Targeting Glutamine Metabolism and PD-L1: A Novel Anti-tumor Pas de Deux.

In this issue of Molecular Cell, Byun et al. (2020) find that the dual targeting of glutamine metabolism and the PD-L1 checkpoint inhibitor augments anti-tumor immunity. Mechanistically, decreased glutamine availability attenuated S-glutathionylation of SERCA, resulting in an increase in cytosolic calcium, enhanced NF-κB activity, and upregulation of programmed death-ligand 1.

Post-translational modification-centric base editor screens to assess phosphorylation site functionality in high throughput.

Signaling pathways that drive gene expression are typically depicted as having a dozen or so landmark phosphorylation and transcriptional events. In reality, thousands of dynamic post-translational modifications (PTMs) orchestrate nearly every cellular function, and we lack technologies to find causal links between these vast biochemical pathways and genetic circuits at scale. Here we describe the high-throughput, functional assessment of phosphorylation sites through the development of PTM-centric base editing coupled to phenotypic screens, directed by temporally resolved phosphoproteomics. Using T cell activation as a model, we observe hundreds of unstudied phosphorylation sites that modulate NFAT transcriptional activity. We identify the phosphorylation-mediated nuclear localization of PHLPP1, which promotes NFAT but inhibits NFκB activity. We also find that specific phosphosite mutants can alter gene expression in subtle yet distinct patterns, demonstrating the potential for fine-tuning transcriptional responses. Overall, base editor screening of PTM sites provides a powerful platform to dissect PTM function within signaling pathways.

Single-Molecule DNA Methylation Reveals Unique Epigenetic Identity Profiles of T Helper Cells.

Both identity and plasticity of CD4 T helper (Th) cells are regulated in part by epigenetic mechanisms. However, a method that reliably and readily profiles DNA base modifications is still needed to finely study Th cell differentiation. Cytosine methylation in CpG context (5mCpG) and cytosine hydroxymethylation (5hmCpG) are DNA modifications that identify stable cell phenotypes, but their potential to characterize intermediate cell transitions has not yet been evaluated. To assess transition states in Th cells, we developed a method to profile Th cell identity using Cas9-targeted single-molecule nanopore sequencing. Targeting as few as 10 selected genomic loci, we were able to distinguish major in vitro polarized murine T cell subtypes, as well as intermediate phenotypes, by their native DNA 5mCpG patterns. Moreover, by using off-target sequences, we were able to infer transcription factor activities relevant to each cell subtype. Detection of 5mCpG and 5hmCpG was validated on intestinal Th17 cells escaping transforming growth factor ß control, using single-molecule adaptive sampling. A total of 21 differentially methylated regions mapping to the 10-gene panel were identified in pathogenic Th17 cells relative to their nonpathogenic counterpart. Hence, our data highlight the potential to exploit native DNA methylation profiling to study physiological and pathological transition states of Th cells.

Microsimulation Models on Mental Health: A Critical Review of the Literature.

OBJECTIVES: To retrieve and synthesize the literature on existing mental health-specific microsimulation models or generic microsimulation models used to examine mental health, and to critically appraise them. METHODS: All studies on microsimulation and mental health published in English in MEDLINE, Embase, PsycINFO, and EconLit between January 1, 2010, and September 30, 2022, were considered. Snowballing, Google searches, and searches on specific journal websites were also undertaken. Data extraction was done on all studies retrieved and the reporting quality of each model was assessed using the Quality Assessment Reporting for Microsimulation Models checklist, a checklist developed by the research team. A narrative synthesis approach was used to synthesize the evidence. RESULTS: Among 227 potential hits, 19 studies were found to be relevant. Some studies covered existing economic-demographic models, which included a component on mental health and were used to answer mental-health-related research questions. Other studies were focused solely on mental health and included models that were developed to examine the impact of specific policies or interventions on specific mental disorders or both. Most models examined were of medium quality. The main limitations included the use of model inputs based on self-reported and/or cross-sectional data, small and/or nonrepresentative samples and simplifying assumptions, and lack of model validation. CONCLUSIONS: This review found few high-quality microsimulation models on mental health. Microsimulation models developed specifically to examine mental health are important to guide healthcare delivery and service planning. Future research should focus on developing high-quality mental health-specific microsimulation models with wide applicability and multiple functionalities.

Optical coherence tomography angiography in herpetic leucoma.

BACKGROUND: Herpes simplex virus (HSV) keratitis remains a leading infectious cause of blindness worldwide. Although all forms of HSV keratitis are commonly recurrent, the risk is greatest in stromal keratitis, which is the most likely to result in corneal scarring, thinning, and neovascularization. Recent studies showed the ability of Optical Coherence Tomography Angiography (OCTA) to detect and study vascular abnormalities in the anterior segment, including abnormal corneal vessels. This study intends to investigate the potential of OCTA device to image and describe quantitatively the vascularization in eyes diagnosed with herpetic leucoma and to discuss and review the usefulness of this technique in this pathology. METHODS: A Cross-sectional study was made, including 17 eyes of 15 patients with leucoma secondary to herpetic keratitis. All eyes underwent anterior segment Slit-Lamp photography (SLP), and OCTA with en-face, b-scans and c-scans imaging. The vessel density (VD) was analyzed in the inferior, nasal and temporal corneal margin in all patients, and in the central area, in eyes with central corneal neovascularization (CoNV). The measurements were calculated after binarization with ImageJ software, using OCTA scans with 6 × 6 mm in a depth of 800 µm. RESULTS: Patients included had a mean age 53.267 ± 21.542 (years ± SD). The mean total vessel area was 50.907% ± 3.435%. VD was higher in the nasal quadrant (51.156% ± 4.276%) but there were no significant differences between the three analyzed areas (p = 0.940). OCTA was able to identify abnormal vessels when SLP apparently showed no abnormal vessels; OCTA was able to distinguish between larger and smaller vessels even in central cornea; OCTA scans allowed the investigation of several corneal planes and the relation of them with clinical findings. CONCLUSIONS: OCTA can be useful in both qualitative and quantitative follow-up of patients and may become a non-invasive alternative to objectively monitor treatment response in eyes with corneal vascularization due to herpetic infection.

Incidence of COVID-19 in 902 Patients With Immunomediated Inflammatory Diseases Treated With Biologics and Targeted Synthetic Disease-Modifying Antirheumatic Drugs-Findings From the BIOCOVID Study.

OBJECTIVES: The aim of this study was to examine the incidence of coronavirus disease 2019 (COVID-19) among patients with immunomediated inflammatory diseases (IMIDs) treated with biologic or targeted synthetic disease-modifying antirheumatic drugs (bDMARDs and tsDMARDs) and to evaluate the influence of either IMIDs or related therapies on the incidence and evolution of COVID-19. METHODS: This observational, cross-sectional study was conducted from January 31, 2020, to May 15, 2020. Data of 902 patients were obtained from clinical records in hospitals, primary care units, and community pharmacies. Inclusion criteria were adults with IMIDs treated with bDMARDs or tsDMARDs who started therapy 3 months prior to study commencement. Patients with poor adherence to treatments were excluded. COVID-19 was classified as "definitive" (severe acute respiratory syndrome coronavirus 2 polymerase chain reaction [PCR]-positive), "possible" (characteristic symptoms and negative PCR), and "suspected" (characteristic symptoms but PCR not performed). RESULTS: COVID-19 was diagnosed in 70 patients (11 definitive, 19 possible, and 40 suspected). The cumulative incidence of definitive COVID-19 was 1.2%. When considering all cases, the incidence was 7.8%. Patients on biosimilars tumor necrosis factor blockers were more likely to have a diagnosis of COVID-19 (odds ratio, 2.308; p < 0.001). Patients on anti-B-cell therapies had a lower incidence of infections (p = 0.046). Low rates of hospitalization (14.3%), pneumonia (14.3%), death (2.9%), or thrombosis (2.9%) were observed, and 94.3% of patients recovered. CONCLUSIONS: The cumulative incidence of confirmed cases of COVID-19 was similar to the general population, with generally low hospitalization, intensive care management, and mortality rates. COVID-19 incidence was less frequent in patients with more severe immunosuppression.

Is food insecurity related to health-care use, access and absenteeism?

OBJECTIVE: Food insecurity (FI) is defined as uncertain access to healthy food in quantity and quality. We hypothesize that FI may be associated with greater health-care use and absenteeism because it may amplify the effect of diseases; also, FI may be associated with reduced health-care access because it reflects economic vulnerability. The present study estimates the association between FI and health-care use and access, and absenteeism. DESIGN: Cross-sectional data collected in 2015-2016. Health-care use was measured as the number of consultations, taking any drug and having been hospitalized in the past year. Health-care access was measured by the suspension of medication and having fewer consultations due to financial constraints. Absenteeism was measured by the weeks of sickness leave. Binary variables were modelled as a function of FI using logistic regressions; continuous variables were modelled as a function of FI using negative binomial and zero-inflated negative binomial regressions. Covariates were included sequentially. SETTING: Portugal. PARTICIPANTS: Non-institutionalized adults from the EpiDoc3 cohort (n 5648). RESULTS: FI was significantly associated with health-care use before controlling for socio-economic conditions and quality of life. Moderate/severe FI was positively related to the suspension of medicines (adjusted OR = 4·68; 95 % CI 3·11, 6·82) and to having fewer consultations (adjusted OR = 3·98; 95 % CI 2·42, 6·37). FI and absenteeism were not significantly associated. CONCLUSIONS: Our results support the hypothesis that FI reflects precariousness, which hinders access to health care. The greater use of health care among food-insecure people is explained by their worse quality of life and lower socio-economic condition, so that the specific role of poor nutrition is unclear.

Assessing the uptake of incentivised physical health checks for people with serious mental illness: a cohort study in primary care.

BACKGROUND: People with serious mental illness are more likely to experience physical illnesses. The onset of many of these illnesses can be prevented if detected early. Physical health screening for people with serious mental illness is incentivised in primary care in England through the Quality and Outcomes Framework (QOF). GPs are paid to conduct annual physical health checks on patients with serious mental illness, including checks of body mass index (BMI), cholesterol, and alcohol consumption. AIM: To assess the impact of removing and reintroducing QOF financial incentives on uptake of three physical health checks (BMI, cholesterol, and alcohol consumption) for patients with serious mental illness. DESIGN AND SETTING: Cohort study using UK primary care data from the Clinical Practice Research Datalink between April 2011 and March 2020. METHOD: A difference-in-difference analysis was employed to compare differences in the uptake of physical health checks before and after the intervention, accounting for relevant observed and unobserved confounders. RESULTS: An immediate change was found in uptake after physical health checks were removed from, and after they were added back to, the QOF list. For BMI, cholesterol, and alcohol checks, the overall impact of removal was a reduction in uptake of 14.3, 6.8, and 11.9 percentage points, respectively. The reintroduction of BMI screening in the QOF increased the uptake by 10.2 percentage points. CONCLUSION: This analysis supports the hypothesis that QOF incentives lead to better uptake of physical health checks.

Reduced cardiovascular risk score following bilateral cataract phacoemulsification surgery: A retrospective observational cohort study.

OBJECTIVE: To assess the cardiovascular risk (CV risk) change following bilateral phacoemulsification cataract surgery. METHODS: We performed a retrospective observation cohort study on 112 selected patients who underwent uncomplicated bilateral cataract surgery at Centro Hospitalar de Entre o Douro e Vouga (CHEDV) between 2018 and 2019. This patient cohort was further subdivided in 2 different groups: Good VA - no to mild visual impairment, ≤0.48 LogMAR; Bad VA - moderate to severe visual impairment, >0.48 LogMAR. We compared the changes in the CV risk score components in our patient cohort and between subgroups Good VA and Bad VA, before and after surgery, using paired t-test or Wilcoxon rank-sum test, and repeated measures ANOVA with Tukey post-hoc tests, respectively. Visual Acuity (VA) before and after surgery was correlated with the patients' CV risk score. At last, linear regression models were built to explain changes in CV risk variables considering the change in VA. RESULTS: Cataract surgery resulted in improved VA. Notably, following surgery our patient cohort showed reduced low-density lipoprotein (LDL) levels after surgery, from 111.17±36.26 mg/dL to 104.22±37.53 mg/dL, and reduced systolic arterial pressure (SAP), from 139.1±15.0 mmHg to 133.7±12.0 mmHg. Ultimately, this translated to an improved CV risk score within 6 months of cataract surgery, from 17.39±11.44% to 16.51±11.27%. Of note, these improvements were mostly present in the Bad VA group of patients, where baseline VA and incidence of dyslipidemia were worse. CONCLUSION: Our results suggest that phacoemulsification cataract surgery may be an important tool in addressing CV risk.

Microwave Synthesis of Visible-Light-Activated g-C3N4/TiO2 Photocatalysts.

The preparation of visible-light-driven photocatalysts has become highly appealing for environmental remediation through simple, fast and green chemical methods. The current study reports the synthesis and characterization of graphitic carbon nitride/titanium dioxide (g-C3N4/TiO2) heterostructures through a fast (1 h) and simple microwave-assisted approach. Different g-C3N4 amounts mixed with TiO2 (15, 30 and 45 wt. %) were investigated for the photocatalytic degradation of a recalcitrant azo dye (methyl orange (MO)) under solar simulating light. X-ray diffraction (XRD) revealed the anatase TiO2 phase for the pure material and all heterostructures produced. Scanning electron microscopy (SEM) showed that by increasing the amount of g-C3N4 in the synthesis, large TiO2 aggregates composed of irregularly shaped particles were disintegrated and resulted in smaller ones, composing a film that covered the g-C3N4 nanosheets. Scanning transmission electron microscopy (STEM) analyses confirmed the existence of an effective interface between a g-C3N4 nanosheet and a TiO2 nanocrystal. X-ray photoelectron spectroscopy (XPS) evidenced no chemical alterations to both g-C3N4 and TiO2 at the heterostructure. The visible-light absorption shift was indicated by the red shift in the absorption onset through the ultraviolet-visible (UV-VIS) absorption spectra. The 30 wt. % of g-C3N4/TiO2 heterostructure showed the best photocatalytic performance, with a MO dye degradation of 85% in 4 h, corresponding to an enhanced efficiency of almost 2 and 10 times greater than that of pure TiO2 and g-C3N4 nanosheets, respectively. Superoxide radical species were found to be the most active radical species in the MO photodegradation process. The creation of a type-II heterostructure is highly suggested due to the negligible participation of hydroxyl radical species in the photodegradation process. The superior photocatalytic activity was attributed to the synergy of g-C3N4 and TiO2 materials.

Motor and cognitive response to intensive multidisciplinary therapy: the first reported case of congenital Zika virus syndrome.

PURPOSE: To provide a detailed description of the development of the first case of congenital Zika syndrome (CZS) to be reported in the literature worldwide. CASE DESCRIPTION: This report describes the case of a child with CZS monitored from pregnancy until four years of age, with periodic evaluations of head circumference, weight, height, motor function according to the Gross Motor Function Measure (GMFM-88), and the occurrence of comorbidities. OUTCOMES: The child's birth weight and length were normal (z-score = 1.1 and -1.95, respectively), while head circumference was below the expected value (z-score = -3.15). At 48 months, head circumference reached 43 cm (z-score = -4.48). During daily home physiotherapy sessions, the child achieved developmental milestones, standing unsupported at 17 months, with a GMFM-88x score of 137. With specialist therapy, the child walked independently at 36 months and a total GMFM-66 score of 214 was achieved by 42 months. In the four years of follow-up, the child was hospitalized four times for different reasons. No convulsive seizures occurred. CONCLUSIONS: Despite severe neurological impairment, the child's weight and height are adequate for age, with motor and cognitive function improving over the first four years of life.

Proteome-wide base editor screens to assess phosphorylation site functionality in high-throughput.

Signaling pathways that drive gene expression are typically depicted as having a dozen or so landmark phosphorylation and transcriptional events. In reality, thousands of dynamic post-translational modifications (PTMs) orchestrate nearly every cellular function, and we lack technologies to find causal links between these vast biochemical pathways and genetic circuits at scale. Here, we describe "signaling-to-transcription network" mapping through the development of PTM-centric base editing coupled to phenotypic screens, directed by temporally-resolved phosphoproteomics. Using T cell activation as a model, we observe hundreds of unstudied phosphorylation sites that modulate NFAT transcriptional activity. We identify the phosphorylation-mediated nuclear localization of the phosphatase PHLPP1 which promotes NFAT but inhibits NFκB activity. We also find that specific phosphosite mutants can alter gene expression in subtle yet distinct patterns, demonstrating the potential for fine-tuning transcriptional responses. Overall, base editor screening of PTM sites provides a powerful platform to dissect PTM function within signaling pathways.

Enhanced Fe-TiO2 Solar Photocatalysts on Porous Platforms for Water Purification.

In this study, polyethylene glycol-modified titanium dioxide (PEG-modified TiO2) nanopowders were prepared using a fast solvothermal method under microwave irradiation, and without any further calcination processes. These nanopowders were further impregnated on porous polymeric platforms by drop-casting. The effect of adding iron with different molar ratios (1, 2, and 5%) of iron precursor was investigated. The characterization of the produced materials was carried out by scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and Raman spectroscopy. Optical characterization of all the materials was also carried out. SEM showed that pure TiO2 and Fe-TiO2 nanostructures presented similar nanosized and spherical particles, which uniformly covered the substrates. From XRD, pure TiO2 anatase was obtained for all nanopowders produced, which was further confirmed by Raman spectroscopy on the impregnated substrates. XPS and UV-VIS absorption spectroscopy emission spectra revealed that the presence of Fe ions on the Fe-TiO2 nanostructures led to the introduction of new intermediate energy levels, as well as defects that contributed to an enhancement in the photocatalytic performance. The photocatalytic results under solar radiation demonstrated increased photocatalytic activity in the presence of the 5% Fe-TiO2 nanostructures (Rhodamine B degradation of 85% after 3.5 h, compared to 74% with pure TiO2 for the same exposure time). The photodegradation rate of RhB dye with the Fe-TiO2 substrate was 1.5-times faster than pure TiO2. Reusability tests were also performed. The approach developed in this work originated novel functionalized photocatalytic platforms, which were revealed to be promising for the removal of organic dyes from wastewater.

Regulatory T cell differentiation is controlled by αKG-induced alterations in mitochondrial metabolism and lipid homeostasis.

Suppressive regulatory T cell (Treg) differentiation is controlled by diverse immunometabolic signaling pathways and intracellular metabolites. Here we show that cell-permeable α-ketoglutarate (αKG) alters the DNA methylation profile of naive CD4 T cells activated under Treg polarizing conditions, markedly attenuating FoxP3+ Treg differentiation and increasing inflammatory cytokines. Adoptive transfer of these T cells into tumor-bearing mice results in enhanced tumor infiltration, decreased FoxP3 expression, and delayed tumor growth. Mechanistically, αKG leads to an energetic state that is reprogrammed toward a mitochondrial metabolism, with increased oxidative phosphorylation and expression of mitochondrial complex enzymes. Furthermore, carbons from ectopic αKG are directly utilized in the generation of fatty acids, associated with lipidome remodeling and increased triacylglyceride stores. Notably, inhibition of either mitochondrial complex II or DGAT2-mediated triacylglyceride synthesis restores Treg differentiation and decreases the αKG-induced inflammatory phenotype. Thus, we identify a crosstalk between αKG, mitochondrial metabolism and triacylglyceride synthesis that controls Treg fate.

Aged biochar changed copper availability and distribution among soil fractions and influenced corn seed germination in a copper-contaminated soil.

Biochar has been recommended as a multi-beneficial amendment for the in situ remediation of heavy metals contaminated soils due to its high recalcitrance, stability, specific surface area and retention capacity, which leads to a long-lasting influence on the immobilization of soil contaminants. The influence of biochar on the availability of heavy metals such as copper is not fully understood and may be related to a change in copper association with soils fractions. Therefore, a long-time laboratory incubation study was set up as a completely randomized design to test the effect of biochar from different sources (coconut husks-CHB, orange bagasse-OBB and sewage sludge-SSB) at two rates of application (30 and 60 t ha-1) on the distribution of copper in a copper-contaminated soil after 24 months incubation. Copper distribution was evaluated through a sequential extraction procedure that fractionated copper into five fractions: F1 (soluble and exchangeable), F2 (specifically bound), F3 (organic matter bound), F4 (Fe and Mn oxide bound) and F5 (residual). Copper availability, soil pH and organic matter were also evaluated. Corn seeds were germinated in the incubated biochar soil to investigate the effect of biochar on seed germination and plantlets characteristics. All biochars increased soil pH and the concentration of oxidizable organic matter, and reduced copper availability after the 24 months incubation. CHB caused a discrete influence on copper distribution among soil fractions. OBB30 increased F1 (54.5%), F3 (24.0%), F4 (32.2%) and F5 (64.1%), and reduced F2 (39.8%); OBB60 reduced F1 (61.8%), F2 (16.5%) and F3 (16.0%) and increased F4 (18.0%) and F5 (84.4%). SSB30 strongly reduced Cu concentration in F1 (96.2%), F2 (34.0%), and F3 (22.2%), and increased F4 (54.4%); SSB60 reduced F1 (57.5%) and F3 (59.4%). Considering the high stability of biochar, the association of copper to the organic fraction leads to a long-time reduction in copper availability in the contaminated soil, which can reduce the cost and increase the efficiency of the remediation process. SSB reduced seed germination but produced vigorous and well-developed plantlets. Therefore, with proper production procedure to reduce the volatile matter content, SSB may not interfere with seed germination and has the greatest potential to be used for the remediation of copper-contaminated sites.

Dysregulation of glycerophospholipid metabolism during Behçet's disease contributes to a pro-inflammatory phenotype of circulating monocytes.

Behçet's disease (BD) is a relapsing, multisystem and inflammatory condition characterized by systemic vasculitis of small and large vessels. Although the etiopathogenesis of BD remains unknown, immune-mediated mechanisms play a major role in the development of the disease. BD patients present leukocyte infiltration in the mucocutaneous lesions as well as neutrophil hyperactivation. In contrast to neutrophils, whose involvement in the pathogenesis of BD has been extensively studied, the biology of monocytes during BD is less well known. In this study, we analyzed the phenotype and function of circulating monocytes of 38 BD patients from Hospital of Braga. In addition, we evaluated the impact of inflammatory and metabolomic plasma environment on monocyte biology. We observed a worsening of mitochondrial function, with lower mitochondrial mass and increased ROS production, on circulating monocytes of BD patients. Incubation of monocytes from healthy donors with the plasma of BD patients mimicked the observed phenotype, strongly suggesting the involvement of serum mediators. BD patients, regardless of their symptoms, had higher serum pro-inflammatory TNF-α and IP-10 levels and IL-1ß/IL-1RA ratio. Untargeted metabolomic analysis identified a dysregulation of glycerophospholipid metabolism on BD patients, where a significant reduction of phospholipids was observed concomitantly with an increase of lysophospholipids and fatty acids. These observations converged to an enhanced phospholipase A2 (PLA2) activation. Indeed, inhibition of PLA2 with dexamethasone or the downstream cyclooxygenase (COX) enzyme with ibuprofen was able to significantly revert the mitochondrial dysfunction observed on monocytes of BD patients. Our results show that the plasma inflammatory environment coupled with a dysregulation of glycerophospholipid metabolism in BD patients contribute to a dysfunction of circulating monocytes.

EUS-FNA Diagnosis with Core Biopsy of Pancreatic Metastases from Primary Breast Cancer.

BACKGROUND: The pancreas as a site of metastasis of other primary tumors is a rare event. Pancreatic metastases may occur years after the start of treatment of a neoplasm of another organ or may be the initial manifestation of an unidentified primary tumor. The most commonly reported primary sites for pancreatic metastases are the kidneys, lungs, breast, bowel, and skin (melanoma). Case Summary. The authors report a case of pancreatic metastasis derived from a primary breast cancer that underwent endoscopic ultrasound fine-needle aspiration (EUS-FNA) core biopsy to obtain tissue, which made it possible to perform an immunohistochemical study. CONCLUSION: We emphasize the importance of outpatient follow-up after the treatment of a neoplasia and the completion of control exams. In addition, we should always be aware of the finding of a secondary lesion in patients who have already been diagnosed with cancer, even if it is located in unusual organs, as in this case, where two metastases of a breast carcinoma to the pancreas were detected.

Instituintes e instituídos na formação médica: movimentos desencadeados pelo Programa Mais Médicos / Instituting and instituted in medical education: movements triggered by the Mais Médicos (More Doctors) Program

RESUMO O presente estudo deteve-se no mapeamento das forças intervenientes no processo de implantação dos cursos de medicina criados a partir do Programa Mais Médicos (PMM), bem como nos efeitos dessas sobre as práticas de formação e sobre os sujeitos que as vivenciam. O campo de investigação foram dois novos cursos de medicina, nas regiões Sul e Nordeste do País. Por meio de abordagem qualitativa de pesquisa, fundamentada no método cartográfico, constatou-se que dois conjuntos de forças operam nos cursos, expressões do instituído e do instituinte na formação médica. No campo do instituído, destacaram-se as influências do modelo biomédico, do mercado de trabalho e dos movimentos de polarização política em curso no cenário nacional. Entre as forças instituintes, tiveram destaque os movimentos estudantis pela mudança na formação, os de reafirmação do Sistema Único de Saúde e da saúde coletiva, e aqueles que apoiam a formação focada em um perfil generalista. Em resumo, a proposta do Programa para a formação médica operou como dispositivo de interferência nesses cursos quando associada a um contexto grupal de construção coletiva, gestão compartilhada do curso e práticas pedagógicas ancoradas na perspectiva da produção sócio-histórica do processo saúde-doença-atenção e da própria instituição medicina.

ABSTRACT The present study focused on mapping the forces involved in implementing the medical programs created from the Mais Médicos Program (MMP) and their effects on training practices and subjects who experience them. The field of research was two new medical programs in the South and Northeast regions of the country. We found that two sets of forces operate in the programs through a qualitative research approach based on the cartographic method, expressions of the instituted and instituting in medical education. The influences of the biomedical model, labor market, and the movements of political polarization underway in the national scenario were highlighted in the field of the instituted. The student movements for change in education, those to reaffirm the Unified Health System and collective health, and those that support training focused on a generalist profile stood out among the instituting forces. In summary, the program's proposal for medical education operated as an interference device in these programs when associated with a group context of collective construction, shared management of the programs, and pedagogical practices anchored in the perspective of the socio-historical production of the health-disease-care process and the medical institution.

Reforming the Portuguese mental health system: an incentive-based approach.

BACKGROUND: To promote an effective mental health system, the World Health Organization recommends the involvement of primary care in prevention and treatment of mild diseases and community-based care for serious mental illnesses. Despite a prevalence of lifetime mental health disorders above 30%, Portugal is failing to achieve such recommendations. It was argued that this failure is partly due to inadequate financing mechanisms of mental health care providers. This study proposes an innovative payment model for mental health providers oriented toward incentivising best practices. METHODS: We performed a comprehensive review of healthcare providers' payment schemes and their related incentives, and a narrative review of best practices in mental health prevention and care. We designed an alternative payment model, on the basis of the literature, and then we presented it individually, through face-to-face interviews, to a panel of 22 experts with different backgrounds and experience, and from southern and northern Portuguese regions, asking them to comment on the model and provide suggestions. Then, after a first round of interviews, we revised our model, which we presented to experts again for their approval, and provide new suggestions and comments, if deemed necessary. This approach is close to what is generally known as the Delphi technique, although it was not applied in a rigid way. RESULTS: We designed a four-dimension model that focused on (i) the prevention of mental disorders early in life; (ii) the detection of mental disorders in childhood and adolescence; (iii) the implementation of a collaborative stepped care model for depression; and (iv) the integrated community-based care for patients with serious mental illnesses. First, we recommend a bundled payment to primary care practices for the follow-up of children with special needs or at risk under 2 years of age. Second, we propose a pay-for-performance scheme for all primary care practices, based on the number of users under 18 years old who are provided with check-up consultations. Third, we propose a pay-for-performance scheme for all primary care practices, based on the implementation of collaborative stepped care for depression. Finally, we propose a value-based risk-adjusted bundled payment for patients with serious mental illness. CONCLUSIONS: The implementation of evidence-based best practices in mental health needs to be supported by adequate payment mechanisms. Our study shows that mental health experts, including decision makers, agree with using economic tools to support best practices, which were also consensual.