The competitive NMDA antagonist CPP protects substantia nigra neurons from MPTP-induced degeneration in primates

Degeneration of nigrostriatal dopaminergic neurons is the primary histopathological feature of Parkinson's disease. The neurotoxin MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) induces a neurological syndrome in man and non-human primates very similar to idiopathic Parkinson's disease by selectively destroying dopaminergic nigrostriatal neurons. This gives rise to the hypothesis that Parkinson's disease may be caused by endogenous or environmental toxins. Endogenous excitatory amino acids (EAAs) such as L-glutamate could be involved in neurodegenerative disorders including Parkinson's disease. We report in this study that the competitive NMDA antagonist CPP (3-((+/-)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid) protects nigral tyrosine hydroxylase (TH) positive neurons from degeneration induced by systemic treatment with MPTP in common marmosets. This indicates that EAAs are involved in the pathophysiological cascade of MPTP-induced neuronal cell death and that EAA antagonists may offer a neuroprotective therapy for Parkinson's disease

How to feed the cities? Co-creating inclusive, healthy and sustainable city region food systems

People drive transitions. Current urban living conditions, specifically food systems, challenge the health, wellbeing and coherence of individuals and whole societies, and for effective change toward resilient communities, people need to reinvent the way they produce, distribute and consume food. Consequently, in their communities' people are creating foodscapes and governing the transition toward sustainable local food systems. Here, we introduce a conceptual framework to develop this transformation through empowering the urban multi-stakeholder society as the agent of this process. To do so, we reviewed scientific evidence and experiences from seven selected City Regions (Albacete, Baku, Dresden, Izmir, Ljubljana, Megara, and Valparaiso) as case studies and conducted a SWOT analysis to explore the capacity of food systems to enhance multi-functionality of urban landscapes, with special focus on social cohesion and quality of life. We grasp existing policies; hone them and leverage policies and strategies toward human-centered actions for future proofing food systems.Peer Reviewe

Combined Hepatocellular Cholangiocarcinomas; Analysis of a Large Database

Aim Combined hepatocellular cholangiocarcinoma (combined tumor) has been described as either a variant of hepatoma or a variant of cholangiocarcinoma. Prior studies evaluated fewer than 50 patients with combined tumors, precluding multivariate analyses. Posited was the notion that analysis of a large database would yield more definite answers. Methods This study used SEER (Surveillance, Epidemiology, and End Results Program of the National Cancer Institute) to analyze 282 combined tumors, 2,035 intrahepatic cholangiocarcinomas, and 19,336 hepatomas between the years 1973-2003. Multinomial logit regression calculated point estimates and 95% confidence intervals (c.i.) for relative risk (rr). Cox regression calculated point estimates and 95% confidence intervals (c.i.) for hazard ratios (ĥ). Results Men less often had cholangiocarcinomas than they had combined tumors (rr = 0.63, c.i. = 0.49-0.81). Hepatomas less often than combined tumors presented with distant spread (rr = 0.56, c.i. = 0.43-0.72). Men (rr = 1.50, c.i. = 1.17-1.93) and patients with a known Asian or Pacific birthplace (rr = 2.36, c.i. = 1.56-3.56) more often had hepatomas than they had combined tumors. Among patients not known to have an Asian/Pacific birthplace, a diagnosis of cholangiocarcinoma (ĥ = 0.72, c.i. = 0.63-0.82) or hepatoma (ĥ = 0.75, c.i. = 0.66-0.86) provided a better prognosis than did a diagnosis of combined tumor. Conclusion Combined tumors differ from hepatomas and cholangiocarcinomas in terms of distribution and survival patterns in the population; they should be considered neither cholangiocarcinomas nor hepatomas

The Use of a Driving Simulator to Assess Senior Driver Performance: Increasing Situational Awareness Through Post-Drive One-on-One Advisement

Older drivers are over-represented in angled impact crashes and experience a higher fatality rate than their younger counterparts. Due to the gradual deterioration of the senses, diminished cognitive processing capabilities and decreased mobility and flexibility, it is more difficult for older drivers to gather and process information about their environment. This can lead older drivers to incorrectly perceive their driving environment as safe, when in reality it is not. The current study investigates whether post-drive feedback following a simulated drive can effectively change older drivers’ attitudes about their own driving ability and influence them to incorporate additional compensatory behaviors into their day-to-day driving

Pancreas Cancer Survival in the Gemcitabine Era

After multiple positive studies, gemcitabine, approved for the treatment of pancreas cancer by the FDA in 1977, became standard of care. Whether this therapeutic advance has translated into longer survival for pancreas cancer patients in general has not been established. This study, derived from SEER (Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute) data, compared the survival experiences of the gemcitabine (1998–2004) and pre-gemcitabine (1988–1997) eras for 7,151 patients who had metastatic disease and did not undergo extirpative surgery, 14,369 patients who had not undergone surgery and had metastases, 5,042 patients who had undergone surgery and did not have metastases, and 5,011 patients who had undergone surgery and had metastases. Calculated survival time ratios (TR) were adjusted for radiotherapy history, grade, nodal status, loco-regional extent of disease, age, race, and gender. For those who did not undergo extirpative surgery, improvements in survival in the gemcitabine era (1998–2004) versus the prior time period (1988–1997) seen for patients with metastatic cancer (TR = 1.20, 95% c.i. 1.15–1.25) were not seen for those without metastatic cancer (TR = 1.05, 95% c.i. 1.00–1.15). For those who did undergo extirpative surgery, improvements were much more dramatic for those with metastatic cancer (TR = 1.61, 95% c.i. 1.45–1.80) than those without metastases (TR = 1.23, 95% c.i. 1.15–1.31). The results are consistent with the notion that the promising findings with respect to gemcitabine in the controlled clinical trials have found expression in the general population of patients with pancreas cancer

Use of the wound healing trajectory as an outcome determinant for acute wound healing

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72454/1/j.1524-475x.2000.00511.x.pd

Palonosetron compared with ondansetron in pediatric cancer patients: multicycle analysis of a randomized Phase III study

Aim: To investigate across multiple cycles the efficacy and safety of palonosetron in the prevention of chemotherapy-induced nausea and vomiting in pediatric cancer patients receiving highly or moderately emetogenic chemotherapy (HEC/MEC). Patients & methods: Patients were randomly assigned to 10, 20 mu g/kg palonosetron or 3 x 150 mu g/kg ondansetron for up to four cycles of HEC/MEC. Results: In all on-study chemotherapy cycles, complete response rates were higher in patients in the 20 mu g/kg palonosetron group than the ondansetron group. Treatment-emergent adverse events were comparable between the palonosetron 20 mu g/kg and ondansetron groups. Conclusion: Over four cycles of HEC/MEC, 20 mu g/kg palonosetron was an efficacious and safe treatment for the prevention of chemotherapy-induced nausea and vomiting in pediatric cancer patients