the MRSA infection. Although the combination was safe in most patients (94%), a patient with liver cirrhosis died of multiorgan failure secondary to sodium overload. There were no episodes of breakthrough bacteremia or relapse. Fosfomycin plus imipenem was an effective and safe combination when used as rescue therapy for complicated MRSA bloodstream infections and deserves further clinical evaluation as initial therapy in these infections. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  15. 14 CFR 121.106 - ETOPS Alternate Airport: Rescue and fire fighting service.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 14 Aeronautics and Space 3 2013-01-01 2013-01-01 false ETOPS Alternate Airport: Rescue and fire... and Flag Operations § 121.106 ETOPS Alternate Airport: Rescue and fire fighting service. (a) Except as... available at each airport listed as an ETOPS Alternate Airport in a dispatch or flight release. (1) For...

  16. 14 CFR 121.106 - ETOPS Alternate Airport: Rescue and fire fighting service.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 14 Aeronautics and Space 3 2014-01-01 2014-01-01 false ETOPS Alternate Airport: Rescue and fire... and Flag Operations § 121.106 ETOPS Alternate Airport: Rescue and fire fighting service. (a) Except as... available at each airport listed as an ETOPS Alternate Airport in a dispatch or flight release. (1) For...

  17. 14 CFR 121.106 - ETOPS Alternate Airport: Rescue and fire fighting service.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 3 2012-01-01 2012-01-01 false ETOPS Alternate Airport: Rescue and fire... and Flag Operations § 121.106 ETOPS Alternate Airport: Rescue and fire fighting service. (a) Except as... available at each airport listed as an ETOPS Alternate Airport in a dispatch or flight release. (1) For...

  18. Green tea polyphenol (−)-epigallocatechin-3-gallate triggered hepatotoxicity in mice: Responses of major antioxidant enzymes and the Nrf2 rescue pathway

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wang, Dongxu; Wang, Yijun; Wan, Xiaochun

    (−)-Epigallocatechin-3-gallate (EGCG), a constituent of green tea, has been suggested to have numerous health-promoting effects. On the other hand, high-dose EGCG is able to evoke hepatotoxicity. In the present study, we elucidated the responses of hepatic major antioxidant enzymes and nuclear factor erythroid 2-related factor 2 (Nrf2) rescue pathway to high-dose levels of EGCG in Kunming mice. At a non-lethal toxic dose (75 mg/kg, i.p.), repeated EGCG treatments markedly decreased the levels of superoxide dismutase, catalase, and glutathione peroxidase. As a rescue response, the nuclear distribution of Nrf2 was significantly increased; a battery of Nrf2-target genes, including heme oxygenase 1more » (HO1), NAD(P)H:quinone oxidoreductase 1 (NQO1), glutathione S-transferase (GST), and those involved in glutathione and thioredoxin systems, were all up-regulated. At the maximum tolerated dose (45 mg/kg, i.p.), repeated EGCG treatments did not disturb the major antioxidant defense. Among the above-mentioned genes, only HO1, NQO1, and GST genes were significantly but modestly up-regulated, suggesting a comprehensive and extensive activation of Nrf2-target genes principally occurs at toxic levels of EGCG. At a lethal dose (200 mg/kg, i.p.), a single EGCG treatment dramatically decreased not only the major antioxidant defense but also the Nrf2-target genes, demonstrating that toxic levels of EGCG are able to cause a biphasic response of Nrf2. Overall, the mechanism of EGCG-triggered hepatotoxicity involves suppression of major antioxidant enzymes, and the Nrf2 rescue pathway plays a vital role for counteracting EGCG toxicity. - Highlights: • EGCG at maximum tolerated dose does not disturb hepatic major antioxidant defense. • EGCG at maximum tolerated dose modestly upregulates hepatic Nrf2 target genes. • EGCG at toxic dose suppresses hepatic major antioxidant enzymes. • EGCG at non-lethal toxic dose pronouncedly activates hepatic Nrf2 rescue response. • EGCG at lethal dose substantially suppresses hepatic Nrf2 pathway.« less

  19. The wildlife research & rescue programme for mammals at Hulu Terengganu Hydroelectric Project (HTHEP), Terengganu, Peninsular Malaysia

    NASA Astrophysics Data System (ADS)

    Nur-Syuhada, N.; Magintan, D.; Siti-Hajar, A. R.; Aisah, M. S.; Shukor, M. N.

    2016-11-01

    During the inundation of the Hulu Terengganu Hydroelectric Project in October 2014, a wildlife rescue programme was conducted to rescue animals found trapped within the expanding 61.6 km2 reservoir. A total of 244 mammals from 30 species, representing 12 families were rescued by various methods included baited live trapping, catchpoles, hoop nets and by hand. The order Rodentia recorded the highest amount of rescued individuals at 20.9%, followed by Primate (18.9), Dermoptera (11.1), Carnivora (0.8) and Pholidota (0.4). The genus Rattus recorded the highest individuals rescued (51 individuals) probably due to the rapid clear-cut logging of the forest prior to inundation. Notable mammals of high conservational value rescued included Manis javanicus (Pangolin), Presbytis melalophos siamensis (Mitred Leaf Monkey), Trachypithecus obscurus (Dusky Leaf Monkey), Hylobates lar (White Handed Gibbon), Nycticebus coucang (Slow Loris), Galeopterus variegatus (Sunda Colugo), Callosciurus nigrovittatus (Sunda Black-banded Squirrel), Ratufa spp. (Giant Squirrels), and Sundasciurus hippurus (Horse-tailed Squirrel). Various data and biological samples were collected from the mammals rescued prior to their release at the nearest forest reserves. Rescue operation enabled the inventory and comprehensive data collection of various arboreal and rare mammal species that are hard to capture using the traditional survey method.

  20. Electronic search and rescue aids

    NASA Technical Reports Server (NTRS)

    Trudell, B. J.

    1980-01-01

    There are two elements to the basic electronic search and rescue problem: a means for immediately alerting potential rescuers and an effective method to guide the rescue forces to the scene of the emergency. An Emergency Locator Transmitter (ELT) used by aircraft or an Emergency Position Indicating Radio Beacon (EPIRB) used by maritime vessels has the capability of providing for both an immediate alert and a homing signal to assist rescue forces in locating the site of the distress. This paper describes the development of ELT/EPIRB systems. Emphasis is placed on the SARSAT project, the COSPAS/SARSAT project, and an experimental 406 MHz ELT/EPIRB system.

  1. Comparison of Two Different Intranasal Doses of Dexmedetomidine in Children for Magnetic Resonance Imaging Sedation.

    PubMed

    Tug, Aslihan; Hanci, Ayse; Turk, Hacer Sebnem; Aybey, Ferda; Isil, Canan Tulay; Sayin, Pinar; Oba, Sibel

    2015-12-01

    Anaesthetic agents used for magnetic resonance imaging (MRI) in paediatric patients should cause few adverse effects and allow fast anaesthetic induction and recovery. The administration route is also important and should be minimally invasive. In this study, we aimed to compare two different doses of intranasal dexmedetomidine applied to children for MRI sedation. Sixty patients between 1 and 10 years of age with American Society of Anesthesiologists Physical Status classification I or II who were scheduled for MRI were recruited into this prospective, randomized, double-blind study. Intranasal dexmedetomidine was administered at doses of 3 µg kg(-1) (Group 1) and 4 µg kg(-1) (Group 2) before imaging. Heart rate (HR), peripheral oxygen saturation, respiratory rate and Ramsay Sedation Scale (RSS) scores were recorded before the anaesthetic induction of sedation and every 10 min until discharge. If intranasal sedation failed, an intravenous cannula was placed and propofol was applied as a rescue anaesthetic. Bispectral Index (BIS) scores were also recorded before and after MRI. We recorded onset time of sedation, mood at separation from parents (defined as parental separation score), imaging quality, MRI duration, rescue anaesthetic requirement, total duration of sedation, recovery duration, parents' satisfaction and adverse effects. The results related to age, weight and adverse effects were not statistically different between the groups. The parental separation score was significantly higher in Group 2 (P = 0.003). Rescue anaesthetic requirement was significantly higher in Group 1 (P = 0.002). The results related to recovery duration, MRI duration, parents' satisfaction, onset time of sedation and total duration of sedation were not statistically different. HR was significantly lower in all time intervals compared with basal values in both groups. In Group 2, RSS scores were significantly higher in the 30th, 40th and 50th min. The BIS scores in Group 2 were lower at the 50th min. Neither bradycardia nor oxygen desaturation were observed. Imaging studies were completed successfully in all patients. Based on lower rescue anaesthetic requirements, sufficient sedation and parental separation scores in Group 2, intranasal dexmedetomidine 4 µg kg(-1) was more efficient than intranasal dexmedetomidine 3 µg kg(-1). The intranasal route may be an alternative noninvasive route to apply drugs for MRI sedation in paediatric patients. Trial registration ClinicalTrials.gov: NCT02299232.

  2. Pds5 regulators segregate cohesion and condensation pathways in Saccharomyces cerevisiae

    PubMed Central

    Tong, Kevin; Skibbens, Robert V.

    2015-01-01

    Cohesins are required both for the tethering together of sister chromatids (termed cohesion) and subsequent condensation into discrete structures—processes fundamental for faithful chromosome segregation into daughter cells. Differentiating between cohesin roles in cohesion and condensation would provide an important advance in studying chromatin metabolism. Pds5 is a cohesin-associated factor that is essential for both cohesion maintenance and condensation. Recent studies revealed that ELG1 deletion suppresses the temperature sensitivity of pds5 mutant cells. However, the mechanisms through which Elg1 may regulate cohesion and condensation remain unknown. Here, we report that ELG1 deletion from pds5-1 mutant cells results in a significant rescue of cohesion, but not condensation, defects. Based on evidence that Elg1 unloads the DNA replication clamp PCNA from DNA, we tested whether PCNA overexpression would similarly rescue pds5-1 mutant cell cohesion defects. The results indeed reveal that elevated levels of PCNA rescue pds5-1 temperature sensitivity and cohesion defects, but do not rescue pds5-1 mutant cell condensation defects. In contrast, RAD61 deletion rescues the condensation defect, but importantly, neither the temperature sensitivity nor cohesion defects exhibited by pds5-1 mutant cells. In combination, these findings reveal that cohesion and condensation are separable pathways and regulated in nonredundant mechanisms. These results are discussed in terms of a new model through which cohesion and condensation are spatially regulated. PMID:25986377

  3. Pds5 regulators segregate cohesion and condensation pathways in Saccharomyces cerevisiae.

    PubMed

    Tong, Kevin; Skibbens, Robert V

    2015-06-02

    Cohesins are required both for the tethering together of sister chromatids (termed cohesion) and subsequent condensation into discrete structures-processes fundamental for faithful chromosome segregation into daughter cells. Differentiating between cohesin roles in cohesion and condensation would provide an important advance in studying chromatin metabolism. Pds5 is a cohesin-associated factor that is essential for both cohesion maintenance and condensation. Recent studies revealed that ELG1 deletion suppresses the temperature sensitivity of pds5 mutant cells. However, the mechanisms through which Elg1 may regulate cohesion and condensation remain unknown. Here, we report that ELG1 deletion from pds5-1 mutant cells results in a significant rescue of cohesion, but not condensation, defects. Based on evidence that Elg1 unloads the DNA replication clamp PCNA from DNA, we tested whether PCNA overexpression would similarly rescue pds5-1 mutant cell cohesion defects. The results indeed reveal that elevated levels of PCNA rescue pds5-1 temperature sensitivity and cohesion defects, but do not rescue pds5-1 mutant cell condensation defects. In contrast, RAD61 deletion rescues the condensation defect, but importantly, neither the temperature sensitivity nor cohesion defects exhibited by pds5-1 mutant cells. In combination, these findings reveal that cohesion and condensation are separable pathways and regulated in nonredundant mechanisms. These results are discussed in terms of a new model through which cohesion and condensation are spatially regulated.

  4. Exploring the Interplay between Rescue Drugs, Data Imputation, and Study Outcomes: Conceptual Review and Qualitative Analysis of an Acute Pain Data Set.

    PubMed

    Singla, Neil K; Meske, Diana S; Desjardins, Paul J

    2017-12-01

    In placebo-controlled acute surgical pain studies, provisions must be made for study subjects to receive adequate analgesic therapy. As such, most protocols allow study subjects to receive a pre-specified regimen of open-label analgesic drugs (rescue drugs) as needed. The selection of an appropriate rescue regimen is a critical experimental design choice. We hypothesized that a rescue regimen that is too liberal could lead to all study arms receiving similar levels of pain relief (thereby confounding experimental results), while a regimen that is too stringent could lead to a high subject dropout rate (giving rise to a preponderance of missing data). Despite the importance of rescue regimen as a study design feature, there exist no published review articles or meta-analysis focusing on the impact of rescue therapy on experimental outcomes. Therefore, when selecting a rescue regimen, researchers must rely on clinical factors (what analgesics do patients usually receive in similar surgical scenarios) and/or anecdotal evidence. In the following article, we attempt to bridge this gap by reviewing and discussing the experimental impacts of rescue therapy on a common acute surgical pain population: first metatarsal bunionectomy. The function of this analysis is to (1) create a framework for discussion and future exploration of rescue as a methodological study design feature, (2) discuss the interplay between data imputation techniques and rescue drugs, and (3) inform the readership regarding the impact of data imputation techniques on the validity of study conclusions. Our findings indicate that liberal rescue may degrade assay sensitivity, while stringent rescue may lead to unacceptably high dropout rates.

  5. Deep brain stimulation, histone deacetylase inhibitors and glutamatergic drugs rescue resistance to fear extinction in a genetic mouse model

    PubMed Central

    Whittle, Nigel; Schmuckermair, Claudia; Gunduz Cinar, Ozge; Hauschild, Markus; Ferraguti, Francesco; Holmes, Andrew; Singewald, Nicolas

    2013-01-01

    Anxiety disorders are characterized by persistent, excessive fear. Therapeutic interventions that reverse deficits in fear extinction represent a tractable approach to treating these disorders. We previously reported that 129S1/SvImJ (S1) mice show no extinction learning following normal fear conditioning. We now demonstrate that weak fear conditioning does permit fear reduction during massed extinction training in S1 mice, but reveals specific deficiency in extinction memory consolidation/retrieval. Rescue of this impaired extinction consolidation/retrieval was achieved with d-cycloserine (N-methly-d-aspartate partial agonist) or MS-275 (histone deacetylase (HDAC) inhibitor), applied after extinction training. We next examined the ability of different drugs and non-pharmacological manipulations to rescue the extreme fear extinction deficit in S1 following normal fear conditioning with the ultimate aim to produce low fear levels in extinction retrieval tests. Results showed that deep brain stimulation (DBS) by applying high frequency stimulation to the nucleus accumbens (ventral striatum) during extinction training, indeed significantly reduced fear during extinction retrieval compared to sham stimulation controls. Rescue of both impaired extinction acquisition and deficient extinction consolidation/retrieval was achieved with prior extinction training administration of valproic acid (a GABAergic enhancer and HDAC inhibitor) or AMN082 [metabotropic glutamate receptor 7 (mGlu7) agonist], while MS-275 or PEPA (AMPA receptor potentiator) failed to affect extinction acquisition in S1 mice. Collectively, these data identify potential beneficial effects of DBS and various drug treatments, including those with HDAC inhibiting or mGlu7 agonism properties, as adjuncts to overcome treatment resistance in exposure-based therapies. This article is part of a Special Issue entitled ‘Cognitive Enhancers’. PMID:22722028

  6. Endoscopic sphenopalatine ganglion blockade efficacy in pain control after endoscopic sinus surgery.

    PubMed

    Al-Qudah, Mohannad

    2016-03-01

    The objective of this study was to evaluate the efficacy of bilateral endoscopic injection of lidocaine with epinephrine in the sphenopalatine ganglion at the end of endoscopic sinus surgery (ESS) in controlling postoperative pain and rescue analgesic requirements. A prospective, double blinded, placebo-controlled clinical trial of 60 patients with chronic rhinosinusitis (CRS) undergoing general anesthesia for ESS was undertaken. Patients were randomized to receive injection of 2 mL of 2% lidocaine with epinephrine or 2 mL saline at the end of surgery. Postoperatively, patients were observed for 24 hours. Pain severity was reported immediately, 6 hours, and 24 hours after surgery using a 10-cm visual analog scale (VAS). The need of rescue analgesia was recorded and compared between the 2 groups. The 2 groups were matched in demographic and intraoperative details. Postoperative pain severity average was 3.4, 3.0, and 1.6 in the saline group compared to 1.6, 1.7, and 1.0 in the lidocaine group. These differences reached statically significant for the first 2 follow-up intervals. Also, there was significant difference in the whole-day postoperative average score between the 2 groups (2.6 vs 1.4). Twelve patients in the saline group required rescue analgesia compared to 5 in the lidocaine group. The average rescue analgesia dose was 27.5 mg of tramadol in the saline group vs 11.6 in the lidocaine group. These differences were statistically significant. No complications were reported in either group. Sphenopalatine ganglion injection of lidocaine at the end of surgery is safe, simple, noninvasive, and an effective method of short-term pain control after sinus surgery. © 2015 ARS-AAOA, LLC.

  7. Glycosylation of Cblns attenuates their receptor binding.

    PubMed

    Rong, Yongqi; Bansal, Parmil K; Wei, Peng; Guo, Hong; Correia, Kristen; Parris, Jennifer; Morgan, James I

    2018-05-18

    Cbln1 is the prototype of a family (Cbln1-Cbln4) of secreted glycoproteins and is essential for normal synapse structure and function in cerebellum by bridging presynaptic Nrxn to postsynaptic Grid2. Here we report the effects of glycosylation on the in vitro receptor binding properties of Cblns. Cbln1, 2 and 4 harbor two N-linked glycosylation sites, one at the N-terminus is in a region implicated in Nrxn binding and the second is in the C1q domain, a region involved in Grid2 binding. Mutation (asparagine to glutamine) of the N-terminal site, increased neurexin binding whereas mutation of the C1q site markedly increased Grid2 binding. These mutations did not influence subunit composition of Cbln trimeric complexes (mediated through the C1q domain) nor their assembly into hexamers (mediated by the N-terminal region). Therefore, glycosylation likely masks the receptor binding interfaces of Cblns. As Cbln4 has undetectable Grid2 binding in vitro we assessed whether transgenic expression of wild type Cbln4 or its glycosylation mutants rescued the Cbln1-null phenotype in vivo. Cbln4 partially rescued and both glycosylation mutants completely rescued ataxia in cbln1-null mice. Thus Cbln4 has intrinsic Grid2 binding that is attenuated by glycosylation, and glycosylation mutants exhibit gain of function in vivo. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  8. Absence of Wip1 partially rescues Atm deficiency phenotypes in mice

    PubMed Central

    Darlington, Yolanda; Nguyen, Thuy-Ai; Moon, Sung-Hwan; Herron, Alan; Rao, Pulivarthi; Zhu, Chengming; Lu, Xiongbin; Donehower, Lawrence A.

    2011-01-01

    Wildtype p53-Induced Phosphatase 1 (WIP1) is a serine/threonine phosphatase that dephosphorylates proteins in the ataxia telangiectasia mutated (ATM)-initiated DNA damage response pathway. WIP1 may play a homeostatic role in ATM signaling by returning the cell to a normal pre-stress state following completion of DNA repair. To better understand the effects of WIP1 on ATM signaling, we crossed Atm-deficient mice to Wip1-deficient mice and characterized phenotypes of the double knockout progeny. We hypothesized that the absence of Wip1 might rescue Atm deficiency phenotypes. Atm null mice, like ATM-deficient humans with the inherited syndrome ataxia telangiectasia, exhibit radiation sensitivity, fertility defects, and are T-cell lymphoma prone. Most double knockout mice were largely protected from lymphoma development and had a greatly extended lifespan compared to Atm null mice. Double knockout mice had increased p53 and H2AX phosphorylation and p21 expression compared to their Atm null counterparts, indicating enhanced p53 and DNA damage responses. Additionally, double knockout splenocytes displayed reduced chromosomal instability compared to Atm null mice. Finally, doubly null mice were partially rescued from infertility defects observed in Atm null mice. These results indicate that inhibition of WIP1 may represent a useful strategy for cancer treatment in general and A-T patients in particular. PMID:21765465

  9. White Sands Space Harbor Area 1, Crash/Rescue Standby Support GPS ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    White Sands Space Harbor Area 1, Crash/Rescue Standby Support GPS Buildings, East side of Runway 17/35, approximately 2,650 feet north of intersection with Runway 23/05, White Sands, Dona Ana County, NM

  10. Space Rescue

    NASA Technical Reports Server (NTRS)

    Muratore, John F.

    2007-01-01

    Space Rescue has been a topic of speculation for a wide community of people for decades. Astronauts, aerospace engineers, diplomats, medical and rescue professionals, inventors and science fiction writers have all speculated on this problem. Martin Caidin's 1964 novel Marooned dealt with the problems of rescuing a crew stranded in low earth orbit. Legend at the Johnson Space Center says that Caidin's portrayal of a Russian attempt to save the American crew played a pivotal role in convincing the Russians to join the real joint Apollo-Soyuz mission. Space Rescue has been a staple in science fiction television and movies portrayed in programs such as Star Trek, Stargate-SG1 and Space 1999 and movies such as Mission To Mars and Red Planet. As dramatic and as difficult as rescue appears in fictional accounts, in the real world it has even greater drama and greater difficulty. Space rescue is still in its infancy as a discipline and the purpose of this chapter is to describe the issues associated with space rescue and the work done so far in this field. For the purposes of this chapter, the term space rescue will refer to any system which allows for rescue or escape of personnel from situations which endanger human life in a spaceflight operation. This will span the period from crew ingress prior to flight through crew egress postlanding. For the purposes of this chapter, the term primary system will refer to the spacecraft system that a crew is either attempting to escape from or from which an attempt is being made to rescue the crew.

  11. Administration of exogenous 1,25(OH)2D3 normalizes overactivation of the central renin-angiotensin system in 1α(OH)ase knockout mice.

    PubMed

    Zhang, Wei; Chen, Lulu; Zhang, Luqing; Xiao, Ming; Ding, Jiong; Goltzman, David; Miao, Dengshun

    2015-02-19

    Previously, we reported that active vitamin D deficiency in mice causes secondary hypertension and cardiac dysfunction, but the underlying mechanism remains largely unknown. To clarify whether exogenous active vitamin D rescues hypertension by normalizing the altered central renin-angiotensin system (RAS) via an antioxidative stress mechanism, 1-alpha-hydroxylase [1α(OH)ase] knockout mice [1α(OH)ase(-/-)] and their wild-type littermates were fed a normal diet alone or with 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], or a high-calcium, high-phosphorus "rescue" diet with or without antioxidant N-acetyl-l-cysteine (NAC) supplementation for 4 weeks. Compared with their wild-type littermates, 1α(OH)ase(-/-)mice had high mean arterial pressure, increased levels of renin, angiotensin II (Ang II), and Ang II type 1 receptor, and increased malondialdehyde levels, but decreased anti-peroxiredoxin I and IV proteins and the antioxidative genes glutathione reductase (Gsr) and glutathione peroxidase 4 (Gpx4) in the brain samples. Except Ang II type 1 receptor, these pathophysiological changes were rescued by exogenous 1,25(OH)2D3 or NAC plus rescue diet, but not by rescue diet alone. We conclude that 1,25(OH)2D3 normalizes the altered central RAS in 1α(OH)ase(-/-)mice, at least partially, through a central antioxidative mechanism. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  12. Environment enrichment rescues the neurodegenerative phenotypes in presenilins-deficient mice.

    PubMed

    Dong, Suzhen; Li, Chunxia; Wu, Pu; Tsien, Joe Z; Hu, Yinghe

    2007-07-01

    Presenilin (PS) 1 and 2 conditional double knockout (cDKO) mice show progressive memory dysfunction and forebrain degeneration. Gene expression profiling results revealed a strong activation of immunity and inflammation responses in the brains of 10-month-old cDKO mice. As environmental enrichment (EE) has been shown to be able to improve memory and induce neurogenesis of the brain, we assessed the effects of EE on the memory performance and the neurodegeneration in cDKO mice. We found that EE effectively enhanced memory and partially rescued the forebrain atrophy of the cDKO mice. Our results suggest that immunity and inflammation could play important roles in the neurodegeneration of cDKO mice. Furthermore, the beneficial effects of EE may be associated with the inhibition of the expression of immunity and inflammation-related genes in the brain.

  13. Knockout-Rescue Embryonic Stem Cell-Derived Mouse Reveals Circadian-Period Control by Quality and Quantity of CRY1.

    PubMed

    Ode, Koji L; Ukai, Hideki; Susaki, Etsuo A; Narumi, Ryohei; Matsumoto, Katsuhiko; Hara, Junko; Koide, Naoshi; Abe, Takaya; Kanemaki, Masato T; Kiyonari, Hiroshi; Ueda, Hiroki R

    2017-01-05

    To conduct comprehensive characterization of molecular properties in organisms, we established an efficient method to produce knockout (KO)-rescue mice within a single generation. We applied this method to produce 20 strains of almost completely embryonic stem cell (ESC)-derived mice ("ES mice") rescued with wild-type and mutant Cry1 gene under a Cry1 -/- :Cry2 -/- background. A series of both phosphorylation-mimetic and non-phosphorylation-mimetic CRY1 mutants revealed that multisite phosphorylation of CRY1 can serve as a cumulative timer in the mammalian circadian clock. KO-rescue ES mice also revealed that CRY1-PER2 interaction confers a robust circadian rhythmicity in mice. Surprisingly, in contrast to theoretical predictions from canonical transcription/translation feedback loops, the residues surrounding the flexible P loop and C-lid domains of CRY1 determine circadian period without changing the degradation rate of CRY1. These results suggest that CRY1 determines circadian period through both its degradation-dependent and -independent pathways. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Pharmacological Modulation of Three Modalities of CA1 Hippocampal Long-Term Potentiation in the Ts65Dn Mouse Model of Down Syndrome

    PubMed Central

    Scott-McKean, Jonah J.; Roque, Adriano L.; Surewicz, Krystyna; Johnson, Mark W.; Surewicz, Witold K.

    2018-01-01

    The Ts65Dn mouse is the most studied animal model of Down syndrome. Past research has shown a significant reduction in CA1 hippocampal long-term potentiation (LTP) induced by theta-burst stimulation (TBS), but not in LTP induced by high-frequency stimulation (HFS), in slices from Ts65Dn mice compared with euploid mouse-derived slices. Additionally, therapeutically relevant doses of the drug memantine were shown to rescue learning and memory deficits in Ts65Dn mice. Here, we observed that 1 μM memantine had no detectable effect on HFS-induced LTP in either Ts65Dn- or control-derived slices, but it rescued TBS-induced LTP in Ts65Dn-derived slices to control euploid levels. Then, we assessed LTP induced by four HFS (4xHFS) and found that this form of LTP was significantly depressed in Ts65Dn slices when compared with LTP in euploid control slices. Memantine, however, did not rescue this phenotype. Because 4xHFS-induced LTP had not yet been characterized in Ts65Dn mice, we also investigated the effects of picrotoxin, amyloid beta oligomers, and soluble recombinant human prion protein (rPrP) on this form of LTP. Whereas ≥10 μM picrotoxin increased LTP to control levels, it also caused seizure-like oscillations. Neither amyloid beta oligomers nor rPrP had any effect on 4xHFS-induced LTP in Ts65Dn-derived slices. PMID:29849573

  15. 30 CFR 75.1714-3 - Self-rescue devices; inspection, testing, maintenance, repair, and recordkeeping.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... devices by a person trained to perform such functions. (b) After each time a self-rescue device is worn or... person trained to perform this function. Self-rescue devices with broken seals or which are damaged so... accurate to within +1 gram. A device that weighs more than 10 grams over its original weight shall be...

  16. [Analysis of actions taken by medical rescue teams in the Polish Emergency Medical Servies system. Is the model of division into specialistad basic teams reasonable?].

    PubMed

    Guła, Przemysław; Wejnarski, Arkadiusz; Moryto, Remigiusz; Gałazkowski, Robert; Swiezewski, Stanisław

    2014-01-01

    The Polish Emergency Medical Services (EMS) system is based on two types of medical rescue teams (MRT): specialist (S)--with system doctors and basic (B)--only paramedics. The aim of this study is to assess the reasonability of dividing medical rescue teams into specialist and basic. The retrospective analysis of medical cards of rescue activities performed during 21,896 interventions by medical rescue teams, 15,877 of which--by basic medical rescue teams (B MRT) and 6,019--by specialist medical rescue teams (S MRT). The procedures executed by both types of teams were compared. In the analysed group of dispatches, 56.4% were unrelated to medical emergencies. Simultaneously, 52.7% of code 1 interventions and 59.2% of code 2 interventions did not result in transporting the patient to the hospital. The qualification of S teams' dispatches is characterised by a higher number of assigned codes 1 (53.2% vs. 15.9%). It is worth emphasising that the procedures that can be applied exclusively by system doctors do not exceed 1% of interventions. Moreover, the number of the actions performed in medical emergencies in the secured region by the S team that is dispatched as the first one is comparable to that performed by B teams. The low need for usinq S teams'aid by B teams (0.92% of the interventions) was also indicated. This study points to the necessity to discuss the implementation of straightforward principles of call qualification and the optimisation of the system doctors' role in prehospital activities.

  17. Elevating Integrin-linked Kinase Expression has Rescued Hippocampal Neurogenesis and Memory Deficits in an AD animal Model.

    PubMed

    Xu, Xu-Feng; Wang, You-Cui; Zong, Liang; Chen, Zhe-Yu; Li, Yan

    2018-05-19

    Alterations in adult neurogenesis have been regarded as a major cause of cognitive impairment in Alzheimer's disease (AD). The underlying mechanism of neurogenesis deficiency in AD remains unclear. In this study, we reported that Integrin-linked Kinase (ILK) protein levels and phosphorylation were significantly decreased in the hippocampus of APP/PS1 mice. Increased ILK expression of dentate gyrus (DG) rescued the hippocampus-dependent neurogenesis and memory deficits in APP/PS1 mice. Moreover, we demonstrated that the effect of ILK overexpression in the hippocampus was exerted via AKT-GSK3β pathway. Finally, we found that Fluoxetine, a selective serotonin reuptake inhibitor, could improve the impaired hippocampal neurogenesis and memory by enhancing ILK-AKT-GSK3β pathway activity in APP/PS1 mice. Thus, these findings demonstrated the effects of ILK on neurogenesis and memory recovery, suggesting that ILK is an important therapeutic target for AD prevention and treatment. Copyright © 2018. Published by Elsevier B.V.

  18. A Capability-Based Approach to Analyzing the Effectiveness and Robustness of an Offshore Patrol Vessel in the Search and Rescue Mission

    DTIC Science & Technology

    2012-12-01

    13 D. NPSS MODEL DEVELOPMENT...COMPARISON: NPSS MODEL WITH ITALIAN MODEL ...................51 IV. CONCLUSIONS AND RECOMMENDATIONS...58 1. Italian Model Recommendations ......................................................58 2. NPSS Model

  19. Properties and natural occurrence of maternal-effect selfish genes ('Medea' factors) in the red flour beetle, tribolium castaneum

    PubMed

    Beeman; Friesen

    1999-05-01

    Maternally acting selfish genes, termed 'Medea' factors, were found to be widespread in wild populations of Tribolium castaneum collected in Europe, North and South America, Africa and south-east Asia, but were rare or absent in populations from Australia and the Indian subcontinent. We detected at least four distinct genetic loci in at least two different linkage groups that exhibit the Medea pattern of differential mortality of genotypes within maternal families. Although each M factor tested had similar properties of maternal lethality to larvae and zygotic self-rescue, M factors representing distinct loci did not show cross-rescue. Alleles at two of these loci, M1 and M4, were by far the most prevalent, M4 being the predominant type. M2 and M3 were each found only once, in Pakistan and Japan, respectively. Although M1 could be genetically segregated from M4 and maintained as a purified stock, the M1 factor invariably co-occurred with M4 in field populations, whereas M4 usually occurred in the absence of other Medea factors. The dominant maternal lethal action of M1 could be selectively inactivated (reverted) by gene-knockout gamma irradiation with retention of zygotic rescue activity.

  20. The group II metabotropic glutamate receptor agonist LY354740 and the D2 receptor antagonist haloperidol reduce locomotor hyperactivity but fail to rescue spatial working memory in GluA1 knockout mice.

    PubMed

    Boerner, Thomas; Bygrave, Alexei M; Chen, Jingkai; Fernando, Anushka; Jackson, Stephanie; Barkus, Chris; Sprengel, Rolf; Seeburg, Peter H; Harrison, Paul J; Gilmour, Gary; Bannerman, David M; Sanderson, David J

    2017-04-01

    Group II metabotropic glutamate receptor agonists have been suggested as potential anti-psychotics, at least in part, based on the observation that the agonist LY354740 appeared to rescue the cognitive deficits caused by non-competitive N-methyl-d-aspartate receptor (NMDAR) antagonists, including spatial working memory deficits in rodents. Here, we tested the ability of LY354740 to rescue spatial working memory performance in mice that lack the GluA1 subunit of the AMPA glutamate receptor, encoded by Gria1, a gene recently implicated in schizophrenia by genome-wide association studies. We found that LY354740 failed to rescue the spatial working memory deficit in Gria1 -/- mice during rewarded alternation performance in the T-maze. In contrast, LY354740 did reduce the locomotor hyperactivity in these animals to a level that was similar to controls. A similar pattern was found with the dopamine receptor antagonist haloperidol, with no amelioration of the spatial working memory deficit in Gria1 -/- mice, even though the same dose of haloperidol reduced their locomotor hyperactivity. These results with LY354740 contrast with the rescue of spatial working memory in models of glutamatergic hypofunction using non-competitive NMDAR antagonists. Future studies should determine whether group II mGluR agonists can rescue spatial working memory deficits with other NMDAR manipulations, including genetic models and other pharmacological manipulations of NMDAR function. © 2017 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  1. Enhancing dopaminergic signaling and histone acetylation promotes long-term rescue of deficient fear extinction.

    PubMed

    Whittle, N; Maurer, V; Murphy, C; Rainer, J; Bindreither, D; Hauschild, M; Scharinger, A; Oberhauser, M; Keil, T; Brehm, C; Valovka, T; Striessnig, J; Singewald, N

    2016-12-06

    Extinction-based exposure therapy is used to treat anxiety- and trauma-related disorders; however, there is the need to improve its limited efficacy in individuals with impaired fear extinction learning and to promote greater protection against return-of-fear phenomena. Here, using 129S1/SvImJ mice, which display impaired fear extinction acquisition and extinction consolidation, we revealed that persistent and context-independent rescue of deficient fear extinction in these mice was associated with enhanced expression of dopamine-related genes, such as dopamine D1 (Drd1a) and -D2 (Drd2) receptor genes in the medial prefrontal cortex (mPFC) and amygdala, but not hippocampus. Moreover, enhanced histone acetylation was observed in the promoter of the extinction-regulated Drd2 gene in the mPFC, revealing a potential gene-regulatory mechanism. Although enhancing histone acetylation, via administering the histone deacetylase (HDAC) inhibitor MS-275, does not induce fear reduction during extinction training, it promoted enduring and context-independent rescue of deficient fear extinction consolidation/retrieval once extinction learning was initiated as shown following a mild conditioning protocol. This was associated with enhanced histone acetylation in neurons of the mPFC and amygdala. Finally, as a proof-of-principle, mimicking enhanced dopaminergic signaling by L-dopa treatment rescued deficient fear extinction and co-administration of MS-275 rendered this effect enduring and context-independent. In summary, current data reveal that combining dopaminergic and epigenetic mechanisms is a promising strategy to improve exposure-based behavior therapy in extinction-impaired individuals by initiating the formation of an enduring and context-independent fear-inhibitory memory.

  2. Multi-agent cooperation rescue algorithm based on influence degree and state prediction

    NASA Astrophysics Data System (ADS)

    Zheng, Yanbin; Ma, Guangfu; Wang, Linlin; Xi, Pengxue

    2018-04-01

    Aiming at the multi-agent cooperative rescue in disaster, a multi-agent cooperative rescue algorithm based on impact degree and state prediction is proposed. Firstly, based on the influence of the information in the scene on the collaborative task, the influence degree function is used to filter the information. Secondly, using the selected information to predict the state of the system and Agent behavior. Finally, according to the result of the forecast, the cooperative behavior of Agent is guided and improved the efficiency of individual collaboration. The simulation results show that this algorithm can effectively solve the cooperative rescue problem of multi-agent and ensure the efficient completion of the task.

  3. Beneficial effects of vitamin C treatment on pregnant rats exposed to formaldehyde: Reversal of immunosuppression in the offspring

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ibrahim, Beatriz Silva; Barioni, Éric Diego; Helua

    Inhalation of formaldehyde (FA) during the pregnancy induces oxidative stress in the uterus, and here we hypothesized that this mechanism may be responsible for the impaired immune response detected in the offspring. In order to investigate the protective effects of Vitamin C on the oxidative stress induced by FA in the uterine microenvironment, pregnant Wistar rats were treated with vitamin C (150 mg/kg, gavage) or vehicle (distilled water, gavage) 1 h before FA exposure (0.92 mg/m{sup 3}, 1 h/day, 5 days/week), for 21 days, and the 30 days old offspring were submitted to LPS injection (Salmonella abortus equi, 5 mg/kg,more » i.p.). The enhanced gene expression of iNOS, COX-1 and COX-2 and decreased gene expression of SOD-2 in the uterus of FA exposed mothers was rescued by Vit C treatment. Moreover, vitamin C rescued the impaired immune response elicited by LPS in the offspring from FA exposed mothers, by increasing the number of blood and bone marrow leukocytes, and augmenting gene expression of IL-6 and reducing mRNA levels of IL-10 and IFN in the lungs. Vitamin C treatment did not rescue the impaired TLR4-NF-kB pathway in the lung of the offspring, suggesting that FA-induced uterine oxidative stress affects other inflammatory pathways activated by LPS in the offspring. Together, data obtained here confirm our hypothesis that FA-induced oxidative stress in the uterine microenvironment modifies the programming mechanisms of the immune defenses of offspring, leading to an impaired host defense. - Highlights: • FA exposure during pregnancy induces oxidative stress in the uterus. • Vitamin C treatment blunted the oxidative stress in uterus induced by FA exposure. • Oxidative stress in uterus after FA exposure impairs the immune response of offspring. • Vitamin C in pregnant rats rescued the impaired immune response in the offspring.« less

  4. Rescue of protein expression defects may not be enough to abolish the pro-arrhythmic phenotype of long QT type 2 mutations.

    PubMed

    Perry, Matthew D; Ng, Chai Ann; Phan, Kevin; David, Erikka; Steer, Kieran; Hunter, Mark J; Mann, Stefan A; Imtiaz, Mohammad; Hill, Adam P; Ke, Ying; Vandenberg, Jamie I

    2016-07-15

    Most missense long QT syndrome type 2 (LQTS2) mutations result in Kv11.1 channels that show reduced levels of membrane expression. Pharmacological chaperones that rescue mutant channel expression could have therapeutic potential to reduce the risk of LQTS2-associated arrhythmias and sudden cardiac death, but only if the mutant Kv11.1 channels function normally (i.e. like WT channels) after membrane expression is restored. Fewer than half of mutant channels exhibit relatively normal function after rescue by low temperature. The remaining rescued missense mutant Kv11.1 channels have perturbed gating and/or ion selectivity characteristics. Co-expression of WT subunits with gating defective missense mutations ameliorates but does not eliminate the functional abnormalities observed for most mutant channels. For patients with mutations that affect gating in addition to expression, it may be necessary to use a combination therapy to restore both normal function and normal expression of the channel protein. In the heart, Kv11.1 channels pass the rapid delayed rectifier current (IKr ) which plays critical roles in repolarization of the cardiac action potential and in the suppression of arrhythmias caused by premature stimuli. Over 500 inherited mutations in Kv11.1 are known to cause long QT syndrome type 2 (LQTS2), a cardiac electrical disorder associated with an increased risk of life threatening arrhythmias. Most missense mutations in Kv11.1 reduce the amount of channel protein expressed at the membrane and, as a consequence, there has been considerable interest in developing pharmacological agents to rescue the expression of these channels. However, pharmacological chaperones will only have clinical utility if the mutant Kv11.1 channels function normally after membrane expression is restored. The aim of this study was to characterize the gating phenotype for a subset of LQTS2 mutations to assess what proportion of mutations may be suitable for rescue. As an initial screen we used reduced temperature to rescue expression defects of mutant channels expressed in Xenopus laevis oocytes. Over half (∼56%) of Kv11.1 mutants exhibited functional gating defects that either dramatically reduced the amount of current contributing to cardiac action potential repolarization and/or reduced the amount of protective current elicited in response to premature depolarizations. Our data demonstrate that if pharmacological rescue of protein expression defects is going to have clinical utility in the treatment of LQTS2 then it will be important to assess the gating phenotype of LQTS2 mutations before attempting rescue. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

  5. Intraoperative use of a reflective blanket (Sirius rescue sheet) for temperature management in dogs less than 10 kg.

    PubMed

    Tünsmeyer, J; Bojarski, I; Nolte, I; Kramer, S

    2009-07-01

    To compare the effects of the Sirius rescue sheet with gel pads versus gel pads alone on intraoperative body temperature in dogs less than 10 kg. Forty small breed dogs undergoing elective surgical procedures were randomly assigned to two groups. One group was intraoperatively laid on warmed gel pads, and the other group was additionally wrapped in a Sirius rescue sheet. Oesophageal body temperature was determined every 10 minutes and compared between groups. Temperature of gel pads was measured preoperatively and postoperatively to compare heat loss of the gel pads between groups. The body temperature of dogs wrapped with the Sirius rescue sheet increased intraoperatively. In dogs just lying on warmed gel pads, a decrease in mean body temperature was revealed and mean body temperatures differed between groups after 40 minutes. Extent of heat loss from the gel pads did not differ between the groups. The Sirius rescue sheet, used in addition to warmed gel pads, led to higher intraoperative body temperatures in small breed dogs undergoing surgical procedures to the extremities and the head. The cost-effectiveness and ease of handling make this a useful addition to clinical practice.

  6. These Things We Do, Personnel Recovery in the Conflicts of Southeast Asia, 1964-1976

    DTIC Science & Technology

    2012-04-01

    losses. Rescue Buildup in Southeast Asia, 1964-1969 The first Air Force causalities in Southeast Asia occurred when a C -47B was shot down over Laos...South Vietnamese Air Force for rescue and recovery. The first Ranch Hand C -123 crashed on February 2, 1962; nine days later by the first Farm Gate SC...assigned the primary mission of providing rescue escort (RESCORT) with A-1s, callsign “Sandy” or “ Spad .” The A-1’s had two orbits in Laos and have

  7. Genetic rescue, the greater prairie chicken and the problem of conservation reliance in the Anthropocene

    PubMed Central

    Mussmann, S. M.; Douglas, M. R.; Anthonysamy, W. J. B.; Davis, M. A.; Simpson, S. A.; Louis, W.

    2017-01-01

    A central question in conservation is how best to manage biodiversity, despite human domination of global processes (= Anthropocene). Common responses (i.e. translocations, genetic rescue) forestall potential extirpations, yet have an uncertain duration. A textbook example is the greater prairie chicken (GRPC: Tympanuchus cupido pinnatus), where translocations (1992–1998) seemingly rescued genetically depauperate Illinois populations. We re-evaluated this situation after two decades by genotyping 21 microsatellite loci from 1831 shed feathers across six leks in two counties over 4 years (2010–2013). Low migration rates (less than 1%) established each county as demographically independent, but with declining-population estimates (4 year average N = 79). Leks were genetically similar and significantly bottlenecked, with low effective population sizes (average Ne = 13.1; 4 year Ne/N = 0.166). Genetic structure was defined by 12 significantly different family groups, with relatedness r = 0.31 > half-sib r = 0.25. Average heterozygosity, indicating short-term survival, did not differ among contemporary, pre- and post-translocated populations, whereas allelic diversity did. Our results, the natural history of GRPC (i.e. few leks, male dominance hierarchies) and its controlled immigration suggest demographic expansion rather than genetic rescue. Legal protection under the endangered species act (ESA) may enhance recovery, but could exacerbate political–economic concerns on how best to manage ‘conservation-reliant’ species, for which GRPC is now an exemplar. PMID:28386428

  8. Functional census of mutation sequence spaces: The example of p53 cancer rescue mutants

    PubMed Central

    Danziger, Samuel A.; Swamidass, S. Joshua; Zeng, Jue; Dearth, Lawrence R.; Lu, Qiang; Chen, Jonathan H.; Cheng, Jainlin; Hoang, Vinh P.; Saigo, Hiroto; Luo, Ray; Baldi, Pierre; Brachmann, Rainer K.; Lathrop, Richard H.

    2009-01-01

    Many biomedical problems relate to mutant functional properties across a sequence space of interest, e.g., flu, cancer, and HIV. Detailed knowledge of mutant properties and function improves medical treatment and prevention. A functional census of p53 cancer rescue mutants would aid the search for cancer treatments from p53 rescue. We devised a general methodology for conducting a functional census of a mutation sequence space, and conducted a double-blind predictive test on the functional rescue property of 71 novel putative p53 cancer rescue mutants iteratively predicted in sets of 3. Double-blind predictive accuracy (15-point moving window) rose from 47% to 86% over the trial (r = 0.74). Code and data are available upon request1. PMID:17048398

  9. Self-rescue strategies for EVA crewmembers equipped with the SAFER backpack

    NASA Technical Reports Server (NTRS)

    Williams, Trevor; Baughman, David

    1994-01-01

    An extravehicular astronaut who becomes separated from a space station has three options available: grappling the station immediately by means of a 'shepherd's crook' device; rescue by either a second crewmember flying an MMU or a robotic-controlled MMU; or self-rescue by means of a propulsive system. The first option requires very fast response by a tumbling astronaut; the second requires constant availability of an MMU, as well as a rendezvous procedure thousands of feet from the station. This paper will consider the third option, propulsive self-rescue. In particular, the capability of the new Simplified Aid for EVA Rescue (SAFER) propulsive backpack, which is to be tested on STS-64 in Sep. 1994, will be studied. This system possesses an attitude hold function that can automatically detumble an astronaut after separation. On-orbit tests of candidate self-rescue systems have demonstrated the need for such a feature. SAFER has a total delta(v) capability of about 10 fps, to cover both rotations and translations, compared with a possible separation rate of 2.5 fps. But the delta(v) required for self-rescue is critically dependent on the delay before return can be initiated, as a consequence of orbital effects. A very important practical question is then whether the total delta(v) of SAFER is adequate to perform self-rescue for worst case values of separation speed, time to detumble, and time for the astronaut to visually acquire the station. This paper shows that SAFER does indeed have sufficient propellant to carry out self-rescue in all realistic separation cases, as well as in cases which are considerably more severe than anything likely to be encountered in practice. The return trajectories and total delta(v)'s discussed are obtained by means of an 'inertial line-of-sight targeting' scheme, derived in the paper, which allows orbital effects to be corrected by making use of the visual information available to the pilot, namely the line-of-sight direction to the station relative to the stars.

  10. Adenovirally transduced bone marrow stromal cells differentiate into pigment epithelial cells and induce rescue effects in RCS rats.

    PubMed

    Arnhold, Stefan; Heiduschka, Peter; Klein, Helmut; Absenger, Yvonne; Basnaoglu, Serkan; Kreppel, Florian; Henke-Fahle, Sylvia; Kochanek, Stefan; Bartz-Schmidt, Karl-Ulrich; Addicks, Klaus; Schraermeyer, Ulrich

    2006-09-01

    To determine the potential of adenovirally transduced bone marrow stromal cells (BMSCs) to differentiate into retinal pigment epithelial-like cells and to evaluabe possible rescue effects after transplantation into the retinas of Royal College of Surgeons (RCS) rats. Through a high-capacity adenoviral vector expressing either green fluorescent protein (GFP) or pigment epithelial-derived factor (PEDF), rat MSCs were transduced in vitro before subretinal transplantation into Wistar rats or, alternatively, RCS rats. Two months after cell injection, the rats were killed and the eyes enucleated. The eyes were then investigated light microscopically or processed for electron microscopic investigations. Cell differentiation and integration were analyzed immunocytochemically using antibodies against cytokeratin and the tight junction protein ZO-1. Electroretinography was performed 16 days after injection of cells, to check whether a functional rescue could be detected. In vitro experiments in cocultured human MSCs and human RPE cells showed that MSCs adopted RPE-like characteristics. In grafting experiments, some rat MSCs integrate into the host RPE cell layer of Wistar and RCS rats, indicated by their hexagonal morphology. Subretinally transplanted cells express the epithelial marker cytokeratin and establish tight junctions with the host RPE cells. Furthermore, rescue effects can be demonstrated after grafting of vector-transduced and nontransduced MSCs in semithin sections of dystrophic retinas. Ultrastructurally, MSCs can be detected on top of host RPE and in close contact with photoreceptor outer segments phagocytosing rod outer segments. Taken together, these results raise the possibility that MSCs have the potency to replace diseased RPE cells and deliver therapeutic proteins into the subretinal space to protect photoreceptor cells from degeneration.

  11. Physical capacity of rescue personnel in the mining industry

    PubMed Central

    Stewart, Ian B; McDonald, Michael D; Hunt, Andrew P; Parker, Tony W

    2008-01-01

    Background The mining industry has one of the highest occupational rates of serious injury and fatality. Mine staff involved with rescue operations are often required to respond to physically challenging situations. This paper describes the physical attributes of mining rescue personnel. Methods 91 rescue personnel (34 ± 8.6 yrs, 1.79 ± 0.07 m, 90 ± 15.0 kg) participating in the Queensland Mines Rescue Challenge completed a series of health-related and rescue-related fitness tasks. Health-related tasks comprised measurements of aerobic capacity (VO2max), abdominal endurance, abdominal strength, flexibility, lower back strength, leg strength, elbow flexion strength, shoulder strength, lower back endurance, and leg endurance. Rescue-related tasks comprised an incremental carry (IC), coal shovel (CS), and a hose drag (HD), completed in this order. Results Cardiovascular (VO2max) and muscular endurance was average or below average compared with the general population. Isometric strength did not decline with age. The rescue-related tasks were all extremely demanding with heart rate responses averaging greater than 88% of age predicted maximal heart rates. Heart rate recovery responses were more discriminating than heart rates recorded during the tasks, indicating the hose drag as the most physically demanding of the tasks. Conclusion Relying on actual rescues or mining related work to provide adequate training is generally insufficient to maintain, let alone increase, physical fitness. It is therefore recommended that standards of required physical fitness be developed and mines rescue personnel undergo regularly training (and assessment) in order to maintain these standards. PMID:18847510

  12. Cost-Effectiveness Analysis of Nasal Continuous Positive Airway Pressure Versus Nasal High Flow Therapy as Primary Support for Infants Born Preterm.

    PubMed

    Huang, Li; Roberts, Calum T; Manley, Brett J; Owen, Louise S; Davis, Peter G; Dalziel, Kim M

    2018-05-01

    To compare the cost-effectiveness of 2 common "noninvasive" modes of respiratory support for infants born preterm. An economic evaluation was conducted as a component of a multicenter, randomized control trial from 2013 to 2015 enrolling infants born preterm at ≥28 weeks of gestation with respiratory distress, <24 hours old, who had not previously received endotracheal intubation and mechanical ventilation or surfactant. The economic evaluation was conducted from a healthcare sector perspective and the time horizon was from birth until death or first discharge. The cost-effectiveness of continuous positive airway pressure (CPAP) vs high-flow with "rescue" CPAP backup and high-flow without rescue CPAP backup (as sole primary support) were analyzed by using the hospital cost of inpatient stay in a tertiary center and the rates of endotracheal intubation and mechanical ventilation during admission. Hospital inpatient cost records for 435 infants enrolled in all Australian centers were obtained. With "rescue" CPAP backup, an incremental cost-effectiveness ratio was estimated of A$179 000 (US$123 000) per ventilation avoided if CPAP was used compared with high flow. Without rescue CPAP backup, cost per ventilation avoided was A$7000 (US$4800) if CPAP was used compared with high flow. As sole primary support, CPAP is highly likely to be cost-effective compared with high flow. Neonatal units choosing to use only one device should apply CPAP as primary respiratory support. Compared with high-flow with rescue CPAP backup, CPAP is unlikely to be cost-effective if willingness to pay per ventilation avoided is less than A$179 000 (US$123 000). Copyright © 2018 Elsevier Inc. All rights reserved.

  13. Confined space emergency response: assessing employer and fire department practices.

    PubMed

    Wilson, Michael P; Madison, Heather N; Healy, Stephen B

    2012-01-01

    An emergency response plan for industrial permit-required confined space entry is essential for employee safety and is legally required. Maintaining a trained confined space rescue team, however, is costly and technically challenging. Some employers turn to public fire departments to meet their emergency response requirements. The confined space emergency response practices of employers and fire departments have not been previously assessed. We present (1) federal data on the U.S. occurrence between 1992 and 2005 of confined space fatal incidents involving toxic and/or oxygen-deficient atmospheres; (2) survey data from 21 large companies on permit-required confined space emergency response practices; (3) data on fire department arrival times; and (4) estimates by 10 senior fire officers of fire department rescue times for confined space incidents. Between 1992 and 2005, 431 confined space incidents that met the case definition claimed 530 lives, or about 0.63% of the 84,446 all-cause U.S. occupational fatal injuries that occurred during this period. Eighty-seven (20%) incidents resulted in multiple fatalities. Twelve (57%) of 21 surveyed companies reported that they relied on the fire department for permit-required confined space emergency response. Median fire department arrival times were about 5 min for engines and 7 min for technical rescue units. Fire department confined space rescue time estimates ranged from 48 to 123 min and increased to 70 and 173 min when hazardous materials were present. The study illustrates that (1) confined space incidents represent a small but continuing source of fatal occupational injuries in the United States; (2) a sizeable portion of employers may be relying on public fire departments for permit-required confined space emergency response; and (3) in the event of a life-threatening emergency, fire departments usually are not able to effect a confined space rescue in a timely manner. We propose that the appropriate role for the fire department is to support a properly trained and equipped on-site rescue team and to provide advanced life support intervention following extrication and during ambulance transportation.

  14. Randomized, controlled, multicentre clinical trial of the antipyretic effect of intravenous paracetamol in patients admitted to hospital with infection.

    PubMed

    Tsaganos, Thomas; Tseti, Ioulia K; Tziolos, Nikolaos; Soumelas, Georgios-Stefanos; Koupetori, Marina; Pyrpasopoulou, Athina; Akinosoglou, Karolina; Gogos, Charalambos; Tsokos, Nikolaos; Karagiannis, Asterios; Sympardi, Styliani; Giamarellos-Bourboulis, Evangelos J

    2017-04-01

    No randomized study has been conducted to investigate the use of intravenous paracetamol (acetaminophen, APAP) for the management of fever due to infection. The present study evaluated a new ready-made infusion of paracetamol. Eighty patients with a body temperature onset ≥38.5°C in the previous 24 h due to infection were randomized to a single administration of placebo (n = 39) or 1 g paracetamol (n = 41), and their temperature was recorded at standard intervals. Rescue medication with 1 g paracetamol was allowed. Serum samples were collected for the measurement of APAP and its metabolites. The primary endpoint was defervescence, defined as a core temperature ≤37.1°C. During the first 6 h, defervescence was achieved in 15 (38.5%) patients treated with placebo compared with 33 (80.5%) patients treated with paracetamol 1 g (P < 0.0001). The median time to defervescence with paracetamol 1 g was 3 h. Rescue medication was given to 15 (38.5%) and five (12.2%) patients allocated to placebo and paracetamol, respectively (P = 0.007); nine (60.0%) and two (40.0%) of these patients, respectively, experienced defervescence. No further antipyretic medication was needed for patients becoming afebrile with rescue medication. Serum glucuronide-APAP concentrations were significantly greater in the serum of patients who did not experience defervescence with paracetamol. The efficacy of paracetamol was not affected by serum creatinine. No drug-related adverse events were reported. The 1 g paracetamol formulation has a rapid and sustainable antipyretic effect on fever due to infection. Its efficacy is dependent on hepatic metabolism. © 2016 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

  15. Randomized, controlled, multicentre clinical trial of the antipyretic effect of intravenous paracetamol in patients admitted to hospital with infection

    PubMed Central

    Tsaganos, Thomas; Tseti, Ioulia K.; Tziolos, Nikolaos; Soumelas, Georgios‐Stefanos; Koupetori, Marina; Pyrpasopoulou, Athina; Akinosoglou, Karolina; Gogos, Charalambos; Tsokos, Nikolaos; Karagiannis, Asterios; Sympardi, Styliani

    2016-01-01

    Aim No randomized study has been conducted to investigate the use of intravenous paracetamol (acetaminophen, APAP) for the management of fever due to infection. The present study evaluated a new ready‐made infusion of paracetamol. Methods Eighty patients with a body temperature onset ≥38.5°C in the previous 24 h due to infection were randomized to a single administration of placebo (n = 39) or 1 g paracetamol (n = 41), and their temperature was recorded at standard intervals. Rescue medication with 1 g paracetamol was allowed. Serum samples were collected for the measurement of APAP and its metabolites. The primary endpoint was defervescence, defined as a core temperature ≤37.1°C. Results During the first 6 h, defervescence was achieved in 15 (38.5%) patients treated with placebo compared with 33 (80.5%) patients treated with paracetamol 1 g (P < 0.0001). The median time to defervescence with paracetamol 1 g was 3 h. Rescue medication was given to 15 (38.5%) and five (12.2%) patients allocated to placebo and paracetamol, respectively (P = 0.007); nine (60.0%) and two (40.0%) of these patients, respectively, experienced defervescence. No further antipyretic medication was needed for patients becoming afebrile with rescue medication. Serum glucuronide‐APAP concentrations were significantly greater in the serum of patients who did not experience defervescence with paracetamol. The efficacy of paracetamol was not affected by serum creatinine. No drug‐related adverse events were reported. Conclusions The 1 g paracetamol formulation has a rapid and sustainable antipyretic effect on fever due to infection. Its efficacy is dependent on hepatic metabolism. PMID:27792836

  16. Nicotinate-Curcumin Impedes Foam Cell Formation from THP-1 Cells through Restoring Autophagy Flux

    PubMed Central

    Gu, Hong-Feng; Li, Hai-Zhe; Tang, Ya-Ling; Tang, Xiao-Qing; Zheng, Xi-Long; Liao, Duan-Fang

    2016-01-01

    Our previous studies have indicated that a novel curcumin derivate nicotinate-curcumin (NC) has beneficial effects on the prevention of atherosclerosis, but the precise mechanisms are not fully understood. Given that autophagy regulates lipid metabolism, the present study was designed to investigate whether NC decreases foam cell formation through restoring autophagy flux in oxidized low-density lipoprotein (ox-LDL)-treated THP-1 cells. Our results showed that ox-LDL (100 μg/ml) was accumulated in THP-1 cells and impaired autophagy flux. Ox-LDL-induced impairment of autophagy was enhanced by treatment with the autophagy inhibitor chloroquine (CQ) and rescued by the autophagy inducer rapamycin. The aggregation of ox-LDL was increased by CQ, but decreased by rapamycin. In addition, colocalization of lipid droplets with LC3-II was remarkably reduced in ox-LDL group. In contrast, NC (10 μM) rescued the impaired autophagy flux by significantly increasing level of LC3-II, the number of autophagolysosomes, and the degradation of p62 in ox-LDL-treated THP-1 cells. Inhibition of the PI3K-Akt-mTOR signaling was required for NC-rescued autophagy flux. Notably, our results showed that NC remarkably promoted the colocalization of lipid droplets with autophagolysosomes, increased efflux of cholesterol, and reduced ox-LDL accumulation in THP-1 cells. However, treatment with 3-methyladenine (3-MA) or CQ reduced the protective effects of NC on lipid accumulation. Collectively, the findings suggest that NC decreases lipid accumulation in THP-1 cells through restoring autophagy flux, and further implicate that NC may be a potential therapeutic reagent to reverse atherosclerosis. PMID:27128486

  17. Health status and physical fitness of mines rescue brigadesmen.

    PubMed

    Tomaskova, Hana; Jirak, Zdenek; Lvoncik, Samuel; Buzga, Marek; Zavadilova, Vladislava; Trlicova, Michaela

    2015-01-01

    The aim of the study was to assess health status of regular and part-time mines rescue brigadesmen. A group of 685 mines rescue brigadesmen was examined within the preventive testing - a basic internal, biochemistry and anthropometric examination, physical fitness testing. The average age of the subjects was 41.96±7.18 years, the average exposure in mining was 20±8.1 years, out of that 11.95±7.85 years as mines rescue brigadesmen. Elevated levels of total serum cholesterol (T-CH) and low-density lipoprotein cholesterol (LDL-CH) were found in over 1/2 of the subjects. Systolic hypertension (systolic blood pressure (SBP) ≥ 140 mm Hg) was confirmed in 34%, overweight (body mass index (BMI) ≥ 25) in 62.3% and obesity (BMI ≥ 30) in 20.4% of the examined mines rescue brigadesmen. The metabolic syndrome was found in 15.2% of persons. The highest physical fitness was found in mines rescue brigadesmen and the lowest in mine officers. Limit values of maximum oxygen uptake (VO2 max/kg) determined by the management of the mine rescue station were not reached by every 3rd of all mines rescue brigadesmen. Compared with the control group of the Czech and Slovak population, the rescuers are taller, have greater BMI, higher percentage of body fat in all age categories and proportionally to that they achieve a higher maximum minute oxygen uptake; however, in relative values per kg of body weight their physical fitness is practically the same as that of the controls. The prevalence of risk factors of cardiovascular diseases and VO2 max/kg in the group of the mines rescue brigadesmen is comparable with that in the general untrained Czech population. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

  18. Comparison of 0.25% Ropivacaine for Intraperitoneal Instillation v/s Rectus Sheath Block for Postoperative Pain Relief Following Laparoscopic Cholecystectomy: A Prospective Study

    PubMed Central

    Naithani, Udita; Singariya, Geeta; Gupta, Sunanda

    2016-01-01

    Introduction As Laparoscopic Cholecystectomy (LC) is not a totally pain free procedure, with the pain being most intense on the day of surgery and on the following day. Various techniques are available for postoperative pain relief like intraperitoneal instillation of local anaesthetics and rectus sheath block (RSB)which may provide effective pain relief. Aim To compare the efficacy of preemptive administration (initiated before the surgical procedure) of intraperitoneal instillation and rectus sheath block using ropivacaine for postoperative analgesia after laparoscopic cholecystectomy. Materials and Methods A total of 75 selected patients were randomly assigned to three equal groups as Group R, who received bilateral RSB with 0.25 % ropivacaine 15 ml on either side; Group I, who received intraperitoneal instillation of 0.25% ropivacaine 50 ml and Group C (Control group), who received only rescue analgesic on pain. These were compared regarding postoperative analgesia in terms of Visual Analog Scale (0-10 cm), Prince Henry Hospital Pain Score (0-3), time to first dose of rescue analgesic (tramadol), total rescue analgesic consumption in 48 hours, patient satisfaction scores (1-7) and adverse effects. Results The time to first rescue analgesic was significantly longer in Group R (16.16±4.73h) and Group I (7.84±1.34h) as compared to Group C (1.72±0.67h), p<0.001. Mean tramadol consumption in 48h for each patient was significantly less in Group R (148±54.92mg) and Group I (202±33.78mg) as compared to Group C (298±22.73mg) p<0.001. Postoperative pain scores were also significantly less in Group R and Group I as compared to Group C during first 6 hours, p<0.05. The difference in above parameters was also significant between Group R and Group I, p<0.05. Thus order of postoperative analgesia effect was: Group R > Group I > Group C. Rescue analgesic requirement showed a 32.21% reduction in Group I and 50.33% reduction in Group R as compared to Group C. Patient Satisfaction Scores (PSS) showed a significant difference among groups with acceptable PSS scores as: Group R (92%) v/s Group I (40%) v/s Group C (20%) p<0.001. Conclusion Pre-emptive administration of rectus sheath block or intraperitoneal instillation of 0.25% ropivacaine was found effective in providing better postoperative analgesia as compared to control group after laparoscopic cholecystectomy. Among these two techniques, rectus sheath block was found to be superior over intraperitoneal instillation. PMID:27656533

  19. [Rescue helicopters in secondary missions].

    PubMed

    Gorgass, B; Frey, G

    1977-11-03

    During the last five years, we have had to fly 560 primary and 1150 secondary missions with the rescue helicopter of the Ulm Rescue Centre. This relationship of approximately 1 : 2 is distinctly different from the numbers obtained in other helicopter bases. The geographical location and structure of the hospitals within range of the Ulm rescue helicopter account for the large proportion of urgent secondary missions. The evaluation of these secondary missions concurs with the ADAC statistics and shows that the quick transport of the emergency doctor to the scene of the emergency, is only one component in the functions of the rescue helicopter. During primary and secondary missions, the ability to transport emergency patients to the nearest qualified hospital by helicopter, which is a mobile intensive care unit, is of equal importance. In the future, rescue helicopters will have to take these requirements into account by providing the necessary equipment and more especially, by providing sufficient space to carry out emergency diagnostic and therapeutic treatment.

  20. Smurf1 plays a role in EGF inhibition of BMP2-induced osteogenic differentiation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lee, Hye-Lim; Park, Hyun-Jung; Kwon, Arang

    2014-05-01

    It has been demonstrated that epidermal growth factor (EGF) plays a role in supporting the proliferation of bone marrow stromal cells in bone but inhibits their osteogenic differentiation. However, the mechanism underlying EGF inhibition of osteoblast differentiation remains unclear. Smurf1 is an E3 ubiquitin ligase that targets Smad1/5 and Runx2, which are critical transcription factors for bone morphogenetic protein 2 (BMP2)-induced osteoblast differentiation. In this study, we investigated the effect of EGF on the expression of Smurf1, and the role of Smurf1 in EGF inhibition of osteogenic differentiation using C2C12 cells, a murine myoblast cell line. EGF increased Smurf1 expression,more » which was blocked by inhibiting the activity of either JNK or ERK. Chromatin immunoprecipitation and Smurf1 promoter assays demonstrated that c-Jun and Runx2 play roles in the EGF induction of Smurf1 transcription. EGF suppressed BMP2-induced expression of osteogenic marker genes, which were rescued by Smurf1 knockdown. EGF downregulated the protein levels of Runx2 and Smad1 in a proteasome-dependent manner. EGF decreased the transcriptional activity of Runx2 and Smurf1, which was partially rescued by Smurf1 silencing. Taken together, these results suggest that EGF increases Smurf1 expression via the activation of JNK and ERK and the subsequent binding of c-Jun and Runx2 to the Smurf1 promoter and that Smurf1 mediates the inhibitory effect of EGF on BMP2-induced osteoblast differentiation. - Highlights: • EGF increases the expression level of Smurf1 in mesenchymal precursor cells. • EGF reduces the protein levels and transcriptional activity of Runx2 and Smad1. • EGF suppresses BMP2-induced osteogenic differentiation, which is rescued by Smurf1 knockdown.« less

  1. Arenavirus reverse genetics for vaccine development

    PubMed Central

    Ortiz-Riaño, Emilio; Cheng, Benson Yee Hin; Carlos de la Torre, Juan

    2013-01-01

    Arenaviruses are important human pathogens with no Food and Drug Administration (FDA)-licensed vaccines available and current antiviral therapy being limited to an off-label use of the nucleoside analogue ribavirin of limited prophylactic efficacy. The development of reverse genetics systems represented a major breakthrough in arenavirus research. However, rescue of recombinant arenaviruses using current reverse genetics systems has been restricted to rodent cells. In this study, we describe the rescue of recombinant arenaviruses from human 293T cells and Vero cells, an FDA-approved line for vaccine development. We also describe the generation of novel vectors that mediate synthesis of both negative-sense genome RNA and positive-sense mRNA species of lymphocytic choriomeningitis virus (LCMV) directed by the human RNA polymerases I and II, respectively, within the same plasmid. This approach reduces by half the number of vectors required for arenavirus rescue, which could facilitate virus rescue in cell lines approved for human vaccine production but that cannot be transfected at high efficiencies. We have shown the feasibility of this approach by rescuing both the Old World prototypic arenavirus LCMV and the live-attenuated vaccine Candid#1 strain of the New World arenavirus Junín. Moreover, we show the feasibility of using these novel strategies for efficient rescue of recombinant tri-segmented both LCMV and Candid#1. PMID:23364194

  2. African Swine Fever Virus NP868R Capping Enzyme Promotes Reovirus Rescue during Reverse Genetics by Promoting Reovirus Protein Expression, Virion Assembly, and RNA Incorporation into Infectious Virions

    PubMed Central

    Eaton, Heather E.; Kobayashi, Takeshi; Dermody, Terence S.; Johnston, Randal N.

    2017-01-01

    ABSTRACT Reoviruses, like many eukaryotic viruses, contain an inverted 7-methylguanosine (m7G) cap linked to the 5′ nucleotide of mRNA. The traditional functions of capping are to promote mRNA stability, protein translation, and concealment from cellular proteins that recognize foreign RNA. To address the role of mRNA capping during reovirus replication, we assessed the benefits of adding the African swine fever virus NP868R capping enzyme during reovirus rescue. C3P3, a fusion protein containing T7 RNA polymerase and NP868R, was found to increase protein expression 5- to 10-fold compared to T7 RNA polymerase alone while enhancing reovirus rescue from the current reverse genetics system by 100-fold. Surprisingly, RNA stability was not increased by C3P3, suggesting a direct effect on protein translation. A time course analysis revealed that C3P3 increased protein synthesis within the first 2 days of a reverse genetics transfection. This analysis also revealed that C3P3 enhanced processing of outer capsid μ1 protein to μ1C, a previously described hallmark of reovirus assembly. Finally, to determine the rate of infectious-RNA incorporation into new virions, we developed a new recombinant reovirus S1 gene that expressed the fluorescent protein UnaG. Following transfection of cells with UnaG and infection with wild-type virus, passage of UnaG through progeny was significantly enhanced by C3P3. These data suggest that capping provides nontraditional functions to reovirus, such as promoting assembly and infectious-RNA incorporation. IMPORTANCE Our findings expand our understanding of how viruses utilize capping, suggesting that capping provides nontraditional functions to reovirus, such as promoting assembly and infectious-RNA incorporation, in addition to enhancing protein translation. Beyond providing mechanistic insight into reovirus replication, our findings also show that reovirus reverse genetics rescue is enhanced 100-fold by the NP868R capping enzyme. Since reovirus shows promise as a cancer therapy, efficient reovirus reverse genetics rescue will accelerate production of recombinant reoviruses as candidates to enhance therapeutic potency. NP868R-assisted reovirus rescue will also expedite production of recombinant reovirus for mechanistic insights into reovirus protein function and structure. PMID:28298603

  3. The effect of Ku on telomere replication time is mediated by telomere length but is independent of histone tail acetylation.

    PubMed

    Lian, Hui-Yong; Robertson, E Douglas; Hiraga, Shin-ichiro; Alvino, Gina M; Collingwood, David; McCune, Heather J; Sridhar, Akila; Brewer, Bonita J; Raghuraman, M K; Donaldson, Anne D

    2011-05-15

    DNA replication in Saccharomyces cerevisiae proceeds according to a temporal program. We have investigated the role of the telomere-binding Ku complex in specifying late replication of telomere-proximal sequences. Genome-wide analysis shows that regions extending up to 80 kb from telomeres replicate abnormally early in a yku70 mutant. We find that Ku does not appear to regulate replication time by binding replication origins directly, nor is its effect on telomere replication timing mediated by histone tail acetylation. We show that Ku instead regulates replication timing through its effect on telomere length, because deletion of the telomerase regulator Pif1 largely reverses the short telomere defect of a yku70 mutant and simultaneously rescues its replication timing defect. Consistent with this conclusion, deleting the genome integrity component Elg1 partially rescued both length and replication timing of yku70 telomeres. Telomere length-mediated control of replication timing requires the TG(1-3) repeat-counting component Rif1, because a rif1 mutant replicates telomeric regions early, despite having extended TG(1-3) tracts. Overall, our results suggest that the effect of Ku on telomere replication timing results from its impact on TG(1-3) repeat length and support a model in which Rif1 measures telomere repeat length to ensure that telomere replication timing is correctly programmed.

  4. Importance of teamwork, communication and culture on failure-to-rescue in the elderly.

    PubMed

    Ghaferi, A A; Dimick, J B

    2016-01-01

    Surgical mortality increases significantly with age. Wide variations in mortality rates across hospitals suggest potential levers for improvement. Failure-to-rescue has been posited as a potential mechanism underlying these differences. A review was undertaken of the literature evaluating surgery, mortality, failure-to-rescue and the elderly. This was followed by a review of ongoing studies and unpublished work aiming to understand better the mechanisms underlying variations in surgical mortality in elderly patients. Multiple hospital macro-system factors, such as nurse staffing, available hospital technology and teaching status, are associated with differences in failure-to-rescue rates. There is emerging literature regarding important micro-system factors associated with failure-to-rescue. These are grouped into three broad categories: hospital resources, attitudes and behaviours. Ongoing work to produce interventions to reduce variations in failure-to-rescue rates include a focus on teamwork, communication and safety culture. Researchers are using novel mixed-methods approaches and theories adapted from organizational studies in high-reliability organizations in an effort to improve the care of elderly surgical patients. Although elderly surgical patients experience failure-to-rescue events at much higher rates than their younger counterparts, patient-level effects do not sufficiently explain these differences. Increased attention to the role of organizational dynamics in hospitals' ability to rescue these high-risk patients will establish high-yield interventions aimed at improving patient safety. © 2015 BJS Society Ltd Published by John Wiley & Sons Ltd.

  5. Characteristics of relinquishing and adoptive owners of horses associated with U.S. nonprofit equine rescue organizations.

    PubMed

    Holcomb, Kathryn E; Stull, Carolyn L; Kass, Philip H

    2012-01-01

    Nonprofit equine rescue organizations in the United States provide care for relinquished horses and may offer adoption programs. With an estimated 100,000 "unwanted" horses per year and few municipal shelters providing wholesale euthanasia, there is a need to minimize the number of unwanted horses and maximize their successful transition to new caregivers. This study's objectives were to characterize the relinquishing and adoptive owners interacting with nonprofit rescue organizations. Nonprofit organizations (n = 144) in 37 states provided information by survey on 280 horses relinquished between 2006 and 2009, from which 73 were adopted. Results show the majority of relinquishing owners were women, whereas adoptive owners were primarily families or couples. Most relinquishing owners had previous equine experience and had owned the horse for 1 to 5 years; about half owned 1 other horse. Three quarters of the adoptive owners possessed additional horses housed on their property. The primary use for rehomed horses was for riding or driving. These findings will serve to help develop effective education programs for responsible horse ownership and optimize acceptance criteria and successful adoption strategies of horses by nonprofit organizations.

  6. The effects of preoperative oral administration of carprofen or tramadol on postoperative analgesia in dogs undergoing cutaneous tumor removal

    PubMed Central

    Karrasch, Nicole M.; Lerche, Phillip; Aarnes, Turi K.; Gardner, Heather L.; London, Cheryl A.

    2015-01-01

    This prospective, blinded, controlled clinical study compared the effects of pre-emptive oral administration of carprofen or tramadol on pain scores and analgesic requirement in dogs undergoing cutaneous tumor removal. Thirty-six client-owned dogs presenting for cutaneous tumor removal were randomly assigned to receive carprofen, tramadol, or no treatment prior to surgery. Pain was assessed using a visual analog scale (VAS), the Modified Glasgow Composite Measure Pain Score (MGCMPS), and algometry at enrollment, prior to premedication, at extubation, then hourly for the first 4 h, and every 4 h for 24 h. Dogs scoring ≥ 7 (MGCMPS), or having a VAS measurement ≥ 40 mm were given rescue analgesia. There were no significant differences in pain VAS, MGCMPS, or algometry. There were no differences in rescue analgesia requirement, or time to rescue analgesia among groups. Carprofen, tramadol, or no pre-emptive analgesia, combined with pre-operative hydromorphone and rescue analgesia, resulted in satisfactory analgesia in the 24-hour postoperative period. PMID:26246627

  7. The effects of preoperative oral administration of carprofen or tramadol on postoperative analgesia in dogs undergoing cutaneous tumor removal.

    PubMed

    Karrasch, Nicole M; Lerche, Phillip; Aarnes, Turi K; Gardner, Heather L; London, Cheryl A

    2015-08-01

    This prospective, blinded, controlled clinical study compared the effects of pre-emptive oral administration of carprofen or tramadol on pain scores and analgesic requirement in dogs undergoing cutaneous tumor removal. Thirty-six client-owned dogs presenting for cutaneous tumor removal were randomly assigned to receive carprofen, tramadol, or no treatment prior to surgery. Pain was assessed using a visual analog scale (VAS), the Modified Glasgow Composite Measure Pain Score (MGCMPS), and algometry at enrollment, prior to premedication, at extubation, then hourly for the first 4 h, and every 4 h for 24 h. Dogs scoring ≥ 7 (MGCMPS), or having a VAS measurement ≥ 40 mm were given rescue analgesia. There were no significant differences in pain VAS, MGCMPS, or algometry. There were no differences in rescue analgesia requirement, or time to rescue analgesia among groups. Carprofen, tramadol, or no pre-emptive analgesia, combined with pre-operative hydromorphone and rescue analgesia, resulted in satisfactory analgesia in the 24-hour postoperative period.

  8. Caspase-1 Inflammasome Activation Mediates Homocysteine-Induced Pyrop-Apoptosis in Endothelial Cells

    PubMed Central

    Xi, Hang; Zhang, Yuling; Xu, Yanjie; Yang, William Y; Jiang, Xiaohua; Sha, Xiaojin; Cheng, Xiaoshu; Wang, Jingfeng; Qin, Xuebin; Yu, Jun; Ji, Yong; Yang, Xiaofeng; Wang, Hong

    2016-01-01

    Rationale Endothelial injury is an initial mechanism mediating cardiovascular disease. Objective Here, we investigated the effect of hyperhomocysteinemia (HHcy) on programed cell death in endothelial cells (EC). Methods and Results We established a novel flow-cytometric gating method to define pyrotosis (Annexin V−/Propidium iodide+). In cultured human EC, we found that: 1). Hcy and Lipopolysaccharide (LPS) individually and synergistically induced inflammatory pyroptotic and non-inflammatory apoptotic cell death. 2). Hcy/LPS induced caspase-1 activation prior to caspase-8, -9, -3 activations. 3). Caspase-1/3 inhibitors rescued Hcy/LPS-induced pyroptosis/apoptosis, but caspase-8/9 inhibitors had differential rescue effect. 4). Hcy/LPS induced NLRP3 protein, caused NLRP3-containing inflammasome assembly, caspase-1 activation and IL-1β cleavage/activation. 5). Hcy/LPS elevated intracellular reactive oxidative species (ROS). 6). Intracellular oxidative gradient determined cell death destiny as intermediate intracellular ROS levels are associated with pyroptosis, whereas, high ROS corresponded to apoptosis. 7). Hcy/LPS induced mitochondrial membrane potential collapse and cytochrome-c release, and increased Bax/Bcl-2 ratio which were attenuated by antioxidants and caspase-1 inhibitor. 8). Antioxidants extracellular superoxide dismutase and catalase prevented Hcy/LPS-induced caspase-1 activation, mitochondrial dysfunction and pyroptosis/apoptosis. In cystathionine β-synthase deficient (Cbs−/−) mice, severe HHcy induced caspase-1 activation in isolated lung EC and caspase-1 expression in aortic endothelium, and elevated aortic caspase-1,9 protein/activity and Bax/Bcl-2 ratio in Cbs−/− aorta and HUVEC. Finally, Hcy-induced DNA fragmentation was reversed in caspase-1−/− EC. HHcy-induced aortic endothelial dysfunction was rescued in caspase-1−/− and NLRP3−/− mice. Conclusion HHcy preferentially induces EC pyroptosis via caspase-1-dependent inflammasome activation leading to endothelial dysfunction. We termed caspase-1 responsive pyroptosis and apoptosis as pyrop-apoptosis. PMID:27006445

  9. 78 FR 35933 - Agency Forms Undergoing Paperwork Reduction Act Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-14

    ... collection strategies, including self- report pre-and post-test instruments for assessing trainee reaction.... Knowledge Test. Mine Escape/Continuous Mining Pre/Post-Training 30 1 6/60 participants. Knowledge Test. Mine Rescue/Longwall Mining Pre/Post-Training 30 1 6/60 participants. Knowledge Test. Mine Rescue/Continuous...

  10. Fibroblast growth factor rescues brain endothelial cells lacking presenilin 1 from apoptotic cell death following serum starvation.

    PubMed

    Gama Sosa, Miguel A; De Gasperi, Rita; Hof, Patrick R; Elder, Gregory A

    2016-07-22

    Presenilin 1 (Psen1) is important for vascular brain development and is known to influence cellular stress responses. To understand the role of Psen1 in endothelial stress responses, we investigated the effects of serum withdrawal on wild type (wt) and Psen1-/- embryonic brain endothelial cells. Serum starvation induced apoptosis in Psen1-/- cells but did not affect wt cells. PI3K/AKT signaling was reduced in serum-starved Psen1-/- cells, and this was associated with elevated levels of phospho-p38 consistent with decreased pro-survival AKT signaling in the absence of Psen1. Fibroblast growth factor (FGF1 and FGF2), but not vascular endothelial growth factor (VEGF) rescued Psen1-/- cells from serum starvation induced apoptosis. Inhibition of FGF signaling induced apoptosis in wt cells under serum withdrawal, while blocking γ-secretase activity had no effect. In the absence of serum, FGF2 immunoreactivity was distributed diffusely in cytoplasmic and nuclear vesicles of wt and Psen1-/- cells, as levels of FGF2 in nuclear and cytosolic fractions were not significantly different. Thus, sensitivity of Psen1-/- cells to serum starvation is not due to lack of FGF synthesis but likely to effects of Psen1 on FGF release onto the cell surface and impaired activation of the PI3K/AKT survival pathway.

  11. 1,25-Dihydroxyvitamin D deficiency accelerates alveolar bone loss independent of aging and extracellular calcium and phosphorus.

    PubMed

    Gong, Aixiu; Chen, Jie; Wu, Jun; Li, Jing; Wang, Lin; Goltzman, David; Miao, Dengshun

    2018-04-10

    Vitamin D is critical for bone homeostasis and immunomodulation. We therefore assessed whether 1,25-dihydroxyvitamin D (1,25(OH) 2 D) deficiency in mice with targeted deletion of the gene encoding 25-hydroxyvitaminD-1αhydroxylase [1α(OH)ase] (1αOH)ase -/- mice) results in alveolar bone loss and periodontal inflammation in vivo. 10-week-old and 12-month-old 1α(OH)ase -/- mice and wild-type littermates were fed a normal diet or a rescue diet, and the phenotype of the periodontium was then analyzed using micro-computed tomography, histology, immunohistochemistry and real-time RT-PCR. Alveolar bone loss was increased and maxillary bone mineral density (BMD), osteoblast numbers and the number of osterix-positive cells were decreased significantly in 1α(OH)ase -/- mice compared with wild-type mice. Although aging from 10 weeks to 12 months accentuated these changes, and a rescue diet reduced them, the alterations in the 1α(OH)ase -/- mice exceeded the effects of aging and diet change. Nuclear factor kappa light-chain-enhancer of activated B cells (NF-кB) p65 and CD3 positive cells, and the gene expression levels of interleukin (IL)-1β, tumor necrosis factor-α (TNF-α), matrix metalloproteinase (MMP) -3 and -8 were all increased significantly in periodontal tissues of 1α(OH)ase -/- mice compared with wild-type mice. Aging from 10 weeks to 12 months also accentuated these changes, and a rescue diet reduced them, however, the alterations in the 1α(OH)ase -/- mice exceeded the effects of aging and diet change. 1,25(OH) 2 D deficiency in the 1α(OH)ase -/- mice accelerated alveolar bone loss by inhibiting osteoblastic bone formation and enhancing periodontal tissue degeneration in a calcium and phosphorus as well as age independent manner. This article is protected by copyright. All rights reserved. © 2018 American Academy of Periodontology.

  12. Inhibition of Chlorine-Induced Lung Injury by the Type 4 Phosphodiesterase Inhibitor Rolipram

    PubMed Central

    Chang, Weiyuan; Chen, Jing; Schlueter, Connie F.; Rando, Roy J.; Pathak, Yashwant V.; Hoyle, Gary W.

    2012-01-01

    Chlorine is a highly toxic respiratory irritant that when inhaled causes epithelial cell injury, alveolar-capillary barrier disruption, airway hyperreactivity, inflammation, and pulmonary edema. Chlorine is considered a chemical threat agent, and its release through accidental or intentional means has the potential to result in mass casualties from acute lung injury. The type 4 phosphodiesterase inhibitor rolipram was investigated as a rescue treatment for chlorine-induced lung injury. Rolipram inhibits degradation of the intracellular signaling molecule cyclic AMP. Potential beneficial effects of increased cyclic AMP levels include inhibition of pulmonary edema, inflammation, and airway hyperreactivity. Mice were exposed to chlorine (whole body exposure, 228–270 ppm for 1 h) and were treated with rolipram by intraperitoneal, intranasal, or intramuscular (either aqueous or nanoemulsion formulation) delivery starting 1 h after exposure. Rolipram administered intraperitoneally or intranasally inhibited chlorine-induced pulmonary edema. Minor or no effects were observed on lavage fluid IgM (indicative of plasma protein leakage), KC (Cxcl1, neutrophil chemoattractant), and neutrophils. All routes of administration inhibited chlorine-induced airway hyperreactivity assessed 1 day after exposure. The results of the study suggest that rolipram may be an effective rescue treatment for chlorine-induced lung injury and that both systemic and targeted administration to the respiratory tract were effective routes of delivery. PMID:22763362

  13. Dual PDF signaling pathways reset clocks via TIMELESS and acutely excite target neurons to control circadian behavior.

    PubMed

    Seluzicki, Adam; Flourakis, Matthieu; Kula-Eversole, Elzbieta; Zhang, Luoying; Kilman, Valerie; Allada, Ravi

    2014-03-01

    Molecular circadian clocks are interconnected via neural networks. In Drosophila, PIGMENT-DISPERSING FACTOR (PDF) acts as a master network regulator with dual functions in synchronizing molecular oscillations between disparate PDF(+) and PDF(-) circadian pacemaker neurons and controlling pacemaker neuron output. Yet the mechanisms by which PDF functions are not clear. We demonstrate that genetic inhibition of protein kinase A (PKA) in PDF(-) clock neurons can phenocopy PDF mutants while activated PKA can partially rescue PDF receptor mutants. PKA subunit transcripts are also under clock control in non-PDF DN1p neurons. To address the core clock target of PDF, we rescued per in PDF neurons of arrhythmic per⁰¹ mutants. PDF neuron rescue induced high amplitude rhythms in the clock component TIMELESS (TIM) in per-less DN1p neurons. Complete loss of PDF or PKA inhibition also results in reduced TIM levels in non-PDF neurons of per⁰¹ flies. To address how PDF impacts pacemaker neuron output, we focally applied PDF to DN1p neurons and found that it acutely depolarizes and increases firing rates of DN1p neurons. Surprisingly, these effects are reduced in the presence of an adenylate cyclase inhibitor, yet persist in the presence of PKA inhibition. We have provided evidence for a signaling mechanism (PKA) and a molecular target (TIM) by which PDF resets and synchronizes clocks and demonstrates an acute direct excitatory effect of PDF on target neurons to control neuronal output. The identification of TIM as a target of PDF signaling suggests it is a multimodal integrator of cell autonomous clock, environmental light, and neural network signaling. Moreover, these data reveal a bifurcation of PKA-dependent clock effects and PKA-independent output effects. Taken together, our results provide a molecular and cellular basis for the dual functions of PDF in clock resetting and pacemaker output.

  14. Dual PDF Signaling Pathways Reset Clocks Via TIMELESS and Acutely Excite Target Neurons to Control Circadian Behavior

    PubMed Central

    Seluzicki, Adam; Flourakis, Matthieu; Kula-Eversole, Elzbieta; Zhang, Luoying; Kilman, Valerie; Allada, Ravi

    2014-01-01

    Molecular circadian clocks are interconnected via neural networks. In Drosophila, PIGMENT-DISPERSING FACTOR (PDF) acts as a master network regulator with dual functions in synchronizing molecular oscillations between disparate PDF(+) and PDF(−) circadian pacemaker neurons and controlling pacemaker neuron output. Yet the mechanisms by which PDF functions are not clear. We demonstrate that genetic inhibition of protein kinase A (PKA) in PDF(−) clock neurons can phenocopy PDF mutants while activated PKA can partially rescue PDF receptor mutants. PKA subunit transcripts are also under clock control in non-PDF DN1p neurons. To address the core clock target of PDF, we rescued per in PDF neurons of arrhythmic per01 mutants. PDF neuron rescue induced high amplitude rhythms in the clock component TIMELESS (TIM) in per-less DN1p neurons. Complete loss of PDF or PKA inhibition also results in reduced TIM levels in non-PDF neurons of per01 flies. To address how PDF impacts pacemaker neuron output, we focally applied PDF to DN1p neurons and found that it acutely depolarizes and increases firing rates of DN1p neurons. Surprisingly, these effects are reduced in the presence of an adenylate cyclase inhibitor, yet persist in the presence of PKA inhibition. We have provided evidence for a signaling mechanism (PKA) and a molecular target (TIM) by which PDF resets and synchronizes clocks and demonstrates an acute direct excitatory effect of PDF on target neurons to control neuronal output. The identification of TIM as a target of PDF signaling suggests it is a multimodal integrator of cell autonomous clock, environmental light, and neural network signaling. Moreover, these data reveal a bifurcation of PKA-dependent clock effects and PKA-independent output effects. Taken together, our results provide a molecular and cellular basis for the dual functions of PDF in clock resetting and pacemaker output. PMID:24643294

  15. Personnel Recovery: Strategic Importance and Impact

    DTIC Science & Technology

    2012-12-01

    other rescues performed in earlier conflicts. The saga of Bolar 34 joined the lore of rescue missions that grace the proud history of our nation. 15...the proud history of our nation.1 As this vignette highlights, such dramatic rescue events, referred to as personnel recovery (PR), quickly capture...community has evolved from and with these events. Lastly, it assesses the impact of PR by pre- senting an amalgamation of noted lessons , which can prove

  16. Enhancing dopaminergic signaling and histone acetylation promotes long-term rescue of deficient fear extinction

    PubMed Central

    Whittle, N; Maurer, V; Murphy, C; Rainer, J; Bindreither, D; Hauschild, M; Scharinger, A; Oberhauser, M; Keil, T; Brehm, C; Valovka, T; Striessnig, J; Singewald, N

    2016-01-01

    Extinction-based exposure therapy is used to treat anxiety- and trauma-related disorders; however, there is the need to improve its limited efficacy in individuals with impaired fear extinction learning and to promote greater protection against return-of-fear phenomena. Here, using 129S1/SvImJ mice, which display impaired fear extinction acquisition and extinction consolidation, we revealed that persistent and context-independent rescue of deficient fear extinction in these mice was associated with enhanced expression of dopamine-related genes, such as dopamine D1 (Drd1a) and -D2 (Drd2) receptor genes in the medial prefrontal cortex (mPFC) and amygdala, but not hippocampus. Moreover, enhanced histone acetylation was observed in the promoter of the extinction-regulated Drd2 gene in the mPFC, revealing a potential gene-regulatory mechanism. Although enhancing histone acetylation, via administering the histone deacetylase (HDAC) inhibitor MS-275, does not induce fear reduction during extinction training, it promoted enduring and context-independent rescue of deficient fear extinction consolidation/retrieval once extinction learning was initiated as shown following a mild conditioning protocol. This was associated with enhanced histone acetylation in neurons of the mPFC and amygdala. Finally, as a proof-of-principle, mimicking enhanced dopaminergic signaling by L-dopa treatment rescued deficient fear extinction and co-administration of MS-275 rendered this effect enduring and context-independent. In summary, current data reveal that combining dopaminergic and epigenetic mechanisms is a promising strategy to improve exposure-based behavior therapy in extinction-impaired individuals by initiating the formation of an enduring and context-independent fear-inhibitory memory. PMID:27922638

  17. Sympathetic sprouting drives hippocampal cholinergic reinnervation that prevents loss of a muscarinic receptor-dependent long-term depression at CA3-CA1 synapses.

    PubMed

    Scheiderer, Cary L; McCutchen, Eve; Thacker, Erin E; Kolasa, Krystyna; Ward, Matthew K; Parsons, Dee; Harrell, Lindy E; Dobrunz, Lynn E; McMahon, Lori L

    2006-04-05

    Degeneration of septohippocampal cholinergic neurons results in memory deficits attributable to loss of cholinergic modulation of hippocampal synaptic circuits. A remarkable consequence of cholinergic degeneration is the sprouting of noradrenergic sympathetic fibers from the superior cervical ganglia into hippocampus. The functional impact of sympathetic ingrowth on synaptic physiology has never been investigated. Here, we report that, at CA3-CA1 synapses, a Hebbian form of long-term depression (LTD) induced by muscarinic M1 receptor activation (mLTD) is lost after medial septal lesion. Unexpectedly, expression of mLTD is rescued by sympathetic sprouting. These effects are specific because LTP and other forms of LTD are unaffected. The rescue of mLTD expression is coupled temporally with the reappearance of cholinergic fibers in hippocampus, as assessed by the immunostaining of fibers for VAChT (vesicular acetylcholine transporter). Both the cholinergic reinnervation and mLTD rescue are prevented by bilateral superior cervical ganglionectomy, which also prevents the noradrenergic sympathetic sprouting. The new cholinergic fibers likely originate from the superior cervical ganglia because unilateral ganglionectomy, performed when cholinergic reinnervation is well established, removes the reinnervation on the ipsilateral side. Thus, the temporal coupling of the cholinergic reinnervation with mLTD rescue, together with the absence of reinnervation and mLTD expression after ganglionectomy, demonstrate that the autonomic-driven cholinergic reinnervation is essential for maintaining mLTD after central cholinergic cell death. We have discovered a novel phenomenon whereby the autonomic and central nervous systems experience structural rearrangement to replace lost cholinergic innervation in hippocampus, with the consequence of preserving a form of LTD that would otherwise be lost as a result of cholinergic degeneration.

  18. Comparison of rescue and relief activities within 72 hours of the atomic bombings in Hiroshima and Nagasaki.

    PubMed

    Matsunari, Yuko; Yoshimoto, Nao

    2013-12-01

    To clarify the factors and reasons for the differences in the outcomes of rescue and relief efforts in Hiroshima and Nagasaki, mainly focusing on the numbers of rescue/relief staffs and casualties in the period within 72 hours of the atomic bombings in August 1945. By retrieving the data and information from the records and reports concerning the disasters in the two cities, together with other publications as to the damages by the atomic bombings and subsequent rescue-relief activities, and restoration activities. It seems that there was less damage in Nagasaki, where a stronger atomic bomb was used than in Hiroshima. There were crucial geographic factors that led to the different effects in terms of the numbers of victims; however, systematic organization and mobilization of rescue and relief staffs, maintenance of functional transportation, and advanced medical knowledge and public warning with regard to disaster all may have contributed to a lower death toll and increase in survivors in Nagasaki.

  19. NOAA - Search and Rescue Satellite Aided Tracking - Welcome

    Science.gov Websites

    through May 18, 2018 Number of People Rescued in Calendar Year 2018 in the United States: 98 Rescues at sea: 58 people rescued in 19 incidents Aviation rescues: 9 people rescued in 5 incidents Terrestrial PLB rescues: 31 people rescued in 16 incidents Worldwide - Over 43,000+ people rescued (since 1982

  20. Neuroprotective effect of rotigotine against complex I inhibitors, MPP⁺ and rotenone, in primary mesencephalic cell culture.

    PubMed

    Radad, Khaled; Scheller, Dieter; Rausch, Wolf-Dieter; Reichmann, Heinz; Gille, Gabrielle

    2014-01-01

    Dopamine agonists are suggested to be more efficacious in treating Parkinson's disease (PD) as they have neuroprotective properties in addition to their receptor-related actions. The present study was designed to investigate the neuroprotective effects of rotigotine, a D3/D2/D1 dopamine receptor agonist, against the two powerful complex I inhibitors, 1-methyl-4-phenylpyridinium (MPP+) and rotenone, in primary mesencephalic cell culture relevant to PD. Primary mesencephalic cell cultures were prepared from embryonic mouse mesencephala at gestation day 14. Three sets of cultures were treated with rotigotine alone, rotigotine and MPP⁺, and rotigotine and rotenone to investigate the effect of rotigotine on the survival of dopaminergic neurons against age-, MPP⁺- and rotenone-induced cell death. At the end of each treatment, cultures were fixed and stained immunohistochemically against tyrosine hydroxylase (TH). The effect of rotigotine against rotenone-induced reactive oxygen species (ROS) production was measured using CH-H2DCFDA fluorescence dye. Rotigotine alone did not influence the survival of tyrosine hydroxylase immunoreactive (THir) neurons except at 10 µM, it significantly decreased the number of THir neurons by 40% compared to untreated controls. Treatment of cultures with 0.01 µM rotigotine rescued 10% of THir neurons against MPP⁺-induced cell death. Rotigotine was also found to significantly rescue 20% of THir neurons at 0.01 µM of rotenone-treated cultures. Using of CH-H2DCFDA fluorescence dye, it was found that rotigotine significantly attenuated ROS production compared to rotenone-treated cultures. Rotigotine provides minor protection against MPP⁺ and rescues a significant number of THir neurons against rotenone in primary mesencephalic cell cultures relevant to PD.

  1. The Mysterious Rescue of adg1-1/tpt-2 – an Arabidopsis thaliana Double Mutant Impaired in Acclimation to High Light – by Exogenously Supplied Sugars

    PubMed Central

    Heinrichs, Luisa; Schmitz, Jessica; Flügge, Ulf-Ingo; Häusler, Rainer E.

    2012-01-01

    An Arabidopsis thaliana double mutant (adg1-1/tpt-2) defective in the day- and night-path of photoassimilate export from the chloroplast due to a knockout in the triose phosphate/phosphate translocator (TPT; tpt-2) and a lack of starch [mutation in ADP glucose pyrophosphorylase (AGPase); adg1-1] exhibits severe growth retardation, a decrease in the photosynthetic capacity, and a high chlorophyll fluorescence (HCF) phenotype under high light conditions. These phenotypes could be rescued when the plants were grown on sucrose (Suc) or glucose (Glc). Here we address the question whether Glc-sensing hexokinase1 (HXK1) defective in the Glc insensitive 2 (gin2-1) mutant is involved in the sugar-dependent rescue of adg1-1/tpt-2. Triple mutants defective in the TPT, AGPase, and HXK1 (adg1-1/tpt-2/gin2-1) were established as homozygous lines and grown together with Col-0 and Landsberg erecta (Ler) wild-type plants, gin2-1, the adg1-1/tpt-2 double mutant, and the adg1-1/tpt-2/gpt2-1 triple mutant [additionally defective in the glucose 6-phosphate/phosphate translocator 2 (GPT2)] on agar in the presence or absence of 50 mM of each Glc, Suc, or fructose (Fru). The growth phenotype of the double mutant and both triple mutants could be rescued to a similar extent only by Glc and Suc, but not by Fru. All three sugars were capable of rescuing the HCF and photosynthesis phenotype, irrespectively of the presence or absence of HXK1. Quantitative RT-PCR analyses of sugar-responsive genes revealed that plastidial HXK (pHXK) was up-regulated in adg1-1/tpt-2 plants grown on sugars, but showed no response in adg1-1/tpt-2/gin2-1. It appears likely that soluble sugars are directly taken up by the chloroplasts and enter further metabolism, which consumes ATP and NADPH from the photosynthetic light reaction and thereby rescues the photosynthesis phenotype of the double mutant. The implication of sugar turnover and probably signaling inside the chloroplasts for the concept of retrograde signaling is discussed. PMID:23233856

  2. 30 CFR 48.25 - Training of new miners; minimum courses of instruction; hours of instruction.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...-rescue and respiratory devices. The course shall include instruction and demonstration in the use, care, and maintenance of self-rescue and respiratory devices, where applicable. (3) Transportation controls and communication systems. The course shall include instruction on the procedures in effect for riding...

  3. 30 CFR 48.25 - Training of new miners; minimum courses of instruction; hours of instruction.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...-rescue and respiratory devices. The course shall include instruction and demonstration in the use, care, and maintenance of self-rescue and respiratory devices, where applicable. (3) Transportation controls and communication systems. The course shall include instruction on the procedures in effect for riding...

  4. 30 CFR 48.25 - Training of new miners; minimum courses of instruction; hours of instruction.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...-rescue and respiratory devices. The course shall include instruction and demonstration in the use, care, and maintenance of self-rescue and respiratory devices, where applicable. (3) Transportation controls and communication systems. The course shall include instruction on the procedures in effect for riding...

  5. 30 CFR 48.25 - Training of new miners; minimum courses of instruction; hours of instruction.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...-rescue and respiratory devices. The course shall include instruction and demonstration in the use, care, and maintenance of self-rescue and respiratory devices, where applicable. (3) Transportation controls and communication systems. The course shall include instruction on the procedures in effect for riding...

  6. Post-traumatic stress among rescue workers after terror attacks in Norway.

    PubMed

    Skogstad, L; Heir, T; Hauff, E; Ekeberg, Ø

    2016-10-01

    On 22 July 2011, Norway was struck by two terror attacks. Seventy-seven people were killed, and many injured. Rescue workers from five occupational groups and unaffiliated volunteers faced death and despair to assist victims. To investigate the level of, and associations between, demographic variables, exposure and work-related variables and post-traumatic stress symptoms (PTSS). A cross-sectional study of general and psychosocial health care personnel, police officers, firefighters, affiliated and unaffiliated volunteers were conducted ~10 months after the terror attacks. The respondents answered a self-reported questionnaire. Post-traumatic stress disorder (PTSD) Checklist - specific (PCL-S) assessed PTSS. There were 1790 participants; response rate was 61%. About 70% of the professional rescue workers had previous work experience with similar tasks or had participated in training or disaster drills. They assessed the rescue work as a success. Firefighters and unaffiliated volunteers reported more perceived threat compared with the other groups. Among the professional personnel, the prevalence of sub-threshold PTSD (PCL 35-49) was 2% and possible PTSD (PCL ≥ 50) 0.3%. The corresponding figures among the unaffiliated volunteers were 24% and 15%, respectively. In the multivariate analysis, female gender (β = 1.7), witnessing injured/dead (β = 2.0), perceived threat (β = 1.1), perceived obstruction in rescue work (β = 1.6), lower degree of previous training (β = -0. 9) and being unaffiliated volunteers (β = 8.3) were significantly associated with PTSS. In the aftermath of a terror attack, professional rescue workers appear to be largely protected from post-traumatic stress reactions, while unaffiliated volunteers seem to be at higher risk. © The Author 2016. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  7. Hospital delivery volume, severe obstetrical morbidity, and failure to rescue.

    PubMed

    Friedman, Alexander M; Ananth, Cande V; Huang, Yongmei; D'Alton, Mary E; Wright, Jason D

    2016-12-01

    In the setting of persistently high risk for maternal death and severe obstetric morbidity, little is known about the relationship between hospital delivery volume and maternal outcomes. The objectives of this analysis were (1) to determine maternal risk for severe morbidity during delivery hospitalizations by hospital delivery volume in the United States and (2) to characterize, by hospital volume, the risk for death in the setting of severe obstetric morbidity, a concept known as failure to rescue. This cohort study evaluated 50,433,539 delivery hospitalizations across the United States from 1998-2010. The main outcome measures were (1) severe morbidity that was defined as a composite of any 1 of 15 diagnoses that are representative of acute organ injury and critical illness and (2) failure to rescue that was defined as death in the setting of severe morbidity. The prevalence of severe morbidity rose from 471.2-751.5 cases per 100,000 deliveries from 1998-2010, which was an increase of 59.5%. Failure to rescue was highest in 1998 (1.5%), decreased to 0.6% in 2007, and rose to 0.9% in 2010. In models that were adjusted for comorbid risk and hospital factors, both low and high annualized delivery volume were associated with increased risk for failure to rescue and severe morbidity. However, the relative importance of hospital volume for both outcomes compared with other factors was relatively small. Although low-and high-delivery volume are associated with increased risk for both failure to rescue and severe maternal morbidity, other factors, in particular characteristics of individual centers, may be more important in the determination of outcomes. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. 78 FR 12756 - Proposed Data Collections Submitted for Public Comment and Recommendations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-25

    ... strategies, including self- report pre-and post-test instruments for assessing trainee reaction and measuring... Knowledge Test. Mine Escape/Continuous Mining Pre/Post- 30 1 6/60 3 participants. Training Knowledge Test. Mine Rescue/Longwall Mining Pre/Post- 30 1 6/60 3 participants. Training Knowledge Test. Mine Rescue...

  9. Acupuncture and pharmacopuncture are as effective as morphine or carprofen for postoperative analgesia in bitches undergoing ovariohysterectomy.

    PubMed

    Luna, Stelio Pacca Loureiro; Martino, Irene Di; Lorena, Silvia Elaine Rodolfo de Sá; Capua, Maria Luisa Buffo de; Lima, Alfredo Feio da Maia; Santos, Bianca Paiva Costa Rodrigues dos; Brondani, Juliana Tabarelli; Vesce, Giancarlo

    2015-12-01

    To investigate the analgesic effect of acupuncture (AP) or micro-dose pharmacopuncture (PA), using carprofen or morphine, in bitches undergoing ovariohysterectomy (OHE). Thirty five dogs were randomly assigned to five groups after sedation with acepromazine IM: AP, 0.5 mg.kg(-1) of morphine subcutaneously (SC), 4 mg.kg(-1) of carprofen SC, and PA with 0.05 mg.kg(-1) of morphine or 0.4 mg.kg(-1) of carprofen. Anaesthesia was induced with propofol and maintained with isoflurane. Pain was assessed after OHE by a blind observer for 24h, by dynamic visual analogue scale (DIVAS), Glasgow (CMPS-SF), Melbourne (UMPS) and Colorado University pain scale (CSU). Animals reaching 33% of the UMPS score received rescue analgesia with morphine IM. Non parametric data were analysed by Kruskal-Wallis or Friedman tests where applicable, followed by Dunn's test. Parametric data were analysed by two way ANOVA, followed by Tukey test. There were no differences among groups in number of rescue analgesia. Except for the DIVAS score where animals treated with morphine had the lowest score compared with AP and carprofen, at 1h after surgery, there were no other differences among groups. Acupuncture or pharmacopuncture were equally effective as morphine or carprofen to control postoperative pain in bitches undergoing ovariohysterectomy.

  10. Effects of heroin on rat prosocial behavior.

    PubMed

    Tomek, Seven E; Stegmann, Gabriela M; Olive, M Foster

    2018-05-04

    Opioid use disorders are characterized in part by impairments in social functioning. Previous research indicates that laboratory rats, which are frequently used as animal models of addiction-related behaviors, are capable of prosocial behavior. For example, under normal conditions, when a 'free' rat is placed in the vicinity of rat trapped in a plastic restrainer, the rat will release or 'rescue' the other rat from confinement. The present study was conducted to determine the effects of heroin on prosocial behavior in rats. For 2 weeks, rats were given the opportunity to rescue their cagemate from confinement, and the occurrence of and latency to free the confined rat was recorded. After baseline rescuing behavior was established, rats were randomly selected to self-administer heroin (0.06 mg/kg/infusion i.v.) or sucrose pellets (orally) for 14 days. Next, rats were retested for rescuing behavior once daily for 3 days, during which they were provided with a choice between freeing the trapped cagemate and continuing to self-administer their respective reinforcer. Our results indicate that rats self-administering sucrose continued to rescue their cagemate, whereas heroin rats chose to self-administer heroin and not rescue their cagemate. These findings suggest that rats with a history of heroin self-administration show deficits in prosocial behavior, consistent with specific diagnostic criteria for opioid use disorder. Behavioral paradigms providing a choice between engaging in prosocial behavior and continuing drug use may be useful in modeling and investigating the neural basis of social functioning deficits in opioid addiction. © 2018 Society for the Study of Addiction.

  11. Increased Risk Proneness or Social Withdrawal? The Effects of Shortened Life Expectancy on the Expression of Rescue Behavior in Workers of the ant Formica cinerea (Hymenoptera: Formicidae).

    PubMed

    Miler, Krzysztof; Symonowicz, Beata; Godzińska, Ewa J

    2017-01-01

    In social insects behavioral consequences of shortened life expectancy include, among others, increased risk proneness and social withdrawal. We investigated the impact of experimental shortening of life expectancy of foragers of the ant Formica cinerea achieved by their exposure to carbon dioxide on the expression of rescue behavior, risky pro-social behavior, tested by means of two bioassays during which a single worker (rescuer) was confronted with a nestmate (victim) attacked by a predator (antlion larva capture bioassay) or immobilized by an artificial snare (entrapment bioassay). Efficacy of carbon dioxide poisoning in shortening life expectancy was confirmed by the analysis of ant mortality. Rescue behavior observed during behavioral tests involved digging around the victim, transport of the sand covering the victim, pulling the limbs/antennae/mandibles of the victim, direct attack on the antlion (in antlion larva capture tests), and snare biting (in entrapment tests). The rate of occurrence of rescue behavior was lower in ants with shortened life expectancy, but that effect was significant only in the case of the entrapment bioassay. Similarly, only in the case of the entrapment bioassay ants with shortened life expectancy displayed rescue behavior after a longer latency and devoted less time to that behavior than ants from the control groups. Our results demonstrated that in ant workers shortened life expectancy may lead to reduced propensity for rescue behavior, most probably as an element of the social withdrawal syndrome that had already been described in several studies on behavior of moribund ants and honeybees.

  12. A Prospective, Observational Study to Evaluate the Role of Gabapentin as Preventive Analgesic in Thyroidectomy under General Anesthesia.

    PubMed

    Hema, Vadakkoot Raghavan; Ramadas, Konnanath Thekkethil; Biji, Kannammadathy Poulose; Indu, Suseela; Arun, Aravind

    2017-01-01

    Effective management of postoperative pain is a part of well-organized perioperative care, which helps in reduced morbidity and improved patient satisfaction. Preventive analgesia can reduce acute and chronic pain by blocking the noxious inputs to pain pathways, preventing sensitization. Studies have reported efficacy of gabapentin as a preventive analgesic in perioperative pain. In this study, we aimed to determine whether preoperative gabapentin reduced postoperative pain and tramadol consumption after thyroidectomy under general anesthesia. Sixty patients scheduled for thyroidectomy were allocated to two groups of thirty each for this prospective, observational study. Patients in Group A and Group B received oral gabapentin 600 mg (6 × 10 -4 kg) and diazepam 10 mg (1 × 10 -5 kg), respectively, 2 h prior to surgery. Tramadol was given as rescue analgesic for postoperative pain with a verbal rating score of two. The analgesic efficacy of preoperative gabapentin was assessed in terms of postoperative pain scores at rest or swallowing, time to first rescue analgesic, and total tramadol consumption for 24 h. Ramsay sedation score and side effects of drug were also looked into. Postoperative pain scores and total tramadol consumption were significantly lower in Group A during 24 h ( P = 0.00). Time to first rescue analgesic was significantly prolonged in Group A ( P = 0.001). Side effects were comparable. Oral gabapentin is effective as a preventive analgesic in reducing postoperative pain and tramadol consumption after thyroidectomy under general anesthesia.

  13. Effects of environmental conditions on point-of-care cardiac biomarker test performance during a simulated rescue: implications for emergency and disaster response.

    PubMed

    Louie, Richard F; Ferguson, William J; Curtis, Corbin M; Vy, John H; Tang, Chloe S; Kost, Gerald J

    2013-01-01

    To characterize the effects of environmental stress on point-of-care (POC) cardiac biomarker testing during a simulated rescue. Multiplex test cassettes for cardiac troponin I (cTnI), brain natriuretic peptide (BNP), CK-MB, myoglobin, and D-dimer were exposed to environmental stresses simulating a 24-hour rescue from Hawaii to the Marshall Islands and back. We used Tenney environmental chambers (T2RC and BTRC) to simulate flight conditions (20°C, 10 percent relative humidity) and ground conditions (22.3-33.9°C, 73-77 percent). We obtained paired measurements using stressed versus control (room temperature) cassettes at seven time points (T1-7 with T1,2,6,7 during flight and T3-5 on ground). We analyzed paired differences (stressed minus control) with Wilcoxon signed rank test. We assessed the impact on decision-making at clinical thresholds. cTnI results from stressed test cassettes (n = 10) at T4 (p < 0.05), T5 (p < 0.01), and T7 (p < 0.05) differed significantly from control, when testing samples with median cTnI concentration of 90 ng/L. During the ground rescue, 36.7 percent (11/30) of cTnI measurements from stressed cassettes generated significantly lowered results. At T5, 20 percent (2/10) of cTnI results were highly discrepant-stressed cassettes reported normal results, when control results were >100 ng/L. With sample median concentration of 108 pg/mL, BNP results from stressed test cassettes differed significantly from controls (p < 0.05). Despite modest, short-term temperature elevation, environmental stresses led to erroneous results. False negative cTnI and BNP results potentially could miss acute myocardial infarction and congestive heart failure, confounded treatment, and increased mortality and morbidity. Therefore, rescuers should protect POC reagents from temperature extremes.

  14. [Efficacy of dolutegravir in treatment-experienced patients: the SAILING and VIKING trials].

    PubMed

    Moreno, Santiago; Berenguer, Juan

    2015-03-01

    Dolutegravir is an HIV integrase inhibitor with a high genetic barrier to resistance and is active against raltegravir- and/or elvitegravir-resistant strains. The clinical development of dolutegravir for HIV infection rescue therapy is based on 3 clinical trials. In the SAILING trial, dolutegravir (5 mg once daily) in combination with 2 other antiretroviral agents was well tolerated and showed greater virological effect than raltegravir (400 mg twice daily) in the treatment of integrase inhibitor-naïve adults with virological failure infected with HIV strains with at least two-class drug resistance. The VIKING studies were designed to evaluate the efficacy of dolutegravir as rescue therapy in treatment-experienced patients infected with HIV strains with resistance mutations to raltegravir and/or elvitegravir. VIKING-1-2 was a dose-ranging phase IIb trial. VIKING-3 was a phase III trial in which dolutegravir (50 mg twice daily) formed part of an optimized regimen and proved safe and effective in this difficult-to-treat group of patients. Dolutegravir is the integrase inhibitor of choice for rescue therapy in multiresistant HIV infection, both in integrase inhibitor-naïve patients and in those previously treated with raltegravir or elvitegravir. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

  15. The association between alcohol, medicinal drug use and post-traumatic stress symptoms among Norwegian rescue workers after the 22 July twin terror attacks.

    PubMed

    Bogstrand, Stig Tore; Skogstad, Laila; Ekeberg, Øivind

    2016-09-01

    The aim of this study was to assess whether the use of alcohol and medicinal drugs among rescue workers as a consequence of the 22 July terrorist attack was associated with post-traumatic stress symptoms, and explore if there were differences between affiliated and unaffiliated rescue workers. Ten months after the bombing in the Oslo government district and the shooting at the youth camp on Utøya Island, a cross-sectional study of 1790 rescue and healthcare workers was conducted. The questionnaire included information on medicinal drug and alcohol use, experiences during rescue work and PTSS. Few rescue workers reported alcohol (6.8% n = 119) or medicinal drug (5.5% n = 95) use as a consequence of participation in the 22 July terror attacks. Alcohol and medicinal drug use was associated with an elevated level of PTSS among the rescue workers who reported to use medicinal drugs (11.1 95% CI: 5.7-21.8) or alcohol (10.0 95% CI: 5.2-19.0) as a consequence of the terror attacks. The study found a low level of post-traumatic stress symptoms (PTSS) and alcohol and medicinal drug use among the rescue workers after the terror attacks in Norway on 22 July 2011. There was a strong association between both medicinal drug and alcohol use and elevated PTSS. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Coconut oil protects cortical neurons from amyloid beta toxicity by enhancing signaling of cell survival pathways.

    PubMed

    Nafar, F; Clarke, J P; Mearow, K M

    2017-05-01

    Alzheimer's disease is a progressive neurodegenerative disease that has links with other conditions that can often be modified by dietary and life-style interventions. In particular, coconut oil has received attention as having potentially having benefits in lessening the cognitive deficits associated with Alzheimer's disease. In a recent report, we showed that neuron survival in cultures co-treated with coconut oil and Aβ was rescued compared to cultures exposed only to Aβ. Here we investigated treatment with Aβ for 1, 6 or 24 h followed by addition of coconut oil for a further 24 h, or treatment with coconut oil for 24 h followed by Aβ exposure for various periods. Neuronal survival and several cellular parameters (cleaved caspase 3, synaptophysin labeling and ROS) were assessed. In addition, the influence of these treatments on relevant signaling pathways was investigated with Western blotting. In terms of the treatment timing, our data indicated that coconut oil rescues cells pre-exposed to Aβ for 1 or 6 h, but is less effective when the pre-exposure has been 24 h. However, pretreatment with coconut oil prior to Aβ exposure showed the best outcomes. Treatment with octanoic or lauric acid also provided protection against Aβ, but was not as effective as the complete oil. The coconut oil treatment reduced the number of cells with cleaved caspase and ROS labeling, as well as rescuing the loss of synaptophysin labeling observed with Aβ treatment. Treatment with coconut oil, as well as octanoic, decanoic and lauric acids, resulted in a modest increase in ketone bodies compared to controls. The biochemical data suggest that Akt and ERK activation may contribute to the survival promoting influence of coconut oil. This was supported by observations that a PI3-Kinase inhibitor blocked the rescue effect of CoOil on Aβ amyloid toxicity. Further studies into the mechanisms of action of coconut oil and its constituent medium chain fatty acids are warranted. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Pharmacological Correction of Trafficking Defects in ATP-sensitive Potassium Channels Caused by Sulfonylurea Receptor 1 Mutations*

    PubMed Central

    Martin, Gregory M.; Rex, Emily A.; Devaraneni, Prasanna; Denton, Jerod S.; Boodhansingh, Kara E.; DeLeon, Diva D.; Stanley, Charles A.; Shyng, Show-Ling

    2016-01-01

    ATP-sensitive potassium (KATP) channels play a key role in mediating glucose-stimulated insulin secretion by coupling metabolic signals to β-cell membrane potential. Loss of KATP channel function due to mutations in ABCC8 or KCNJ11, genes encoding the sulfonylurea receptor 1 (SUR1) or the inwardly rectifying potassium channel Kir6.2, respectively, results in congenital hyperinsulinism. Many SUR1 mutations prevent trafficking of channel proteins from the endoplasmic reticulum to the cell surface. Channel inhibitors, including sulfonylureas and carbamazepine, have been shown to correct channel trafficking defects. In the present study, we identified 13 novel SUR1 mutations that cause channel trafficking defects, the majority of which are amenable to pharmacological rescue by glibenclamide and carbamazepine. By contrast, none of the mutant channels were rescued by KATP channel openers. Cross-linking experiments showed that KATP channel inhibitors promoted interactions between the N terminus of Kir6.2 and SUR1, whereas channel openers did not, suggesting the inhibitors enhance intersubunit interactions to overcome channel biogenesis and trafficking defects. Functional studies of rescued mutant channels indicate that most mutants rescued to the cell surface exhibited WT-like sensitivity to ATP, MgADP, and diazoxide. In intact cells, recovery of channel function upon trafficking rescue by reversible sulfonylureas or carbamazepine was facilitated by the KATP channel opener diazoxide. Our study expands the list of KATP channel trafficking mutations whose function can be recovered by pharmacological ligands and provides further insight into the structural mechanism by which channel inhibitors correct channel biogenesis and trafficking defects. PMID:27573238

  18. KSC-2014-3807

    NASA Image and Video Library

    2014-09-11

    Cape Canaveral, Fla. – At Fire Station 1 at NASA’s Kennedy Space Center in Florida, Fire and Rescue personnel salute or stand at attention as the American flag is raised during a ceremony held by Kennedy’s Fire and Rescue personnel. Kennedy Fire and Rescue Services commemorated the 13th anniversary of 9/11 with a ceremony that included a minute of silence at 10:28 a.m., which was the moment of collapse of the north tower of the World Trade Center. Photo credit: Jim Grossmann

  19. KSC-2014-3806

    NASA Image and Video Library

    2014-09-11

    Cape Canaveral, Fla. – At Fire Station 1 at NASA’s Kennedy Space Center in Florida, Fire and Rescue personnel stand at attention as the American flag is raised during a ceremony held by Kennedy’s Fire and Rescue personnel. Kennedy Fire and Rescue Services commemorated the 13th anniversary of 9/11 with a ceremony that included a minute of silence at 10:28 a.m., which was the moment of collapse of the north tower of the World Trade Center. Photo credit: Jim Grossmann

  20. KSC-2014-3808

    NASA Image and Video Library

    2014-09-11

    Cape Canaveral, Fla. – At Fire Station 1 at NASA’s Kennedy Space Center in Florida, Fire and Rescue personnel salute or stand at attention as the American flag is raised during a ceremony held by Kennedy’s Fire and Rescue personnel. Kennedy Fire and Rescue Services commemorated the 13th anniversary of 9/11 with a ceremony that included a minute of silence at 10:28 a.m., which was the moment of collapse of the north tower of the World Trade Center. Photo credit: Jim Grossmann

  1. CSAR (Combat, Search and Rescue) Aide: Design Requirements for a Combat Search and Rescue Decision Support System for Joint Rescue Coordination Centers

    DTIC Science & Technology

    1989-06-01

    with acetate depicting intelligence estimates of the order of battle (updated manually by intelligence specialists), in regulations, manuals , and a...mundane tasks (e.g. typing messages, filling out forms, and chasing down data) must be performed manually . The possibility of an important fact...formulate the requirements for CSAR AIDE. 2-1 D?cisiion Support Systems A Decision Support System (DSS) is a "systea ( manual or automated) that

  2. A survey of the relationship between work schedule and its effect on the fatigue of rescue personnel in Isfahan with a standard method of CIS202

    PubMed Central

    Habibi, Ehsanollah; Soury, Shiva; Vardanjani, Hassan Rajabi; Khodarahmi, Behnam; Dehghan, Habibollah; Hosseini, Mohsen; Esmaeli, Hamid; Khademi, Abolfazl

    2015-01-01

    Context: Fatigue is a factor that can have negative effects on family life, social relationship and work. Work schedule is one of the affective factors on personnel's fatigue in different jobs. In this study, the work schedule and its effect on rescue personnel in Isfahan are explored. Aims: The purpose of this study was to investigate the relationship between work schedules and fatigue among rescue personnel. Settings and Design: This study is periodical and has been conducted on 72 employees of rescue personnel in Isfahan. Materials and Methods: Random sampling was done and the primary data that was collected through fatigue assessment questionnaire after being conducted as a pilot study on 10% of samples were collected to confirm the validity of this study. Finally, the data was given to SPSS11.5 software and were analyzed by descriptive statistics and linear digression. Results: The results showed that from the statistical point of view some parts of work schedules like work hours satisfaction, resting time and work order on total fatigue are effective in linear and inverse way but the item “predictibility of work conditions” does not have a meaningful relationship with total fatigue. Furthermore, the results showed that there is a meaningful and inverse relationship with work hours, resting time and work order with mental fatigue and also the work schedule has a meaningful, linear and inverse relation with mental fatigue and total fatigue. Conclusions: By increasing the satisfaction of working hours, increasing resting time and also with an increase of work order the total fatigue of rescue personnel will decrease. PMID:27462640

  3. RESCUE OF BROMODICHLOROMETHANE-INDUCED PREGNANCY LOSS IN THE F344 RAT BY EXOGENOUS PROGESTERONE AND HCG

    EPA Science Inventory

    Rescue of bromodichloromethane-induced pregnancy loss in the F344 rat by exogenous progesterone and hCG.

    Susan R. Bielmeier1, Deborah S. Best2 and Michael G. Narotsky2

    1 Curriculum in Toxicology, Univ. of North Carolina, Chapel Hill, NC, USA
    2 Reproductive Toxico...

  4. [Examination of work-related stress and coping strategies among ambulance- and air-ambulance workers].

    PubMed

    Schiszler, Bence; Karamánné Pakai, Annamária; Szabó, Zoltán; Raposa, László Bence; Pónusz, Róbert; Radnai, Balázs; Endrei, Dóra

    2016-11-01

    Among Hungary's health sector workers the presence of a high level of stress is known, which can affect the individual. The aim of the authors was to uncover major risk factors causing work-related stress, as well as its extent, and positive and negative coping strategies among ground and aerial rescue workers. From June until October 2015, a national survey was conducted among Hungarian rescue workers. An own questionnaire and Rahe Stress and coping validated short questionnaire online form were used. A total of 141 persons took part in the survey. As compared to air-ambulance workers, ground rescue workers were exposed to higher work-related stress effects (p<0.01), resulting in a much larger variety of physical and psychological symptoms (p<0.05). Based on Global Stress and Coping Index effective coping mechanisms were observed among air rescue workers (p<0.01). It is important to perform regular professional theoretical and practical training. Human resource management should pay attention on occupational stress reduction. Orv. Hetil., 2016, 157(45), 1802-1808.

  5. Limited evolutionary rescue of locally adapted populations facing climate change.

    PubMed

    Schiffers, Katja; Bourne, Elizabeth C; Lavergne, Sébastien; Thuiller, Wilfried; Travis, Justin M J

    2013-01-19

    Dispersal is a key determinant of a population's evolutionary potential. It facilitates the propagation of beneficial alleles throughout the distributional range of spatially outspread populations and increases the speed of adaptation. However, when habitat is heterogeneous and individuals are locally adapted, dispersal may, at the same time, reduce fitness through increasing maladaptation. Here, we use a spatially explicit, allelic simulation model to quantify how these equivocal effects of dispersal affect a population's evolutionary response to changing climate. Individuals carry a diploid set of chromosomes, with alleles coding for adaptation to non-climatic environmental conditions and climatic conditions, respectively. Our model results demonstrate that the interplay between gene flow and habitat heterogeneity may decrease effective dispersal and population size to such an extent that substantially reduces the likelihood of evolutionary rescue. Importantly, even when evolutionary rescue saves a population from extinction, its spatial range following climate change may be strongly narrowed, that is, the rescue is only partial. These findings emphasize that neglecting the impact of non-climatic, local adaptation might lead to a considerable overestimation of a population's evolvability under rapid environmental change.

  6. [Establishement for regional pelvic trauma database in Hunan Province].

    PubMed

    Cheng, Liang; Zhu, Yong; Long, Haitao; Yang, Junxiao; Sun, Buhua; Li, Kanghua

    2017-04-28

    To establish a database for pelvic trauma in Hunan Province, and to start the work of multicenter pelvic trauma registry.
 Methods: To establish the database, literatures relevant to pelvic trauma were screened, the experiences from the established trauma database in China and abroad were learned, and the actual situations for pelvic trauma rescue in Hunan Province were considered. The database for pelvic trauma was established based on the PostgreSQL and the advanced programming language Java 1.6.
 Results: The complex procedure for pelvic trauma rescue was described structurally. The contents for the database included general patient information, injurious condition, prehospital rescue, conditions in admission, treatment in hospital, status on discharge, diagnosis, classification, complication, trauma scoring and therapeutic effect. The database can be accessed through the internet by browser/servicer. The functions for the database include patient information management, data export, history query, progress report, video-image management and personal information management.
 Conclusion: The database with whole life cycle pelvic trauma is successfully established for the first time in China. It is scientific, functional, practical, and user-friendly.

  7. The Argos contribution to the demonstration of the effectiveness of a satellite-based search and rescue system

    NASA Astrophysics Data System (ADS)

    Rolland, R.

    The use of the CNES/NASA/NOAA Argos environmental-research instrumentation on the Tiros-N series of satellites as a search and rescue location-finding system for trans-Atlantic yacht races during 1979-1982 is described. The transmission beacons, satellite equipment, data-processing center, and data distribution facilities of Argos are characterized and illustrated; the nine race rescue operations in which Argos was involved are listed and discussed; and the deficiencies of Argos are shown to be fully corrected in the 406-MHz location system developed for Sarsat.

  8. Acute stress symptoms, dissociation, and depression among rescue personnel 24 hours after the Bet-Yehoshua train crash in Israel:the effect of gender.

    PubMed

    Palgi, Yuval; Ben-Ezra, Menachem; Essar, Nir; Sofer, Hilik; Haber, Yeela

    2009-01-01

    The effect of immediate exposure to traumatic events and gender differences is under-studied in the literature. Most studies focus on acute stress disorder (ASD) and post-traumatic stress disorder (PTSD) phases in order to measure gender differences, and tend to neglect the immediate exposure to the disaster. The main hypothesis was that female rescue personnel would exhibit higher levels of acute stress symptoms, dissociation, and depressive symptoms in the 24 hours following a traumatic event. Twenty-three rescue personnel participated in a search and rescue operation at the Bet-Yehoshua train crash in Israel. The rescue personnel group was divided based on gender. Each participant completed a demographic questionnaire including questions that assessed psychological symptoms and issues such as perceived threat to life, the Impact of Event Scale Revised (IES-R), the Dissociative Experience Scale (DES), and the Center of Epidemiologic Studies Depression questionnaire (CES-D). Statistical inferences were calculated using t-tests and chi-square tests, along with testing of covariance (MANCOVA) in order to indentify which factors are related to psychiatric symptomatology following the immediate exposure to disaster. The results suggest that among rescue personnel, women did not differ in their levels of acute stress, dissociation, and depressive symptoms from men. These results suggest the possibility that the gender differences in reactions to traumatic events do not emerge in the acute stress reactions (ASR) phase (up to 24 hours after the event), but later on when people have time to process the trauma. Another possibility that may explain the discrepancy between this study and the common knowledge in the literature is that women rescue personnel are considered a highly selected group, which does not reflect on the general population of women. More studies are needed in order to substantiate these results.

  9. Clinically relevant hypoglycemia prediction metrics for event mitigation.

    PubMed

    Harvey, Rebecca A; Dassau, Eyal; Zisser, Howard C; Bevier, Wendy; Seborg, Dale E; Jovanovič, Lois; Doyle, Francis J

    2012-08-01

    The purpose of this study was to develop a method to compare hypoglycemia prediction algorithms and choose parameter settings for different applications, such as triggering insulin pump suspension or alerting for rescue carbohydrate treatment. Hypoglycemia prediction algorithms with different parameter settings were implemented on an ambulatory dataset containing 490 days from 30 subjects with type 1 diabetes mellitus using the Dexcom™ (San Diego, CA) SEVEN™ continuous glucose monitoring system. The performance was evaluated using a proposed set of metrics representing the true-positive ratio, false-positive rate, and distribution of warning times. A prospective, in silico study was performed to show the effect of using different parameter settings to prevent or rescue from hypoglycemia. The retrospective study results suggest the parameter settings for different methods of hypoglycemia mitigation. When rescue carbohydrates are used, a high true-positive ratio, a minimal false-positive rate, and alarms with short warning time are desired. These objectives were met with a 30-min prediction horizon and two successive flags required to alarm: 78% of events were detected with 3.0 false alarms/day and 66% probability of alarms occurring within 30 min of the event. This parameter setting selection was confirmed in silico: treating with rescue carbohydrates reduced the duration of hypoglycemia from 14.9% to 0.5%. However, for a different method, such as pump suspension, this parameter setting only reduced hypoglycemia to 8.7%, as can be expected by the low probability of alarming more than 30 min ahead. The proposed metrics allow direct comparison of hypoglycemia prediction algorithms and selection of parameter settings for different types of hypoglycemia mitigation, as shown in the prospective in silico study in which hypoglycemia was alerted or treated with rescue carbohydrates.

  10. 30 CFR 49.14 - [Reserved

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false [Reserved] 49.14 Section 49.14 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR EDUCATION AND TRAINING MINE RESCUE TEAMS Mine Rescue Teams for Underground Coal Mines § 49.14 [Reserved] ...

  11. 30 CFR 49.14 - [Reserved

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false [Reserved] 49.14 Section 49.14 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR EDUCATION AND TRAINING MINE RESCUE TEAMS Mine Rescue Teams for Underground Coal Mines § 49.14 [Reserved] ...

  12. 30 CFR 49.14 - [Reserved

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false [Reserved] 49.14 Section 49.14 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR EDUCATION AND TRAINING MINE RESCUE TEAMS Mine Rescue Teams for Underground Coal Mines § 49.14 [Reserved] ...

  13. 30 CFR 49.14 - [Reserved

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false [Reserved] 49.14 Section 49.14 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR EDUCATION AND TRAINING MINE RESCUE TEAMS Mine Rescue Teams for Underground Coal Mines § 49.14 [Reserved] ...

  14. 30 CFR 49.14 - [Reserved

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 false [Reserved] 49.14 Section 49.14 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR EDUCATION AND TRAINING MINE RESCUE TEAMS Mine Rescue Teams for Underground Coal Mines § 49.14 [Reserved] ...

  15. Rescue of CD8+ T cell vaccine memory following sublethal γ irradiation.

    PubMed

    McFarland, Hugh I; Berkson, Julia D; Lee, Jay P; Elkahloun, Abdel G; Mason, Karen P; Rosenberg, Amy S

    2015-07-31

    Sublethal γ irradiation eliminates CD8+ T cell mediated memory responses. In this work, we explored how these memory responses could be rescued in the aftermath of such exposure. We utilized two models of CD8+ T cell mediated immunity: a mouse model of Listeria monocytogenes (LM) infection in which CD8+ T cells specific for LM expressed antigens (Listeriolysin O, LLO) can be tracked, and a murine skin graft model in which CD8+ T cells mediate rejection across a MHC class I (D(d)) disparity. In the LM immunized mice, LL0 specific CD8+ T memory cells were lost on irradiation, preserved with rapid revaccination with an attenuated strain 1-3 days post-irradiation (PI), and these mice survived a subsequent wild type LM challenge. A genetic "signature of rescue" identified a group of immune-associated mRNA maintained or upregulated following irradiation and rescue. A number of these factors, including IL-36γ, dectin-2 (Clec4n), and mir101c are upregulated rapidly after exposure of mice to sublethal γ radiation alone and are sustained by early, but not later rescue. Such factors will be evaluated as potential therapeutics to replace individual vaccines for global rescue of CD8+ T memory cell responses following sublethal γ irradiation. The skin allograft model mirrored that of the LM model in that the accelerated D(d) skin allograft rejection response was lost in mice exposed to sublethal γ radiation, but infusion of allogeneic D(d) expressing bone marrow cells 1-4 days PI preserved the CD8+ T memory mediated accelerated rejection response, further suggesting that innate immune responses may not always be essential to rescue of CD8+ memory T cells following γ irradiation. Published by Elsevier Ltd.

  16. Retrospective on the construction and practice of a state-level emergency medical rescue team.

    PubMed

    Lei, Zhang; Haitao, Guo; Xin, Wang; Yundou, Wang

    2014-10-01

    For the past few years, disasters like earthquakes, landslides, mudslides, tsunamis, and traffic accidents have occurred with an ever-growing frequency, coverage, and intensity greatly beyond the expectation of the public. In order to respond effectively to disasters and to reduce casualties and property damage, countries around the world have invested more efforts in the theoretical study of emergency medicine and the construction of emergency medical rescue forces. Consequently, emergency medical rescue teams of all scales and types have come into being and have played significant roles in disaster response work. As the only state-level emergency medical rescue force from the Chinese People's Armed Police Forces, the force described here has developed, through continuous learning and practice, a characteristic mode in terms of grouping methods, equipment system construction, and training.

  17. Opioid overdose prevention and naloxone rescue kits: what we know and what we don't know.

    PubMed

    Kerensky, Todd; Walley, Alexander Y

    2017-01-07

    The opioid use and overdose crisis is persistent and dynamic. Opioid overdoses were initially driven in the 1990s and 2000s by the increasing availability and misuse of prescription opioids. More recently, opioid overdoses are increasing at alarming rates due to wider use of heroin, which in some places is mixed with fentanyl or fentanyl derivatives. Naloxone access for opioid overdose rescue is one of the US Department of Health and Human Services' three priority areas for responding to the opioid crisis. This article summarizes the known benefits of naloxone access and details unanswered questions about overdose education and naloxone rescue kits. Hopefully future research will address these knowledge gaps, improve the effectiveness of opioid overdose education and naloxone distribution programs, and unlock the full promise of naloxone rescue kits.

  18. Effective and Safe Use of Glucocorticosteroids for Rescue of Late ARDS

    PubMed Central

    Diana, Paolo; Money, Dustin T.; Gelvin, Michael G.

    2017-01-01

    We describe a case of severe refractory hypoxemia requiring prolonged extra corporeal membrane oxygenation (ECMO) support in a case of postpartum acute respiratory distress syndrome (ARDS). The clinical course was marked by persistently poor lung compliance and several complications of ECMO, that is, significant hemolysis, hemothorax, and intracranial bleeding. We report marked improvement of lung mechanics and respiratory function, leading to accelerated separation from ECMO, following rescue administration of low dose methylprednisolone 24 days after the onset of ARDS. Corticosteroid treatment was safe and well tolerated. In contrast with the conclusions of the 2006 ARDS Network trial, our report establishes a case in support of the use of low dose methylprednisolone as a safe and effective rescue treatment option in selected subsets of patients with nonresolving ARDS. PMID:28337348

  19. Lung Function in Rescue Workers at the World Trade Center after 7 Years

    PubMed Central

    Aldrich, Thomas K.; Gustave, Jackson; Hall, Charles B.; Cohen, Hillel W.; Webber, Mayris P.; Zeig-Owens, Rachel; Cosenza, Kaitlyn; Christodoulou, Vasilios; Glass, Lara; Al-Othman, Fairouz; Weiden, Michael D.; Kelly, Kerry J.; Prezant, David J.

    2016-01-01

    Background The terrorist attacks on the World Trade Center on September 11, 2001, exposed thousands of Fire Department of New York City (FDNY) rescue workers to dust, leading to substantial declines in lung function in the first year. We sought to determine the longer-term effects of exposure. Methods Using linear mixed models, we analyzed the forced expiratory volume in 1 second (FEV1) of both active and retired FDNY rescue workers on the basis of spirometry routinely performed at intervals of 12 to 18 months from March 12, 2000, to September 11, 2008. Results Of the 13,954 FDNY workers who were present at the World Trade Center between September 11, 2001, and September 24, 2001, a total of 12,781 (91.6%) participated in this study, contributing 61,746 quality-screened spirometric measurements. The median follow-up was 6.1 years for firefighters and 6.4 years for emergency-medical-services (EMS) workers. In the first year, the mean FEV1 decreased significantly for all workers, more for firefighters who had never smoked (a reduction of 439 ml; 95% confidence interval [CI], 408 to 471) than for EMS workers who had never smoked (a reduction of 267 ml; 95% CI, 263 to 271) (P<0.001 for both comparisons). There was little or no recovery in FEV1 during the subsequent 6 years, with a mean annualized reduction in FEV1 of 25 ml per year for firefighters and 40 ml per year for EMS workers. The proportion of workers who had never smoked and who had an FEV1 below the lower limit of the normal range increased during the first year, from 3% to 18% for firefighters and from 12% to 22% for EMS workers, stabilizing at about 13% for firefighters and 22% for EMS workers during the subsequent 6 years. Conclusions Exposure to World Trade Center dust led to large declines in FEV1 for FDNY rescue workers during the first year. Overall, these declines were persistent, without recovery over the next 6 years, leaving a substantial proportion of workers with abnormal lung function. PMID:20375403

  20. Helicobacter pylori first-line and rescue treatments in the presence of penicillin allergy.

    PubMed

    Gisbert, Javier P; Barrio, Jesús; Modolell, Inés; Molina-Infante, Javier; Aisa, Angeles Perez; Castro-Fernández, Manuel; Rodrigo, Luis; Cosme, Angel; Gisbert, Jose Luis; Fernández-Bermejo, Miguel; Marcos, Santiago; Marín, Alicia C; McNicholl, Adrián G

    2015-02-01

    Helicobacter pylori eradication is a challenge in penicillin allergy. To assess the efficacy and safety of first-line and rescue treatments in patients allergic to penicillin. Prospective multicenter study. Patients allergic to penicillin were given a first-line treatment comprising (a) 7-day omeprazole-clarithromycin-metronidazole and (b) 10-day omeprazole-bismuth-tetracycline-metronidazole. Rescue treatments were as follows: (a) bismuth quadruple therapy; (b) 10-day PPI-clarithromycin-levofloxacin; and (c) 10-day PPI-clarithromycin-rifabutin. Eradication was confirmed by (13)C-urea breath test. Compliance was determined through questioning and recovery of empty medication envelopes. Adverse effects were evaluated by questionnaires. In total, 267 consecutive treatments were included. (1) First-line treatment: Per-protocol and intention-to-treat eradication rates with omeprazole-clarithromycin-metronidazole were 59 % (62/105; 95 % CI 49-62 %) and 57 % (64/112; 95 % CI 47-67 %). Respective figures for PPI-bismuth-tetracycline-metronidazole were 75 % (37/49; 95 % CI 62-89 %) and 74 % (37/50; 95 % CI (61-87 %) (p < 0.05). Compliance with treatment was 94 and 98 %, respectively. Adverse events were reported in 14 % with both regimens (all mild). (2) Second-line treatment: Intention-to-treat eradication rate with omeprazole-clarithromycin-levofloxacin was 64 % both after triple and quadruple failure; compliance was 88-100 %, with 23-29 % adverse effects (all mild). (3) Third-/fourth-line treatment: Intention-to-treat eradication rate with PPI-clarithromycin-rifabutin was 22 %. In allergic to penicillin patients, a first-line treatment with a bismuth-containing quadruple therapy (PPI-bismuth-tetracycline-metronidazole) seems to be a better option than the triple PPI-clarithromycin-metronidazole regimen. A levofloxacin-based regimen (together with a PPI and clarithromycin) represents a second-line rescue option in the presence of penicillin allergy.

  1. Interface between hospital and fire authorities--a concept for management of incidents in hospitals.

    PubMed

    Gretenkort, Peter; Harke, Henning; Blazejak, Jan; Pache, Bernd; Leledakis, Georgios

    2002-01-01

    Although every hospital needs a security plan for the support of immobile patients who do not possess autonomous escape capabilities, little information exists to assist in the development of practical patient evacuation methods. 1) In hospitals during disasters, incident leadership of the fire authorities can be supported effectively by hospital executives experienced in the management of mass casualties; and 2) As an alternative for canvas carry sheets, rescue drag sheets can be employed for emergency, elevator-independent, patient evacuation. A hospital evacuation exercise was planned and performed to obtain experiences in incident command and to permit calculation of elevator-independent patient transport times. Performance of incident leadership was observed by means of pre-defined checklists. The effectiveness and efficiency of carrying teams with five persons each were compared to those with a rescue drag sheet employed by a single person. Incident command for hospitals during a disaster is enhanced considerably by pre-defined and trained executives who are placed at the immediate disposal of the fire authorities. For elevator-independent patient transport, the rescue drag sheet was superior to conventional carrying measures because of a reduced number of transport personnel required to move each patient. With this method, patient transport times averaged 54 m/min. flat and 18 seconds for one floor descent. Experiences from a hospital during an evacuation exercise provided decision criteria for changes in the disaster preparedness plan. Hospital incident leadership was assigned to executives-in-charge in close co-operation with the fire authorities. All beds were equipped with a rescue drag sheet. Both concepts may help to cope with an emergency evacuation of a hospital.

  2. Efficacy and safety of olanzapine combined with aprepitant, palonosetron, and dexamethasone for preventing nausea and vomiting induced by cisplatin-based chemotherapy in gynecological cancer: KCOG-G1301 phase II trial.

    PubMed

    Abe, Masakazu; Hirashima, Yasuyuki; Kasamatsu, Yuka; Kado, Nobuhiro; Komeda, Satomi; Kuji, Shiho; Tanaka, Aki; Takahashi, Nobutaka; Takekuma, Munetaka; Hihara, Hanako; Ichikawa, Yoshikazu; Itonaga, Yui; Hirakawa, Tomoko; Nasu, Kaei; Miyagi, Kanoko; Murakami, Junko; Ito, Kimihiko

    2016-02-01

    Olanzapine is effective in chemotherapy-induced nausea and vomiting (CINV). In patients receiving highly emetogenic chemotherapy (HEC), its efficacy was reported as rescue therapy for breakthrough emesis refractory to triplet therapy (palonosetron, aprepitant, and dexamethasone). However, its preventive effects with triplet therapy for CINV are unknown. This study aimed to investigate efficacy and safety of preventive use of olanzapine with triplet therapy for CINV of HEC. This study is a prospective multicenter study conducted by Kansai Clinical Oncology Group. Forty chemo-naïve gynecological cancer patients receiving HEC with cisplatin (≥50 mg/m(2)) were enrolled. Oral olanzapine (5 mg) was administered with triplet therapy a day prior to cisplatin administration and on days 1-5. The primary endpoint was complete response (no vomiting and no rescue) rate for the overall phase (0-120 h post-chemotherapy). Secondary endpoints were complete response rate for acute phase (0-24 h post-chemotherapy) and delayed phase (24-120 h post-chemotherapy) and complete control (no vomiting, no rescue, and no significant nausea) rate and total control (no vomiting, no rescue, and no nausea) rate for each phase. These endpoints were evaluated during the first cycle of chemotherapy. Complete response rates for acute, delayed, and overall phases were 97.5, 95.0, and 92.5 %, respectively. Complete control rates were 92.5, 87.5, and 82.5 %, respectively. Total control rates were 87.5, 67.5, and 67.5 %, respectively. There were no grade 3 or 4 adverse events. Preventive use of olanzapine combined with triplet therapy gives better results than those from previously reported studies of triplet therapy.

  3. A new helper phage for improved monovalent display of Fab molecules.

    PubMed

    Beaber, John W; Tam, Eric M; Lao, Llewelyn S; Rondon, Isaac J

    2012-02-28

    Phage display technology is a powerful tool for the identification of novel antibodies for drug discovery. Phage display libraries have been constructed with massive diversity, but their use may be hindered by limited antibody display levels when rescued with the M13KO7 helper phage. Variants of M13KO7 have been constructed previously that increase the levels of display of rescued phage, but all produce phage that display multiple copies of the antibody fragment on their surface and have reduced titer and infectivity. In this study, we describe a new helper phage, XP5, which increased the display level of Fab molecules more than two-fold compared to phage rescued with M13KO7. XP5 uses a combination of ribosome binding site spacing alterations and rare codon clusters to reduce the expression of pIII from the helper phage. This reduction in pIII expression leads to an increase in the incorporation of pIII-Fab fusions during phage rescue. The rescued phage displayed a single copy of the Fab molecule, preventing any avidity effects during the selection process. This also suggests that the percentage of the population of phage displaying a Fab molecule is increased when rescued with XP5. Additionally, the phage titers and infectivity are comparable to libraries rescued with M13KO7. After two rounds of panning we observed a nearly 5-fold increase in the number of antigen binding Fab molecules compared to panning conducted with the same library rescued with M13KO7. The nature of the mutations in XP5 makes it a universal substitute for M13KO7 in pIII-based phage display, compatible with most phagemids and bacterial strains. Copyright © 2011 Elsevier B.V. All rights reserved.

  4. Clioquinol and vitamin B12 (cobalamin) synergistically rescue the lead-induced impairments of synaptic plasticity in hippocampal dentate gyrus area of the anesthetized rats in vivo.

    PubMed

    Chen, W-H; Wang, M; Yu, S-S; Su, L; Zhu, D-M; She, J-Q; Cao, X-J; Ruan, D-Y

    2007-07-13

    Lead (Pb(2+)) exposure in development induces impairments of synaptic plasticity in the hippocampal dentate gyrus (DG) area of the anesthetized rats in vivo. The common chelating agents have many adverse effects and are incapable of alleviating lead-induced neurotoxicity. Recently, CQ, clioquinol (5-chloro-7-iodo-8-hydroxy-quinoline), which is a transition metal ion chelator and/or ionophore with low affinity for metal ions, has yielded some promising results in animal models and clinical trials related to dysfunctions of metal ions. In addition, CQ-associated side effects are believed to be overcome with vitamin B12 (VB12) supplementation. To determine whether CQ treatment could rescue impairments of synaptic plasticity induced by chronic Pb(2+) exposure, we investigated the input/output functions (I/Os), paired-pulse reactions (PPRs) and long-term potentiation (LTP) of different treatment groups in hippocampal DG area of the anesthetized rat in vivo by recording field potentials and measured hippocampal Pb(2+) concentrations of different treatment groups by PlasmaQuad 3 inductive coupled plasma mass spectroscopy. The results show: CQ alone does not rescue the lead-induced impairments of synaptic plasticity in hippocampal DG area of the anesthetized rats in vivo; VB12 alone partly rescues the lead-induced impairments of LTP; however the co-administration of CQ and VB12 totally rescues these impairments of synaptic plasticity and moreover, the effects of CQ and VB12 co-administration are specific to the lead-exposed animals.

  5. N-acetylcysteine and vitamin E rescue animal longevity and cellular oxidative stress in pre-clinical models of mitochondrial complex I disease.

    PubMed

    Polyak, Erzsebet; Ostrovsky, Julian; Peng, Min; Dingley, Stephen D; Tsukikawa, Mai; Kwon, Young Joon; McCormack, Shana E; Bennett, Michael; Xiao, Rui; Seiler, Christoph; Zhang, Zhe; Falk, Marni J

    2018-04-01

    Oxidative stress is a known contributing factor in mitochondrial respiratory chain (RC) disease pathogenesis. Yet, no efficient means exists to objectively evaluate the comparative therapeutic efficacy or toxicity of different antioxidant compounds empirically used in human RC disease. We postulated that pre-clinical comparative analysis of diverse antioxidant drugs having suggested utility in primary RC disease using animal and cellular models of RC dysfunction may improve understanding of their integrated effects and physiologic mechanisms, and enable prioritization of lead antioxidant molecules to pursue in human clinical trials. Here, lifespan effects of N-acetylcysteine (NAC), vitamin E, vitamin C, coenzyme Q10 (CoQ10), mitochondrial-targeted CoQ10 (MS010), lipoate, and orotate were evaluated as the primary outcome in a well-established, short-lived C. elegans gas-1(fc21) animal model of RC complex I disease. Healthspan effects were interrogated to assess potential reversal of their globally disrupted in vivo mitochondrial physiology, transcriptome profiles, and intermediary metabolic flux. NAC or vitamin E fully rescued, and coenzyme Q, lipoic acid, orotic acid, and vitamin C partially rescued gas-1(fc21) lifespan toward that of wild-type N2 Bristol worms. MS010 and CoQ10 largely reversed biochemical pathway expression changes in gas-1(fc21) worms. While nearly all drugs normalized the upregulated expression of the "cellular antioxidant pathway", they failed to rescue the mutant worms' increased in vivo mitochondrial oxidant burden. NAC and vitamin E therapeutic efficacy were validated in human fibroblast and/or zebrafish complex I disease models. Remarkably, rotenone-induced zebrafish brain death was preventable partially with NAC and fully with vitamin E. Overall, these pre-clinical model animal data demonstrate that several classical antioxidant drugs do yield significant benefit on viability and survival in primary mitochondrial disease, where their major therapeutic benefit appears to result from targeting global cellular, rather than intramitochondria-specific, oxidative stress. Clinical trials are needed to evaluate whether the two antioxidants, NAC and vitamin E, that show greatest efficacy in translational model animals significantly improve the survival, function, and feeling of human subjects with primary mitochondrial RC disease. Copyright © 2018 Elsevier Inc. All rights reserved.

  6. RNA Interference Screen to Identify Kinases That Suppress Rescue of ΔF508-CFTR.

    PubMed

    Trzcińska-Daneluti, Agata M; Chen, Anthony; Nguyen, Leo; Murchie, Ryan; Jiang, Chong; Moffat, Jason; Pelletier, Lawrence; Rotin, Daniela

    2015-06-01

    Cystic Fibrosis (CF) is an autosomal recessive disorder caused by mutations in the gene encoding the Cystic fibrosis transmembrane conductance regulator (CFTR). ΔF508-CFTR, the most common disease-causing CF mutant, exhibits folding and trafficking defects and is retained in the endoplasmic reticulum, where it is targeted for proteasomal degradation. To identify signaling pathways involved in ΔF508-CFTR rescue, we screened a library of endoribonuclease-prepared short interfering RNAs (esiRNAs) that target ∼750 different kinases and associated signaling proteins. We identified 20 novel suppressors of ΔF508-CFTR maturation, including the FGFR1. These were subsequently validated by measuring channel activity by the YFP halide-sensitive assay following shRNA-mediated knockdown, immunoblotting for the mature (band C) ΔF508-CFTR and measuring the amount of surface ΔF508-CFTR by ELISA. The role of FGFR signaling on ΔF508-CFTR trafficking was further elucidated by knocking down FGFRs and their downstream signaling proteins: Erk1/2, Akt, PLCγ-1, and FRS2. Interestingly, inhibition of FGFR1 with SU5402 administered to intestinal organoids (mini-guts) generated from the ileum of ΔF508-CFTR homozygous mice resulted in a robust ΔF508-CFTR rescue. Moreover, combination of SU5402 and VX-809 treatments in cells led to an additive enhancement of ΔF508-CFTR rescue, suggesting these compounds operate by different mechanisms. Chaperone array analysis on human bronchial epithelial cells harvested from ΔF508/ΔF508-CFTR transplant patients treated with SU5402 identified altered expression of several chaperones, an effect validated by their overexpression or knockdown experiments. We propose that FGFR signaling regulates specific chaperones that control ΔF508-CFTR maturation, and suggest that FGFRs may serve as important targets for therapeutic intervention for the treatment of CF. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  7. Expression of the genetic suppressor element 24.2 (GSE24.2) decreases DNA damage and oxidative stress in X-linked dyskeratosis congenita cells.

    PubMed

    Manguan-Garcia, Cristina; Pintado-Berninches, Laura; Carrillo, Jaime; Machado-Pinilla, Rosario; Sastre, Leandro; Pérez-Quilis, Carme; Esmoris, Isabel; Gimeno, Amparo; García-Giménez, Jose Luis; Pallardó, Federico V; Perona, Rosario

    2014-01-01

    The predominant X-linked form of Dyskeratosis congenita results from mutations in DKC1, which encodes dyskerin, a protein required for ribosomal RNA modification that is also a component of the telomerase complex. We have previously found that expression of an internal fragment of dyskerin (GSE24.2) rescues telomerase activity in X-linked dyskeratosis congenita (X-DC) patient cells. Here we have found that an increased basal and induced DNA damage response occurred in X-DC cells in comparison with normal cells. DNA damage that is also localized in telomeres results in increased heterochromatin formation and senescence. Expression of a cDNA coding for GSE24.2 rescues both global and telomeric DNA damage. Furthermore, transfection of bacterial purified or a chemically synthesized GSE24.2 peptide is able to rescue basal DNA damage in X-DC cells. We have also observed an increase in oxidative stress in X-DC cells and expression of GSE24.2 was able to diminish it. Altogether our data indicated that supplying GSE24.2, either from a cDNA vector or as a peptide reduces the pathogenic effects of Dkc1 mutations and suggests a novel therapeutic approach.

  8. Snyder-Robinson Syndrome: Rescuing the Disease-Causing Effect of G56S mutant by Small Molecule Binding

    NASA Astrophysics Data System (ADS)

    Zhang, Zhe; Martiny, Virginie; Lagorce, David; Alexov, Emil; Miteva, Maria; Clemson University Team; Université Paris Diderot Team

    2013-03-01

    Snyder-Robinson Syndrome (SRS) is an X-linked mental retardation disorder, which is caused by defects in a particular gene coding for the spermine synthase (SMS) protein. Among the missense mutations known to be disease-causing is the G56S, which is positioned at the interface of the SMS homo-dimer. Previous computational and experimental investigations have shown that G56S mutation destabilizes the homo-dimer and thus greatly reduces the SMS enzymatic activity. In this study, we explore the possibility of mitigating the effect of G56S mutation by binding small molecules to suitable pockets around the mutation site. It is done by combined efforts of molecular dynamics simulations and in silico screening. The binding of selected molecules was calculated to fully compensate the effect of the mutation and rescue the wild type dimer affinity. This work was supported by NIH, NLM grant. No. 1R03LM009748

  9. Superoxide dismutating molecules rescue the toxic effects of PINK1 and parkin loss.

    PubMed

    Biosa, Alice; Sanchez-Martinez, Alvaro; Filograna, Roberta; Terriente-Felix, Ana; Alam, Sarah M; Beltramini, Mariano; Bubacco, Luigi; Bisaglia, Marco; Whitworth, Alexander J

    2018-05-01

    Reactive oxygen species exert important functions in regulating several cellular signalling pathways. However, an excessive accumulation of reactive oxygen species can perturb the redox homeostasis leading to oxidative stress, a condition which has been associated to many neurodegenerative disorders. Accordingly, alterations in the redox state of cells and mitochondrial homeostasis are established hallmarks in both familial and sporadic Parkinson's disease cases. PINK1 and Parkin are two genes which account for a large fraction of autosomal recessive early-onset forms of Parkinson's disease and are now firmly associated to both mitochondria and redox homeostasis. In this study we explored the hypothesis that superoxide anions participate in the generation of the Parkin and PINK1 associated phenotypic effect by testing the capacity of endogenous and exogenous superoxide dismutating molecules to rescue the toxic effects induced by loss of PINK1 or Parkin, in both cellular and fly models. Our results demonstrate the positive effect of an increased level of superoxide dismutase proteins on the pathological phenotypes, both in vitro and in vivo. A more pronounced effectiveness for mitochondrial SOD2 activity points to the superoxide radicals generated in the mitochondrial matrix as the prime suspect in the definition of the observed phenotypes. Moreover, we also demonstrate the efficacy of a SOD-mimetic compound, M40403, to partially ameliorate PINK1/Parkin phenotypes in vitro and in vivo. These results support the further exploration of SOD-mimetic compounds as a therapeutic strategy against Parkinson's disease.

  10. Methadone in combination with acepromazine as premedication prior to neutering in the cat.

    PubMed

    Bortolami, Elisa; Murrell, Joanna C; Slingsby, Louisa S

    2013-03-01

    To investigate the safety, sedative and analgesic properties of methadone in combination with acepromazine prior to neutering in cats. Controlled clinical, block randomized, prospective, blinded study designed for regulatory purposes. 24 female and 21 male healthy cats. Cats received one of three opioids combined with acepromazine (0.05 mg kg(-1) ) intramuscularly (IM) for premedication: Group 1: buprenorphine (0.02 mg kg(-1) ), group 2: methadone (0.5 mg kg(-1) ), group 3 butorphanol (0.4 mg kg(-1) ). Sedation was assessed 30 minutes after premedication using a visual analogue scale (VAS) and simple descriptive scale. Anaesthesia was induced with alfaxalone and maintained with isoflurane in oxygen. Surgical ovariohysterectomy or castration was performed. Pain was assessed using an interactive VAS (IVAS) and mechanical nociceptive threshold (MNT) with a pressure rate onset device. Methadone (0.5 mg kg(-1) IM) and meloxicam (0.2 mg kg(-1) subcutaneously) were provided 6 and 8 hours after premedication respectively, or together as rescue analgesia (IVAS above 50). Sedation scores, induction agent dose, pain scores at all time points and rescue analgesia were not statistically different between groups. In methadone treated cats there was no significant variation in MNT over time, suggesting a possible anti-hyperalgesic action, whereas in the other two groups lower thresholds were recorded at various time points after surgery compared to baseline. No cats required rescue analgesia after the second dose of methadone. No perioperative adverse effects occurred. Methadone provided comparable sedation and analgesia to both buprenorphine and butorphanol when combined with acepromazine. Differences in analgesic efficacy between opioids might have been undetectable because of the surgical model and surgeon competency. Nevertheless, methadone is an effective analgesic in cats and its administration prior to feline neutering may be advantageous. © 2012 The Authors. Veterinary Anaesthesia and Analgesia. © 2012 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesiologists.

  11. 2017 American Heart Association Focused Update on Pediatric Basic Life Support and Cardiopulmonary Resuscitation Quality: An Update to the American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care.

    PubMed

    Atkins, Dianne L; de Caen, Allan R; Berger, Stuart; Samson, Ricardo A; Schexnayder, Stephen M; Joyner, Benny L; Bigham, Blair L; Niles, Dana E; Duff, Jonathan P; Hunt, Elizabeth A; Meaney, Peter A

    2018-01-02

    This focused update to the American Heart Association guidelines for cardiopulmonary resuscitation (CPR) and emergency cardiovascular care follows the Pediatric Task Force of the International Liaison Committee on Resuscitation evidence review. It aligns with the International Liaison Committee on Resuscitation's continuous evidence review process, and updates are published when the International Liaison Committee on Resuscitation completes a literature review based on new science. This update provides the evidence review and treatment recommendation for chest compression-only CPR versus CPR using chest compressions with rescue breaths for children <18 years of age. Four large database studies were available for review, including 2 published after the "2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care." Two demonstrated worse 30-day outcomes with chest compression-only CPR for children 1 through 18 years of age, whereas 2 studies documented no difference between chest compression-only CPR and CPR using chest compressions with rescue breaths. When the results were analyzed for infants <1 year of age, CPR using chest compressions with rescue breaths was better than no CPR but was no different from chest compression-only CPR in 1 study, whereas another study observed no differences among chest compression-only CPR, CPR using chest compressions with rescue breaths, and no CPR. CPR using chest compressions with rescue breaths should be provided for infants and children in cardiac arrest. If bystanders are unwilling or unable to deliver rescue breaths, we recommend that rescuers provide chest compressions for infants and children. © 2017 American Heart Association, Inc.

  12. Inhibition of chlorine-induced lung injury by the type 4 phosphodiesterase inhibitor rolipram.

    PubMed

    Chang, Weiyuan; Chen, Jing; Schlueter, Connie F; Rando, Roy J; Pathak, Yashwant V; Hoyle, Gary W

    2012-09-01

    Chlorine is a highly toxic respiratory irritant that when inhaled causes epithelial cell injury, alveolar-capillary barrier disruption, airway hyperreactivity, inflammation, and pulmonary edema. Chlorine is considered a chemical threat agent, and its release through accidental or intentional means has the potential to result in mass casualties from acute lung injury. The type 4 phosphodiesterase inhibitor rolipram was investigated as a rescue treatment for chlorine-induced lung injury. Rolipram inhibits degradation of the intracellular signaling molecule cyclic AMP. Potential beneficial effects of increased cyclic AMP levels include inhibition of pulmonary edema, inflammation, and airway hyperreactivity. Mice were exposed to chlorine (whole body exposure, 228-270 ppm for 1 h) and were treated with rolipram by intraperitoneal, intranasal, or intramuscular (either aqueous or nanoemulsion formulation) delivery starting 1h after exposure. Rolipram administered intraperitoneally or intranasally inhibited chlorine-induced pulmonary edema. Minor or no effects were observed on lavage fluid IgM (indicative of plasma protein leakage), KC (Cxcl1, neutrophil chemoattractant), and neutrophils. All routes of administration inhibited chlorine-induced airway hyperreactivity assessed 1 day after exposure. The results of the study suggest that rolipram may be an effective rescue treatment for chlorine-induced lung injury and that both systemic and targeted administration to the respiratory tract were effective routes of delivery. Copyright © 2012 Elsevier Inc. All rights reserved.

  13. Mechanism of mesenchymal stem cell-induced neuron recovery and anti-inflammation.

    PubMed

    Huang, Peng; Gebhart, Nichole; Richelson, Elliott; Brott, Thomas G; Meschia, James F; Zubair, Abba C

    2014-10-01

    After ischemic or hemorrhagic stroke, neurons in the penumbra surrounding regions of irreversible injury are vulnerable to delayed but progressive damage as a result of ischemia and hemin-induced neurotoxicity. There is no effective treatment to rescue such dying neurons. Mesenchymal stem cells (MSCs) hold promise for rescue of these damaged neurons. In this study, we evaluated the efficacy and mechanism of MSC-induced neuro-regeneration and immune modulation. Oxygen-glucose deprivation (OGD) was used in our study. M17 neuronal cells were subjected to OGD stress then followed by co-culture with MSCs. Rescue effects were evaluated using proliferation and apoptosis assays. Cytokine assay and quantitative polymerase chain reaction were used to explore the underlying mechanism. Antibody and small molecule blocking experiments were also performed to further understand the mechanism. We showed that M17 proliferation was significantly decreased and the rate of apoptosis increased after exposure to OGD. These effects could be alleviated via co-culture with MSCs. Tumor necrosis factor-α was found elevated after OGD stress and was back to normal levels after co-culture with MSCs. We believe these effects involve interleukin-6 and vascular endothelial growth factor signaling pathways. Our studies have shown that MSCs have anti-inflammatory properties and the capacity to rescue injured neurons. Copyright © 2014 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  14. Genetic evidence that thyroid hormone is indispensable for prepubertal insulin-like growth factor-I expression and bone acquisition in mice.

    PubMed

    Xing, Weirong; Govoni, Kristen E; Donahue, Leah Rae; Kesavan, Chandrasekhar; Wergedal, Jon; Long, Carlin; Bassett, J H Duncan; Gogakos, Apostolos; Wojcicka, Anna; Williams, Graham R; Mohan, Subburaman

    2012-05-01

    Understanding how bone growth is regulated by hormonal and mechanical factors during early growth periods is important for optimizing the attainment of peak bone mass to prevent or postpone the occurrence of fragility fractures later in life. Using genetic mouse models that are deficient in thyroid hormone (TH) (Tshr(-/-) and Duox2(-/-)), growth hormone (GH) (Ghrhr(lit/lit)), or both (Tshr(-/-); Ghrhr(lit/lit)), we demonstrate that there is an important period prior to puberty when the effects of GH are surprisingly small and TH plays a critical role in the regulation of skeletal growth. Daily administration of T3/T4 during days 5 to 14, the time when serum levels of T3 increase rapidly in mice, rescued the skeletal deficit in TH-deficient mice but not in mice lacking both TH and GH. However, treatment of double-mutant mice with both GH and T3/T4 rescued the bone density deficit. Increased body fat in the TH-deficient as well as TH/GH double-mutant mice was rescued by T3/T4 treatment during days 5 to 14. In vitro studies in osteoblasts revealed that T3 in the presence of TH receptor (TR) α1 bound to a TH response element in intron 1 of the IGF-I gene to stimulate transcription. In vivo studies using TRα and TRβ knockout mice revealed evidence for differential regulation of insulin-like growth factor (IGF)-I expression by the two receptors. Furthermore, blockade of IGF-I action partially inhibited the biological effects of TH, thus suggesting that both IGF-I-dependent and IGF-I-independent mechanisms contribute to TH effects on prepubertal bone acquisition. Copyright © 2012 American Society for Bone and Mineral Research.

  15. Carnitine protects the nematode Caenorhabditis elegans from glucose-induced reduction of survival depending on the nuclear hormone receptor DAF-12

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Deusing, Dorothé Jenni, E-mail: Dorothe.J.Deusing@ernaehrung.uni-giessen.de; Beyrer, Melanie, E-mail: m.beyrer@web.de; Fitzenberger, Elena, E-mail: Elena.Fitzenberger@ernaehrung.uni-giessen.de

    Besides its function in transport of fatty acids into mitochondria in order to provide substrates for β-oxidation, carnitine has been shown to affect also glucose metabolism and to inhibit several mechanisms associated with diabetic complications. In the present study we used the mev-1 mutant of the nematode Caenorhabditis elegans fed on a high glucose concentration in liquid media as a diabetes model and tested the effects of carnitine supplementation on their survival under heat-stress. Carnitine at 100 μM completely prevented the survival reduction that was caused by the application of 10 mM glucose. RNA-interference for sir-2.1, a candidate genes mediating the effectsmore » of carnitine revealed no contribution of the sirtuin for the rescue of survival. Under daf-12 RNAi rescue of survival by carnitine was abolished. RNA-interference for γ-butyrobetaine hydroxylase 2, encoding the key enzyme for carnitine biosynthesis did neither increase glucose toxicity nor prevent the rescue of survival by carnitine, suggesting that the effects of carnitine supplementation on carnitine levels were significant. Finally, it was demonstrated that neither the amount of lysosomes nor the proteasomal activity were increased by carnitine, excluding that protein degradation pathways, such as autophagy or proteasomal degradation, are involved in the protective carnitine effects. In conclusion, carnitine supplementation prevents the reduction of survival caused by glucose in C. elegans in dependence on a nuclear hormone receptor which displays high homologies to the vertebrate peroxisomal proliferator activated receptors. - Highlights: • Carnitine protects from glucose-induced reduction of stress-resistance. • Carnitine acts via the PPAR homolog DAF-12 on glucose toxicity. • Carnitine protects from glucose toxicity independent of protein degradation.« less

  16. GDF11 Does not Rescue Aging-Related Pathological Hypertrophy

    PubMed Central

    Smith, Shavonn C.; Zhang, Xiaoxiao; Zhang, Xiaoying; Gross, Polina; Starosta, Timothy; Mohsin, Sadia; Franti, Michael; Gupta, Priyanka; Hayes, David; Myzithras, Maria; Kahn, Julius; Tanner, James; Weldon, Steven M.; Khalil, Ashraf; Guo, Xinji; Sabri, Abdelkarim; Chen, Xiongwen; MacDonnell, Scott; Houser, Steven R.

    2015-01-01

    Rationale GDF11 (Growth Differentiation Factor 11) is a member of the transforming growth factor β (TGFβ) super family of secreted factors. A recent study showed that reduced GDF11 blood levels with aging was associated with pathological cardiac hypertrophy (PCH), and restoring GDF11 to normal levels in old mice rescued PCH. Objective To determine if and by what mechanism GDF11 rescues aging dependent PCH. Methods and Results 24-month-old C57BL/6 mice were given a daily injection of either recombinant (r) GDF11 at 0.1mg/kg or vehicle for 28 days. rGDF11 bioactivity was confirmed in-vitro. After treatment, rGDF11 levels were significantly increased but there was no significant effect on either heart weight (HW) or body weight (BW). HW/BW ratios of old mice were not different from 8 or 12 week-old animals, and the PCH marker ANP was not different in young versus old mice. Ejection fraction, internal ventricular dimension, and septal wall thickness were not significantly different between rGDF11 and vehicle treated animals at baseline and remained unchanged at 1, 2 and 4 weeks of treatment. There was no difference in myocyte cross-sectional area rGDF11 versus vehicle-treated old animals. In vitro studies using phenylephrine-treated neonatal rat ventricular myocytes (NRVM), to explore the putative anti-hypertrophic effects of GDF11, showed that GDF11 did not reduce NRVM hypertrophy, but instead induced hypertrophy. Conclusions Our studies show that there is no age-related PCH in disease free 24-month-old C57BL/6 mice and that restoring GDF11 in old mice has no effect on cardiac structure or function. PMID:26383970

  17. Utilization of non-US educated nurses in US hospitals: implications for hospital mortality

    PubMed Central

    Neff, Donna Felber; Cimiotti, Jeannie; Sloane, Douglas M.; Aiken, Linda H.

    2013-01-01

    Objectives To determine whether, and under what circumstance, US hospital employment of non-US-educated nurses is associated with patient outcomes. Design Observational study of primary data from 2006 to 2007 surveys of hospital nurses in four states (California, Florida, New Jersey and Pennsylvania). The direct and interacting effects of hospital nurse staffing and the percentage of non-US-educated nurses on 30-day surgical patient mortality and failure-to-rescue were estimated before and after controlling for patient and hospital characteristics. Participants Data from registered nurse respondents practicing in 665 hospitals were pooled with patient discharge data from state agencies. Main Outcomes Measure(s) Thirty-day surgical patient mortality and failure-to-rescue. Results The effect of non-US-educated nurses on both mortality and failure-to-rescue is nil in hospitals with lower than average patient to nurse ratios, but pronounced in hospitals with average and poor nurse to patient ratios. In hospitals in which patient-to-nurse ratios are 5:1 or higher, mortality is higher when 25% or more nurses are educated outside of the USA than when <25% of nurses are non-US-educated. Moreover, the effect of having >25% non-US-educated nurses becomes increasingly deleterious as patient-to-nurse ratios increase beyond 5:1. Conclusions Employing non-US-educated nurses has a negative impact on patient mortality except where patient-to-nurse ratios are lower than average. Thus, US hospitals should give priority to achieving adequate nurse staffing levels, and be wary of hiring large percentages of non-US-educated nurses unless patient-to-nurse ratios are low. PMID:23736834

  18. Soluble factor(s) from bone marrow cells can rescue lethally irradiated mice by protecting endogenous hematopoietic stem cells.

    PubMed

    Zhao, Yi; Zhan, Yuxia; Burke, Kathleen A; Anderson, W French

    2005-04-01

    Ionizing radiation-induced myeloablation can be rescued via bone marrow transplantation (BMT) or administration of cytokines if given within 2 hours after radiation exposure. There is no evidence for the existence of soluble factors that can rescue an animal after a lethal dose of radiation when administered several hours postradiation. We established a system that could test the possibility for the existence of soluble factors that could be used more than 2 hours postirradiation to rescue animals. Animals with an implanted TheraCyte immunoisolation device (TID) received lethal-dose radiation and then normal bone marrow Lin- cells were loaded into the device (thereby preventing direct interaction between donor and recipient cells). Animal survival was evaluated and stem cell activity was tested with secondary bone marrow transplantation and flow cytometry analysis. Donor cell gene expression of five antiapoptotic cytokines was examined. Bone marrow Lin- cells rescued lethally irradiated animals via soluble factor(s). Bone marrow cells from the rescued animals can rescue and repopulate secondary lethally irradiated animals. Within the first 6 hours post-lethal-dose radiation, there is no significant change of gene expression of the known radioprotective factors TPO, SCF, IL-3, Flt-3 ligand, and SDF-1. Hematopoietic stem cells can be protected in lethally irradiated animals by soluble factors produced by bone marrow Lin- cells.

  19. The marijuana component cannabidiol inhibits beta-amyloid-induced tau protein hyperphosphorylation through Wnt/beta-catenin pathway rescue in PC12 cells.

    PubMed

    Esposito, Giuseppe; De Filippis, Daniele; Carnuccio, Rosa; Izzo, Angelo A; Iuvone, Teresa

    2006-03-01

    Alzheimer's disease (AD) is the most common age-related neurodegenerative disorder. A massive accumulation of beta-amyloid (Abeta) peptide aggregates has been proposed as pivotal event in AD. Abeta-induced toxicity is accompanied by a variegated combination of events including oxidative stress. The Wnt pathway has multiple actions in the cascade of events triggered by Abeta, and drugs that rescue Wnt activity may be considered as novel therapeutics for AD treatment. Cannabidiol, a non-psychoactive marijuana component, has been recently proposed as an antioxidant neuroprotective agent in neurodegenerative diseases. Moreover, it has been shown to rescue PC12 cells from toxicity induced by Abeta peptide. However, the molecular mechanism of cannabidiol-induced neuroprotective effect is still unknown. Here, we report that cannabidiol inhibits hyperphosphorylation of tau protein in Abeta-stimulated PC12 neuronal cells, which is one of the most representative hallmarks in AD. The effect of cannabidiol is mediated through the Wnt/beta-catenin pathway rescue in Abeta-stimulated PC12 cells. These results provide new molecular insight regarding the neuroprotective effect of cannabidiol and suggest its possible role in the pharmacological management of AD, especially in view of its low toxicity in humans.

  20. Rescue Effects and Underlying Mechanisms of Intragland Shh Gene Delivery on Irradiation-Induced Hyposalivation.

    PubMed

    Hai, Bo; Zhao, Qingguo; Qin, Lizheng; Rangaraj, Dharanipathy; Gutti, Veera R; Liu, Fei

    2016-05-01

    Irreversible hypofunction of salivary glands is common in head and neck cancer survivors treated with radiotherapy and can only be temporarily relieved with current treatments. We found in an inducible sonic hedgehog (Shh) transgenic mouse model that transient activation of the Hedgehog pathway after irradiation rescued salivary gland function in males by preserving salivary stem/progenitor cells and parasympathetic innervation. To translate these findings into feasible clinical application, we evaluated the effects of Shh gene transfer to salivary glands of wild-type mice on irradiation-induced hyposalivation. Shh or control GFP gene was delivered by noninvasive retrograde ductal instillation of corresponding adenoviral vectors. In both male and female mice, Shh gene delivery efficiently activated Hedgehog/Gli signaling, and significantly improved stimulated saliva secretion and preserved saliva-producing acinar cells after irradiation. In addition to preserving parasympathetic innervation through induction of neurotrophic factors, Shh gene delivery also alleviated the irradiation damage of the microvasculature, likely via inducing angiogenic factors, but did not expand the progeny of cells responsive to Hedgehog/Gli signaling. These data indicate that transient activation of the Hedgehog pathway by gene delivery is promising to rescue salivary function after irradiation in both sexes, and the Hedgehog/Gli pathway may function mainly in cell nonautonomous manners to achieve the rescue effect.

  1. The usefulness of interpectoral block as an analgesic technique in breast cancer surgery.

    PubMed

    Ortiz de la Tabla González, R; Gómez Reja, P; Moreno Rey, D; Pérez Naranjo, C; Sánchez Martín, I; Echevarría Moreno, M

    2018-04-01

    To compare the analgesic efficacy of continuous interpectoral block (CIPB) compared to intravenous analgesia (IV) after breast surgery. A prospective, comparative and randomised study of women aged from 18-75years, ASAI-III, operated for breast cancer. In group1 (CIPB) after general anaesthetic, an ultrasound-guided interpectoral catheter was placed and 30mL of 0.5% ropivacaine was administered through it. In the event of an increase in heart rate and blood pressure >15% after the surgical incision, intravenous fentanyl 1μg·kg -1 was administered, repeating the dose as necessary. In the postoperative period, perfusion of ropivacaine 0.2% 5mL·h -1 ; with PCA bolus 5mL/30minutes was administered through the catheter for 24hours and rescue analgesia prescribed with 5mg subcutaneous morphine chloride. In group2 (IV), after induction of general anaesthesia, intravenous fentanyl was administered in the same way as in the other group. The patients received metamizole 2g with dexketoprofen 50mg and ondansetron 4mg postoperatively followed by perfusion of metamizole 4%, tramadol 0.2% and ondansetron 0.08% 2ml·h -1 ; with PCA bolus 2mL/20min for 24hours. The same rescue analgesia was prescribed. The principal variables recorded were pain at rest and during movement, according to a simple verbal scale (VAS 0-10) and the rescue analgesia required on discharge from recovery, at 12 and at 24hours. 137 patients were included: 81 in group1 (59.12%) and 56 in group2 (40.87%). No significant differences were observed in the analgesia between either group, but differences were observed in the dose of intraoperative fentanyl (P<.05). Differences that were not significant were observed in the rescue analgesia required on recovery (10% fewer on group1). Both techniques provided effective postoperative analgesia, but the CIPB group required significantly less intraoperative fentanyl. Copyright © 2017 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

  2. 30 CFR 48.5 - Training of new miners; minimum courses of instruction; hours of instruction.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... the procedures for reporting hazards. (2) Self-rescue and respiratory devices. The course shall be... use, care, and maintenance of self-rescue and respiratory devices used at the mine; (ii) Hands-on... checkout system in effect at the mine; the procedures for riding on and in mine conveyances; the controls...

  3. 30 CFR 48.5 - Training of new miners; minimum courses of instruction; hours of instruction.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... the procedures for reporting hazards. (2) Self-rescue and respiratory devices. The course shall be... use, care, and maintenance of self-rescue and respiratory devices used at the mine; (ii) Hands-on... checkout system in effect at the mine; the procedures for riding on and in mine conveyances; the controls...

  4. 30 CFR 48.5 - Training of new miners; minimum courses of instruction; hours of instruction.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... the procedures for reporting hazards. (2) Self-rescue and respiratory devices. The course shall be... use, care, and maintenance of self-rescue and respiratory devices used at the mine; (ii) Hands-on... checkout system in effect at the mine; the procedures for riding on and in mine conveyances; the controls...

  5. 30 CFR 48.5 - Training of new miners; minimum courses of instruction; hours of instruction.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... the procedures for reporting hazards. (2) Self-rescue and respiratory devices. The course shall be... use, care, and maintenance of self-rescue and respiratory devices used at the mine; (ii) Hands-on... checkout system in effect at the mine; the procedures for riding on and in mine conveyances; the controls...

  6. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Raymond, David W.; Gaither, Katherine N.; Polsky, Yarom

    Sandia National Laboratories (Sandia) has a long history in developing compact, mobile, very high-speed drilling systems and this technology could be applied to increasing the rate at which boreholes are drilled during a mine accident response. The present study reviews current technical approaches, primarily based on technology developed under other programs, analyzes mine rescue specific requirements to develop a conceptual mine rescue drilling approach, and finally, proposes development of a phased mine rescue drilling system (MRDS) that accomplishes (1) development of rapid drilling MRDS equipment; (2) structuring improved web communication through the Mine Safety & Health Administration (MSHA) web site;more » (3) development of an improved protocol for employment of existing drilling technology in emergencies; (4) deployment of advanced technologies to complement mine rescue drilling operations during emergency events; and (5) preliminary discussion of potential future technology development of specialized MRDS equipment. This phased approach allows for rapid fielding of a basic system for improved rescue drilling, with the ability to improve the system over time at a reasonable cost.« less

  7. Rescue of volume-regulated anion current by bestrophin mutants with altered charge selectivity.

    PubMed

    Chien, Li-Ting; Hartzell, H Criss

    2008-11-01

    Mutations in human bestrophin-1 are linked to various kinds of retinal degeneration. Although it has been proposed that bestrophins are Ca(2+)-activated Cl(-) channels, definitive proof is lacking partly because mice with the bestrophin-1 gene deleted have normal Ca(2+)-activated Cl(-) currents. Here, we provide compelling evidence to support the idea that bestrophin-1 is the pore-forming subunit of a cell volume-regulated anion channel (VRAC) in Drosophila S2 cells. VRAC was abolished by treatment with RNAi to Drosophila bestrophin-1. VRAC was rescued by overexpressing bestrophin-1 mutants with altered biophysical properties and responsiveness to sulfhydryl reagents. In particular, the ionic selectivity of the F81C mutant changed from anionic to cationic when the channel was treated with the sulfhydryl reagent, sodium (2-sulfonatoethyl) methanethiosulfonate (MTSES(-)) (P(Cs)/P(Cl) = 0.25 for native and 2.38 for F81C). The F81E mutant was 1.3 times more permeable to Cs(+) than Cl(-). The finding that VRAC was rescued by F81C and F81E mutants with different biophysical properties shows that bestrophin-1 is a VRAC in S2 cells and not simply a regulator or an auxiliary subunit. F81C overexpressed in HEK293 cells also exhibits a shift of ionic selectivity after MTSES(-) treatment, although the effect is quantitatively smaller than in S2 cells. To test whether bestrophins are VRACs in mammalian cells, we compared VRACs in peritoneal macrophages from wild-type mice and mice with both bestrophin-1 and bestrophin-2 disrupted (best1(-/-)/best2(-/-)). VRACs were identical in wild-type and best1(-/-)/best2(-/-) mice, showing that bestrophins are unlikely to be the classical VRAC in mammalian cells.

  8. 46 CFR 160.156-11 - Fabrication of prototype rescue boats and fast rescue boats for approval.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 6 2012-10-01 2012-10-01 false Fabrication of prototype rescue boats and fast rescue boats for approval. 160.156-11 Section 160.156-11 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY... Boats and Fast Rescue Boats (SOLAS) § 160.156-11 Fabrication of prototype rescue boats and fast rescue...

  9. 46 CFR 160.156-13 - Approval inspections and tests for prototype rescue boats and fast rescue boats.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... boats and fast rescue boats. 160.156-13 Section 160.156-13 Shipping COAST GUARD, DEPARTMENT OF HOMELAND... EQUIPMENT Rescue Boats and Fast Rescue Boats (SOLAS) § 160.156-13 Approval inspections and tests for prototype rescue boats and fast rescue boats. (a) After the Commandant notifies the manufacturer that the...

  10. 46 CFR 160.156-11 - Fabrication of prototype rescue boats and fast rescue boats for approval.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 6 2014-10-01 2014-10-01 false Fabrication of prototype rescue boats and fast rescue boats for approval. 160.156-11 Section 160.156-11 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY... Boats and Fast Rescue Boats (SOLAS) § 160.156-11 Fabrication of prototype rescue boats and fast rescue...

  11. 46 CFR 160.156-11 - Fabrication of prototype rescue boats and fast rescue boats for approval.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 6 2013-10-01 2013-10-01 false Fabrication of prototype rescue boats and fast rescue boats for approval. 160.156-11 Section 160.156-11 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY... Boats and Fast Rescue Boats (SOLAS) § 160.156-11 Fabrication of prototype rescue boats and fast rescue...

  12. 46 CFR 160.156-13 - Approval inspections and tests for prototype rescue boats and fast rescue boats.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... boats and fast rescue boats. 160.156-13 Section 160.156-13 Shipping COAST GUARD, DEPARTMENT OF HOMELAND... EQUIPMENT Rescue Boats and Fast Rescue Boats (SOLAS) § 160.156-13 Approval inspections and tests for prototype rescue boats and fast rescue boats. (a) After the Commandant notifies the manufacturer that the...

  13. 46 CFR 160.156-13 - Approval inspections and tests for prototype rescue boats and fast rescue boats.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... boats and fast rescue boats. 160.156-13 Section 160.156-13 Shipping COAST GUARD, DEPARTMENT OF HOMELAND... EQUIPMENT Rescue Boats and Fast Rescue Boats (SOLAS) § 160.156-13 Approval inspections and tests for prototype rescue boats and fast rescue boats. (a) After the Commandant notifies the manufacturer that the...

  14. Carprofen provides better post-operative analgesia than tramadol in dogs after enucleation: A randomized, masked clinical trial

    PubMed Central

    Delgado, Cherlene; Bentley, Ellison; Hetzel, Scott; Smith, Lesley J

    2015-01-01

    Objective To compare analgesia provided by carprofen or tramadol in dogs after enucleation. Design Randomized, masked trial Animals Forty-three dogs Procedures Client-owned dogs admitted for routine enucleation were randomly assigned to receive either carprofen or tramadol orally 2 hours prior to surgery and 12 hours after the first dose. Dogs were scored for pain at baseline, and postoperatively at 0.25, 0.5, 1, 2, 4, 6, 8, 24, and 30 hours after extubation. Dogs received identical premedication and inhalation anesthesia regimens, including premedication with hydromorphone. If the total pain score was ≥9, if there was a score ≥ 3 in any one category, or if the visual analog scale score (VAS) was ≥35 combined with a palpation score of >0, rescue analgesia (hydromorphone) was administered and treatment failure was recorded. Characteristics between groups were compared with a Student’s t-test and Fisher’s exact test. The incidence of rescue was compared between groups using a log rank test. Pain scores and VAS scores between groups were compared using repeated measures ANOVA. Results There was no difference in age (p=0.493), gender (p=0.366) or baseline pain scores (p=0.288) between groups. Significantly more dogs receiving tramadol required rescue analgesia (6/21) compared to dogs receiving carprofen (1/22; p=0.035). Pain and VAS scores decreased linearly over time (p=0.038, p<0.001, respectively). There were no significant differences in pain (p=0.915) or VAS scores (p=0.372) between groups at any time point (dogs were excluded from analysis after rescue). Conclusions and Clinical Relevance This study suggests that carprofen, with opioid premedication, provides more effective post-operative analgesia than tramadol in dogs undergoing enucleation. PMID:25459482

  15. Rate of bleeding-related episodes in adult patients with primary immune thrombocytopenia: a retrospective cohort study using a large administrative medical claims database in the US.

    PubMed

    Altomare, Ivy; Cetin, Karynsa; Wetten, Sally; Wasser, Jeffrey S

    2016-01-01

    Immune thrombocytopenia (ITP) is a rare disorder characterized by low platelet counts and an increased tendency to bleed. The goal of ITP therapy is to treat or prevent bleeding. Actual rates of bleeding are unknown. Clinical trial data may not reflect real-world bleeding rates because of the inclusion of highly refractory patients and more frequent use of rescue therapy. We used administrative medical claims data in the US to examine the occurrence of bleeding-related episodes (BREs) - a composite end point including bleeding and/or rescue therapy use - in adults diagnosed with primary ITP (2008-2012). BRE rates were calculated overall and by ITP phase and splenectomy status. Patients were followed from ITP diagnosis until death, disenrollment from the health plan, or June 30, 2013, whichever came first. We identified 6,651 adults diagnosed with primary ITP over the study period (median age: 53 years; 59% female). During 13,064 patient-years of follow-up, 3,768 patients (57%) experienced ≥1 BRE (1.08 BREs per patient-year; 95% confidence interval: 1.06-1.10). The majority (58%) of BREs consisted of rescue therapy use only. Common bleeding types were gastrointestinal hemorrhage, hematuria, ecchymosis, and epistaxis. Intracranial hemorrhage was reported in 74 patients (1%). Just over 7% of patients underwent splenectomy. Newly diagnosed and splenectomized patients had elevated BRE rates. We provide current real-world estimates of BRE rates in adults with primary ITP. The majority of ITP patients experienced ≥1 BRE, and over half were defined by rescue therapy use alone. This demonstrates the importance of examining both bleeding and rescue therapy use to fully assess disease burden.

  16. Pharmacological Correction of Trafficking Defects in ATP-sensitive Potassium Channels Caused by Sulfonylurea Receptor 1 Mutations.

    PubMed

    Martin, Gregory M; Rex, Emily A; Devaraneni, Prasanna; Denton, Jerod S; Boodhansingh, Kara E; DeLeon, Diva D; Stanley, Charles A; Shyng, Show-Ling

    2016-10-14

    ATP-sensitive potassium (K ATP ) channels play a key role in mediating glucose-stimulated insulin secretion by coupling metabolic signals to β-cell membrane potential. Loss of K ATP channel function due to mutations in ABCC8 or KCNJ11, genes encoding the sulfonylurea receptor 1 (SUR1) or the inwardly rectifying potassium channel Kir6.2, respectively, results in congenital hyperinsulinism. Many SUR1 mutations prevent trafficking of channel proteins from the endoplasmic reticulum to the cell surface. Channel inhibitors, including sulfonylureas and carbamazepine, have been shown to correct channel trafficking defects. In the present study, we identified 13 novel SUR1 mutations that cause channel trafficking defects, the majority of which are amenable to pharmacological rescue by glibenclamide and carbamazepine. By contrast, none of the mutant channels were rescued by K ATP channel openers. Cross-linking experiments showed that K ATP channel inhibitors promoted interactions between the N terminus of Kir6.2 and SUR1, whereas channel openers did not, suggesting the inhibitors enhance intersubunit interactions to overcome channel biogenesis and trafficking defects. Functional studies of rescued mutant channels indicate that most mutants rescued to the cell surface exhibited WT-like sensitivity to ATP, MgADP, and diazoxide. In intact cells, recovery of channel function upon trafficking rescue by reversible sulfonylureas or carbamazepine was facilitated by the K ATP channel opener diazoxide. Our study expands the list of K ATP channel trafficking mutations whose function can be recovered by pharmacological ligands and provides further insight into the structural mechanism by which channel inhibitors correct channel biogenesis and trafficking defects. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  17. Solving an emergency rescue materials problem under the joint reserves mode of government and framework agreement suppliers

    PubMed Central

    Sun, Xiao-Qing; Zhu, Rui; Li, Ming; Miao, Wang

    2017-01-01

    Emergency rescue material reserves are vital for the success of emergency rescue activities. In this study, we consider a situation where a government owned distribution center and framework agreement suppliers jointly store emergency rescue materials. Using a scenario-based approach to represent demand uncertainty, we propose a comprehensive transportation pattern for the following supply chain: “suppliers—government distribution center—disaster area.” Using a joint reserves model that includes the government and framework agreement suppliers, we develop a non-linear mathematic model that determines the choices of the framework suppliers, the corresponding optimal commitment quantities, and the quantity of materials that are stored at a government distribution center. Finally, we use IBM ILOG CPLEX to solve the numerical examples to verify the effectiveness of the mode and perform sensitivity analyses on the relevant parameters. PMID:29077722

  18. Final Environmental Assessment: Proposed Fire Crash Rescue Station, Hill Air Force Base, Utah

    DTIC Science & Technology

    2008-10-02

    storage shed (Building 16) would be demolished and converted to parking ( see Figure 1 for the approximate locations). 1.3 Need for the Action The...existing facilities ( see Section 2.3.3.1), and other potential locations for siting the proposed fire crash rescue station ( see Section 2.3.3.2). 2.3...during scoping meetings, but eliminated from detailed consideration ( see Section 1.7.3) include: • geology and surface soils (seismicity, topography

  19. A Novel Expression Cassette of Lyssavirus Shows that the Distantly Related Mokola Virus Can Rescue a Defective Rabies Virus Genome

    PubMed Central

    Le Mercier, Philippe; Jacob, Yves; Tanner, Kyle; Tordo, Noël

    2002-01-01

    By comparing three expression vectors for the rabies virus (Rv) minigenome, we show that the characteristic of the Rv RNA is important for efficient rescue despite its not being crucial for replication. Moreover, we show that the coexpression of the viral proteins from helper Rv and Mokola virus could rescue the Rv minigenome while Rv-related European bat lyssavirus 1 could not, suggesting that the signals controlling transcription and replication are conserved in the distantly related Rv and Mokola virus. PMID:11799201

  20. Efficacy of Magnesium Sulphate as an Adjunct to Ropivacaine in Local Infiltration for Postoperative Pain Following Lower Segment Caesarean Section.

    PubMed

    Kundra, Sandeep; Singh, Rupinder M; Singh, Gaganpreet; Singh, Tania; Jarewal, Vikrant; Katyal, Sunil

    2016-04-01

    Intravenous and peri-articular magnesium has been shown to reduce perioperative analgesic consumption. With this background, subcutaneous infiltration was hypothesized to potentiate the subcutaneous infiltration of local anaesthetic agent. To comparatively evaluate the efficacy of magnesium sulphate as an adjunct to ropivacaine in local infiltration for postoperative pain following lower segment cesarean section. Sixty parturients undergoing cesarean delivery were randomized to either group A or B in a double blinded manner. After uterine and muscle closure but before skin closure, Group A was administered local subcutaneous wound infiltration of Injection (Inj) ropivacaine 0.75% 150 milligram (mg) or 20 millilitres(ml) whereas, group B patients were given a local subcutaneous wound infiltration of Inj magnesium sulphate 750 mg (1.5 ml of Inj 50% Magnesium sulphate) added to Inj ropivacaine 0.75% (18.5 ml) making a total volume of 20 ml. In postoperative period, Heart rate (HR), Mean Arterial Pressure (MAP), Visual Analogue Score (VAS), supplemental analgesic consumption and timing of each subsequent analgesic was noted for the initial 24 hours. There was no difference in the timings for the requirement of first Intravenous (IV) rescue analgesic among both the groups (p=0.279). However, the need for 2(nd) and 3(rd) doses of rescue analgesics was significantly later in group B and the difference was statistically significant with p-value of 0.034 and 0.031 respectively. The number of patients who were administered 2(nd), 3(rd) and 4(th) doses of rescue analgesics was significantly greater in group A as compared to group B. None of the patients in group B needed more than 4 doses of rescue analgesia while in group A, 5 patients were administered a rescue analgesic for 5(th) time. The cumulative analgesic requirement in the initial 24 hours was also greater in group A as compared to group B and the difference was statistically significant (p =0.01). The incidence of adverse effects was similar in both the groups. Subcutaneous infiltration of magnesium along with local anaesthetic prolongs the analgesic efficacy of local anaesthetic and is not associated with any significant adverse effects.

  1. A Strategy To Isolate Modifiers of Caenorhabditis elegans Lethal Mutations: Investigating the Endoderm Specifying Ability of the Intestinal Differentiation GATA Factor ELT-2.

    PubMed

    Wiesenfahrt, Tobias; Duanmu, Jingjie; Snider, Frances; Moerman, Don; Au, Vinci; Li-Leger, Erica; Flibotte, Stephane; Parker, Dylan M; Marshall, Craig J; Nishimura, Erin Osborne; Mains, Paul E; McGhee, James D

    2018-05-04

    The ELT-2 GATA factor normally functions in differentiation of the C. elegans endoderm, downstream of endoderm specification. We have previously shown that, if ELT-2 is expressed sufficiently early, it is also able to specify the endoderm and to replace all other members of the core GATA-factor transcriptional cascade (END-1, END-3, ELT-7). However, such rescue requires multiple copies (and presumably overexpression) of the end-1p :: elt-2 cDNA transgene; a single copy of the transgene does not rescue. We have made this observation the basis of a genetic screen to search for genetic modifiers that allow a single copy of the end-1p :: elt-2 cDNA transgene to rescue the lethality of the end-1 end-3 double mutant. We performed this screen on a strain that has a single copy insertion of the transgene in an end-1 end-3 background. These animals are kept alive by virtue of an extrachromosomal array containing multiple copies of the rescuing transgene; the extrachromosomal array also contains a toxin under heat shock control to counterselect for mutagenized survivors that have been able to lose the rescuing array. A screen of ∼14,000 mutagenized haploid genomes produced 17 independent surviving strains. Whole genome sequencing was performed to identify genes that incurred independent mutations in more than one surviving strain. The C. elegans gene tasp-1 was mutated in four independent strains. tasp-1 encodes the C. elegans homolog of Taspase, a threonine-aspartic acid protease that has been found, in both mammals and insects, to cleave several proteins involved in transcription, in particular MLL1/trithorax and TFIIA. A second gene, pqn-82 , was mutated in two independent strains and encodes a glutamine-asparagine rich protein. tasp-1 and pqn-82 were verified as loss-of-function modifiers of the end-1p :: elt-2 transgene by RNAi and by CRISPR/Cas9-induced mutations. In both cases, gene loss leads to modest increases in the level of ELT-2 protein in the early endoderm although ELT-2 levels do not strictly correlate with rescue. We suggest that tasp-1 and pqn-82 represent a class of genes acting in the early embryo to modulate levels of critical transcription factors or to modulate the responsiveness of critical target genes. The screen's design, rescuing lethality with an extrachromosomal transgene followed by counterselection, has a background survival rate of <10 -4 without mutagenesis and should be readily adapted to the general problem of identifying suppressors of C. elegans lethal mutations. Copyright © 2018 Wiesenfahrt et al.

  2. DRAGON ROUGE: The Rescue of Hostages in the Congo

    DTIC Science & Technology

    1980-01-01

    the colonial period. In this study the names in effect in 1964 will be used; however, the initial listings and Map 1 will contain both names. 2 OMMO...recently, in its traditionally skull-bashing manner, against unruly nationalist demonstrators. The perceived loyalty and effectiveness of the Force was... effectiveness of his expanding gendarmerie, he committed the ultimate sin for an African nationalist: he hired white mercenaries. Now, Tshombe was perceived not

  3. An Indel Polymorphism in the Hybrid Incompatibility Gene Lethal Hybrid Rescue of Drosophila Is Functionally Relevant

    PubMed Central

    Maheshwari, Shamoni; Barbash, Daniel A.

    2012-01-01

    Hybrid incompatibility (HI) genes are frequently observed to be rapidly evolving under selection. This observation has led to the attractive conjecture that selection-derived protein-sequence divergence is culpable for incompatibilities in hybrids. The Drosophila simulans HI gene Lethal hybrid rescue (Lhr) is an intriguing case, because despite having experienced rapid sequence evolution, its HI properties are a shared function inherited from the ancestral state. Using an unusual D. simulans Lhr hybrid rescue allele, Lhr2, we here identify a conserved stretch of 10 amino acids in the C terminus of LHR that is critical for causing hybrid incompatibility. Altering these 10 amino acids weakens or abolishes the ability of Lhr to suppress the hybrid rescue alleles Lhr1 or Hmr1, respectively. Besides single-amino-acid substitutions, Lhr orthologs differ by a 16-aa indel polymorphism, with the ancestral deletion state fixed in D. melanogaster and the derived insertion state at very high frequency in D. simulans. Lhr2 is a rare D. simulans allele that has the ancestral deletion state of the 16-aa polymorphism. Through a series of transgenic constructs we demonstrate that the ancestral deletion state contributes to the rescue activity of Lhr2. This indel is thus a polymorphism that can affect the HI function of Lhr. PMID:22865735

  4. [Thermal injuries in the OEAMTC air rescue service. Epidemiological characteristics of burns/scalds in children and adults].

    PubMed

    Selig, H F; Nagele, P; Lumenta, D B; Voelckel, W G; Trimmel, H; Hüpfl, M; Kamolz, L P

    2014-04-01

    Few data exist on the epidemiological characteristics of thermal injuries in prehospital emergency care, especially in the context of air rescue. Therefore, this study aimed to analyze the epidemiology of pediatric and adult thermal injuries in the helicopter emergency medical service (HEMS) run by the Austrian Automobile Motorcycle Touring Club (OEAMTC) air rescue service from an almost nationwide sample. All OEAMTC-HEMS rescue missions flown for thermal injuries in 2009 were retrospectively reviewed. Primary (n=88) and secondary missions (n=17) were collated and all primary missions were analyzed in detail. In total 71 out of 16,100 (0.4 %) primary HEMS rescue missions were for patients suffering from burns or scalds (children n=27, adults n=44). The proportion of major burns (burns covering >20 % of the total body surface area) was 40.7 % in children and 54.5 % in adults, 44 (62 %) burn/scald injuries were related to the head/neck, 37 (52.1 %) to the upper limbs and 10 (14.1 %) to the anogenital region. More than half of the victims (63.4%) suffered potentially life-threatening injury. In HEMS thermal injuries are infrequent but mostly life-threatening. Differences in epidemiological characteristics of pediatric and adult burns/scalds may have important operational, training and public health implications.

  5. A Prospective, Observational Study to Evaluate the Role of Gabapentin as Preventive Analgesic in Thyroidectomy under General Anesthesia

    PubMed Central

    Hema, Vadakkoot Raghavan; Ramadas, Konnanath Thekkethil; Biji, Kannammadathy Poulose; Indu, Suseela; Arun, Aravind

    2017-01-01

    Background: Effective management of postoperative pain is a part of well-organized perioperative care, which helps in reduced morbidity and improved patient satisfaction. Preventive analgesia can reduce acute and chronic pain by blocking the noxious inputs to pain pathways, preventing sensitization. Studies have reported efficacy of gabapentin as a preventive analgesic in perioperative pain. In this study, we aimed to determine whether preoperative gabapentin reduced postoperative pain and tramadol consumption after thyroidectomy under general anesthesia. Materials and Methods: Sixty patients scheduled for thyroidectomy were allocated to two groups of thirty each for this prospective, observational study. Patients in Group A and Group B received oral gabapentin 600 mg (6 × 10−4 kg) and diazepam 10 mg (1 × 10−5 kg), respectively, 2 h prior to surgery. Tramadol was given as rescue analgesic for postoperative pain with a verbal rating score of two. The analgesic efficacy of preoperative gabapentin was assessed in terms of postoperative pain scores at rest or swallowing, time to first rescue analgesic, and total tramadol consumption for 24 h. Ramsay sedation score and side effects of drug were also looked into. Results: Postoperative pain scores and total tramadol consumption were significantly lower in Group A during 24 h (P = 0.00). Time to first rescue analgesic was significantly prolonged in Group A (P = 0.001). Side effects were comparable. Conclusion: Oral gabapentin is effective as a preventive analgesic in reducing postoperative pain and tramadol consumption after thyroidectomy under general anesthesia. PMID:28928577

  6. Failure to Rescue, Rescue Surgery and Centralization of Postoperative Complications: A Challenge for General and Acute Care Surgeons.

    PubMed

    Zago, Mauro; Bozzo, Samantha; Carrara, Giulia; Mariani, Diego

    2017-01-01

    To explore the current literature on the failure to rescue and rescue surgery concepts, to identify the key items for decreasing the failure to rescue rate and improve outcome, to verify if there is a rationale for centralization of patients suffering postoperative complications. There is a growing awareness about the need to assess and measure the failure to rescue rate, on institutional, regional and national basis. Many factors affect failure to rescue, and all should be individually analyzed and considered. Rescue surgery is one of these factors. Rescue surgery assumes an acute care surgery background. Measurement of failure to rescue rate should become a standard for quality improvement programs. Implementation of all clinical and organizational items involved is the key for better outcomes. Preparedness for rescue surgery is a main pillar in this process. Centralization of management, audit, and communication are important as much as patient centralization. Celsius.

  7. The effect of CSF-1 administration on lung maturation in a mouse model of neonatal hyperoxia exposure.

    PubMed

    Jones, Christina V; Alikhan, Maliha A; O'Reilly, Megan; Sozo, Foula; Williams, Timothy M; Harding, Richard; Jenkin, Graham; Ricardo, Sharon D

    2014-09-06

    Lung immaturity due to preterm birth is a significant complication affecting neonatal health. Despite the detrimental effects of supplemental oxygen on alveolar formation, it remains an important treatment for infants with respiratory distress. Macrophages are traditionally associated with the propagation of inflammatory insults, however increased appreciation of their diversity has revealed essential functions in development and regeneration. Macrophage regulatory cytokine Colony-Stimulating Factor-1 (CSF-1) was investigated in a model of neonatal hyperoxia exposure, with the aim of promoting macrophages associated with alveologenesis to protect/rescue lung development and function. Neonatal mice were exposed to normoxia (21% oxygen) or hyperoxia (Hyp; 65% oxygen); and administered CSF-1 (0.5 μg/g, daily × 5) or vehicle (PBS) in two treatment regimes; 1) after hyperoxia from postnatal day (P)7-11, or 2) concurrently with five days of hyperoxia from P1-5. Lung structure, function and macrophages were assessed using alveolar morphometry, barometric whole-body plethysmography and flow cytometry. Seven days of hyperoxia resulted in an 18% decrease in body weight and perturbation of lung structure and function. In regime 1, growth restriction persisted in the Hyp + PBS and Hyp + CSF-1 groups, although perturbations in respiratory function were resolved by P35. CSF-1 increased CSF-1R+/F4/80+ macrophage number by 34% at P11 compared to Hyp + PBS, but was not associated with growth or lung structural rescue. In regime 2, five days of hyperoxia did not cause initial growth restriction in the Hyp + PBS and Hyp + CSF-1 groups, although body weight was decreased at P35 with CSF-1. CSF-1 was not associated with increased macrophages, or with functional perturbation in the adult. Overall, CSF-1 did not rescue the growth and lung defects associated with hyperoxia in this model; however, an increase in CSF-1R+ macrophages was not associated with an exacerbation of lung injury. The trophic functions of macrophages in lung development requires further elucidation in order to explore macrophage modulation as a strategy for promoting lung maturation.

  8. Impaired tissue growth is mediated by checkpoint kinase 1 (CHK1) in the integrated stress response

    PubMed Central

    Malzer, Elke; Daly, Marie-Louise; Moloney, Aileen; Sendall, Timothy J.; Thomas, Sally E.; Ryder, Edward; Ryoo, Hyung Don; Crowther, Damian C.; Lomas, David A.; Marciniak, Stefan J.

    2010-01-01

    The integrated stress response (ISR) protects cells from numerous forms of stress and is involved in the growth of solid tumours; however, it is unclear how the ISR acts on cellular proliferation. We have developed a model of ISR signalling with which to study its effects on tissue growth. Overexpression of the ISR kinase PERK resulted in a striking atrophic eye phenotype in Drosophila melanogaster that could be rescued by co-expressing the eIF2α phosphatase GADD34. A genetic screen of 3000 transposon insertions identified grapes, the gene that encodes the Drosophila orthologue of checkpoint kinase 1 (CHK1). Knockdown of grapes by RNAi rescued eye development despite ongoing PERK activation. In mammalian cells, CHK1 was activated by agents that induce ER stress, which resulted in a G2 cell cycle delay. PERK was both necessary and sufficient for CHK1 activation. These findings indicate that non-genotoxic misfolded protein stress accesses DNA-damage-induced cell cycle checkpoints to couple the ISR to cell cycle arrest. PMID:20682638

  9. Genetic or pharmacological activation of the Drosophila PGC-1α ortholog spargel rescues the disease phenotypes of genetic models of Parkinson's disease.

    PubMed

    Ng, Chee-Hoe; Basil, Adeline H; Hang, Liting; Tan, Royston; Goh, Kian-Leong; O'Neill, Sharon; Zhang, Xiaodong; Yu, Fengwei; Lim, Kah-Leong

    2017-07-01

    Despite intensive research, the etiology of Parkinson's disease (PD) remains poorly understood and the disease remains incurable. However, compelling evidence gathered over decades of research strongly support a role for mitochondrial dysfunction in PD pathogenesis. Related to this, PGC-1α, a key regulator of mitochondrial biogenesis, has recently been proposed to be an attractive target for intervention in PD. Here, we showed that silencing of expression of the Drosophila PGC-1α ortholog spargel results in PD-related phenotypes in flies and also seem to negate the effects of AMPK activation, which we have previously demonstrated to be neuroprotective, that is, AMPK-mediated neuroprotection appears to require PGC-1α. Importantly, we further showed that genetic or pharmacological activation of the Drosophila PGC-1α ortholog spargel is sufficient to rescue the disease phenotypes of Parkin and LRRK2 genetic fly models of PD, thus supporting the proposed use of PGC-1α-related strategies for neuroprotection in PD. Copyright © 2017 National Neuroscience Institute. Published by Elsevier Inc. All rights reserved.

  10. Breeding for seedless grapes using Chinese wild Vitis spp. II. In vitro embryo rescue and plant development.

    PubMed

    Ji, Wei; Wang, Yuejin

    2013-12-01

    Since 1982, the embryo rescue technique has been widely applied to embryo germination of stenospermic grapes in cross-breeding programmes. This project aimed to: (1) use embryos to breed new seedless cultivars of Vitis vinifera as the female parents utilising wild Chinese Vitis spp. as the male parents; and (2) develop an efficient method for in vitro embryo rescue and plant development. Among the different genotypes, the productions of hybrid plants were significantly different, ranged from 21.1% ('Ruby Seedless' × 'Beichun') to only 1.1% ('Pink Seedless' × 'Beichun'), except for the combinations from which no surviving seedlings were obtained. We collected hybridisation fruits from 28 June to 3 August, and obtained their best sampling times described within days after flowering. The highest rates of embryo formation (24.3%) and plant development (91.4%) were found when ovules of 'Ruby Seedless' were cultured in MM4 + 500 mg L(-1) mashed banana. Seven new hybrids of V. vinifera with wild Chinese Vitis spp. were obtained. As a result of early nuclear-free character identification, 17 seedless grape lines were obtained. An efficient system of seedless grape breeding through embryo rescue was also established. © 2013 Society of Chemical Industry.

  11. Late-onset cone photoreceptor degeneration induced by R172W mutation in Rds and partial rescue by gene supplementation.

    PubMed

    Conley, Shannon; Nour, May; Fliesler, Steven J; Naash, Muna I

    2007-12-01

    R172W is a common mutation in the human retinal degeneration slow (RDS) gene, associated with a late-onset dominant macular dystrophy. In this study, the authors characterized a mouse model that closely mimics the human phenotype and tested the feasibility of gene supplementation as a disease treatment strategy. Transgenic mouse lines carrying the R172W mutation were generated. The retinal phenotype associated with this mutation in a low-expresser line (L-R172W) was examined, both structurally (histology with correlative immunohistochemistry) and functionally (electroretinography). By examining animals over time and with various rds genetic backgrounds, the authors evaluated the dominance of the defect. To assess the efficacy of gene transfer therapy as a treatment for this defect, a previously characterized transgenic line expressing the normal mouse peripherin/Rds (NMP) was crossed with a higher-expresser Rds line harboring the R172W mutation (H-R172W). Functional, structural, and biochemical analyses were used to assess rescue of the retinal disease phenotype. In the wild-type (WT) background, L-R172W mice exhibited late-onset (12-month) dominant cone degeneration without any apparent effect on rods. The degeneration was slightly accelerated (9 months) in the rds(+/-) background. L-R172W retinas did not form outer segments in the absence of endogenous Rds. With use of the H-R172W line on an rds(+/-) background for proof-of-principle genetic supplementation studies, the NMP transgene product rescued rod and cone functional defects and supported outer segment integrity up to 3 months of age, but the rescue effect did not persist in older (11-month) animals. The R172W mutation leads to dominant cone degeneration in the mouse model, regardless of the expression level of the transgene. In contrast, effects of the mutation on rods are dose dependent, underscoring the usefulness of the L-R172W line as a faithful model of the human phenotype. This model may prove helpful in future studies on the mechanisms of cone degeneration and for elucidating the different roles of Rds in rods and cones. This study provides evidence that Rds genetic supplementation can be used to partially rescue visual function. Although this strategy is capable of rescuing haploinsufficiency, it does not rescue the long-term degeneration associated with a gain-of-function mutation.

  12. 78 FR 35974 - Proposed Information Collection; Comment Request; Coal Mine Rescue Teams; Arrangements for...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-14

    ... Request; Coal Mine Rescue Teams; Arrangements for Emergency Medical Assistance and Transportation for... Part 49, Mine Rescue Teams, Subpart B--Mine Rescue Teams for Underground Coal Mines, sets standards related to the availability of mine rescue teams; alternate mine rescue capability for small and remote...

  13. Advanced missions safety. Volume 3: Appendices. Part 1: Space shuttle rescue capability

    NASA Technical Reports Server (NTRS)

    1972-01-01

    The space shuttle rescue capability is analyzed as a part of the advanced mission safety study. The subjects discussed are: (1) mission evaluation, (2) shuttle configurations and performance, (3) performance of shuttle-launched tug system, (4) multiple pass grazing reentry from lunar orbit, (5) ground launched ascent and rendezvous time, (6) cost estimates, and (7) parallel-burn space shuttle configuration.

  14. Farnesyltransferase haplodeficiency reduces neuropathology and rescues cognitive function in a mouse model of Alzheimer disease.

    PubMed

    Cheng, Shaowu; Cao, Dongfeng; Hottman, David A; Yuan, LiLian; Bergo, Martin O; Li, Ling

    2013-12-13

    Isoprenoids and prenylated proteins have been implicated in the pathophysiology of Alzheimer disease (AD), including amyloid-β precursor protein metabolism, Tau phosphorylation, synaptic plasticity, and neuroinflammation. However, little is known about the relative importance of the two protein prenyltransferases, farnesyltransferase (FT) and geranylgeranyltransferase-1 (GGT), in the pathogenesis of AD. In this study, we defined the impact of deleting one copy of FT or GGT on the development of amyloid-β (Aβ)-associated neuropathology and learning/memory impairments in APPPS1 double transgenic mice, a well established model of AD. Heterozygous deletion of FT reduced Aβ deposition and neuroinflammation and rescued spatial learning and memory function in APPPS1 mice. Heterozygous deletion of GGT reduced the levels of Aβ and neuroinflammation but had no impact on learning and memory. These results document that farnesylation and geranylgeranylation play differential roles in AD pathogenesis and suggest that specific inhibition of protein farnesylation could be a potential strategy for effectively treating AD.

  15. Fitness consequences of nest desertion in an endangered host, the least Bell's vireo

    USGS Publications Warehouse

    Kus, Barbara E.

    2002-01-01

    Recent analyses of the impact of cowbird parasitism on host productivity suggest that while parasitism reduces productivity on a per-nest basis, the ability of pairs to desert parasitized nests and renest allows them to achieve productivity comparable to that of unparasitized pairs. This has implications for the management of several endangered species that are highly vulnerable to parasitism and consequently the target of cowbird control programs. I calculated seasonal nesting effort (number of nests per pair) and productivity of 568 pairs of Least Bell's Vireos (Vireo bellii pusillus) monitored over 11 years at the San Luis Rey River in San Diego County, California (where cowbird trapping has reduced, but not eliminated, parasitism), assigning pairs to one of three groups: (1) deserters, (2) rescued (parasitized pairs with nests “rescued” from probable failure by the removal of cowbird eggs), and (3) unparasitized. Parasitized pairs attempted significantly more nests per season than did unparasitized pairs, with deserters producing more nests than rescued pairs. However, productivity of deserting pairs was significantly lower than that of both rescued and unparasitized pairs, largely because subsequent nests of deserting pairs were also parasitized. Seasonal productivity of rescued and unparasitized pairs was comparable, indicating that in this species, reduction of cowbird impacts through nest manipulation to remove cowbird eggs is effective. Desertion by Least Bell's Vireos does not appear to be an adequate natural defense against parasitism, suggesting the need for continued cowbird control while vireo populations are re-established.

  16. Regular use of acetaminophen or acetaminophen-codeine combinations and prescription of rescue therapy with non-steroidal anti-inflammatory drugs: a population-based study in primary care.

    PubMed

    Vannacci, Alfredo; Lombardi, Niccolò; Simonetti, Monica; Fornasari, Diego; Fanelli, Andrea; Cricelli, Iacopo; Cricelli, Claudio; Lora Aprile, Pierangelo; Lapi, Francesco

    2017-06-01

    There are contrasting positions concerning the benefit-risk ratio of acetaminophen use for osteoarthritis (OA)-related pain. To clarify the effectiveness of acetaminophen or acetaminophen-codeine combinations according to their regimen of use, we evaluated whether being a regular user (adherent) of these medications decreased the occurrence of rescue therapy with non-steroidal anti-inflammatory drugs (NSAIDs). Using the Health Search IMS Health Longitudinal Patient Database, we formed a cohort of patients aged ≥18 years and newly treated with acetaminophen or acetaminophen-codeine combinations for OA between 1 January 2001 and 31 December 2013. These patients were followed up for one year in which they were categorized as regular or irregular users of these medications according to a variable medication possession ratio (VMPR) ≥ 50% or lower. We operationally defined the rescue therapy as the use of any NSAIDs prescribed for OA-related pain. Overall, 40,029 patients (69.5% females; mean age: 68 ± 13.57) treated with acetaminophen or acetaminophen-codeine combinations formed the cohort. After the first year of treatment, regular users showed a statistically significantly lower risk of being prescribed with rescue therapy with NSAIDs (OR = 0.89; 95% CI 0.84-0.96). These findings show that regular use of acetaminophen or acetaminophen-codeine combinations may reduce the need for NSAIDs to treat OA-related pain.

  17. Prognostic significance of clinical presentation, induction and rescue treatment in 42 cases of canine centroblastic diffuse large B-cell multicentric lymphoma in the United Kingdom.

    PubMed

    Davies, O; Szladovits, B; Polton, G; Garden, O A; Leo, C; Lara-Garcia, A

    2018-06-01

    Canine lymphoma is a heterogeneous group of diseases and many previous studies have evaluated the response of a mixed population of lymphoma cases to one specific treatment protocol. The aim of this retrospective study was to describe the outcome and prognostic factors in 42 cases of multicentric centroblastic diffuse large B-cell lymphoma treated with either a COP-type (35%) or CHOP-type (64%) induction chemotherapy. The objective response rate to induction therapy was 94%; entire dogs had a greater rate of complete vs partial remissions than neutered dogs (P = .017). Median progression-free survival for the first remission (PFS1) was 182 days; absence of anaemia at diagnosis (P = .002) and pretreatment neutrophil:lymphocyte ratio (NLR) below 9.44 (P = .015) were independently predictive of longer PFS1. Fifty-eight percent of dogs received rescue protocols with an objective response rate of 81%; 31% of dogs received further rescue protocols (up to a total of 5) and the median number of protocols administered were 2. Median overall survival (OS) was 322 days, the 1-year survival rate was 38% and the 2-year survival rate was 9%. Lymphocyte:monocyte ratio above 1.43 (P = .031), NLR below 11.44 (P = .009), the combination of induction and rescue therapy (P = .030) and the total number of doxorubicin doses used (P = .002) were independently predictive of longer OS. Use of a COP-type protocol induction compared with CHOP did not undermine OS providing doxorubicin was used as rescue therapy. © 2017 John Wiley & Sons Ltd.

  18. Pharmacological Chaperones of the Dopamine Transporter Rescue Dopamine Transporter Deficiency Syndrome Mutations in Heterologous Cells*

    PubMed Central

    Lam, Vincent M.; Salahpour, Ali

    2016-01-01

    A number of pathological conditions have been linked to mutations in the dopamine transporter gene, including hereditary dopamine transporter deficiency syndrome (DTDS). DTDS is a rare condition that is caused by autosomal recessive loss-of-function mutations in the dopamine transporter (DAT), which often affects transporter trafficking and folding. We examined the possibility of using pharmacological chaperones of DAT to rescue DTDS mutations. After screening a set of known DAT ligands for their ability to increase DAT surface expression, we found that bupropion and ibogaine increased DAT surface expression, whereas others, including cocaine and methylphenidate, had no effect. Bupropion and ibogaine increased wild type DAT protein levels and also promoted maturation of the endoplasmic reticulum (ER)-retained DAT mutant K590A. Rescue of K590A could be blocked by inhibiting ER to Golgi transport using brefeldin A. Furthermore, knockdown of coat protein complex II (COPII) component SEC24D, which is important in the ER export of wild type DAT, also blocked the rescue effects of bupropion and ibogaine. These data suggest that bupropion and ibogaine promote maturation of DAT by acting as pharmacological chaperones in the ER. Importantly, both drugs rescue DAT maturation and functional activity of the DTDS-associated mutations A314V and R445C. Together, these results are the first demonstration of pharmacological chaperoning of DAT and suggest this may be a viable approach to increase DAT levels in DTDS and other conditions associated with reduced DAT function. PMID:27555326

  19. Search and Rescue. Auxiliary Operational Specialty Course. Student Text.

    ERIC Educational Resources Information Center

    Coast Guard, Washington, DC.

    This text, based on the National Search and Rescue (SAR) Plan, was prepared to provide a course of study on common procedures for SAR operations so that any basically qualified person in the U.S. Coast Guard Auxiliary can effectively accomplish a SAR mission and act as on-scene commander if required. There are 13 chapters: Introduction to Search…

  20. Effect of edaravone on favorable outcome in patients with acute cerebral large vessel occlusion: subanalysis of RESCUE-Japan Registry.

    PubMed

    Miyaji, Yuki; Yoshimura, Shinichi; Sakai, Nobuyuki; Yamagami, Hiroshi; Egashira, Yusuke; Shirakawa, Manabu; Uchida, Kazutaka; Kageyama, Hirohito; Tomogane, Yusuke

    2015-01-01

    The data of the nationwide prospective registry of acute cerebral large vessel occlusion (LVO; RESCUE-Japan Registry) were analyzed to know the effect of edaravone, a free radical scavenger, on clinical outcome at 90 days after onset. In this registry, patients with acute cerebral LVO admitted within 24 h after onset were prospectively registered. The effect of various factors including endovascular treatment (EVT), intravenous recombinant tissue plasminogen activator (IV rt-PA), and other medication including edaravone on favorable outcome (modified Rankin scale 0-1) was analyzed. Of the 1,454 registered patients, 1,442 patients (99.2%) had the information of edaravone were analyzed. In total, edaravone group had more patients with favorable outcome compared to non-edaravone group (22.9% vs. 13.8%, p = 0.0006). Edaravone increased favorable outcome in patients treated with IV rt-PA (29.4% vs. 11.1%, p = 0.0107), but not with EVT (21.2% vs. 13.9%, p = 0.309). Logistic regression analysis revealed that higher National Institutes of Health Stroke Scale (NIHSS) score on admission [odds ratio (OR) 0.875, 95% confidence interval (CI) 0.858-0.894] and advanced age (OR 0.963, 95%CI 0.952-0.975) were significantly related to unfavorable outcome. In contrast, IV rt-PA (OR 2.489, 95%CI 1.867-3.319), EVT (OR 1.375, 95%CI 1.013-1.865), and edaravone (OR 1.483, 95%CI 1.027-2.143) were significantly associated with favorable outcome. This analysis indicated that IV rt-PA, EVT, and edaravone were effective to obtain favorable outcome in patients with acute LVO. Combination IV rt-PA with edaravone was more effective.

  1. Effect of Edaravone on Favorable Outcome in Patients with Acute Cerebral Large Vessel Occlusion: Subanalysis of RESCUE-Japan Registry

    PubMed Central

    MIYAJI, Yuki; YOSHIMURA, Shinichi; SAKAI, Nobuyuki; YAMAGAMI, Hiroshi; EGASHIRA, Yusuke; SHIRAKAWA, Manabu; UCHIDA, Kazutaka; KAGEYAMA, Hirohito; TOMOGANE, Yusuke

    2015-01-01

    The data of the nationwide prospective registry of acute cerebral large vessel occlusion (LVO; RESCUE-Japan Registry) were analyzed to know the effect of edaravone, a free radical scavenger, on clinical outcome at 90 days after onset. In this registry, patients with acute cerebral LVO admitted within 24 h after onset were prospectively registered. The effect of various factors including endovascular treatment (EVT), intravenous recombinant tissue plasminogen activator (IV rt-PA), and other medication including edaravone on favorable outcome (modified Rankin scale 0–1) was analyzed. Of the 1,454 registered patients, 1,442 patients (99.2%) had the information of edaravone were analyzed. In total, edaravone group had more patients with favorable outcome compared to non-edaravone group (22.9% vs. 13.8%, p = 0.0006). Edaravone increased favorable outcome in patients treated with IV rt-PA (29.4% vs. 11.1%, p = 0.0107), but not with EVT (21.2% vs. 13.9%, p = 0.309). Logistic regression analysis revealed that higher National Institutes of Health Stroke Scale (NIHSS) score on admission [odds ratio (OR) 0.875, 95% confidence interval (CI) 0.858–0.894] and advanced age (OR 0.963, 95%CI 0.952–0.975) were significantly related to unfavorable outcome. In contrast, IV rt-PA (OR 2.489, 95%CI 1.867–3.319), EVT (OR 1.375, 95%CI 1.013–1.865), and edaravone (OR 1.483, 95%CI 1.027–2.143) were significantly associated with favorable outcome. This analysis indicated that IV rt-PA, EVT, and edaravone were effective to obtain favorable outcome in patients with acute LVO. Combination IV rt-PA with edaravone was more effective. PMID:25739433

  2. 46 CFR 199.203 - Marshalling of liferafts.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... LIFESAVING SYSTEMS FOR CERTAIN INSPECTED VESSELS Additional Requirements for Passenger Vessels § 199.203 Marshalling of liferafts. (a) Each passenger vessel must have a lifeboat or rescue boat for each six liferafts when— (1) Each lifeboat and rescue boat is loaded with its full complement of persons; and (2) The...

  3. 46 CFR 108.560 - Rescue boats.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 4 2010-10-01 2010-10-01 false Rescue boats. 108.560 Section 108.560 Shipping COAST... Lifesaving Equipment § 108.560 Rescue boats. Each unit must carry at least one rescue boat. Each rescue boat must be approved under approval series 160.156. A lifeboat is accepted as a rescue boat if it also...

  4. 46 CFR 108.560 - Rescue boats.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 4 2013-10-01 2013-10-01 false Rescue boats. 108.560 Section 108.560 Shipping COAST... Lifesaving Equipment § 108.560 Rescue boats. Each unit must carry at least one rescue boat. Each rescue boat must be approved under approval series 160.156. A lifeboat is accepted as a rescue boat if it also...

  5. Cost-effectiveness of the highly effective direct-acting antivirals in the treatment of chronic hepatitis C in Hong Kong.

    PubMed

    Lo, Angeline Oi-Shan; Chan, Henry Lik-Yuen; Wong, Vincent Wai-Sun; Wong, Grace Lai-Hung

    2017-05-01

    In Asia-Pacific where cost is a major concern, peginterferon plus ribavirin (PR) often remain as the standard of care in chronic hepatitis C (CHC) treatment, while the direct-acting antivirals (DAAs) are commonly recommended as retreatment. Newer DAAs can achieve a sustained virological response (SVR) of nearly 100% with pan-genotypic coverage, that is "Highly Effective DAAs." We aimed to investigate the most desirable cost range for the Highly Effective DAAs using Hong Kong as an example. Markov modeling was performed using PR as the reference strategy. The cost-effectiveness of the Highly Effective DAAs was compared with sofosbuvir-PR (first-line and rescue) and boceprevir-PR therapies. A 50-year-old genotype 1b hepatitis C virus (HCV) infected treatment-naïve patient with METAVIR F3 was used as the base case scenario to reflect the commonest HCV genotype in Hong Kong. The use of PR would incur a lifetime cost of US$35,854 and effectiveness of 14.85 quality-adjusted life-year (QALY). Sofosbuvir-PR as first-line treatment was dominated by other regimes. If Sofosbuvir-PR rescue therapy was used, the drug cost of Highly Effective DAAs should be set below US$43,553, with a cost-effectiveness ratio (CER) of US$3035/QALY compared with PR. In regions where Boceprevir-PR was still used as first-line therapy, the desirable drug cost of Highly Effective DAAs would be below US$56,985 to achieve a CER of US$5427/QALY. The most desirable costs of the Highly Effective DAAs would be below US$43,553 if Sofosbuvir-PR rescue therapy is used and below US$56,985 if Boceprevir-PR therapy is used. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

  6. Management of limb fractures in a teaching hospital: comparison between Wenchuan and Yushu earthquakes.

    PubMed

    Min, Li; Tu, Chong-qi; Liu, Lei; Zhang, Wen-li; Yi, Min; Song, Yue-ming; Huang, Fu-guo; Yang, Tian-fu; Pei, Fu-xing

    2013-01-01

    To comparatively analyze the medical records of patients with limb fractures as well as rescue strategy in Wenchuan and Yushu earthquakes so as to provide references for post-earthquake rescue. We retrospectively investigated 944 patients sustaining limb fractures, including 891 in Wenchuan earthquake and 53 in Yushu earthquake, who were admitted to West China Hospital (WCH) of Sichuan University. In Wenchuan earthquake, WCH met its three peaks of limb fracture patients influx, on post-earthquake day (PED) 2, 8 and 14 respectively. Between PED 3-14, 585 patients were transferred from WCH to other hospitals outside the Sichuan Province. In Yushu earthquake, the maximum influx of limb fracture patients happened on PED 3, and no one was shifted to other hospitals. Both in Wenchuan and Yushu earthquakes, most limb fractures were caused by blunt strike and crush/burying. In Wenchuan earthquake, there were 396 (396/942, 42.0%) open limb fractures, including 28 Gustilo I, 201 Gustilo II and 167 Gustilo III injuries. But in Yushu earthquake, the incidence of open limb fracture was much lower (6/61, 9.8%). The percent of patients with acute complications in Wenchuan earthquake (167/891, 18.7%) was much higher than that in Yushu earthquake (5/53, 3.8%). In Wenchuan earthquake rescue, 1 018 surgeries were done, composed of debridement in 376, internal fixation in 283, external fixation in 119, and vacuum sealing drainage in 117, etc. While among the 64 surgeries in Yushu earthquake rescue, the internal fixation for limb fracture was mostly adopted. All patients received proper treatment and survived except one who died due to multiple organs failure in Wenchuan earthquake. Provision of suitable and sufficient medical care in a catastrophe can only be achieved by construction of sophisticated national disaster medical system, prediction of the injury types and number of injuries, and confirmation of participating hospitals?exact role. Based on the valuable rescue experiences after Wenchuan earthquake, the rescue was faster, more orderly and effective in Yushu earthquake. Nevertheless, there is still a long way to go in the development of a stronger emergent response to the disasters.

  7. 46 CFR 10.109 - Classification of endorsements.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... survival craft and rescue boats other than fast rescue boats (PSC). (16) Proficiency in survival craft and rescue boats other than fast rescue boats—limited (PSC—limited). (17) Proficiency in fast rescue boats...

  8. Error analysis for relay type satellite-aided search and rescue systems

    NASA Technical Reports Server (NTRS)

    Marini, J. W.

    1977-01-01

    An analysis was made of the errors in the determination of the position of an emergency transmitter in a satellite aided search and rescue system. The satellite was assumed to be at a height of 820 km in a near circular near polar orbit. Short data spans of four minutes or less were used. The error sources considered were measurement noise, transmitter frequency drift, ionospheric effects and error in the assumed height of the transmitter. The errors were calculated for several different transmitter positions, data rates and data spans. The only transmitter frequency used was 406 MHz, but the results can be scaled to different frequencies. In a typical case, in which four Doppler measurements were taken over a span of two minutes, the position error was about 1.2 km.

  9. Oral pregabalin for postoperative pain relief after third molar extraction: a randomized controlled clinical trial.

    PubMed

    Olmedo-Gaya, Maria Victoria; Manzano-Moreno, Francisco J; Galvez-Mateos, Rafael; González-Rodriguez, Maria Paloma; Talero-Sevilla, Cristina; Vallecillo-Capilla, Manuel

    2016-09-01

    The aim of this randomized controlled clinical trial was to evaluate the efficacy and safety of pregabalin administered pre- and postoperatively in patients with pain and swelling due to the surgical removal of impacted lower third molars. The final study sample comprised 60 volunteers (23 males and 37 females). Group 1 (n = 30) received 75 mg oral pregabalin 1 h before surgery and 1 h after surgery. Group 2 (n = 30) served as a control group and received no pregabalin. Both groups were administered with 650 mg paracetamol every 8 h for 2 days. Postoperative pain intensity and swelling were measured using a visual analog scale (VAS); pain relief experienced was reported using a four-point verbal rating scale (VRS); the rescue medication requirement, adverse effects, and global impression of the medication were also recorded. No significant difference in pain intensity (VAS) was observed between the groups. However, fewer rescue medication tablets were needed by pregabalin-treated patients than by controls (p = 0.021). The frequency and intensity of adverse effects were significantly higher in pregabalin-treated patients (p < 0.001), although no serious adverse events occurred. No significant difference in the degree of swelling was observed in any measurement except that from mandibular angle to lip junction, which showed lesser inflammation in the pregabalin group at 24 h post-surgery (p = 0.011). The global opinion on the medication received was more positive in the pregabalin group (p = 0.042). The administration of pregabalin reduces the requirement for rescue medication after third molar surgery and results in a more constant pain level, with fewer peaks of pain intensity. These findings suggest that pregabalin may be useful to control acute postoperative pain. Adverse effects are known to be reduced at the low pregabalin dose used in our study.

  10. Management of Multi-Casualty Incidents in Mountain Rescue: Evidence-Based Guidelines of the International Commission for Mountain Emergency Medicine (ICAR MEDCOM).

    PubMed

    Blancher, Marc; Albasini, François; Elsensohn, Fidel; Zafren, Ken; Hölzl, Natalie; McLaughlin, Kyle; Wheeler, Albert R; Roy, Steven; Brugger, Hermann; Greene, Mike; Paal, Peter

    2018-06-01

    Blancher, Marc, François Albasini, Fidel Elsensohn, Ken Zafren, Natalie Hölzl, Kyle McLaughlin, Albert R. Wheeler III, Steven Roy, Hermann Brugger, Mike Greene, and Peter Paal. Management of multi-casualty incidents in mountain rescue: Evidence-based guidelines of the International Commission for Mountain Emergency Medicine (ICAR MEDCOM). High Alt Med Biol. 19:131-140, 2018. Multi-Casualty Incidents (MCI) occur in mountain areas. Little is known about the incidence and character of such events, and the kind of rescue response. Therefore, the International Commission for Mountain Emergency Medicine (ICAR MEDCOM) set out to provide recommendations for the management of MCI in mountain areas. Details of MCI occurring in mountain areas related to mountaineering activities and involving organized mountain rescue were collected. A literature search using (1) PubMed, (2) national mountain rescue registries, and (3) lay press articles on the internet was performed. The results were analyzed with respect to specific aspects of mountain rescue. We identified 198 MCIs that have occurred in mountain areas since 1956: 137 avalanches, 38 ski lift accidents, and 23 other events, including lightning injuries, landslides, volcanic eruptions, lost groups of people, and water-related accidents. General knowledge on MCI management is required. Due to specific aspects of triage and management, the approach to MCIs may differ between those in mountain areas and those in urban settings. Mountain rescue teams should be prepared to manage MCIs. Knowledge should be reviewed and training performed regularly. Cooperation between terrestrial rescue services, avalanche safety authorities, and helicopter crews is critical to successful management of MCIs in mountain areas.

  11. The lived experience of rescuing people who have driven into floodwater: Understanding challenges and identifying areas for providing support.

    PubMed

    Keech, Jacob J; Smith, Stephanie R; Peden, Amy E; Hagger, Martin S; Hamilton, Kyra

    2018-06-11

    Drowning is a major public health issue, with risk increasing during times of flood. Driving though floodwater is a major risk factor for flood-related drowning and injury, and despite widespread public health campaigns, many people continue to undertake this risky behaviour and require rescue. We aimed to identify key challenges faced by emergency services personnel when rescuing those who have driven into floodwater, and to identify strategies for supporting rescuers in this important role. Australian flood rescue operators (N=8) who had previously rescued a driver who had driven through floodwater, participated in semi-structured interviews. Data were analysed using thematic analysis. Four challenges emerged from their experiences: Involvement of untrained personnel, varying information provided by emergency telephone operators, behaviour of drivers complicating the rescue, people sightseeing floods or flood rescues, or ignoring closed roads providing sources of distraction and frustration. We propose five strategies for translating these results into practice, including: training and protocol development for (1) emergency personnel and (2) telephone operators, (3) training for rescuers regarding non-compliant rescuees, (4) educating the public, and (5) increasing compliance with closed roads. Current findings provide valuable insights into how rescuers can be supported in performing their roles, and implementation of these strategies has the potential to reduce fatalities occurring due to driving through floodwater. SO WHAT?: The strategies presented have the potential to reduce the frequency and improve the outcomes of floodwater rescues, aiding in the prevention of injury and death. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  12. Stimulation of mTORC1 with L-leucine Rescues Defects Associated with Roberts Syndrome

    PubMed Central

    Xu, Baoshan; Lee, Kenneth K.; Zhang, Lily; Gerton, Jennifer L.

    2013-01-01

    Roberts syndrome (RBS) is a human disease characterized by defects in limb and craniofacial development and growth and mental retardation. RBS is caused by mutations in ESCO2, a gene which encodes an acetyltransferase for the cohesin complex. While the essential role of the cohesin complex in chromosome segregation has been well characterized, it plays additional roles in DNA damage repair, chromosome condensation, and gene expression. The developmental phenotypes of Roberts syndrome and other cohesinopathies suggest that gene expression is impaired during embryogenesis. It was previously reported that ribosomal RNA production and protein translation were impaired in immortalized RBS cells. It was speculated that cohesin binding at the rDNA was important for nucleolar form and function. We have explored the hypothesis that reduced ribosome function contributes to RBS in zebrafish models and human cells. Two key pathways that sense cellular stress are the p53 and mTOR pathways. We report that mTOR signaling is inhibited in human RBS cells based on the reduced phosphorylation of the downstream effectors S6K1, S6 and 4EBP1, and this correlates with p53 activation. Nucleoli, the sites of ribosome production, are highly fragmented in RBS cells. We tested the effect of inhibiting p53 or stimulating mTOR in RBS cells. The rescue provided by mTOR activation was more significant, with activation rescuing both cell division and cell death. To study this cohesinopathy in a whole animal model we used ESCO2-mutant and morphant zebrafish embryos, which have developmental defects mimicking RBS. Consistent with RBS patient cells, the ESCO2 mutant embryos show p53 activation and inhibition of the TOR pathway. Stimulation of the TOR pathway with L-leucine rescued many developmental defects of ESCO2-mutant embryos. Our data support the idea that RBS can be attributed in part to defects in ribosome biogenesis, and stimulation of the TOR pathway has therapeutic potential. PMID:24098154

  13. Stimulation of mTORC1 with L-leucine rescues defects associated with Roberts syndrome.

    PubMed

    Xu, Baoshan; Lee, Kenneth K; Zhang, Lily; Gerton, Jennifer L

    2013-01-01

    Roberts syndrome (RBS) is a human disease characterized by defects in limb and craniofacial development and growth and mental retardation. RBS is caused by mutations in ESCO2, a gene which encodes an acetyltransferase for the cohesin complex. While the essential role of the cohesin complex in chromosome segregation has been well characterized, it plays additional roles in DNA damage repair, chromosome condensation, and gene expression. The developmental phenotypes of Roberts syndrome and other cohesinopathies suggest that gene expression is impaired during embryogenesis. It was previously reported that ribosomal RNA production and protein translation were impaired in immortalized RBS cells. It was speculated that cohesin binding at the rDNA was important for nucleolar form and function. We have explored the hypothesis that reduced ribosome function contributes to RBS in zebrafish models and human cells. Two key pathways that sense cellular stress are the p53 and mTOR pathways. We report that mTOR signaling is inhibited in human RBS cells based on the reduced phosphorylation of the downstream effectors S6K1, S6 and 4EBP1, and this correlates with p53 activation. Nucleoli, the sites of ribosome production, are highly fragmented in RBS cells. We tested the effect of inhibiting p53 or stimulating mTOR in RBS cells. The rescue provided by mTOR activation was more significant, with activation rescuing both cell division and cell death. To study this cohesinopathy in a whole animal model we used ESCO2-mutant and morphant zebrafish embryos, which have developmental defects mimicking RBS. Consistent with RBS patient cells, the ESCO2 mutant embryos show p53 activation and inhibition of the TOR pathway. Stimulation of the TOR pathway with L-leucine rescued many developmental defects of ESCO2-mutant embryos. Our data support the idea that RBS can be attributed in part to defects in ribosome biogenesis, and stimulation of the TOR pathway has therapeutic potential.

  14. Psychiatric disorders after terrorist bombings among rescue workers and bombing survivors in Nairobi and rescue workers in Oklahoma City.

    PubMed

    Zhang, Gus; Pfefferbaum, Betty; Narayanan, Pushpa; Lee, Sungkyu; Thielman, Samuel; North, Carol S

    2016-02-01

    To examine the prevalence of psychopathology in 52 male rescue workers responding to the 1998 U.S. Embassy bombing in Nairobi, Kenya, comparing them with 176 male rescue workers responding to the 1995 Oklahoma City, Oklahoma, bombing and with 105 directly exposed male civilian survivors of the Nairobi bombing. The Diagnostic Interview Schedule/Disaster Supplement assessed pre-disaster and post-disaster psychiatric disorders and variables related to demographics, exposure, disaster perceptions, and coping in all 3 disaster subgroups. The most prevalent post-disaster disorders were posttraumatic stress disorder (PTSD) (22%) and major depressive disorder (MDD) (27%) among Nairobi rescue workers, which were more than 2 and 4 times higher, respectively, than among Oklahoma City rescue workers. Alcohol use disorder was the most prevalent pre- and post-disaster disorder among Oklahoma City rescue workers. Nairobi rescue workers had a prevalence of PTSD and MDD not significantly different from Nairobi civilian survivors. Nairobi rescue workers were more symptomatic than Oklahoma City rescue workers and were as symptomatic as Nairobi civilian survivors. The vulnerability of Nairobi rescue workers to psychological sequelae may be a reflection of their volunteer, rather than professional, status. These findings contribute to understanding rescue worker mental health, especially among volunteer rescue workers, with potential implications for the importance of professional status of rescue workers in conferring protection from adverse mental health outcomes.

  15. Postnatally elevated levels of insulin-like growth factor (IGF)-II fail to rescue the dwarfism of IGF-I-deficient mice except kidney weight.

    PubMed

    Moerth, Corinna; Schneider, Marlon R; Renner-Mueller, Ingrid; Blutke, Andreas; Elmlinger, Martin W; Erben, Reinhold G; Camacho-Hübner, Cecilia; Hoeflich, Andreas; Wolf, Eckhard

    2007-01-01

    This study tested whether elevated levels of IGF-II in the postnatal period can rescue the dwarfism in IGF-I-deficient mice. Heterozygous Igf1 mutant mice [I(+/-) II(wt)] were crossed with heterozygous Igf1 mutant, phosphoenolpyruvate carboxykinase promoter IGF-II transgenic mice [I(+/-) II(tg)], and [I(+/+) II(wt)], [I(+/+) II(tg)], [I(-/-) II(wt)], and [I(-/-) II(tg)] offspring were investigated. IGF-II levels were 11- and 6-fold higher in male and female [I(-/-) II(tg)] vs. [I(-/-) II(wt)] animals. Western ligand blot analysis revealed markedly reduced activities of 30- and 32-kDa IGF binding proteins (IGFBPs) (most likely IGFBP-1 and IGFBP-2) and the 39- to 43-kDa IGFBP-3 double band in serum from IGF-I-deficient mice. These binding proteins were partially restored by overexpression of IGF-II. Analysis of weight data from the early postnatal period until d 60 showed that, in the absence of IGF-I, elevated levels of IGF-II have no effect on body weight gain. A detailed analysis of body proportions, bone parameters, and organ weights of 60-d-old mice also failed to show effects of IGF-II with one important exception: in Igf1 mutant and also Igf1 intact male mice, IGF-II overexpression significantly increased absolute (+32.4 and +28.6%; P < 0.01) and relative kidney weights (+29.0 and +22.4%; P < 0.001). These changes in kidney weight were associated with reduced phosphorylation of p38 MAPK. In summary, our genetic model shows that substantial amounts of IGF-II in the circulation do not rescue the postnatal growth deficit of IGF-I-deficient mice but increase absolute and relative kidney weights of normal and IGF-I-deficient male mice, suggesting a gender-specific role of IGF-II for kidney growth.

  16. Inhibition of microtubules and dynein rescues human immunodeficiency virus type 1 from owl monkey TRIMCyp-mediated restriction in a cellular context-specific fashion.

    PubMed

    Pawlica, Paulina; Dufour, Caroline; Berthoux, Lionel

    2015-04-01

    IFN-induced restriction factors can significantly affect the replicative capacity of retroviruses in mammals. TRIM5α (tripartite motif protein 5, isoform α) is a restriction factor that acts at early stages of the virus life cycle by intercepting and destabilizing incoming retroviral cores. Sensitivity to TRIM5α maps to the N-terminal domain of the retroviral capsid proteins. In several New World and Old World monkey species, independent events of retrotransposon-mediated insertion of the cyclophilin A (CypA)-coding sequence in the trim5 gene have given rise to TRIMCyp (also called TRIM5-CypA), a hybrid protein that is active against some lentiviruses in a species-specific fashion. In particular, TRIMCyp from the owl monkey (omkTRIMCyp) very efficiently inhibits human immunodeficiency virus type 1 (HIV-1). Previously, we showed that disrupting the integrity of microtubules (MTs) and of cytoplasmic dynein complexes partially rescued replication of retroviruses, including HIV-1, from restriction mediated by TRIM5α. Here, we showed that efficient restriction of HIV-1 by omkTRIMCyp was similarly dependent on the MT network and on dynein complexes, but in a context-dependent fashion. When omkTRIMCyp was expressed in human HeLa cells, restriction was partially counteracted by pharmacological agents targeting MTs or by small interfering RNA-mediated inhibition of dynein. The same drugs (nocodazole and paclitaxel) also rescued HIV-1 from restriction in cat CRFK cells, although to a lesser extent. Strikingly, neither nocodazole, paclitaxel nor depletion of the dynein heavy chain had a significant effect on the restriction of HIV-1 in an owl monkey cell line. These results suggested the existence of cell-specific functional interactions between MTs/dynein and TRIMCyp. © 2015 The Authors.

  17. VDR deficiency affects alveolar bone and cementum apposition in mice.

    PubMed

    Zhang, Xueming; Rahemtulla, Firoz; Zhang, Ping; Thomas, Huw F

    2011-07-01

    To compare the mineralisation density (MD), morphology and histology of alveolar bone and cementum amongst VDR +/+, VDR -/-, and VDR -/- groups supplemented with a diet TD 96348, containing 20% lactose, 2.0% calcium and 1.25% phosphorous. Four groups of mice (6 mice/group) were identified by genotyping: VDR +/+ mice (VDR wild type), VDR -/- mice (VDR deficient), VDR -/- offsprings derived from VDR -/- parents receiving a supplemental diet (early rescued), and VDR -/- mice fed with a supplemental diet beginning at age one month (late rescued). All mice were sacrificed at age 70.5 days. Micro-CT was used to compare MD and morphology of alveolar bone and cementum. H-E and Toluidine blue staining was used to examine the ultrastructure of the alveolar bone and cementum at matched locations. In VDR -/- group, alveolar bone and cementum failed to mineralise normally. Early rescue increased MD of alveolar bone in VDR -/- mice with excessive alveolar bone formation, but which not observed in late rescue group. MD and morphology of cementum-dentine complex in both early and late rescue groups were comparable with VDR +/+ group when feeding with high-calcium rescue diet. VDR affects alveolar bone mineralisation and formation systemically and locally. However, cementum apposition and mineralisation is mainly regulated by calcium concentrations in serum. Copyright © 2010 Elsevier Ltd. All rights reserved.

  18. Molecular mechanism of action of pharmacoperone rescue of misrouted GPCR mutants: the GnRH receptor.

    PubMed

    Janovick, Jo Ann; Patny, Akshay; Mosley, Ralph; Goulet, Mark T; Altman, Michael D; Rush, Thomas S; Cornea, Anda; Conn, P Michael

    2009-02-01

    The human GnRH receptor (hGnRHR), a G protein-coupled receptor, is a useful model for studying pharmacological chaperones (pharmacoperones), drugs that rescue misfolded and misrouted protein mutants and restore them to function. This technique forms the basis of a therapeutic approach of rescuing mutants associated with human disease and restoring them to function. The present study relies on computational modeling, followed by site-directed mutagenesis, assessment of ligand binding, effector activation, and confocal microscopy. Our results show that two different chemical classes of pharmacoperones act to stabilize hGnRHR mutants by bridging residues D(98) and K(121). This ligand-mediated bridge serves as a surrogate for a naturally occurring and highly conserved salt bridge (E(90)-K(121)) that stabilizes the relation between transmembranes 2 and 3, which is required for passage of the receptor through the cellular quality control system and to the plasma membrane. Our model was used to reveal important pharmacophoric features, and then identify a novel chemical ligand, which was able to rescue a D(98) mutant of the hGnRHR that could not be rescued as effectively by previously known pharmacoperones.

  19. Rescue of fragile X syndrome phenotypes in Fmr1 KO mice by a BKCa channel opener molecule

    PubMed Central

    2014-01-01

    Background Fragile X Syndrome (FXS) is the most common form of inherited intellectual disability and is also associated with autism spectrum disorders. Previous studies implicated BKCa channels in the neuropathogenesis of FXS, but the main question was whether pharmacological BKCa stimulation would be able to rescue FXS neurobehavioral phenotypes. Methods and results We used a selective BKCa channel opener molecule (BMS-204352) to address this issue in Fmr1 KO mice, modeling the FXS pathophysiology. In vitro, acute BMS-204352 treatment (10 μM) restored the abnormal dendritic spine phenotype. In vivo, a single injection of BMS-204352 (2 mg/kg) rescued the hippocampal glutamate homeostasis and the behavioral phenotype. Indeed, disturbances in social recognition and interaction, non-social anxiety, and spatial memory were corrected by BMS-204352 in Fmr1 KO mice. Conclusion These results demonstrate that the BKCa channel is a new therapeutic target for FXS. We show that BMS-204352 rescues a broad spectrum of behavioral impairments (social, emotional and cognitive) in an animal model of FXS. This pharmacological molecule might open new ways for FXS therapy. PMID:25079250

  20. The effect of caudal vs intravenous morphine on early extubation and postoperative analgesic requirements for stage 2 and 3 single-ventricle palliation: a double blind randomized trial.

    PubMed

    Stuth, Eckehard A E; Berens, Richard J; Staudt, Susan R; Robertson, Frederick A; Scott, John P; Stucke, Astrid G; Hoffman, George M; Troshynski, Todd J; Tweddell, James S T; Zuperku, Edward J

    2011-04-01

    High-dose single-shot caudal morphine has been postulated to facilitate early extubation and to lower initial analgesic requirements after staged single-ventricle (SV) palliation. With Institutional Review Board approval and written informed parental consent, 64 SV children aged 75-1667 days were randomized to pre-incisional caudal morphine-bupivacaine (100 μg·kg(-1) morphine (concentration 0.1%), mixed with 0.25% bupivacaine with 1 : 200,000 epinephrine, total 1 ml·kg(-1)) and postcardiopulmonary bypass (CPB) intravenous (IV) droperidol (75 μg·kg(-1)) ('active caudal group') or pre-incisional caudal saline (1 ml·kg(-1)) and post-CPB IV morphine (150 μg·kg(-1)) with droperidol (75 μg·kg(-1)) ('active IV group'). Assignment remained concealed from families and the care teams throughout the trial. Early extubation failure rates (primary or reintubation within 24 h), time to first postoperative rescue morphine analgesia, and 12-h postoperative morphine requirements were assessed for extubated patients. Thirty-one (12 stage 2) SV patients received caudal morphine and 32 (15 stage 2) received IV morphine. Extubation failure rates were 6/31 (19%) for caudal and 5/32 (16%) for IV morphine. For successfully extubated patients (n = 54), active caudal treatment significantly delayed the need for postoperative rescue morphine in stage 3 patients (P = 0.02) but not in stage 2 patients (P = 0.189) (Kaplan-Meier survival analysis with LogRank test). The reduction in 12-h postoperative morphine requirements with active caudal treatment did not reach significance (P = 0.085) but morphine requirements were significantly higher for stage 2 compared with stage 3 patients (P < 0.001) (two-way anova in n = 50 extubated patients). High-dose caudal morphine with bupivacaine delayed the need for rescue morphine analgesia in stage 3 patients. All stage 2 patients required early rescue morphine and had significantly higher postoperative 12-h morphine requirements than stage 3 patients. Early extubation is feasible for the majority of stage 2 and 3 SV patients regardless of analgesic regimen. The study was underpowered to assess differences in extubation failure rates. © 2011 Blackwell Publishing Ltd.

  1. The Pain and the Gain of Rescuing Historic Science Data: The Nimbus Data Rescue Project

    NASA Astrophysics Data System (ADS)

    Gallaher, D. W.; Campbell, G. G.

    2015-12-01

    While technology of our satellite systems have greatly improved the quality of observations over the past 50 years, it is the legacy of the first global coverage environment satellites, the Nimbus systems launched by NASA in the mid-1960s, that marks the beginning of a unique perspective from space. Such early data can extend our climate record and provide important context in longer-term climate changes. Unfortunately, the Nimbus data nearly disappeared before its value was recognized and attempts to recover the data were undertaken. While the Nimbus data was never truly lost, it was in a form that could not be read and was not organized in a way that could be accessed with modern computer systems. The rescue and recovery of the Nimbus data began in 2007 with an initiative by the NASA Goddard Space Flight Center. Without the Goddard efforts, the early Nimbus data might be forever dark. The Nimbus Rescue Project has just completed processing and archival of the Nimbus 4 visible and infrared observations from 1970 and 1971. This adds to our rescue efforts from Nimbus 1, 2 and 3 for 1964, 1966 and 1969. The procedures to recover the Nimbus data, from both film and tape, could be used by other data rescue projects, however the algorithms presented will tend to be Nimbus specific. The compositing of the mapped minimum brightness over weekly intervals resulted in never before seen views of the Polar Regions, such as a visible light view of the Antarctic ice extent from October 1970 (Figure 1). The Nimbus data recovery and reprocessing into modern formats was important, however it was the utility of the data as a part of the satellite climate record that made it valuable. Data rescue projects are often both difficult and time consuming but the data they bring back to the science community makes these efforts worthwhile.

  2. Mucuna pruriens (Velvet bean) rescues motor, olfactory, mitochondrial and synaptic impairment in PINK1B9 Drosophila melanogaster genetic model of Parkinson's disease.

    PubMed

    Poddighe, Simone; De Rose, Francescaelena; Marotta, Roberto; Ruffilli, Roberta; Fanti, Maura; Secci, Pietro Paolo; Mostallino, Maria Cristina; Setzu, Maria Dolores; Zuncheddu, Maria Antonietta; Collu, Ignazio; Solla, Paolo; Marrosu, Francesco; Kasture, Sanjay; Acquas, Elio; Liscia, Anna

    2014-01-01

    The fruit fly Drosophila melanogaster (Dm) mutant for PTEN-induced putative kinase 1 (PINK1B9) gene is a powerful tool to investigate physiopathology of Parkinson's disease (PD). Using PINK1B9 mutant Dm we sought to explore the effects of Mucuna pruriens methanolic extract (Mpe), a L-Dopa-containing herbal remedy of PD. The effects of Mpe on PINK1B9 mutants, supplied with standard diet to larvae and adults, were assayed on 3-6 (I), 10-15 (II) and 20-25 (III) days old flies. Mpe 0.1% significantly extended lifespan of PINK1B9 and fully rescued olfactory response to 1-hexanol and improved climbing behavior of PINK1B9 of all ages; in contrast, L-Dopa (0.01%, percentage at which it is present in Mpe 0.1%) ameliorated climbing of only PINK1B9 flies of age step II. Transmission electron microscopy analysis of antennal lobes and thoracic ganglia of PINK1B9 revealed that Mpe restored to wild type (WT) levels both T-bars and damaged mitochondria. Western blot analysis of whole brain showed that Mpe, but not L-Dopa on its own, restored bruchpilot (BRP) and tyrosine hydroxylase (TH) expression to age-matched WT control levels. These results highlight multiple sites of action of Mpe, suggesting that its effects cannot only depend upon its L-Dopa content and support the clinical observation of Mpe as an effective medication with intrinsic ability of delaying the onset of chronic L-Dopa-induced long-term motor complications. Overall, this study strengthens the relevance of using PINK1B9 Dm as a translational model to study the properties of Mucuna pruriens for PD treatment.

  3. Emergency material allocation and scheduling for the application to chemical contingency spills under multiple scenarios.

    PubMed

    Liu, Jie; Guo, Liang; Jiang, Jiping; Jiang, Dexun; Wang, Peng

    2017-01-01

    In the emergency management relevant to chemical contingency spills, efficiency emergency rescue can be deeply influenced by a reasonable assignment of the available emergency materials to the related risk sources. In this study, an emergency material scheduling model (EMSM) with time-effective and cost-effective objectives is developed to coordinate both allocation and scheduling of the emergency materials. Meanwhile, an improved genetic algorithm (IGA) which includes a revision operation for EMSM is proposed to identify the emergency material scheduling schemes. Then, scenario analysis is used to evaluate optimal emergency rescue scheme under different emergency pollution conditions associated with different threat degrees based on analytic hierarchy process (AHP) method. The whole framework is then applied to a computational experiment based on south-to-north water transfer project in China. The results demonstrate that the developed method not only could guarantee the implementation of the emergency rescue to satisfy the requirements of chemical contingency spills but also help decision makers identify appropriate emergency material scheduling schemes in a balance between time-effective and cost-effective objectives.

  4. Intraocular gene transfer of ciliary neurotrophic factor rescues photoreceptor degeneration in RCS rats.

    PubMed

    Huang, Shun-Ping; Lin, Po-Kang; Liu, Jorn-Hon; Khor, Chin-Ni; Lee, Yih-Jing

    2004-01-01

    Ciliary neurotrophic factor (CNTF) is known as an important factor in the regulation of retinal cell growth. We used both recombinant CNTF and an adenovirus carrying the CNTF gene to regulate retinal photoreceptor expression in a retinal degenerative animal, Royal College of Surgeons (RCS) rats. Cells in the outer nuclear layer of the retinae from recombinant-CNTF-treated, adenoviral-CNTF-treated, saline-operated, and contralateral untreated preparations were examined for those exhibiting CNTF photoreceptor protective effects. Cell apoptosis in the outer nuclear layer of the retinae was also detected. It was found that CNTF had a potent effect on delaying the photoreceptor degeneration process in RCS rats. Furthermore, adenovirus CNTF gene transfer was proven to be better at rescuing photoreceptors than that when using recombinant CNTF, since adenoviral CNTF prolonged the photoreceptor protection effect. The function of the photoreceptors was also examined by taking electroretinograms of different animals. Adenoviral-CNTF-treated eyes showed better retinal function than did the contralateral control eyes. This study indicates that adenoviral CNTF effectively rescues degenerating photoreceptors in RCS rats. Copyright 2004 National Science Council, ROC and S. Karger AG, Basel

  5. Helicopter Mountain Rescue in Slovenia from 2011 to 2015.

    PubMed

    Deeb, Janina Golob; Walter, Nicholas; Carrico, Caroline; Gašperin, Miha; Deeb, George R

    2018-03-01

    The popularity of adventure recreation in wilderness areas across the world continues to increase. Nevertheless, the risk of injury and illness remains significant. The purpose of this study is to analyze the mountain rescue operations performed in Slovenia between 2011 and 2015. This retrospective study reports mountain rescue operations documented by the Slovenian National Mountain Rescue Association. The annual number of ground-based and helicopter-based rescues were identified and compared. For 2015, the indication for rescue and the severity of injury were also analyzed, specifically for interventions requiring the use of a helicopter. From 2011 through 2015, the number of rescues remained consistent with an annual average of 413 (SD ±15; range, 393-434) rescues. However, the percentage of ground-based rescues varied significantly year by year (P=0.016), with highest rate in 2014 (68%) and the lowest in 2015 (56%). In 2015, 434 mountain rescue operations were reported in Slovenia. Injury accounted for 44%, illness for 10%, and fatality for 9% of the rescues. In 37%, no illness or injury was reported. Helicopter rescue was used in 190 (44%) of all interventions. Among the 190 helicopter rescues, 49% of patients had nonfatal injuries, 29% required no medical treatment, 15% had illness, and 7% had fatal injuries. A significant number of mountain rescue operations were conducted in Slovenia from 2011 through 2015. Most of these were needed for injured, ill, or deceased persons. A notable number of rescues in 2015 required a helicopter. Copyright © 2017 Wilderness Medical Society. Published by Elsevier Inc. All rights reserved.

  6. A Practice of Rescue Robot Contest in Junior High Schools

    NASA Astrophysics Data System (ADS)

    Kawada, Kazuo; Nagamatsu, Masayasu; Yamamoto, Toru

    The rescue robot contest for junior high school students was created to give students an opportunity to design a robot to rescue the victims under large scale disasters. The activity was not only intended as an humanitarian project but also aiming at students to : (1) take the role of victims and imagining the situation from his or her perspective, (2) enhance thinking skills, creativity through the problem solving processes and, (3) work cooperatively in groups. From results of questionnaire for the participated students, important factors for further implementation as curriculum of technology education are implied.

  7. 33 CFR 149.314 - What are the approval and stowage requirements for rescue boats?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... requirements for rescue boats? 149.314 Section 149.314 Navigation and Navigable Waters COAST GUARD, DEPARTMENT... requirements for rescue boats? (a) Rescue boats must be approved under approval series 160.156. A lifeboat is acceptable as a rescue boat if it also meets the requirements for a rescue boat under approval series 160.156...

  8. 33 CFR 149.314 - What are the approval and stowage requirements for rescue boats?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... requirements for rescue boats? 149.314 Section 149.314 Navigation and Navigable Waters COAST GUARD, DEPARTMENT... requirements for rescue boats? (a) Rescue boats must be approved under approval series 160.156. A lifeboat is acceptable as a rescue boat if it also meets the requirements for a rescue boat under approval series 160.156...

  9. 33 CFR 149.314 - What are the approval and stowage requirements for rescue boats?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... requirements for rescue boats? 149.314 Section 149.314 Navigation and Navigable Waters COAST GUARD, DEPARTMENT... requirements for rescue boats? (a) Rescue boats must be approved under approval series 160.156. A lifeboat is acceptable as a rescue boat if it also meets the requirements for a rescue boat under approval series 160.156...

  10. 33 CFR 149.314 - What are the approval and stowage requirements for rescue boats?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... requirements for rescue boats? 149.314 Section 149.314 Navigation and Navigable Waters COAST GUARD, DEPARTMENT... requirements for rescue boats? (a) Rescue boats must be approved under approval series 160.156. A lifeboat is acceptable as a rescue boat if it also meets the requirements for a rescue boat under approval series 160.156...

  11. 33 CFR 149.314 - What are the approval and stowage requirements for rescue boats?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... requirements for rescue boats? 149.314 Section 149.314 Navigation and Navigable Waters COAST GUARD, DEPARTMENT... requirements for rescue boats? (a) Rescue boats must be approved under approval series 160.156. A lifeboat is acceptable as a rescue boat if it also meets the requirements for a rescue boat under approval series 160.156...

  12. 46 CFR 12.615 - Requirements to qualify for an STCW endorsement in proficiency in survival craft and rescue boats...

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... proficiency in survival craft and rescue boats other than lifeboats and fast rescue boats-limited (PSC-limited... lifeboats and fast rescue boats-limited (PSC-limited). (a) To qualify for an STCW endorsement in proficiency in survival craft and rescue boats other than lifeboats and fast rescue boats-limited (PSC-limited...

  13. Structure-activity relations of successful pharmacologic chaperones for rescue of naturally occurring and manufactured mutants of the gonadotropin-releasing hormone receptor.

    PubMed

    Janovick, Jo Ann; Goulet, Mark; Bush, Eugene; Greer, Jonathan; Wettlaufer, David G; Conn, P Michael

    2003-05-01

    We expressed a test system of wild-type (WT) rat (r) and human (h) gonadotropin-releasing hormone (GnRH) receptors (GnRHRs), including naturally occurring (13) and manufactured (five) "loss-of-function" mutants of the GnRHR. These were used to assess the ability of different GnRH peptidomimetics to rescue defective GnRHR mutants and determine their effect on the level of membrane expression of the WT receptors. Among the manufactured mutants were the shortest rGnRHR C-terminal truncation mutant that resulted in receptor loss-of-function (des(325-327)-rGnRHR), two nonfunctional deletion mutants (des(237-241)-rGnRHR and des(260-265)-rGnRHR), two nonfunctional Cys mutants (C(229)A-rGnRHR and C(278)A-rGnRHR); the naturally occurring mutants included all 13 full-length GnRHR point mutations reported to date that result in full or partial human hypogonadotropic hypogonadism. The 10 peptidomimetics assessed as potential rescue molecules ("pharmacoperones") are from three differing chemical pedigrees (indoles, quinolones, and erythromycin-derived macrolides) and were originally developed as GnRH peptidomimetic antagonists. These structures were selected for this study because of their predicted ability to permeate the cell membrane and interact with a defined affinity with the GnRH receptor. All peptidomimetics studied with an IC(50) value (for hGnRHR)

  14. Making a bad thing worse: effects of communication of results of an epidemiological study after an aviation disaster.

    PubMed

    Verschuur, M; Spinhoven, P; van Emmerik, A; Rosendaal, F

    2007-10-01

    Cognitions attributing health complaints to disaster exposure are associated with more severe health complaints and are therefore a promising target for interventions. Little is known about the best strategy to modify such cognitions following exposure to a technological disaster at the community level. In 1992, a Boeing 747 crashed in a residential area in Amsterdam, the Netherlands. Persisting rumours about the possible toxic cargo of the plane led to increasing health concerns among the residents and rescue workers involved in the disaster. The current study investigates (a) the effectiveness of providing information on the health consequences of exposure to the aviation disaster to residents and rescue workers with varying degrees of exposure to the disaster, and (b) individual characteristics which may moderate the effectiveness of the health information provided. A total of 1019 rescue workers and 453 residents involved with varying degrees in the disaster participated in an epidemiological investigation and 1736 rescue workers and 339 residents, all involved, participated in an individual medical examination. Participants were assessed at baseline and 6 weeks after communication of the results of the epidemiological study. Main outcome measures evaluated health anxiety, somatic sensitivity, reassurance by a physician, psychopathology, post-traumatic stress symptoms, fatigue and quality of life. All participants reported elevated levels of psychopathology and fatigue, increased anxiety and uncertainties about their health 6 weeks after communication of the study results irrespective of the degree of exposure to the disaster. In particular, the conviction that health complaints were caused by toxic exposure was related to more severe health complaints and worries in both rescue workers and residents. Our study shows that communication about the health consequences of exposure to an aviation disaster at the community level has no symptom reducing or reassuring effects. Tailoring of the communication to individual characteristics such as existing expectancies may enhance its impact.

  15. The earthquake disaster risk characteristic and the problem in the earthquake emergency rescue of mountainous southwestern Sichuan

    NASA Astrophysics Data System (ADS)

    Yuan, S.; Xin, C.; Ying, Z.

    2016-12-01

    In recent years, earthquake disaster occurred frequently in Chinese mainland, the secondary disaster which have been caused by it is more serious in mountainous region. Because of the influence of terrain and geological conditions, the difficulty of earthquake emergency rescue work greatly increased, rescue force is also urged. Yet, it has been studied less on earthquake emergency rescue in mountainous region, the research in existing equipment whether can meet the actual needs of local earthquake emergency rescue is poorly. This paper intends to discuss and solve these problems. Through the mountainous regions Ganzi and Liangshan states in Sichuan field research, we investigated the process of earthquake emergency response and the projects for rescue force after an earthquake, and we also collected and collated local rescue force based data. By consulting experts and statistical analyzing the basic data, there are mainly two problems: The first is about local rescue force, they are poorly equipped and lack in the knowledge of medical help or identify architectural structure. There are no countries to establish a sound financial investment protection mechanism. Also, rescue equipment's updates and maintenance; The second problem is in earthquake emergency rescue progress. In the complicated geologic structure of mountainous regions, traffic and communication may be interrupted by landslides and mud-rock flows after earthquake. The outside rescue force may not arrive in time, rescue equipment was transported by manpower. Because of unknown earthquake disaster information, the local rescue force was deployed unreasonable. From the above, the local government worker should analyze the characteristics of the earthquake disaster in mountainous regions, and research how to improve their earthquake emergency rescue ability. We think they can do that by strengthening and regulating the rescue force structure, enhancing the skills and knowledge, training rescue workers, outfitting the light and portable rescue equipment, improving the public's self and mutual aid ability. All these measures will help local government reach the final goal of reducing the earthquake disaster.

  16. Nobiletin, a citrus flavonoid that improves memory impairment, rescues bulbectomy-induced cholinergic neurodegeneration in mice.

    PubMed

    Nakajima, Akira; Yamakuni, Tohru; Haraguchi, Mitsuya; Omae, Naoki; Song, Si-Young; Kato, Chieko; Nakagawasai, Osamu; Tadano, Takeshi; Yokosuka, Akihito; Mimaki, Yoshihiro; Sashida, Yutaka; Ohizumi, Yasushi

    2007-09-01

    We have recently reported that nobiletin, a citrus flavonoid, improves impaired memory in olfactory-bulbectomized (OBX) mice, which have been widely utilized as a useful paradigm that shares some major clinical features of Alzheimer's disease. Here, we examined the effects of nobiletin on OBX-induced cholinergic neurodegeneration in mice. OBX mice showed reduced acetylcholinesterase (AChE) staining and choline acetyltransferase (ChAT) expression in the hippocampus. An 11-day administration of nobiletin rescued OBX-induced decrease in the density of AChE-staining and ChAT expression in the hippocampus. These results suggest that nobiletin rescues OBX-induced cholinergic neurodegeneration, accompanied by improvement of impaired memory in OBX mice.

  17. Effect of Advanced Location Methods on Search and Rescue Duration for General Aviation Aircraft Accidents in the Contiguous United States

    ERIC Educational Resources Information Center

    Wallace, Ryan J.

    2013-01-01

    The purpose of this study was to determine the impact of advanced search and rescue devices and techniques on search duration for general aviation aircraft crashes. The study assessed three categories of emergency locator transmitters, including 121.5 MHz, 406 MHz, and GPS-Assisted 406 MHz devices. The impact of the COSPAS-SARSAT organization…

  18. Collaboration between Extension and Industry: Coordination and Assessment of Technical Large Animal Emergency Rescue Training

    ERIC Educational Resources Information Center

    Porr, C. A. Shea; Shultz, Alyx M.; Gimenez, Rebecca; Splan, Rebecca K.

    2016-01-01

    Rescuing large animals from emergency situations can be fraught with dangers not only to the animals but also to the rescuers. People involved at the scene of such an emergency are most likely to include first responders, horse owners, and veterinarians. These groups need to be aware of how they can best work together to effect a safe and…

  19. 30 CFR 49.40 - Requirements for large coal mines.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Requirements for large coal mines. 49.40 Section 49.40 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR EDUCATION AND TRAINING MINE RESCUE TEAMS Mine Rescue Teams for Underground Coal Mines § 49.40 Requirements for large coal...

  20. 30 CFR 49.40 - Requirements for large coal mines.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Requirements for large coal mines. 49.40 Section 49.40 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR EDUCATION AND TRAINING MINE RESCUE TEAMS Mine Rescue Teams for Underground Coal Mines § 49.40 Requirements for large coal...

  1. 30 CFR 49.30 - Requirements for small coal mines.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Requirements for small coal mines. 49.30 Section 49.30 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR EDUCATION AND TRAINING MINE RESCUE TEAMS Mine Rescue Teams for Underground Coal Mines § 49.30 Requirements for small coal...

  2. 30 CFR 49.40 - Requirements for large coal mines.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Requirements for large coal mines. 49.40 Section 49.40 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR EDUCATION AND TRAINING MINE RESCUE TEAMS Mine Rescue Teams for Underground Coal Mines § 49.40 Requirements for large coal...

  3. 30 CFR 49.30 - Requirements for small coal mines.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Requirements for small coal mines. 49.30 Section 49.30 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR EDUCATION AND TRAINING MINE RESCUE TEAMS Mine Rescue Teams for Underground Coal Mines § 49.30 Requirements for small coal...

  4. 30 CFR 49.40 - Requirements for large coal mines.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Requirements for large coal mines. 49.40 Section 49.40 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR EDUCATION AND TRAINING MINE RESCUE TEAMS Mine Rescue Teams for Underground Coal Mines § 49.40 Requirements for large coal...

  5. 30 CFR 49.40 - Requirements for large coal mines.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Requirements for large coal mines. 49.40 Section 49.40 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR EDUCATION AND TRAINING MINE RESCUE TEAMS Mine Rescue Teams for Underground Coal Mines § 49.40 Requirements for large coal...

  6. 30 CFR 49.30 - Requirements for small coal mines.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Requirements for small coal mines. 49.30 Section 49.30 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR EDUCATION AND TRAINING MINE RESCUE TEAMS Mine Rescue Teams for Underground Coal Mines § 49.30 Requirements for small coal...

  7. 30 CFR 49.30 - Requirements for small coal mines.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Requirements for small coal mines. 49.30 Section 49.30 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR EDUCATION AND TRAINING MINE RESCUE TEAMS Mine Rescue Teams for Underground Coal Mines § 49.30 Requirements for small coal...

  8. 30 CFR 49.30 - Requirements for small coal mines.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Requirements for small coal mines. 49.30 Section 49.30 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR EDUCATION AND TRAINING MINE RESCUE TEAMS Mine Rescue Teams for Underground Coal Mines § 49.30 Requirements for small coal...

  9. 40 CFR 1054.660 - What are the provisions for exempting emergency rescue equipment?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... certified to current emission standards under the following conditions if the equipment will be used solely in emergency rescue situations: (1) You must determine annually that no engines certified to current... situations” means firefighting or other situations in which a person is retrieved from imminent danger. (c...

  10. 42 CFR 84.3 - Respirators for mine rescue or other emergency use in mines.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 1 2014-10-01 2014-10-01 false Respirators for mine rescue or other emergency use in mines. 84.3 Section 84.3 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES APPROVAL OF RESPIRATORY PROTECTIVE...

  11. 42 CFR 84.3 - Respirators for mine rescue or other emergency use in mines.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Respirators for mine rescue or other emergency use in mines. 84.3 Section 84.3 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES APPROVAL OF RESPIRATORY PROTECTIVE...

  12. 42 CFR 84.3 - Respirators for mine rescue or other emergency use in mines.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 1 2013-10-01 2013-10-01 false Respirators for mine rescue or other emergency use in mines. 84.3 Section 84.3 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES APPROVAL OF RESPIRATORY PROTECTIVE...

  13. 42 CFR 84.3 - Respirators for mine rescue or other emergency use in mines.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 1 2012-10-01 2012-10-01 false Respirators for mine rescue or other emergency use in mines. 84.3 Section 84.3 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES APPROVAL OF RESPIRATORY PROTECTIVE...

  14. 42 CFR 84.3 - Respirators for mine rescue or other emergency use in mines.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 1 2011-10-01 2011-10-01 false Respirators for mine rescue or other emergency use in mines. 84.3 Section 84.3 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES APPROVAL OF RESPIRATORY PROTECTIVE...

  15. In vivo growth rates are poorly correlated with phage therapy success in a mouse infection model.

    PubMed

    Bull, J J; Otto, G; Molineux, I J

    2012-02-01

    Two classes of phages yield profoundly different levels of recovery in mice experimentally infected with an Escherichia coli O18:K1:H7 strain. Phages requiring the K1 capsule for infection (K1-dep) rescue virtually all infected mice, whereas phages not requiring the capsule (K1-ind) rescue modest numbers (∼30%). To rescue infected mice, K1-ind phages require at least a 10(6)-fold-higher inoculum than K1-dep phages. Yet their in vivo growth dynamics are only modestly inferior to those of K1-dep phages, and competition between the two phage types in the same mouse reveals only a slight growth advantage for the K1-dep phage. The in vivo growth rate seems unlikely to be the primary determinant of phage therapy success. An alternative explanation is that the success of K1-dep phages is due substantially to their proteomic composition. They encode an enzyme that degrades the K1 capsule, which has been shown in other work to be sufficient to cure infection in the complete absence of phages.

  16. Evaluation of the perioperative analgesic efficacy of buprenorphine, compared with butorphanol, in cats.

    PubMed

    Warne, Leon N; Beths, Thierry; Holm, Merete; Carter, Jennifer E; Bauquier, Sébastien H

    2014-07-15

    To compare the analgesic effects of buprenorphine and butorphanol in domestic cats. 2-phase positive-controlled randomized masked clinical trial. 39 healthy female cats (10 in phase 1 and 29 in phase 2). Cats admitted for ovariohysterectomy received buprenorphine (4 in phase 1; 14 in phase 2) or butorphanol (6 in phase 1; 15 in phase 2). In phase 1, cats were premedicated with buprenorphine (0.02 mg/kg [0.009 mg/lb], IM) or butorphanol (0.4 mg/kg [0.18 mg/lb], IM), in combination with medetomidine. Anesthesia was induced with propofol (IV) and maintained with isoflurane in oxygen. After extubation, medetomidine was antagonized with atipamezole. A validated multidimensional composite scale was used to assess signs of pain after surgery starting 20 minutes after extubation and continuing for up to 360 minutes, and pain score comparisons were made between the 2 groups. Phase 2 proceeded similar to phase 1 with the following addition: during wound closure, cats from the butorphanol and buprenorphine groups received butorphanol (0.4 mg/kg, IM) or buprenorphine (0.02 mg/kg, IM), respectively. Phase 1 of the study was stopped after 10 cats were ovariohysterectomized because 9 of 10 cats required rescue analgesia at the first evaluation. In phase 2, at the first pain evaluation, pain scores from the buprenorphine group were lower, and all cats from the butorphanol group required rescue analgesia. None of the cats from the buprenorphine group required rescue analgesia at any time. Buprenorphine (0.02 mg/kg, IM) given before surgery and during wound closure provided adequate analgesia for 6 hours following ovariohysterectomy in cats, whereas butorphanol did not.

  17. Dose finding study of granisetron in patients receiving high-dose cisplatin chemotherapy. The Granisetron Study Group.

    PubMed Central

    Riviere, A.

    1994-01-01

    The efficacy and safety of three different doses of granisetron (2 micrograms kg-1, group A; 10 micrograms kg-1, group B; 40 micrograms kg-1, group C) were compared in a randomised, double-blind study of 157 patients due to receive high-dose cisplatin therapy (mean dose > 97 mg m-2). In each group, up to two 3 mg rescue doses of granisetron were allowed if more than mild nausea or vomiting occurred. In group A 30.8%, in group B 61.5% and in group C 67.9% of patients were complete responders (i.e. no vomiting or nothing worse than mild nausea) during the first 24 h. These differences are significant between groups A and B, and A and C. There were no statistically significant differences in any efficacy variable between the 10 micrograms kg-1 and 40 micrograms kg-1 groups, although in each case the trend favoured the higher dose. Additional rescue doses resulted in resolved or improved symptoms in 95.3% for the first rescue dose and 93.3% for the second. Over the 7 days of the study, 82.7%, 82.7% and 86.8% of patients in groups A, B and C respectively were treated with granisetron alone. Headache was the most common side-effect, reported by 9.6% of patients; the majority of headaches were mild. There was no difference between the treatment groups regarding the adverse event rate. We concluded that prophylactic doses of 10 or 40 micrograms kg-1 lead to a safe and satisfactory degree of control of nausea and vomiting induced by high-dose cisplatin. PMID:8180032

  18. Physiological roles of trehalose in Leptinotarsa larvae revealed by RNA interference of trehalose-6-phosphate synthase and trehalase genes.

    PubMed

    Shi, Ji-Feng; Xu, Qing-Yu; Sun, Qiang-Kun; Meng, Qing-Wei; Mu, Li-Li; Guo, Wen-Chao; Li, Guo-Qing

    2016-10-01

    Trehalose is proposed to serve multiple physiological roles in insects. However, its importance remains largely unconfirmed. In the present paper, we knocked down either a trehalose biosynthesis gene (trehalose-6-phosphate synthase, LdTPS) or each of three degradation genes (soluble trehalases LdTRE1a, LdTRE1b or membrane-bound LdTRE2) in Leptinotarsa decemlineata by RNA interference (RNAi). Knockdown of LdTPS decreased trehalose content and caused larval and pupal lethality. The LdTPS RNAi survivors consumed a greater amount of foliage, obtained a heavier body mass, accumulated more glycogen, lipid and proline, and had a smaller amount of chitin compared with the controls. Ingestion of trehalose but not glucose rescued the food consumption increase and larval mass rise, increased survivorship, and recovered glycogen, lipid and chitin to the normal levels. In contrast, silencing of LdTRE1a increased trehalose content and resulted in larval and pupal lethality. The surviving LdTRE1a RNAi hypomorphs fed a smaller quantity of food, had a lighter body weight, depleted lipid and several glucogenic amino acids, and contained a smaller amount of chitin. Neither trehalose nor glucose ingestion rescued these LdTRE1a RNAi defects. Silencing of LdTRE1b caused little effects. Knockdown of LdTRE2 caused larval death, increased trehalose contents in several tissues and diminished glycogen in the brain-corpora cardiaca-corpora allata complex (BCC). Feeding glucose but not trehalose partially rescued the high mortality rate and recovered glycogen content in the BCC. It seems that trehalose is involved in feeding regulation, sugar absorption, brain energy supply and chitin biosynthesis in L. decemlineata larvae. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Examining the interrelationship of migraine onset, duration, and time to treatment.

    PubMed

    Landy, Stephen H; Runken, M Chris; Bell, Christopher F; Higbie, Rachel L; Haskins, Lisa S

    2012-03-01

    The objective of this study is to investigate migraines, both longitudinally and cross-sectionally, to understand the impact that time of treatment has on migraine duration and the patients' return to daily functioning. Several studies have explored the relationship between migraine treatment and its impact on migraine duration; however, the interrelationship of migraine onset and impact of treatment timing on migraine resolution is not completely understood. Five hundred and nine migraineurs completed 1 online baseline survey and a diary survey after each of their next 3 migraines. All subjects were 18 or older and were employed full time. Migraine episodes treated within 1 hour were significantly shorter on average than those treated after 1 hour (9.1 hours vs 12.3 hours) (P < .05). Over-the-counter medication was the most frequently reported first-line treatment (44%) followed by an oral triptan (30%), another prescription medication (14%), and combination therapy (4%). Rescue treatment was reported in 57% of attacks. The majority of over-the-counter (69%) and another prescription (55%) treated attacks required rescue whereas only 39% of first-line triptan attacks required rescue. Treating migraines early with an oral triptan-containing therapy appears to be a very effective method for reducing migraine duration and preventing the need for additional medication. Our findings also suggest that physicians should spend more time educating patients how to identify migraines early. Understanding the relationship between these key factors will provide insight into appropriate treatment and management of migraines, and more importantly, equip patients with the tools necessary to improve their outcomes and overall impact on functioning. © 2011 American Headache Society.

  20. Rescue of dopamine transporter function in hypoinsulinemic rats by a D2 receptor-ERK-dependent mechanism.

    PubMed

    Owens, W Anthony; Williams, Jason M; Saunders, Christine; Avison, Malcolm J; Galli, Aurelio; Daws, Lynette C

    2012-02-22

    The dopamine (DA) transporter (DAT) is a major target for abused drugs and a key regulator of extracellular DA. A rapidly growing literature implicates insulin as an important regulator of DAT function. We showed previously that amphetamine (AMPH)-evoked DA release is markedly impaired in rats depleted of insulin with the diabetogenic agent streptozotocin (STZ). Similarly, functional magnetic resonance imaging experiments revealed that the blood oxygenation level-dependent signal following acute AMPH administration in STZ-treated rats is reduced. Here, we report that these deficits are restored by repeated, systemic administration of AMPH (1.78 mg/kg, every other day for 8 d). AMPH stimulates DA D(2) receptors indirectly by increasing extracellular DA. Supporting a role for D(2) receptors in mediating this "rescue," the effect was completely blocked by pre-treatment of STZ-treated rats with the D(2) receptor antagonist raclopride before systemic AMPH. D(2) receptors regulate DAT cell surface expression through ERK1/2 signaling. In ex vivo striatal preparations, repeated AMPH injections increased immunoreactivity of phosphorylated ERK1/2 (p-ERK1/2) in STZ-treated but not control rats. These data suggest that repeated exposure to AMPH can rescue, by activating D(2) receptors and p-ERK signaling, deficits in DAT function that result from hypoinsulinemia. Our data confirm the idea that disorders influencing insulin levels and/or signaling, such as diabetes and anorexia, can degrade DAT function and that insulin-independent pathways are present that may be exploited as potential therapeutic targets to restore normal DAT function.

  1. Post-Traumatic Stress Symptoms and Burnout Among Medical Rescue Workers 4 Years After the Great East Japan Earthquake: A Longitudinal Study.

    PubMed

    Kawashima, Yuzuru; Nishi, Daisuke; Noguchi, Hiroko; Usuki, Masato; Yamashita, Akihiro; Koido, Yuichi; Okubo, Yoshiro; Matsuoka, Yutaka J

    2016-12-01

    This study aimed to evaluate factors associated with post-traumatic stress disorder (PTSD) symptoms and burnout 4 years after the Great East Japan Earthquake among medical rescue workers in Disaster Medical Assistance Teams (DMATs). We examined participants' background characteristics, prior health condition, rescue work experiences, and the Peritraumatic Distress Inventory (PDI) score at 1 month after the earthquake. Current psychological condition was assessed by the Impact of Event Scale-Revised and Maslach Burnout Inventory administered 4 years after the earthquake. By applying univariate and multivariate linear regression analyses, we assessed the relative value of the PDI and other baseline variables for PTSD symptoms and burnout at 4 years after the earthquake. We obtained baseline data from 254 participants during April 2 to 22, 2011. Of the 254 participants, 188 (74.0%) completed the follow-up assessment. PDI score 1 month after the earthquake was associated with symptoms of PTSD (β=0.35, P<.01) and burnout (β=0.21, P<.01). Stress before deployment was a related factor for burnout 4 years after the earthquake in these medical rescue workers (β=2.61, P<.04). It seems important for DMAT headquarters to establish a routine system for assessing the PDI of medical rescue workers after deployment and screen those workers who have high stress prior to deployment (Disaster Med Public Health Preparedness. 2016;10:848-853).

  2. A Novel Locomotion-based Validation Assay for Candidate Drugs Using Drosophila DYT1 Disease Model

    DTIC Science & Technology

    2013-11-01

    the genome using the same parental fly line, minimizing the effect of surrounding sequences and genetic variations on the ...locomotion and GTPC cyclrohydolase protein levels; (3) supplementation of dopamine can partially rescue the locomotion defects of Drosophila larvae...8217- GCGAACAACCAAAAAATCATTGAGATAATAAACTCCTCCATTAG-3’) to make dtorsin cDNA that lacks GAC (D307) (Fig. 1) respectively. After confirming mutated sequences , the insert was again

  3. FUS and TARDBP but Not SOD1 Interact in Genetic Models of Amyotrophic Lateral Sclerosis

    PubMed Central

    Kabashi, Edor; Bercier, Valérie; Lissouba, Alexandra; Liao, Meijiang; Brustein, Edna; Rouleau, Guy A.; Drapeau, Pierre

    2011-01-01

    Mutations in the SOD1 and TARDBP genes have been commonly identified in Amyotrophic Lateral Sclerosis (ALS). Recently, mutations in the Fused in sarcoma gene (FUS) were identified in familial (FALS) ALS cases and sporadic (SALS) patients. Similarly to TDP-43 (coded by TARDBP gene), FUS is an RNA binding protein. Using the zebrafish (Danio rerio), we examined the consequences of expressing human wild-type (WT) FUS and three ALS–related mutations, as well as their interactions with TARDBP and SOD1. Knockdown of zebrafish Fus yielded a motor phenotype that could be rescued upon co-expression of wild-type human FUS. In contrast, the two most frequent ALS–related FUS mutations, R521H and R521C, unlike S57Δ, failed to rescue the knockdown phenotype, indicating loss of function. The R521H mutation caused a toxic gain of function when expressed alone, similar to the phenotype observed upon knockdown of zebrafish Fus. This phenotype was not aggravated by co-expression of both mutant human TARDBP (G348C) and FUS (R521H) or by knockdown of both zebrafish Tardbp and Fus, consistent with a common pathogenic mechanism. We also observed that WT FUS rescued the Tardbp knockdown phenotype, but not vice versa, suggesting that TARDBP acts upstream of FUS in this pathway. In addition we observed that WT SOD1 failed to rescue the phenotype observed upon overexpression of mutant TARDBP or FUS or upon knockdown of Tardbp or Fus; similarly, WT TARDBP or FUS also failed to rescue the phenotype induced by mutant SOD1 (G93A). Finally, overexpression of mutant SOD1 exacerbated the motor phenotype caused by overexpression of mutant FUS. Together our results indicate that TARDBP and FUS act in a pathogenic pathway that is independent of SOD1. PMID:21829392

  4. FUS and TARDBP but not SOD1 interact in genetic models of amyotrophic lateral sclerosis.

    PubMed

    Kabashi, Edor; Bercier, Valérie; Lissouba, Alexandra; Liao, Meijiang; Brustein, Edna; Rouleau, Guy A; Drapeau, Pierre

    2011-08-01

    Mutations in the SOD1 and TARDBP genes have been commonly identified in Amyotrophic Lateral Sclerosis (ALS). Recently, mutations in the Fused in sarcoma gene (FUS) were identified in familial (FALS) ALS cases and sporadic (SALS) patients. Similarly to TDP-43 (coded by TARDBP gene), FUS is an RNA binding protein. Using the zebrafish (Danio rerio), we examined the consequences of expressing human wild-type (WT) FUS and three ALS-related mutations, as well as their interactions with TARDBP and SOD1. Knockdown of zebrafish Fus yielded a motor phenotype that could be rescued upon co-expression of wild-type human FUS. In contrast, the two most frequent ALS-related FUS mutations, R521H and R521C, unlike S57Δ, failed to rescue the knockdown phenotype, indicating loss of function. The R521H mutation caused a toxic gain of function when expressed alone, similar to the phenotype observed upon knockdown of zebrafish Fus. This phenotype was not aggravated by co-expression of both mutant human TARDBP (G348C) and FUS (R521H) or by knockdown of both zebrafish Tardbp and Fus, consistent with a common pathogenic mechanism. We also observed that WT FUS rescued the Tardbp knockdown phenotype, but not vice versa, suggesting that TARDBP acts upstream of FUS in this pathway. In addition we observed that WT SOD1 failed to rescue the phenotype observed upon overexpression of mutant TARDBP or FUS or upon knockdown of Tardbp or Fus; similarly, WT TARDBP or FUS also failed to rescue the phenotype induced by mutant SOD1 (G93A). Finally, overexpression of mutant SOD1 exacerbated the motor phenotype caused by overexpression of mutant FUS. Together our results indicate that TARDBP and FUS act in a pathogenic pathway that is independent of SOD1.

  5. Online Learning Techniques for Improving Robot Navigation in Unfamiliar Domains

    DTIC Science & Technology

    2010-12-01

    In In Proceedings of the 1996 Symposium on Human Interaction and Complex Systems, pages 276–283, 1996. 6.1 [15] Colin Campbell and Kristin P. Bennett...ISBN 0-262-19450-3. 5.1 [104] Jean Scholtz, Jeff Young, Jill L. Drury , and Holly A. Yanco. Evaluation of human-robot interaction awareness in search...2004. 6.1 [147] Holly A. Yanco and Jill L. Drury . Rescuing interfaces: A multi-year study of human-robot interaction at the AAAI robot rescue

  6. MiR-144 regulates hematopoiesis and vascular development by targeting meis1 during zebrafish development.

    PubMed

    Su, Zhenhong; Si, Wenxia; Li, Lei; Zhou, Bisheng; Li, Xiuchun; Xu, Yan; Xu, Chengqi; Jia, Haibo; Wang, Qing K

    2014-04-01

    Hematopoiesis is a dynamic process by which peripheral blood lineages are developed. It is a process tightly regulated by many intrinsic and extrinsic factors, including transcriptional factors and signaling molecules. However, the epigenetic regulation of hematopoiesis, for example, regulation via microRNAs (miRNAs), remains incompletely understood. Here we show that miR-144 regulates hematopoiesis and vascular development in zebrafish. Overexpression of miR-144 inhibited primitive hematopoiesis as demonstrated by a reduced number of circulating blood cells, reduced o-dianisidine staining of hemoglobin, and reduced expression of hbαe1, hbβe1, gata1 and pu.1. Overexpression of miR-144 also inhibited definitive hematopoiesis as shown by reduced expression of runx1 and c-myb. Mechanistically, miR-144 regulates hematopoiesis by repressing expression of meis1 involved in hematopoiesis. Both real-time RT-PCR and Western blot analyses showed that overexpression of miR-144 repressed expression of meis1. Bioinformatic analysis predicts a target binding sequence for miR-144 at the 3'-UTR of meis1. Deletion of the miR-144 target sequence eliminated the repression of meis1 expression mediated by miR-144. The miR-144-mediated abnormal phenotypes were partially rescued by co-injection of meis1 mRNA and could be almost completely rescued by injection of both meis1 and gata1 mRNA. Finally, because meis1 is involved in vascular development, we tested the effect of miR-144 on vascular development. Overexpression of miR-144 resulted in abnormal vascular development of intersegmental vessels in transgenic zebrafish with Flk1p-EGFP, and the defect was rescued by co-injection of meis1 mRNA. These findings establish miR-144 as a novel miRNA that regulates hematopoiesis and vascular development by repressing expression of meis1. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. SAP97 Controls the Trafficking and Resensitization of the Beta-1-Adrenergic Receptor through Its PDZ2 and I3 Domains

    PubMed Central

    Nooh, Mohammed M.; Naren, Anjaparavanda P.; Kim, Sung-Jin; Xiang, Yang K.; Bahouth, Suleiman W.

    2013-01-01

    Previous studies have determined that the type-1 PDZ sequence at the extreme carboxy-terminus of the ß1-adrenergic receptor (ß1-AR) binds SAP97 and AKAP79 to organize a scaffold involved in trafficking of the ß1-AR. In this study we focused on characterizing the domains in SAP97 that were involved in recycling and resensitization of the ß1-AR in HEK-293 cells. Using a SAP97 knockdown and rescue strategy, we determined that PDZ-deletion mutants of SAP97 containing PDZ2 rescued the recycling and resensitization of the ß1-AR. Among the three PDZs of SAP97, PDZ2 displayed the highest affinity in binding to the ß1-AR. Expression of isolated PDZ2, but not the other PDZs, inhibited the recycling of the ß1-AR by destabilizing the macromolecular complex involved in trafficking and functional resensitization of the ß1-AR. In addition to its PDZs, SAP97 contains other protein interacting domains, such as the I3 sequence in the SRC homology-3 (SH3) domain, which binds to AKAP79. Deletion of I3 from SAP97 (ΔI3-SAP97) did not affect the binding of SAP97 to the ß1-AR. However, ΔI3-SAP97 could not rescue the recycling of the ß1-AR because it failed to incorporate AKAP79/PKA into the SAP97-ß1-AR complex. Therefore, bipartite binding of SAP97 to the ß1-AR and to AKAP79 is necessary for SAP97-mediated effects on recycling, externalization and functional resensitization of the ß1-AR. These data establish a prominent role for PDZ2 and I3 domains of SAP97 in organizing the ß1-adrenergic receptosome involved in connecting the ß1-AR to trafficking and signaling networks. PMID:23696820

  8. Correlations between FEV1 and patient-reported outcomes: A pooled analysis of 23 clinical trials in patients with chronic obstructive pulmonary disease.

    PubMed

    Donohue, James F; Jones, Paul W; Bartels, Christian; Marvel, Jessica; D'Andrea, Peter; Banerji, Donald; Morris, David G; Patalano, Francesco; Fogel, Robert

    2018-04-01

    In clinical trials of inhaled bronchodilators, chronic obstructive pulmonary disease (COPD) guidelines recommend that patient-reported outcomes (PROs) are assessed alongside lung function. How these endpoints are related is unclear. Pooled longitudinal data from 23 randomised controlled COPD studies were analyzed (N = 23,213). Treatments included long-acting β 2 agonists, long-acting muscarinic antagonists (LABAs or LAMAs) and the LABA/LAMA combination QVA149. Outcome measures were Transition Dyspnoea Index (TDI) and St. George's Respiratory Questionnaire (SGRQ) scores, COPD exacerbation frequency and rescue medication use. Relationships between changes in trough forced expiratory volume in one second (ΔFEV 1 ) and outcomes following treatment were assessed using correlations of data summaries and model-based analysis: generalized linear mixed-effect regression modelling to determine if ΔFEV 1 could predict patient outcomes with different treatments. Mean age was 64 years, 73% were male, and most had moderate (45%) or severe (52%) disease. Statistically significant correlations were observed between ΔFEV 1 and each outcome measure (exacerbations Rs = 0.05; rescue medication, SGRQ, TDI, r = 0.11-0.16; all p < .001). Patients with greater improvements in trough FEV 1 had on average better SGRQ and TDI scores, fewer exacerbations, and used less rescue medication. For SGRQ and TDI scores, minimal clinically important differences were observed over the range of pooled ΔFEV 1 values. Model-based predictions confirmed the treatment effect was partly explained by changes in FEV 1 from baseline with improvements in PROs observed across all treatments when trough FEV 1 improved. Across all endpoints active treatments were better than placebo (p < .0001), and LABA/LAMA treatment resulted in numerically better treatment outcomes than either monocomponent. These data suggest that FEV 1 improvements post-bronchodilation correlate with PRO improvements. Further improvements in patient outcomes may be expected by maximizing lung function improvements. Registration details for the 23 randomised controlled studies used in this pooled analysis are supplied in Additional File 4. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Functional divergence of MYB-related genes, WEREWOLF and AtMYB23 in Arabidopsis.

    PubMed

    Tominaga-Wada, Rumi; Nukumizu, Yuka; Sato, Shusei; Kato, Tomohiko; Tabata, Satoshi; Wada, Takuji

    2012-01-01

    Epidermal cell differentiation in Arabidopsis is studied as a model system to understand the mechanisms that determine the developmental end state of plant cells. MYB-related transcription factors are involved in cell fate determination. To examine the molecular basis of this process, we analyzed the functional relationship of two R2R3-type MYB genes, AtMYB23 (MYB23) and WEREWOLF (WER). MYB23 is involved in leaf trichome formation. WER represses root-hair formation. Swapping domains between MYB23 and WER, we found that a low homology region of MYB23 might be involved in ectopic trichome initiation on hypocotyls. MYB23 and all MYB23-WER (MW) chimeric transgenes rescued the increased root-hair phenotype of the wer-1 mutant. Although WER did not rescue the gl1-1 no-trichome phenotype, MYB23 and all MW chimeric transgenes rescued gl1-1. These results suggest that MYB23 acquired a specific function for trichome differentiation during evolution.

  10. Effect of magnesium added to local anesthetics for caudal anesthesia on postoperative pain in pediatric surgical patients: A systematic review and meta-analysis with Trial Sequential Analysis.

    PubMed

    Kawakami, Hiromasa; Mihara, Takahiro; Nakamura, Nobuhito; Ka, Koui; Goto, Takahisa

    2018-01-01

    Magnesium has been investigated as an adjuvant for neuraxial anesthesia, but the effect of caudal magnesium on postoperative pain is inconsistent. The aim of this systematic review and meta-analysis was to evaluate the analgesic effect of caudal magnesium. We searched six databases, including trial registration sites. Randomized clinical trials reporting the effect of caudal magnesium on postoperative pain after general anesthesia were eligible. The risk ratio for use of rescue analgesics after surgery was combined using a random-effects model. We also assessed adverse events. The I2 statistic was used to assess heterogeneity. We assessed risk of bias with Cochrane domains. We controlled type I and II errors due to sparse data and repetitive testing with Trial Sequential Analysis. We assessed the quality of evidence with GRADE. Four randomized controlled trials (247 patients) evaluated the need for rescue analgesics. In all four trials, 50 mg of magnesium was administered with caudal ropivacaine. The results suggested that the need for rescue analgesia was reduced significantly by caudal magnesium administration (risk ratio 0.45; 95% confidence interval 0.24-0.86). There was considerable heterogeneity as indicated by an I2 value of 62.5%. The Trial Sequential Analysis-adjusted confidence interval was 0.04-5.55, indicating that further trials are required. The quality of evidence was very low. The rate of adverse events was comparable between treatment groups. Caudal magnesium may reduce the need for rescue analgesia after surgery, but further randomized clinical trials with a low risk of bias and a low risk of random errors are necessary to assess the effect of caudal magnesium on postoperative pain and adverse events. University Hospital Medical Information Network Clinical Trials Registry UMIN000025344.

  11. Sick-leave and help seeking among rescue workers after the terror attacks in Norway, 2011.

    PubMed

    Gjerland, Astrid; Pedersen, May Janne Botha; Ekeberg, Øivind; Skogstad, Laila

    2015-12-01

    Several studies have addressed psychological problems after terror attacks, especially among victims. Fewer have addressed possible health consequences among rescue workers involved with terror attacks. This study's aim was to investigate the levels of sick-leave and psychological help seeking among rescue workers involved in the terror attacks in Norway on July 22, 2011, and to identify associations between sick-leave and background-, exposure- and work-related variables. This cross-sectional study included five groups of professional rescue personnel and one group of unaffiliated volunteers. The questionnaire was distributed approximately 10 months after the terror attacks, with a response rate of 61.3 % (N = 1790). A total of 9.7 % of participants self-reported sick-leave. The rate varied from 2.4 % among police officers to 14.5 % among unaffiliated volunteers, p < .001. There were 0.0-1.2 % of the professionals who were on sick-leave for more than 2 weeks and 5.5 % among the unaffiliated volunteers. More unaffiliated volunteers (42.6 %) and psychosocial personnel (16.3 %) consulted a psychologist or psychiatrist compared to other groups (3-9 %), p < .001. General healthcare providers (OR 6.1), psychosocial personnel (OR 6.3) and unaffiliated volunteers (OR 5.7) were associated with sick-leave, together with unwanted stress reactions (OR 1.6) and starting work on July 22 (OR 1.6). A small minority of professional rescue workers reported sick-leave for more than 2 weeks, and few had sought psychological help. Unaffiliated volunteers reported more stress symptoms, longer sick-leave duration and more psychological help seeking. This group may benefit from more support.

  12. Rescue Sedation With Intranasal Dexmedetomidine for Pediatric Ophthalmic Examination After Chloral Hydrate Failure: A Randomized, Controlled Trial.

    PubMed

    Gan, Xiaoliang; Lin, Haotian; Chen, Jingjing; Lin, Zhuoling; Lin, Yiquan; Chen, Weirong

    2016-06-01

    It is a challenge to rescue ophthalmology examinations performed in children in the sedation room after initial chloral hydrate failure. Intranasal dexmedetomidine can be used in rescue sedation in children undergoing computed tomography. The present study aimed to assess the efficacy and tolerability of intranasal dexmedetomidine use in children undergoing ophthalmic examination after chloral hydrate failure. Sixty uncooperative pediatric patients with cataract (aged 5-36 months; weight, 7-15 kg) presented for follow-up ophthalmic examination. Patients who experienced chloral hydrate failure were randomized to 1 of 2 groups to receive intranasal dexmedetomidine 1 or 2 μg/kg for rescue sedation. Each group contained 30 patients. The primary outcome was the rate of a successful ophthalmic examination. Secondary outcomes included sedation onset time, recovery time, duration of examination, discharge time, and adverse events, including percentage of heart rate reduction, respiratory depression, vomiting, and postsedative agitation. A successful ophthalmic examination was achieved in 93.3% (28/30) of patients in the 2-μg/kg dose group and in 66.7% (20/30) of patients in the 1-μg/kg dose group (P = 0.021). The onset time, recovery time, and discharge time did not significantly differ between the 2 groups. None of the patients required clinical intervention due to heart rate reduction, and none of the patients in either group experienced vomiting, respiratory depression, or agitation after the administration of dexmedetomidine. In children undergoing ophthalmic examination, intranasal dexmedetomidine can be administered in the sedation room for rescue sedation after chloral hydrate failure, with the 2-μg/kg dose being more efficacious than the 1-μg/kg dose, as measured by success rate. ClinicalTrials.gov identifier: NCT02077712. Copyright © 2016 Elsevier HS Journals, Inc. All rights reserved.

  13. Sustaining Statewide Disaster Response Capabilities from a Fire Service Perspective

    DTIC Science & Technology

    2013-03-01

    2010). These increased capabilities can be vital to the success of response operations that involve automobile accidents, train wrecks , boat...Trench Rescue  Subterranean Rescue  Dive Rescue  Wilderness Rescue 2. 1670 Operations and Training for Technical Search and Rescue Incidents The

  14. The 4Rs of Aquatic Rescue: educating the public about safety and risks of bystander rescue.

    PubMed

    Moran, Kevin; Webber, Jonathon; Stanley, Teresa

    2017-09-01

    From 1980 to 2014, 87 persons drowned in New Zealand while attempting to rescue others; all incidents occurred in open water and most (80%) fatalities were male. While bystander rescue has been promoted as a way of preventing drowning, little is known about the knowledge base that informs potential rescuers. This study utilized a family water safety programme to promote a resource entitled the 4Rs of Aquatic Rescue. Participants (n = 174) completed a pre-intervention survey and were then provided with information and access to electronic resources on safe bystander rescue techniques. Most respondents (71%) had never been taught rescue techniques, and males were more confident of their rescue ability. Upon completion of the programme, significant differences were evident in respondents' understanding of rescue safety, but this did not translate to greater confidence or disposition towards performing a rescue. Ways of promoting bystander safety around water are discussed and recommendations for future studies are made.

  15. Evolutionary rescue in vertebrates: evidence, applications and uncertainty

    PubMed Central

    Vander Wal, E.; Garant, D.; Festa-Bianchet, M.; Pelletier, F.

    2013-01-01

    The current rapid rate of human-driven environmental change presents wild populations with novel conditions and stresses. Theory and experimental evidence for evolutionary rescue present a promising case for species facing environmental change persisting via adaptation. Here, we assess the potential for evolutionary rescue in wild vertebrates. Available information on evolutionary rescue was rare and restricted to abundant and highly fecund species that faced severe intentional anthropogenic selective pressures. However, examples from adaptive tracking in common species and genetic rescues in species of conservation concern provide convincing evidence in favour of the mechanisms of evolutionary rescue. We conclude that low population size, long generation times and limited genetic variability will result in evolutionary rescue occurring rarely for endangered species without intervention. Owing to the risks presented by current environmental change and the possibility of evolutionary rescue in nature, we suggest means to study evolutionary rescue by mapping genotype → phenotype → demography → fitness relationships, and priorities for applying evolutionary rescue to wild populations. PMID:23209171

  16. Role of mammalian homologue of Caenorhabditis elegans unc-13-1 (Munc13-1) in the recruitment of newcomer insulin granules in both first and second phases of glucose-stimulated insulin secretion in mouse islets.

    PubMed

    Xie, L; Zhu, D; Gaisano, H Y

    2012-10-01

    We have previously reported that the haplodeficient Munc13-1(+/-) mouse exhibits impaired biphasic glucose-stimulated insulin secretion (GSIS), causing glucose intolerance mimicking type 2 diabetes. Glucagon-like peptide-1 (GLP-1) can bypass these insulin-secretory defects in type 2 diabetes, but the mechanism of exocytotic events mediated by GLP-1 in rescuing insulin secretion is unclear. The total internal reflection fluorescence microscopy (TIRFM) technique was used to examine single insulin granule fusion events in mouse islet beta cells. There was no difference in the density of docked granules in the resting state between Munc13-1(+/+) and Munc13-1(+/-) mouse islet beta cells. While exocytosis of previously docked granules in Munc13-1(+/-) beta cells is reduced during high-K(+) stimulation as expected, we now find a reduction in additional exocytosis events that account for the major portion of GSIS, namely two types of newcomer granules, one which has a short docking time (short-dock) and another undergoing no docking before exocytosis (no-dock). As mammalian homologue of Caenorhabditis elegans unc-13-1 (Munc13-1) is a phorbol ester substrate, phorbol ester could partially rescue biphasic GSIS in Munc13-1-deficient beta cells by enhancing recruitment of short-dock newcomer granules for exocytosis. The more effective rescue of biphasic GSIS by GLP-1 than by phorbol was due to increased recruitment of both short-dock and no-dock newcomer granules. Phorbol ester and GLP-1 potentiation of biphasic GSIS are brought about by recruitment of distinct populations of newcomer granules for exocytosis, which may be mediated by Munc13-1 interaction with syntaxin-SNARE complexes other than that formed by syntaxin-1A.

  17. Efficacy and safety of parecoxib/phloroglucinol combination therapy versus parecoxib monotherapy for acute renal colic: a randomized, double-blind clinical trial.

    PubMed

    Fu, Weihua; Yao, Jiwei; Li, Qianwei; Wang, Yongquan; Wu, Xiaojun; Zhou, Zhansong; Li, Wei-Bing; Yan, Jun-An

    2014-05-01

    To investigate whether the addition of phloroglucinol to parecoxib could improve the efficacy in patients with acute renal colic. Patients of acute renal colic were randomly allocated to receive intravenous Parecoxib 40 mg plus placebo or Parecoxib 40 mg plus phloroglucinol 80 mg, respectively. Pain intensity was recorded using a visual analog scale (VAS) before drug administration and 5, 15, 30, 60, and 120 min after treatment start. The primary outcome was the mean pain intensity difference (PID) at each checkpoint and the effectiveness of drugs (≥ 50 % decrease in VAS score at the end checkpoint). The need for rescue analgesics and the incidence of adverse effects were considered as secondary outcome of the study. Among 236 patients enrolled in the study, 119 patients received intravenous parecoxib plus placebo and 114 patients received intravenous parecoxib plus phloroglucinol, the remaining 3 patients given up treatment. Baseline demographics were similar between two groups. There are significant differences in the PID at 15 and 30 min between two groups (P15 min = 0.011, P30 min = 0.013). Rescue analgesics were required by 17 patients (14.3 %) receiving parecoxib, 7 patients (6.1 %) receiving parecoxib plus phloroglucinol (P = 0.041). There were no differences in PID at other checkpoints between two groups, as well as in the incidence of adverse events and the drug effectiveness. Parecoxib in combination with phloroglucinol for acute renal colic has a faster action, also reduces the demand of rescue analgesics.

  18. Intelligent systems for urban search and rescue: challenges and lessons learned

    NASA Astrophysics Data System (ADS)

    Jacoff, Adam; Messina, Elena; Weiss, Brian A.

    2003-09-01

    Urban search and rescue (USAR) is one of the most dangerous and time-critical non-wartime activities. Researchers have been developing hardware and software to enable robots to perform some search and rescue functions so as to minimize the exposure of human rescue personnel to danger and maximize the survival of victims. Significant progress has been achieved, but much work remains. USAR demands a blending of numerous specialized technologies. An effective USAR robot must be endowed with key competencies, such as being able to negotiate collapsed structures, find victims and assess their condition, identify potential hazards, generate maps of the structure and victim locations, and communicate with rescue personnel. These competencies bring to bear work in numerous sub-disciplines of intelligent systems (or artificial intelligence) such as sensory processing, world modeling, behavior generation, path planning, and human-robot interaction, in addition to work in communications, mechanism design and advanced sensors. In an attempt to stimulate progress in the field, reference USAR challenges are being developed and propagated worldwide. In order to make efficient use of finite research resources, the robotic USAR community must share a common understanding of what is required, technologically, to attain each competency, and have a rigorous measure of the current level of effectiveness of various technologies. NIST is working with partner organizations to measure the performance of robotic USAR competencies and technologies. In this paper, we describe the reference test arenas for USAR robots, assess the current challenges within the field, and discuss experiences thus far in the testing effort.

  19. Pharmacological Chaperones of the Dopamine Transporter Rescue Dopamine Transporter Deficiency Syndrome Mutations in Heterologous Cells.

    PubMed

    Beerepoot, Pieter; Lam, Vincent M; Salahpour, Ali

    2016-10-14

    A number of pathological conditions have been linked to mutations in the dopamine transporter gene, including hereditary dopamine transporter deficiency syndrome (DTDS). DTDS is a rare condition that is caused by autosomal recessive loss-of-function mutations in the dopamine transporter (DAT), which often affects transporter trafficking and folding. We examined the possibility of using pharmacological chaperones of DAT to rescue DTDS mutations. After screening a set of known DAT ligands for their ability to increase DAT surface expression, we found that bupropion and ibogaine increased DAT surface expression, whereas others, including cocaine and methylphenidate, had no effect. Bupropion and ibogaine increased wild type DAT protein levels and also promoted maturation of the endoplasmic reticulum (ER)-retained DAT mutant K590A. Rescue of K590A could be blocked by inhibiting ER to Golgi transport using brefeldin A. Furthermore, knockdown of coat protein complex II (COPII) component SEC24D, which is important in the ER export of wild type DAT, also blocked the rescue effects of bupropion and ibogaine. These data suggest that bupropion and ibogaine promote maturation of DAT by acting as pharmacological chaperones in the ER. Importantly, both drugs rescue DAT maturation and functional activity of the DTDS-associated mutations A314V and R445C. Together, these results are the first demonstration of pharmacological chaperoning of DAT and suggest this may be a viable approach to increase DAT levels in DTDS and other conditions associated with reduced DAT function. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  20. Post-traumatic stress disorder status in a rescue group after the Wenchuan earthquake relief

    PubMed Central

    Huang, Junhua; Liu, Qunying; Li, Jinliang; Li, Xuejiang; You, Jin; Zhang, Liang; Tian, Changfu; Luan, Rongsheng

    2013-01-01

    Previous studies have suggested that the incidence of post-traumatic stress disorder in earthquake rescue workers is relatively high. Risk factors for this disorder include demographic characteristics, earthquake-related high-risk factors, risk factors in the rescue process, personality, social support and coping style. This study examined the current status of a unit of 1 040 rescue workers who participated in earthquake relief for the Wenchuan earthquake that occurred on May 12th, 2008. Post-traumatic stress disorder was diagnosed primarily using the Clinician-Administered Post-traumatic Stress Disorder Scale during structured interviews. Univariate and multivariate statistical analyses were used to examine major risk factors that contributed to the incidence of post-traumatic stress disorder. Results revealed that the incidence of this disorder in the rescue group was 5.96%. The impact factors in univariate analysis included death of family members, contact with corpses or witnessing of the deceased or seriously injured, near-death experience, severe injury or mental trauma in the rescue process and working at the epicenter of the earthquake. Correlation analysis suggested that post-traumatic stress disorder was positively correlated with psychotic and neurotic personalities, negative coping and low social support. Impact factors in multivariate logistic regression analysis included near-death experience, severe injury or mental trauma, working in the epicenter of the rescue, neurotic personality, negative coping and low social support, among which low social support had the largest odds ratio of 20.42. Findings showed that the occurrence of post-traumatic stress disorder was the result of the interaction of multiple factors. PMID:25206499

  1. Copper Transporter ATP7A Protects Against Endothelial Dysfunction in Type 1 Diabetic Mice by Regulating Extracellular Superoxide Dismutase

    PubMed Central

    Sudhahar, Varadarajan; Urao, Norifumi; Oshikawa, Jin; McKinney, Ronald D.; Llanos, Roxana M.; Mercer, Julian F.B.; Ushio-Fukai, Masuko; Fukai, Tohru

    2013-01-01

    Oxidative stress and endothelial dysfunction contribute to vascular complication in diabetes. Extracellular superoxide dismutase (SOD3) is one of the key antioxidant enzymes that obtains copper via copper transporter ATP7A. SOD3 is secreted from vascular smooth muscles cells (VSMCs) and anchors at the endothelial surface. The role of SOD3 and ATP7A in endothelial dysfunction in type 1 diabetes mellitus (T1DM) is entirely unknown. Here we show that the specific activity of SOD3, but not SOD1, is decreased, which is associated with increased O2•− production in aortas of streptozotocin-induced and genetically induced Ins2Akita T1DM mice. Exogenous copper partially rescued SOD3 activity in isolated T1DM vessels. Functionally, acetylcholine-induced, endothelium-dependent relaxation is impaired in T1DM mesenteric arteries, which is rescued by SOD mimetic tempol or gene transfer of SOD3. Mechanistically, ATP7A expression in T1DM vessels is dramatically decreased whereas other copper transport proteins are not altered. T1DM-induced endothelial dysfunction and decrease of SOD3 activity are rescued in transgenic mice overexpressing ATP7A. Furthermore, SOD3-deficient T1DM mice or ATP7A mutant T1DM mice augment endothelial dysfunction and vascular O2•− production versus T1DM mice. These effects are in part due to hypoinsulinemia in T1DM mice, since insulin treatment, but not high glucose, increases ATP7A expression in VSMCs and restores SOD3 activity in the organoid culture of T1DM vessels. In summary, a decrease in ATP7A protein expression contributes to impaired SOD3 activity, resulting in O2•− overproduction and endothelial dysfunction in blood vessels of T1DM. Thus, restoring copper transporter function is an essential therapeutic approach for oxidant stress–dependent vascular and metabolic diseases. PMID:23884884

  2. Mortality among rescue and recovery workers and community members exposed to the September 11, 2001 World Trade Center terrorist attacks, 2003-2014.

    PubMed

    Jordan, Hannah T; Stein, Cheryl R; Li, Jiehui; Cone, James E; Stayner, Leslie; Hadler, James L; Brackbill, Robert M; Farfel, Mark R

    2018-05-01

    Multiple chronic health conditions have been associated with exposure to the September 11, 2001 World Trade Center (WTC) terrorist attacks (9/11). We assessed whether excess deaths occurred during 2003-2014 among persons directly exposed to 9/11, and examined associations of 9/11-related exposures with mortality risk. Deaths occurring in 2003-2014 among members of the World Trade Center Health Registry, a cohort of rescue/recovery workers and lower Manhattan community members who were exposed to 9/11, were identified via linkage to the National Death Index. Participants' overall levels of 9/11-related exposure were categorized as high, intermediate, or low. We calculated standardized mortality ratios (SMR) using New York City reference rates from 2003 to 2012. Proportional hazards were used to assess associations of 9/11-related exposures with mortality, accounting for age, sex, race/ethnicity and other potential confounders. We identified 877 deaths among 29,280 rescue/recovery workers (3.0%) and 1694 deaths among 39,643 community members (4.3%) during 308,340 and 416,448 person-years of observation, respectively. The SMR for all causes of death was 0.69 [95% confidence interval (CI) 0.65-0.74] for rescue/recovery workers and 0.86 (95% CI 0.82-0.90) for community members. SMRs for diseases of the cardiovascular and respiratory systems were significantly lower than expected in both groups. SMRs for several other causes of death were significantly elevated, including suicide among rescue recovery workers (SMR 1.82, 95% CI 1.35-2.39), and brain malignancies (SMR 2.25, 95% CI 1.48-3.28) and non-Hodgkin's lymphoma (SMR 1.79, 95% CI 1.24-2.50) among community members. Compared to low exposure, both intermediate [adjusted hazard ratio (AHR) 1.36, 95% CI 1.10-1.67] and high (AHR 1.41, 95% CI 1.06-1.88) levels of 9/11-related exposure were significantly associated with all-cause mortality among rescue/recovery workers (p-value for trend 0.01). For community members, intermediate (AHR 1.13, 95% CI 1.01-1.27), but not high (AHR 1.14, 95% CI 0.94-1.39) exposure was significantly associated with all-cause mortality (p-value for trend 0.03). AHRs for associations of overall 9/11-related exposure with heart disease- and cancer-related mortality were similar in magnitude to those for all-cause mortality, but with 95% CIs crossing the null value. Overall mortality was not elevated. Among specific causes of death that were significantly elevated, suicide among rescue/recovery workers is a plausible long-term consequence of 9/11 exposure, and is potentially preventable. Elevated mortality due to other causes, including non-Hodgkin's lymphoma and brain cancer, and small but statistically significant associations of 9/11-related exposures with all-cause mortality hazard warrant additional surveillance. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  3. Ten years of helicopter emergency medical services in Germany: do we still need the helicopter rescue in multiple traumatised patients?

    PubMed

    Andruszkow, Hagen; Hildebrand, Frank; Lefering, Rolf; Pape, Hans-Christoph; Hoffmann, Reinhard; Schweigkofler, Uwe

    2014-10-01

    Helicopter emergency medical service (HEMS) has been established in the preclinical treatment of multiple traumatised patients despite an ongoing controversy towards the potential benefit. Celebrating the 20th anniversary of TraumaRegister DGU(®) of the German Trauma Society (DGU) the presented study intended to provide an overview of HEMS rescue in Germany over the last 10 years analysing the potential beneficial impact of a nationwide helicopter rescue in multiple traumatised patients. We analysed TraumaRegister DGU(®) including multiple traumatised patients (ISS ≥ 16) between 2002 and 2012. In-hospital mortality was defined as main outcome. An adjusted, multivariate regression with 13 confounders was performed to evaluate the potential survival benefit. 42,788 patients were included in the present study. 14,275 (33.4%) patients were rescued by HEMS and 28,513 (66.6%) by GEMS. Overall, 66.8% (n=28,569) patients were transported to a level I trauma centre and 28.2% (n=12,052) to a level II trauma centre. Patients rescued by HEMS sustained a higher injury severity compared to GEMS (ISS HEMS: 29.5 ± 12.6 vs. 27.5 ± 11.8). Helicopter rescue teams performed more on-scene interventions, and mission times were increased in HEMS rescue (HEMS: 77.2 ± 28.7 min. vs. GEMS: 60.9 ± 26.9 min.). Linear regression analysis revealed that the frequency of HEMS rescue has decreased significantly between 2002 and 2012. In case of transportation to level I trauma centres a decrease of 1.7% per year was noted (p<0.001) while a decline of 1.6% per year (p<0.001) was measured for level II trauma centre admissions. According to multivariate logistic regression HEMS was proven a positive independent survival predictor between 2002 and 2012 (OR 0.863; 95%-CI 0.800-0.930; Nagelkerkes-R(2) 0.539) with only little differences between each year. This study was able to prove an independent survival benefit of HEMS in multiple traumatised patients during the last 10 years. Despite this fact, a constant decline of HEMS rescue missions was found in multiple trauma patients due to unknown reasons. We concluded that HEMS should be used more often in case of trauma in order to guarantee the proven benefit for multiple traumatised patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Transgenic rescue demonstrates involvement of the Ian5 gene in T cell development in the rat.

    PubMed

    Michalkiewicz, Mieczyslaw; Michalkiewicz, Teresa; Ettinger, Ruth A; Rutledge, Elizabeth A; Fuller, Jessica M; Moralejo, Daniel H; Van Yserloo, Brian; MacMurray, Armand J; Kwitek, Anne E; Jacob, Howard J; Lander, Eric S; Lernmark, Ake

    2004-10-04

    A single point mutation in a novel immune-associated nucleotide gene 5 (Ian5) coincides with severe T cell lymphopenia in BB rats. We used a transgenic rescue approach in lymphopenic BB-derived congenic F344.lyp/lyp rats to determine whether this mutation is responsible for lymphopenia and to establish the functional importance of this novel gene. A 150-kb P1 artificial chromosome (PAC) transgene harboring a wild-type allele of the rat Ian5 gene restored Ian5 transcript and protein levels, completely rescuing the T cell lymphopenia in the F344.lyp/lyp rats. This successful complementation provides direct functional evidence that the Ian5 gene product is essential for maintaining normal T cell levels. It also demonstrates that transgenic rescue in the rat is a practical and definitive method for revealing the function of a novel gene.

  5. Di (2-ethylhexyl) phthalate inhibits growth of mouse ovarian antral follicles through an oxidative stress pathway

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wang, Wei, E-mail: weiwang2@illinois.edu; Craig, Zelieann R., E-mail: zelieann@illinois.edu; Basavarajappa, Mallikarjuna S., E-mail: mbasava2@illinois.edu

    2012-01-15

    Di (2-ethylhexyl) phthalate (DEHP) is a plasticizer that has been shown to inhibit growth of mouse antral follicles, however, little is known about the mechanisms by which DEHP does so. Oxidative stress has been linked to follicle growth inhibition as well as phthalate-induced toxicity in non-ovarian tissues. Thus, we hypothesized that DEHP causes oxidative stress and that this leads to inhibition of the growth of antral follicles. To test this hypothesis, antral follicles isolated from CD-1 mice (age 31–35 days) were cultured with vehicle control (dimethylsulfoxide [DMSO]) or DEHP (1–100 μg/ml) ± N-acetyl cysteine (NAC, an antioxidant at 0.25–1 mM).more » During culture, follicles were measured daily. At the end of culture, follicles were collected and processed for in vitro reactive oxygen species (ROS) assays to measure the presence of free radicals or for measurement of the expression and activity of various key antioxidant enzymes: Cu/Zn superoxide dismutase (SOD1), glutathione peroxidase (GPX) and catalase (CAT). The results indicate that DEHP inhibits the growth of follicles compared to DMSO control and that NAC (0.25–1 mM) blocks the ability of DEHP to inhibit follicle growth. Furthermore, DEHP (10 μg/ml) significantly increases ROS levels and reduces the expression and activity of SOD1 compared to DMSO controls, whereas NAC (0.5 mM) rescues the effects of DEHP on ROS levels and SOD1. However, the expression and activity of GPX and CAT were not affected by DEHP treatment. Collectively, these data suggest that DEHP inhibits follicle growth by inducing production of ROS and by decreasing the expression and activity of SOD1. -- Highlights: ► DEHP inhibits growth and increases reactive oxygen species in ovarian antral follicles in vitro. ► NAC rescues the effects of DEHP on the growth and reactive oxygen species levels in follicles. ► DEHP decreases the expression and activity of Cu/Zn superoxide dismutase, which can be rescued by NAC, in antral follicles.« less

  6. MLN4924 sensitizes monocytes and maturing dendritic cells for TNF-dependent and -independent necroptosis.

    PubMed

    El-Mesery, Mohamed; Seher, Axel; Stühmer, Thorsten; Siegmund, Daniela; Wajant, Harald

    2015-03-01

    MLN4924 prevents the formation of active cullin-RING ubiquitin ligase complexes and thus inhibits NF-κB signalling. Here, we evaluated the effects of this compound on monocytes and dendritic cells (DCs). Monocytes and DCs were challenged with TNF or LPS in the presence and absence of MLN4924. The effects of MLN4924 on cellular viability, pro-inflammatory gene induction and DC maturation were investigated using the MTT assay, elisa and FACS analysis. Mechanisms of cell death induction were evaluated by using inhibitors of caspases, RIPK1 and MLKL. MLN4924 inhibited NF-κB activation and sensitized monocytes and immature DCs (iDCs) for TNFR1-induced cell death. Neither the caspase inhibitor zVAD-fmk, the RIPK1 inhibitor necrostatin-1 (nec-1) nor the MLKL inhibitor necrosulfonamide (NSA) alone prevented TNF-induced cell death. A combination of zVAD-fmk and nec-1 or NSA, however, rescued monocytes and iDCs from MLN4924/TNF-induced cell death indicating that MLN4924 affects anti-apoptotic and anti-necrotic activities in TNFR1 signalling. MLN4924 also converted the response of iDCs to LPS from maturation to cell death. LPS-induced cell death in MLN4924-treated iDCs was again only effectively blocked by cotreatment with zVAD-fmk and nec-1 or NSA. Noteworthy, MLN4924/LPS-induced cell death was almost completely independent of endogenous TNF. MLN4924 also strongly inhibited maturation and activation of iDCs that were rescued from cell death by zVAD-fmk and nec-1. Our data reveal a strong dual suppressive effect of MLN4924 on DC activity. The targeting of NAE by MLN4924 could be a new way to treat inflammatory diseases. © 2014 The British Pharmacological Society.

  7. The Coumarin Derivative Osthole Stimulates Adult Neural Stem Cells, Promotes Neurogenesis in the Hippocampus, and Ameliorates Cognitive Impairment in APP/PS1 Transgenic Mice.

    PubMed

    Kong, Liang; Hu, Yu; Yao, Yingjia; Jiao, Yanan; Li, Shaoheng; Yang, Jingxian

    2015-01-01

    It is believed that neuronal death caused by abnormal deposition of amyloid-beta peptide is the major cause of the cognitive decline in Alzheimer's disease. Adult neurogenesis plays a key role in the rescue of impaired neurons and amelioration of cognitive impairment. In the present study, we demonstrated that osthole, a natural coumarin derivative, was capable of promoting neuronal stem cell (NSC) survival and inducing NSC proliferation in vitro. In osthole-treated APP/PS1 transgenic mice, a significant improvement in learning and memory function was seen, which was associated with a significant increase in the number of new neurons (Ki67(+)/NF-M(+)) and a decrease in apoptotic cells in the hippocampal region of the brain. These observations suggested that osthole promoted NSC proliferation, supported neurogenesis, and thus efficiently rescued impaired neurons in the hippocampus and ameliorated cognitive impairment. We also found that osthole treatment activated the Notch pathway and upregulated the expression of self-renewal genes Notch 1 and Hes 1 mRNA in NSCs. However, when Notch activity was blocked by the γ-secretase inhibitor DAPT, the augmentation of Notch 1 and Hes 1 protein was ameliorated, and the proliferation-inducing effect of osthole was abolished, suggesting that the effects of osthole are at least in part mediated by activation of the Notch pathway.

  8. 46 CFR 108.560 - Rescue boats.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 4 2014-10-01 2014-10-01 false Rescue boats. 108.560 Section 108.560 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) A-MOBILE OFFSHORE DRILLING UNITS DESIGN AND EQUIPMENT Lifesaving Equipment § 108.560 Rescue boats. Each unit must carry at least one rescue boat. Each rescue boat...

  9. 46 CFR 108.560 - Rescue boats.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 4 2012-10-01 2012-10-01 false Rescue boats. 108.560 Section 108.560 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) A-MOBILE OFFSHORE DRILLING UNITS DESIGN AND EQUIPMENT Lifesaving Equipment § 108.560 Rescue boats. Each unit must carry at least one rescue boat. Each rescue boat...

  10. 46 CFR 108.560 - Rescue boats.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 4 2011-10-01 2011-10-01 false Rescue boats. 108.560 Section 108.560 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) A-MOBILE OFFSHORE DRILLING UNITS DESIGN AND EQUIPMENT Lifesaving Equipment § 108.560 Rescue boats. Each unit must carry at least one rescue boat. Each rescue boat...

  11. 46 CFR 199.262 - Rescue boats.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Rescue boats. 199.262 Section 199.262 Shipping COAST... SYSTEMS FOR CERTAIN INSPECTED VESSELS Additional Requirements for Cargo Vessels § 199.262 Rescue boats. (a) Each cargo vessel must carry at least one rescue boat. Each rescue boat must be approved under approval...

  12. 46 CFR 199.262 - Rescue boats.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 7 2011-10-01 2011-10-01 false Rescue boats. 199.262 Section 199.262 Shipping COAST... SYSTEMS FOR CERTAIN INSPECTED VESSELS Additional Requirements for Cargo Vessels § 199.262 Rescue boats. (a) Each cargo vessel must carry at least one rescue boat. Each rescue boat must be approved under approval...

  13. 46 CFR 199.160 - Rescue boat embarkation, launching and recovery arrangements.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 7 2014-10-01 2014-10-01 false Rescue boat embarkation, launching and recovery... Vessels § 199.160 Rescue boat embarkation, launching and recovery arrangements. (a) Each rescue boat must... be used to meet this requirement. (b) Each rescue boat embarkation and launching arrangement must...

  14. 46 CFR 199.262 - Rescue boats.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 7 2012-10-01 2012-10-01 false Rescue boats. 199.262 Section 199.262 Shipping COAST... SYSTEMS FOR CERTAIN INSPECTED VESSELS Additional Requirements for Cargo Vessels § 199.262 Rescue boats. (a) Each cargo vessel must carry at least one rescue boat. Each rescue boat must be approved under approval...

  15. 46 CFR 199.262 - Rescue boats.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 7 2014-10-01 2014-10-01 false Rescue boats. 199.262 Section 199.262 Shipping COAST... SYSTEMS FOR CERTAIN INSPECTED VESSELS Additional Requirements for Cargo Vessels § 199.262 Rescue boats. (a) Each cargo vessel must carry at least one rescue boat. Each rescue boat must be approved under approval...

  16. 46 CFR 199.160 - Rescue boat embarkation, launching and recovery arrangements.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 7 2012-10-01 2012-10-01 false Rescue boat embarkation, launching and recovery... Vessels § 199.160 Rescue boat embarkation, launching and recovery arrangements. (a) Each rescue boat must... be used to meet this requirement. (b) Each rescue boat embarkation and launching arrangement must...

  17. 46 CFR 199.262 - Rescue boats.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 7 2013-10-01 2013-10-01 false Rescue boats. 199.262 Section 199.262 Shipping COAST... SYSTEMS FOR CERTAIN INSPECTED VESSELS Additional Requirements for Cargo Vessels § 199.262 Rescue boats. (a) Each cargo vessel must carry at least one rescue boat. Each rescue boat must be approved under approval...

  18. 46 CFR 199.160 - Rescue boat embarkation, launching and recovery arrangements.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 7 2013-10-01 2013-10-01 false Rescue boat embarkation, launching and recovery... Vessels § 199.160 Rescue boat embarkation, launching and recovery arrangements. (a) Each rescue boat must... be used to meet this requirement. (b) Each rescue boat embarkation and launching arrangement must...

  19. 46 CFR 199.160 - Rescue boat embarkation, launching and recovery arrangements.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Rescue boat embarkation, launching and recovery... Vessels § 199.160 Rescue boat embarkation, launching and recovery arrangements. (a) Each rescue boat must... be used to meet this requirement. (b) Each rescue boat embarkation and launching arrangement must...

  20. 46 CFR 199.160 - Rescue boat embarkation, launching and recovery arrangements.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 7 2011-10-01 2011-10-01 false Rescue boat embarkation, launching and recovery... Vessels § 199.160 Rescue boat embarkation, launching and recovery arrangements. (a) Each rescue boat must... be used to meet this requirement. (b) Each rescue boat embarkation and launching arrangement must...

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