Near Infrared Biomimetic Hybrid Magnetic Nanocarrier for MRI-Guided Thermal Therapy.

Cell-membrane hybrid nanoparticles (NPs) are designed to improve drug delivery, thermal therapy, and immunotherapy for several diseases. Here, we report the development of distinct biomimetic magnetic nanocarriers containing magnetic nanoparticles encapsulated in vesicles and IR780 near-infrared dyes incorporated in the membranes. Distinct cell membranes are investigated, red blood cell (RBC), melanoma (B16F10), and glioblastoma (GL261). Hybrid nanocarriers containing synthetic lipids and a cell membrane are designed. The biomedical applications of several systems are compared. The inorganic nanoparticle consisted of Mn-ferrite nanoparticles with a core diameter of 15 ± 4 nm. TEM images show many multicore nanostructures (∼40 nm), which correlate with the hydrodynamic size. Ultrahigh transverse relaxivity values are reported for the magnetic NPs, 746 mM-1s-1, decreasing respectively to 445 mM-1s-1 and 278 mM-1s-1 for the B16F10 and GL261 hybrid vesicles. The ratio of relaxivities r2/r1 decreased with the higher encapsulation of NPs and increased for the biomimetic liposomes. Therapeutic temperatures are achieved by both, magnetic nanoparticle hyperthermia and photothermal therapy. Photothermal conversion efficiency ∼25-30% are reported. Cell culture revealed lower wrapping times for the biomimetic vesicles. In vivo experiments with distinct routes of nanoparticle administration were investigated. Intratumoral injection proved the nanoparticle-mediated PTT efficiency. MRI and near-infrared images showed that the nanoparticles accumulate in the tumor after intravenous or intraperitoneal administration. Both routes benefit from MRI-guided PTT and demonstrate the multimodal theranostic applications for cancer therapy.

An Integrated ANN-PRA/DP4+ Tandem Computational Approach Contributing to the Ordering of the Heliannuol Family.

Heliannuols are a unique class of sesquiterpenes isolated mostly from Helianthus annuus, commonly known as sunflower. The interesting allelopathic properties, combined with their unprecedented carbon skeletons, have drawn wide attention to phytochemistry and synthetic groups. So far, 14 heliannuols (heliannuols A-N) have been described in the literature, although some of them have not yet been validated by total synthesis. Moreover, the structural proposal of some compounds was based on the similarity of NMR data reported for previously isolated analogues (which in many instances turned out to be incorrect), coupled with little or no stereochemical analysis. Consequently, the structural reassignment is a recurring theme in heliannuol's family. Through a rigorous and comprehensive quantum chemical simulation of NMR parameters, encompassing an integrated ANN-PRA/DP4+ tandem approach, we intended to advance unexplored directions regarding the structure of the entire heliannuol family. Furthermore, we found that the size of the fused ring significantly influences the signals corresponding to the aromatic ring, making this discovery an excellent diagnostic tool for quickly determining the core structure of these compounds.

Evaluation of the Effects of Food Safety Training on the Microbiological Load Present in Equipment, Surfaces, Utensils, and Food Manipulator's Hands in Restaurants.

Training food handlers is essential to ensure food safety. However, the efficacy of training programs relying solely on theoretical information remains uncertain and often fails to induce significant changes in inadequate food practices. Training programs in good hygiene and food safety practices that integrate theoretical and practical approaches have emerged as a vital tool, enabling food handlers to apply their knowledge during work hours and clarify doubts. This study aimed to assess the impact of food safety training based on theoretical and on-the-job training on the microbiological counts of equipment, surfaces, utensils, and food handler (FH) hands. The hygiene and food safety conditions of four restaurants were analyzed through facility checklists, employee questionnaires, and microbiological analyses conducted before and after training. Eight sample collection moments were conducted at each restaurant before and after training. The pre-training results indicate that 15% and 26% of analyses for Enterobacteriaceae and total mesophilic aerobic bacteria (TMB), respectively, did not comply with hygiene safety limits. Additionally, 31% and 64% of Enterobacteriaceae and TMB values, respectively, exceeded safety limits on food handler hands. Positive cases of coagulase-positive Staphylococcus (CoPS) resulted from unprotected wounds on some FH hands. The presence of Listeria monocytogenes in drains was also identified as a concern. Following training, significant differences in results were observed. In many cases, there was a reduction of over 80% in microbial load for Enterobacteriaceae and TMB collected from equipment, surfaces, utensils, and food handler hands. The presence of L. monocytogenes in drains was also eliminated after food safety training. In conclusion, this study underscores the importance of effective training in improving food safety practices.

Valorization of baobab seeds (Adansonia digitata) as a coffee-like beverage: evaluation of roasting time on bioactive compounds.

The baobab tree (Adansonia digitata) can be found in sub-Saharan Africa, and its fruit presents high nutritional value. However, baobab seeds are often discarded and their potential remains underutilized. This study aimed to investigate the effect of roasting time (30/55/80/105 min at 200 °C) on the physical-chemical properties of baobab seeds and the bioactive compounds in a coffee-like beverage. The results showed a decrease in moisture, Aw (water activity), and hardness of baobab seeds with increasing roasting time. These changes resulted from moisture loss, caramelization, and Maillard reactions, which also affected appearance when compared with unroasted baobab seeds. The pH of the beverage decreased to a value of around 6.01 after 105 min of roasting. The total phenolic content and antioxidant activity of the beverage increased with roasting time, reaching 851.2 mg GAE/100 g (after 80 min) and 18.9 mmol Fe2+/100 g (after 55 min), respectively. The caffeine content remained stable around 16 mg/100 g from 55 to 105 min, lower than that of unroasted coffee beans and decaffeinated coffee. These findings suggest the potential for valorizing baobab seeds in the development of a new coffee-like beverage with lower caffeine content.

Tooth discoloration induced by endodontic sealers and cervical limit: 1-year in vitro evaluation.

This laboratory study aimed to evaluate the influence of endodontic sealer and cervical limit of root filling on the discoloration of root canal treated teeth. Bovine incisors were randomly distributed into six experimental groups and control (n=21/group), according to the endodontic sealer used [AH Plus (AP); MTA Fillapex (MF) and Sealer Plus BC (SPB)] and the cervical limit of root filling [dental cervix (DC) or 2 mm in apical direction (2mm-AD)]. Tooth discoloration (ΔE) was evaluated by a digital spectrophotometer using the CIED2000 method. Color assessments were performed immediately before (baseline), 1 week, 1, 3, 6 months, and 1 year after obturation. Data were analyzed by ANOVA and Tukey's post-hoc tests (α=5%). Teeth filled with the three sealers showed perceptible tooth discoloration (ΔE≥2.7) in 1 week, maintaining similar values over time. There was a significant difference between MF and SPB sealers in the 2mm-AD groups. In addition, 2mm-AD groups promoted significantly lower discoloration than DC groups for AH (3 months) and SPB (1 and 3 months) sealer,s. Teeth filled with AP, MF, and SPB sealers displayed discoloration from 1 week to one year, with differences between MF and SPB sealers. A cervical limit of filling material at 2 mm from the dental cervix seems more advisable, promoting lower crown discoloration.

Prevalence and risk factors for acquired long QT syndrome in the emergency department: a retrospective observational study.

BACKGROUND: Long QT syndrome (LQTS) is a heterogeneous syndrome that may be congenital or, more frequently, acquired. The real-world prevalence of acquired LQTS (aLQTS) in the emergency department (ED) remains to be determined. The aim of this study was to determine prevalence of aLQTS and its impact on symptoms on ED admissions. METHODS: Electrocardiograms (ECG) of 5,056 consecutively patients admitted in the ED of a tertiary hospital between January 28th and March 17th of 2020 were reviewed. All patients with aLQTS were included. Clinical data with a focus on QT prolonging drugs and clinical factors were recorded. Statistical comparison was made between the groups with and without corrected QT (QTc) interval greater than 500 ms (value that is considered severely increased). RESULTS: A total of 383 ECGs with prolonged QTc were recognized, corresponding to a prevalence of aLQTS at admission of 7.82%. Patients with aLQTS were more commonly men (53.3%) with an age of (73.49±14.79) years old and QTc interval of (505.3±32.4) ms. Only 20.4% of these patients with aLQTS were symptomatic. No ventricular arrhythmias were recorded. Patients with QT interval greater than 500 ms were more frequently female (59.5%; P<0.001) and were more frequently on QT prolonging drugs (77.3%; P=0.025). Main contributing factor was intake of antibiotics (odds ratio [OR] 4.680) followed by female gender (OR 2.473) and intake of antipsychotics (OR 1.925). CONCLUSION: aLQTS is particularly prevalent in the ED. Female patients on antibiotics and antipsychotics are at particularly high risk. Efforts must be made to avoid, detect and treat aLQTS as early as possible.

Progress for carbon dioxide geological storage in West Macedonia: A field and laboratory-based survey.

Background: It is widely acknowledged that carbon dioxide (CO 2), a greenhouse gas, is largely responsible for climatic changes that can lead to warming or cooling in various places. This disturbs natural processes, creating instability and fragility of natural and social ecosystems. To combat climate change, without compromising technology advancements and maintaining production costs at acceptable levels, carbon capture and storage (CCS) technologies can be deployed to advance a non-disruptive energy transition. Capturing CO 2 from industrial processes such as thermoelectric power stations, refineries, and cement factories and storing it in geological mediums is becoming a mature technology. Part of the Mesohellenic Basin, situated in Greek territory, is proposed as a potential area for CO 2 storage in saline aquifers. This follows work previously done in the StrategyCCUS project, funded by the EU. The work is progressing under the Pilot Strategy, funded by the EU. Methods: The current investigation includes geomechanical and petrophysical methods to characterise sedimentary formations for their potential to hold CO 2 underground. Results: Samples were found to have both low porosity and permeability while the corresponding uniaxial strength for the Tsotyli formation was 22 MPa, for Eptechori 35 MPa and Pentalofo 74 MPa. Conclusions: The samples investigated indicate the potential to act as cap-rocks due to low porosity and permeability, but fluid pressure within the rock should remain within specified limits; otherwise, the rock may easily fracture and result in CO 2 leakage or/and deform to allow the flow of CO 2. Further investigation is needed to identify reservoir rocks as well more sampling to allow for statistically significant results.

Corrigendum: Methylmercury impact on adult neurogenesis: is the worst yet to come from recent Brazilian environmental disasters?

[This corrects the article DOI: 10.3389/fnagi.2020.591601.].

Generating parallel representations of position and identity in the olfactory system.

In Drosophila, a dedicated olfactory channel senses a male pheromone, cis-vaccenyl acetate (cVA), promoting female courtship while repelling males. Here, we show that separate cVA-processing streams extract qualitative and positional information. cVA sensory neurons respond to concentration differences in a 5-mm range around a male. Second-order projection neurons encode the angular position of a male by detecting inter-antennal differences in cVA concentration, which are amplified through contralateral inhibition. At the third circuit layer, we identify 47 cell types with diverse input-output connectivity. One population responds tonically to male flies, a second is tuned to olfactory looming, while a third integrates cVA and taste to coincidentally promote female mating. The separation of olfactory features resembles the mammalian what and where visual streams; together with multisensory integration, this enables behavioral responses appropriate to specific ethological contexts.

Do flies dream of protein? How the gut regulates sleep depth.

A recent study by Titos et al. in Cell shows that protein-rich diets are strong modulators of sleep depth in Drosophila and identifies the gut-secreted neuropeptide CCHa1 as the mediator of this effect. In the brain, CCHa1 controls dopamine release from a small set of neurons, thereby modulating arousability by integrating internal state with sensory information.

Genome-Wide Association Study for Root Morphology and Phosphorus Acquisition Efficiency in Diverse Maize Panels.

Maximizing soil exploration through modifications of the root system is a strategy for plants to overcome phosphorus (P) deficiency. Genome-wide association with 561 tropical maize inbred lines from Embrapa and DTMA panels was undertaken for root morphology and P acquisition traits under low- and high-P concentrations, with 353,540 SNPs. P supply modified root morphology traits, biomass and P content in the global maize panel, but root length and root surface area changed differentially in Embrapa and DTMA panels. This suggests that different root plasticity mechanisms exist for maize adaptation to low-P conditions. A total of 87 SNPs were associated to phenotypic traits in both P conditions at -log10(p-value) ≥ 5, whereas only seven SNPs reached the Bonferroni significance. Among these SNPs, S9_137746077, which is located upstream of the gene GRMZM2G378852 that encodes a MAPKKK protein kinase, was significantly associated with total seedling dry weight, with the same allele increasing root length and root surface area under P deficiency. The C allele of S8_88600375, mapped within GRMZM2G044531 that encodes an AGC kinase, significantly enhanced root length under low P, positively affecting root surface area and seedling weight. The broad genetic diversity evaluated in this panel suggests that candidate genes and favorable alleles could be exploited to improve P efficiency in maize breeding programs of Africa and Latin America.

Attention-Deficit/Hyperactivity Disorder Animal Model Presents Retinal Alterations and Methylphenidate Has a Differential Effect in ADHD versus Control Conditions.

Attention-Deficit/Hyperactivity Disorder (ADHD) is one of the most prevalent neurodevelopmental disorders. Interestingly, children with ADHD seem to experience more ophthalmologic abnormalities, and the impact of methylphenidate (MPH) use on retinal physiology remains unclear. Thus, we aimed to unravel the retina's structural, functional, and cellular alterations and the impact of MPH in ADHD versus the control conditions. For that, spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY) were used as animal models of ADHD and the controls, respectively. Animals were divided into four experimental groups as follows: WKY vehicle (Veh; tap water), WKY MPH (1.5 mg/kg/day), SHR Veh, SHR MPH. Individual administration was performed by gavage between P28-P55. Retinal physiology and structure were evaluated at P56 followed by tissue collection and analysis. The ADHD animal model presents the retinal structural, functional, and neuronal deficits, as well as the microglial reactivity, astrogliosis, blood-retinal barrier (BRB) hyperpermeability and a pro-inflammatory status. In this model, MPH had a beneficial effect on reducing microgliosis, BRB dysfunction, and inflammatory response, but did not correct the neuronal and functional alterations in the retina. Curiously, in the control animals, MPH showed an opposite effect since it impaired the retinal function, neuronal cells, and BRB integrity, and also promoted both microglia reactivity and upregulation of pro-inflammatory mediators. This study unveils the retinal alterations in ADHD and the opposite effects induced by MPH in the retina of ADHD and the control animal models.

Orchard Net Covers Improve Resistance to Cherry Cracking Disorder.

Orchard net cover improves plant physiology, yield and fruit quality, pest and disease control, and anticipates fruit ripening. Moreover, this crop technology has been used to reduce natural cherry cracking (NCC). This is a serious physiological disorder that cracks the epidermis, the hypodermis, and the storage parenchyma layers of the fruit due to rainfall events near the harvest and it is related to low fruit osmotic potential and/or high fruit water permeability. This work aims to study the effect of orchard net cover on sweet cherry trees, cv. Early Bigi, in two harvesting years (2019 and 2021). The NCC, the induced cracking index (CI), and the cracking type incidence were determined. In addition, epicuticular and intra-cuticular wax content, biometric and physicochemical parameters were also evaluated. Net cover reduced the natural cracking index by 40%. High fruit weight values were observed in covered trees comparing to the control ones, with increases of 45% and 13%, in 2019 and 2021, respectively. A positive correlation was observed between CI and total soluble solids and a negative correlation between CI and wax content. Therefore, with forecasts of worsening heavy precipitation events near harvest, protecting cherry trees with nets will increase resistance to fruit cracking.

Tooth discoloration induced by endodontic sealers and cervical limit: 1-year in vitro evaluation

Abstract This laboratory study aimed to evaluate the influence of endodontic sealer and cervical limit of root filling on the discoloration of root canal treated teeth. Bovine incisors were randomly distributed into six experimental groups and control (n=21/group), according to the endodontic sealer used [AH Plus (AP); MTA Fillapex (MF) and Sealer Plus BC (SPB)] and the cervical limit of root filling [dental cervix (DC) or 2 mm in apical direction (2mm-AD)]. Tooth discoloration (ΔE) was evaluated by a digital spectrophotometer using the CIED2000 method. Color assessments were performed immediately before (baseline), 1 week, 1, 3, 6 months, and 1 year after obturation. Data were analyzed by ANOVA and Tukey's post-hoc tests (α=5%). Teeth filled with the three sealers showed perceptible tooth discoloration (ΔE≥2.7) in 1 week, maintaining similar values over time. There was a significant difference between MF and SPB sealers in the 2mm-AD groups. In addition, 2mm-AD groups promoted significantly lower discoloration than DC groups for AH (3 months) and SPB (1 and 3 months) sealer,s. Teeth filled with AP, MF, and SPB sealers displayed discoloration from 1 week to one year, with differences between MF and SPB sealers. A cervical limit of filling material at 2 mm from the dental cervix seems more advisable, promoting lower crown discoloration.

Resumo O presente estudo laboratorial teve como objetivo avaliar a influência do cimento endodôntico e do limite cervical da obturação radicular na alteração de cor de dentes tratados endodonticamente. Incisivos bovinos foram distribuídos aleatoriamente em seis grupos experimentais e um controle (n=21/grupo), de acordo com o cimento endodôntico utilizado [AH Plus (AP); MTA Fillapex (MF) e Sealer Plus BC (SPB)] e o limite cervical da obturação [Colo dentário (CD) ou 2mm na direção apical (2mm-DA)]. A alteração de cor (ΔE) foi avaliada por um espectofotômetro digital usando o método CIED2000. As avaliações de cor foram realizadas imediatamente antes (baseline), 1 semana, 1, 3, 6 meses e 1 ano após a obturação. Os dados foram analisados pelos testes ANOVA e post-hoc de Tuckey (α=5%). Dentes obturados com os três cimentos apresentaram alteração de cor perceptível (ΔE≥2.7) em 1 semana, mantendo valores semelhantes ao longo do tempo. Houve uma diferença significativa entre os cimentos MF e SPB nos grupos 2mm-DA. Além disso, os grupos 2mm-DA promoveram uma alteração de cor significativamente menor do que o grupos CD para os cimentos AH (3 meses) e SPB (1 e 3 meses). Os dentes obturados com os cimentos AH, MF e SPB apresentaram alteração de cor entre 1 semana a um ano, com diferenças entre os cimentos MF e SPB. O limite cervical do material obturador a 2mm do colo dentário parece mais aconselhável, promovendo menor alteração de cor da coroa dentária.

Microplastic Contamination and Ecological Status of Freshwater Ecosystems: A Case Study in Two Northern Portuguese Rivers.

BACKGROUND: Most European rivers have not yet achieved "good" ecological status. In addition, the presence and abundance of microplastics (MPs) in freshwater is a matter of great concern to the scientific community. METHODOLOGY: This study assesses the ecological status of four sampling sites of Selho (S1-S4) and Costa-Couros (C1-C4) rivers (Guimarães, Portugal), and the abundance of MPs in sediments and benthic macroinvertebrates (Oligochaeta) from those sites. RESULTS: All sites of both rivers under higher pressure did not reach a "good" ecological status (S2-S3, C2-C4) based on the macroinvertebrate community. High levels of nutrients were observed at all sites in both rivers (except C2), especially phosphorus. In the Oligochaeta's gut of Costa-Couros river, the high number of MPs seems to be associated with their weight (95.25 ± 25.61 to 1069.00 ± 385.30 MPs g/fresh weight), suggesting the existence of malnutrition and digestive disorders, whereas the highest number of MPs in gut (134.00 ± 30.36 to 558.6 ± 100.70 MPs g/fresh weight) were found for the heaviest organisms of Selho. CONCLUSIONS: Thus, sites with higher ecological status do not necessarily have lower abundance of MPs. In the sediments, urbanization seems to be the main driver for MP contamination. MP contamination is pervasive across the sediments and Oligochaeta's gut in both rivers. Since MPs have the potential to cause harm to environmental and human health, it is essential to monitor not only the ecological status of freshwaters, but also emerging pollutants such as MPs.

Chronic Methylmercury Intoxication Induces Systemic Inflammation, Behavioral, and Hippocampal Amino Acid Changes in C57BL6J Adult Mice.

Methylmercury (MeHg) is highly toxic to the human brain. Although much is known about MeHg neurotoxic effects, less is known about how chronic MeHg affects hippocampal amino acids and other neurochemical markers in adult mice. In this study, we evaluated the MeHg effects on systemic lipids and inflammation, hippocampal oxidative stress, amino acid levels, neuroinflammation, and behavior in adult male mice. Challenged mice received MeHg in drinking water (2 mg/L) for 30 days. We assessed weight gain, total plasma cholesterol (TC), triglycerides (TG), endotoxin, and TNF levels. Hippocampal myeloperoxidase (MPO), malondialdehyde (MDA), acetylcholinesterase (AChE), amino acid levels, and cytokine transcripts were evaluated. Mice underwent open field, object recognition, Y, and Barnes maze tests. MeHg-intoxicated mice had higher weight gain and increased the TG and TC plasma levels. Elevated circulating TNF and LPS confirmed systemic inflammation. Higher levels of MPO and MDA and a reduction in IL-4 transcripts were found in the hippocampus. MeHg-intoxication led to increased GABA and glycine, reduced hippocampal taurine levels, delayed acquisition in the Barnes maze, and poor locomotor activity. No significant changes were found in AChE activity and object recognition. Altogether, our findings highlight chronic MeHg-induced effects that may have long-term mental health consequences in prolonged exposed human populations.

Membrane Technology for Valorization of Mango Peel Extracts.

Mango peel is rich in nutritional and functional compounds, such as carbohydrates, dietary fibers, proteins, and phenolic compounds, with high potential to be applied in the food industry. Most of the investigation about recovery of bioactive compounds from fruit bioproducts involves extraction techniques and further separation of target compounds. There is still a lack of information about the potential of membrane processes to recover the nutritive/functional compounds present in aqueous extracts of those bioproducts. This research is addressed to study the performance of ultrafiltration (UF), followed by nanofiltration (NF) of UF permeates, to fractionate the compounds present in aqueous extracts of mango peel. Both UF and NF concentration processes were carried up to a volume concentration factor of 2.0. Membranes with molecular weight cut-offs of 25 kDa and 130 Da were used in the UF and NF steps, respectively. UF and NF concentrates showed antioxidant activity, attributed to the presence of phenolic compounds, with rejections of about 75% and 98.8%, respectively. UF membranes totally rejected the higher molecular weight compounds, and NF membranes almost totally concentrated the fermentable monosaccharides and disaccharides. Therefore, it is envisaged that NF concentrates can be utilized by the food industry or for bioenergy production.

A 6-month trial of memantine for nystagmus and associated phenomena in oculopalatal tremor.

Introduction: Oculopalatal tremor (OPT) is a late manifestation of a Guillain-Mollaret triangle lesion. Memantine has been shown to improve nystagmus in OPT, but its long-term efficacy and putative distinct effects on each plane of nystagmus and on associated phenomena (e.g., gravity perception) are largely unknown. Methods: We conducted a 6-month open-label study to evaluate the effect of memantine in OPT patients. Baseline (visit 1), 2 (visit 2), and 6 months (visit 3) assessments included video-oculography, best corrected visual acuity (BCVA), visual function questionnaire (VFQ25), palatal tremor frequency, and subjective visual vertical (SVV). Memantine was titrated to 20 mg per day and stopped after 6 months. Results: We included six patients (5 females; mean age 68.5+/-9.7). At visit 2, nystagmus improved >50% only along the horizontal plane in two patients, while worsening >50% along the vertical and horizontal planes in 4 and 1 patients, respectively. At visit 3, previous improvement of nystagmus along the horizontal plane in two patients was not sustained, and it further worsened >50% along the vertical plane in 4. The mean vertical velocity and amplitude of nystagmus in the left eye significantly worsened from visit 2 to visit 3 (p = 0.028). Throughout the study, nystagmus frequency remained unchanged (p = 0.074), BCVA improved in both eyes (p = 0.047, p = 0.017), SVV progression was unpredictable (p = 0.513), and the mean VFQ-25 score (p = 0.223) and mean palatal frequency remained unchanged. Conclusion: The long-term use of memantine 20 mg per day in OPT produced a modest and only transient improvement in nystagmus, predominantly along the horizontal plane. Visual acuity improved, albeit without relevant changes in vision-related quality of life.

Predictors of physical activity promotion in clinical practice: a cross-sectional study among medical doctors.

BACKGROUND: Physical activity is a major determinant of physical and mental health. International recommendations identify health professionals as pivotal agents to tackle physical inactivity. This study sought to characterize medical doctors' clinical practices concerning the promotion of patients' physical activity, while also exploring potential predictors of the frequency and content of these practices, including doctors' physical activity level and sedentary behaviours. METHODS: A cross-sectional study assessed physical activity promotion in clinical practice with a self-report questionnaire delivered through the national medical prescription software (naturalistic survey). Physical activity and sedentary behaviours were estimated using the International Physical Activity Questionnaire (short form). Indicators of medical doctors' attitudes, knowledge, confidence, barriers, and previous training concerning physical activity promotion targeting their patients were also assessed. Multiple regression analysis was performed to identify predictors of physical activity promotion frequency by medical doctors, including sociodemographic, attitudes and knowledge-related variables, and physical activity behaviours as independent variables. RESULTS: A total of 961 medical doctors working in the Portuguese National Health System participated (59% women, mean age 44 ± 13 years) in the study. The majority of the participants (84.6%) reported to frequently promote patients' physical activity. Five predictors of physical activity promotion frequency emerged from the multiple regression analysis, explaining 17.4% of the dependent variable (p < 0.001): working in primary healthcare settings (p = 0.037), having a medical specialty (p = 0.030), attributing a high degree of relevance to patients' physical activity promotion in healthcare settings (p < 0.001), being approached by patients to address physical activity (p < 0.001), and having higher levels of physical activity (p = 0.001). CONCLUSIONS: The sample of medical doctors approached reported a high level of engagement with physical activity promotion. Physical activity promotion frequency seems to be influenced by the clinical practice setting, medical career position and specialty, attitudes towards physical activity, and perception of patients´ interest on the topic, as well as medical doctors' own physical activity levels.

The neuronal logic of how internal states control food choice.

When deciding what to eat, animals evaluate sensory information about food quality alongside multiple ongoing internal states1-10. How internal states interact to alter sensorimotor processing and shape decisions such as food choice remains poorly understood. Here we use pan-neuronal volumetric activity imaging in the brain of Drosophila melanogaster to investigate the neuronal basis of internal state-dependent nutrient appetites. We created a functional atlas of the ventral fly brain and find that metabolic state shapes sensorimotor processing across large sections of the neuropil. By contrast, reproductive state acts locally to define how sensory information is translated into feeding motor output. These two states thus synergistically modulate protein-specific food intake and food choice. Finally, using a novel computational strategy, we identify driver lines that label neurons innervating state-modulated brain regions and show that the newly identified 'borboleta' region is sufficient to direct food choice towards protein-rich food. We thus identify a generalizable principle by which distinct internal states are integrated to shape decision making and propose a strategy to uncover and functionally validate how internal states shape behaviour.