The Gilded Clot: Review of Metal-Modulated Platelet Activation, Coagulation, and Fibrinolysis.

The processes of blood coagulation and fibrinolysis that in part maintain the physical integrity of the circulatory system and fluidity of its contents are complex as they are critical for life. While the roles played by cellular components and circulating proteins in coagulation and fibrinolysis are widely acknowledged, the impact of metals on these processes is at best underappreciated. In this narrative review we identify twenty-five metals that can modulate the activity of platelets, plasmatic coagulation, and fibrinolysis as determined by in vitro and in vivo investigations involving several species besides human beings. When possible, the molecular interactions of the various metals with key cells and proteins of the hemostatic system were identified and displayed in detail. It is our intention that this work serve not as an ending point, but rather as a fair evaluation of what mechanisms concerning metal interactions with the hemostatic system have been elucidated, and as a beacon to guide future investigation.

The Achilles Tendon Response to a Bout of Running is not affected by Triceps Surae Stretch Training in Runners.

An acute bout of distance running decreases Achilles tendon CSA. The purpose of this study was to examine if three-week stretch training of the Achilles tendon alters the Achilles tendon thinning response to running. Thirty-three recreational runners were divided into a control group (n = 17) and an intervention group (n = 16). The intervention included a three-week soleus stretch (knee flexed) and gastrocnemius stretch (knee extended). Three gastrocnemius stretches and three soleus stretches were performed each day, six days per week. Stretches were held for 30 s per repetition for a total duration of 180 s per leg per day. Achilles tendon CSA and range of motion measures were completed pre and post-run before and after the three-week stretching intervention. The runs prior to and following the three-week stretch training intervention both resulted in a 6% decrease in Achilles tendon CSA (p < 0.0001). There was no interaction across time between control and intervention groups in CSA (p = 0.446). Only the intervention group experienced a significant increase in dorsiflexion range of motion following the stretch training (p = 0.009). We therefore conclude that even when an increased dorsiflexion range of motion occurs, three weeks of triceps surae stretching does not alter the response of the Achilles tendon CSA.

Structure-function analysis of SAP97, a modular scaffolding protein that drives dendrite growth.

Activation of AMPA receptors assembled with the GluA1 subunit can promote dendrite growth in a manner that depends on its direct binding partner, SAP97. SAP97 is a modular scaffolding protein that has at least seven recognizable protein-protein interaction domains. Several complementary approaches were employed to show that the dendrite branching promoting action of full length SAP97 depends on ligand(s) that bind to the PDZ3 domain. Ligand(s) to PDZ1, PDZ2 and I3 domains also contribute to dendrite growth. The ability of PDZ3 ligand(s) to promote dendrite growth depends on localization at the plasma membrane along with GluA1 and SAP97. These results suggest that the assembly of a multi-protein complex at or near synapses is vital for the translation of AMPA-R activity into dendrite growth.

Does overwinter temperature affect maternal body composition and egg traits in yellow perch Perca flavescens?

Female yellow perch Perca flavescens exposed to three overwinter temperature regimes (4, 8 and 13° C) for 150 days spawned in markedly different proportions upon spring warming (37% of females in 4° C v. 64 and 91% in 8 and 13° C treatments, respectively), but exhibited no differences in fecundity, egg size or egg lipid content. Females held at 4° C also exhibited less within-clutch egg size variation than females held at 13° C. Moreover, eggs differed among temperature treatments in the overall proportions of 18 fatty acids, with the colder treatments resulting in potentially higher quality eggs containing more of the unsaturated fatty acids C16:1, C22:6-n3 and C18:2 cis. Female somatic condition also varied with temperature. Maternal somatic growth and protein content increased while lipid content decreased in 13° C compared to the colder treatments. There were, however, no differences among treatments in the fatty acid composition of maternal muscle. These results suggest that the temperatures experienced during winter may be less influential to P. flavescens egg size or number, which may exhibit relatively little plasticity in this species, but can alter both the number of females that spawn and the overall composition of eggs and maternal somatic tissues, which may have implications for future reproductive success.

Selective changes in single cell GABA(A) receptor subunit expression and function in temporal lobe epilepsy.

Temporal lobe epilepsy is the most prevalent seizure disorder in adults. Compromised inhibitory neurotransmitter function in the hippocampus contributes to the hyperexcitability generating this condition, but the underlying molecular mechanisms are unknown. Combining patch-clamp recording and single-cell mRNA amplification (aRNA) techniques in single dentate granule cells, we demonstrate that expression of GABA(A) receptor subunit mRNAs is substantially altered in neurons from epileptic rats. These changes in gene expression precede epilepsy onset by weeks and correlate with profound alterations in receptor function, indicating that aberrant GABA(A) receptor expression and function has an essential role in the process of epileptogenesis.

Rufinamide for the treatment of epileptic spasms.

OBJECTIVE: The purpose of this study was to determine the safety and efficacy of rufinamide for treatment of epileptic spasms. METHODS: We retrospectively reviewed patients treated with rufinamide for epileptic spasms from January 2009 to March 2010. Age, presence of hypsarrhythmia, change in seizure frequency following rufinamide initiation, and side effects were assessed. Patients who had a ≥ 50% reduction in spasm frequency were considered responders. RESULTS: Of all 107 children treated with rufinamide during the study period, 38 (36%) had epileptic spasms. Median patient age was 7 years (range: 17 months to 23). One patient had hypsarrhythmia at the time of treatment with rufinamide, and 9 other patients had a history of hypsarrhythmia. Median starting dose of rufinamide was 9 mg/kg/day (range: 2-18) and median final treatment dose was 39 mg/kg/day (range: 8-92). All patients were receiving concurrent antiepileptic drug therapy, with the median number of antiepileptic drugs being 3 (range: 2-6). Median duration of follow-up since starting rufinamide was 171 days (range: 10-408). Responder rate was 53%. Median reduction in spasm frequency was 50% (interquartile range=-56 to 85%, P<0.05). Two patients (5%) achieved a >99% reduction in spasms. Rufinamide was discontinued in 7 of 38 patients (18%) because of lack of efficacy, worsening seizures, or other side effects. Minor side effects were reported in 14 of 38 patients (37%). CONCLUSIONS: Rufinamide appears to be a well-tolerated and efficacious adjunctive therapeutic option for children with epileptic spasms. A prospective study is warranted to validate our observations.

The Morfeo Study: A 1-year follow-up of complications of vegetative state in a dedicated facility.

OBJECTIVES: Vegetative State (VS) implies significant issues. The aim of the MORFEO study is to identify the most relevant complications in VS patients and to supply clinicians and policy-makers with data derived from the analysis of a cohort of patients treated in a dedicated long-term facility setting. METHODS: A cohort of 22 VS patients treated between 2003 and 2007 were enrolled and followed up for 1 year. The information recorded were: Disability Rating Scale (DRS), Levels of Cognitive Functioning (LCF), pressure sores, nutritional status, neurological complications, articular complications (passive range of motion-ROM), deep-vein thrombosis and infections. The Kolmogorov-Smirnov test was used to verify the normal distribution of the variables. The indicators of complications were analysed with the Friedman test (continuous variables) and with the Cochran Q test (dichotomous variables). RESULTS: DRS and LCF values showed no significant variation. The number of pressure sores decreased. The nutritional status remained satisfying. The ROM worsened in lower limb joints; a trend (p = ns) towards an improved range was observed in shoulders and elbows. Fifteen infections were recorded. CONCLUSIONS: The data that proved significant suggest a minimum set of quality-of-care indicators in VS patients: pressure sores follow-up, nutritional status, ROM and incidence of infections.

Temporal and geospatial trends of pediatric cancer incidence in Nebraska over a 24-year period.

BACKGROUND: Data from the Surveillance, Epidemiology, and End Results (SEER) revealed that the incidence of pediatric cancer in Nebraska exceeded the national average during 2009-2013. Further investigation could help understand these patterns. METHODS: This retrospective cohort study investigated pediatric cancer (0-19 years old) age adjusted incidence rates (AAR) in Nebraska using the Nebraska Cancer Registry. SEER AARs were also calculated as a proxy for pediatric cancer incidence in the United States (1990-2013) and compared to the Nebraska data. Geographic Information System (GIS) mapping was also used to display the spatial distribution of cancer in Nebraska at the county level. Finally, location-allocation analysis (LAA) was performed to identify a site for the placement of a medical center to best accommodate rural pediatric cancer cases. RESULTS: The AAR of pediatric cancers was 173.3 per 1,000,000 in Nebraska compared to 167.1 per 1,000,000 in SEER. The AAR for lymphoma was significantly higher in Nebraska (28.1 vs. 24.6 per 1,000,000; p = 0.009). For the 15-19 age group, the AAR for the 3 most common pediatric cancers were higher in Nebraska (p < 0.05). Twenty-three counties located >2 h driving distance to care facilities showed at least a 10% higher incidence than the overall state AAR. GIS mapping identified a second potential treatment site that would alleviate this geographic burden. CONCLUSIONS: Regional differences within Nebraska present a challenge for rural populations. Novel use of GIS mapping to highlight regional differences and identify solutions for access to care issues could be used by similar states.

Transformation of NIH 3T3 cells by cotransfection with c-src and nuclear oncogenes.

pp60c-src, the cellular homolog of the Rous sarcoma virus transforming protein, does not completely transform cells even when present at high levels, but has been shown to be involved in polyomavirus-induced transformation when activated by polyomavirus middle T (pmt)-antigen binding. Here we show that cotransfection, but not solo transfection, of expression plasmids for c-src and either adenovirus E1A, v-myc, c-myc, or the 5' half of polyomavirus large T (pltN) antigen into NIH 3T3 cells induces anchorage-independent growth, enhanced focus formation, and, for pltN cotransfection, tumorigenicity in adult NFS mice. Enhancement of transformation was not observed with polyomavirus small t (pst) antigen. Cotransfection of c-src with pltN induced modification of pp60c-src that altered its electrophoretic mobility and in vivo phosphorylation state and stimulated its in vitro kinase activity. Similar alterations were not seen after c-src-E1A cotransfection, suggesting that at least two different mechanisms of enhancement are involved.

Lemons into lemonade.

A booming economy can make layoffs in the biotechnology industry a blessing in disguise.