A Guerra Dispendiosa do Tratamento do Cancro: o Exemplo do Carcinoma de Células Renais em Portugal

info:eu-repo/semantics/publishedVersio

A Guerra Dispendiosa do Tratamento do Cancro: o Exemplo do Carcinoma de Células Renais em Portugal

info:eu-repo/semantics/publishedVersio

From L-Dopa to Dihydroxyphenylacetaldehyde: A Toxic Biochemical Pathway Plays a Vital Physiological Function in Insects

One protein in Aedes aegypti, classified into the aromatic amino acid decarboxylase (AAAD) family based on extremely high sequence homology (∼70%) with dopa decarboxylase (Ddc), was biochemically investigated. Our data revealed that this predicted AAAD protein use L-dopa as a substrate, as does Ddc, but it catalyzes the production of 3,4-dihydroxylphenylacetaldehyde (DHPAA) directly from L-dopa and apparently has nothing to do with the production of any aromatic amine. The protein is therefore named DHPAA synthase. This subsequently led to the identification of the same enzyme in Drosophila melanogaster, Anopheles gambiae and Culex quinquefasciatus by an initial prediction of putative DHPAA synthase based on sequence homology and subsequent verification of DHPAA synthase identity through protein expression and activity assays. DHPAA is highly toxic because its aldehyde group readily reacts with the primary amino groups of proteins, leading to protein crosslinking and inactivation. It has previously been demonstrated by several research groups that Drosophila DHPAA synthase was expressed in tissues that produce cuticle materials and apparent defects in regions of colorless, flexible cuticular structures have been observed in its gene mutants. The presence of free amino groups in proteins, the high reactivity of DHPAA with the free amino groups, and the genetically ascertained function of the Drosophila DHPAA synthase in the formation of colorless, flexible cuticle, when taken together, suggest that mosquito and Drosophila DHPAA synthases are involved in the formation of flexible cuticle through their reactive DHPAA-mediated protein crosslinking reactions. Our data illustrate how a seemingly highly toxic pathway can serve for an important physiological function in insects

Ambulatory health service users' experience of waiting time and expenditure and factors associated with the perception of low quality of care in Mexico

<p>Abstract</p> <p>Background</p> <p>A principal reason for low use of public health care services is the perception of inferior quality of care. Studying health service user (HSU) experiences with their care and their perception of health service quality is critical to understanding health service utilization. The aim of this study was to define reference points for some aspects of health care quality and to analyze which HSU experiences resulted in perceptions of overall low quality of care.</p> <p>Methods</p> <p>Data from the National Health Survey 2006 were used to compare the experiences of HSUs with their ambulatory care at Ministry of Health and affiliated institutions (MOH), social security institutions (SSI) and private institutions (PrivI). Reference points of quality of care related to waiting time and expenditure were defined for each of the three types of institutions by analyzing HSU experiences rated as 'acceptable'. A multivariable logistic regression model was used to identify the principal factors associated with the general perception of low quality of care.</p> <p>Results</p> <p>A total of 11,959 HSUs were included in the analysis, of whom 37.6% (n = 4,500) HSUs received care at MOH facilities; 31.2% (n = 3,730) used SSI and 31.2% (n = 3,729) PrivI. An estimated travel and waiting time of 10 minutes respectively was rated as acceptable by HSUs from all institutions. The differences between the waiting time rated as acceptable and the actual waiting time were the largest for SSI (30 min) in comparison to MoH (20 min) and PrivI (5 min) users. The principal factors associated with an overall perception of low quality of care are type of institution (OR 4.36; 95% CI 2.95-6.44), waiting time (OR 3.20; 95% CI 2.35-4.35), improvement of health after consultation (OR 2.93; CI 2.29-3.76) and consultation length of less than 20 minutes (2.03; 95% CI 1.60-2.57).</p> <p>Conclusions</p> <p>The reference points derived by the HSUs' own ratings are useful in identifying where quality improvements are required. Prioritizing the reduction of waiting times and improving health status improvement after consultation would increase overall quality of care ratings.</p

Dengue in Thailand and Cambodia: An Assessment of the Degree of Underrecognized Disease Burden Based on Reported Cases

Dengue is a major public health problem especially in tropical and subtropical countries of Asia and Latin-America. An effective dengue vaccine is not yet available, but several vaccine candidates are currently being evaluated in clinical trials. Accurate country-level incidence data are crucial to assess the cost-effectiveness of such vaccines and will assist policy-makers in making vaccine introduction decisions. Existing national surveillance systems are often passive and are designed to monitor trends and to detect disease outbreaks. Our analyses of data from prospectively followed cohorts with laboratory confirmation of dengue cases show that, in Thailand and Cambodia, dengue incidence is underrecognized by more than 8-fold. The magnitude of the outpatient burden caused by dengue is not assessed or reflected by the national surveillance data. We estimate that a median of more than 340,000 symptomatic dengue virus infections occurred annually in children less than 15 years of age in Thailand in Cambodia between 2003 and 2007

Cerebellar astrocytes co-express several ADP receptors. Presence of functional P2Y13-like receptors

Astrocytes exhibit a form of excitability based on variations of intracellular Ca2+ concentration in response to various stimuli, including ADP, ATP, UTP and dinucleotides. Here, we investigate the presence of the recently cloned ADP-sensitive receptors, P2Y12 and P2Y13 subtypes, which are negatively coupled to adenylate cyclase, in cerebellar astrocytes. We checked the effect of specific agonists, 2-methylthioadenosine diphosphate (2MeSADP) and ADP, on adenylate cyclase stimulation induced by isoproterenol. Both agonists significantly reduced the cAMP accumulation induced by isoproterenol. The inhibitory effect was concentration-dependent with IC50 values of 46 ± 13 and 23 ± 14 nM for 2MeSADP and ADP, respectively. The experiments were carried out in the presence of MRS-2179, a specific antagonist of P2Y1 receptor, to avoid any contribution of this receptor. Using fura-2 microfluorimetry we also proved that astrocytes responded to 2MeSADP stimulations with calcium responses in the absence and also in the presence of MRS-2179. Both effects, inhibition of adenylate cyclase and intracellular calcium mobilization, were not modified by 2MeSAMP, an antagonist of P2Y12 receptor, suggesting that were mediated by P2Y13-like receptors

Learning curves of basic laparoscopic psychomotor skills in SINERGIA VR simulator

Purpose: Surgical simulators are currently essential within any laparoscopic training program because they provide a low-stakes, reproducible and reliable environment to acquire basic skills. The purpose of this study is to determine the training learning curve based on different metrics corresponding to five tasks included in SINERGIA laparoscopic virtual reality simulator. Methods: Thirty medical students without surgical experience participated in the study. Five tasks of SINERGIA were included: Coordination, Navigation, Navigation and touch, Accurate grasping and Coordinated pulling. Each participant was trained in SINERGIA. This training consisted of eight sessions (R1–R8) of the five mentioned tasks and was carried out in two consecutive days with four sessions per day. A statistical analysis was made, and the results of R1, R4 and R8 were pair-wise compared with Wilcoxon signed-rank test. Significance is considered at P value <0.005. Results: In total, 84.38% of the metrics provided by SINERGIA and included in this study show significant differences when comparing R1 and R8. Metrics are mostly improved in the first session of training (75.00% when R1 and R4 are compared vs. 37.50% when R4 and R8 are compared). In tasks Coordination and Navigation and touch, all metrics are improved. On the other hand, Navigation just improves 60% of the analyzed metrics. Most learning curves show an improvement with better results in the fulfillment of the different tasks. Conclusions: Learning curves of metrics that assess the basic psychomotor laparoscopic skills acquired in SINERGIA virtual reality simulator show a faster learning rate during the first part of the training. Nevertheless, eight repetitions of the tasks are not enough to acquire all psychomotor skills that can be trained in SINERGIA. Therefore, and based on these results together with previous works, SINERGIA could be used as training tool with a properly designed training program