"I go I die, I stay I die, better to stay and die in my house": understanding the barriers to accessing health care in Timor-Leste.

BACKGROUND: Despite public health care being free at the point of delivery in Timor-Leste, wealthier patients access hospital care at nearly twice the rate of poorer patients. This study seeks to understand the barriers driving inequitable utilisation of hospital services in Timor-Leste from the perspective of community members and health care managers. METHODS: This multisite qualitative study in Timor-Leste conducted gender segregated focus groups (n = 8) in eight districts, with 59 adults in urban and rural settings, and in-depth interviews (n = 8) with the Director of community health centres. Communication was in the local language, Tetum, using a pre-tested interview schedule. Approval was obtained from community and national stakeholders, with written consent from participants. RESULTS: Lack of patient transport is the critical cross-cutting issue preventing access to hospital care. Without it, many communities resort to carrying patients by porters or on horseback, walking or paying for (unaffordable) private arrangements to reach hospital, or opt for home-based care. Other significant out-of-pocket expenses for hospital visits were blood supplies from private suppliers; accommodation and food for the patient and family members; and repatriation of the deceased. Entrenched nepotism and hospital staff denigrating patients' hygiene and personal circumstances were also widely reported. Consequently, some respondents asserted they would never return to hospital, others delayed seeking treatment or interrupted their treatment to return home. Most considered traditional medicine provided an affordable, accessible and acceptable substitute to hospital care. Obtaining a referral for higher level care was not a significant barrier to gaining access to hospital care. CONCLUSIONS: Onerous physical, financial and socio-cultural barriers are preventing or discouraging people from accessing hospital care in Timor-Leste. Improving access to quality primary health care at the frontline is a key strategy for ensuring universal access to health care, pursued alongside initiatives to overcome the multi-faceted barriers to hospital care experienced by the vulnerable. Improving the availability and functioning of patient transport services, provision of travel subsidies to patients and their families and training hospital staff in standards of professional care are some options available to government and donors seeking faster progress towards universal health coverage in Timor-Leste

Fabrication of a MEMS micromirror based on bulk silicon micromachining combined with grayscale lithography

A 1D MEMS (Micro-Electro-Mechanical Systems) mirror for LiDAR applications, based on vertically asymmetric comb-drive electrostatic actuators, is presented in this work employing a novel fabrication process. This novel micromachining process combines typical SOI-based bulk micromachining and grayscale lithography, enabling the fabrication of combs actuators with asymmetric heights using a single lithography step in the active layer. With this technique, the fabrication process is simplified, and the overall costs are reduced since the number of required lithography steps decrease. The fabricated mirrors present self-aligned electrodes with a 2.8 mu m gap and asymmetric heights of the movable and the fixed electrodes of 20 mu m and 50 mu m, respectively. These asymmetric actuators are an essential feature for the operation mode of this device, enabling both in resonant and static mode operation. A mirror field of view (FOV) of 54 degrees at 838 Hz was achieved under low-pressure, when resonantly operated, and a FOV of 0.8 degrees in the static mode.This work was supported by the European Structural and Investment Funds in the FEDER Component through the Operational Competitiveness and Internationalization Programme (COMPETE 2020) under Project 037902 (POCI-01-0247-FEDER-037902). The work of Carlos Ferreira was supported by the Fundacao para a Ciencia e Tecnologia (FCT) under Grant PD/BDE/135102/2017. Subject Editor M. Rais-Zadeh

Molecular dynamics-guided discovery of an ago-allosteric modulator for GPR40/FFAR1

The long-chain fatty acid receptor FFAR1/GPR40 binds agonists in both an interhelical site between the extracellular segments of transmembrane helix (TM)-III and TM-IV and a lipid-exposed groove between the intracellular segments of these helices. Molecular dynamics simulations of FFAR1 with agonist removed demonstrated a major rearrangement of the polar and charged anchor point residues for the carboxylic acid moiety of the agonist in the interhelical site, which was associated with closure of a neighboring, solvent-exposed pocket between the extracellular poles of TM-I, TM-II, and TM-VII. A synthetic compound designed to bind in this pocket, and thereby prevent its closure, was identified through structure-based virtual screening and shown to function both as an agonist and as an allosteric modulator of receptor activation. This discovery of an allosteric agonist for a previously unexploited, dynamic pocket in FFAR1 demonstrates both the power of including molecular dynamics in the drug discovery process and that this specific, clinically proven, but difficult, antidiabetes target can be addressed by chemotypes different from existing ligands

Evidences of herbal medicine-derived natural products effects in inflammatory lung diseases

Pulmonary inflammation is a hallmark of many respiratory diseases such as asthma, chronic obstructive pulmonary disease (COPD), and acute respiratory syndrome distress (ARDS). Most of these diseases are treated with anti-inflammatory therapy in order to prevent or to reduce the pulmonary inflammation. Herbal medicine-derived natural products have been used in folk medicine and scientific studies to evaluate the value of these compounds have grown in recent years. Many substances derived from plants have the biological effects in vitro and in vivo, such as flavonoids, alkaloids, and terpenoids. Among the biological activities of natural products derived from plants can be pointed out the anti-inflammatory, antiviral, antiplatelet, antitumor anti-allergic activities, and antioxidant. Although many reports have evaluated the effects of these compounds in experimental models, studies evaluating clinical trials are scarce in the literature. This review aims to emphasize the effects of these different natural products in pulmonary diseases in experimental models and in humans and pointing out some possible mechanisms of action.CNPq [300546/2012-2, 304465/2012-7, 476877/2012-1]FAPESP [2010/14831-3, 2011/15817-7, 2008/55359-5]Instituto de Ciências Ambientais, Químicas e Farmacêuticas, Federal University of São Paulo, Diadema-SP 09972-270, BrazilSchool of Medicine, University of São Paulo, São Paulo-SP 01246903, BrazilInstituto de Saúde e Sociedade, Federal University of São Paulo, Santos-SP 11015-020, BrazilInstituto de Ciências Ambientais, Químicas e Farmacêuticas, Federal University of São Paulo, Diadema-SP 09972-270, BrazilInstituto de Saúde e Sociedade, Federal University of São Paulo, Santos-SP 11015-020, BrazilCNPq: 300546/2012-2CNPq: 304465/2012-7CNPq: 476877/2012-1FAPESP: 2010/14831-3FAPESP: 2011/15817-7FAPESP: 2008/55359-5Web of Scienc

Structurally Related Monoterpenes p-Cymene, Carvacrol and Thymol Isolated from Essential Oil from Leaves of Lippia sidoides Cham. (Verbenaceae) Protect Mice against Elastase-Induced Emphysema

Background: Chronic obstructive pulmonary disease (COPD) is characterized by irreversible airflow obstruction and inflammation. Natural products, such as monoterpenes, displayed anti-inflammatory and anti-oxidant activities and can be used as a source of new compounds to COPD treatment. Our aim was to evaluate, in an elastase-induced pulmonary emphysema in mice, the effects of and underlying mechanisms of three related natural monoterpenes (p-cymene, carvacrol and thymol) isolated from essential oil from leaves Lippia sidoides Cham. (Verbenaceae). Methods: Mices received porcine pancreatic elastase (PPE) and were treated with p-cymene, carvacrol, thymol or vehicle 30 min later and again on 7th, 14th and 28th days. Lung inflammatory profile and histological sections were evaluated. Results: In the elastase-instilled animals, the tested monoterpenes reduced alveolar enlargement, macrophages and the levels of IL-1 beta, IL-6, IL-8 and IL-17 in bronchoalveolar lavage fluid (BALF), and collagen fibers, MMP-9 and p-65-NF-kappa B-positive cells in lung parenchyma (p < 0.05). All treatments attenuated levels of 8-iso-PGF2 alpha but only thymol was able to reduced exhaled nitric oxide (p < 0.05). Conclusion: Monoterpenes p-cymene, carvacrol and thymol reduced lung emphysema and inflammation in mice. No significant differences among the three monoterpenes treatments were found, suggesting that the presence of hydroxyl group in the molecular structure of thymol and carvacrol do not play a central role in the anti-inflammatory effects.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Laboratorio de Investigacao Medica, Hospital das Clinicas, Faculdade de Medicina, University of Sao Paulo (LIM)Univ Fed Sao Paulo, Dept Biol Sci, BR-09913030 Diadema, BrazilUniv Sao Paulo, Sch Med, Dept Med, BR-01246903 Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Dept Exact Sci & Earth, BR-09913030 Diadema, BrazilFed Univ ABC, Ctr Nat Sci & Humanities, BR-09606045 Santo Andre, SP, BrazilUniv Fed Sao Paulo, Dept Biosci, Campus Baixada Santista, BR-11015020 Santos, SP, BrazilDepartment of Biological Science, Universidade Federal de São Paulo, Diadema 09913-030, BrazilDepartment of Exact Science and Earth, Universidade Federal de São Paulo, Diadema 09913-030, BrazilDepartment of Bioscience, Federal University of São Paulo, Campus Baixada Santista, Santos 11015-020, SP, BrazilCNPq: 300546/2012-2CNPq: 304465/2012-7CNPq: 476877/2012-1CNPq: 306278/2015-4FAPESP: 2011/51739-0FAPESP: 2013/02881-4FAPESP: 2008/55359-5FAPESP: 2015/11936-2FAPESP: 2014/25689-4LIM: LIM20Web of Scienc

Evaluating the ability of an artificial-intelligence cloud-based platform designed to provide information prior to locoregional therapy for breast cancer in improving patient's satisfaction with therapy: the CINDERELLA trial

Background: Breast cancer therapy improved significantly, allowing for different surgical approaches for the same disease stage, therefore offering patients different aesthetic outcomes with similar locoregional control. The purpose of the CINDERELLA trial is to evaluate an artificial-intelligence (AI) cloud-based platform (CINDERELLA platform) vs the standard approach for patient education prior to therapy. Methods: A prospective randomized international multicentre trial comparing two methods for patient education prior to therapy. After institutional ethics approval and a written informed consent, patients planned for locoregional treatment will be randomized to the intervention (CINDERELLA platform) or controls. The patients in the intervention arm will use the newly designed web-application (CINDERELLA platform, CINDERELLA APProach) to access the information related to surgery and/or radiotherapy. Using an AI system, the platform will provide the patient with a picture of her own aesthetic outcome resulting from the surgical procedure she chooses, and an objective evaluation of this aesthetic outcome (e.g., good/fair). The control group will have access to the standard approach. The primary objectives of the trial will be i) to examine the differences between the treatment arms with regards to patients' pre-treatment expectations and the final aesthetic outcomes and ii) in the experimental arm only, the agreement of the pre-treatment AI-evaluation (output) and patient's post-therapy self-evaluation. Discussion: The project aims to develop an easy-to-use cost-effective AI-powered tool that improves shared decision-making processes. We assume that the CINDERELLA APProach will lead to higher satisfaction, better psychosocial status, and wellbeing of breast cancer patients, and reduce the need for additional surgeries to improve aesthetic outcome

Broadened T-cell Repertoire Diversity in ivIg-treated SLE Patients is Also Related to the Individual Status of Regulatory T-cells

Intravenous IgG (ivIg) is a therapeutic alternative for lupus erythematosus, the mechanism of which remains to be fully understood. Here we investigated whether ivIg affects two established sub-phenotypes of SLE, namely relative oligoclonality of circulating T-cells and reduced activity of CD4 + Foxp3+ regulatory T-cells (Tregs) reflected by lower CD25 surface density.Octapharma research funding; Fundação para a Ciência e a Tecnologia postdoctoral fellowships: (SFRH/BPD/20806/2004, SFRH/BPD/34648/2007); FCT Programa Pessoa travel grant

Applying the Maternal Near Miss Approach for the Evaluation of Quality of Obstetric Care: A Worked Example from a Multicenter Surveillance Study

Objective. To assess quality of care of women with severe maternal morbidity and to identify associated factors. Method. This is a national multicenter cross-sectional study performing surveillance for severe maternal morbidity, using the World Health Organization criteria. the expected number of maternal deaths was calculated with the maternal severity index (MSI) based on the severity of complication, and the standardized mortality ratio (SMR) for each center was estimated. Analyses on the adequacy of care were performed. Results. 17 hospitals were classified as providing adequate and 10 as nonadequate care. Besides almost twofold increase in maternal mortality ratio, the main factors associated with nonadequate performance were geographic difficulty in accessing health services (P < 0.001), delays related to quality of medical care (P = 0.012), absence of blood derivatives (P = 0.013), difficulties of communication between health services (P = 0.004), and any delay during the whole process (P = 0.039). Conclusions. This is an example of how evaluation of the performance of health services is possible, using a benchmarking tool specific to Obstetrics. in this study the MSI was a useful tool for identifying differences in maternal mortality ratios and factors associated with nonadequate performance of care.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Univ Campinas UNICAMP, Sch Med Sci, Dept Obstet & Gynaecol, BR-13083881 Campinas, SP, BrazilCtr Res Reprod Hlth Campinas Cemicamp, BR-13083888 Campinas, SP, BrazilUniv Fed Amazonas, Manaus, Amazonas, BrazilSch Med Sci, CISAM, Recife, PE, BrazilUniv Fed Ceara, Fortaleza, Ceara, BrazilUniv Fed Bahia, Salvador, BA, BrazilHosp Geral Cesar Cals, Fortaleza, Ceara, BrazilHosp Geral Fortaleza, Fortaleza, Ceara, BrazilMaternidade Odete Valadares, Belo Horizonte, MG, BrazilHosp Materno Infantil, Goiania, Go, BrazilInst Materno Infantil Pernambuco, Recife, PE, BrazilUniv Fed Pernambuco, Recife, PE, BrazilUniv Fed Campina Grande, Campina Grande, PB, BrazilUniv Fed Maranhao, Sao Luis, MA, BrazilUniv Fed Parana, BR-80060000 Curitiba, Parana, BrazilUniv Fed Paraiba, BR-58059900 Joao Pessoa, Paraiba, BrazilHosp Maternidade Fernando Magalhaes, Rio de Janeiro, RJ, BrazilUniv Fed Rio Grande do Sul, Porto Alegre, RS, BrazilHosp Maternidade Celso Pierro, Campinas, SP, BrazilInst Fernandes Figueira Fiocruz, Rio de Janeiro, RJ, BrazilHosp Israelita Albert Einstein, São Paulo, BrazilUniv State São Paulo, Botucatu, SP, BrazilJundiai Sch Med, Jundiai, SP, BrazilUniv São Paulo, BR-14049 Ribeirao Preto, SP, BrazilSanta Casa Limeira, Limeira, SP, BrazilSanta Casa Sao Carlos, Sao Carlos, SP, BrazilMaternidade Leonor Mendes de Barros, São Paulo, BrazilUniversidade Federal de São Paulo, São Paulo, BrazilUniversidade Federal de São Paulo, São Paulo, BrazilCNPq: 402702/2008-5Web of Scienc

Adherence to treatment in allergic rhinitis using mobile technology. The MASK Study

Background: Mobile technology may help to better understand the adherence to treatment. MASK-rhinitis (Mobile Airways Sentinel NetworK for allergic rhinitis) is a patient-centred ICT system. A mobile phone app (the Allergy Diary) central to MASK is available in 22 countries. Objectives: To assess the adherence to treatment in allergic rhinitis patients using the Allergy Diary App. Methods: An observational cross-sectional study was carried out on all users who filled in the Allergy Diary from 1 January 2016 to 1 August 2017. Secondary adherence was assessed by using the modified Medication Possession Ratio (MPR) and the Proportion of days covered (PDC) approach. Results: A total of 12143 users were registered. A total of 6949 users reported at least one VAS data recording. Among them, 1887 users reported >= 7 VAS data. About 1195 subjects were included in the analysis of adherence. One hundred and thirty-six (11.28%) users were adherent (MPR >= 70% and PDC = 70% and PDC = 1.50) and 176 (14.60%) were switchers. On the other hand, 832 (69.05%) users were non-adherent to medications (MPR Conclusion and clinical relevance: Adherence to treatment is low. The relative efficacy of continuous vs on-demand treatment for allergic rhinitis symptoms is still a matter of debate. This study shows an approach for measuring retrospective adherence based on a mobile app. This also represents a novel approach for analysing medication-taking behaviour in a real-world setting.Peer reviewe