Demonstration project on epilepsy in Brazil - Outcome assessment

Purpose: To assess the outcome of patients with epilepsy treated at primary care health units under the framework of the demonstration project on epilepsy in Brazil, part of the WHO/ILAE/IBE Global Campaign Against Epilepsy. Method. We assessed the outcome of patients treated at four primary health units. The staff of the health units underwent information training in epilepsy. The outcome assessment was based on: 1) reduction of seizure frequency, 2) subjective perception from the patient's and the physician's point of view, 3) reduction of absenteeism, 4) social integration (school and work), and 5) sense of independence. Results: A total of 181 patients (93 women - 51%) with a mean age of 38 (range from 2 to 86) years were studied. The mean follow-up was 26 months (range from 1 to 38 months, 11 patients had follow-up of less than 12 months). Seizure frequency was assessed based on a score system, ranging from 0 (no seizure in the previous 24 months) to 7 (> 10 seizure/day). The baseline median seizure-frequency score was 3 (one to three seizures per month). At the end of the study the median seizure-frequency score was 1 (one to three seizures per year). The patients' and relatives' opinions were that in the majority (59%) the health status had improved a lot, some (19%) had improved a little, 20% experienced no change and in 2% the health status was worse. With regard to absenteeism, social integration and sense of independence, there were some modest improvements only. Discussion: The development of a model of epilepsy treatment at primary health level based on the existing health system, with strategic measures centred on the health care providers and the community, has proved to be effective providing important reductions in seizure frequency, as well as in general well being. This model can be applied nationwide, as the key elements already exist provided that strategic measures are put forward in accordance with local health providers and managers

The grapevine (Vitis vinifera) aquaporin VvNIP2;1 is a silicon channel localized at the plasma membrane highly expressed in roots

Silicon (Si) supplementation has been shown to improve plant tolerance to different stresses and its accumulation in the aerial organs is mediated by NIP2;1 aquaporins (Lsi channels) and Lsi2-type exporters in roots. In the present study, we tested the hypothesis that grapevine expresses a functional NIP2;1 that accounts for root Si uptake and, eventually, Si accumulation in leaves. Own-rooted grapevine cuttings of the cultivar Vinhão accumulated over 0.2 % Si (dw) in leaves when irrigated with 1.5 mM Si for one month, while Si was undetected in control leaves. Real-time PCR showed that VvNIP2;1 was highly expressed in roots and in green berries. The transient transformation of tobacco leaf epidermal cells mediated by Agrobacterium tumefaciens confirmed VvNIP2;1 localization at the plasma membrane. Transport experiments in oocytes showed that VvNIP2;1 mediates Si and arsenite uptake, whereas permeability studies revealed that VvNIP2;1 expressed in yeast is unable to transport water and glycerol. Si supplementation to pigmented grape cultured cells (cv. Gamay Freáux) had no impact on the total phenolic and anthocyanin content, as well as the growth rate and VvNIP2;1 expression. Long-term experiments should help determine the extent of Si uptake over time and if gapevine can benefit from Si fertilizationinfo:eu-repo/semantics/acceptedVersio

Demonstration project on epilepsy in Brazil - Situation assessment

Purpose: To provide a situation assessment of services for people with epilepsy in the context of primary health care, as part of the Demonstration Project on Epilepsy in Brazil, part of the WHO/ILAE/IBE Global Campaign 'Epilepsy out of the shadows'. Methods: We performed a door-to-door epidemiological survey in three areas to assess the prevalence of epilepsy and its treatment gap. We surveyed a sample of 598 primary health care workers from different regions of Brazil to assess their perceptions of the management of people with epilepsy in the primary care setting. Results: The lifetime prevalence of epilepsy was 9.2/1,000 people [95% Cl 8.4-10.0] and the estimated prevalence of active epilepsy was 5.4/1,000 people. Thirty-eight percent of patients with active epilepsy were on inadequate treatment, including 19% who were taking no medication. The survey of health workers showed that they estimated that 60% of patients under their care were seizure-free. They estimated that 55% of patients were on monotherapy and that 59% had been referred to neurologists. The estimated mean percentage of patients who were working or studying was 56%. Most of the physicians (73%) did not feel confident in managing people with epilepsy. Discussion: The epidemiological survey in the areas of the Demonstration Project showed that the prevalence of epilepsy is similar to that in other resource-poor countries, and that the treatment gap is high. One factor contributing to the treatment gap is inadequacy of health care delivery. The situation could readily be improved in Brazil, as the primary health care system has the key elements required for epilepsy management. To make this effective and efficient requires: i) an established referral network, ii) continuous provision of AEDs, iii) close monitoring of epilepsy management via the notification system (Sistema de lnformacao da Atencao Basica - SIAB) and iv) continuous education of health professionals. The educational program should be broad spectrum and include not only medical management, but also psycho-social aspects of epilepsy

Calibration of myocardial T2 and T1 against iron concentration.

BACKGROUND: The assessment of myocardial iron using T2* cardiovascular magnetic resonance (CMR) has been validated and calibrated, and is in clinical use. However, there is very limited data assessing the relaxation parameters T1 and T2 for measurement of human myocardial iron. METHODS: Twelve hearts were examined from transfusion-dependent patients: 11 with end-stage heart failure, either following death (n=7) or cardiac transplantation (n=4), and 1 heart from a patient who died from a stroke with no cardiac iron loading. Ex-vivo R1 and R2 measurements (R1=1/T1 and R2=1/T2) at 1.5 Tesla were compared with myocardial iron concentration measured using inductively coupled plasma atomic emission spectroscopy. RESULTS: From a single myocardial slice in formalin which was repeatedly examined, a modest decrease in T2 was observed with time, from mean (± SD) 23.7 ± 0.93 ms at baseline (13 days after death and formalin fixation) to 18.5 ± 1.41 ms at day 566 (p<0.001). Raw T2 values were therefore adjusted to correct for this fall over time. Myocardial R2 was correlated with iron concentration [Fe] (R2 0.566, p<0.001), but the correlation was stronger between LnR2 and Ln[Fe] (R2 0.790, p<0.001). The relation was [Fe] = 5081•(T2)-2.22 between T2 (ms) and myocardial iron (mg/g dry weight). Analysis of T1 proved challenging with a dichotomous distribution of T1, with very short T1 (mean 72.3 ± 25.8 ms) that was independent of iron concentration in all hearts stored in formalin for greater than 12 months. In the remaining hearts stored for <10 weeks prior to scanning, LnR1 and iron concentration were correlated but with marked scatter (R2 0.517, p<0.001). A linear relationship was present between T1 and T2 in the hearts stored for a short period (R2 0.657, p<0.001). CONCLUSION: Myocardial T2 correlates well with myocardial iron concentration, which raises the possibility that T2 may provide additive information to T2* for patients with myocardial siderosis. However, ex-vivo T1 measurements are less reliable due to the severe chemical effects of formalin on T1 shortening, and therefore T1 calibration may only be practical from in-vivo human studies

Cryptosporidium Priming Is More Effective than Vaccine for Protection against Cryptosporidiosis in a Murine Protein Malnutrition Model

Cryptosporidium is a major cause of severe diarrhea, especially in malnourished children. Using a murine model of C. parvum oocyst challenge that recapitulates clinical features of severe cryptosporidiosis during malnutrition, we interrogated the effect of protein malnutrition (PM) on primary and secondary responses to C. parvum challenge, and tested the differential ability of mucosal priming strategies to overcome the PM-induced susceptibility. We determined that while PM fundamentally alters systemic and mucosal primary immune responses to Cryptosporidium, priming with C. parvum (106 oocysts) provides robust protective immunity against re-challenge despite ongoing PM. C. parvum priming restores mucosal Th1-type effectors (CD3+CD8+CD103+ T-cells) and cytokines (IFNγ, and IL12p40) that otherwise decrease with ongoing PM. Vaccination strategies with Cryptosporidium antigens expressed in the S. Typhi vector 908htr, however, do not enhance Th1-type responses to C. parvum challenge during PM, even though vaccination strongly boosts immunity in challenged fully nourished hosts. Remote non-specific exposures to the attenuated S. Typhi vector alone or the TLR9 agonist CpG ODN-1668 can partially attenuate C. parvum severity during PM, but neither as effectively as viable C. parvum priming. We conclude that although PM interferes with basal and vaccine-boosted immune responses to C. parvum, sustained reductions in disease severity are possible through mucosal activators of host defenses, and specifically C. parvum priming can elicit impressively robust Th1-type protective immunity despite ongoing protein malnutrition. These findings add insight into potential correlates of Cryptosporidium immunity and future vaccine strategies in malnourished children

Patients’ experience of recurrent/metastatic head and neck squamous cell carcinoma and their perspective on the EORTC QLQC30 and QLQ-H&amp;N35 questionnaires: a qualitative study

Abstract Background Head and neck squamous cell carcinoma (HNSCC) and its associated treatments may affect all aspects of patients’ health-related quality of life (HRQoL). Although the EORTC QLQ-H&N35 is regularly administered to patients with HNSCC, there is a paucity of studies re-assessing the conceptual relevance of this patient-reported outcome (PRO) measure from a patient perspective. Furthermore, the content validity of the EORTC QLQ-C30 has not been widely documented in patients with recurrent and/or metastatic HNSCC. The objectives of this study were to understand patients’ experiences of recurrent/metastatic HNSCC and its treatments, and to evaluate the conceptual relevance and acceptability of the EORTC QLQ-C30 and QLQ-H&N35 from a patient perspective for use in clinical trials. Methods A literature review and clinician interviews were conducted to inform in-depth semi-structured telephone interviews with US patients who had received treatment for recurrent and/or metastatic HNSCC in the preceding 12 months. Interview transcripts were analysed thematically using ATLAS.ti v7; patient quotes were coded to identify concepts and themes to develop a conceptual model of HNSCC experience. Results Fourteen patients were interviewed (71% male, aged 35–84 years). Patients reported few symptoms pre-diagnosis including neck lump/swelling (n = 7/14, 50%) and/or difficulty swallowing (n = 3/14, 21%). Treatments generally comprised surgery and chemotherapy and/or radiotherapy. A number of side effects from all treatments were reported. Numbness, difficulty speaking and pain were the most reported side effects of surgery (n = 4/8, 50%); weight loss and fatigue were the most reported side effects of chemotherapy and/or radiotherapy (n = 8/13, 61%). All side effects negatively impacted patients’ HRQoL. Patients generally found the QLQ-C30 and QLQ H&N35 content to be understandable and conceptually relevant; excessive mucous production and neuropathic symptoms were among the suggested additions. Conclusions HNSCC and its diverse symptoms and treatments have a negative impact on many aspects of patients’ lives. A number of reported symptoms including difficulty speaking and swallowing, localised pain and fatigue may be important for treatment benefit evaluation in clinical trials from a patient perspective. The QLQ-C30 and QLQ-H&N35 are generally relevant and suitable for use in clinical trials. However, some items could be amended/added to ensure conceptual comprehensiveness of these measures