X-ray absorption analysis of the active site of Streptomyces antibioticus Tyrosinase upon binding of transition state analogue inhibitors

The key structural features that define the reaction mechanism of the binuclear copper enzyme Tyrosinase (Ty) from Streptomyces antibioticus were investigated by X-ray absorption spectroscopy. The data for the met form, the halide bound derivative and the adduct with the competitive inhibitor and transition state analogue Kojic acid were analysed using the recently developed MXAN package. This analysis permitted the definition of structural clusters that include all atoms within 5 A from the metal ions of the active site. The data obtained for the different forms provide validation of the structural models previously proposed on the basis of the magnetic properties investigated by both pulsed EPR and paramagnetic NMR spectroscopies. The structural model of the reaction center obtained in this solution study is compared with the crystallographic structures recently proposed for several derivatives of bacterial Ty to suggest that only one of these structures is relevant to solution conditions. (C) 2007 Elsevier Inc. All rights reserved

Running power: lab based vs. portable devices measurements and its relationship with aerobic power

In recent years, different companies have developed devices that estimate \u201crunning power\u201d. The main objective of this paper is to evaluate the effect of running speed on aerobic and running powers measured using force plates and by different devices. The second objective is to evaluate the relationship between aerobic power and running powers measured using force plates and by different devices. We enrolled 11 subjects in the study, they performed 5-min running trials at 2.22, 2.78, 3.33, 3.89 and 4.44 m/s respectively on a force-measuring treadmill while we collected metabolic data. We calculated running power as the dot product of ground reaction force and velocity of the centre of mass and compared it to the running power estimates of three devices: Skillrun (Technogym), Stryd Summit Powermeter (Stryd) and Garmin HRM-Run (Garmin). We found statistically significant linear correlations with running powers measured by all devices and running speed. Although absolute running power measurements were different among devices, an increase of 1 m/s in running speed translated to an increase of 0.944 W/kg in running power (p < 0.001). We found statistically significant linear correlations with running powers measured by all devices and aerobic power, in particular: as aerobic power increases by 1 W/kg, running power increases by 0.218 W/kg for all devices (p < 0.001). For level treadmill running, across speeds, running power measured by commercially available devices reflects force-based measurements and it can be a valuable metric, providing quasi real-time feedback during training sessions and competitions. Highlights We evaluated the effect of running speed on aerobic and running powers measured using force plates and by different devices. We also compared the relationship between aerobic power and running powers measured using force plates and by different devices. We found statistically significant linear correlations with running powers measured by all devices and aerobic power, in particular: as aerobic power increases by 1 W/kg, running power increases by 0.218 W/kg for all devices. For level treadmill running, across speeds, running power measured by commercially available devices reflects force-based measurements and it can be a valuable metric, providing quasi real-time feedback during training sessions and competitions

Cancer of the anal region

Cancer of the anal region represents 3-3.5% of all anorectal tumours. The peak incidence is between 58 and 64 years. Since 1960 an increased incidence among men younger than 45 years, and among women has been observed. The number of women diagnosed with anal canal cancer (7 per 1000000 person per years) is twice as much as that of men, while anal margins cancers are more frequent in men (4 per 1000000 person per years). Tumour extension determines the different treatment strategies, aiming at definite cure, with a conservative approach. Small tumours can be resected without mutilating surgery, while for larger tumours combination of chemotherapy and radiotherapy is the standard treatment, even though a combination of chemotherapy and radiotherapy has been recently introduced. Long-term quality of life (QOL) scores are acceptable, with the exception of patients who experience severe anal dysfunction

Improving the primary care consultation for diabetes and depression through digital medical interview assistant systems: Narrative review

10.2196/18109Journal of Medical Internet Research228e1810

Evaluation of the inhaled dose across different microenvironments

The principal aim of the INSIDE project (INdividual air pollution exposure, extracellular vescicles SIgnaling and hypertensive disorder DEvelopment in pregnancy) is to assess the molecular effects of environmental exposure to airborne particulate matter (PM) of susceptible subject. Different approaches are considered to evaluate these effects, including an exposure-effect study performed on a selected population. The short-term exposure to different pollutants (PM and NO2) was evaluated considering 51 subjects recruited from October 2017 to April 2018. Each subject was asked to carry personal instruments for few hours before a clinical evaluation (blood and cardiological examination) from home to hospital. Instruments used in the study were: (I) CairClip-CairPol (NO2) and (II) Aerocet 831-Aerosol Mass Monitor, Met One Instruments (size-fractionated PM). Moreover, a (III) smartphone with a GPS application and a (IV) Time Activity Diary (TAD) were used in this study to acquire information about the microenvironments (MEs) visited by subjects during the monitoring sessions. The experimental design of the project allowed to further investigate issues related to the mode of exposure: through the analysis of TADs and GPS data, it was possible to document the time spent by each subject in the different MEs and characterize the average exposure and inhaled dose associated to different MEs. The microenvironmental inhaled dose of pollutants was estimated considering the average exposure to PM and NO2, the time spent across these MEs and the specific ventilation rate of each subject. Moreover, to understand which of these parameters has the major impact of the dose model, a sensitivity analysis was performed, on the total and on the MEs dataset

Does V600E BRAF mutation predict vinorelbine efficacy? A proof-of-concept from a lung micropapillary adenocarcinoma metastatic to the breast

BRAF mutations occur in about 3% of all lung adenocarcinomas and V600E missense mutation characterizes about half of BRAFmutated lung adenocarcinomas and is significantly associated with micropapillary pattern and shorter disease-free and overall survival rates. In this report, we report a challenging case of a patient with a metastatic micropapillary adenocarcinoma of the lung harbouring V600E BRAF mutation who experienced a surprising protracted clinical response to metronomic vinorelbine. The possible association between the V600E BRAF mutation pathway and the effective use of vinca alkaloid is discussed

Is the combination of Cetuximab with chemo-radiotherapy regimens worthwhile in the treatment of locally advanced head and neck cancer? A review of current evidence

The administration of Cetuximab in combination with radiotherapy and chemotherapy has shown clear survival improvements within the locally advanced and the relapsed/metastatic settings respectively. These results have provided the clinical rational for the inclusion of Cetuximab into chemo-radiation regimens. Trials assessing the combination of Cetuximab with induction chemotherapy, concomitant chemo-radiotherapy or both are reviewed. Taken together, their results suggest that the addition of Cetuximab is promising in trials of induction chemotherapy, showing almost uniformly response rates higher than historical controls. In combination with concomitant hyperfractionated radiotherapy and Cisplatin the results of the RTOG 0522 trial do not suggest any benefit. However a positive effect cannot be excluded with other schedules. Although feasibility has been universally suggested, adding Cetuximab implies some toxicity enhancement. Single local and systemic toxicities are more frequent and supposedly the overall treatment intensity is increased. Moreover the drug-specific toxicities are potentially severe and deserve timely recognition and management. (C) 2012 Elsevier Ireland Ltd. All rights reserved

Hospital admission of cancer patients: Avoidable practice or necessary care?

BackgroundCancer patients are frequently admitted to hospital due to acute conditions or refractory symptoms. This occurs through the emergency departments and requires medical oncologists to take an active role. The use of acute-care hospital increases in the last months of life.Patients and methodsWe aimed to describe the admissions to a medical oncology inpatient service within a 16-month period with respect to patients and tumor characteristics, and the outcome of the hospital stay.Results672 admissions of 454 patients were analysed. The majority of admissions were urgent (74.1%), and were due to uncontrolled symptoms (79.6%). Among the chief complaints, dyspnoea occurred in 15.7%, pain in 15.2%, and neurological symptoms in 14.5%. The majority of the hospitalizations resulted in discharge to home (60.6%); in 26.5% the patient died and in 11.0% was transferred to a hospice. Admissions due to symptoms correlated with a longer hospital stay and a higher incidence of in-hospital death.ConclusionWe suggest that hospital use is not necessarily a sign of inappropriately aggressive care: inpatient care is probably an unavoidable step in the cancer trajectory. Optimization of inpatient supportive procedures should be a specific task of modern medical oncology